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Sample records for weekly oral bisphosphonates

  1. Comparative gastrointestinal safety of weekly oral bisphosphonates

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    Katz, J. N.; Brookhart, M. A.; Stürmer, T.; Stedman, M. R.; Levin, R.; Solomon, D. H.

    2012-01-01

    Summary Weekly bisphosphonates are the primary agents used to treat osteoporosis. Although these agents are generally well tolerated, serious gastrointestinal adverse events, including hospitalization for gastrointestinal bleed, may arise. We compared the gastrointestinal safety between weekly alendronate and weekly risedronate and found no important difference between new users of these agents. Introduction Weekly bisphosphonates are the primary agents prescribed for osteoporosis. We examined the comparative gastrointestinal safety between weekly bisphosphonates. Methods We studied new users of weekly alendronate and weekly risedronate from June 2002 to August 2005 among enrollees in a state-wide pharmaceutical benefit program for seniors. Our primary outcome was hospitalization for upper gastrointestinal bleed. Secondary outcomes included outpatient diagnoses for upper gastrointestinal disease, symptoms, endoscopic procedures, use of gastroprotective agents, and switching between therapies. We used Cox proportional hazard models to compare outcomes between agents within 120 days of treatment initiation, adjusting for propensity score quintiles. We also examined composite safety outcomes and stratified results by age and prior gastrointestinal history. Results A total of 10,420 new users were studied, mean age=79 years (SD, 6.9), and 95% women. We observed 31 hospitalizations for upper gastrointestinal bleed (0.91 per 100 person-years) within 120 days of treatment initiation. Adjusting for covariates, there was no difference in hospitalization for upper gastrointestinal bleed among those treated with risedronate compared with alendronate (HR, 1.12; 95%CI, 0.55 to 2.28). Risedronate switching rates were lower; otherwise, no differences were observed for secondary or composite outcomes. Conclusions We found no important difference in gastrointestinal safety between weekly oral bisphosphonates. PMID:19266138

  2. Early dental implant failure in patient associated with oral bisphosphonates

    Directory of Open Access Journals (Sweden)

    Ridhimaa Gupta

    2012-01-01

    Full Text Available Oral bisphosphonates are routinely prescribed to post menopausal women. These have shown to increase the risk of osteonecrosis. However, this action may be augmented by local factors. A case report is presented showing an early implant failure in a patient taking oral bisphosphonates. Two implants were placed in left maxillary incisor area. Central incisor was associated with a previous endodontic failure and extraction. Lateral incisor was avulsed 3 years back. After 4 weeks of an implant placement, necrotic bone was evident along with the failing implant in central incisor area. This case report emphasizes on the incidence and an increased risk of implant failure in patients taking oral bisphosphonates.

  3. Gastrointestinal tolerability with ibandronate after previous weekly bisphosphonate treatment

    Directory of Open Access Journals (Sweden)

    Richard Derman

    2009-09-01

    Full Text Available Richard Derman1, Joseph D Kohles2, Ann Babbitt31Department of Obstetrics and Gynecology, Christiana Hospital, Newark, DE, USA; 2Roche, Nutley, NJ, USA; 3Greater Portland Bone and Joint Specialists, Portland, ME, USAAbstract: Data from two open-label trials (PRIOR and CURRENT of women with postmenopausal osteoporosis or osteopenia were evaluated to assess whether monthly oral and quarterly intravenous (IV ibandronate dosing improved self-reported gastrointestinal (GI tolerability for patients who had previously experienced GI irritation with bisphosphonate (BP use. In PRIOR, women who had discontinued daily or weekly BP treatment due to GI intolerance received monthly oral or quarterly IV ibandronate for 12 months. The CURRENT subanalysis included women receiving weekly BP treatment who switched to monthly oral ibandronate for six months. GI symptom severity and frequency were assessed using the Osteoporosis Patient Satisfaction Questionnaire™. In PRIOR, mean GI tolerability scores increased significantly at month 1 from screening for both treatment groups (oral: 79.3 versus 54.1; IV: 84.4 versus 51.0; p < 0.001 for both. Most patients reported improvement in GI symptom severity and frequency from baseline at all post-screening assessments (>90% at Month 10. In the CURRENT subanalysis >60% of patients reported improvements in heartburn or acid reflux and >70% indicated improvement in other stomach upset at month 6. Postmenopausal women with GI irritability with daily or weekly BPs experienced improvement in symptoms with extended dosing monthly or quarterly ibandronate compared with baseline.Keywords: ibandronate, osteoporosis, bisphosphonate, gastrointestinal

  4. Oral bisphosphonates and colon cancer

    DEFF Research Database (Denmark)

    Eiken, Pia; Vestergaard, Peter

    2015-01-01

    Bisphosphonates (BPs) are widely used as the main treatment for osteoporosis. In vitro and animal studies suggest that use of BPs may have a potential for colorectal cancer (CRC) prevention. Safety and efficacy in terms of osteoporosis prevention have only been evaluated in randomized controlled ...

  5. Eliminating the need for fasting with oral administration of bisphosphonates

    DEFF Research Database (Denmark)

    Pazianas, Michael; Abrahamsen, Bo; Ferrari, Serge

    2013-01-01

    Bisphosphonates are the major treatment of choice for osteoporosis, given that they are attached preferentially by bone and significantly reduce the risk of fractures. Oral bisphosphonates are poorly absorbed (usually less than 1% for nitrogen-containing bisphosphonates) and when taken with food ......, eliminates the need for fasting without affecting the bioavailability of risedronate or its efficacy....

  6. Atrial fibrillation in fracture patients treated with oral bisphosphonates

    DEFF Research Database (Denmark)

    Abrahamsen, B; Eiken, P; Brixen, K

    2009-01-01

    -2005). SUBJECTS: Fracture patients beginning bisphosphonates (n = 15 795) were matched with unexposed fracture patients of the same age, sex and fracture type (n = 31 590). RESULTS: Incidence rates of AF were 16.5/1000 person years in untreated fracture patients and 20.6/1000 person years in bisphosphonate users...... to adherence. There was no increased risk of ischaemic stroke and an increased risk of myocardial infarction was not significant after adjustment for comorbidity. CONCLUSIONS: The increased occurrence of AF in fracture patients who are users of oral bisphosphonates should be attributed to targeting...

  7. Documenting the use of calcium supplements with oral bisphosphonates.

    Science.gov (United States)

    Nye, Ann Marie; Hamrick, Irene; Rauch, Allison; Pound, Melanie W; Shelton, Penny S

    2013-01-01

    Patients receiving an oral bisphosphonate for treatment of osteopenia or osteoporosis without adequate calcium intake are not optimally treated. Physicians prescribing bisphosphonates may not consistently document calcium supplementation recommendations. This is a retrospective chart review of osteoporotic or osteopenic outpatients with an active prescription for an oral bisphosphonate. This cross-sectional study was designed to determine the point prevalence of calcium supplementation recommendations by physicians. Academic family medicine outpatient clinics. Of the 1,229 patients with osteoporosis or osteopenia, 425 patients had an active prescription for an oral bisphosphonate and were included in the study. The active/inactive medication list and physician clinic notes in the electronic medical record were reviewed for documentation regarding calcium. The primary endpoint was the percentage of patients on bisphosphonates also receiving calcium. The secondary endpoint was the identification of demographic characteristics associated with lower use of calcium. The patient sample was 94% female, 69% white, with a mean body mass index of 27, and mean age of 72 years. Of the 425 patients, 387 (91.1%) were taking calcium or had a documented recommendation for calcium supplementation. Of the demographic characteristics evaluated, only age was statistically significantly different, with an average age of 76 years in the calcium group and 66 years of age in the noncalcium group. In this study, 91% of outpatients who were prescribed a bisphosphonate also were taking calcium or had it recommended to them. The only statistically significant difference between groups was greater age for those who received calcium.

  8. Treatment of osteoporosis in women intolerant of oral bisphosphonates.

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    Aspray, Terry J; Francis, Roger M

    2012-01-01

    In the past 15 years, oral bisphosphonate therapy has become the mainstay of pharmacological management in patients with osteoporosis. In the UK, alendronate is the drug of first choice, based on clinical efficacy data and cost. However, some patients are unable to take oral bisphosphonates for a number of reasons. In this article, we review the practical management of such cases, including strategies for monitoring adherence and switching to alternative oral agents (e.g. risedronate, strontium ranelate, raloxifene). In some cases, alternative parenteral agents may be considered, including intravenous bisphosphonates, parathyroid hormone therapies and denosumab. Specific concerns about safe prescribing are considered, when prescribing potent anti-resorptive medications, particularly relating to renal function and vitamin D deficiency. Finally, consideration is given to clinical risk factors, including aspects of lifestyle which may be modified to decrease fracture risk.

  9. Potential therapeutic effects of oral bisphosphonates on the intestine.

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    Pazianas, Michael; Russell, R Graham G

    2011-12-01

    Bisphosphonates are the principal drugs prescribed for the prevention of osteoporotic fractures. They are bone specific but poorly absorbed. In oral formulations, almost 99% of the administered dose remains within the intestinal tract and reaches the small and large bowel. Although the nitrogen-containing bisphosphonates can irritate the distal esophageal/gastric mucosa, they improve drug-induced colitis in animal models and exhibit antitumor properties on intestinal cells in vitro. Several recent epidemiological studies provide evidence of a reduced risk of colorectal cancer in osteoporotic patients treated with oral bisphosphonates, notably alendronate. In this review, we will explore the possible mechanisms of action underlying these effects and raise the question of whether these agents might be used in the chemoprophylaxis against colorectal cancer. © 2012 New York Academy of Sciences.

  10. Risk of Severe Upper Gastrointestinal Complications among Oral Bisphosphonate Users

    OpenAIRE

    Arianna Ghirardi; Lorenza Scotti; Antonella Zambon; Gianluca Della Vedova; Luca Cavalieri D'oro; Francesco Lapi; Francesco Cipriani; Caputi, Achille P; Alberto Vaccheri; Dario Gregori; Rosaria Gesuita; Annarita Vestri; Tommaso Staniscia; Giampiero Mazzaglia; Giovanni Corrao

    2013-01-01

    BACKGROUND: Oral bisphosphonates (BPs) are the primary agents for the treatment of osteoporosis. Although BPs are generally well tolerated, serious gastrointestinal adverse events have been observed. AIM: To assess the risk of severe upper gastrointestinal complications (UGIC) among BP users by means of a large study based on a network of Italian healthcare utilization databases. METHODS: A nested case-control study was carried out by including 110,220 patients aged 45 years or older who, fro...

  11. Eliminating the need for fasting with oral administration of bisphosphonates

    Directory of Open Access Journals (Sweden)

    Pazianas M

    2013-10-01

    Full Text Available Michael Pazianas,1 Bo Abrahamsen,2,3 Serge Ferrari,4 R Graham G Russell1,5 1The Botnar Research Center and Oxford University Institute of Musculoskeletal Sciences, Oxford, UK; 2Department of Medicine F, Gentofte Hospital, Hellerup, 3Odense Patient data Explorative Network (OPEN Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; 4Division of Bone Diseases, Faculty of Medicine, Geneva University Hospital, Geneva, Switzerland; 5Mellanby Centre for Bone Research, University of Sheffield, Sheffield, UK Abstract: Bisphosphonates are the major treatment of choice for osteoporosis, given that they are attached preferentially by bone and significantly reduce the risk of fractures. Oral bisphosphonates are poorly absorbed (usually less than 1% for nitrogen-containing bisphosphonates and when taken with food or beverages create complexes that cannot be absorbed. For this reason, they must be taken on an empty stomach, and a period of up to 2 hours must elapse before the consumption of any food or drink other than plain water. This routine is not only inconvenient but can lead to discontinuation of treatment, and when mistakenly taken with food, may result in misdiagnosis of resistance to or failure of treatment. The development of an enteric-coated delayed-release formulation of risedronate with the addition of the calcium chelator, ethylenediaminetetraacetic acid (EDTA, a widely used food stabilizer, eliminates the need for fasting without affecting the bioavailability of risedronate or its efficacy. Keywords: bisphosphonates, osteoporosis treatment, absorption, EDTA, osteoclasts

  12. Successful treatment of SAPHO syndrome with an oral bisphosphonate.

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    Ichikawa, Jiro; Sato, Eiichi; Haro, Hirotaka; Ando, Takashi; Maekawa, Singo; Hamada, Yoshiki

    2009-04-01

    The etiology of the synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome remains unclear and treatment with various drugs for SAPHO syndrome often fails. But recently the effectiveness of intravenous bisphosphonates (BPs) for SAPHO syndrome has been reported in many cases and the use of intravenous BPs as first choice drug has been thought to be effective. On the other hand, serious side effects of intravenous BPs were reported in some cases. This is the first reported case of successful treatment of SAPHO syndrome with an oral BPs, the use of which is safer and more practical than intravenous BPs.

  13. Oral bisphosphonate use and total knee/hip implant survival

    DEFF Research Database (Denmark)

    Prieto-Alhambra, Daniel; Lalmohamed, Arief; Abrahamsen, Bo

    2014-01-01

    OBJECTIVE: Aseptic loosening is the most common cause of revision arthroplasty. Bisphosphonates could minimize this through their antiresorptive effects. This study was undertaken to investigate the association between bisphosphonate use and implant survival. METHODS: A retrospective cohort study...

  14. Dental implants in patients treated with oral bisphosphonates: a bibliographic review.

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    Montoya-Carralero, José-Maria; Parra-Mino, Pablo; Ramírez-Fernández, Piedad; Morata-Murcia, Isabel Maria; Mompeán-Gambín, Maria del Carmen; Calvo-Guirado, José-Luis

    2010-01-01

    Bisphosphonates inhibit bone resorption and are used to treat a range of pathologies, including Paget disease, osteoporosis, multiple myeloma and metastases associated with breast or prostate cancer. At present, there is no effective treatment for bisphosphonate induced osteonecrosis, so prevention is extremely important. Since quality of life deteriorates for those suffering osteonecrosis, maximum precautions should be taken with patients at risk, and especially whenever oral surgery, including dental implant placement, is contemplated. Dentists and oral or maxillofacial surgeons must keep up to date with the latest approaches to prevention, particularly when treating patients who are presently taking, or who will be taking bisphosphonates and are also candidates for dental implants.

  15. Once-weekly teriparatide improves glucocorticoid-induced osteoporosis in patients with inadequate response to bisphosphonates.

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    Seno, Takahiro; Yamamoto, Aihiro; Kukida, Yuji; Hirano, Aiko; Kida, Takashi; Nakabayashi, Amane; Fujioka, Kazuki; Nagahara, Hidetake; Fujii, Wataru; Murakami, Ken; Oda, Ryo; Fujiwara, Hiroyoshi; Kohno, Masataka; Kawahito, Yutaka

    2016-01-01

    Patients with glucocorticoid-induced osteoporosis (GIOP) are at very high risk of fracture, and patients with severe GIOP often experience fractures during treatment with bisphosphonates. Teriparatide (TPTD) is the only currently available anabolic agent expected to be effective for GIOP. Once-weekly TPTD decreased bone resorption marker with primary osteoporosis different from daily TPTD, but it has not yet been tested with GIOP. To evaluate the efficacy of once-weekly TPTD for patients with GIOP and inadequate response to bisphosphonates. Patients with GIOP and collagen diseases treated with prednisolone for at least 6 months with inadequate responses to bisphosphonates were administered once-weekly TPTD. Bone density of the lumbar spine and femoral neck, measured as percent young adult mean (YAM); serum concentrations of cross-linked N-terminal telopeptides of type I collagen (NTx), bone alkaline phosphatase (BAP), and calcium; and FRAX were measured at baseline and 6, 12 and 18 months after starting TPTD. Of the 12 GIOP patients with collagen diseases enrolled, nine (seven females, two males; mean age 57.4 ± 11.1 years) completed treatment, including six with systemic lupus erythematosus, two with rheumatoid arthritis, and one with adult onset still disease. Only one new fracture event, a lumbar compression fracture, occurred during the study period, although seven patients experienced eight fracture events within 18 months before starting TPTD (p = 0.04). Lumbar spine YAM significantly improved at 18 months (p = 0.04), whereas femoral neck YAM did not (p = 0.477). Serum NTx, BAP, Ca, and FRAX were not significantly affected by TPTD treatment. Once-weekly TPTD reduces fracture events and increases bone density of the lumbar spine of GIOP patients with inadequate response to bisphosphonates.

  16. Risk of severe upper gastrointestinal complications among oral bisphosphonate users.

    Directory of Open Access Journals (Sweden)

    Arianna Ghirardi

    Full Text Available BACKGROUND: Oral bisphosphonates (BPs are the primary agents for the treatment of osteoporosis. Although BPs are generally well tolerated, serious gastrointestinal adverse events have been observed. AIM: To assess the risk of severe upper gastrointestinal complications (UGIC among BP users by means of a large study based on a network of Italian healthcare utilization databases. METHODS: A nested case-control study was carried out by including 110,220 patients aged 45 years or older who, from 2003 until 2005, were treated with oral BPs. Cases were the 862 patients who experienced the outcome (hospitalization for UGIC until 2007. Up to 20 controls were randomly selected for each case. Conditional logistic regression model was used to estimate odds ratio (OR associated with current use of BPs after adjusting for several covariates. A set of sensitivity analyses was performed in order to account for sources of systematic uncertainty. RESULTS: The adjusted OR for current use of BPs with respect to past use was 0.94 (95% CI 0.81 to 1.08. There was no evidence that this risk changed either with BP type and regimen, or concurrent use of other drugs or previous hospitalizations. CONCLUSIONS: No evidence was found that current use of BPs increases the risk of severe upper gastrointestinal complications compared to past use.

  17. Risk of Severe Upper Gastrointestinal Complications among Oral Bisphosphonate Users

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    Ghirardi, Arianna; Scotti, Lorenza; Zambon, Antonella; Della Vedova, Gianluca; Cavalieri D'oro, Luca; Lapi, Francesco; Cipriani, Francesco; Caputi, Achille P.; Vaccheri, Alberto; Gregori, Dario; Gesuita, Rosaria; Vestri, Annarita; Staniscia, Tommaso; Mazzaglia, Giampiero; Corrao, Giovanni

    2013-01-01

    Background Oral bisphosphonates (BPs) are the primary agents for the treatment of osteoporosis. Although BPs are generally well tolerated, serious gastrointestinal adverse events have been observed. Aim To assess the risk of severe upper gastrointestinal complications (UGIC) among BP users by means of a large study based on a network of Italian healthcare utilization databases. Methods A nested case-control study was carried out by including 110,220 patients aged 45 years or older who, from 2003 until 2005, were treated with oral BPs. Cases were the 862 patients who experienced the outcome (hospitalization for UGIC) until 2007. Up to 20 controls were randomly selected for each case. Conditional logistic regression model was used to estimate odds ratio (OR) associated with current use of BPs after adjusting for several covariates. A set of sensitivity analyses was performed in order to account for sources of systematic uncertainty. Results The adjusted OR for current use of BPs with respect to past use was 0.94 (95% CI 0.81 to 1.08). There was no evidence that this risk changed either with BP type and regimen, or concurrent use of other drugs or previous hospitalizations. Conclusions No evidence was found that current use of BPs increases the risk of severe upper gastrointestinal complications compared to past use. PMID:24348985

  18. Safety of intravenous and oral bisphosphonates and compliance with dosing regimens.

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    Conte, PierFranco; Guarneri, Valentina

    2004-01-01

    Patients with advanced cancers--particularly breast and prostate cancers--are at high risk for bone metastasis, leading to accelerated bone resorption and clinically significant skeletal morbidity. Bisphosphonates are effective inhibitors of bone resorption and reduce the risk of skeletal complications in patients with bone metastases. The standard routes of administration for bisphosphonates used in clinical practice are either oral or i.v. infusion. Oral administration of bisphosphonates is complicated by poor bioavailability (generally Pharmaceuticals; Princeton, NJ), must be administered at high oral doses (1,600-3,200 mg/day) to achieve therapeutic effects, which leads to poor tolerability and compliance with oral dosing regimens. Infusion of bisphosphonates is associated with dose- and infusion-rate-dependent effects on renal function. In particular, high bisphosphonate doses (e.g., 1,500 mg clodronate) can cause severe renal toxicity unless infused slowly over many hours. In contrast, the newer, more potent bisphosphonates effectively inhibit bone resorption at micromolar concentrations, and the small doses required can be administered via relatively short i.v. infusions without adversely affecting renal function. Zoledronic acid (Zometa; Novartis Pharmaceuticals Corp.; East Hanover, NJ) is a new generation bisphosphonate, and the recommended dose of 4 mg can be safely infused over 15 minutes. The 90-mg dose of pamidronate (Aredia; Novartis Pharmaceuticals Corp.) and the 6-mg dose of ibandronate (Bondronat; Hoffmann-La Roche Inc.; Nutley, NJ) require 1- to 4-hour infusions. Intravenous bisphosphonates require less frequent dosing (once a month) and are generally well tolerated with long-term use in patients with bone metastases. Zoledronic acid has demonstrated the broadest clinical activity in patients with bone metastases.

  19. Subtrochanteric stress fractures in patients on oral bisphosphonate therapy: an emerging problem.

    LENUS (Irish Health Repository)

    Murphy, Colin G

    2012-01-31

    The emergence of a new variant of subtrochanteric stress fractures of the femur, affecting patients on oral bisphosphonate therapy, has only recently been described. This fracture is often preceded by pain and distinctive radiographic changes (lateral cortical thickening), and associated with a characteristic fracture pattern (transverse fracture line and medial cortical spike). A retrospective review (2007-2009) was carried out for patients who were taking oral bisphosphonates and who sustained a subtrochanteric fracture after a low velocity injury. Eleven fractures were found in 10 patients matching the inclusion criteria outlined. All were females, and taking bisphosphonates for a mean of 43 years. Five of the 10 patients mentioned prodromal symptoms, for an average of 9.4 months before the fracture. Although all fractures were deemed low velocity, 5 of 11 were even atraumatic. Two patients had previously sustained contralateral subtrochanteric fractures. Plain radiographs of two patients showed lateral cortical thickening on the contralateral unfractured femur; the bisphosphonate therapy was stopped and close surveillance was started. Patients taking oral bisphosphonates may be at risk of a new variant of stress fracture of the proximal femur. Awareness of the symptoms is the key to ensure that appropriate investigations are undertaken.

  20. Subtrochanteric stress fractures in patients on oral bisphosphonate therapy: an emerging problem.

    Science.gov (United States)

    Murphy, Colin G; O'Flanagan, Shay; Keogh, Peter; Kenny, Patrick

    2011-10-01

    The emergence of a new variant of subtrochanteric stress fractures of the femur, affecting patients on oral bisphosphonate therapy, has only recently been described. This fracture is often preceded by pain and distinctive radiographic changes (lateral cortical thickening), and associated with a characteristic fracture pattern (transverse fracture line and medial cortical spike). A retrospective review (2007-2009) was carried out for patients who were taking oral bisphosphonates and who sustained a subtrochanteric fracture after a low velocity injury. Eleven fractures were found in 10 patients matching the inclusion criteria outlined. All were females, and taking bisphosphonates for a mean of 43 years. Five of the 10 patients mentioned prodromal symptoms, for an average of 9.4 months before the fracture. Although all fractures were deemed low velocity, 5 of 11 were even atraumatic. Two patients had previously sustained contralateral subtrochanteric fractures. Plain radiographs of two patients showed lateral cortical thickening on the contralateral unfractured femur; the bisphosphonate therapy was stopped and close surveillance was started. Patients taking oral bisphosphonates may be at risk of a new variant of stress fracture of the proximal femur. Awareness of the symptoms is the key to ensure that appropriate investigations are undertaken.

  1. Oral bisphosphonates and risk of subtrochanteric or diaphyseal femur fractures in a population-based cohort.

    Science.gov (United States)

    Kim, Seo Young; Schneeweiss, Sebastian; Katz, Jeffrey N; Levin, Raisa; Solomon, Daniel H

    2011-05-01

    Bisphosphonates are the primary therapy for postmenopausal and glucocorticoid-induced osteoporosis. Case series suggest a potential link between prolonged use of bisphosphonates and low-energy fracture of subtrochanteric or diaphyseal femur as a consequence of oversuppression of bone resorption. Using health care utilization data, we conducted a propensity score-matched cohort study to examine the incidence rates (IRs) and risk of subtrochanteric or diaphyseal femur fractures among oral bisphosphonate users compared with raloxifene or calcitonin users. A Cox proportional hazards model evaluated the risk of these fractures associated with duration of osteoporosis treatment. A total of 104 subtrochanteric or diaphyseal femur fractures were observed among 33,815 patients. The estimated IR of subtrochanteric or diaphyseal femur fractures per 1000 person-years was 1.46 [95% confidence interval (CI) 1.11-1.88] among the bisphosphonate users and 1.43 (95% CI 1.06-1.89) among raloxifene/calcitonin users. No significant association between bisphosphonate use and subtrochanteric or diaphyseal femur fractures was found [hazard ratio (HR) = 1.03, 95% CI 0.70-1.52] compared with raloxifene/calcitonin. Even with this large study size, we had little precision in estimating the risk of subtrochanteric or diaphyseal femur fractures in patients treated with bisphosphonates for longer than 5 years (HR = 2.02, 95% CI 0.41-10.00). The occurrence of subtrochanteric or diaphyseal femur fracture was rare. There was no evidence of an increased risk of subtrochanteric or diaphyseal femur fractures in bisphosphonate users compared with raloxifene/calcitonin users. However, this study cannot exclude the possibility that long-term bisphosphonate use may increase the risk of these fractures.

  2. Prophylaxis and antibiotic therapy in management protocols of patients treated with oral and intravenous bisphosphonates

    Science.gov (United States)

    Bermúdez-Bejarano, Elena-Beatriz; Serrera-Figallo, María-Ángeles; Gutiérrez-Corrales, Aida; Romero-Ruiz, Manuel-María; Castillo-de-Oyagüe, Raquel; Gutiérrez-Pérez, José-Luis

    2017-01-01

    Introduction Osteonecrosis of the jaw (MRONJ) linked to bisphosphonate treatment has specific characteristics that render its therapeutic management challenging for clinicians. Poor response to standard treatment makes it essential to take special precautions when treating this type of disease; therefore, antibiotic prophylaxis and/or antibiotic therapy have been proposed as effective and helpful tools in these situations. Objectives This article seeks to assess published evidence in order to evaluate the different protocols used for antibiotic prophylaxis and/or antibiotic therapy in the general context of patients treated with bisphosphonates. Material and Methods A literature review of the last 10 years was carried out in PubMed using the following keywords: “antibiotic prophylaxis and osteonecrosis,” “bisphosphonates AND osteonecrosis AND dental management,” “bisphosphonate AND osteonecrosis AND antibiotic prophylaxis AND oral surgery.” A total of 188 articles were obtained, of which 18 were ultimately selected. Results and Discussion In patients treated with oral and intravenous bisphosphonates without chemotherapy-associated osteonecrosis of the jaw, antibiotic prophylaxis prior to oral surgery is an important tool to avoid osteonecrosis and promote healing of the affected area. If the patient previously exhibited chemotherapy-associated osteonecrosis after tooth extraction, antibiotic prophylaxis is indicated to prevent recurrent osteonecrosis and promote healing of the extraction site. If chemotherapy-associated osteonecrosis is already present, antibiotic therapy is a vital part of conservative management to reduce the symptomatology of MRONJ and keep it from worsening. Finally, a lack of clinical data and randomized controlled trials makes it difficult to choose the most appropriate protocol for the various clinical situations studied. Key words:Bisphosphonates, antibiotic prophylaxis, maxillary osteonecrosis, antibiotic treatment. PMID

  3. Osteonecrosis of the Torus Palatinus in the Setting of Long-Term Oral Bisphosphonate Use--A Case Report.

    Science.gov (United States)

    Ryan, Joshua L; Larson, Eric

    2016-01-01

    Bisphosphonates are medications used orally and intravenously for a variety of conditions including cancer metastatic to bone, hypercalcemia of malignancy, Paget's disease and osteoporosis. Osteonecrosis of the jaw has been related to bisphosphonate use. Osteonecrosis of the jaw most commonly occurs in the setting of intravenous bisphosphonate use and concomitant dental work or trauma. Oral bisphosphonates have much less risk of osteonecrosis of the jaw. We present an interesting case of a patient on an oral bisphosphonate for an extended period of time (nine years), with a torus palatinus, who burned her palate while eating a slice of pizza. Over six months later, she presented with an area of denuded bone and diagnosis consistent with osteonecrosis of the torus palatinus.

  4. Cost-effectiveness of combined oral bisphosphonate therapy and falls prevention exercise for fracture prevention in the USA.

    Science.gov (United States)

    Mori, T; Crandall, C J; Ganz, D A

    2017-02-01

    We developed a Markov microsimulation model among hypothetical cohorts of community-dwelling US white women without prior major osteoporotic fractures over a lifetime horizon. At ages 75 and 80, adding 1 year of exercise to 5 years of oral bisphosphonate therapy is cost-effective at a conventionally accepted threshold compared with bisphosphonates alone.

  5. Bisphosphonates and oral pathology II. Osteonecrosis of the jaws: review of the literature before 2005.

    Science.gov (United States)

    Estefanía Fresco, Ruth; Ponte Fernández, Ruth; Aguirre Urizar, José Manuel

    2006-11-01

    Bisphosphonates are bone-turnover modulating drugs which are used in the management of a number of bone diseases ranging from osteoporosis to neoplasic pathology-associated osteolysis. In the last years a number of cases of osteonecrosis of the jaws associated with these drugs have been reported. In this review we analyze the cases published in the literature indexed from 2003 to December 2005. During this period 246 cases were reported, being more frequently associated with women in the sixth decade of life. More frequently associated bisphosphonates were the nitrogenated bisphosphonates (pamidronate, zolendronic acid) and the most common oral antecedent was a dental extraction. Nevertheless more than 25% of the cases were spontaneous. The most frequent site was the mandible and most of the cases presented clinical evidence of bone exposure and pain. Different treatments have been proposed with different antibiotic therapies with or without surgery, showing in general terms an uncertain prognosis with low healing rates.

  6. Predictors of Adherence to Oral Bisphosphonate Therapy: A Register-based National Open Cohort Study

    DEFF Research Database (Denmark)

    Hansen, Carrinna; Pedersen, B D; Konradsen, Hanne;

    Abstract: Aim: To assess adherence to oral bisphosphonates and determine what predicts early cessation of treatment as opposed to low refill compliance. We hypothesized that patients who stopped treatment very early would differ in demographics and comorbidity from other patients with poor adhere...... with increasing age and in patients taking proton pump inhibitors. These findings suggest that other factors — such as patient understanding, education level and socioeconomics may be more important determinants of adherence to osteoporosis treatment....

  7. Risk factors of osteonecrosis of the jaw after tooth extraction in osteoporotic patients on oral bisphosphonates

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Ho Gui; Hwang, Jae Joon; Lee, Jeong Hee; Kim, Young Hyun; Na, Ji Yeon; Han, Sang Sun [Dept. of Oral and Maxillofacial Radiology, Yonsei University, College of Dentistry, Seoul (Korea, Republic of)

    2017-03-15

    The aim of this study was to investigate the incidence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) after tooth extraction in patients with osteoporosis on oral bisphosphonates in Korea and to evaluate local factors affecting the development of BRONJ. The clinical records of 320 patients who underwent dental extraction while receiving oral bisphosphonates were reviewed. All patients had a healing period of more than 6 months following the extractions. Each patient's clinical record was used to assess the incidence of BRONJ; if BRONJ occurred, a further radiographic investigation was carried out to obtain a more definitive diagnosis. Various local factors including age, gender, extraction site, drug type, duration of administration, and C-terminal telopeptide (CTx) level were retrieved from the patients' clinical records for evaluating their effect on the incidence of BRONJ. Among the 320 osteoporotic patients who underwent tooth extraction, 11 developed BRONJ, reflecting an incidence rate of 3.44%. Out of the local factors that may affect the incidence of BRONJ, gender, drug type, and CTx level showed no statistically significant effects, while statistically significant associations were found for age, extraction site, and duration of administration. The incidence of BRONJ increased with age, was greater in the mandible than the maxilla, and was associated with a duration of administration of more than 3 years. Tooth extraction in patients on oral bisphosphonates requires careful consideration of their age, the extraction site, and the duration of administration, and close postoperative follow-up should be carried out to facilitate effective early management.

  8. Radiologic Findings of Oral Bisphosphonate-Related Osteonecrosis of the Maxilla, Complicated by Actinomycosis: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yi Kyung; Kim, Hyung Jin; Kim, Eun Hee; Chung, Seung Kyu; Hong, Jong Rak [Samsung Medical Center, Seoul (Korea, Republic of)

    2010-01-15

    Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a rare, but serious complication, which has recently been more frequently reported. However, this entity is unfamiliar to radiologists. We report a case of BRONJ complicated by actinomycosis following a tooth extraction in a 68-year-old woman who has been treated with oral bisphosphonate for treatment of osteoporosis over the last 3 years and 3 months

  9. Plasticity of Myeloid Cells during Oral Barrier Wound Healing and the Development of Bisphosphonate-related Osteonecrosis of the Jaw.

    Science.gov (United States)

    Sun, Yujie; Kaur, Kawaljit; Kanayama, Keiichi; Morinaga, Kenzo; Park, Sil; Hokugo, Akishige; Kozlowska, Anna; McBride, William H; Li, Jun; Jewett, Anahid; Nishimura, Ichiro

    2016-09-23

    Injury to the barrier tissue initiates a rapid distribution of myeloid immune cells from bone marrow, which guide sound wound healing. Bisphosphonates, a widely used anti-bone resorptive drug with minimal systemic side effects, have been linked to an abnormal wound healing in the oral barrier tissue leading to, in some cases, osteonecrosis of the jaw (ONJ). Here we report that the development of ONJ may involve abnormal phenotypic plasticity of Ly6G+/Gr1+ myeloid cells in the oral barrier tissue undergoing tooth extraction wound healing. A bolus intravenous zoledronate (ZOL) injection to female C57Bl/6 mice followed by maxillary first molar extraction resulted in the development of ONJ-like lesion during the second week of wound healing. The multiplex assay of dissociated oral barrier cells exhibited the secretion of cytokines and chemokines, which was significantly modulated in ZOL mice. Tooth extraction-induced distribution of Ly6G+/Gr1+ cells in the oral barrier tissue increased in ZOL mice at week 2. ONJ-like lesion in ZOL mice contained Ly6G+/Gr1+ cells with abnormal size and morphology as well as different flow cytometric staining intensity. When anti-Ly6G (Gr1) antibody was intraperitoneally injected for 5 days during the second week of tooth extraction, CD11b+GR1(hi) cells in bone marrow and Ly6G+ cells in the oral barrier tissue were depleted, and the development of ONJ-like lesion was significantly attenuated. This study suggests that local modulation of myeloid cell plasticity in the oral barrier tissue may provide the basis for pathogenesis and thus therapeutic as well as preventive strategy of ONJ.

  10. The effects of switching daily teriparatide to oral bisphosphonates or denosumab in patients with primary osteoporosis.

    Science.gov (United States)

    Ebina, Kosuke; Hashimoto, Jun; Kashii, Masafumi; Hirao, Makoto; Kaneshiro, Shoichi; Noguchi, Takaaki; Tsukamoto, Yasunori; Yoshikawa, Hideki

    2017-01-01

    The aim of this 12-month, observational study was to compare the effects of switching daily teriparatide (TPTD) to oral bisphosphonates (BP) therapy or denosumab (DMAb) therapy in patients with primary osteoporosis. Patients [n = 78; 71 postmenopausal women and seven men; mean age 76.3 (64-94) years; mean duration of prior daily TPTD therapy 20.1 (6-24) months] were allocated to either the (1) "switch-to-BP" group [n = 36; weekly alendronate 35 mg (n = 19), weekly risedronate 17.5 mg (n = 12), monthly minodronate 50 mg (n = 5)]; or (2) "switch-to-DMAb" group (n = 42; 60 mg sc every 6 months) based on each physicians' decision. Changes in bone mineral density (BMD) and serum bone turnover markers were monitored every 6 months. No significant difference was observed in baseline clinical characteristics between the groups. After 12 months, the increase in BMD was significantly greater in the switch-to-DMAb group compared to the switch-to-BP group: lumbar spine (6.2 vs. 2.6 %; P < 0.01), total hip (4.2 vs. 1.1 %; P < 0.05), and femoral neck (3.5 vs. 1.4 %; P < 0.05). In addition, the patients in the switch-to-DMAb group showed a significant decrease compared to those in the switch-to-BP group in TRACP-5b (-55.8 vs. -32.8 %; P < 0.01) and ucOC (-85.5 vs. -65.0 %; P < 0.001), while no significant difference was observed in PINP (-67.5 vs. -62.1 %). Switching daily TPTD to DMAb significantly increased BMD and decreased bone resorption marker compared to switching to oral BP at 12 months, and thus may provide an effective sequential treatment option after daily TPTD treatment.

  11. Cost of non-persistence with oral bisphosphonates in post-menopausal osteoporosis treatment in France

    Directory of Open Access Journals (Sweden)

    Cotté François-Emery

    2011-06-01

    Full Text Available Abstract Background During the last decade, oral bisphosphonates (BP became the most widely prescribed pharmacologic class for post-menopausal osteoporosis. However, many surveys revealed the important issue of poor persistence with those drugs resulting in a failure of treatment to reduce fracture risk sufficiently. Using a published Markov model, this study analyses the economic impact of non-persistence with bisphosphonates in the context of the introduction of generics in France. Methods Direct costs of vertebral, hip and wrist fracture were assessed and included in an existing 10-year Markov model developed to analyse consequences of non-persistence. Three alternatives of comparison were set: no treatment, real-world persistence, and ideal persistence. Simulated patients' characteristics matched those from a French observational study and the real-world adherence alternative employed persistence data from published database analysis. The risk of fracture of menopausal women and the risk reduction associated with the drugs were based on results reported in clinical trials. Incremental cost-effectiveness ratios (ICERs were calculated first between real-world adherence and no treatment alternatives, and second between ideal and real-world persistence alternatives. The cost of non-persistence was defined as the difference between total cost of ideal and real-world persistence alternatives. Results Within fractured women population, mean costs of 10-year management of fracture were significantly different between the three alternatives with €7,239 (± €4,783, €6,711 (± €4,410 and €6,134 (± €3,945 in the no-treatment, the real-world and ideal persistence alternatives, respectively (p Conclusion Within term, improving persistence with oral bisphosphonates should be economically dominant on levels currently known in real-world. Given this potential savings, ambitious adherence-enhancing interventions should be considered in

  12. Interaction between Bisphosphonates and Mineral Water: Study of Oral Risedronate Absorption in Rats.

    Science.gov (United States)

    Itoh, Akihisa; Akagi, Yuuki; Shimomura, Hitoshi; Aoyama, Takao

    2016-01-01

    Bisphosphonates are antiosteoporotic agents prescribed for patients with osteoporosis. Drug package inserts for bisphosphonate supplements indicate that their bioavailability is reduced by high levels of metal cations (Ca(2+), Mg(2+), etc.). However, standards for these cations in water used for taking risedronate have not been defined. Here, we examined the effect of calcium and magnesium in mineral waters on the bioavailability of the third-generation bisphosphonate, risedronate, following oral administration in rats. As risedronate is unchanged and eliminated renally, risedronate absorption was estimated from the amount excreted in the urine. Risedronate was dissolved in mineral water samples and administered orally at 0.35 mg/kg. Urine samples were collected for 24 h after dosing. Risedronate was extracted from urine using ion-pair solid-phase cartridges and quantified by HPLC with UV detection (262 nm). Cumulative recovery of risedronate was calculated from the amount excreted in the urine. The 24-h recovery of risedronate from evian® (0.32±0.02% [mean±standard deviation (S.D.)], n=4) and Contrex(®) (0.22±0.05%) mineral waters was significantly lower than that from tap water (0.47±0.04%, prisedronate in calcium chloride and magnesium chloride aqueous solutions of the same hardness (822 mg/L) was 54% (0.27±0.04%) and 12% (0.51±0.08%) lower, respectively, compared with ultrapure water; suggesting that absorption of risedronate declines as the calcium concentration of mineral waters increases. Consumption of mineral waters containing high levels of calcium (80 mg/L or above), such as evian® and Contrex(®), is therefore not recommended when taking risedronate.

  13. Oral bisphosphonates do not increase the risk of severe upper gastrointestinal complications: A nested case-control study

    NARCIS (Netherlands)

    A. Ghirardi (Arianna); L. Scotti (Lorenza); G.D. Vedova (Gianluca); L.C. D'Oro (Luca); F. Lapi (Francesco); F. Cipriani (Francesco); A.P. Caputi (Achille); A. Vaccheri (Alberto); D Gregori (Dario); R. Gesuita (Rosaria); A. Vestri (Annarita); T. Staniscia (Tommaso); G. Mazzaglia (Giampiero); G. Corrao (Giovanni); E. Sessa (E.); V. Arcoraci (Vincenzo); A. Parodi (Andrea); A. Zambon (A.); N. Montanaro (N.); C. Piccinni (C.); C. Suzzi (C.); A. Puccini (A.); M.C.J.M. Sturkenboom (Miriam); P. Geppetti (P.); L. Sati (L.); M. Di Bari (M.); F. Forlan (F.); F. Carle (F.); A. Menna (A.); R. Valenti (Renato)

    2014-01-01

    textabstractBackground: Data on the effect of oral bisphosphonates (BPs) on risk of upper gastrointestinal complications (UGIC) are conflicting. We conducted a large population-based study from a network of Italian healthcare utilization databases aimed to assess the UGIC risk associated with use of

  14. International Osteoporosis Foundation and European Calcified Tissue Society Working Group. Recommendations for the screening of adherence to oral bisphosphonates.

    Science.gov (United States)

    Diez-Perez, A; Naylor, K E; Abrahamsen, B; Agnusdei, D; Brandi, M L; Cooper, C; Dennison, E; Eriksen, E F; Gold, D T; Guañabens, N; Hadji, P; Hiligsmann, M; Horne, R; Josse, R; Kanis, J A; Obermayer-Pietsch, B; Prieto-Alhambra, D; Reginster, J-Y; Rizzoli, R; Silverman, S; Zillikens, M C; Eastell, R

    2017-03-01

    Adherence to oral bisphosphonates is low. A screening strategy is proposed based on the response of biochemical markers of bone turnover after 3 months of therapy. If no change is observed, the clinician should reassess the adherence to the treatment and also other potential issues with the drug.

  15. Impact of the training on the compliance and persistence of weekly bisphosphonate treatment in postmenopausal osteoporosis: a randomized controlled study.

    Science.gov (United States)

    Tüzün, Şansın; Akyüz, Gülseren; Eskiyurt, Nurten; Memiş, Asuman; Kuran, Banu; İçağasıoğlu, Afitap; Sarpel, Tunay; Özdemir, Ferda; Özgirgin, Neşe; Günaydın, Rezzan; Cakçı, Aytül; Yurtkuran, Merih

    2013-01-01

    Long-term patient adherence to osteoporosis treatment is poor despite proven efficacy. In this study, we aimed to assess the impact of active patient training on treatment compliance and persistence in patients with postmenopausal osteoporosis. In the present national, multicenter, randomized controlled study, postmenopausal osteoporosis patients (45-75 years) who were on weekly bisphosphonate treatment were randomized to active training (AT) and passive training (PT) groups and followed-up by 4 visits after the initial visit at 3 months interval during 12 months of the treatment. Both groups received a bisphosphonate usage guide and osteoporosis training booklets. Additionally, AT group received four phone calls (at 2(nd), 5(th), 8(th), and 11(th) months) and participated to four interactive social/training meetings held in groups of 10 patients (at 3(rd), 6(th), 9(th), and 12(th) months). The primary evaluation criteria were self-reported persistence and compliance to the treatment and the secondary evaluation criteria was quality life of the patients assessed by 41-item Quality of Life European Foundation for Osteoporosis (QUALEFFO-41) questionnaire. Of 448 patients (mean age 62.4±7.7 years), 226 were randomized to AT group and 222 were randomized to PT group. Among the study visits, the most common reason for not receiving treatment regularly was forgetfulness (54.9% for visit 2, 44.3% for visit 3, 51.6% for visit 4, and 43.8% for visit 5), the majority of the patients always used their drugs regularly on recommended days and dosages (63.8% for visit 2, 60.9% for visit 3, 72.1% for visit 4, and 70.8% for visit 5), and most of the patients were highly satisfied with the treatment (63.4% for visit 2, 68.9% for visit 3, 72.4% for visit 4, and 65.2% for visit 5) and wanted to continue to the treatment (96.5% for visit 2, 96.5% for visit 3, 96.9% for visit 4, and 94.4% for visit 5). QUALEFFO scores of the patients in visit 1 significantly improved in visit 5 (37.7

  16. International Osteoporosis Foundation and European Calcified Tissue Society Working Group. Recommendations for the screening of adherence to oral bisphosphonates

    DEFF Research Database (Denmark)

    Diez-Perez, Adolfo; Naylor, K E; Abrahamsen, B

    2017-01-01

    Adherence to oral bisphosphonates is low. A screening strategy is proposed based on the response of biochemical markers of bone turnover after 3 months of therapy. If no change is observed, the clinician should reassess the adherence to the treatment and also other potential issues with the drug...... Tissue Society have convened a working group to propose a screening strategy to detect a lack of adherence to these drugs. The question to answer was whether the bone turnover markers (BTMs) PINP and CTX can be used to identify low adherence in patients with postmenopausal osteoporosis initiating oral...... bisphosphonates for osteoporosis. The findings of the TRIO study specifically address this question and were used as the basis for testing the hypothesis. RESULTS: Based on the findings of the TRIO study, specifically addressing this question, the working group recommends measuring PINP and CTX at baseline and 3...

  17. Treatment with intravenous pamidronate is a good alternative in case of gastrointestinal side effects or contraindications for oral bisphosphonates

    Directory of Open Access Journals (Sweden)

    Dijkmans Ben AC

    2009-07-01

    Full Text Available Abstract Background In case of contraindications or intolerance during treatment with oral bisphosphonates (OB, administration of pamidronate intravenously is a widely used alternative. In this study we compared the effect on change in bone mineral density (BMD of the spine and hip during long term treatment with pamidronate iv in comparison to OB. Methods We studied 61 patients receiving treatment for at least two years. In case of contraindications or intolerance (within 3 months of an OB, pamidronate iv was started. BMD was measured on a Hologic 4500 and a Lunar DPX-IQ at the spine (L1-L4 and total hip. Results Thirty-one patients were enrolled in the OB group and 30 in the intravenous pamidronate group. Mean follow-up duration (SD was 4.3 (1.3 years. We observed a significant increase (p Conclusion We conclude that intravenous pamidronate is a good alternative for oral bisphosphonates in the treatment of osteoporosis in patients with contraindications or intolerance during treatment with oral bisphosphonates.

  18. Prevalence of osteonecrosis of the jaw and oral characteristics of oncologic patients treated with bisphosphonates at the General Hospital of Mexico

    Science.gov (United States)

    2016-01-01

    Objectives To determine the prevalence and oral characteristics of cancer patients treated with bisphosphonates in the oncology and maxillofacial prosthesis departments of the General Hospital of Mexico between 2011 and 2013. Materials and Methods This cross-sectional study included patients who received prior treatment with bisphosphonates; an intraoral examination was performed by 2 standardized examiners. Results The prevalence of bisphosphonate-related necrosis in 75 patients was 2.6%; the most common malignancy was breast cancer (84.0%), followed by prostate cancer (16.0%). Exostosis was present in 9.3% of patients and the mean Decayed, Missing, Filled Teeth index was 4.64; 44.0% of the study group had a Community Periodontal Index value between 2 and 2.9 (mean, 0.60). Conclusion A detailed intraoral assessment must be performed before initiating treatment with bisphosphonates to identify risk factors for osteonecrosis. PMID:28053907

  19. Oral microbiota and host innate immune response in bisphosphonate-related osteonecrosis of the jaw

    Institute of Scientific and Technical Information of China (English)

    Smruti Pushalkar; Deepak Saxena; Xin Li; Zoya Kurago; Lalitha V Ramanathapuram; Satoko Matsumura; Kenneth E Fleisher; Robert Glickman; Wenbo Yan; Yihong Li

    2014-01-01

    Bacterial biofilms have emerged as potential critical triggers in the pathogenesis of bisphosphonate (BP)-related osteonecrosis of the jaw (ONJ) or BRONJ. BRONJ lesions have shown to be heavily colonized by oral bacteria, most of these difficult to cultivate and presents many clinical challenges. The purpose of this study was to characterize the bacterial diversity in BRONJ lesions and to determine host immune response. We examined tissue specimens from three cohorts (n530);patients with periodontal disease without a history of BP therapy (Control, n510), patients with periodontal disease having history of BP therapy but without ONJ (BP, n55) and patients with BRONJ (BRONJ, n515). Denaturing gradient gel electrophoresis of polymerase chain reaction (PCR)-amplified 16S rRNA gene fragments revealed less bacterial diversity in BRONJ than BP and Control cohorts. Sequence analysis detected six phyla with predominant affiliation to Firmicutes in BRONJ (71.6%), BP (70.3%) and Control (59.1%). Significant differences (P,0.05) in genera were observed, between Control/BP, Control/BRONJ and BP/BRONJ cohorts. Enzyme-linked immunosorbent assay (ELISA) results indicated that the levels of myeloperoxidase were significantly lower, whereas interleukin-6 and tumor necrosis factor-alpha levels were moderately elevated in BRONJ patients as compared to Controls. PCR array showed significant changes in BRONJ patients with downregulation of host genes, such as nucleotide-binding oligomerization domain containing protein 2, and cathepsin G, the key modulators for antibacterial response and upregulation of secretory leukocyte protease inhibitor, proteinase 3 and conserved helix–loop–helix ubiquitous kinase. The results suggest that colonization of unique bacterial communities coupled with deficient innate immune response is likely to impact the pathogenesis of ONJ.

  20. Oral Bisphosphonates and Upper Gastrointestinal Cancer Risks in Asians with Osteoporosis: A Nested Case-Control Study Using National Retrospective Cohort Sample Data from Korea.

    Directory of Open Access Journals (Sweden)

    Sun-Young Jung

    Full Text Available Bisphosphonate can irritate the gastrointestinal mucosa and increase the risk of esophageal or gastric cancer. The relatively high prevalence of upper gastrointestinal cancers and the widespread use of bisphosphonate in Korea call for further investigation. We conducted a case-control study to evaluate the risk of esophageal or gastric cancer after exposure to oral bisphosphonates in Korean patients with osteoporosis.We used the National Health Insurance Service-National Sample Cohort database of Korea from 2002 to 2013. Among osteoporotic patients (>40 years, cases were defined as incident diagnosis of esophageal or gastric cancer between 2006 and 2013. For each case, four controls were matched for age, sex, and income level by type of insurance. We categorized bisphosphonate use as non-user, recent user, past user, and past and recent user, depending on prescription in two periods (1 to 2 years and 2 to 4 years prior to the index date. We also assessed the duration of bisphosphonate use by measuring cumulative duration of exposure (CDE. To examine the association between oral bisphosphonates and esophageal or gastric cancer, we estimated adjusted odds ratios (aORs and 95% confidence intervals (CIs using conditional logistic regression analysis, adjusting for concomitant diseases.A total of 1,708 cases and 6,832 controls were identified. The aORs (95% CIs of recent, past, and continuous bisphosphonate use compared to non-users were 1.18 (0.93-1.51, 1.04 (0.83-1.29, and 1.25 (0.95-1.58, respectively. In addition, no significant association was observed by CDE, even when different outcome definitions were applied.This study did not prove an increased risk of esophageal or gastric cancer risk associated with bisphosphonate use, with respect to both risk windows and duration of exposure, in an Asian population-based, real-world setting.

  1. Oral bisphosphonates do not increase the risk of severe upper gastrointestinal complications: A nested case-control study

    OpenAIRE

    Ghirardi, Arianna; Scotti, Lorenza; Vedova, Gianluca; D'Oro, Luca; Lapi, Francesco; Cipriani, Francesco; Caputi, Achille; Vaccheri, Alberto; Gregori, Dario; Gesuita, Rosaria; Vestri, Annarita; Staniscia, Tommaso; Mazzaglia, Giampiero; Corrao, Giovanni; Sessa, E

    2014-01-01

    textabstractBackground: Data on the effect of oral bisphosphonates (BPs) on risk of upper gastrointestinal complications (UGIC) are conflicting. We conducted a large population-based study from a network of Italian healthcare utilization databases aimed to assess the UGIC risk associated with use of BPs in the setting of secondary prevention of osteoporotic fractures.Methods: A nested case-control study was carried out within a cohort of 68,970 patients aged 45 years or older, who have been h...

  2. Osteonecrosis of jaw associated with bisphosphonate use

    Directory of Open Access Journals (Sweden)

    Ashu Rastogi

    2012-01-01

    Full Text Available Bisphosphonates are associated with osteonecrosis of the jaw (ONJ that is defined as an area of exposed, nonvital bone in the maxilla or mandible persisting over 6-8 weeks. We describe a case of 55-year-old female who developed ONJ after tooth extraction and had been receiving oral ibandronate for osteoporosis. Diagnosis of ONJ was confirmed on CT scan. The patient was managed conservatively as she denied teriparatide therapy because of cost constraints.

  3. The impact of preadmission oral bisphosphonate use on 30-day mortality following stroke: a population-based cohort study of 100,043 patients

    Directory of Open Access Journals (Sweden)

    Christensen DH

    2015-08-01

    Full Text Available Diana Hedevang Christensen,1,2 Erzsébet Horváth-Puhó,1 Morten Schmidt,1 Christian Fynbo Christiansen,1 Lars Pedersen,1 Bente Lomholt Langdahl,2 Reimar Wernich Thomsen1 1Department of Clinical Epidemiology, 2Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark Purpose: Bisphosphonate use has been associated with increased risk of fatal stroke. We examined the association between preadmission use of oral bisphosphonates and 30-day mortality following hospitalization for stroke. Patients and methods: We conducted a nationwide population-based cohort study using medical databases and identified all patients in Denmark with a first-time hospitalization for stroke between 1 July 2004 and 31 December 2012 (N=100,043. Cox regression was used to compute adjusted hazard ratios as a measure of 30-day mortality rate ratios (MRRs associated with bisphosphonate current use (prescription filled within 90 days prior to the stroke or recent use (prescription filled in the 90–180 days prior to the stroke. Current use was further classified as new or long-term use. Results: We found 51,982 patients with acute ischemic stroke (AIS, 11,779 with intracerebral hemorrhage (ICH, 4,528 with subarachnoid hemorrhage (SAH, and 31,754 with unspecified stroke. Absolute 30-day mortality risks were increased among current vs nonusers of bisphosphonates for AIS (11.9% vs 8.5%, ICH (43.2% vs 34.5%, SAH (40.3% vs 23.2%, and unspecified strokes (18.8% vs 14.0%. However, in adjusted analyses, current bisphosphonate use did not increase 30-day mortality from AIS (MRR, 0.87; 95% confidence interval [CI]: 0.75, 1.01; ICH (MRR, 1.05; 95% CI: 0.90, 1.23; SAH (MRR, 1.15; 95% CI: 0.83, 1.61; or unspecified stroke (MRR, 0.94; 95% CI: 0.81, 1.09. Likewise, no association with mortality was found for recent use. Adjusted analyses by type of bisphosphonate showed increased mortality following stroke among new users of etidronate (MRR, 1.40; 95% CI

  4. Four-week oral toxicity study with erythritol in rats

    NARCIS (Netherlands)

    Til, H.P.; Modderman, J.

    1996-01-01

    Erythritol was orally administered to Wistar rats at dietary levels of 0, 5, and 10% for 4 weeks. Soft stools and diarrhea were observed in male and female animals of the 10% group and in female animals of the 5% group. These symptoms disappeared during the course of the study. Mean body weights of

  5. Four-week oral toxicity study with erythritol in rats

    NARCIS (Netherlands)

    Til, H.P.; Modderman, J.

    1996-01-01

    Erythritol was orally administered to Wistar rats at dietary levels of 0, 5, and 10% for 4 weeks. Soft stools and diarrhea were observed in male and female animals of the 10% group and in female animals of the 5% group. These symptoms disappeared during the course of the study. Mean body weights of

  6. Oral 4-week and 13-week toxicity studies of polyvinyl acetate vinyl laurate copolymer in rats.

    Science.gov (United States)

    Messinger, Horst; Bär, Albert

    2014-10-01

    Polyvinyl acetate vinyl laurate copolymer (PVAcVL) is a useful component of gum base for chewing gum production. The safety of PVAcVL was examined in a 4-week and a 13-week oral toxicity study in rats. Finely powdered PVAcVL was administered with the diet at levels of 1.25%, 2.0% and 5% in the 4-week study and 1.25%, 2.5% and 5% in the 13-week study. There were no treatment related effects on mortality, bodyweight gains feed efficiency, ophthalmoscopic findings, hematological and clinical chemical parameters, neurobehavioral observations as well as gross and histopathological changes of standard organs and tissues. The highest dose tested in the 13-week study (3783 and 4396mg/kgbw/d for males and females, respectively) proved to be a NOAEL.

  7. Oral squamous cell carcinoma arising in a patient after hematopoietic stem cell transplantation with bisphosphonate-related osteonecrosis of the jaws.

    Science.gov (United States)

    Arduino, Paolo G; Scully, Crispian; Chiusa, Luigi; Broccoletti, Roberto

    2015-01-01

    A 55-year-old man with a history of acute myeloid leukaemia treated with hematopoietic stem cell transplantation and with a 5-year history of bisphosphonate-related osteonecrosis of the jaws, following 12 cycles of intravenous zoledronic acid therapy, presented in December 2009 with a history of increasingly severe unilateral lower jaw pain. Oral examination revealed, as previously, exposed bone in the left mandible, but also a new exophytic mass on the lower-left buccal mucosa. Biopsy confirmed a diagnosis of oral squamous cell carcinoma. To the best of our knowledge, this is the first report of an oral squamous cell carcinoma that appeared adjacent to an area of osteochemonecrosis.

  8. Physicians' perspectives on the treatment of osteoporosis patients with bisphosphonates

    Directory of Open Access Journals (Sweden)

    Gu T

    2016-02-01

    Full Text Available Tao Gu,1 Debra F Eisenberg Lawrence,1 Judith J Stephenson,1 Jingbo Yu2 1HealthCore, Wilmington, DE, 2Merck & Co., Inc., Kenilworth, NJ, USA Background: Noncompliance with bisphosphonate therapy among osteoporosis patients attenuates the reduction of fracture risk. The objective of this study was to assess physicians’ prescribing considerations, preferences for osteoporosis treatments, and perceptions of patients’ compliance with oral bisphosphonates. Methods: This was an online survey of US physicians identified in the HealthCore Integrated Research Database (HIRDSM as prescribing oral bisphosphonates to women aged ≥55 years. The survey gauged physicians’ prescribing considerations and preferences for various types of osteoporosis medications. The physicians were asked to predict patient persistence and compliance, and rate various reasons for noncompliance. Results: Bone mineral density, long-term medication use (eg, corticosteroids, and a history of fracture were ranked as major considerations by 94.9%, 88.6%, and 86.7% of participating physicians (N=158, respectively, when deciding whether to treat an osteoporosis patient. Most physicians expressed a preference for prescribing weekly or monthly oral bisphosphonates, for both newly diagnosed patients (54.4% and 34.2%, respectively and long-term users of oral bisphosphonates (40.5% and 36.1%, respectively. Most physicians (23.4% always, 58.9% sometimes incorporated a drug holiday into their prescribing patterns. Although most physicians predicted that more than half of the patients would comply with the prescribed medication for at least a year, 17.7% predicted that less than half of the patients would be compliant in the 1st year, and 29.7% predicted the same result for compliance beyond 1 year. In the opinion of the majority of physicians, the major reasons for noncompliance with oral bisphosphonates were intolerance of a medication due to a gastrointestinal condition (71.5% and

  9. Incidence of fractures of the femur, including subtrochanteric, up to 8 years since initiation of oral bisphosphonate therapy

    DEFF Research Database (Denmark)

    Pazianas, M; Abrahamsen, B; Wang, Y;

    2012-01-01

    In a cohort study of users of bisphosphonates, we evaluated the incidence of fragility fractures at all sites on the femur following for up to 8 years of therapy with alendronate or risedronate. We did not find evidence for a reversal of fracture protection with long-term use of bisphosphonates. ...

  10. Incidence and Predictors of Multiple Fractures Despite High Adherence to Oral Bisphosphonates: A Binational Population-Based Cohort Study.

    Science.gov (United States)

    Hawley, Samuel; Javaid, M Kassim; Rubin, Katrine H; Judge, Andrew; Arden, Nigel K; Vestergaard, Peter; Eastell, Richard; Diez-Perez, Adolfo; Cooper, Cyrus; Abrahamsen, Bo; Prieto-Alhambra, Daniel

    2016-01-01

    Oral bisphosphonates (BPs) are highly effective in preventing fractures and are recommended first-line therapies for patients with osteoporosis. We identified the incidence and predictors of oral BP treatment failure, defined as the incidence of two or more fractures while on treatment (≥2 FWOT) among users with high adherence. Fractures were considered from 6 months after treatment initiation and up to 6 months after discontinuation. Data from computerized records and pharmacy invoices were obtained from Sistema d'Informació per al Desenvolupament de l'Investigació en Atenció Primària (SIDIAP; Catalonia, Spain) and Danish Health Registries (Denmark) for all incident users of oral BPs in 2006-2007 and 2000-2001, respectively. Fine and Gray survival models using backward-stepwise selection (p-entry 0.049; p- exit 0.10) and accounting for the competing risk of therapy cessation were used to identify predictors of ≥2 FWOT among patients having persisted with treatment ≥6 months with overall medication possession ratio (MPR) ≥80%. Incidence of ≥2 FWOT was 2.4 (95% confidence interval [CI], 1.8 to 3.2) and 1.7 (95% CI, 1.2 to 2.2) per 1000 patient-years (PYs) within Catalonia and Denmark, respectively. Older age was predictive of ≥2 FWOT in both Catalonian and Danish cohorts: subhazard ratio (SHR) = 2.28 (95% CI, 1.11 to 4.68) and SHR = 2.61 (95% CI, 0.98 to 6.95), respectively, for 65 to history of recent or older fracture, SHR = 3.40 (95% CI, 1.50 to 7.68) and SHR = 2.08 (95% CI: 1.04-4.15), respectively (Denmark). Even among highly adherent users of oral BP therapy, a minority sustain multiple fractures while on treatment. Older age was predictive of increased risk within both study populations, as was history of recent/old fracture and dementia within one but not both populations. Additional and/or alternative strategies should be investigated for these patients. © 2015 American Society for Bone and Mineral Research.

  11. Incidence and Predictors of Multiple Fractures Despite High Adherence to Oral Bisphosphonates

    DEFF Research Database (Denmark)

    Hawley, Samuel; Javaid, M Kassim; Rubin, Katrine H

    2016-01-01

    with high adherence. Fractures were considered after six months from treatment initiation and up to six months after discontinuation. Data from computerized records and pharmacy invoices were obtained from Sistema d'Informació per al Desenvolupament de l'Investigació en Atenció Primària (SIDIAP) (Catalonia...... predictors of ≥2 FWOT among patients having persisted with treatment ≥6months with overall medication possession ratio (MPR) ≥80%. Incidence of ≥2 FWOT was 2.4 (95% Confidence Interval (CI): 1.8-3.2) and 1.7 (95% CI: 1.2-2.2) per 1000 Person Years (PYs) within Catalonia and Denmark respectively. Older age...... of ≥2 FWOT identified within only one cohort were dementia, SHR = 4.46 (95% CI: 1.02-19.4) (SIDIAP) and history of recent or older fracture, SHR = 3.40 (95% CI: 1.50-7.68) and SHR = 2.08 (95% CI: 1.04-4.15) respectively (Denmark). Even among highly adherent users of oral BP therapy, a minority sustain...

  12. An unusual case of atrophic mandible fracture in a patient with osteogenesis imperfecta and on oral bisphosphonate therapy: Case report

    Directory of Open Access Journals (Sweden)

    Abdulrahman Al-Osaimi

    2014-04-01

    Full Text Available Fractures of severely atrophic (height < 10 mm edentulous mandibles are infrequent and challenging to manage. Factors such as sclerotic bone and decreased vascularity combined with systemic diseases complicate the management of such fractures. Osteogenesis imperfecta (OI is a heterogeneous group of inherited disorders of type I collagen metabolism. Patients with OI characteristically present with histories of long bone fractures, deformities, blue sclerae, and opalescent dentin. However, fractures of the facial skeleton are rare. Bisphosphonate therapy has been proven to effectively reduce the fracture risk in patients with OI. The purpose of this clinical report is to present an unusual case of spontaneous fracture of the atrophic mandible in a patient with OI. Despite open reduction and internal fixation (ORIF with miniplate osteosynthesis, the patient developed a second fracture at a screw placement site distal to the first fracture. The patient was successfully treated with ORIF using locking reconstruction plates fixed in the symphyseal and angle regions. Bone healing following ORIF was normal, and no clinical sign of osteonecrosis as a result of bisphosphonate therapy was observed. Patients with OI can present with spontaneous fractures of already weakened mandibles. Although such fractures can be managed with care using established protocols, further research is required to examine the effects of concomitant medication, such as bisphosphonates.

  13. A Review of Bisphosphonates and Bisphosphonate-related Osteonecrosis of the Jaw

    Directory of Open Access Journals (Sweden)

    Zargaran M.

    2011-10-01

    Full Text Available Statement of Problems: Bisphosphonates are a class of agents used in treating a variety of bone diseases, including osteoporosis, multiple myeloma and hypocalcemia due to malignancy. Despite the benefits related to the use of these medications, in recent years, numerous cases of bisphosphonate-related osteonecrosis of the jaws (BRONJ of patients treated with oral/IV bisphosphonates have been reported. The BRONJ phenomenon is a serious complication, presenting as an exposure of alveolar bone either spontaneously or secondary to invasive oral surgical procedures.Purpose: This review aimed to warn dentists and dental specialists about BRONJ and propose guidelines for diagnosis, staging, management and treatment selection based on the available data and the authors’ experiences.Conclusion: All the patients treated with oral or IV bisphosphonate therapyare are at risk of BRONJ. Suggested guidelines for these two applied forms of bisphosphonates vary. In IV bisphosphonate therapy, all dentoalveolar surgeries are contraindicated and should be avoided. However, the indications are more controversial in the cases of bisphosphonates administered via the oral route and are related to the duration of treatment.

  14. Adjuvant bisphosphonates in early breast cancer

    DEFF Research Database (Denmark)

    Hadji, P; Coleman, R E; Wilson, C

    2016-01-01

    regulatory approval for either of these potential indications. This consensus paper provides a review of the evidence and offers guidance to breast cancer clinicians on the use of bisphosphonates in early breast cancer. Using the nominal group methodology for consensus, a systematic review of the literature...... significant benefits of bisphosphonates on the development of bone metastases and breast cancer mortality in post-menopausal women or those receiving ovarian suppression therapy. Therefore, the panel recommends that bisphosphonates (either intravenous zoledronic acid or oral clodronate) are considered as part...

  15. Ethylbenzene: 4- and 13-week rat oral toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Mellert, Werner; Deckardt, Klaus; Kaufmann, Wolfgang; Ravenzwaay, Bennard van [BASF Aktiengesellschaft, Department of Product Safety, Ludwigshafen (Germany)

    2007-05-15

    Ethylbenzene was administered to groups of male and female Wistar rats by gavage for 4 (n = 5/dose/sex) and 13 weeks (n = 10/dose/sex) (OECD 408) at doses of 0 (vehicle control), 75, 250, and 750 mg/kg bodyweight/day (mg/kg bw/day), administered am/pm as half doses. In the 4-week study, {>=}250 mg/kg increased serum alanine aminotransferase, total bilirubin and cholesterol, liver weights and centrilobular hepatocyte hypertrophy, and kidney weights; males also had post-dose salivation, increased urinary epithelial cell casts and cells, and hyaline droplet nephropathy. In the 13-week study, {>=}250 mg/kg increased water consumption and produced post-dose salivation. Liver-related effects: increased serum alanine aminotransferase, gamma-glutamyltransferase, bilirubin, total protein, albumin and globulins, cholesterol, liver weights and centrilobular hepatocyte hypertrophy, and reduced prothrombin times. Kidney-related effects: increased serum potassium, calcium, magnesium, kidney weights, and (males only) urea and hyaline droplets in renal tubular epithelium, and reduced sodium (females only); creatinine was reduced in 750 mg/kg males. The NOAEL of ethylbenzene in these studies, based on hepatocyte hypertrophy and liver- and kidney-related clinical chemistry changes, was 75 mg/kg bw/day. (orig.)

  16. Adjuvant aqueous ozone in the treatment of bisphosphonate induced necrosis of the jaws: report of two cases and long-term follow-up.

    Science.gov (United States)

    Brozoski, M A; Lemos, C A; Da Graça Naclério-Homem, M; Deboni, M C Z

    2014-01-01

    Bisphosphonate induced necrosis of the jaws (BONJ) does not have a unique protocol of treatment and many therapeutic approaches have been arising in oral medicine with debatable results. A male and a female attended the University Oral Surgery Clinic presenting oral bone lesions induced by intravenous and oral bisphosphonates respectively as complications of dental extraction. Treatment included daily mouthwashes and weekly intra oral irrigations with 4 mg/L of aqueous-ozone, antibiotic therapy and sequential superficial debridment for sequestrectomies. Long-standing follow-ups showed complete mucosa covering of exposed bone area and resolution of purulent secretion. Antibacterial and antifungal properties of aqueous ozone may have played important roles in the treatment. The outcome measured intra oral examination and panoramic radiographs of the affected bone. The application of aqueous ozone daily mouthwashes and weekly professional irrigation were safe; free from adverse effects, easily of handling and worked as an important adjuvant therapeutic strategy for the treatment of BONJ.

  17. Bisphosphonate treatment recommendations for oncologists.

    Science.gov (United States)

    von Moos, Roger

    2005-01-01

    Renal safety is an important consideration for oncologists who are treating patients with bisphosphonates. In recent years, there has been increasing awareness about the development of bisphosphonate-induced nephrotoxicity. This has emerged mainly from increased clinical experience with zoledronic acid (Zometa); Novartis Pharmaceuticals Corporation, East Hanover, NJ, http://www.pharma.us.novartis.com). For this reason, the U.S. and European product labels for i.v. zoledronic acid were recently updated to include additional renal safety cautions, including dose adjustment in patients with mild-to-moderate renal impairment. However, renal toxicity is not a class effect. The product label for ibandronate (Bondronat), F. Hoffmann-La Roche Ltd., Basel, Switzerland, http://www.roche.com) has remained unchanged since the launch of the drug in the European Union in 2003. Ibandronate does not require mandatory monitoring of kidney function prior to each infusion. In addition, ibandronate can be used in patients with varying degrees of renal impairment. It also can be used without restrictions for nephrotoxic medications, and dose adjustment is only required in patients with severe renal impairment. Clinical implications of the renal safety of ibandronate include reducing the physician and nursing time needed for managing the adverse renal events associated with bisphosphonate therapy and dosing based on renal function. There also are no added renal safety risks and fewer inconvenient hospital visits with ibandronate therapy. In addition to i.v. ibandronate, an oral formulation of the drug is available. Oral ibandronate therapy is especially desirable because the medication is convenient (with a small, once-daily tablet that can be taken at home), reducing the health care costs associated with infusions. Clinical studies also indicate that 50 mg oral ibandronate has an efficacy similar to that of i.v. bisphosphonates and is associated with a low incidence of adverse

  18. Subchronic (13-week) oral toxicity study of α-cyclodextrin in dogs

    NARCIS (Netherlands)

    Lina, B.A.R.; Bär, A.

    2004-01-01

    The oral toxicity of α-cyclodextrin (α-CD) was examined in a 13-week feeding study in which groups of Beagle dogs received α-CD in the diet at concentrations of 0 (control), 5, 10, or 20% (4dogs/sex/group). No treatment-related changes were noted in behavior or appearance of the dogs and no mortalit

  19. Subchronic (13-week) oral toxicity study of y-cyclodextrin in dogs

    NARCIS (Netherlands)

    Til, H.P.; Bär, A.

    1998-01-01

    The oral toxicity of γ-cyclodextrin (γ- CD) was examined in a 13-week feeding study in which four groups of four male and four female Beagle dogs received γ-CD in the diet at concentrations of 0 (control), 5, 10, or 20%. No treatment-related changes were noted in behavior or appearance of the dogs a

  20. Radiographic features of bisphosphonate therapy in pediatric patients

    Energy Technology Data Exchange (ETDEWEB)

    Grissom, L.E.; Theodore Harcke, H. [Dept. of Medical Imaging, Alfred I. duPont Hospital for Children, Nemours Children' s Clinic, Wilmington, DE (United States)

    2003-04-01

    Background: Pediatric patients are being treated with bisphosphonates for low bone mineral density. Skeletal radiographic findings have been described with bisphosphonates given orally and intravenously. Objective: To determine and describe the radiographic findings of cyclic intravenous bisphosphonate therapy in the growing skeleton. Materials and methods: Retrospective review of radiographs of 32 patients with osteogenesis imperfecta or cerebral palsy treated with intravenous bisphosphonates on a quarterly schedule. Results: Principal observations were metaphyseal bands and increased bone mineral density. The bands varied in spacing according to the age of the patient, rate of growth, and the location of the metaphysis. Fractures continued to be seen in patients with osteogenesis imperfecta. Conclusion: Cyclic bisphosphonate therapy results in distinctive radiographic findings in the growing skeleton. (orig.)

  1. BISPHOSPHONATE-INDUCED MAXILLOFACIAL OSTEONECROSIS IN OSTEOPOROTIC INDIVIDUALS

    Science.gov (United States)

    da Silva Santos, Paulo Sérgio; Oliveira, Márcio Augusto; Felix, Valtuir Barbosa

    2015-01-01

    Bisphosphonate-related osteonecrosis of the maxillae may be an important complication of long-term osteoporosis treatment. The possibility of osteonecrosis of the maxillae in patients exposed to nitrogenated bisphosphonates was first described in 2003. Since then, case reports and retrospective studies have demonstrated higher percentages of occurrence of osteonecrosis in patients who have used or are using bisphosphonates. Although this complication may be spontaneous, invasive oral procedures have a role as risk factors associated with dental procedures such as tooth extractions and other bone operations. In addition, tooth infections and periodontal disease have been reported to be the main risk factors for development of bisphosphonate-induced osteonecrosis of the maxillae. For this reason, dentists, general clinicians, orthopedists, geriatricians and oral-maxillofacial surgeons need to be aware of this problem and work in a multidisciplinary environment, thereby stimulating early diagnosis and prevention of further potential cases. PMID:27027044

  2. Bisphosphonate Treatment and Pregnancy

    Science.gov (United States)

    ... They are also used in the treatment of Gaucher disease. For more information on Gaucher disease, see the MotherToBaby fact sheet at http: / / www. mothertobaby. org/ files/ Gaucher_ disease. pdf . Bisphosphonates work to decrease the rate of ...

  3. Safety of bisphosphonates

    DEFF Research Database (Denmark)

    Pazianas, Michael; Abrahamsen, Bo

    2011-01-01

    the other reported associations with adverse events, osteonecrosis of the jaw (ONJ) and subtrochanteric fractures have attracted most of the attention mainly because their pathophysiology remains unclear. However, overall, only a very small proportion of patients treated with bisphosphonates, especially...

  4. Bisphosphonates: clinical experience.

    Science.gov (United States)

    Coleman, Robert E

    2004-01-01

    Bone is a preferred site of metastasis for many solid tumors, and the complications associated with bone metastases can result in significant skeletal morbidity including severe bone pain, pathologic fracture, spinal cord compression, and hypercalcemia of malignancy (HCM). Bisphosphonates are the current standard of care for preventing skeletal complications associated with bone metastases. Clinical trials investigating the benefit of bisphosphonate therapy have used a composite end point defined as a skeletal-related event (SRE) or bone event, which typically includes pathologic fracture, spinal cord compression, radiation or surgery to bone, and HCM. Bisphosphonates have been shown to significantly reduce the incidence of these events in patients with bone metastases. Zoledronic acid (Zometa; Novartis Pharmaceuticals Corp.; East Hanover, NJ), pamidronate (Aredia; Novartis Pharmaceuticals Corp.), clodronate (Bonefos; Anthra Pharmaceuticals; Princeton, NJ), and ibandronate (Bondronat; Hoffmann-La Roche Inc.; Nutley, NJ) all have demonstrated efficacy superior to that of placebo in patients with breast cancer. Zoledronic acid is the only bisphosphonate that has been compared directly with pamidronate, and it was shown by multiple event analysis to be significantly more effective at reducing the risk of an SRE. In patients with prostate cancer, clodronate, etidronate (Didronel; Procter and Gamble Pharmaceuticals, Inc.; Cincinnati, OH), and pamidronate have demonstrated transient palliation of bone pain. However, zoledronic acid is the only bisphosphonate to demonstrate both significant and sustained pain reduction and a significantly lower incidence and longer time to onset of SREs compared with placebo. Zoledronic acid is also the only bisphosphonate to demonstrate efficacy in patients with bone metastases from a variety of other solid tumors, including lung cancer and renal cell carcinoma. In conclusion, bisphosphonates effectively reduce skeletal complications in

  5. Toxicokinetic assessment of methylphenidate (Ritalin) in a 13-week oral toxicity study in dogs.

    Science.gov (United States)

    Bakhtiar, Ray; Ramos, Luis; Tse, Francis L S

    2004-01-01

    Ritalin or methylphenidate (MPH) is often prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. The therapeutic activity of MPH is principally due to D-threo-[2R,2'R]-MPH. Hence, in order to establish a kinetic relationship between doses and exposure levels in a non-rodent species, a 13-week oral (capsule) toxicity study of D-threo-[2R,2'R]-MPH was performed in beagle dogs. A previously reported chiral liquid chromatography tandem mass spectrometry (LC-MS/MS) with a limit of quantification (LLOQ) of 1.09 ng/ml was utilized. The results of this study indicated that MPH appeared to be rapidly absorbed in dogs following oral administration. The peak concentration was reached within 1-2 h. Based on the area under the curve (AUC) values, the plasma exposure of D-MPH was over-proportional to the dose. With the exception of two groups of animals (male/female, 7.5 mg/kg/day on day 1 and male/female, 3.0 mg/kg/day on week 7), the data showed no difference in MPH concentrations between the male and female dogs. Taking the statistical variations into account, concentrations of D-MPH that were observed after 7.5 mg/kg/day doses of D-MPH and 15 mg/kg/day doses of the racemate were similar. Following the racemate doses, the concentrations of L-MPH were consistently higher than those of the D-isomer. No accumulation of MPH was observed after 13 weeks of repeated daily administration.

  6. Effect of third molar surgery on oral health-related quality of life in the first postoperative week using Dutch version of oral health impact profile-14

    NARCIS (Netherlands)

    van Wijk, A.; Kieffer, J.M.; Lindeboom, J.H.

    2009-01-01

    Purpose: The present study investigated the effect of third molar surgery on oral health-related quality of life, related to pain and clinical variables, in the first postoperative week using the Dutch version of the 14-item Oral Health Impact Profile. Materials and Methods: A total of 50 patients,

  7. [Bisphosphonate-related osteonecrosis of the jaw].

    Science.gov (United States)

    Atanes-Bonome, P; Atanes-Bonome, A; Ríos-Lage, P; Atanes-Sandoval, A D

    2014-04-01

    The bisphosphonates are stable inorganic pyrophosphate analogs that have demonstrated their efficacy in treatment of osteolytic lesions associated with bony metastases, and multiple myeloma, malignant hypercalcemia, Paget's disease, and osteoporosis. Several publications within the last few years have suggested that osteonecrosis of the jaw is associated with bisphosphonate therapy. The diagnosis and management strategies of the patients with bisphosphonate-related osteonecrosis of the jaw is very difficult. It is important for patients to be informed of the risk of this complication, so that they have the opportunity to assess the need for dental treatment before starting therapy. Preventive measures must be taken before, during, and after treatment with bisphosphonates. If osteonecrosis of the jaw is present, management should be conservative: oral chlorhexidine and antibiotics. Surgical treatment should be reserved for those patients who are symptomatic. Copyright © 2013 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  8. Diagnóstico, prevención y tratamiento de la osteonecrosis de los maxilares por bisfosfonatos: Recomendaciones de la Sociedad Española de Cirugía Oral y Maxilofacial (SECOM Diagnosis, prevention, and treatment of bisphosphonate-associated osteonecrosis of the jaw: Recommendations of the Spanish Society of Oral and Maxillofacial Surgery (SECOM

    Directory of Open Access Journals (Sweden)

    L.M. Junquera

    2008-06-01

    Full Text Available Los bisfosfonatos son análogos estables de los pirofosfatos inorgánicos que han demostrado su eficacia para el tratamiento de diversas patologías, como las lesiones osteolíticas asociadas a metástasis óseas o al mieloma múltiple, la hipercalcemia maligna, la enfermedad de Paget y la osteoporosis. En la actualidad se podría hablar, al menos académicamente, de dos entidades con diferentes grados de información científica: las osteonecrosis en relación con la administración intravenosa de estos medicamentos y las osteonecrosis en relación con la administración oral de los mismos. Para el primer grupo las estrategias de prevención y tratamiento empiezan a estar consolidadas, mientras que para el segundo se precisará de una mayor documentación científica para alcanzar este objetivo. Facilitar el diagnóstico clínico y complementario de las osteonecrosis por bisfosfonatos por parte de los especialistas de la salud oral (cirujanos orales y maxilofaciales, odontólogos y estomatólogos. Los objetivos del presente artículo son explicitar las medidas preventivas más apropiadas para limitar el número de casos de esta patología, a la luz de los conocimientos actuales, detallar la forma de tratamiento más reconocida para los diferentes estadios de la osteonecrosis, una vez establecida así como proporcionar un documento para la buena praxis médica y odontológica en los pacientes que padecen esta enfermedad o estén en riesgo de sufrirla. Este documento ha sido aprobado por la Comisión Científica de la SECOM.The bisphosphonates are stable inorganic pyrophosphate analogs that have demonstrated their efficacy in the treatment of a variety of pathologies, such as osteolytic lesions associated with bony metastases or multiple myeloma, malignant hypercalcemia, Paget’s disease, and osteoporosis. Currently, two disease entities supported by different degrees of scientific evidence can be characterized, at least academically

  9. BISPHOSPHONATE-INDUCED OSTEONECROSIS OF THE JAW AND GUIDELINES FOR DIAGNOSIS, STAGING AND DENTAL MANAGEMENT: REVIEW

    Directory of Open Access Journals (Sweden)

    Santosh

    2014-06-01

    Full Text Available : Bisphosphonate-associated osteonecrosis of the jaw, often abbreviated as BON, BON of the jaw or even BRONJ, is a recently discovered dental phenomenon that may lead to surgical complication in the form of impaired wound healing following oral or periodontal surgery or endodontic therapy. 1 In 2003, the first reports describing osteonecrosis of the jaw in patients receiving bisphosphonates were published. About 95% of these cases occurred among cancer patients receiving high-dose intravenous bisphosphonates. Approximately 5% of the reported cases have been in osteoporosis patients receiving low-dose bisphosphonate therapy

  10. Pharmacokinetics and pharmacodynamics of oral testosterone enanthate plus dutasteride for 4 weeks in normal men: implications for male hormonal contraception.

    Science.gov (United States)

    Amory, John K; Kalhorn, Thomas F; Page, Stephanie T

    2008-01-01

    Oral administration of testosterone enanthate (TE) and dutasteride increases serum testosterone and might be useful for male hormonal contraception. To ascertain the contraceptive potential of oral TE and dutasteride by determining the degree of gonadotropin suppression mediated by 4 weeks of oral TE plus dutasteride, 20 healthy young men were randomly assigned to 4 weeks of either 400 mg oral TE twice daily or 800 mg oral TE once daily in a double-blinded, controlled fashion at a single site. All men received 0.5 mg dutasteride daily. Blood for measurement of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, dihydrotesterone (DHT), and estradiol was obtained prior to treatment, weekly during treatment, and 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours after the morning dose on the last day of treatment. FSH was significantly suppressed throughout treatment with 800 mg TE once daily and after 4 weeks of treatment with 400 mg TE twice daily. LH was significantly suppressed after 2 weeks of treatment with 800 mg TE, but not with 400 mg TE. Serum DHT was suppressed and serum estradiol increased during treatment in both groups. High-density lipoprotein cholesterol was suppresed during treatment, but liver function tests, hematocrit, creatinine, mood, and sexual function were unaffected. The administration of 800 mg oral TE daily combined with dutasteride for 28 days significantly suppresses gonadotropins without untoward side effects and might have utility as part of a male hormonal contraceptive regimen.

  11. Microscopic Evaluation of the Effect of Oral Microbiota on the Development of Bisphosphonate-Related Osteonecrosis of the Jaws in Rats

    Directory of Open Access Journals (Sweden)

    Felipe M. Silveira

    2017-01-01

    Full Text Available Objectives: Osteonecrosis of the jaws is a side effect associated with the use of bisphosphonates. Using histologic analysis, this study aimed to evaluate the influence of microbial colonies in the development of osteonecrosis in the jaws of rats subjected to nitrogenous and non-nitrogenous bisphosphonates, undergoing surgical procedures. Material and Methods: Thirty-four rats (Rattus norvegicus, Wistar strain were allocated randomly into three groups: 12 animals treated with zoledronic acid; 12 animals treated with clodronate; and 10 animals treated with saline. Sixty days after the start of treatment, the animals underwent three extractions of the upper right molars. After 120 days of drug administration, the rats were killed. Histologic analysis was performed on specimens stained with hematoxylin and eosin by the technique of manual counting points using Image-Pro Plus software on images of the right hemimaxilla. Results: Osteonecrosis was induced in the test groups. There was no statistically significant association between the presence of microbial colonies and the presence of non-vital bone (Kruskal-Wallis, P > 0.05. Conclusions: Use of zoledronic acid was associated with non-vital bone and the results suggested that the presence of microbial colonies does not lead to osteonecrosis.

  12. Bisphosphonate-Related Osteonecrosis of the Jaws: a real Challenge for Dentists

    Directory of Open Access Journals (Sweden)

    Ioana-Auriţa Albu

    2015-06-01

    Full Text Available Background: Osteonecrosis of the jaw is a serious complication associated with oral and intravenous bisphosphonate therapy. Its pathogenesis is not well understood and its management is difficult. The aim of ourstudy was to evaluate the awareness of dentists in Târgu Mureş on the possibilities of treating patients who are treated with bisphosphonate in dental offices.

  13. Safety and tolerability of zoledronic acid and other bisphosphonates in osteoporosis management

    Directory of Open Access Journals (Sweden)

    Luca Dalle Carbonare

    2010-08-01

    Full Text Available Luca Dalle Carbonare, Mirko Zanatta, Adriano Gasparetto, Maria Teresa ValentiClinic of Internal Medicine D, Department of Medicine, University of Verona, ItalyAbstract: Bisphosphonates (BPs are widely used in the treatment of postmenopausal ­osteoporosis and other metabolic bone diseases. They bind strongly to bone matrix and reduce bone loss through inhibition of osteoclast activity. They are classified as nitrogen- and non-nitrogen-containing bisphosphonates (NBPs and NNBPs, respectively. The former inhibit farnesyl diphosphate synthase while the latter induce the production of toxic analogs of adenosine triphosphate. These mechanisms of action are associated with different antifracture efficacy, and NBPs show the most powerful action. Moreover, recent evidence indicates that NBPs can also stimulate osteoblast activity and differentiation. Several randomized control trials have demonstrated that NBPs significantly improve bone mineral density, suppress bone turnover, and reduce the incidence of both vertebral and nonvertebral fragility fractures. Although they are generally considered safe, some side effects are reported (esophagitis, acute phase reaction, hypocalcemia, uveitis, and compliance with therapy is often inadequate. In particular, gastrointestinal discomfort is frequent with the older daily oral administrations and is responsible for a high proportion of discontinuation. The most recent weekly and monthly formulations, and in particular the yearly infusion of zoledronate, significantly improve persistence with treatment, and optimize clinical, densitometric, and antifracture outcomes.Keywords: bisphosphonates, osteoporosis, safety, tolerability, zoledronic acid

  14. Bisphosphonate-Related Osteonecrosis of the Jaw: A Review of the Literature

    Directory of Open Access Journals (Sweden)

    Eder Alberto Sigua-Rodriguez

    2014-01-01

    Full Text Available Bisphosphonates (BPs are a class of drugs used to treat osteoporosis and malignant bone metastasis. BPs show high binding capacity to the bone matrix, especially in sites of active bone metabolism. The American Society for Bone and Mineral Research defines BRONJ as “an area of exposed bone in the maxillofacial region that has not healed within 8 weeks after identification by a healthcare provider in a patient who is receiving or has been exposed to a bisphosphonate and has not had radiation therapy to the craniofacial region.” Bisphosphonate-related osteonecrosis of the jaw (BRONJ can adversely affect quality of life, as it may produce significant morbidity. The American Association of Oral and Maxillofacial Surgeons (AAOMS considers as vitally important that information on BRONJ be disseminated to other dental and medical specialties. The purpose of this work is to offer a perspective on how dentists should manage patients on BPs, to show the benefits of accurately diagnosing BRONJ, and to present diagnostic aids and treatments strategies for the condition.

  15. Assessment of thirteen-week subchronic oral toxicity of cyadox in Beagle dogs.

    Science.gov (United States)

    Wang, Xu; Zhou, Wen; Ihsan, Awais; Chen, Dongmei; Cheng, Guyue; Hao, Haihong; Liu, Zhenli; Wang, Yulian; Yuan, Zonghui

    2015-11-01

    Cyadox (2-formylquinoxaline-N(1),N(4)-dioxide cyanocetylhydrazone) is a new antimicrobial agent and growth-promoter to be used in food-producing animals. Although its toxicity has been clearly documented in rodents, no study is available in non-rodent animals. Therefore, we studied the subchronic effects of cyadox in Beagle dogs to provide additional information with which to establish safety criteria for human exposure. For this purpose, 36 Beagle dogs, 18 males and 18 females, were divided into four groups and fed diets containing 0, 100, 450 and 2500 mg/kg of cyadox, respectively, for 13 weeks. It was found that there were no significant changes among the examined parameters, except for an increase in the level of serum potassium (K(+)) in 2500 mg/kg cyadox group in males at week 13 of the study. However, the K(+) level returned to normal during the recovery period. In conclusion, cyadox showed slight effects in Beagle dogs in the subchronic oral toxicity study. The no-observed-adverse-effect level of cyadox was considered to be 450 mg/kg diet, which equates to approximately 15.3-15.4 mg/kg b.w./day. The study provided subchronic effects of cyadox in Beagle dogs, suggesting that cyadox might present mild toxicity in non-rodents.

  16. Adverse Effects of Bisphosphonates

    DEFF Research Database (Denmark)

    Abrahamsen, Bo

    2010-01-01

    Use of bisphosphonates has been growing steadily in the last decade. This follows the introduction of simpler dosing regimes, the availability of lower-priced generics, and concerns about the safety of hormone-replacement therapy. Bisphosphonates have a relatively good safety record and are toler......Use of bisphosphonates has been growing steadily in the last decade. This follows the introduction of simpler dosing regimes, the availability of lower-priced generics, and concerns about the safety of hormone-replacement therapy. Bisphosphonates have a relatively good safety record...... and are tolerated by the majority of patients, but serious adverse events have been recorded in some cases. Only the most common of adverse effects are robustly observable in clinical trials. In general, studies were not powered to detect effects that were lower in incidence than fractures. This review of adverse...... compared with the risk of osteoporotic fractures, at least in patients with the same risk of fractures as those in the phase III trials. It is biologically plausible that atypical fragility fractures could follow from suppression of bone remodeling, but high-quality studies proving causality are lacking...

  17. Adverse effects of bisphosphonates

    DEFF Research Database (Denmark)

    Abrahamsen, Bo

    2010-01-01

    Use of bisphosphonates has been growing steadily in the last decade. This follows the introduction of simpler dosing regimes, the availability of lower-priced generics, and concerns about the safety of hormone-replacement therapy. Bisphosphonates have a relatively good safety record and are toler......Use of bisphosphonates has been growing steadily in the last decade. This follows the introduction of simpler dosing regimes, the availability of lower-priced generics, and concerns about the safety of hormone-replacement therapy. Bisphosphonates have a relatively good safety record...... and are tolerated by the majority of patients, but serious adverse events have been recorded in some cases. Only the most common of adverse effects are robustly observable in clinical trials. In general, studies were not powered to detect effects that were lower in incidence than fractures. This review of adverse...... compared with the risk of osteoporotic fractures, at least in patients with the same risk of fractures as those in the phase III trials. It is biologically plausible that atypical fragility fractures could follow from suppression of bone remodeling, but high-quality studies proving causality are lacking...

  18. Management of bisphosphonate-related osteonecrosis of the jaw with a platelet-rich fibrin membrane: technical report.

    Science.gov (United States)

    Soydan, Sıdıka Sinem; Uckan, Sina

    2014-02-01

    Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a challenging complication resulting from the long-term application of bisphosphonates. In most cases, BRONJ occurs after a surgical procedure involving the jawbone. Currently, the management of BRONJ remains controversial, and there is no definitive treatment other than palliative methods. Platelet-rich fibrin (PRF) represents a relatively new biotechnology for the stimulation and acceleration of tissue healing and bone regeneration. This technical note describes the total closure of moderate bone exposure in persistent BRONJ in 2 weeks with a double-layer PRF membrane. PRF may stimulate gingival healing and act as a barrier membrane between the alveolar bone and the oral cavity. PRF may offer a fast, easy, and effective alternative method for the closure of bone exposure in BRONJ.

  19. Safety evaluation of orally administered afoxolaner in 8-week-old dogs.

    Science.gov (United States)

    Drag, Marlene; Saik, Judith; Harriman, Jay; Larsen, Diane

    2014-04-02

    The safety profile of afoxolaner, a new isoxazoline molecule, was evaluated following the regulatory requirements when administered six times orally in a soft chewable formulation at a dose of at least 1×, 3× or 5× the maximum exposure dose (6.3mg/kg) in 8-week-old Beagle dogs. Thirty-two healthy puppies (16 males and 16 females) were enrolled and allocated randomly to one of four treatment groups. Treatments were administered at three, one-month dose intervals (Days 0, 28 and 56) followed by three, 2-week dose intervals (Days 84, 98 and 112). The study ended at Day 126. The groups were: Group 1: non-treated control; Group 2: afoxolaner chews administered at a dosage of at least 6.3mg/kg (1×); Group 3: afoxolaner chews administered at a dosage of at least 18.9 mg/kg (3×); and Group 4: afoxolaner chews administered at a dosage of at least 31.5mg/kg (5×). All dogs were examined for general health twice a day beginning on at least Day-14. Physical examinations, and blood collections for clinical pathology analysis and afoxolaner plasma concentrations, were performed throughout the study. On Day 126, 2 weeks following the last treatment, all dogs were humanely euthanized prior to the conduction of a full necropsy with tissue collection. No afoxolaner-related changes were observed in growth, physical variables, clinical pathology variables, or tissues examined histologically. No clinically or statistically significant health abnormalities related to the administration of afoxolaner were observed. Vomiting and diarrhea were observed sporadically across all groups including the controls. The kinetics of afoxolaner plasma concentrations was linear following 6 doses of 6.3, 18.9 and 31.5mg/kg and dose proportionality was demonstrated. There were no statistical differences (pafoxolaner was shown to be safe when administered repeatedly in a soft chewable formulation at up to 5× the maximum exposure dose in dogs as young as 8 weeks of age.

  20. Seguridad de los bifosfonatos Safety of bisphosphonates

    Directory of Open Access Journals (Sweden)

    M. A. Vidal

    2011-02-01

    Full Text Available Existe una amplia indicación de uso y la mayoría de los tratamientos con bifosfonatos son prolongados en el tiempo, lo que ha favorecido la aparición de nuevos efectos adversos asociados a su uso: la osteonecrosis de los maxilares (ONM, el dolor grave, las fracturas atípicas, la estomatitis y los trastornos inflamatorios oculares. El objetivo de este artículo es hacer un repaso del estado actual de la seguridad de estos fármacos, describiendo la aparición de los nuevos efectos adversos. Los bifosfonatos pueden dividirse en dos tipos en función de su estructura química y mecanismo de acción, la presencia o no de nitrógeno en su molécula conlleva diferencias de potencia. No disponemos de pruebas que nos permitan identificar a los pacientes que presenten un riesgo más elevado de desarrollar ONM para tomar las medidas preventivas oportunas. No se ha podido demostrar la relación causal de los bifosfonatos con las fracturas atípicas, pero se recomienda prescribir bifosfonatos en pacientes que se recuperan de una fractura reciente. Tampoco existe evidencia de que los bifosfonatos sean los causantes del dolor óseo, muscular o articular, pero hay tener en cuenta en la mayoría de las ocasiones que el dolor desaparece al suspender el tratamiento con bifosfonatos. No se pueden establecer conclusiones definitivas para establecer una relación causal entre la utilización de bifosfonatos y el aumento del riesgo de FA. Habrá que considerar la existencia de otros factores de riesgo e individualizar, así como vigilar la posible aparición de alteraciones del ritmo cardiaco. No se ha podido confirmar la existencia de un mayor riesgo de padecer cáncer esofágico asociado a la toma de bifosfonatos. No obstante, la FDA recomienda no prescribir bifosfonatos orales a los pacientes con esófago de Barret.Bisphosphonates are widely indicated, and most therapies using bisphosphonates are given long-term, which has favored the emergence of new

  1. Effects of 3 weeks GMP oral administration on glutamatergic parameters in mice neocortex.

    Science.gov (United States)

    Ganzella, Marcelo; Moreira, Julia Dubois; Almeida, Roberto Farina; Böhmer, Ana Elisa; Saute, Jonas Alex Morales; Holmseth, Silvia; Souza, Diogo Onofre

    2012-03-01

    Overstimulation of the glutamatergic system (excitotoxicity) is involved in various acute and chronic brain diseases. Several studies support the hypothesis that guanosine-5'-monophosphate (GMP) can modulate glutamatergic neurotransmission. The aim of this study was to evaluate the effects of chronically administered GMP on brain cortical glutamatergic parameters in mice. Additionally, we investigated the neuroprotective potential of the GMP treatment submitting cortical brain slices to oxygen and glucose deprivation (OGD). Moreover, measurements of the cerebrospinal fluid (CSF) purine levels were performed after the treatment. Mice received an oral administration of saline or GMP during 3 weeks. GMP significantly decreases the cortical brain glutamate binding and uptake. Accordingly, GMP reduced the immunocontent of the glutamate receptors subunits, NR2A/B and GluR1 (NMDA and AMPA receptors, respectively) and glutamate transporters EAAC1 and GLT1. GMP treatment significantly reduced the immunocontent of PSD-95 while did not affect the content of Snap 25, GLAST and GFAP. Moreover, GMP treatment increased the resistance of neocortex to OGD insult. The chronic GMP administration increased the CSF levels of GMP and its metabolites. Altogether, these findings suggest a potential modulatory role of GMP on neocortex glutamatergic system by promoting functional and plastic changes associated to more resistance of mice neocortex against an in vitro excitotoxicity event.

  2. Safety evaluation of orally administered afoxolaner and milbemycin oxime in eight-week-old dogs.

    Science.gov (United States)

    Drag, M; Saik, J; Harriman, J; Letendre, L; Yoon, S; Larsen, D

    2016-11-27

    The safety profile of afoxolaner (an isoxazoline molecule) when combined with milbemycin oxime (a macrocyclic lactone) was evaluated according to the regulatory requirements when administered six times orally in a soft chewable formulation at a dose of at least 1×, 3×, or 5× the maximum exposure dose in 8-week-old Beagle dogs. Thirty-two healthy puppies (16 males and 16 females) were enrolled and allocated randomly to one of four treatment groups. Three doses were administered at 28-day intervals (Days 0, 28, and 56), followed by three additional doses administered with 14-day intervals (Days 84, 98, and 112). The study ended on Day 126. Treatment groups were as follows: Group 1: untreated, sham-dosed control; Group 2: afoxolaner/milbemycin oxime chews administered at a dose of at least 5 and 1 mg/kg, respectively (1×); Group 3: afoxolaner/milbemycin oxime chews administered at a dose of at least 15 and 3 mg/kg, respectively (3); and Group 4: afoxolaner/milbemycin oxime chews administered at a dose of at least 25 and 5 mg/kg, respectively (5×). All dogs were examined for general health twice a day beginning on Day -14. Physical examinations, and blood collections for clinical pathology analysis and afoxolaner and milbemycin oxime plasma concentrations, were performed throughout the study. No afoxolaner/milbemycin oxime treatment-related changes were observed in growth, physical variables, clinical pathology variables, or tissues examined histologically. No clinically relevant or statistically significant health abnormalities related to the administration of afoxolaner/milbemycin oxime were observed. No signs of macrocyclic lactone sensitivity were observed at any time during the study. Vomiting and diarrhea were observed sporadically across all groups including the controls. Based upon the results of this study, afoxolaner/milbemycin oxime soft chewables were shown to be safe when administered repeatedly at up to 5× the maximum exposure dose in dogs as

  3. Osteonecrosis caused by Bisphosphonates: a clinical case

    Science.gov (United States)

    SPINELLI, D.; DE VICO, G.; BONINO, M.; BARLATTANI, A.; BOLLERO, P.; BARLATTANI, A.

    2010-01-01

    SUMMARY The osteonecrosis of the maxillares caused by bisphosphonates (OMB) either wrongly known or not reconised in earlier times became nowadays very important among the dentists and maxillo-facials surgeons because of the potential serious consequences that might bring in the oral cave of the patients, who are suffering already for their base condition. The goal of our work was to verify if a deep treatment and an attentive observation with a close follow-up can bring to the resolution of serious cases of ostenecrosis of the maxillares by bisphosphonantes. Although without a statistic value our case report put the basis for a chance to execute wider casistic studies. PMID:23285372

  4. Bisphosphonate-related osteonecrosis of the jaw: An insight

    Directory of Open Access Journals (Sweden)

    Shalini Kapoor

    2013-01-01

    Full Text Available Bisphosphonates are potent inhibitors of osteoclast activity that reduce bone turnover and re-establish the balance between bone resorption and formation. They are effective in multiple clinical settings including postmenopausal osteoporosis, low bone mass in men, and drug-induced bone loss. Bisphosphonate-associated osteonecrosis of jaws (BRONJ may result in serious oral complications, such as osteomyelitis and chronic exposure of necrotic bone. Dentists must be familiar with this disorder and pay special attention to all patients on bisphosphonate therapy due to their defective osteoclast function and reduced osseous tissue vascularity, leading to impaired wound healing and progressive necrosis of jaw bones. The purpose of this article is to review the history and pathogenesis of BRONJ, provide guidance to dentists on possible measures to prevent and manage patients with BRONJ.

  5. Bisphosphonate treatment in primary breast cancer: results from a randomised comparison of oral pamidronate versus no pamidronate in patients with primary breast cancer

    DEFF Research Database (Denmark)

    Kristensen, B.; Ejlertsen, B.; Mouridsen, H.T.

    2008-01-01

    PURPOSE AND PATIENTS: During the period from January 1990 to January 1996 a total of 953 patients with lymph node negative primary breast cancer were randomised to oral pamidronate (n=460) 150 mg twice daily for 4 years or no adjuvant pamidronate (n=493) in order to investigate whether oral pamid...... the trial do not support a beneficial effect of oral pamidronate on the occurrence of bone metastases or fractures in patients with primary breast cancer receiving adjuvant chemotherapy Udgivelsesdato: 2008......PURPOSE AND PATIENTS: During the period from January 1990 to January 1996 a total of 953 patients with lymph node negative primary breast cancer were randomised to oral pamidronate (n=460) 150 mg twice daily for 4 years or no adjuvant pamidronate (n=493) in order to investigate whether oral...... pamidronate can prevent the occurrence of bone metastases and fractures. The patients received adjuvant chemotherapy, loco-regional radiation therapy, but no endocrine treatment. RESULTS: During the follow-up period the number of patients with pure bone metastases was 35 in the control group and 31...

  6. The Effect of Bisphosphonate Treatment on Blood Lipid Parameters in Patients with Postmenopausal Osteoporosis

    Directory of Open Access Journals (Sweden)

    Canan Tıkız

    2005-03-01

    Full Text Available Bisphosphonates are currently the most preferred class of drugs used for the treatment of metabolic bone disease such as osteoporosis and Paget’s disease. Although their exact mechanism has not been identified, the compounds containing amino group (amino bisphosphonates were shown to decrease osteoclast activation by inhibiting mevalonate pathway. Because mevalonate pathway is essential in production of cholesterol, these compounds could also interfere with cholesterol synthesis. In the present study, the effects of aminobisphosphonates on lipid parameters in subjects who were diagnosed as osteoporosis were investigated. For this reason, 50 postmenopausal osteoporotic subjects were included in the study and 25 of them (mean age:54±9 years received alendronate sodium (70mg/week and the remaining 25 subjects (mean age:55±8 years were given risedronate sodium (35mg/week. Blood samples were analyzed at baseline and at the end of sixth months. Total cholesterol, high density cholesterol (HDL-chol, low density cholesterol (LDL-chol, triglyceride, apolipoprotein A (Apo-A, apolipoprotein B (Apo-B and lipoprotein (a (Lip a were investigated as lipid parameters. Total alkaline phophatase (TAP, bone-specific alkaline phophatase (BAP, osteocalcine (OCL and urine deoxyprydolin (DPD levels were assessed as bone remodeling markers. After six month treatment period, while significant changes were observed in bone remodeling parameters (p0.05. Our results suggest that moderate-term oral aminobisfosphonate treatment has no significant effect on blood lipid parameters.

  7. A systematic review and economic evaluation of bisphosphonates for the prevention of fragility fractures.

    Science.gov (United States)

    Davis, Sarah; Martyn-St James, Marrissa; Sanderson, Jean; Stevens, John; Goka, Edward; Rawdin, Andrew; Sadler, Susi; Wong, Ruth; Campbell, Fiona; Stevenson, Matt; Strong, Mark; Selby, Peter; Gittoes, Neil

    2016-10-01

    Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture. To evaluate the clinical effectiveness and safety of bisphosphonates [alendronic acid (Fosamax(®) and Fosamax(®) Once Weekly, Merck Sharp & Dohme Ltd), risedronic acid (Actonel(®) and Actonel Once a Week(®), Warner Chilcott UK Ltd), ibandronic acid (Bonviva(®), Roche Products Ltd) and zoledronic acid (Aclasta(®), Novartis Pharmaceuticals UK Ltd)] for the prevention of fragility fracture and to assess their cost-effectiveness at varying levels of fracture risk. For the clinical effectiveness review, six electronic databases and two trial registries were searched: MEDLINE, EMBASE, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Web of Science and BIOSIS Previews, Clinicaltrials.gov and World Health Organization International Clinical Trials Registry Platform. Searches were limited by date from 2008 until September 2014. A systematic review and network meta-analysis (NMA) of effectiveness studies were conducted. A review of published economic analyses was undertaken and a de novo health economic model was constructed. Discrete event simulation was used to estimate lifetime costs and quality-adjusted life-years (QALYs) for each bisphosphonate treatment strategy and a strategy of no treatment for a simulated cohort of patients with heterogeneous characteristics. The model was populated with effectiveness evidence from the systematic review and NMA. All other parameters were estimated from published sources. A NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Fracture risk was estimated from patient characteristics using the QFracture(®) (QFracture-2012 open source revision 38, Clinrisk Ltd, Leeds, UK) and FRAX(®) (web version 3.9, University of Sheffield, Sheffield, UK) tools. The relationship between fracture risk and incremental net benefit (INB) was

  8. Sub-chronic (13-week) oral toxicity study in rats with recombinant human lactoferrin produced in the milk of transgenic cows

    NARCIS (Netherlands)

    Appel, M.J.; Veen, H.A. van; Vietsch, H.; Salaheddine, M.; Nuijens, J.H.; Ziere, B.; Loos, F. de

    2006-01-01

    The oral toxicity of recombinant human lactoferrin (rhLF) produced in the milk of transgenic cows was investigated in Wistar rats by daily administration via oral gavage for 13 consecutive weeks, 7 days per week. The study used four groups of 20 rats/sex/dose. The control group received physiologica

  9. Effect of ethane-1-hydroxy-1,1-bisphosphonate (EHBP) on endochondral ossification lesions induced by a lethal oral dose of uranyl nitrate

    Energy Technology Data Exchange (ETDEWEB)

    Bozal, C.B.; Ubios, A.M. [University of Buenos Aires, Department of Histology and Embryology, Buenos Aires (Argentina); Martinez, A.B. [National University of Rosario, Department of Pharmacology (Argentina); Cabrini, R.L. [National Atomic Energy Commission, Department of Radiobiology (Argentina)

    2005-08-01

    A 350 mg/kg body weight (b.w.) oral dose of uranyl nitrate (UN) caused 100% mortality in mice three days after administration, due to resulting kidney lesions. Mortality decreased 50% after an oral (o) or subcutaneous (sc) dose of bisodic etidronate (EHBP). Given that bone is also a target organ for uranium (U) in acute intoxication, the aim of this work was to study the effect of exposure to a lethal oral dose of UN on endochondral ossification, and the latter's response to EHBP treatment. One hundred male Balb/c mice weighing 25 g were assigned to one of ten groups. Group I served as control. Group II received a lethal 350 mg/kg b.w. oral dose of UN by gavage. Groups III, IV, VII, and VIII received an equal dose of UN immediately followed by a single 500 mg/kg oral dose of EHBP in groups III and VII and a single 50 mg/kg subcutaneous dose of EHBP in groups IV and VIII. Groups V and IX only received a single 500 mg/kg oral dose of EHBP, and groups VI and X received a single 50 mg/kg subcutaneous dose of EHBP. The animals in groups II, III, IV, V, and VI were sacrificed 48 h after the onset of the experiment, whereas those in groups VII, VIII, IX, and X were killed at 14 days. Histologic and histomorphometric studies were performed on the femurs to determine growth cartilage width, bone volume, and metaphyseal bone activity. Our results showed that all growth cartilage and metaphyseal bone histomorphometric parameters were significantly lower in animals exposed to UN at 48 h than in controls. EHPB administration was found to prevent this condition at 48 h reaching similar values to those of controls. Although histomorphometric values did not reach control values at 14 days, they were higher than those of animals exposed to UN at 48 h not treated with EHBP. It is noteworthy that these values also decreased in animals only receiving EHBP at 14 days. Our results show that EHBP effectively ameliorates the adverse effects of a lethal dose of UN on endochondral

  10. Comparing Osteoporosis Drugs: The Bisphosphonates

    Science.gov (United States)

    Drugs to Treat Low Bone Density Comparing Osteoporosis Drugs: The Bisphosphonates What is osteoporosis (low bone density)? Osteoporosis is a condition in which the body does not build enough new bone. ...

  11. The relationship between bisphosphonate use and demographic characteristics of male osteoporosis patients

    Directory of Open Access Journals (Sweden)

    Alev Cevikoi

    2011-01-01

    Full Text Available INTRODUCTION: This study aimed to investigate a number of demographic characteristics in males with osteoporosis (OP treated with bisphosphonate and determine whether any of these measures could act as an effective indicator of medication persistence and compliance. MATERIAL AND METHOD: Among the patients with OP who applied to our clinic and were prescribed weekly oral bisphosphonate treatment, 89 patients over 50 years of age were included in this study. The demographic characteristics of these patients were evaluated. The number of medications used by the patients over the past 1 and 3 years were counted, and the persistence and compliance with bisphosphonate treatment was estimated. The patients were divided into two groups: fully compliant and noncompliant subjects. The two groups of patients were compared separately for 1 and 3 years while considering their demographic characteristics. RESULTS: The mean age of the 89 patients included in the study was 62.43 + 9.41 years. Comparisons among the studied demographic characteristics during the 1-year period of medication use indicated that the educational status of the fully compliant patients was higher. During the 3-year period of medication use, educational status was the only demographic characteristic that was determined to be significantly lower in the noncompliant patients than in the fully compliant group. CONCLUSION: Although deficiencies in medication persistence and compliance during osteoporosis treatment can lead to serious health and social problems in both genders, the causes of these deficiencies have not been thoroughly clarified. We suggest that the educational status of the patient may contribute to these deficiencies.

  12. Incident acute pseudogout and prior bisphosphonate use: Matched case–control study in the UK-Clinical Practice Research Datalink

    Science.gov (United States)

    Roddy, Edward; Muller, Sara; Paskins, Zoe; Hider, Samantha L.; Blagojevic-Bucknall, Milisa; Mallen, Christian D.

    2017-01-01

    Abstract Oral bisphosphonates are the most commonly used drugs to treat postmenopausal osteoporosis. Acute pseudogout is anecdotally reported to occur following bisphosphonate initiation but empirical data are lacking. We investigated whether treatment with oral bisphosphonates is a risk factor for incident acute pseudogout. A matched case–control study was undertaken using data from the UK-Clinical Practice Research Datalink. Adults who consulted for incident acute pseudogout between 1987 and 2012 were each matched for gender, age at pseudogout diagnosis, and general practice to up to 4 control subjects without pseudogout. The exposure of interest was a prescription for an oral bisphosphonate issued within the 60-day period prior to the date of incident acute pseudogout. Associations between incident acute pseudogout and prior bisphosphonate prescription were examined using conditional logistic regression, adjusting for hyperparathyroidism, osteoarthritis, rheumatoid arthritis, hemochromatosis, hypophosphatasia, and prescriptions for diuretics and oral corticosteroids. Two thousand eleven acute pseudogout cases were compared with 8013 matched controls without acute pseudogout (mean age [standard deviation] 72 years [14]; 52% male). One hundred twenty-three cases (6.1%) had received an oral bisphosphonate prescription in the 60-day exposure period compared with 305 controls (3.8%) (adjusted incidence rate ratio [IRR] 1.33; 95% confidence interval [CI] 1.05–1.69). This association was stronger in females (adjusted IRR 1.49; 95% CI 1.15–1.94) and was nonsignificant in males (0.83; 0.48–1.44). Incident acute pseudogout was associated with prescription of an oral bisphosphonate in the preceding 60 days. Prescribers should be aware of acute pseudogout as a possible side effect of bisphosphonate treatment. Further research is needed to explore the risks conferred by different bisphosphonates and the mechanism underlying this association. PMID:28328803

  13. Effects of acute and 2-week administration of oral salbutamol on exercise performance and muscle strength in athletes

    DEFF Research Database (Denmark)

    Hostrup, Morten; Kalsen, Anders; Auchenberg, Michael

    2016-01-01

    Our objective was to investigate effects of acute and 2-week administration of oral salbutamol on repeated sprint ability, exercise performance, and muscle strength in elite endurance athletes. Twenty male elite athletes [VO2max : 69.4 ± 1.8 (Mean ± SE) mL/min/kg], aged 25.9 ± 1.4 years, were...... benefits athletes' sprint ability. Thus, the present study supports the restriction of oral salbutamol in competitive sports........ deltoideus were measured, followed by three repeated Wingate tests. Exercise performance at 110% of VO2max was determined on a bike ergometer. Acute administration of salbutamol increased peak power during first Wingate test by 4.1 ± 1.7% (P 

  14. Comparison of raloxifene and bisphosphonates based on adherence and treatment satisfaction in postmenopausal Asian women.

    Science.gov (United States)

    Pasion, Ellewellyn G; Sivananthan, Shanmugam K; Kung, Annie Wai-Chee; Chen, Sung-Hsiung; Chen, Yen-Jen; Mirasol, Roberto; Tay, Boon Keng; Shah, Ghazanfar Ali; Khan, Mansoor Ali; Tam, Frances; Hall, Belinda J; Thiebaud, Daniel

    2007-01-01

    We evaluated adherence with raloxifene therapy compared with daily bisphosphonate in Asian postmenopausal women at increased risk of osteoporotic fractures. In this 12-month observational study conducted in Asia (Hong Kong, Malaysia, Pakistan, Philippines, Singapore, Taiwan), 984 postmenopausal women (aged 55 years or older) were treated with raloxifene 60 mg/day (n = 707; 72%) or daily bisphosphonate (alendronate 10 mg/day; n = 206; 21%, or risedronate 5 mg/day; n = 71; 7%) during their normal course of care. Patients were assessed at baseline, 6, and 12 months. Baseline characteristics (including age, race, education, menopausal status, and baseline fractures) were comparable between the raloxifene and bisphosphonate groups. More women on raloxifene completed the study compared with those on bisphosphonate (50.2% versus 37.5%; P Patients also took raloxifene for a longer period than bisphosphonate (median, 356 versus 348 days; P = 0.011). Compared with those taking bisphosphonate, significantly fewer patients taking raloxifene discontinued the study because of stopping treatment (5.7% versus 10.1%, P = 0.017) or changing treatment (2.8% versus 9.7%, P patients compared with 0 raloxifene patients. The percentage of patients who had consumed 80% or more of their study medication was similar for raloxifene patients (48-56 weeks; 95.2%) and bisphosphonate patients (48-56 weeks; 93.3%). More raloxifene patients responded that they were satisfied with their medication than bisphosphonate patients at 48-56 weeks (P = 0.002). We concluded that Asian postmenopausal women at increased risk of osteoporotic fractures showed a greater propensity to remain on raloxifene compared with bisphosphonate. The women on raloxifene exhibited lower discontinuation rates and higher treatment satisfaction.

  15. Association of dental and periodontal status with bisphosphonate-related osteonecrosis of the jaws. A retrospective case controlled study

    OpenAIRE

    Kos, Marcin

    2014-01-01

    Introduction To assess the association of oral hygiene, dental caries, and periodontal status with bisphosphonate-related osteonecrosis of the jaws. Material and methods A retrospective case-control study on 81 patients treated for neoplasms with bone metastases. Twenty-nine patients with bone necrosis and 52 controls treated with bisphosphonates were compared using the Oral Hygiene Index, Decay, Missing, Filled Teeth, Community Periodontal Index of Treatment Needs, and Residual Periodontal B...

  16. Heart failure in patients treated with bisphosphonates

    DEFF Research Database (Denmark)

    Grove, Erik; Abrahamsen, B; Vestergaard, P

    2013-01-01

    The aim of this study was to investigate the occurrence of heart failure in patients treated with bisphosphonates.......The aim of this study was to investigate the occurrence of heart failure in patients treated with bisphosphonates....

  17. Bisphosphonates for osteoporosis in primary biliary cirrhosis

    DEFF Research Database (Denmark)

    Rudic, Jelena; Giljaca, Vanja; Krstic, Miodrag N

    2011-01-01

    Bisphosphonates are widely used for treatment of postmenopausal osteoporosis. Patients with primary biliary cirrhosis often have osteoporosis - either postmenopausal or secondary to the liver disease. No systematic review or meta-analysis has assessed the effects of bisphosphonates for osteoporosis...

  18. Bisphosphonates and risk of cardiovascular events: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Dae Hyun Kim

    Full Text Available Some evidence suggests that bisphosphonates may reduce atherosclerosis, while concerns have been raised about atrial fibrillation. We conducted a meta-analysis to determine the effects of bisphosphonates on total adverse cardiovascular (CV events, atrial fibrillation, myocardial infarction (MI, stroke, and CV death in adults with or at risk for low bone mass.A systematic search of MEDLINE and EMBASE through July 2014 identified 58 randomized controlled trials with longer than 6 months in duration that reported CV events. Absolute risks and the Mantel-Haenszel fixed-effects odds ratios (ORs and 95% confidence intervals (CIs of total CV events, atrial fibrillation, MI, stroke, and CV death were estimated. Subgroup analyses by follow-up duration, population characteristics, bisphosphonate types, and route were performed.Absolute risks over 25-36 months in bisphosphonate-treated versus control patients were 6.5% versus 6.2% for total CV events; 1.4% versus 1.5% for atrial fibrillation; 1.0% versus 1.2% for MI; 1.6% versus 1.9% for stroke; and 1.5% versus 1.4% for CV death. Bisphosphonate treatment up to 36 months did not have any significant effects on total CV events (14 trials; ORs [95% CI]: 0.98 [0.84-1.14]; I2 = 0.0%, atrial fibrillation (41 trials; 1.08 [0.92-1.25]; I2 = 0.0%, MI (10 trials; 0.96 [0.69-1.34]; I2 = 0.0%, stroke (10 trials; 0.99 [0.82-1.19]; I2 = 5.8%, and CV death (14 trials; 0.88 [0.72-1.07]; I2 = 0.0% with little between-study heterogeneity. The risk of atrial fibrillation appears to be modestly elevated for zoledronic acid (6 trials; 1.24 [0.96-1.61]; I2 = 0.0%, not for oral bisphosphonates (26 trials; 1.02 [0.83-1.24]; I2 = 0.0%. The CV effects did not vary by subgroups or study quality.Bisphosphonates do not have beneficial or harmful effects on atherosclerotic CV events, but zoledronic acid may modestly increase the risk of atrial fibrillation. Given the large reduction in fractures with bisphosphonates, changes in

  19. Bisphosphonate ISS Flight Experiment

    Science.gov (United States)

    LeBlanc, Adrian; Matsumoto, Toshio; Jones, Jeffrey; Shapiro, Jay; Lang, Thomas; Shackleford, Linda; Smith, Scott M.; Evans, Harlan; Spector, Elizabeth; Ploutz-Snyder, Robert; Sibonga, Jean; Keyak, Joyce; Nakamura, Toshitaka; Kohri, Kenjiro; Ohshima, Hiroshi; Moralez, Gilbert

    2014-01-01

    The bisphosphonate study is a collaborative effort between the NASA and JAXA space agencies to investigate the potential for antiresorptive drugs to mitigate bone changes associated with long-duration spaceflight. Elevated bone resorption is a hallmark of human spaceflight and bed rest (common zero-G analog). We tested whether an antiresorptive drug in combination with in-flight exercise would ameliorate bone loss and hypercalcuria during longduration spaceflight. Measurements include DXA, QCT, pQCT, and urine and blood biomarkers. We have completed analysis of 7 crewmembers treated with alendronate during flight and the immediate postflight (R+exercise device (ARED) during their missions. We previously reported the pre/postflight results of crew taking alendronate during flight (Osteoporosis Int. 24:2105-2114, 2013). The purpose of this report is to present the 12-month follow-up data in the treated astronauts and to compare these results with preliminary data from untreated crewmembers exercising with ARED (ARED control) or without ARED (Pre-ARED control). Results: the table presents DXA and QCT BMD expressed as percentage change from preflight in the control astronauts (18 Pre-ARED and the current 5 ARED-1-year data not yet available) and the 7 treated subjects. As shown previously the combination of exercise plus antiresorptive is effective in preventing bone loss during flight. Bone measures for treated subjects, 1 year after return from space remain at or near baseline values. Except in one region, the treated group maintained or gained bone 1 year after flight. Biomarker data are not currently available for either control group and therefore not presented. However, data from other studies with or without ARED show elevated bone resorption and urinary Ca excretion while bisphosphonate treated subjects show decreases during flight. Comparing the two control groups suggests significant but incomplete improvement in maintaining BMD using the newer exercise

  20. Effects of acute and 2-week administration of oral salbutamol on exercise performance and muscle strength in athletes.

    Science.gov (United States)

    Hostrup, M; Kalsen, A; Auchenberg, M; Bangsbo, J; Backer, V

    2016-01-01

    Our objective was to investigate effects of acute and 2-week administration of oral salbutamol on repeated sprint ability, exercise performance, and muscle strength in elite endurance athletes. Twenty male elite athletes [VO2max: 69.4 ± 1.8 (Mean ± SE) mL/min/kg], aged 25.9 ± 1.4 years, were included in a randomized, double-blinded and placebo-controlled parallel study. At baseline, after acute administration, and again after 2-week administration of the study drugs (8 mg salbutamol or placebo), subjects' maximal voluntary contraction (MVC) of m. quadriceps and isometric endurance of m. deltoideus were measured, followed by three repeated Wingate tests. Exercise performance at 110% of VO2max was determined on a bike ergometer. Acute administration of salbutamol increased peak power during first Wingate test by 4.1 ± 1.7% (P salbutamol increased (P salbutamol had any effect on MVC, exercise performance at 110% of VO2max or on isometric endurance. No differences were observed in the placebo group. In conclusion, salbutamol benefits athletes' sprint ability. Thus, the present study supports the restriction of oral salbutamol in competitive sports.

  1. Caveats of bisphosphonate abuse

    Directory of Open Access Journals (Sweden)

    Sanjay Agarwala

    2016-01-01

    Full Text Available Background: Bisphosphonates (BPs are the common drugs used for the treatment of postmenopausal osteoporosis. Short term benefits of the BPs are well known. However, there are concerns regarding their long term use. The aim of the study was to analyze the association between atypical femoral fractures and BP misuse/abuse as well as study the outcome of management of these fractures. Materials and Methods: A retrospective study of a prospectively studied patients who presented with atypical femoral fractures between January 2010 and August 2012 and were followed up upto June 2014. The cohort consisted of nine female patients (12 fractures with an average age of 71 years (range 58-85 years. Analysis was done for the indications, duration of BP use, configuration of associated fractures and method of treatment. Results: The mean duration of BP use was 6.6 years (range 4-10 years. BP treatment was initiated without sufficient indication and continued without proper review and followup in most cases. Most patients did not followup and continued to consume BPs without any review by the doctors. All patients had prodromal thigh pain of various duration, which was inadequately investigated and managed before the presentation. Two cases with an incomplete fracture and no thigh pain were managed successfully with conservative treatment. The rest were treated by surgery with intramedullary nailing. The average union time was longer and two fractures went into nonunion which required further surgical intervention. Conclusion: Atypical femoral fractures appear to be strongly related to abuse of BPs. Great care is to be exercised at initiation as well as the continuation of BP therapy, and regular review is required. There is a need for improved awareness among physicians about the possibility of such fractures, and interpretation of thigh pain and radiological findings, especially if the patient has been on BPs therapy. Internal fixation for complete

  2. Conservative Treatment of Bisphosphonate-Related Osteonecrosis of the Jaw in Multiple Myeloma Patients

    Directory of Open Access Journals (Sweden)

    Pelagia I. Melea

    2014-01-01

    Full Text Available The use of intravenous bisphosphonates (pamidronate or zoledronic acid is the cornerstone for the management of multiple myeloma-(MM- related bone disease. However, osteonecrosis of the jaw (ONJ is a rare, but sometimes difficult to manage, adverse effect of bisphosphonates therapy. A retrospective review of all MM patients who were treated with bisphosphonates in our department, from 2003 to 2013, and developed ONJ was performed. According to inclusion criteria, 38 patients were studied. All these patients were treated as conservatively as possible according to the American Association of Oral and Maxillofacial Surgeons criteria. Patients were managed with observation, oral antibacterial mouth rinse with chlorhexidine, oral antibiotics, pain control with analgesics, nonsurgical sequestrectomy with or without simultaneous administration of antibiotics, or major surgery with or without antibiotics. Healing of the lesions was achieved in 23 (60% patients who were treated with conservative measures; the median time to healing was 12 months (95% CI: 4–21. The number of bisphosphonates infusions influenced the time to healing: the median time to healing for patients who received 16 infusions was it 14 months P=0.017. We conclude that a primarily nonsurgical approach appears to be a successful management strategy for bisphosphonate-related ONJ.

  3. Long-term radiographic follow-up of bisphosphonate-associated atypical femur fractures

    Energy Technology Data Exchange (ETDEWEB)

    Favinger, Jennifer L. [University of Washington, Department of Radiology, 1959 N.E. Pacific Street, Box 357115, Seattle, WA (United States); Hippe, Daniel [University of Washington, Department of Radiology, Seattle, WA (United States); Ha, Alice S. [University of Washington, Department of Radiology, 4245 Roosevelt Way NE, Box 354755, Seattle, WA (United States)

    2016-05-15

    To evaluate the appearance of bisphosphonate-related femur insufficiency fractures on long-term follow-up radiographic studies and to describe the rate of fracture line obscuration and cortical beak healing over time. In this retrospective study, bisphosphonate-related femur fracture radiographs were reviewed by two radiologists for the presence of a fracture line, callus, and the characteristic cortical beak. Kaplan-Meier curves were used to analyze the time to first indication of healing. Femurs were also subdivided into those who underwent early versus late surgical fixation and those who underwent early versus late discontinuation of bisphosphonate. Clinical data including pain level and medication history were collected. Forty-seven femurs with a bisphosphonate-related femur fracture were identified in 28 women. Eighty-five percent took a bisphosphonate for greater than 5 years and 59 % for greater than 10 years. The median time to beak healing was 265 weeks and the median time to fracture line healing was 56 weeks in the 31 femurs with a baseline fracture. No statistically significant difference was identified between surgical fixation and conservative management. Bisphosphonate-related fractures demonstrate notably prolonged healing time on long-term follow-up. (orig.)

  4. Renal safety in patients treated with bisphosphonates for osteoporosis: a review.

    Science.gov (United States)

    Miller, Paul D; Jamal, Sophie A; Evenepoel, Pieter; Eastell, Richard; Boonen, Steven

    2013-10-01

    Bisphosphonates are widely used for the treatment of osteoporosis and are generally well tolerated. However, the United States Food and Drug Administration safety reports have highlighted the issue of renal safety in bisphosphonate-treated patients. All bisphosphonates carry labeled "warnings" or a contraindication for use in patients with severe renal impairment (creatinine clearance osteoporosis were obtained via PubMed, and were reviewed with support from published articles available on PubMed. Renal safety analyses of pivotal trials of oral alendronate, risedronate, and ibandronate for postmenopausal osteoporosis showed no short-term or long-term effects on renal function. Transient postinfusion increases in serum creatinine have been reported in patients receiving intravenous ibandronate and zoledronic acid; however, studies showed that treatment with these agents did not result in long-term renal function deterioration in clinical trial patients with osteoporosis. All bisphosphonate therapies have "warnings" for use in patients with severe renal impairment. Clinical trial results have shown that even in elderly, frail, osteoporotic patients with renal impairment, intravenous bisphosphonate therapy administration in accordance with the prescribing information did not result in long-term renal function decline. Physicians should follow guidelines for bisphosphonate therapies administration at all times. © 2013 American Society for Bone and Mineral Research.

  5. Long-term treatment with bisphosphonates and their safety in postmenopausal osteoporosis.

    Science.gov (United States)

    Pazianas, Michael; Cooper, Cyrus; Ebetino, F Hal; Russell, R Graham G

    2010-07-21

    Bisphosphonates are the leading drugs for the treatment of osteoporosis. In randomized controlled trials (RCTs), alendronate, risedronate, and zoledronate have shown to reduce the risk of vertebral, nonvertebral, and hip fractures, whereas RCTs with ibandronate show antifracture efficacy at vertebral sites. Bisphosphonates are generally well tolerated and safe. Nevertheless, adverse events have been noted, and it is important to consider the strength of the evidence for causal relationships. Effects on the gastrointestinal tract and kidney function are well recognized, as are transient acute-phase reactions. Atrial fibrillation was first identified as a potential adverse event in a zoledronate trial, but subsequent trials and analyses failed to substantiate an association with bisphosphonates. Case reports have suggested a relationship between oral bisphosphonates and esophageal cancer, but this has not been demonstrated in epidemiologic studies. A possible association between bisphosphonate use and osteonecrosis of the jaw (ONJ) has also been suggested. However, the risk of ONJ in patients with osteoporosis appears to be very low, with no evidence from prospective RCTs of a causal association. There are reports of occasional occurrence of subtrochanteric or diaphyseal fractures in osteoporotic patients, but an association with bisphosphonate therapy is not substantiated by epidemiologic studies or prospective RCTs.

  6. Positive predictive values of the coding for bisphosphonate therapy among cancer patients in the Danish National Patient Registry

    Directory of Open Access Journals (Sweden)

    Nielsson MS

    2012-08-01

    Full Text Available Malene Schou Nielsson,1 Rune Erichsen,1 Trine Frøslev,1 Aliki Taylor,2 John Acquavella,2 Vera Ehrenstein11Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Center for Observational Research International, Amgen Ltd Thousand Oaks, CA, USA Background: The purpose of this study was to estimate the positive predictive value (PPV of the coding for bisphosphonate treatment in selected cancer patients from the Danish National Patient Registry (DNPR.Methods: Through the DNPR, we identified all patients with recorded cancer of the breast, prostate, lung, kidney, and with multiple myeloma. We restricted the study sample to patients with bisphosphonate treatment recorded during an admission to Aalborg Hospital, Denmark, from 2005 through 2009. We retrieved and reviewed medical records of these patients from the initial cancer diagnosis onwards to confirm or rule out bisphosphonate therapy. We calculated the PPV of the treatment coding as the proportion of patients with confirmed bisphosphonate treatment.Results: We retrieved and reviewed the medical records of 60 cancer patients with treatment codes corresponding to bisphosphonate therapy. Recorded code corresponded to treatment administered intravenously for 59 of 60 patients, corresponding to a PPV of 98.3% (95% confidence interval 92.5–99.8. In the remaining patient, bisphosphonate treatment was also confirmed but was an orally administered bisphosphonate; thus, the treatment for any bisphosphonate regardless of administration was confirmed for all 60 patients (PPV of 100%, 95% confidence interval 95.9–100.0.Conclusion: The PPV of bisphosphonate treatment coding among cancer patients in the DNPR is very high and the recorded treatment nearly always corresponds to intravenous administration.Keywords: bisphosphonate, neoplasm metastases, predictive value of tests, validation studies

  7. Bisphosphonate adverse effects, lessons from large databases

    DEFF Research Database (Denmark)

    Abrahamsen, Bo

    2010-01-01

    To review the latest findings on bisphosphonate safety from health databases, in particular sources that can provide incidence rates for stress fractures, osteonecrosis of the jaw (ONJ), atrial fibrillation and gastrointestinal lesions including esophageal cancer. The main focus is on bisphosphon......To review the latest findings on bisphosphonate safety from health databases, in particular sources that can provide incidence rates for stress fractures, osteonecrosis of the jaw (ONJ), atrial fibrillation and gastrointestinal lesions including esophageal cancer. The main focus...

  8. Bisphosphonate-associated atypical subtrochanteric femur fracture.

    Science.gov (United States)

    Wolin, Ely A; Banks, Kevin P; Vroman, Penny J

    2015-03-01

    Bisphosphonates help prevent progressive bone mineralization loss and subsequent osteoporotic fractures. However, long-term bisphosphonate therapy paradoxically increases the risk of a unique injury called an atypical subtrochanteric femur fracture. Despite this, the benefits of bisphosphonates outweigh the risks, because far more pathologic fractures are prevented than induced. The early identification of atypical subtrochanteric femur fractures is important as there is high associated morbidity and mortality. We describe a case of a 76-y-old woman with a completed bisphosphonate-associated atypical subtrochanteric femur fracture.

  9. Thirteen-week oral dose toxicity study of Oligonol containing oligomerized polyphenols extracted from lychee and green tea.

    Science.gov (United States)

    Kitadate, Kentaro; Homma, Kohei; Roberts, Ashley; Maeda, Takahiro

    2014-02-01

    Oligonol is a functional food containing catechin-type monomers and proanthocyanidin oligomer converted from polymer forms via a novel manufacturing process. The catechin component of green tea extract has been associated with nasal toxicity in rats following subchronic exposure. To assess the potential for Oligonol to induce nasal toxicity a 13-week repeated oral dose toxicity study was conducted in rats using doses of 100, 300, and 1000 mg/kg/d. Clinical signs and mortality were not affected by Oligonol treatment. Compound-colored stools and an increase in food consumption were observed in some treated groups; however, there were no treatment-related differences in terminal body weights or with respect to the results of the gross postmortem examinations. Histopathological evaluation of the nasal cavity tissues revealed no treatment-related lesions. The results from this toxicity study indicate that Oligonol does not induce nasal toxicity and further supports the results of previous studies demonstrating the safety of Oligonol for human consumption.

  10. Bisphosphonate-associated osteonecrosis of the jaws

    Directory of Open Access Journals (Sweden)

    Pankaj Agarwal

    2012-01-01

    Full Text Available Bisphosphonates constitute a group of drugs capable of modulating bone turnover and reduce its remodeling when an excessive resorption occurs. This is why they are indicated in a large group of bone diseases like postmenopausal osteoporosis or osteolysis associated with breast cancer or multiple myeloma. Over the last few years and due to their extensive use, many cases of complications associated with their use have been published. Among the most important possible adverse effects are the oral ones, with the appearance of ulcerations and, especially, osteonecrosis of the jaws associated with this therapy. In this paper, we have analyzed the general characteristics of these drugs and their mechanisms of action as well as the described adverse effects, especially oral and maxillofacial, have been made special reference, regarding the prevention of osteonecrosis of the jaws, heightened by cases described in the medical and odontological literature. The preventive protocol backs up the fundamental role of the odontologist in the effective prevention of this process before, during and after the treatment.

  11. Effectiveness of bisphosphonate analogues and functional electrical stimulation on attenuating post-injury osteoporosis in spinal cord injury patients- a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Ke-Vin Chang

    Full Text Available BACKGROUND: Various pharmacologic and non-pharmacologic approaches have been applied to reduce sublesional bone loss after spinal cord injury (SCI, and the results are inconsistent across the studies. The objective of this meta-analysis was to investigate whether the two most-studied interventions, bisphosphonate analogues and functional electrical stimulation (FES, could effectively decrease bone mineral density (BMD attenuation and/or restore lost BMD in the SCI population. METHODS: Randomized controlled trials, quasi-experimental studies, and prospective follow-up studies employing bisphosphonates or FES to treat post-SCI osteoporosis were identified in PubMed and Scopus. The primary outcome was the percentage of BMD change from baseline measured by dual-energy X-ray absorptiometry (DEXA or computed tomography (CT. Data were extracted from four points: the 3rd, 6th, 12th, and 18th month after intervention. RESULTS: A total of 19 studies were included in the analysis and involved 364 patients and 14 healthy individuals. Acute SCI participants treated with bisphosphonate therapy demonstrated a trend toward less bone loss than participants who received placebos or usual care. A significant difference in BMD decline was noted between both groups at the 3rd and 12th month post-medication. The subgroup analysis failed to show the superiority of intravenous bisphosphonate over oral administration. Regarding FES training, chronic SCI patients had 5.96% (95% CI, 2.08% to 9.84%, 7.21% (95%CI, 1.79% to 12.62%, and 9.56% (95% CI, 2.86% to 16.26% increases in BMD at the 3rd, 6th, and 12th months post-treatment, respectively. The studies employing FES ≥ 5 days per week were likely to have better effectiveness than studies using FES ≤ 3 days per week. CONCLUSIONS: Our meta-analysis indicated bisphosphonate administration early following SCI effectively attenuated sublesional bone loss. FES intervention for chronic SCI patients could significantly

  12. Atypical fractures on long term bisphosphonates therapy.

    LENUS (Irish Health Repository)

    Hussein, W

    2011-01-01

    Bisphosphonates reduce fractures risk in patients with osteoporosis. A new pattern of fractures is now being noted in patients on prolonged bisphosphonate therapy. We report a case of an atypical femoral fracture with preceding pain and highlight the characteristics of these fractures.

  13. Evaluation of a subchronic (13-week) oral toxicity study, preceded by an in utero exposure phase, with arachidonic acid oil derived from Mortierella alpina in rats

    NARCIS (Netherlands)

    Hempenius, R.A.; Lina, B.A.R.; Haggitt, R.C.

    2000-01-01

    Arachidonic acid oil (ARA-oil) derived from the fungus Mortierella alpina for use in infant nutrition was tested in a subchronic (13-week) oral toxicity study in rats, preceded by an in utero exposure phase. The ARA-oil was administered as admixture to the rodent diet at dose levels of 3000 ppm, 15,

  14. Evaluation of a subchronic (13-week) oral toxicity study, preceded by an in utero exposure phase, with arachidonic acid oil derived from Mortierella alpina in rats

    NARCIS (Netherlands)

    Hempenius, R.A.; Lina, B.A.R.; Haggitt, R.C.

    2000-01-01

    Arachidonic acid oil (ARA-oil) derived from the fungus Mortierella alpina for use in infant nutrition was tested in a subchronic (13-week) oral toxicity study in rats, preceded by an in utero exposure phase. The ARA-oil was administered as admixture to the rodent diet at dose levels of 3000 ppm,

  15. Evaluation of a subchronic (13-week) oral toxicity study, preceded by an in utero exposure phase, with arachidonic acid oil derived from Mortierella alpina in rats

    NARCIS (Netherlands)

    Hempenius, R.A.; Lina, B.A.R.; Haggitt, R.C.

    2000-01-01

    Arachidonic acid oil (ARA-oil) derived from the fungus Mortierella alpina for use in infant nutrition was tested in a subchronic (13-week) oral toxicity study in rats, preceded by an in utero exposure phase. The ARA-oil was administered as admixture to the rodent diet at dose levels of 3000 ppm, 15,

  16. Dose finding study of oral PSC 833 combined with weekly intravenous etoposide in children with relapsed or refractory solid tumours.

    Science.gov (United States)

    Pein, F; Pinkerton, R; Berthaud, P; Pritchard-Jones, K; Dick, G; Vassal, G

    2007-09-01

    PSC 833 is an effective MDR1 reversal agent in vitro, including studies with paediatric cancer cell lines such as neuroblastoma and rhabdomyosarcoma. This study was performed to determine the safety profile, dose limiting toxicity (DLT) and maximum tolerated dose (MTD) in children with solid tumours and to determine the influence of PSC 833 on the pharmacokinetics of co-administered etoposide. Each patient received one cycle of intravenous etoposide (100 mg/m2 daily for 3 days on three consecutive weeks) to document baseline pharmacokinetics, and subsequently the same schedule using a dose of 50 mg/m2 was given combined with PSC 833 given orally every 6h at a starting dose of 4 mg/kg. Thirty two eligible patients (23 male, median age 8.3 years) were enrolled. Neuroblastoma and rhabdomyosarcoma were the common disease types. Brain tumours were excluded. DLT was defined as any non-haematological grade 3-4 toxicity (common toxicity criteria) and using a specific toxicity scale for cerebellar toxicity. The MDT was defined as the first dose below which 2 or more patients per dose level experienced DLT. Grade 1-2 ataxia occurred in cohorts 2 and 3 (4 and 5 mg/kg, respectively). Three patients developed grade 3 neurotoxicity in the 6 mg/kg cohort and this defined the MTD. Six responses were observed (2 CR, 4 PR). Pharmacokinetic studies indicated that the clearance of etoposide was reduced by approximately 50% when combined with PSC 833. It is concluded that the toxicity profile and MDT is similar in both children and adults, as is the effect on etoposide metabolism. The study demonstrated the feasibility and safety of carrying out a paediatric phase 1 trial across European boundaries and acts as a model for future cooperative studies in rare cancers among children.

  17. Semaglutide, a Once-Weekly Human GLP-1 Analog, Does Not Reduce the Bioavailability of the Combined Oral Contraceptive, Ethinylestradiol/Levonorgestrel

    OpenAIRE

    Kapitza, Christoph; Nosek, Leszek; Jensen, Lene; Hartvig, Helle; Jensen, Christine B; Flint, Anne

    2015-01-01

    The effect of semaglutide, a once-weekly human glucagon-like peptide-1 (GLP-1) analog in development for type 2 diabetes (T2D), on the bioavailability of a combined oral contraceptive was investigated. Postmenopausal women with T2D (n = 43) on diet/exercise ± metformin received ethinylestradiol (0.03 mg)/levonorgestrel (0.15 mg) once daily for 8 days before (semaglutide-free) and during (steady-state 1.0 mg) semaglutide treatment (subcutaneous once weekly; dose escalation: 0.25 mg 4 weeks; 0....

  18. Bisphosphonate-related osteonecrosis of the jaw complicated by Ludwig's angina.

    Science.gov (United States)

    Yang, Rong-Hsin; Shen, Shu-Huei; Li, Wing-Yin; Chu, Yum-Kung

    2015-01-01

    Ludwig's angina is a life-threatening cellulitis that involves the submandibular and sublingual spaces. It often occurs after an infection of the roots of the teeth. However, modern dental care and use of antibiotics for oral infections have made Ludwig's angina rare. We present here a cancer patient exhibiting the sequential features of bisphosphonate related osteonecrosis of the jaw on bone scan complicating with Ludwig's angina. This report highlights the need for medical practitioners to be alert to these rare combinations in the compromised patient after bisphosphonate therapy. To the best of our knowledge, no case of Ludwig's angina secondary to osteonecrosis of the jaw has been reported.

  19. Important aspects regarding the role of microorganisms in bisphosphonate-related osteonecrosis of the jaws.

    Science.gov (United States)

    Boff, Renata Chiapinotto; Salum, Fernanda Gonçalves; Figueiredo, Maria Antonia; Cherubini, Karen

    2014-08-01

    Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is an important side effect of bisphosphonates, whose etiopathogenesis has not been completely elucidated. Theories pointing to bone turnover and angiogenesis inhibition, as well as effects on epithelial cells of oral mucosa and the role of microorganisms have been reported. Nevertheless, the true contribution of each one of these factors to BRONJ is unknown. We present here a literature review focusing on important aspects regarding the role of microorganisms in BRONJ development. Knowledge about specific microbiota and its role in the etiopathogenesis of this disease can help the optimisation of preventive and therapeutic interventions in patients with or at-risk for BRONJ.

  20. Long-term treatment with bisphosphonates and their safety in postmenopausal osteoporosis

    Directory of Open Access Journals (Sweden)

    Michael Pazianas

    2010-07-01

    Full Text Available Michael Pazianas1, Cyrus Cooper1,2, F Hal Ebetino3, R Graham G Russell1,41The Botnar Research Centre and Oxford University Institute of Musculoskeletal Sciences, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Diseases, Nuffield Orthopaedic Centre, Headington, Oxford, UK; 2MRC Epidemiology Resource Centre, University of Southampton, Southampton General Hospital, Southampton, UK; 3Warner Chilcott, New Jersey, USA; 4The Mellanby Centre for Bone Research, Department of Human Metabolism, Sheffield University Medical School, Sheffield, UKAbstract: Bisphosphonates are the leading drugs for the treatment of osteoporosis. In ­randomized controlled trials (RCTs, alendronate, risedronate, and zoledronate have shown to reduce the risk of vertebral, nonvertebral, and hip fractures, whereas RCTs with ibandronate show antifracture efficacy at vertebral sites. Bisphosphonates are generally well tolerated and safe. Nevertheless, adverse events have been noted, and it is important to consider the strength of the evidence for causal relationships. Effects on the gastrointestinal tract and kidney function are well recognized, as are transient acute-phase reactions. Atrial fibrillation was first identified as a potential adverse event in a zoledronate trial, but subsequent trials and analyses failed to substantiate an association with bisphosphonates. Case reports have suggested a relationship between oral bisphosphonates and esophageal cancer, but this has not been demonstrated in epidemiologic studies. A possible association between bisphosphonate use and osteonecrosis of the jaw (ONJ has also been suggested. However, the risk of ONJ in patients with osteoporosis appears to be very low, with no evidence from prospective RCTs of a causal association. There are reports of occasional occurrence of subtrochanteric or diaphyseal fractures in osteoporotic patients, but an association with bisphosphonate therapy is not substantiated by

  1. Repurposing of bisphosphonates for the prevention and therapy of nonsmall cell lung and breast cancer

    Science.gov (United States)

    Stachnik, Agnes; Yuen, Tony; Iqbal, Jameel; Sgobba, Miriam; Lu, Ping; Colaianni, Graziana; Ji, Yaoting; Zhu, Ling-Ling; Kim, Se-Min; Li, Jianhua; Liu, Peng; Izadmehr, Sudeh; Sangodkar, Jaya; Scherer, Thomas; Mujtaba, Shiraz; Galsky, Matthew; Gomez, Jorge; Epstein, Solomon; Buettner, Christoph; Bian, Zhuan; Zallone, Alberta; Aggarwal, Aneel K.; Haider, Shozeb; New, Maria I.; Sun, Li; Narla, Goutham; Zaidi, Mone

    2014-01-01

    A variety of human cancers, including nonsmall cell lung (NSCLC), breast, and colon cancers, are driven by the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases. Having shown that bisphosphonates, a class of drugs used widely for the therapy of osteoporosis and metastatic bone disease, reduce cancer cell viability by targeting HER1, we explored their potential utility in the prevention and therapy of HER-driven cancers. We show that bisphosphonates inhibit colony formation by HER1ΔE746-A750-driven HCC827 NSCLCs and HER1wt-expressing MB231 triple negative breast cancers, but not by HERlow-SW620 colon cancers. In parallel, oral gavage with bisphosphonates of mice xenografted with HCC827 or MB231 cells led to a significant reduction in tumor volume in both treatment and prevention protocols. This result was not seen with mice harboring HERlow SW620 xenografts. We next explored whether bisphosphonates can serve as adjunctive therapies to tyrosine kinase inhibitors (TKIs), namely gefitinib and erlotinib, and whether the drugs can target TKI-resistant NSCLCs. In silico docking, together with molecular dynamics and anisotropic network modeling, showed that bisphosphonates bind to TKIs within the HER1 kinase domain. As predicted from this combinatorial binding, bisphosphonates enhanced the effects of TKIs in reducing cell viability and driving tumor regression in mice. Impressively, the drugs also overcame erlotinib resistance acquired through the gatekeeper mutation T790M, thus offering an option for TKI-resistant NSCLCs. We suggest that bisphosphonates can potentially be repurposed for the prevention and adjunctive therapy of HER1-driven cancers. PMID:25453078

  2. Systematic reviews of oral complications from cancer therapies, Oral Care Study Group, MASCC/ISOO : methodology and quality of the literature

    NARCIS (Netherlands)

    Brennan, Michael T.; Elting, Linda S.; Spijkervet, Fred K. L.

    Oral complications are commonly experienced by patients undergoing cancer therapies. The Oral Care Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) has completed nine systematic reviews including Bisphosphonate

  3. Prediction of bone density around orthopedic implants delivering bisphosphonate.

    Science.gov (United States)

    Stadelmann, Vincent A; Terrier, Alexandre; Gauthier, O; Bouler, J-M; Pioletti, Dominique P

    2009-06-19

    The fixation of an orthopedic implant depends strongly upon its initial stability. Peri-implant bone may resorb shortly after the surgery. This resorption is directly followed by new bone formation and implants fixation strengthening, the so-called secondary fixation. If the initial stability is not reached, the resorption continues and the implant fixation weakens, which leads to implant loosening. Studies with rats and dogs have shown that a solution to prevent peri-implant resorption is to deliver bisphosphonate from the implant surface. The aims of the study were, first, to develop a model of bone remodeling around an implant delivering bisphosphonate, second, to predict the bisphosphonate dose that would induce the maximal peri-implant bone density, and third to verify in vivo that peri-implant bone density is maximal with the calculated dose. The model consists of a bone remodeling equation and a drug diffusion equation. The change in bone density is driven by a mechanical stimulus and a drug stimulus. The drug stimulus function and the other numerical parameters were identified from experimental data. The model predicted that a dose of 0.3 microg of zoledronate on the implant would induce a maximal bone density. Implants with 0.3 microg of zoledronate were then implanted in rat femurs for 3, 6 and 9 weeks. We measured that peri-implant bone density was 4% greater with the calculated dose compared to the dose empirically described as best. The approach presented in this paper could be used in the design and analysis processes of experiments in local delivery of drug such as bisphosphonate.

  4. Comparative efficacy of the Colgate Actibrush battery-powered toothbrush vs Oral-B CrossAction toothbrush on established plaque and gingivitis: a 6-week clinical study.

    Science.gov (United States)

    Nathoo, S; Rustogi, K N; Petrone, M E; DeVizio, W; Zhang, Y P; Volpe, A R; Proskin, H M

    2000-01-01

    The objective of this clinical program was to compare the efficacy of the Colgate Actibrush battery-powered toothbrush and the Oral-B CrossAction Toothbrush (full head, soft bristle) for the control of supragingival plaque and gingivitis. Two independent clinical studies were conducted: Study 1 (repeated 3 times) was a single-use, examiner-blind clinical study designed to measure the removal of plaque after 24 hours of no oral hygiene. Study 2 was a definitive 6-week, examiner-blind clinical study designed to determine plaque and gingivitis efficacy at 3 and 6 weeks. Sixty-one men and women, who had refrained from using oral hygiene procedures for 24 hours, were entered into the study and stratified into 2 balanced groups according to baseline (prebrushing) plaque and gingivitis scores. For Study 1, Modified Navy Plaque Index (Rustogi Refinement) scores were obtained prebrushing and after a 1-minute supervised brushing with the assigned toothbrush and a commercially available toothpaste. On 3 separate occasions, after 24 hours of no oral hygiene, the Colgate Actibrush battery-powered toothbrush removed significantly more plaque than did the CrossAction Toothbrush. For Study 2, subjects were instructed to brush their teeth twice daily for 1 minute with the assigned toothbrush. Plaque Index scores and Löe-Silness Gingival Index scores were assessed after 3 and 6 weeks. At the 6-week examination, the group using the Colgate Actibrush battery-powered toothbrush exhibited a statistically significant reduction in both supragingival plaque and gingivitis, compared with the group that used the CrossAction Toothbrush. The results of these clinical studies support the conclusion that the Colgate Actibrush battery-powered toothbrush is clinically superior for the control of both supragingival plaque and gingivitis, as compared with the Oral-B CrossAction manual toothbrush.

  5. Canadian consensus practice guidelines for bisphosphonate associated osteonecrosis of the jaw.

    Science.gov (United States)

    Khan, Aliya A; Sándor, George K B; Dore, Edward; Morrison, Archibald D; Alsahli, Mazen; Amin, Faizan; Peters, Edmund; Hanley, David A; Chaudry, Sultan R; Dempster, David W; Glorieux, Francis H; Neville, Alan J; Talwar, Reena M; Clokie, Cameron M; Al Mardini, Majd; Paul, Terri; Khosla, Sundeep; Josse, Robert G; Sutherland, Susan; Lam, David K; Carmichael, Robert P; Blanas, Nick; Kendler, David; Petak, Steven; St-Marie, Louis Georges; Brown, Jacques; Evans, A Wayne; Rios, Lorena; Compston, Juliet E

    2008-07-01

    Following publication of the first reports of osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates in 2003, a call for national multidisciplinary guidelines based upon a systematic review of the current evidence was made by the Canadian Association of Oral and Maxillofacial Surgeons (CAOMS) in association with national and international societies concerned with ONJ. The purpose of the guidelines is to provide recommendations regarding diagnosis, identification of at-risk patients, and prevention and management strategies, based on current evidence and consensus. These guidelines were developed for medical and dental practitioners as well as for oral pathologists and related specialists. The multidisciplinary task force established by the CAOMS reviewed all relevant areas of research relating to ONJ associated with bisphosphonate use and completed a systematic review of current literature. These evidence-based guidelines were developed utilizing a structured development methodology. A modified Delphi consensus process enabled consensus among the multidisciplinary task force members. These guidelines have since been reviewed by external experts and endorsed by national and international medical, dental, oral surgery, and oral pathology societies. RECOMMENDATIONS regarding diagnosis, prevention, and management of ONJ were made following analysis of all current data pertaining to this condition. ONJ has many etiologic factors including head and neck irradiation, trauma, periodontal disease, local malignancy, chemotherapy, and glucocorticoid therapy. High-dose intravenous bisphosphonates have been identified as a risk factor for ONJ in the oncology patient population. Low-dose bisphosphonate use in patients with osteoporosis or other metabolic bone disease has not been causally linked to the development of ONJ. Prevention, staging, and treatment recommendations are based upon collective expert opinion and current data, which has been limited to case

  6. Giant cell tumors close to the knee:treatment by aggressive curettage and cavity filling cementation with internal fixation and oral bisphosphonate%骨水泥填充内固定联合二磷酸盐治疗邻膝关节骨巨细胞瘤

    Institute of Scientific and Technical Information of China (English)

    徐明; 许宋锋; 惠文鹏; 于秀淳

    2011-01-01

    [目的]探讨采用病灶内肿瘤扩大刮除、骨水泥填充并钢板内固定联合二磷酸盐治疗邻膝关节骨巨细胞瘤的临床应用可行性.[方法]回顾分析2008年1月~2010年6月本科治疗的16例邻膝关节骨巨细胞瘤.男7例,女9例,平均年龄38岁(27~78岁).发病部位:股骨远端10例,胫骨近端6例.所有患者术前均经仔细评估确定肿瘤腔的完整性,术中仔细刮除肿瘤组织,应用磨钻及电刀处理瘤腔壁,骨水泥填充修复骨缺损,同时给予钢板内固定.术后均应用二膦酸盐类药物.[结果]本组患者全部获得随访,中位随访15个月,无局部复发及转移发生.参照Enneking肢体功能评分标准,本组患者平均得29分(27~30)分.复查X线片示所有患者内固定均牢靠,无软骨下骨骨折.[结论]对于膝关节周嗣骨巨细胞瘤可以选择病灶扩大刮除、骨水泥充填内固定联合二膦酸盐类药物治疗,该方法具有操作简单、肢体功能恢复理想、近期复发率低、病人易于接受等优点.远期疗效有待进一步观察.%[ Objective] To evaluate the feasibility of treating giant cell tumor (GCT) close to the knee with aggressive curet-tage and cavity filling cementation with internal fixation and oral bisphosphonates. [ Method ] A retrospective analysis was performed in 16 patients who underwent surgical treatment for giant cell tumor close to the knee from January 2008 to June 2010. There were 7 males and 9 females with mean age of 38 years. All tumors were present around the knee: 10 at the distal femur and 6 at the proximal tibia. All patients were carefully assessed before surgery to determine the integrity of the tumor cavity. All patients were treated with aggressive curettage by high-speed burring and cementation with internal fixation. Oral bisphosphonate was given after operation. [Result]The median follow-up of this series was 15 months. All patients continued to be monitored,with none lost to follow

  7. 26-week repeated oral dose toxicity study of UP446, a combination of defined extracts of Scutellaria baicalensis and Acacia catechu, in beagle dogs.

    Science.gov (United States)

    Yimam, Mesfin; Lee, Young Chul; Jia, Qi

    2016-07-01

    The needs for relatively safe botanical alternatives to relieve symptoms associated to arthritis have continued to grow in parallel with the ageing population. UP446, a standardized bioflavonoid composition from the roots of Scutellaria baicalensis and the heartwoods of Acacia catechu, has been used as over the counter joint care dietary supplements and a prescription medical food. Significant safety data have been documented in rodents and human for this composition. Here we evaluated the potential adverse effects of orally administered UP446 in beagle dogs following a 26-week repeated oral dose toxicity study. UP446 at doses of 250, 500 and 1000 mg/kg/day were administered orally to beagle dogs for 26 weeks. A 4-week recovery group from the high dose (1000 mg/kg) and vehicle treated groups were included. No morbidity or mortality was observed for the duration of the study. No significant differences between groups in body weights, food consumption, ophthalmological examinations, electrocardiograms, urinalysis, hematology, clinical chemistry, organ weights, gross pathology and histopathology were documented. Emesis, loose feces and diarrhea were noted in both genders at the 1000 mg/kg treatment groups. These clinical signs were considered to be reversible as they were not evident in the recovery period. In conclusion, the no-observed-adverse-effect-level (NOAEL) of UP446 was considered to be 500 mg/kg/day both in male and female beagle dogs.

  8. Systematic review on the incidence of bisphosphonate related osteonecrosis of the jaw in children diagnosed with osteogenesis imperfecta.

    Science.gov (United States)

    Hennedige, Anusha Adeline; Jayasinghe, Jap; Khajeh, Janette; Macfarlane, Tatiana V

    2013-10-01

    To conduct a systematic review of epidemiological literature to determine the incidence of bisphosphonate related osteonecrosis of the jaw occurring either spontaneously or after dental surgery, in children and adolescents diagnosed with osteogenesis imperfecta. MEDLINE, HMIC and EMBASE were used to search for English-language articles published from 1946 - 2013. Inclusion criteria consisted of population based studies of children and adolescents (24 years and younger) diagnosed with osteogenesis imperfecta, only studies which included a dental examination, and patients treated with intravenous bisphosphonates were included. Articles were excluded if patients had any other co-morbidity which could affect osteonecrosis of the jaw, and those which treated patients with oral bisphosphonates only. Five studies consisting of four retrospective cohort studies and one case series were identified. Study populations ranged from 15 to 278 patients and number of subjects with osteogenesis imperfecta ranged from 15 to 221. Mean duration of intravenous bisphosphonate use ranged from 4.5 to 6.8 years. All patients were clinically examined and no patients were found to have osteonecrosis of the jaw. There is no evidence to support hypothesis of causal relationship between bisphosphonates and osteonecrosis of the jaw in children and adolescents with osteogenesis imperfecta. More prospective studies on bisphosphonate use in osteogenesis imperfecta needs to be carried out.

  9. Role of the CTX Test for evaluation of the risk in diagnostic and treatment of the osteonecrosis of the jaws induced by the use of bisphosphonates

    OpenAIRE

    Lorz DDS, Patricia; Varela DDS, Rodolfo

    2015-01-01

    A literature review was conducted to determine the effectiveness of the C-terminal crosslinking telopeptide (CTX) serologic test, which has been suggested to predict the risk of developing osteonecrosis of the jaw in patients taking oral bisphosphonates. Osteonecrosis of the jaw (ONJ) is a condition that causes avascular necrosis of the alveolar bone, which occurs in patients treated with bisphosphonates. It has been suggested that a CTX value below 100 pg/ml represents a high risk for ONJ , ...

  10. Intravenous bisphosphonates for postmenopausal osteoporosis: safety profiles of zoledronic acid and ibandronate in clinical practice.

    Science.gov (United States)

    Sieber, Patricia; Lardelli, Patrizia; Kraenzlin, Claude A; Kraenzlin, Marius E; Meier, Christian

    2013-02-01

    Intravenous bisphosphonates are widely used for treatment of postmenopausal osteoporosis. They are associated with transient influenza-like symptoms, predominantly after the first zoledronic acid (up to 32 %) or ibandronate (up to 5 %) administration. The experience in clinical practice suggests that the incidence of post-dose symptoms is higher than has been reported in clinical trials. We assessed the safety of annual infusions of zoledronic acid and 3-monthly injections of ibandronate in women with postmenopausal osteoporosis. In this retrospective study we analysed safety data from 272 postmenopausal women treated with zoledronic acid (n = 127; mean age 68.6 ± 9.4 years) or intravenous (IV) ibandronate (n = 145; mean age 69.1 ± 9.0 years). Safety data (including occurrence of acute-phase reactions and osteonecrosis of the jaw) were gathered in phone call interviews by using a standardized questionnaire. The number of patients with adverse events was significantly higher in zoledronic acid as compared to ibandronate-treated patients, primarily because of a larger number of post-dose symptoms after bisphosphonate administrations (54.3 % vs. 33.1 %, p 3 days in approximately 50 % of patients. The incidence of symptoms decreased after subsequent infusions. The rate of influenza-like symptoms was more frequent after zoledronic acid than after IV ibandronate in bisphosphonate-naïve patients but comparable in patients pretreated with oral bisphosphonates. There were no spontaneous reports of osteonecrosis of the jaw, arrhythmia or delayed fracture healing. Although IV bisphosphonates are generally safe, the occurrence of transient influenza-like symptoms after IV bisphosphonates seems to be more frequent in clinical practice than has been reported in clinical trials.

  11. Differential response of idiopathic sporadic tumoral calcinosis to bisphosphonates

    Directory of Open Access Journals (Sweden)

    Karthik Balachandran

    2014-01-01

    Full Text Available Context: Tumoral calcinosis is a disorder of phosphate metabolism characterized by ectopic calcification around major joints. Surgery is the current treatment of choice, but a suboptimal choice in recurrent and multicentric lesions. Aims: To evaluate the efficacy of bisphosphonates for the management of tumoral calcinosis on optimized medical treatment. Settings and Design: The study was done in the endocrine department of a tertiary care hospital in South India. We prospectively studied two patients with recurrent tumoral calcinosis who had failed therapy with phosphate lowering measures. Materials and Methods: After informed consent, we treated both patients with standard age adjusted doses of bisphosphonates for 18 months. The response was assessed by X ray and whole body 99mTc-methylene diphosphonate bone scan at the beginning of therapy and at the end of 1 year. We also estimated serum phosphate levels and urinary phosphate to document serial changes. Results: Two patients (aged 19 and 5 years with recurrent idiopathic hyperphosphatemic tumoral calcinosis, following surgery were studied. Both patients had failed therapy with conventional medical management − low phosphate diet and phosphate binders. They had restriction of joint mobility. Both were given standard doses of oral alendronate and parenteral pamidronate respectively for more than a year, along with phosphate lowering measures. At the end of 1 year, one of the patients had more than 95% and 90% reduction in the size of the lesions in right and left shoulder joints respectively with total improvement in range of motion. In contrast, the other patient (5-year-old had shown no improvement, despite continuing to maintain normophosphatemia following treatment. Conclusions: Bisphosphonate therapy in tumoral calcinosis is associated with lesion resolution and may be used as a viable alternative to surgery, especially in cases with multicentric recurrence or treatment failure to other

  12. Osteonecrosis of the jaw as a possible rare side effect of annual bisphosphonate administration for osteoporosis: A case report

    Directory of Open Access Journals (Sweden)

    Ehrenfeld Michael

    2011-09-01

    Full Text Available Abstract Introduction Osteonecrosis of the jaw is a serious side effect in patients receiving nitrogen-containing bisphosphonates intravenously due to malignant diseases. Albeit far less frequently, osteonecrosis of the jaw has also been reported to occur due to the oral administration of nitrogen-containing bisphosphonates due to osteoporosis. Annual infusions of zoledronic acid have been recommended in order to improve patient compliance, to optimize therapeutic effects and to minimize side effects. To date, osteonecrosis of the jaw has not been linked to the annual administration of bisphosphonates. Case presentation We report the case of a 65-year-old Caucasian woman suffering from osteoporosis who developed early stage osteonecrosis of the jaw in two locations, with chronic infections, after two months of oral bisphosphonate treatment and three annual administrations of zoledronic acid. Our patient was treated by fluorescence-guided resection of the necrotic jaw bone areas; local inflammation was treated by removal of a wisdom tooth and repeat root resections. Histopathology revealed typical hallmarks of osteonecrosis of the jaw. Conclusion Osteonecrosis of the jaw may occur as a consequence of annual administrations of zoledronic acid. It is conceivable that, due to the pharmacological properties of bisphosphonates, a jaw bone that encounters frequent local inflammations is more likely to develop osteonecrosis.

  13. Analysis of different therapeutic protocols for osteonecrosis of the jaw associated with oral and intravenous bisphpsphonates

    Science.gov (United States)

    Bermúdez-Bejarano, Elena-Beatriz; Serrera-Figallo, María-Ángeles; Gutiérrez-Corrales, Aida; Romero-Ruiz, Manuel-María; Castillo-de-Oyagüe, Raquel; Gutiérrez-Pérez, José-Luis; Machuca-Portillo, Guillermo

    2017-01-01

    Introduction Chemotherapy-associated osteonecrosis of the jaw caused by bisphosphonates is an exposure of necrotic bone with more than eight weeks of evolution that is attributable to bisphosphonates and no prior radiation therapy. Its etiopathogenesis remains unknown, although there are two hypotheses that may explain it: the drug’s mechanism of action, and the risk factors that can lead to osteonecrosis. There is a wide range of treatment options for managing chemotherapy-associated osteonecrosis of the jaw, from conservative treatments to surgical procedures of varying levels of invasiveness, which are sometimes supplemented with adjuvant therapies. Objectives The objective of this article is to group the therapeutic options for osteonecrosis of the jaw (ONJ) into seven different protocols and to evaluate their effectiveness in relation to stage of ONJ. Material and Methods A literature review was carried out in PubMed following the PRISMA criteria. A total of 47 were collected after compiling a series of variables that define ONJ, applied treatments, and the clinical results obtained. Results and Discussion The 47 articles selected have a low to average estimated risk of bias and are of moderate to good quality. According to the data obtained, Protocol 3 (conservative treatment, clinical and radiological follow-up, minimally invasive surgical treatment, and adjuvant therapies) is the most favorable approach for ONJ lesions caused by oral bisphosphonates. For lesions caused by intravenous bisphosphonates, Protocol 2 (conservative treatment, clinical and radiological follow-up, minimally invasive surgical treatment, and no adjuvant therapies) is the best approach. When comparing the different stages of ONJ, Protocol 1 (conservative treatment, clinical and radiological follow-up) promotes better healing of Stage 1 ONJ lesions caused by orally administered bisphosphonates, and Protocol 3 is recommended for Stage II. For ONJ lesions attributable to intravenous

  14. Semaglutide, a once-weekly human GLP-1 analog, does not reduce the bioavailability of the combined oral contraceptive, ethinylestradiol/levonorgestrel.

    Science.gov (United States)

    Kapitza, Christoph; Nosek, Leszek; Jensen, Lene; Hartvig, Helle; Jensen, Christine B; Flint, Anne

    2015-05-01

    The effect of semaglutide, a once-weekly human glucagon-like peptide-1 (GLP-1) analog in development for type 2 diabetes (T2D), on the bioavailability of a combined oral contraceptive was investigated. Postmenopausal women with T2D (n = 43) on diet/exercise ± metformin received ethinylestradiol (0.03 mg)/levonorgestrel (0.15 mg) once daily for 8 days before (semaglutide-free) and during (steady-state 1.0 mg) semaglutide treatment (subcutaneous once weekly; dose escalation: 0.25 mg 4 weeks; 0.5 mg 4 weeks; 1.0 mg 5 weeks). Bioequivalence of oral contraceptives was established if 90%CI for the ratio of pharmacokinetic parameters during semaglutide steady-state and semaglutide-free periods was within prespecified limits (0.80-1.25). The bioequivalence criterion was met for ethinylestradiol area under the curve (AUC0-24 h ) for semaglutide steady-state/semaglutide-free; 1.11 (1.06-1.15). AUC0-24 h was 20% higher for levonorgestrel at semaglutide steady-state vs. semaglutide-free (1.20 [1.15-1.26]). Cmax was within bioequivalence criterion for both contraceptives. Reductions (mean ± SD) in HbA1c (-1.1 ± 0.6%) and weight (-4.3 ± 3.1 kg) were observed. Semaglutide pharmacokinetics were compatible with once-weekly dosing; the semaglutide dose and dose-escalation regimen were well tolerated. Adverse events, mainly gastrointestinal, were mild to moderate in severity. Asymptomatic increases in mean amylase and lipase were observed. Three subjects had elevated alanine aminotransferase levels ≥3x the upper limit of normal during semaglutide/oral contraceptive coadministration, which were reported as adverse events, but resolved during follow-up. Semaglutide did not reduce the bioavailability of ethinylestradiol and levonorgestrel.

  15. Subtrochanteric Femoral Insufficiency Fracture Following Bisphosphonate Therapy for Osseous Metastases.

    Science.gov (United States)

    Bush, Lisabeth A; Chew, Felix S

    2008-01-01

    We present the case of an insufficiency fracture of the femoral shaft in a 61-year-old man who had received bisphosphonate therapy to reduce the fracture risk from lytic renal cell carcinoma metastases to the spine. Approximately 1.5 years after beginning monthly intravenous infusions of zoledronic acid (Zometa), the patient complained of persistent thigh pain. Radionuclide bone scan showed mildly increased activity in the lateral subtrochanteric cortex of the right femur, where there was focally increased T2 signal on MRI and a small, triangular ridge or cortical beak on radiographs. The lesion was initially thought to represent a metastasis, but after the patient returned with a transverse femoral shaft fracture through the ridge following minimal trauma, MRI and biopsy of the lesion failed to show any evidence of tumor. We suggest that this fracture is similar to the low-energy proximal femoral shaft fractures recently reported in postmenopausal women who have received oral bisphosphonates for osteoporosis. Suppression of bone turnover may play a role in the development of these fractures.

  16. Pseudoepitheliomatous hyperplasia associated with bisphosphonate-related osteonecrosis of the jaw.

    Science.gov (United States)

    Zustin, Jozef; Reske, Dennis; Zrnc, Tomislav A; Heiland, Max; Scheuer, Hanna A; Assaf, Alexandre T; Friedrich, Reinhard E

    2014-01-01

    Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a well-characterized oral complication of systemic therapy with bisphosphonates. Pseudoepitheliomatous hyperplasia was observed in some of the lesions. Because podoplanin expression has been linked to malignant lesions of the oral mucosa, we aimed to investigate podoplanin expression in the pseudoepitheliomatous hyperplasia. We analyzed archival paraffin- and plastic-embedded specimens from BRONJ using both conventional and immunohistochemical (AE1/AE3, D2-40) staining methods. Eleven out of seventeen BRONJ cases showed pseudoepitheliomatous hyperplasia. All these cases were positive for AE1/AE3 and pseudoepitheliomatous hyperplasia displayed a strong basal and parabasal reaction against podoplanin. The podoplanin expression in pseudoepitheliomatous hyperplasia in BRONJ specimens should not be considered a sign of malignancy. We discuss the current and possible future roles of surgical pathologists in diagnosing morphological changes associated with the development and therapy of BRONJ lesions.

  17. Pharmacokinetics of High-Dose Weekly Oral Vitamin D3 Supplementation during the Third Trimester of Pregnancy in Dhaka, Bangladesh

    Directory of Open Access Journals (Sweden)

    Robert E. Black

    2013-03-01

    Full Text Available A pharmacokinetic study was conducted to assess the biochemical dose-response and tolerability of high-dose prenatal vitamin D3 supplementation in Dhaka, Bangladesh (23°N. Pregnant women at 27–30 weeks gestation (n = 28 were randomized to 70,000 IU once + 35,000 IU/week vitamin D3 (group PH: pregnant, higher dose or 14,000 IU/week vitamin D3 (PL: pregnant, lower dose until delivery. A group of non-pregnant women (n = 16 was similarly administered 70,000 IU once + 35,000 IU/week for 10 weeks (NH: non-pregnant, higher-dose. Rise (∆ in serum 25-hydroxyvitamin D concentration ([25(OHD] above baseline was the primary pharmacokinetic outcome. Baseline mean [25(OHD] were similar in PH and PL (35 nmol/L vs. 31 nmol/L, p = 0.34. A dose-response effect was observed: ∆[25(OHD] at modeled steady-state was 19 nmol/L (95% CI, 1 to 37 higher in PH vs. PL (p = 0.044. ∆[25(OHD] at modeled steady-state was lower in PH versus NH but the difference was not significant (−15 nmol/L, 95% CI −34 to 5; p = 0.13. In PH, 100% attained [25(OHD] ≥ 50 nmol/L and 90% attained [25(OHD] ≥ 80 nmol/L; in PL, 89% attained [25(OHD] ≥ 50 nmol/L but 56% attained [25(OHD] ≥ 80 nmol/L. Cord [25(OHD] (n = 23 was slightly higher in PH versus PL (117 nmol/L vs. 98 nmol/L; p = 0.07. Vitamin D3 was well tolerated; there were no supplement-related serious adverse clinical events or hypercalcemia. In summary, a regimen of an initial dose of 70,000 IU and 35,000 IU/week vitamin D3 in the third trimester of pregnancy was non-hypercalcemic and attained [25(OHD] ≥ 80 nmol/L in virtually all mothers and newborns. Further research is required to establish the safety of high-dose vitamin D3 in pregnancy and to determine if supplement-induced [25(OHD] elevations lead to maternal-infant health benefits.

  18. Residual (ghost) sockets in bisphosphonate use--evidence of poor healing and slow bone turnover.

    Science.gov (United States)

    Shetty, Kishore; Bouquot, J

    2009-01-01

    Patients taking bisphosphonate drug therapy have demonstrated extremely poor alveolar bone healing after relatively minor oral surgical procedures. It would seem logical that extraction sockets could remain visible radiographically for an extended period after surgery, even in cases with soft tissue healing. This article chronicles the case of a patient who had been taking zoledronic acid chronically for metastatic cancer and who demonstrated numerous residual sockets (also known as ghost sockets), with lamina dura outlines that were visible radiographically.

  19. Severe osteonecrosis of the jaws in a compromised patient subjected to bisphosphonate therapy

    Directory of Open Access Journals (Sweden)

    Juliana Dreyer de Menezes

    Full Text Available Bisphosphonate-related osteonecrosis of the jaws is characterized by alveolar bone exposure, especially after mucosal trauma or after surgical procedures, in patients who have previously received or who are currently receiving bisphosphonates without a history of radiation therapy in the maxillofacial region. The condition is refractory to treatment, and attempts at debridement are not completely effective in eradicating the necrotic bone. We report here a case of a severe osteonecrosis of the jaws in a 77-year-old male patient, who had been subjected to chemotherapy and treatment with zoledronic acid and corticosteroid. The patient also had comorbidities such as diabetes and periodontal disease, which might have contributed to the lesion development. Bisphosphonate-related osteonecrosis of the jaws has become a reality in dental clinical practice. Although palliative treatment aiming at controlling pain, infection and injury progression is indicated, the therapeutic strategy is still challenging. So far, the best approach available is prevention, based on oral care before, during, and after bisphosphonate therapy.

  20. Subtrochanteric fractures in bisphosphonate-naive patients

    DEFF Research Database (Denmark)

    Adachi, Jonathan D; Lyles, Kenneth; Boonen, Steven

    2011-01-01

    Our purpose was to characterize the risks of osteoporosis-related subtrochanteric fractures in bisphosphonate-naive individuals. Baseline characteristics of patients enrolled in the HORIZON-Recurrent Fracture Trial with a study-qualifying hip fracture were examined, comparing those who sustained...... incident subtrochanteric fractures with those sustaining other hip fractures. Subjects were bisphosphonate-naive or had a bisphosphonate washout period of 6-24 months and subsequently received an annual infusion of zoledronic acid 5 mg or placebo after low-trauma hip-fracture repair. In total, 2,127 men...... and women were included. Of the qualifying hip fractures, 5.2% were subtrochanteric, 54.8% femoral neck, 33.0% intertrochanteric, and 7.1% other (generally complex fractures of mixed type). Significant baseline (pre-hip fracture) differences were seen between index hip-fracture types, with the percentage...

  1. Bisphosphonate therapy and osteonecrosis of the jaw complicated with a temporal abscess in an elderly woman with rheumatoid arthritis: a case report.

    Science.gov (United States)

    Manzon, Licia; Ettorre, Evaristo; Viscogliosi, Giovanni; Ippoliti, Stefano; Filiaci, Fabio; Ungari, Claudio; Fratto, Giovanni; Agrillo, Alessandro

    2014-01-01

    Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is an adverse drug reaction described as the progressive destruction and death of bone tissue of the mandible or maxilla, in the course of bisphosphonate therapy. Orally administered bisphosphonates, widely used for the treatment of osteoporosis, are rarely associated with BRONJ. Instead, the risk greatly increases whether the patient is concomitantly taking steroid and/or immunosuppressant agents. The aims of this paper are to briefly discuss the evidence of the associations between bisphosphonate therapy and BRONJ, and the effects of co-occurring factors such as the presence of rheumatoid arthritis, dental surgery, and concomitant corticosteroid therapy. In particular, we present the case of an elderly woman with BRONJ suffering from rheumatoid arthritis, with a recent dental extraction and with a very unusual complication: a temporal abscess, who was successfully treated.

  2. Bisphosphonates: An update to the general dentist

    Directory of Open Access Journals (Sweden)

    Varun Dahiya

    2013-01-01

    Full Text Available Bisphosphonates (BP, included under host modulation therapy are drugs that inhibit bone resorption and commonly prescribed to prevent skeletal related changes in malignant diseases of bone and bone diseases such as osteoporosis. The sudden rise of this group of drugs is unfortunately because of the serious complication of osteonecrosis of jaws called Bisphosphonate related osteonecrosis of jaws which leads to many dental related complications. This literature review is undertaken to review the general recommendations to the dentist and clinical implications of BP′s. The implications of BP′s use in dentistry are still being determined.

  3. Bisphosphonates and Atypical Fractures of Femur

    Directory of Open Access Journals (Sweden)

    Tero Yli-Kyyny

    2011-01-01

    Full Text Available Bisphosphonates are the most widely prescribed medicines for the treatment of osteoporosis and have generally been regarded as well-tolerated and safe drugs. Since 2005, there have been numerous case reports about atypical fractures of the femur linked to long-term treatment of osteoporosis with bisphosphonates. Some attempts to characterize pathophysiology and epidemiology of these fractures have been published as well. However, as the American Society for Bone and Mineral Research (ASBMR concluded in their task force report, the subject warrants further studies.

  4. Osteonecrosis of the jaws and bisphosphonates. Report of three cases.

    Science.gov (United States)

    Pastor-Zuazaga, Daniel; Garatea-Crelgo, Joaquín; Martino-Gorbea, Raúl; Etayo-Pérez, Amaya; Sebastián-López, Cristina

    2006-01-01

    Bisphosphonates are recently acquiring increasing relevance in the treatment of several diseases. In line with the increased use of these compounds, cases of mandibular osteonecrosis, and to a lesser extent, maxillary osteonecrosis, are being reported. This necrosis is difficult to treat in patients who usually have a previously limited quality of life. A surgical performance carried out by oral and maxillofacial surgeons, stomatologists and odontologists might lead to bone exposure. A treatment based on conservation and as harmless as possible seems to be the most advisable way of acting with these patients in order to minimize the incidence and treat the complications, once the lesions have been ascertained. We report three cases treated in our service of osteonecrosis of the jaws after exodontics. This side effect should be remembered before starting any surgical treatment in these patients.

  5. Implants delivering bisphosphonate locally increase periprosthetic bone density in an osteoporotic sheep model. A pilot study

    Directory of Open Access Journals (Sweden)

    GVA Stadelmann

    2008-07-01

    Full Text Available It is a clinical challenge to obtain a sufficient orthopaedic implant fixation in weak osteoporotic bone. When the primary implant fixation is poor, micromotions occur at the bone-implant interface, activating osteoclasts, which leads to implant loosening. Bisphosphonate can be used to prevent the osteoclastic response, but when administered systemically its bioavailability is low and the time it takes for the drug to reach the periprosthetic bone may be a limiting factor. Recent data has shown that delivering bisphosphonate locally from the implant surface could be an interesting solution. Local bisphosphonate delivery increased periprosthetic bone density, which leads to a stronger implant fixation, as demonstrated in rats by the increased implant pullout force. The aim of the present study was to verify the positive effect on periprosthetic bone remodelling of local bisphosphonate delivery in an osteoporotic sheep model. Four implants coated with zoledronate and two control implants were inserted in the femoral condyle of ovariectomized sheep for 4 weeks. The bone at the implant surface was 50% higher in the zoledronate-group compared to control group. This effect was significant up to a distance of 400µm from the implant surface. The presented results are similar to what was observed in the osteoporotic rat model, which suggest that the concept of releasing zoledronate locally from the implant to increase the implant fixation is not species specific. The results of this trial study support the claim that local zoledronate could increase the fixation of an implant in weak bone.

  6. Atraumatic tooth extraction in patients taking bisphosphonates: a review of literature and experience with three cases.

    Science.gov (United States)

    Hoefert, Sebastian; Grimm, Martin; Sharghi, Feraydoon; Geist, Andreas; Krimmel, Michael; Reinert, Siegmar

    2014-09-01

    Regev et al. first re-introduced the method of atraumatic tooth extraction with orthodontic elastics in 2008. Since then, the method has been mentioned regularly in literature. Nevertheless, the need for additional more detailed information remains. We present a review of literature and a retrospective analysis of our three patients receiving bisphosphonate medication. Two of our patients suffered from bisphosphonate-related osteonecrosis of the jaw (BRONJ). All three patients underwent atraumatic tooth extraction, which we describe in detail. Regev et al. reported satisfactory results using the novel method. We removed six teeth in two patients with continued chemotherapy or bisphosphonate therapy in a time span of 26.2 ± 16.4 weeks successfully. None of the patients developed exposed bone in the follow-up (7.4 ± 0.2 months). In one case, the technique had to be discontinued due to increasing tooth soreness. Atraumatic tooth extraction seems to be a safe method to prevent bone exposure, even in cases with BRONJ. The time required of our patients for exfoliation exceeded the time mentioned in literature considerably. This proved to be a major limitation. Our cases showed that patients with good compliance, no sore teeth, or painful BRONJ lesions, benefited from atraumatic tooth extraction. One of the method's major advantages might be the possibility to continue chemotherapy and bisphosphonate therapy throughout the treatment.

  7. Influence of Bisphosphonate Treatment on Medullary Macrophages and Osteoclasts: An Experimental Study

    Directory of Open Access Journals (Sweden)

    Natalia Daniela Escudero

    2012-01-01

    Full Text Available Nitrogen-containing bisphosphonates are widely used for treating diverse bone pathologies. They are anticatabolic drugs that act on osteoclasts inhibiting bone resorption. It remains unknown whether the mechanism of action is by decreasing osteoclast number, impairing osteoclast function, or whether they continue to effectively inhibit bone resorption despite the increase in osteoclast number. There is increasing evidence that bisphosphonates also act on bone marrow cells like macrophages and monocytes. The present work sought to evaluate the dynamics of preosteoclast fusion and possible changes in medullary macrophage number in bisphosphonate-treated animals. Healthy female Wistar rats received olpadronate, alendronate, or vehicle during 5 weeks, and 5-bromo-2-deoxyuridine (BrdU on day 7, 28, or 34 of the experiment. Histomorphometric studies were performed to study femurs and evaluate: number of nuclei per osteoclast (N.Nu/Oc; number of BrdU-positive nuclei (N.Nu BrdU+/Oc; percentage of BrdU-positive nuclei per osteoclast (%Nu.BrdU+/Oc; medullary macrophage number (mac/mm2 and correlation between N.Nu/Oc and mac/mm2. Results showed bisphosphonate-treated animals exhibited increased N.Nu/Oc, caused by an increase in preosteoclast fusion rate and evidenced by higher N.Nu BrdU+/Oc, and significantly decreased mac/mm2. Considering the common origin of osteoclasts and macrophages, the increased demand for precursors of the osteoclast lineage may occur at the expense of macrophage lineage precursors.

  8. Relationship between disease stage and renal function in bisphosphonate-related osteonecrosis of the jaw

    Science.gov (United States)

    2017-01-01

    Objectives Bisphosphonate is the primary cause of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Bisphosphonates are eliminated from the human body by the kidneys. It is anticipated that bisphosphonate levels in the body will increase if the kidney is in a weak state or if there is systemic disease that affects kidney function. The aim of this study was to analyze the relevance of renal function in the severity of BRONJ. Materials and Methods Ninety-three patients diagnosed with BRONJ in Pusan National University Dental Hospital from January 2012 to December 2014 were included in this study. All patients underwent a clinical exam, radiographs, and serologic lab test, including urine analysis. The patient's medical history was also taken, including the type of bisphosphonate drug, the duration of administration and drug holiday, route of administration, and other systemic diseases. In accordance with the guidelines of the 2009 position paper of American Association of Oral and Maxillofacial Surgeons, the BRONJ stage was divided into 4 groups, from stage 0 to 3, according to the severity of disease. IBM SPSS Statistics version 21.0 (IBM Co., USA) was used to perform regression analysis with a 0.05% significance level. Results BRONJ stage and renal factor (estimated glomerular filtration rate) showed a moderate statistically significant correlation. In the group with higher BRONJ stage, the creatinine level was higher, but the increase was not statistically significant. Other factors showed no significant correlation with BRONJ stage. There was a high statistically significant correlation between BRONJ stage and ‘responder group’ and ‘non-responder group,’ but there was no significant difference with the ‘worsened group.’ In addition, the age of the patients was a relative factor with BRONJ stage. Conclusion With older age and lower renal function, BRONJ is more severe, and there may be a decrease in patient response to treatment. PMID:28280705

  9. Impact of Actinomyces naeslundii on bisphosphonate-related osteonecrosis of the jaws in ovariectomized rats with periodontitis.

    Science.gov (United States)

    Li, Chun Lei; Seneviratne, Chaminda Jayampath; Huo, Lei; Lu, Weijia William; Zheng, Li Wu

    2015-10-01

    Bisphosphonates-related osteonecrosis of the jaws (BRONJ) is a severe complication of BPs therapy with unknown pathogenesis. This study aimed to evaluate the impact of Actinomyces naeslundii (A. naeslundii) on the progression of BRONJ in ovariectomized (OVX) rat model with periodontal diseases. Sixty rats were randomly assigned into four groups. All rats underwent bilateral ovariectomy. Six weeks after surgery, animals with periodontitis induced by ligature placement were administrated with normal saline (NS), NS &A. naeslundii inoculation, zolecdronic acid (ZA) and ZA &A. naeslundii inoculation for 12 weeks, respectively. Loads of total bacteria and A. naeslundii in the mouth were assessed by real time PCR. After sacrifice, the mandibles were harvested for micro-computed tomography (micro-CT) and histological examination. Real-time PCR demonstrated that A. naeslundii was not routinely found in the rats and ZA treatment did not promote its accumulation. Micro-CT examination disclosed that ligature placement induced significant alveolar bone loss, which was greatly attenuated by ZA treatment and aggravated by A. naeslundii. Histological assessment demonstrated that ZA treatment increased the risk of developing BRONJ-like disease but this condition was not worsen with the presence of A. naeslundii. Our study suggested that oral A. naeslundii inoculation aggravated periodontal disease but not BRONJ in our animal model.

  10. Bisphosphonate adverse effects, lessons from large databases

    DEFF Research Database (Denmark)

    Abrahamsen, Bo

    2010-01-01

    PURPOSE OF REVIEW: To review the latest findings on bisphosphonate safety from health databases, in particular sources that can provide incidence rates for stress fractures, osteonecrosis of the jaw (ONJ), atrial fibrillation and gastrointestinal lesions including esophageal cancer. The main focus...... health databases. However, database studies have limited specificity and sensitivity for atypical fractures and ONJ. Clinical case control studies are recommended....

  11. Survival of dental implants in post-menopausal bisphosphonate users.

    Science.gov (United States)

    Koka, Sreenivas; Babu, Nivedhitha Malli Suresh; Norell, Aaron

    2010-07-01

    To determine whether post-menopausal women with a history of bisphosphonate use are at greater risk for implant failure or osteonecrosis of the jaw (ONJ) than an age- and gender-matched population with no history of bisphosphonate use. A retrospective chart review and phone interview was conducted of patients seen at the Mayo Clinic who had implants placed after November 2006. Bisphosphonate users were identified by medical chart review. Dental implant survival and ONJ incidence were determined in a total of 82 post-menopausal non-bisphosphonate users and 55 post-menopausal bisphosphonate users using a phone interview. Implant failures were recorded and survival percentages were calculated for comparison. ONJ was not observed consequent to implant placement in any of the bisphosphonate users or non-users. In non-users, 163 out of 166 implants were surviving for a cumulative survival rate of 98.19%. In bisphosphonate users, 120 out of 121 implants were surviving for a cumulative survival rate of 99.17%. Dental implants placed in post-menopausal women have the same survival potential regardless of whether patients have a history of bisphosphonate use. Bisphosphonate users who undergo dental implant surgery are at low risk for osteonecrosis of the jaw and a bisphosphonate "drug holiday" is not indicated in these patients. Copyright 2010 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

  12. Evaluation by an Aeronautic Dentist on the Adverse Effects of a Six-Week Period of Microgravity on the Oral Cavity

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    Balwant Rai

    2011-01-01

    Full Text Available Objective. HDT bed rest condition is a simulated microgravity condition in which subject lies on bed inclined −6 degree feet up. To determine the influence of a simulated microgravity (HDT bed rest on oral cavity, 10 healthy male volunteers were studied before, during, just after, and after 6 weeks of the simulated microgravity condition of −6° head-down-tilt (HDT bed rest. Materials and Methods. Facial nerve function, facial sensation, chemosensory system, salivary biomarkers were measured. Results. Lactate dehydrogenase, MIP 1 alpha, malonaldehyde, 8-hydroxydeoxyguanosine, and thiocyanate were found to increase significantly, while flow rate, sodium, potassium, calcium, phosphate, protein, amylase activity, vitamin E and C, and mouth opening were decreased in simulation environments in contradiction to normal. The threshold for monosodium glutamate (MSG and capsaicin increased during microgravity as compared to normal conditions. Moderate pain of teeth, facial oedema, mild pain, loss of sensation of pain and temperature, decreased tongue, and mandibular movement in simulation microgravity environments were observed. Conclusions. These results suggest that reversible effect of microgravity is oedema of face, change in taste, abnormal expression of face, teeth pain, and xerostomia. Further study will be required on large scale on long-term effects of microgravity on oral cavity to prevent the adverse effects.

  13. Risk Assessment of BRONJ in Oncologic Patients Treated with Bisphosphonates: Follow-Up to 18 Months

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    Scilla Sparabombe

    2014-01-01

    Full Text Available Objectives. Bisphosphonates related osteonecrosis of the jaw (BRONJ is a pathological condition characterized by bone exposure or latent infection in patients treated with the drug. The aim of the study is to monitor the BRONJ level of risk health in patients with cancer, according to a preventive clinical protocol, which is firstly aimed at reducing risk factors such as the periodontal infections. Materials and Methods. 10 patients participated in the protocol and were evaluated at baseline and after 3 and 18 months of treatment with bisphosphonates, through full mouth plaque and bleeding scores (FMPS and FMBS, clinical attachment level (CAL measurement, and the occurrence of osteonecrosis. Results. The mean plaque and bleeding were reduced and the CAL has not shown significant changes and in no cases was there manifestation of BRONJ. Conclusion. The protocol proved crucial for the maintenance of good oral health conditions by eliminating the risk of BRONJ during the observation period.

  14. A case of early detection of bisphosphonate-related osteonecrosis of the jaw

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    Miyu Mori

    2015-01-01

    Full Text Available Osteonecrosis of the jaws is an adverse reaction associated with the use of bisphosphonates. Although the diagnosis of bisphosphonate-related osteonecrosis of the jaw (BRONJ is based on symptomatology, it is often detected late because the patients become symptomatic only after osteonecrosis is well established. We describe a case of early oral BRONJ detected by magnetic resonance imaging (MRI accidentally. Head MRI revealed low signal of T1-weight images in left mandibula. Patient had been treated with minodronate for osteoporosis during 18 months. Based on the MRI findings and medication history, early stage BRONJ could be considered. Therefore minodronate was switched to teriparatide. Thereafter mandible pares-thesias, odontalgia and exposed bone were not observed. This case suggests that MRI is useful for the early detection of BRONJ.

  15. Prevalence of bisphosphonate associated osteonecrosis of the jaws in multiple myeloma patients

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    Blum Christina

    2010-07-01

    Full Text Available Abstract Background Bisphosphonate-associated osteonecrosis of the jaws (BP-ONJ is an adverse effect of bisphosphonate treatment with varying reported incidence rates. Methods In two neighboring German cities, prevalence and additional factors of the development of BP-ONJ in multiple myeloma patients with bisphosphonates therapy were recorded using a retrospective (RS and cross-sectional study (CSS design. For the RS, all patients treated from Jan. 2000 - Feb. 2006 were contacted by letter. In the CSS, all patients treated from Oct. 2006 - Mar. 2008 had a physical and dental examination. Additionally, a literature review was conducted to evaluate all articles reporting on BP-ONJ prevalence. PubMed search terms were: bisphosphonat, diphosphonate, osteonecrosis, prevalence and incidence. Results In the RS, data from 81 of 161 patients could be obtained; four patients (4.9% developed BP-ONJ. In the CSS, 16 of 78 patients (20.5% developed BP-ONJ. All patients with BP-ONJ had received zoledronate; 12 of these had had additional bisphosphonates. All except one had an additional trigger factor (tooth extraction [n = 14], dental surgical procedure [n = 2], sharp mylohyoid ridge [n = 3]. Conclusion The prevalence of BP-ONJ may have been underestimated to date. The oral examination of all patients in this CSS might explain the higher prevalence, since even early asymptomatic stages of BP-ONJ and previously unnoticed symptomatic BP-ONJ were recorded. Since nearly all patients with BP-ONJ had an additional trigger factor, oral hygiene and dental care might help to reduce BP-ONJ incidence.

  16. Establishment of an Animal Model of Bisphosphonate-Related Osteonecrosis of the Jaws in Spontaneously Diabetic Torii Rats.

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    Kazuki Takaoka

    Full Text Available We evaluated the side effects of bisphosphonate (BP on tooth extraction socket healing in spontaneously diabetic Torii (SDT rats, an established model of non-obese type 2 diabetes mellitus, to develop an animal model of BP-related osteonecrosis of the jaws (BRONJ.Male Sprague-Dawley (SD rats and SDT rats were randomly assigned to the zoledronic acid (ZOL-treated groups (SD/ZOL or SDT/ZOL or to the control groups (SD/control or SDT/control. Rats in the SD/ZOL or SDT/ZOL groups received an intravenous bolus injection of ZOL (35 μg/kg every 2 weeks. Each group consisted of 6 rats each. Twenty-one weeks after ZOL treatment began, the left maxillary molars were extracted. The rats were euthanized at 2, 4, or 8 weeks after tooth extraction, and the total maxillae were harvested for histological and histochemical studies.In the oral cavity, bone exposure persisted at the tooth extraction site in all rats of the SDT/ZOL group until 8 weeks after tooth extraction. In contrast, there was no bone exposure in SD/control or SDT/control groups, and only 1 of 6 rats in the SD/ZOL group showed bone exposure. Histologically, necrotic bone areas with empty lacunae, microbial colonies, and less invasion by inflammatory cells were observed. The number of tartrate-resistant acid phosphatase-positive osteoclasts was lower in the SDT/ZOL group than in the SD/control group. The mineral apposition rate was significantly lower in the SDT/ZOL group compared with the SD/control group.This study demonstrated the development of BRONJ-like lesions in rats and suggested that low bone turnover with less inflammatory cell infiltration plays an important role in the development of BRONJ.

  17. Bisphosphonate as a Countermeasure to Space Flight-Induced Bone Loss

    Science.gov (United States)

    Spector, Elisabeth; LeBlanc, A.; Sibonga, J.; Matsumoto, T.; Jones, J.; Smith, S. M.; Shackelford, L.; Shapiro, J.; Lang, T.; Evans, H.; Spector, E.; Nakamura, T.; Kohri, K.; Ohshima, H.

    2009-01-01

    flight and two dosing regimens: 1) an oral dose of 70 mg of alendronate taken weekly during flight or 2) a single intravenous (IV) dose of 4 mg of zoledronic acid given several weeks before flight. Currently the study is focusing on the oral option because of NASA s safety concerns with the IV-administered drug. The protocol requests 10 male or female crewmembers on ISS flights of 90 days or longer. Controls are 16 previous ISS crewmembers with QCT scans of the hip performed by these same investigators. The primary outcome measure for this study is hip trabecular bone mineral density measured by QCT, but other measures of bone mass are performed including peripheral QCT (pQCT) and dual-energy x-ray absorptiometry. Serum and urinary bone markers and renal stone risk measured before, during, and after flight are included. Postflight data are currently being collected from 2 ISS crewmembers. Two additional crewmembers will return this spring after 6-month missions. To date no untoward effects have been encountered.

  18. Bisphosphonate-induced atypical subtrochanteric femoral fracture

    OpenAIRE

    2013-01-01

    The use of bisphosphonates (BPs) is universally accepted in the management of osteoporosis. However, a small percentage of patients have been recognised to develop atypical subtrochanteric fractures of the femur with the prolonged use of BPs. We report a rare case of bilateral insufficiency lesions in the proximal femora, where a major subtrochanteric fracture developed with a minor fall. This was successfully treated with internal fixation using proximal femoral nail.

  19. Evolution and etiopathogenesis of bisphosphonates induced osteonecrosis of the jaw

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    Vijay Kumar

    2013-01-01

    Full Text Available Bisphosphonates (BPs is widely used as the first line of treatment choice for osteoporosis, Paget′s disease of bone, bone cancer metastasis and hypercalcemia of malignancy. BPs induced osteonecrosis of the jaw (ONJ is a relatively rare but severe clinical condition cited in English literature since 2003 while exact pathogenesis of BPs induced ONJ is not known until today, but numerous hypotheses were described in recent literature that promote and interlinked the development of BPs induced ONJ. These hypotheses indicate multifactorial nature of its development and factors responsible for that are; long term administration of intravenous nitrogen containing BPs in cancer patients, biological behavior of jaw, antiangiogenic property of BPs and by soft-tissue toxicity etc., All these factors are compounded by the presence of infection that are responsible for lower the pH of the oral cavity, other drugs like administration of corticosteroid, pathologies that cause hypo-calcification of bone, compromised immune response that alters normal healing such as renal transplantation followed by long term oral BPs therapy or chronic diabetic patients receiving BPs therapy and any dentoalveolar trauma. All literature in this review article is search from PubMed, Med-know and Google search engines.

  20. Differential Effects of Silver Nanoparticles and Silver Ions on Tissue Accumulation, Distribution, and Toxicity in the Sprague Dawley Rat Following Daily Oral Gavage Administration for 13 Weeks.

    Science.gov (United States)

    Boudreau, Mary D; Imam, Mohammed S; Paredes, Angel M; Bryant, Matthew S; Cunningham, Candice K; Felton, Robert P; Jones, Margie Y; Davis, Kelly J; Olson, Greg R

    2016-03-01

    There are concerns within the regulatory and research communities regarding the health impact associated with consumer exposure to silver nanoparticles (AgNPs). This study evaluated particulate and ionic forms of silver and particle size for differences in silver accumulation, distribution, morphology, and toxicity when administered daily by oral gavage to Sprague Dawley rats for 13 weeks. Test materials and dose formulations were characterized by transmission electron microscopy (TEM), dynamic light scattering, and inductively coupled mass spectrometry (ICP-MS). Seven-week-old rats (10 rats per sex per group) were randomly assigned to treatments: AgNP (10, 75, and 110 nm) at 9, 18, and 36 mg/kg body weight (bw); silver acetate (AgOAc) at 100, 200, and 400 mg/kg bw; and controls (2 mM sodium citrate (CIT) or water). At termination, complete necropsies were conducted, histopathology, hematology, serum chemistry, micronuclei, and reproductive system analyses were performed, and silver accumulations and distributions were determined. Rats exposed to AgNP did not show significant changes in body weights or intakes of feed and water relative to controls, and blood, reproductive system, and genetic tests were similar to controls. Differences in the distributional pattern and morphology of silver deposits were observed by TEM: AgNP appeared predominantly within cells, while AgOAc had an affinity for extracellular membranes. Significant dose-dependent and AgNP size-dependent accumulations were detected in tissues by ICP-MS. In addition, sex differences in silver accumulations were noted for a number of tissues and organs, with accumulations being significantly higher in female rats, especially in the kidney, liver, jejunum, and colon.

  1. Bisphosphonate Associated Osteonecrosis of the Jaw: An Update on Pathophysiology, Risk Factors, and Treatment

    Directory of Open Access Journals (Sweden)

    Lars Rasmusson

    2014-01-01

    Full Text Available Osteonecrosis of the jaw in patients treated with bisphosphonates is a relatively rare but well known complication at maxillofacial units around the world. It has been speculated that the medication, especially long-term i.v. bisphosphonate treatment, could cause sterile necrosis of the jaws. The aim of this narrative review of the literature was to elaborate on the pathological mechanisms behind the condition and also to gather an update on incidence, risk factors, and treatment of bisphosphonate associated osteonecrosis of the jaw. In total, ninety-one articles were reviewed. All were published in internationally recognized journals with referee systems. We can conclude that necrotic lesions in the jaw seem to be following upon exposure of bone, for example, after tooth extractions, while other interventions like implant placement do not increase the risk of osteonecrosis. Since exposure to the bacterial environment in the oral cavity seems essential for the development of necrotic lesions, we believe that the condition is in fact chronic osteomyelitis and should be treated accordingly.

  2. Bisphosphonate-induced osteonecrosis of the jaws. A clinical study of 21 cases

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    Violetta LIANOU, Maria ALEXOPOULOU, Dimitrios KANOUTOS, Lamprini TROUMPOUKI,

    2011-12-01

    Full Text Available Bisphosphonates are the first-line drugs for osteoporosis, as well as for many types of cancer.One of their side-effects is osteonecrosis of the jaw, which has mainly been associated with their intravenous administration.This article features a clinical study of 21 cases of jaw osteonecrosis – 9 male and 12 female patients, with a mean age of 63 years and established bisphosphonate osteonecrosis of the jaws (BONJ, who were treated either conservatively or surgically in the past five years(2005-2010. Of these 21 patients, 17 were on bisphosphonates due to neoplastic disease and another 4 due to osteoporosis. Anti microbial chemotherapy and oral hygiene was the initial treatment for 10 patients with minor symptoms, while a broad spectrum of surgical treatments – from selected tooth extraction under prophylactic administration of antibiotics to marginal resection of necrotic bone – were used in 11 patients with severe bone exposure, infection and masticatory impairment. The majority of the patients who were surgically treated had a satisfactory outcome with no major complications, while 3 patients died from the main disease during the follow-up period.With in this context, we also present in detail the inclusion and taxonomy criteria for this particular disease, as well as our therapeutic protocols, and review the most significant contributions to the literature

  3. Bisphosphonate-related osteonecrosis of the jaw in patients with multiple myeloma.

    Science.gov (United States)

    Infante Cossío, Pedro; Cabezas Macián, Antonio; Pérez Ceballos, José Luis; Palomino Nicas, Julián; Gutiérrez Pérez, José Luis

    2008-01-01

    To review the main clinical-radiographic, therapeutic, and preventive aspects of osteonecrosis related to intravenous bisphosphonate therapy in patients with multiple myeloma. Between 2005 and 2006, we studied four patients with previous diagnosis of multiple myeloma treated with intravenous zoledronic acid, presenting nonhealing extraction sockets and intraoral exposed bone. We assessed the location of lesions, the relation with previous history of dento-alveolar surgery procedures, the clinical features, the treatments carried out, and the outcomes achieved. All the patients were treated with chlorhexidine mouthwashes and oral amoxycillin-clavulanic acid for long periods of time. Two patients did not respond to the conservative management and needed surgical bone debridement. Dental extractions seem to contribute the development of osteonecrosis of the jaw in patients with multiple myeloma treated with intravenous bisphosphonate therapy. Whereas the pathologic mechanisms are not known, these patients should undergo frequent check-ups before, during, and after bisphosphonate therapy. The management must be symptomatic and palliative, including systemic antibiotics, control of pain, and chlorhexidine mouthwashes during long periods of time.

  4. 双膦酸盐和下颌骨坏死%Bisphosphonates and jaw osteonecrosis

    Institute of Scientific and Technical Information of China (English)

    李彦博; 刘霏霏

    2012-01-01

    Objective: Understanding the physical and chemical properties of bisphosphonates and their pharmacological features and the situation of bisphosphonate - related osteonecrosis of the jaws ( BRONJ). Methods: To present a literature review on bisphosphonates, focusing on their pharmacological features and their reported association with jaw osteonecrosis. Results: Bisphosphonates have been widely prescribed for treatment of diseases characterized by intense bone resorption. These drugs have also been associated with a serious side effect, avascular osteonecrosis of the jaws. The morbidity and lack of treatment response of this condition are serious facts to be considered when prescribing bisphosphonate therapy. The risk -benefit relationship needs to be seriously analyzed, and the treatment pros and cons should be explained to the patient. If the therapy with bisphosphonate is indicated, rigorous oral health adequacy must be performed and periodic evaluation of oral conditions is mandatory. Conlousiotl; Considering the seriousness of the potential occurrence of bisphosphonate - related osteonecrosis of the jaws, caution in prescribing these drugs and careful observation of patients being treated with them seems to be indicated. Lesion prevention in patients undergoing bisphosphonate therapy is essential to prevent and control morbidity associated with advanced destructive lesions.%目的:了解双膦酸盐的理化性质和药理学特性以及与其相关的下颌骨坏死的有关情况.方法:综述双膦酸盐和与其相关的下颌骨坏死的文献.结果:双膦酸盐已经被广泛用于治疗以骨吸收为特点的疾病.这些药物也越来越与下颌骨缺血性坏死这种严重的副作用联系在一起.考虑到下颌骨坏死的发生和对其缺乏有效治疗措施的事实,计划使用双膦酸盐治疗时,应认真分析风险-效益的关系,并向病人说明治疗的利弊.如果要使用双膦酸盐治疗,必须进行严谨的口腔卫生

  5. Effect on morphology, oxidative stress and energy metabolism enzymes in the testes of mice after a 13-week oral administration of melamine and cyanuric acid combination.

    Science.gov (United States)

    Lv, Yingjun; Liu, Zhijun; Tian, Yujie; Chen, Hongbo

    2013-03-01

    Cases of pet poisoning and infant renal calculus have attracted much attention to the toxicity of melamine and its derivatives, such as cyanuric acid. Although individually melamine and cyanuric acid have low toxicity, their simultaneous presence can cause severe damage. Little is known about their adverse effects on the reproductive system. In this study, mice were orally administrated 1, 5 or 25 mg/kg/d of both melamine and cyanuric acid for 13 weeks. Lethargy, rough hair, and reduction of food and water intake and of body and testis weight were found after exposure to the combination, and pathological changes were found in the morphology of the testes, such as disruption of the seminiferous tubule structure, decrease of the spermatogenic cell series and coagulation necrosis. Total antioxidant capacity and superoxide dismutase activities and glutathione concentration was lower and malondialdehyde concentration was higher than in control mice. The activities of malate dehydrogenase, lactate dehydrogenase and Na(+)/K(+)-ATPase were also lower in combination treated mice than in control mice. These results indicate that the combined exposure to both melamine and cyanuric acid damaged testes in mice by either a direct or indirect effect, which may be related to renal failure and secondary anorexia. Oxidative stress and lower energy production levels both contributed to the testicular damage.

  6. Osteonecrosis of the jaw in a patient with rheumatoid artritis treated with an oral aminobisphosphonate: a clinical case report.

    Science.gov (United States)

    Longato, Lorena; Cavalli, Loredana; Marcucci, Gemma; Metozzi, Alessia; Giusti, Francesca; Brandi, Maria Luisa; Piscitelli, Prisco

    2013-05-01

    Osteonecrosis of the jaw (ONJ) has been recently described after intravenous administration of amino-bisphosphonates and - less frequently - in association with the use of oral bisphosphonates. Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) may affect mandible bone (65%), maxilla bone (26%) and rarely (9%) both sites simultaneously. Although causality may never be proven, emerging experimental data have established a strong association between monthly intravenous bisphosphonate administration and ONJ. Current level of evidence does not fully support a cause and effect relationship between the use of oral BPs and ONJ. In this paper, we report a clinical case of BRONJ in a 73 years old woman affected by rheumatoid arthritis (RA) and periodontitis, after three years of treatment with alendronate 70 mg one a week, plus daily calcium and vitamin D. The patient developed a tooth abscess at the lower jaw, accompanied by increased inflammatory markers, that never returned to normal range despite antibiotic therapy, inducing deterioration of joint synovium. The worsening of joint status after the onset of ONJ was reflected by the progressive increase in the number of swollen (SJ) and tender (TJ) joints, by the deterioration of the score DAS 28 (which passed from 5.46 to 7.07), pain (with VAS increasing from 60 to 90), and by a progressively impaired quality of life, as reported using the HAQ score (from 1,25 to 2,5). The patient was switched to antifracture therapy with strontium ranelate and the osteonecrosis was successfully treated with antibiotics, surgical curettage and local ultrasounds.

  7. Differential effects of bisphosphonates on breast cancer cell lines

    NARCIS (Netherlands)

    Verdijk, R.; Franke, H.R.; Wolbers, F.; Vermes, I.

    2007-01-01

    Bisphosphonates may induce direct anti-tumor effects in breast cancers cells in virtro. In this study, six bisphosphonates were administered to three breast caner cell lines. Cell proliferation was measured by quantification of th expressio of Cyclin D1 mRNA. Apoptosis was determined by flow cytome

  8. Are bisphosphonates the suitable anticancer drugs for the elderly?

    Science.gov (United States)

    Santini, Daniele; Fratto, Maria Elisabetta; Galluzzo, Sara; Vincenzi, Bruno; Tonini, Giuseppe

    2009-01-01

    Bone metastases represent an important problem in the elderly. These patients are exposed to a higher risk of developing skeletal-related events (SREs) with a subsequent decrease in quality of life and survival. Bisphosphonates have demonstrated to reduce and delay the appearance of SREs and to improve the quality of life also in elderly bone metastatic patients. Moreover, in vitro and in vivo preclinical studies suggest that bisphosphonates exert direct as well as indirect antitumor effect. Interestingly, recent clinical data confirm these results in bone metastatic cancer patients. However, randomized trials restricted to elderly patients with metastatic bone disease and focused to evaluate survival benefits have not yet been planned even if elderly patients, especially multiple myeloma, prostate and lung cancer patients, have been often included in trials. This review will examine in detail the preclinical rationale for using bisphosphonates as anticancer agents in elderly patients and will critically explore the first retrospective and prospective clinical evidences of an increased survival in patients treated with bisphosphonates. Moreover, we will analyze the safety of bisphosphonates in elderly population and discuss the clinical recommendations expressed by the SIOG Society for the use of bisphosphonates in elderly patients. Randomized clinical trials to assess the role of bisphosphonate therapy in the adjuvant setting are currently in progress and will be described in this review. If the results of these ongoing clinical trials will be positive, the indications for bisphosphonates could increase, including also elderly patients.

  9. Etiologic diagnosis of jaw osteonecrosis, other than bisphosphonate and radiotherapy related osteonecrosis.

    Science.gov (United States)

    Magremanne, M; Picheca, S; Reychler, H

    2014-02-01

    Our purpose was to highlight the various etiologies of maxillo-mandibular osteonecrosis, other than radiotherapy and biphosphonate related osteitis that have been abundantly reported. We performed a PubMed search from August 1, 1972 to August 1, 2012 using the following MeSH terms: "osteonecrosis", "bone", "necrosis", "jaw", "maxilla", "mandible", "palate", "oral", "avascular necrosis", NOT "bisphosphonate" NOT "osteoradionecrosis". Most cases of osteonecrosis were iatrogenic. Viral, mycotic, or bacterial infections were less frequent causes. Cocaine abuse, Wegener's granulomatosis, and N/K lymphoma were other etiologies. It is important to identify the various etiologies rapidly to manage this sometimes very mutilating condition adequately.

  10. [Etiologic diagnosis of jaw osteonecrosis, other than bisphosphonate and radiotherapy related osteitis].

    Science.gov (United States)

    Magremanne, M; Picheca, S; Reychler, H

    2014-02-01

    Our purpose was to highlight the various etiologies of maxillo-mandibular osteonecrosis, other than radiotherapy and biphosphonate related osteitis that have been abundantly reported. We performed a PubMed search from August 1, 1972 to August 1, 2012 using the following MeSH terms: "osteonecrosis", "bone", "necrosis", "jaw", "maxilla", "mandible", "palate", "oral", "avascular necrosis", NOT "bisphosphonate" NOT "osteoradionecrosis". Most cases of osteonecrosis were iatrogenic. Viral, mycotic, or bacterial infections were less frequent causes. Cocaine abuse, Wegener's granulomatosis, and N/K lymphoma were other etiologies. It is important to identify the various etiologies rapidly to manage this sometimes very mutilating condition adequately.

  11. Bisphosphonate therapy and osteonecrosis of the jaw complicated with a temporal abscess in an elderly woman with rheumatoid arthritis: a case report

    Directory of Open Access Journals (Sweden)

    Manzon L

    2014-08-01

    Full Text Available Licia Manzon,1 Evaristo Ettorre,1 Giovanni Viscogliosi,1 Stefano Ippoliti,1 Fabio Filiaci,2 Claudio Ungari,2 Giovanni Fratto,1 Alessandro Agrillo2 1Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences, 2Department of Odontology and Maxillofacial Surgery, “Sapienza” University, Rome, Italy Abstract: Bisphosphonate-related osteonecrosis of the jaw (BRONJ is an adverse drug reaction described as the progressive destruction and death of bone tissue of the mandible or maxilla, in the course of bisphosphonate therapy. Orally administered bisphosphonates, widely used for the treatment of osteoporosis, are rarely associated with BRONJ. Instead, the risk greatly increases whether the patient is concomitantly taking steroid and/or immunosuppressant agents. The aims of this paper are to briefly discuss the evidence of the associations between bisphosphonate therapy and BRONJ, and the effects of co-occurring factors such as the presence of rheumatoid arthritis, dental surgery, and concomitant corticosteroid therapy. In particular, we present the case of an elderly woman with BRONJ suffering from rheumatoid arthritis, with a recent dental extraction and with a very unusual complication: a temporal abscess, who was successfully treated. Keywords: bisphosphonate-related osteonecrosis of the jaw, BRONJ, adverse reaction, steroidsA Letter to Editor has been received and published for this article

  12. Bisphosphonates inactivate human EGFRs to exert antitumor actions

    Science.gov (United States)

    Yuen, Tony; Stachnik, Agnes; Iqbal, Jameel; Sgobba, Miriam; Gupta, Yogesh; Lu, Ping; Colaianni, Graziana; Ji, Yaoting; Zhu, Ling-Ling; Kim, Se-Min; Li, Jianhua; Liu, Peng; Izadmehr, Sudeh; Sangodkar, Jaya; Bailey, Jack; Latif, Yathin; Mujtaba, Shiraz; Epstein, Solomon; Davies, Terry F.; Bian, Zhuan; Zallone, Alberta; Aggarwal, Aneel K.; Haider, Shozeb; New, Maria I.; Sun, Li; Narla, Goutham; Zaidi, Mone

    2014-01-01

    Bisphosphonates are the most commonly prescribed medicines for osteoporosis and skeletal metastases. The drugs have also been shown to reduce cancer progression, but only in certain patient subgroups, suggesting that there is a molecular entity that mediates bisphosphonate action on tumor cells. Using connectivity mapping, we identified human epidermal growth factor receptors (human EGFR or HER) as a potential new molecular entity for bisphosphonate action. Protein thermal shift and cell-free kinase assays, together with computational modeling, demonstrated that N-containing bisphosphonates directly bind to the kinase domain of HER1/2 to cause a global reduction in downstream signaling. By doing so, the drugs kill lung, breast, and colon cancer cells that are driven by activating mutations or overexpression of HER1. Knocking down HER isoforms thus abrogates cell killing by bisphosphonates, establishing complete HER dependence and ruling out a significant role for other receptor tyrosine kinases or the enzyme farnesyl pyrophosphate synthase. Consistent with this finding, colon cancer cells expressing low levels of HER do not respond to bisphosphonates. The results suggest that bisphosphonates can potentially be repurposed for the prevention and therapy of HER family-driven cancers. PMID:25453081

  13. Improvement of pain and regional osteoporotic changes in the foot and ankle by low-dose bisphosphonate therapy for complex regional pain syndrome type I: a case series

    Directory of Open Access Journals (Sweden)

    Wada Takuro

    2011-08-01

    in radioactivity in his foot. One month after the start of oral administration of alendronate (35 mg per week, his bone pain had fallen from a visual analog scale score of 83 out of 100 to 30 out of 100 and, at nine months, was further reduced to 3 out of 100. The treatment was discontinued at 15 months because of successful pain reduction. At 30 months, our patient had no pain and the radiographic findings revealed marked improvement in regional osteoporotic changes. Conclusions We believe low-dose oral administration of bisphosphonate is worth considering for the treatment of idiopathic complex regional pain syndrome type I accompanied by regional osteoporotic change.

  14. Comparison of three intravenous bisphosphonates in cancer-associated hypercalcaemia.

    Science.gov (United States)

    Ralston, S H; Gallacher, S J; Patel, U; Dryburgh, F J; Fraser, W D; Cowan, R A; Boyle, I T

    1989-11-18

    Three intravenous bisphosphonates were compared in the treatment of cancer-associated hypercalcaemia. 48 patients were randomly allocated to one of three treatment groups (each with 16 subjects)--30 mg pamidronate or 600 mg clodronate, both as single intravenous infusions; or etidronate as three infusions of 7.5 mg/kg per day for three consecutive days. Patients were rehydrated with normal saline before bisphosphonate treatment. All three bisphosphonates lowered serum calcium by inhibiting bone resorption; pamidronate was the most potent in this respect. By comparison with the other groups, more patients in the pamidronate group became normocalcaemic, and the effect on serum calcium was apparent sooner and lasted longer.

  15. The bisphosphonates: risks and benefits of long term use

    DEFF Research Database (Denmark)

    Hermann, Anne Pernille; Abrahamsen, Bo

    2013-01-01

    Bisphosphonates are widely used globally as the main treatment for osteoporosis. Both safety and efficacy have only been rigorously evaluated in studies of relatively short duration (3-5 years), with smaller extension studies. The evidence for benefit beyond five years in intervention studies...... is limited and does not include proven efficacy against nonvertebral fractures. Observational studies suggest a sustained benefit against hip fractures. Bisphosphonates are stored in the skeleton for months to years, depending on the degree of bone turnover and the binding properties of the bisphosphonate...

  16. Long-term safety and efficacy of linagliptin as monotherapy or in combination with other oral glucose-lowering agents in 2121 subjects with type 2 diabetes: up to 2 years exposure in 24-week phase III trials followed by a 78-week open-label extension.

    Science.gov (United States)

    Gomis, R; Owens, D R; Taskinen, M-R; Del Prato, S; Patel, S; Pivovarova, A; Schlosser, A; Woerle, H-J

    2012-08-01

    Aim:  The aim of this study was to evaluate the long-term safety, tolerability and efficacy of the dipeptidyl peptidase-4 inhibitor linagliptin given either alone or in combination with other oral glucose-lowering agents in persons with type 2 diabetes. Methods:  A 78-week open-label extension study evaluated subjects who participated in one of four preceding 24-week, randomised, double-blind, placebo-controlled parent trials and who received linagliptin, linagliptin + metformin, linagliptin + metformin + a sulphonylurea or linagliptin + pioglitazone (all with linagliptin administered orally once daily). Individuals receiving one of these treatments during a previous trial continued the same treatment (n = 1532) for up to a total of 102 weeks, whereas those previously receiving placebo were switched to linagliptin (n = 589). All 2121 participants received at least one dose of the trial medication and were included in the primary safety analysis. Results:  In subjects previously receiving active treatment, the glycosylated haemoglobin A(1c) reduction achieved during the 24-week parent trials was sustained through the 78-week extension period (change from baseline to week 102: -0.8%). Drug-related adverse events were experienced by 14.3% of participants. Hypoglycaemia occurred in 13.9% of participants and was similar between those previously receiving treatment (13.6%) and those switching from placebo to linagliptin (14.6%). Hypoglycaemia occurred most frequently with the use of metformin + a sulphonylurea background therapy (11%). Overall, no clinically relevant changes in body weight were observed. Conclusion:  Long-term treatment with linagliptin was well tolerated with no change in the safety profile observed during the extension study. Sustained long-term glycaemic control was maintained for up to 102 weeks with either linagliptin monotherapy or linagliptin in combination with other oral glucose-lowering agents. © 2012

  17. Inflammatory eye reactions in patients treated with bisphosphonates and other osteoporosis medications - cohort analysis using a national prescription database

    DEFF Research Database (Denmark)

    Pazianas, Michael; Clark, Emma M; Eiken, Pia Agnete

    2013-01-01

    ) and hospital data. Between Jan 1, 1997 and Dec 31, 2007, a total of 88,202 patients beginning osteoporosis therapy were identified. Of those patients, 82,404 (93%) began oral bisphosphonates and 5798 (7%) non-bisphosphonates. Topical eye steroids (TES) Within the first year of treatment, 4,769 (5...... 27-37) for raloxifene and 64 (95% CI 49-83) for strontium ranelate. After adjustment for age, Charlson index, and the number of co-medications, pulmonary disease in men was associated with an increased use of TES (odds ratio (OR) 1.48; 95% CI 1.17-1.86, p=0.001). In women, malignant disease (OR 1...

  18. Inflammatory eye reactions with bisphosphonates and other osteoporosis medications

    DEFF Research Database (Denmark)

    Clark, Emma M; Durup, Darshana

    2015-01-01

    Inflammatory eye reactions (IERs) are rare but have been associated with medications to treat osteoporosis. The aim of this review is to summarize the current literature on the association between IERs and specific medications to treat osteoporosis (bisphosphonates, selective estrogen receptor...... of the information available is from spontaneous case reports and case series reporting associations between bisphosphonates and IERs. No case reports describe IERs after other anti-osteoporosis medications. Importantly, some case reports describe recurrence of the IER after affected patients were rechallenged...... with the same or another bisphosphonate, and that no reported cases resolved without discontinuation of the bisphosphonate. However, three large population-based cohort studies have shown conflicting results between osteoporosis treatments and IERs, but overall these studies suggest that IERs may actually...

  19. BISPHOSPHONATE-RELATED OSTEONECROSIS OF THE JAW AND DENTAL IMPLANTS

    Directory of Open Access Journals (Sweden)

    Ala Hassan A. Qamheya

    2016-01-01

    Full Text Available Bisphosphonate (BP is one of the possible riskfactors in the osteonecrosis of the jaw (ON J. Surgical interventions during or after the course of treatment by using BPs may expose the patient under this risk. Animal studies, human studies, case reports, and systematic reviews are used to show the relationship between the use of bisphosphonates and dental implants. In this review data about bisphosphonaterelated osteonecrosis of the jaw (BRON J: incidence, prevention and treatment modalities for the patients who are scheduled for dental implant treatment plan and who have been already treated by dental implants will be investigated. Various views for the relationship between dental implants and bisphosphonates will be analyzed depending on the multifactors: duration, route of uptake, dosage of the drug and patient’s other medications that affect the effects of bisphosphonate. All patients treated with this drug must be informed about the risk of implant loss or possibility of osteonecrosis.

  20. Bisphosphonate-related osteonecrosis of the jaw: specificities

    Directory of Open Access Journals (Sweden)

    Siri Paulo

    2014-09-01

    Full Text Available Bisphosphonate-related osteonecrosis of the jaws (BRONJ is a severe complication that has recently emerged in patients treated with intravenous bisphosphonates for malignant diseases. This complication usually presents after a minor local trauma during a dental treatment. Several etiopathogenic mechanisms of this pathological condition have been proposed, but no model can explain all morphological changes observed at the macroscopic and microscopic level. BRONJ is likely to be related to direct toxicity in the bone and soft tissue cells, due to nitrogen-containing bisphosphonates. This review elucidates the clinical indications and mechanism of action of bisphosphonates, reports some clinical diagnostic criteria for BRONJ, describe the histopathological criteria for BRONJ diagnosis, the potential triggering pathways and the available treatment strategies.

  1. Bisphosphonate anticancer activity in prostate cancer and other genitourinary cancers.

    NARCIS (Netherlands)

    Saad, F.; Mulders, P.F.A.

    2012-01-01

    Anticancer therapies have traditionally been targeted directly against cancer cell growth. However, newer treatment strategies also target the microenvironment that supports metastatic cancer cell growth. Bisphosphonates are the standard of care for maintaining bone health in patients with bone

  2. Long-term follow-up of jaw osteomyelitis associated with bisphosphonate use in a tertiary-care center.

    Science.gov (United States)

    Pigrau-Serrallach, Carlos; Cabral-Galeano, Evelyn; Almirante-Gragera, Benito; Sordé-Masip, Roger; Rodriguez-Pardo, Dolors; Fernandez-Hidalgo, Nuria; Larrosa-Escartín, Nieves; Bescos-Atín, Socorro; Pahissa-Berga, Albert

    2014-01-01

    This study reviews our experience in bisphosphonate-associated jaw osteomyelitis (BJOM), focusing on the incidence, etiology, treatment, and long-term outcome. Retrospective review of the clinical histories adult patients diagnosed with BJOM (1995-2008) in a tertiary hospital. BJOM was found in 30 of 132 (22.7%) consecutive patients with jaw osteomyelitis. The percentage of BJOM cases increased from 8.7% (4/46) in 1995-2005 to 30.2% (26/86) in 2005-2008. Symptoms appeared in a median of 2.5 years after intravenous use, and 4.5 years after oral exposure. Viridans group streptococci were isolated in 83.3% of cases. Actinomyces spp. was found in 16 (39.0%) of 41 bone histologies. All included patients received a median of 6 months of appropiate antibiotic therapy and a surgical procedure (debridament and/or sequestrectomy). Thirteen of 27 cases (48.1%) with long-term follow-up (median 22 months, IQR 25-75 17-28) failed. Clinical failure defined as, persistent infection or relapse, was more frequent in patients receiving intravenous than oral bisphosphonates (11/16 [68.8%] vs. 2/11 [18.2%]; P < .05) and in cases with Actinomyces spp. (7/10 [70.0%] vs6/17 [35.3%]; P = .08). Bisphosphonate therapy is now a frequent cause of JO. BJOM is difficult to cure and relapses are common, particularly in patients exposed to intravenous bisphosphonates. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  3. Bisphosphonates in Langerhans Cell Histiocytosis: An International Retrospective Case Series

    Science.gov (United States)

    Chellapandian, Deepak; Makras, Polyzois; Kaltsas, Gregory; van den Bos, Cor; Naccache, Lamia; Rampal, Raajit; Carret, Anne-Sophie; Weitzman, Sheila; Egeler, R. Maarten; Abla, Oussama

    2016-01-01

    Background Bone is the most common organ of involvement in patients with Langerhans cell histiocytosis (LCH), which is often painful and associated with significant morbidity from pathological fractures. Current first-line treatments include chemotherapy and steroids that are effective but often associated with adverse effects, whereas the disease may reactivate despite an initial response to first-line agents. Bisphosphonates are osteoclast inhibitors that have shown to be helpful in treating bone lesions of LCH. To date, there are no large international studies to describe their role in treating bone lesions of LCH. Method We conducted a multicenter retrospective review of 13 patients with histologically proven LCH, who had received bisphosphonates either at diagnosis or at disease reactivation. Results Ten patients (77%) had a single system bone disease, and 3 (23%) had bone lesions as part of multisystem disease. Median follow-up time post-bisphosphonate therapy was 4.6 years (range, 0.8 to 8.2 years). Treatment with bisphosphonates was associated with significant pain relief in almost all patients. Twelve (92%) achieved resolution of active bone lesions, and 10 out of them had no active disease for a median of 3.5 years (range, 0.8 to 5 years). One patient did not respond. No major adverse effects were reported in this series. Conclusion Bisphosphonates are well-tolerated drugs that can significantly improve bone pain and induce remission in active bone LCH. Future prospective studies evaluating the role of bisphosphonates in LCH are warranted. PMID:27413525

  4. Questioning the association between bisphosphonates and atypical femoral fractures

    Science.gov (United States)

    Pazianas, Michael; Kim, Se-min; Yuen, Tony; Sun, Li; Epstein, Sol; Zaidi, Mone

    2014-01-01

    Bisphosphonates are the first line treatment for osteoporosis. Structurally, they are stable analogues of pyrophosphate and therefore exhibit a high affinity for bone mineral. They reduce bone loss by attenuating the ability of the osteoclast to resorb bone, decreasing activation frequency and the rate of remodelling. Large prospective randomized placebo-control trials provide unequivocal evidence for a reduction in the incidence of fractures.1 Impressively, 40 years since their first use in patients, the safety profile of bisphosphonates has been equally re-assuring.2 Questions have arisen lately as to whether bisphosphonates could cause atypical fractures, a rare type of atraumatic or minimal trauma femur fracture occurring below the great trochanter. This question has prompted calls for a broader examination of the long-term effects of bisphosphonate use. An attempt by the Food and Drug Administration (FDA) to garner consensus and provide definitive views was not successful.3 This has led to continued anxiety among treating physicians and patients alike, resulting in an overall reduction in prescriptions for bisphosphonates and for osteoporosis therapies in general. Here, we provide an overview of the current data on atypical fractures and bisphosphonate use. PMID:25294742

  5. Bisphosphonate Therapy (and Osteonecrosis of the Jaw)

    Science.gov (United States)

    ... cases of individuals having difficulty healing after undergoing tooth extraction or other invasive dental procedures, a phenomenon called ... However, most reported cases occur after oral trauma (tooth extraction or oral surgical procedure). Tobacco use, treatment with ...

  6. Systematic reviews of oral complications from cancer therapies, Oral Care Study Group, MASCC/ISOO : methodology and quality of the literature

    NARCIS (Netherlands)

    Brennan, Michael T.; Elting, Linda S.; Spijkervet, Fred K. L.

    2010-01-01

    Oral complications are commonly experienced by patients undergoing cancer therapies. The Oral Care Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) has completed nine systematic reviews including Bisphosphonate Osteonecrosi

  7. RANK/RANKL/OPG signaling pathways in necrotic jaw bone from bisphosphonate-treated subjects

    Directory of Open Access Journals (Sweden)

    C. Di Nisio

    2015-02-01

    Full Text Available Osteonecrosis of the jaw (ONJ is a chronic complication affecting long-term bisphosphonate-treated subjects, recognized by non-healing exposed bone in the maxillofacial region. The pathophysiological mechanism underlying ONJ has not been fully elucidated. The aim of the present study was to investigate the role of RANK/RANKL/OPG signaling pathway and, in parallel, to evaluate angiogenic and matrix mineralization processes in jaw bone necrotic samples obtained from bisphosphonate-treated subjects with established ONJ. Necrotic bone samples and native bone samples were processed for Light and Field Emission in Lens Scanning Electron Microscope (FEISEM analyses, for Real-Time RT-PCR to evaluate the gene expression of TNFRSF11A (RANK, TNFSF11 (RANKL, and TNFSF11B (OPG and for immunohistochemical analyses of VEGF and BSP expression. Morphological analyses performed by Light microscope and FEISEM show empty osteocytic lacunae and alteration of lamellar organization with degradation of the mineralized bone matrix in necrotic bone samples. A significant increase in TNFRSF11A, TNFSF11, TRAF6 and NFAT2 gene expression, and a reduction of TNFSF11B gene transcription level compared is also showed in necrotic bone compared to control samples. No significant difference of VEGF expression is evidenced, while lower BSP expression in necrotic bone compared to healthy samples is found. Even if the pathogenesis of bisphosphonate-associated ONJ remains unknown, a link between oral pathogens and its development seems to exist. We suppose lipopolysaccharide produced by bacteria colonizing and infecting necrotic bone and the surrounding viable area could trigger RANK/RANKL/OPG signaling pathway and, in this context, osteoclasts activation could be considered as a protective strategy carried out by the host bone tissue to delimitate the necrotic area and to counteract infection.

  8. Risk of femoral shaft and subtrochanteric fractures among users of bisphosphonates and raloxifene

    DEFF Research Database (Denmark)

    Vestergaard, P; Schwartz, F; Rejnmark, L;

    2010-01-01

    Prior studies have suggested an association between bisphosphonate use and subtrochanteric fractures. This cohort study showed an increased risk of subtrochanteric and femoral shaft fractures both before and after the start of drugs against osteoporosis including bisphosphonates. This may suggest...

  9. Efficacy and safety of canagliflozin alone or as add-on to other oral antihyperglycemic drugs in Japanese patients with type 2 diabetes: A 52-week open-label study

    Science.gov (United States)

    Inagaki, Nobuya; Kondo, Kazuoki; Yoshinari, Toru; Kuki, Hideki

    2015-01-01

    Aims/Introduction Canagliflozin is a sodium–glucose cotransporter 2 inhibitor under development for the treatment of type 2 diabetes. Our aim was to examine its efficacy and safety as monotherapy or in combination with commonly used oral antihyperglycemic drugs in Japanese patients with type 2 diabetes. Materials and Methods Patients on diet/exercise alone or diet/exercise plus an oral antihyperglycemic drug (sulfonylurea, glinide, α-glucosidase inhibitor, biguanide, thiazolidinedione or dipeptidyl peptidase-4 inhibitor) were randomized to either 100 or 200 mg canagliflozin while continuing prior therapy. Patients were treated for 52 weeks in an open-label manner. Results Canagliflozin significantly reduced hemoglobin A1c, fasting plasma glucose and bodyweight in all the study groups. Improvements were apparent by 4 weeks of treatment, and were maintained for 52 weeks. The reduction in hemoglobin A1c ranged from −0.80 to −1.06%, and from −0.93 to −1.26% in the 100 and 200 mg canagliflozin groups, respectively. Drug-related adverse events occurred in approximately one-third of patients, and included hypoglycemia/asymptomatic hypoglycemia and pollakiuria. Hypoglycemia/asymptomatic hypoglycemia was most common in patients treated with a sulfonylurea. Most adverse events were classified as mild or moderate in severity. Conclusions The results of the present study confirmed that treatment with canagliflozin resulted in significant reductions in glycemic control and bodyweight that were maintained for 52 weeks of treatment irrespective of whether it was administered as monotherapy or in combination with another oral antihyperglycemic drug. Canagliflozin was well tolerated, with a low incidence of drug-related adverse events. This trial was registered with ClinicalTrials.gov (no. NCT01387737). PMID:25802729

  10. The Active Metabolite of Warfarin (3'-Hydroxywarfarin) and Correlation with INR, Warfarin and Drug Weekly Dosage in Patients under Oral Anticoagulant Therapy: A Pharmacogenetics Study

    OpenAIRE

    2016-01-01

    Objectives Warfarin oral anticoagulant therapy (OAT) requires regular and frequent drug adjustment monitored by INR. Interindividual variability, drug and diet interferences, and genetics (VKORC1 and CYP2C9) make the maintenance/reaching of stable INR a not so easy task. HPLC assessment of warfarin/enantiomers was suggested as a valid monitoring-tool along with INR, but definite results are still lacking. We evaluated possible correlations between INR, warfarin/3’-hydroxywarfarin, and drug we...

  11. Novel 1-hydroxy-1,1-bisphosphonates derived from indazole: synthesis and characterization

    OpenAIRE

    Teixeira, Fátima C.; Antunes, Inês F.; Curto, M. João M.; Neves, M.; Teixeira, António P. S.

    2009-01-01

    Bisphosphonates (BPs) are an important class of drugs used in the treatment of abnormal calcium metabolism diseases. The first syntheses of bisphosphonates derived from indazole, substituted at the N-1, N-2 and C-3 positions are reported. The 1-hydroxy-1,1-bisphosphonates were synthesized from the corresponding carboxylic acid or acyl chloride compounds, by two different methods. These BPs have a side chain with different lengths ((CH2)n, n = 0-5) between the indazole ring and the bisphosphon...

  12. Treatment of osteonecrosis of the jaw related to bisphosphonates and other antiresorptive agents

    Science.gov (United States)

    Oñate-Sánchez, Ricardo-Elías

    2016-01-01

    Background The clinical management of medication-related osteonecrosis of the jaw (MRONJ) in patients treated with bisphosphonates and other antiresorptive agents is subject to controversy. The American Association of Oral and Maxillofacial Surgeons (AAOMS) has developed guidelines for the correct management of the disorder which are revised and updated by a panel of experts. Material and Methods The present systematic review analyzes the different treatments currently used to treat this clinical condition, based on the PRISMA® (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement published in 2009. An electronic Medline search was made of the PubMed database, covering the period 2006-2014. The last search date was 31 December 2014. Results A total of 29 articles were selected from the initial search according to the different drugs implicated in the appearance of osteonecrosis; the treatment modality used according to the stage of the disease; and the recorded success rate. Conclusions It is currently still recommended that the management of MRONJ should be decided according to the stage of the disease – conservative treatment being preferred in early stages without symptoms, while surgical management is preferred in the case of bone exposure with symptoms. Key words:Osteonecrosis, medication, bisphosphonates, treatments, review PMID:27475683

  13. Characteristics of patients initiating raloxifene compared to those initiating bisphosphonates

    Directory of Open Access Journals (Sweden)

    Wang Sara

    2008-12-01

    Full Text Available Abstract Background Both raloxifene and bisphosphonates are indicated for the prevention and treatment of postmenopausal osteoporosis, however these medications have different efficacy and safety profiles. It is plausible that physicians would prescribe these agents to optimize the benefit/risk profile for individual patients. The objective of this study was to compare demographic and clinical characteristics of patients initiating raloxifene with those of patients initiating bisphosphonates for the prevention and treatment of osteoporosis. Methods This study was conducted using a retrospective cohort design. Female beneficiaries (45 years and older with at least one claim for raloxifene or a bisphosphonate in 2003 through 2005 and continuous enrollment in the previous 12 months and subsequent 6 months were identified using a collection of large national commercial, Medicare supplemental, and Medicaid administrative claims databases (MarketScan®. Patients were divided into two cohorts, a combined commercial/Medicare cohort and a Medicaid cohort. Within each cohort, characteristics (demographic, clinical, and resource utilization of patients initiating raloxifene were compared to those of patients initiating bisphosphonate therapy. Group comparisons were made using chi-square tests for proportions of categorical measures and Wilcoxon rank-sum tests for continuous variables. Logistic regression was used to simultaneously examine factors independently associated with initiation of raloxifene versus a bisphosphonate. Results Within both the commercial/Medicare and Medicaid cohorts, raloxifene patients were younger, had fewer comorbid conditions, and fewer pre-existing fractures than bisphosphonate patients. Raloxifene patients in both cohorts were less likely to have had a bone mineral density (BMD screening in the previous year than were bisphosphonate patients, and were also more likely to have used estrogen or estrogen/progestin therapy in the

  14. Relevance of bisphosphonate long-term therapy in radiation therapy of endosteal jaw metastases; Zur Relevanz einer Bisphosphonat-Langzeittherapie bei der Strahlentherapie enossaler Kiefermetastasen

    Energy Technology Data Exchange (ETDEWEB)

    Groetz, K.A. [HSK Dr. Horst-Schmidt-Kliniken, Wiesbaden (Germany). Akademisches Lehrkrankenhaus, Klinik fuer Mund-Kiefer-Gesichtschirurgie; Mainz Univ. (Germany). Klinik und Poliklinik fuer Mund-, Kiefer- und Gesichtschirurgie; Walter, C.; Al-Nawas, B. [Mainz Univ. (Germany). Klinik und Poliklinik fuer Mund-, Kiefer- und Gesichtschirurgie; Kuettner, C. [HSK Dr. Horst-Schmidt-Kliniken, Wiesbaden (Germany). Akademisches Lehrkrankenhaus, Klinik fuer Mund-Kiefer-Gesichtschirurgie

    2007-04-15

    Background and Purpose: Bisphosphonates are used in the treatment of bone metastasis and malignant myeloma. They have been associated with osteonecrosis of the jaw (ONJ) since the year 2003. Etiology and pathogenesis of this clinical problem are not clear. The high rate of newly diagnosed cases is alarming. Based on the collective of two departments of oral and maxillofacial surgery, the results of therapy in the coincidence of systemic bisphosphonate treatment and local radiotherapy (RT) are analyzed. Patients and Methods: In the course of 33 months (01/2003-09/2005), 63 synchronic or metachronic ONJs were seen in 42 patients as newly diagnosed episodes. Three of the 42 patients had an RT of jaw metastasis. Results: Only one patient was followed over the whole treatment period. Under RT she developed a therapy-refractory ONJ similar to osteoradionecrosis at a dose of 40 Gy. She required a wide segmental osteotomy of the mandible resulting in a total loss of masticatory function. In 39 patients with 60 ONJs without RT not a single segmental resection of the mandible was necessary. Conclusion: Local RT in bisphosphonate long-term therapy seems to be a high risk constellation. As long as the pathogenesis of bisphosphonate-associated ONJ is unclear, patients subjected to RT of the head-and-neck area should be treated.

  15. Weekly Performance

    Institute of Scientific and Technical Information of China (English)

    1994-01-01

    There are many retired people living in Beijing. In order to amuse themselves and improve their health, some have formed yangko (folk dance) teams on a voluntary basis. Ordinarily they do the yangko individually and gather to perform on Sundays. Wearing traditional costumes and forming a circle, yangko teams’ members are enthusiastic about their activity, known as a "weekly performance."

  16. Atypical femur fractures associated with bisphosphonates: from prodrome to resolution

    Directory of Open Access Journals (Sweden)

    Braulio Sastre-Jala

    2015-10-01

    Full Text Available Atypical fractures related to the prolonged use of bisphosphonates are caused by low energy mechanisms and are characterized by oblique and transverse lines and frequent bilateralism. We present a clinical case of a patient who we believe illustrates, both in clinical and radiological aspects, the new definition of atypical femur fracture related to treatment using bisphosphonates treated conservatively and successfully with discharge and teriparatide 20 mcg/80 mcl s.c./24h. The appearance of painful symptoms in the upper thigh, especially if bilateral, in patients treated with bisphosphonates for long periods of time, makes it necessary to dismiss bone lesions that might otherwise suggest atypical fracture. In those cases where the fracture is incomplete, restoring bone metabolism through the administration of teriparatide 20 mcg/80 mcl s.c./24h could prevent displaced fractures.

  17. BISPHOSPHONATES IN LANGERHANS CELL HISTIOCYTOSIS: AN INTERNATIONAL RETROSPECTIVE CASE SERIES

    Directory of Open Access Journals (Sweden)

    Deepak Chellapandian

    2016-07-01

    Full Text Available Background: Bone is the most common organ of involvement in patients with Langerhans cell histiocytosis (LCH, which is often painful and associated with significant morbidity from pathological fractures. Current first-line treatments include chemotherapy and steroids that are effective but often associated with adverse effects, whereas the disease may reactivate despite an initial response to first-line agents. Bisphosphonates are osteoclast inhibitors that have shown to be helpful in treating bone lesions of LCH. To date, there are no large international studies to describe their role in treating bone lesions of LCH. Method: We conducted a multicenter retrospective review of 13 patients with histologically proven LCH, who had received bisphosphonates either at diagnosis or at disease reactivation. Results: Ten patients (77% had a single system bone disease, and 3 (23% had bone lesions as part of multisystem disease. Median follow-up time post-bisphosphonate therapy was 4.6 years (range, 0.8 to 8.2 years. Treatment with bisphosphonates was associated with significant pain relief in almost all patients. Twelve  (92% achieved resolution of active bone lesions, and 10 out of them had no active disease for a median of 3.5 years (range, 0.8 to 5 years. One patient did not respond. No major adverse effects were reported in this series.  Conclusion: Bisphosphonates are well-tolerated drugs that can significantly improve bone pain and induce remission in active bone LCH. Future prospective studies evaluating the role of bisphosphonates in LCH are warranted.

  18. Pharmaceutical care and community pharmacists' understanding of bisphosphonate dosing information.

    Science.gov (United States)

    Li, W W; Kendler, D L

    2004-12-01

    To evaluate pharmacists' knowledge of approved dosing information for cyclic etidronate, alendronate and risedronate in the treatment of postmenopausal osteoporosis; and to assess its relationship to demographic and pharmaceutical care factors. Fax-back questionnaire to evaluate pharmacists' knowledge of approved bisphosphonate dosing information and their involvement in pharmaceutical/patient care activities through independent indices. Community pharmacies in both urban and rural settings in British Columbia. Pharmacies surveyed with 22% response rate (163 pharmacists), 47% male and 54% owners/managers. Most were independent (31%) or volunteer chain (28%) pharmacies. Mean bisphosphonate dosing knowledge score was 76 +/- 11% (mean +/- SD). Mean scores (+/-SD) for questions pertaining to alendronate (92 +/- 13%) were higher than risedronate (81 +/- 26%) and etidronate (48 +/- 19). Pharmacists were least familiar with approved dosing instructions regarding the lack of need to remain upright after etidronate dosing, spacing out of etidronate from food/antacids/calcium/vitamins, and whether risedronate may be taken at bedtime. Factors found to affect pharmacists' bisphosphonate knowledge scores included employment in higher volume pharmacies and greater number of years in practice. Pharmacists in the upper tertile of pharmaceutical care index scores had similar bisphosphonate knowledge scores to those delivering less pharmaceutical care. Pharmacist gender, being owner/manager, and continuing education hours were not significantly associated with higher knowledge or pharmaceutical care scores. There is a wide range of knowledge of bisphosphonate dosing and delivery of pharmaceutical care amongst community pharmacists surveyed. Given the importance of proper bisphosphonate dosing to optimize drug absorption and to minimize toxicity, pharmacist education should be a priority.

  19. Bisphosphonate treatment and dental implants: A systematic review

    Science.gov (United States)

    de-Freitas, Nayara-Ribeiro; de-Moura, Marcos-Boaventura; Veloso-Guedes, Cizelene-do-Carmo-Faleiros; Simamoto-Júnior, Paulo-César; de-Magalhães, Denildo

    2016-01-01

    Background To analyze articles that studied patients submitted to diphosphonates therapy and who received dental implants before, during or after bisphosphonate (BP) treatment, compared to healthy patients, analyzing the increase of failure and loss of implants or bisphosphonate related osteonecrosis of the jaw (BRONJ) incidence. Material and Methods The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement was used in this study. The clinical question in “PICO” format was: In patients under bisphosphonate therapy, do dental implants placement, compared to healthy patients, increase the failure and loss of implants or bisphosphonate related osteonecrosis of the jaw incidence? PubMed/MEDLINE was searched for articles published up until April 15, 2015 using a combination of MeSH terms and their Entry terms. Results The search resulted in 375 articles. After selection according to the eligibility criteria, 15 studies fulfilled were included (eight retrospective, one prospective and six case series), with a total of 1339 patients analyzed, 3748 implants placed, 152 loss of implants and 78 cases of BRONJ. Conclusions Due to the lack of randomized clinical trials looking at this theme, further studies with longer follow-up are needed to elucidate the remaining questions. Thus, it is wise to be careful when planning dental implant surgery in patients undergoing bisphosphonate therapy because of the risk of developing BRONJ as well as occurring failure of implant. Moreover, complete systemic condition of the patient must be also taking into considering when such procedures are performed. Key words:Bisphosphonates, diphosphonates, dental implants, osteonecrosis. PMID:27475681

  20. Pharmacokinetics, Safety, and 48-Week Efficacy of Oral Raltegravir in HIV-1–Infected Children Aged 2 Through 18 Years

    Science.gov (United States)

    Nachman, Sharon; Zheng, Nan; Acosta, Edward P.; Teppler, Hedy; Homony, Brenda; Graham, Bobbie; Fenton, Terence; Xu, Xia; Wenning, Larissa; Spector, Stephen A.; Frenkel, Lisa M.; Alvero, Carmelita; Worrell, Carol; Handelsman, Edward; Wiznia, Andrew; Moultrie, Harry; Kindra, Gurpreet; Sanders, Margaret Ann; Williams, Ruth; Jensen, Jennifer; Acevedo, Midnela; Fabregas, Lizbeth; Jurgrau, Andrea; Foca, Marc; Higgins, Alice; Deville, Jaime G.; Nielsen-Saines, Karin; Carter, Michele F.; Swetnam, John; Wilson, Joan; Donnelly, Margaret; Akleh, Siham; Rigaud, Mona; Kaul, Aditya; Patel, Nehali; Gaur, Aditya; Utech, L. Jill; Cardoso, Edmundo; Moreira, Ana Maria; Santos, Breno; Bobat, Raziya; Mngqibisa, Rosie; Burey, Marlene; Abadi, Jacob; Rosenberg, Michael; Luzuriaga, Katherine; Picard, Donna; Pagano-Therrien, Jessica; Dittmer, Sylvia; Ndiweni, Hilda Ntatule; Patel, Amisha; DelRey, Michelle; McMullen-Jackson, Chivon; Paul, Mary E.; Melvin, Ann; Venema-Weiss, Corry; Lane, Jenna; Beneri, Christy; Ferraro, Denise; Infanzon, Erin; McAuley, James B; Aziz, Mariam; McNichols, Maureen; Pelton, Stephen; McLaud, Deb; Clarke, Diana; Zeichner, Steven; Akar, Arezou; Thompson, Deidre; Douglas, Steven D.; Rutstein, Richard M.; Vincent, Carol A.; Vachon, Mary Elizabeth; Cavallo, Martha; Purswani, Murli Udharam; Masheto, Gaerolwe; Ogwu, Anthony; Kakhu, Tebogo; Viani, Rolando M.; Darcey, Anita,; Norris, Kimberly; Burchett, Sandra K.; Kneut, Catherine; Karthas, Nancy; Casey, Denise; Emmanuel, Patricia; Lujan-Zilbermann, Jorge; Rana, Sohail; Houston, Patricia; Mengistab, Mulu; Rathore, Mobeen; Mirza, Ayesha; Gayton, Tabetha; Barr, Emily; Dunn, Jennifer; Hahn, Kerry; Eysallenne, Zulma; Howard, F. Sholar; Graham, Kathleen; Negra, Marinella Della; Queiroz, Wladimir; Lian, Yu Ching; Wara, Diane; Ruel, Ted; VanDyke, Russell; Reilly, Patricia; Bradford, Sheila; van Rensburg, Anita Janse; Dobbels, Els; Bester, Marietjie; Bamji, Mahrukh; Paul, Santa; Sarza, Mirala; Kovacs, Andrea; Homans, James; Spencer, LaShonda; Hofer, Cristna; Abreu, Thalita; Oliveira, Ricardo; Joao, Esau C.; Pinto, Jorge; Ferreira, Flavia; Kakehasi, Fabiana; Cervi, Maria Celia; Isaac, Marcia De Lima; Losso, Marcelo H.; Stankievich, Erica; Foradori, Irene; Tucker, Diane; Church, Joseph; Belzer, Marvin; Hopkins, Johns; Ellen, Jonathan; Agwu, Allison; Laurel, Borkovic

    2014-01-01

    Background. IMPAACT P1066 is a phase I/II open-label multicenter trial to evaluate pharmacokinetics, safety, tolerability, and efficacy of multiple raltegravir formulations in human immunodeficiency virus (HIV)–infected youth. Methods. Dose selection for each cohort (I: 12 to <19 years; II: 6 to <12 years; and III: 2 to <6 years) was based on review of short-term safety (4 weeks) and intensive pharmacokinetic evaluation. Safety data through weeks 24 and 48, and grade ≥3 or serious adverse events (AEs) were assessed. The primary virologic endpoint was achieving HIV RNA <400 copies/mL or ≥1 log10 reduction between baseline and week 24. Results. The targeted pharmacokinetic parameters (AUC0-12h and C12h) were achieved for each cohort, allowing dose selection for 2 formulations. Of 96 final dose subjects, there were 15 subjects with grade 3 or higher clinical AEs (1 subject with drug-related [DR] psychomotor hyperactivity and insomnia); 16 subjects with grade 3 or higher laboratory AEs (1 with DR transaminase elevation); 14 subjects with serious clinical AEs (1 with DR rash); and 1 subjects with serious laboratory AEs (1 with DR transaminase increased). There were no discontinuations due to AEs and no DR deaths. Favorable virologic responses at week 48 were observed in 79.1% of patients, with a mean CD4 increase of 156 cells/µL (4.6%). Conclusions. Raltegravir as a film-coated tablet 400 mg twice daily (6 to <19 years, and ≥25 kg) and chewable tablet 6 mg/kg (maximum dose 300 mg) twice daily (2 to <12 years) was well tolerated and showed favorable virologic and immunologic responses. Clinical Trials Registration NCT00485264. PMID:24145879

  1. Preliminary Assessment of the Oral Toxicity of 1-5-Diazido-3-Nitrazapentane, 2- and 6-Week Feeding Study, Male and Female Rats

    Science.gov (United States)

    1993-02-01

    TAB Unanounced Just1ficato 0, Distribution/ •-• ~~Avallabillty Codoegl IL Dfat f dpeelar - -- I. l Y ma DEPARTMENT OF THE ARMY U. S. ARMY...May 91 Sep 92 TABLE 3. HEMATOLOGY Hematocrit Hemoglobin Erythrocyte Count Total and Differential Leukocyte Counts Mean Cell Volume Mean Cell ...Hemoglobin Mean Cell Hemoglobin Ccncentration TABLE 4. PREDICTED VERSES ACTUAL DAILY DOSE (MG/ML/DAY) (2-WEEK FEEDING STUDY) DANPE SOLUTIONS (MALE RATS

  2. Relative binding affinity of carboxylate-, phosphonate-, and bisphosphonate-functionalized gold nanoparticles targeted to damaged bone tissue

    Energy Technology Data Exchange (ETDEWEB)

    Ross, Ryan D. [Rush University Medical Center, Department of Anatomy and Cell Biology (United States); Cole, Lisa E.; Roeder, Ryan K., E-mail: rroeder@nd.edu [University of Notre Dame, Department of Aerospace and Mechanical Engineering Bioengineering Graduate Program (United States)

    2012-10-15

    Functionalized Au NPs have received considerable recent interest for targeting and labeling cells and tissues. Damaged bone tissue can be targeted by functionalizing Au NPs with molecules exhibiting affinity for calcium. Therefore, the relative binding affinity of Au NPs surface functionalized with either carboxylate (l-glutamic acid), phosphonate (2-aminoethylphosphonic acid), or bisphosphonate (alendronate) was investigated for targeted labeling of damaged bone tissue in vitro. Targeted labeling of damaged bone tissue was qualitatively verified by visual observation and backscattered electron microscopy, and quantitatively measured by the surface density of Au NPs using field-emission scanning electron microscopy. The surface density of functionalized Au NPs was significantly greater within damaged tissue compared to undamaged tissue for each functional group. Bisphosphonate-functionalized Au NPs exhibited a greater surface density labeling damaged tissue compared to glutamic acid- and phosphonic acid-functionalized Au NPs, which was consistent with the results of previous work comparing the binding affinity of the same functionalized Au NPs to synthetic hydroxyapatite crystals. Targeted labeling was enabled not only by the functional groups but also by the colloidal stability in solution. Functionalized Au NPs were stabilized by the presence of the functional groups, and were shown to remain well dispersed in ionic (phosphate buffered saline) and serum (fetal bovine serum) solutions for up to 1 week. Therefore, the results of this study suggest that bisphosphonate-functionalized Au NPs have potential for targeted delivery to damaged bone tissue in vitro and provide motivation for in vivo investigation.

  3. Bisphosphonate related osteonecrosis of the jaws: report of two cases

    Energy Technology Data Exchange (ETDEWEB)

    Han, Jin Woo [College of Dentistry, Gangneung Wonju National University, Gangneung (Korea, Republic of)

    2011-09-15

    Bisphosphonates are compounds used to treat osteoporosis and malignant bone metastasis. Despite the benefits related to the use of these medications, osteonecrosis of the jaws is a significant complication in a subset of patients receiving these drugs. This complication occurs either spontaneously or after a simple dento-alveolar surgery. Recently there were two patients who showed the features of bisphosphonate related osteonecrosis of the jaws (BRONJ) in Gangneung Wonju National University Dental Hospital. The patients revealed the clinical and radiological features of classical osteomyelitis. This report presents two cases of BRONJ which were examined by plain radiography and computed tomography.

  4. Bisphosphonate related osteonecrosis of the jaws: An update

    Directory of Open Access Journals (Sweden)

    R Anil Kumar

    2012-01-01

    Full Text Available Bisphosphonates (BPs have been recommended for the use in patients with various bony lesions such as Paget′s disease, hypercalcemia, osteoporosis, and multiple myeloma. Despite the increasing use and various benefits, bisphosphonate related osteonecrosis of the jaw (BRONJ is a significant complication with significant morbidity. A search of PUBMED journal databases from January 2000 to April 2012 was conducted with the objective of identifying publications regarding BRONJ. Based on the available data current concepts in the diagnosis and management of BRONJ are discussed in this article.

  5. Clinical and image findings in bisphosphonate-related osteonecrosis of the jaws.

    Science.gov (United States)

    Farias, Diogo Silva; Zen Filho, Edson Virgilio; de Oliveira, Thais Feitosa Leitão; Tinôco-Araújo, José Endrigo; Sampieri, Marcelo Bonifácio da Silva; Antunes, Heliton Spíndola; Santos, Paulo Sérgio da Silva

    2013-07-01

    Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is characterized as exposed bone in the jaws for more than 8 weeks in patients with current or previous history of therapy with bisphosphonates (BPs) and no history of radiotherapy in the head and neck. We report a case series of 7 patients with BRONJ and analyze the variations of clinical and imaging signs, correlating them with the presence or absence of bone exposure. Among the patients, 6 were women and 1 was a man, aged 42-79 years. Five of the patients were using zoledronic acid and the other 2 alendronate. The use of BPs varied from 3 to 13 years. In 5 patients, tooth extraction was the triggering event of injuries. Panoramic radiographs and computed tomography (CT) were evaluated by a radiologist blinded to the cases. There were persistent unremodeled extraction socket even several months after tooth extraction in 3 of the cases that were consistent wit CT findings that also showed areas of osteosclerosis and osteolysis. Patients were treated according to the recommendations of the AAOMS, with surgical debridement and antibiotic coverage with amoxicillin in the symptomatic patients. The follow-up of these patients ranged from 8 to 34 months, with a good response to treatment. The image findings in this case series were not specific and showed no difference between each stages of BRONJ (AAOMS, 2009). The image features were similar in presence or absence of exposed bone.

  6. Fructose intervention for 12 weeks does not impair glycemic control or incretin hormone responses during oral glucose or mixed meal tests in obese men

    DEFF Research Database (Denmark)

    Matikainen, N; Söderlund, S; Björnson, E

    2017-01-01

    BACKGROUND AND AIMS: Incretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) are affected early on in the pathogenesis of metabolic syndrome and type 2 diabetes. Epidemiologic studies consistently link high fructose consumption to insulin resistance...... not worsen their glucose, insulin, GLP-1 or PYY responses. A minor increase in GIP response during OGTT occurred in subjects who gained liver fat (p = 0.049). CONCLUSION: In obese males with features of metabolic syndrome, 12 weeks fructose intervention 75 g/day did not change glucose, insulin, GLP-1 or GIP...

  7. Quantitative ultrasound at the hand phalanges in patients with bisphosphonate-related osteonecrosis of the jaws

    Directory of Open Access Journals (Sweden)

    Ana Carolina Fragoso MOTTA

    2015-01-01

    Full Text Available Patients with bisphosphonate-related osteonecrosis of the jaws (BRONJ who received intravenous or oral bisphosphonates (BP were selected for determination of their bone microarchitecture as a risk predictor of BRONJ development. The diagnosis of BRONJ was made based on clinical and radiographic findings. The control group consisted of healthy patients. All patients underwent quantitative and qualitative ultrasound measurements of bone at the hand phalanges carried out using the DBM Sonic BP. Ultrasound bone profile index (UBPI, amplitude-dependent speed of sound (AD-SoS, bone biophysics profile (BBP, and bone transmission time (BTT were measured. The BRONJ group consisted of 17 patients (62 ± 4.24; range: 45-82; 10 (58.8% were male and seven (41.1% were female, of whom 11 (64.7% suffered from multiple myeloma, three (17.6% from osteoporosis, one (5.8% from prostate cancer, one (5.8% from kidney cancer, and one (5.8% from leukemia. Fourteen (82.3% of them received intravenous BP whereas three (17.6% received oral BP. Nine (9/17; 52.9% patients developed bone exposure: two in the maxilla and seven in the mandible. Regarding quantitative parameters, Ad-SoS was low in the BRONJ group, but not significant. The UBPI score was significantly reduced in BRONJ patients with exposed bone when compared to controls (0.47 ± 0.12 vs. 0.70 ± 0.15; p = 0.004. The present study demonstrated that quantitative ultrasound was able to show bone microarchitecture alterations in BRONJ patients, and suggests that these analyses may be an important tool for early detection of bone degeneration associated with BRONJ.

  8. Hypocalcaemia following thyroidectomy unresponsive to oral therapy.

    Science.gov (United States)

    Etheridge, Zac C; Schofield, Christopher; Prinsloo, Peter J J; Sturrock, Nigel D C

    2014-01-01

    Hypocalcaemia due to hypoparathyroidism following thyroidectomy is a relatively common occurrence. Standard treatment is with oral calcium and vitamin D replacement therapy; lack of response to oral therapy is rare. Herein we describe a case of hypoparathyroidism following thyroidectomy unresponsive to oral therapy in a patient with a complex medical history. We consider the potential causes in the context of calcium metabolism including: poor adherence, hungry bone syndrome, malabsorption, vitamin D resistance, bisphosphonate use and functional hypoparathyroidism secondary to magnesium deficiency. Malabsorption due to intestinal hurry was likely to be a contributory factor in this case and very large doses of oral therapy were required to avoid symptomatic hypocalcaemia.

  9. Bisphosphonates in the Prevention of Post-Traumatic Osteoarthritis

    Science.gov (United States)

    2014-07-01

    TITLE: Bisphosphonates in the Prevention of Post-Traumatic Osteoarthritis PRINCIPAL INVESTIGATOR: Christopher Price, Ph.D... osteoarthritis CONTRACT NUMBER Ostearthritis 5b. GRANT NUMBER W81XWH-13-1-0147 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Christopher Price...5   1   INTRODUCTION: This grant focuses on the investigation of a pharmacological treatment for “post-traumatic osteoarthritis

  10. A systematic review of bisphosphonate osteonecrosis (BON) in cancer

    NARCIS (Netherlands)

    Migliorati, Cesar Augusto; Woo, Sook-Bin; Hewson, Ian; Barasch, Andrei; Elting, Linda S.; Spijkervet, Fred K. L.; Brennan, Michael T.

    2010-01-01

    This systematic review aims to examine the prevalence of bisphosphonate osteonecrosis (BON) in the cancer population, prevention and treatment protocols, and quality of life issues. A search of MEDLINE/PubMed and EMBASE form October 2003 to December 31, 2008 was conducted with the objective of ident

  11. Concordance of sustained virologic response at weeks 4, 12 and 24 post-treatment of hepatitis c in the era of new oral direct-acting antivirals: A concise review.

    Science.gov (United States)

    Burgess, Sarah V; Hussaini, Trana; Yoshida, Eric M

    2016-01-01

    The goal of treatment for chronic hepatitis C viral (HCV) infection is to cure the infection rather than suppress the virus. Historically, a sustained virological response (SVR) defined as undetectable HCV RNA at 24 weeks following the completion of treatment was considered the gold standard to define successful eradication of the virus as a primary endpoint in clinical trials. SVR measured at 12 weeks post-treatment has been shown to be highly concordant with SVR24 in trials of pegylated interferon and ribavirin. The appropriateness and durability of SVR12 as the efficacy endpoint with new oral direct-acting antivirals is less established. A literatura search was performed using PubMed, EMBASE and CENTRAL databases to identify any studies that examined the concordance between SVR24 and earlier time points. Two studies and 4 abstracts were found that performed concordance analyses using positive and negative predictive values. Overall, SVR4 and SVR12 were highly concordant with SVR24 with high positive (> 97%) and negative (> 94%) predictive values; however there was a higher risk of HCV relapse occurring after post-treatment week 4. The majority of the data focused on SVR12 and demonstrated that SVR12 reliably predicted SVR24 in several populations infected with HCV (treatment-naïve, prior null responders, different genotypes) using various new oral direct-acting antiviral regimens. In conclusion, the available data suggests that SVR12 is a reliable assessment of HCV eradication and could be used instead of SVR24 for drug development clinical trials assessing efficacy of new direct-acting antivirals. Data on the long-term durability of SVR12 is still needed.

  12. Oxidative stress and hypoxia observed in the kidneys of mice after a 13-week oral administration of melamine and cyanuric acid combination.

    Science.gov (United States)

    Lv, Yingjun; Liu, Peichen; Xiang, Changlu; Yang, Hejun

    2013-12-01

    Both melamine and cyanuric acid have low toxicity, but together they may cause serious lesions to the kidney, via an unknown mechanism. This study was aimed to estimate whether lesions to the kidney were relative to oxidative damage and hypoxia in the kidney after mice exposed to 1mg/kg/day, 5mg/kg/day or 25mg/kg/day of a mixture of melamine and cyanuric acid for 13 weeks. Pathological changes to the kidneys, oxidative stress and energy parameters and hypoxia-inducible factor-1α (HIF-1α) change in the kidneys were evaluated. Pathological changes were found in the distal tubules of kidneys, such as crystals, proteinaceous casts and compensatory expansion, indicating that the mixture induced toxicity to the kidney. The activities of total antioxidant capacity (TAC) and superoxide dismutase (SOD) and the concentration of glutathione (GSH) decreased, while the concentrations of lipid peroxidation (MDA) and protein carbonyl groups (PC) increased after exposure to the mixture, demonstrating that the mixture resulted in imbalance of antioxidant and reactive oxygen species (ROS) and excessive ROS induced oxidant damage to lipid and proteins in kidneys. The activities of malate dehydrogenase (MDH) and succinate dehyrogenase (SDH) decreased, however, the activity of lactic dehydrogenase (LDH) and the concentration of HIF-1α increased after exposure to the mixture. Accordingly, it was concluded that the mixture resulted in a hypoxic state in kidneys and that both oxidative stress and hypoxia contributed to the lesion of kidneys. The exact cause of oxidative damage and hypoxia is not clear, it might be caused by either a direct effect or by an indirect effect, which is secondary to substantial renal damage caused by tubular obstruction due to crystal formation.

  13. Autologous bone marrow stem cell intralesional transplantation repairing bisphosphonate related osteonecrosis of the jaw

    Directory of Open Access Journals (Sweden)

    Cella Luigi

    2011-08-01

    Full Text Available Abstract Purpose Bisphosphonate - related osteonecrosis of the JAW (BRONJ is a well known side effect of bisphosphonate therapies in oncologic and non oncologic patients. Since to date no definitive consensus has been reached on the treatment of BRONJ, novel strategies for the prevention, risk reduction and treatment need to be developed. We report a 75 year old woman with stage 3 BRONJ secondary to alendronate and pamidronate treatment of osteoporosis. The patient was unresponsive to recommended treatment of the disease, and her BRONJ was worsening. Since bone marrow stem cells are know as being multipotent and exhibit the potential for differentiation into different cells/tissue lineages, including cartilage, bone and other tissue, we performed autologous bone marrow stem cell transplantation into the BRONJ lesion of the patient. Methods Under local anesthesia a volume of 75 ml of bone marrow were harvested from the posterior superior iliac crest by aspiration into heparinized siringes. The cell suspension was concentrated, using Ficoll - Hypaque® centrifugation procedures, in a final volume of 6 ml. Before the injection of stem cells into the osteonecrosis, the patient underwent surgical toilet, local anesthesia was done and spongostan was applied as a carrier of stem cells suspension in the bone cavity, then 4 ml of stem cells suspension and 1 ml of patient's activated platelet-rich plasma were injected in the lesion of BRONJ. Results A week later the residual spongostan was removed and two weeks later resolution of symptoms was obtained. Then the lesion improved with progressive superficialization of the mucosal layer and CT scan, performed 15 months later, shows improvement also of bone via concentric ossification: so complete healing of BRONJ (stage 0 was obtained in our patient, and 30 months later the patient is well and without signs of BRONJ. Conclusion To our knowledge this is the first case of BRONJ successfully treated with

  14. Osteonecrose maxilofacial induzida por bisfosfonatos em indivíduos com osteoporose Bisphosphonate-induced maxillofacial osteonecrosis in osteoporotic individuals

    Directory of Open Access Journals (Sweden)

    Paulo Sérgio da Silva Santos

    2011-10-01

    Full Text Available Osteonecrose dos maxilares relacionada aos bisfosfonatos pode ser uma complicação importante do tratamento da osteoporose a longo prazo. A possibilidade de osteonecrose dos maxilares em pacientes expostos a bisfosfonatos nitrogenados foi descrita pela primeira vez em 2003. Desde então, relatos de casos e estudos retrospectivos demonstraram maiores percentuais de ocorrência de osteonecrose em pacientes que fizeram ou fazem uso de bisfosfonatos. Embora esta complicação possa ser espontânea, os procedimentos invasivos orais têm um papel como fatores de risco associados aos procedimentos odontológicos, tais como as extrações dentárias e cirurgias de outros ossos. Além disso, infecções dentárias e doença periodontal são relatadas como principais fatores de risco para o desenvolvimento de osteonecrose dos maxilares induzida por bisfosfonatos. Por isso, dentistas, clínicos gerais, ortopedistas, geriatras e cirurgiões bucomaxilofaciais precisam estar cientes do problema e trabalhar em um ambiente multidisciplinar, incentivando o diagnóstico precoce e a prevenção de novos casos potenciais.Bisphosphonate-related osteonecrosis of the maxillae may be an important complication of long-term osteoporosis treatment. The possibility of osteonecrosis of the maxillae in patients exposed to nitrogenated bisphosphonates was first described in 2003. Since then, case reports and retrospective studies have demonstrated higher percentages of occurrence of osteonecrosis in patients who have used or are using bisphosphonates. Although this complication may be spontaneous, invasive oral procedures have a role as risk factors associated with dental procedures such as tooth extractions and other bone operations. In addition, tooth infections and periodontal disease have been reported to be the main risk factors for development of bisphosphonate-induced osteonecrosis of the maxillae. For this reason, dentists, general clinicians, orthopedists

  15. Subchronic (13-week) oral toxicity study, preceded by an in utero exposure phase, with arachidonate-enriched triglyceride oil (SUNTGA40S) in rats.

    Science.gov (United States)

    Lina, B A R; Wolterbeek, A P M; Suwa, Y; Fujikawa, S; Ishikura, Y; Tsuda, S; Dohnalek, M

    2006-03-01

    Polyunsaturated fatty acids (PUFAs), such as arachidonic acid (ARA) and docosahexaenoic acid (DHA) are natural constituents found in human milk, fish oil or egg yolk. Until recently, infant formulas, though providing the essential fatty acid precursors for these PUFAs, did not contain preformed ARA or DHA. In this study the safety of SUNTGA40S as source of ARA, not only for use in infant formulas but also for nutritional products or food supplements, was evaluated in a subchronic study in Wistar rats, preceded by a 4-week pretreatment period of parental (F(0)) rats and exposure of the F(0) dams throughout mating, gestation and lactation. SUNTGA40S was administered at dietary levels of 0.5%, 1.5% and 5% (wt/wt) adjusted with corn oil to 5.76% added fat. An additional group received 3.65% (wt/wt) SUNTGA40S in conjunction with 2.11% (wt/wt) high DHA Tuna oil, providing an ARA:DHA ratio of 2.7:1. High-fat and low-fat controls received basal diet with or without 5.76% corn-oil supplement. The content, stability and homogeneous distribution of the test substances in the diet were confirmed under study conditions. The administration of SUNTGA40S, with or without DHA oil, did not affect health, growth, fertility or reproductive performance of the parental rats, nor pup characteristics (condition, weight gain, viability, number per litter or sex ratio). In the subchronic study with the offspring (F(1)) rats, no significant differences were found in condition, neurobehavioural observations, ophthalmoscopy, growth, urinalysis or macroscopic and microscopic findings between the test groups and the low-fat or the high-fat controls. In males of the 5% SUNTGA40S and the SUNTGA40S/DHA group, red blood cell counts, haemoglobin concentration and packed cell volume were lower and reticulocytes were slightly higher than in the high-fat and low-fat control groups. Cholesterol, triglycerides and phospholipids in plasma were lower than in the high-fat controls in both sexes in the 5

  16. Alendronate sodium hydrate (oral jelly for the treatment of osteoporosis: review of a novel, easy to swallow formulation

    Directory of Open Access Journals (Sweden)

    Imai K

    2013-06-01

    Full Text Available Kazuhiro Imai Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan Abstract: Osteoporosis is a skeletal disorder characterized by loss of bone mass, decreased bone strength, and an increased risk of bone fracture. The disease progresses with age, especially in postmenopausal women. Japan is one of the most rapidly aging societies worldwide. Japanese individuals over 65 years of age constituted 23.0% of the population in 2010 and 25.1% to 25.2% as of 2013. The estimated number of people with osteoporosis in Japan is currently 13 million. Bisphosphonates increase bone mineral density by inhibiting osteoclast-mediated bone resorption, thereby reducing the risk of fractures. Alendronate sodium hydrate (alendronate is a bisphosphonate that potently inhibits bone resorption and is used to treat osteoporosis. Sufficient water is required to take an alendronate oral tablet; insufficient water could result in digestive system diseases, such as esophageal ulceration. Elderly patients with swallowing difficulty may choke on the tablet. Taking a tablet with oral jelly is a method to prevent digestive system disease and reduce the choking hazard. Once-weekly alendronate oral jelly was approved in 2012 by the Ministry of Health, Labour, and Welfare of Japan as the world's first drug for osteoporosis in a jelly formulation. It consists of a jelly portion and an air portion. The jelly formulation is smoothly discharged by pushing the air portion. Therefore, elderly patients with physical disabilities are able to easily take all of the jelly formulation from the package. In this review, this new formulation of alendronate sodium hydrate (oral jelly is introduced and discussed in terms of osteoporosis treatment. This new formulation provides an alternative so that patients may select a method of dosing tailored to their preferences. Management of osteoporosis involves assessing fracture risk and preventing

  17. Subtrochanteric Fractures in Bisphosphonate-Naive Patients: Results from the HORIZON-Recurrent Fracture Trial

    OpenAIRE

    2011-01-01

    Our purpose was to characterize the risks of osteoporosis-related subtrochanteric fractures in bisphosphonate-naive individuals. Baseline characteristics of patients enrolled in the HORIZON-Recurrent Fracture Trial with a study-qualifying hip fracture were examined, comparing those who sustained incident subtrochanteric fractures with those sustaining other hip fractures. Subjects were bisphosphonate-naive or had a bisphosphonate washout period of 6–24 months and subsequently received an annu...

  18. Are long-term bisphosphonate users a reality?

    DEFF Research Database (Denmark)

    Abrahamsen, B

    2012-01-01

    The prevalence of long-term bisphosphonate use may be low due to low refill compliance and gaps in treatment. An analysis of the prescription history of 58,674 bisphosphonate users in Denmark found that only 2.8 % had received ten dose years of treatment or above. INTRODUCTION: This study aims......) for the period January 1, 1995 to December 31, 2007 was retrieved from the Danish National Prescription Database for descriptive analysis. RESULTS: Of the 58,674 BP users, 46 % were above the age of 75, and 13 % were men. Though 5.9 % had at least a 10-year history of treatment, only half (2.8 %) had received...

  19. Bisphosphonic acids as effective inhibitors of Mycobacterium tuberculosis glutamine synthetase.

    Science.gov (United States)

    Kosikowska, Paulina; Bochno, Marta; Macegoniuk, Katarzyna; Forlani, Giuseppe; Kafarski, Paweł; Berlicki, Łukasz

    2016-12-01

    Inhibition of glutamine synthetase (GS) is one of the most promising strategies for the discovery of novel drugs against tuberculosis. Forty-three bisphosphonic and bis-H-phosphinic acids of various scaffolds, bearing aromatic substituents, were screened against recombinant GS from Mycobacterium tuberculosis. Most of the studied compounds exhibited activities in micromolar range, with N-(3,5-dichlorophenyl)-2-aminoethylidenebisphoshonic acid, N-(3,5-difluorophenyl)-2-aminoethylidene-bisphoshonic acid and N-(3,4-dichlorophenyl)-1-hydroxy-1,1-ethanebisphosphonic acid showing the highest potency with kinetic parameters similar to the reference compound - L-methionine-S-sulfoximine. Moreover, these inhibitors were found to be much more effective against pathogen enzyme than against the human ortholog. Thus, with the bone-targeting properties of the bisphosphonate compounds in mind, this activity/selectivity profile makes these compounds attractive agents for the treatment of bone tuberculosis.

  20. Clinical Observation of Oral Desogestrel Ethinylestradiol in Pregnant 7 Weeks After Drug Abortion%孕7周药物流产后口服去氧孕烯炔雌醇的临床观察

    Institute of Scientific and Technical Information of China (English)

    邓杰

    2015-01-01

    目的:观察分析孕7周药物流产后口服去氧孕烯炔雌醇的临床效果。方法选取药物流产妇女120例作为研究对象,将所有入选患者随机分为治疗组和对照组,每组为60例。治疗组患者从孕囊排出日每天晚上睡前口服1片去氧孕烯炔雌醇片,3周后停止服药;对照组患者在流产后未服用药物,对比两组患者药物流产后阴道出血时间、出血量以及月经转归情况。结果治疗组药物流产后阴道出血时间、出血量以及月经转归情况显著优于对照组,差异具有统计学意义(P<0.05)。结论孕7周药物流产后口服去氧孕烯炔雌醇片显著降低阴道出血量。缩短出血时间,促进月经恢复。%Objective To observe and analyze the clinical effect of oral desogestrel ethinylestradiol pregnant 7 weeks after drug abortion.MethodsSelect 120 cases of drug abortion women as the object of study,al patients were randomly divided into treatment group and control group,60 cases in each group. The patients in the treatment group were discharged on every night before bed oraly 1 tablets desogestrel and ethinylestradiol tablets from gestational sac,3 weeks after cessation of medication; the control group patients do not take medicine on time,amount of bleeding after abortion and menstrual outcome compared two groups of patients with vaginal hemorrhage after drug abortion.Results Time,bleeding and menstrual outcome is better than control group,the treatment group of vaginal bleeding after drug abortion,with significant difference(P<0.05).Conclusion At 7 weeks after drug abortion oral desogestrel and ethinylestradiol tablets significantly reduced the amount of vaginal bleeding. Shorten the bleeding time,and promote the recovery of menstruation.

  1. Subtrochanteric Femoral Insufficiency Fracture Following Bisphosphonate Therapy for Osseous Metastases

    OpenAIRE

    Bush, Lisabeth A.; Chew, Felix S.

    2015-01-01

    We present the case of an insufficiency fracture of the femoral shaft in a 61-year-old man who had received bisphosphonate therapy to reduce the fracture risk from lytic renal cell carcinoma metastases to the spine. Approximately 1.5 years after beginning monthly intravenous infusions of zoledronic acid (Zometa), the patient complained of persistent thigh pain. Radionuclide bone scan showed mildly increased activity in the lateral subtrochanteric cortex of the right femur, where there was foc...

  2. Synthesis of Dinaphtho-dioxaphosphepin-4-oxides, Epoxides and Bisphosphonates

    Institute of Scientific and Technical Information of China (English)

    KASTHURIAH Maddali; UMA RAVI SANKAR Arigala; SIVA KUMAR Bitragunta; SURESH REDDY Cirandur; NAGA RAJU Chamarthi

    2009-01-01

    A few new seven-membered phosphorus heterocyclic compounds and bis-phosphonates (5a-5g, 5f, 5g', 9 and 10) were prepared by the reaction of 4-bromo dioxaphosphepin (2) with various Grignard reagents followed by their oxidation with H2O2. All the compounds were thoroughly characterized by elemental analysis, IR, 1H, 13C, 31PNMR and mass spectral data. Their antimicrobial activity was evaluated and some of them possess significant activity.

  3. Atypical form of active melorheostosis and its treatment with bisphosphonate

    Energy Technology Data Exchange (ETDEWEB)

    Donath, Judit; Poor, Gyula; Kiss, Csaba [National Institute of Rheumatology and Physiotherapy, 1027 Budapest (Hungary); Fornet, Bela [Semmelweis University Department of Radiology, Budapest (Hungary); Genant, Harry [University of California Department of Radiology, San Francisco, California (United States)

    2002-12-01

    We present the case of a 38-year-old man in whom extensive bilateral melorheostosis was associated with elevated serum alkaline phosphatase, swelling of the right foot and progressive deformity of the left hand, left leg and right foot. Radiography, computed tomography and bone scintigraphy were performed. Following treatment with bisphosphonate (30 mg/day of pamidronate for 6 days) infusion, the pain and swelling of his right foot showed improvement and his elevated serum alkaline phosphatase decreased. (orig.)

  4. The “CROMa” Project: A Care Pathway for Clinical Management of Patients with Bisphosphonate Exposure

    Directory of Open Access Journals (Sweden)

    Mauro Capocci

    2014-01-01

    Full Text Available Aim. To describe 7 years of activity of “CROMa” (Coordination of Research on Osteonecrosis of the Jaws project of “Sapienza” University of Rome. Materials and Methods. A preventive and therapeutic care pathway was created for patients with bisphosphonates (BPs exposure. Demographic, social, behavioural, pharmacological, and clinical variables were registered in a dedicated database. Results. In the project, 502 patients, 403 females and 99 males, were observed. Bone pathologies were 79% osteometabolic diseases (OMD and 21% metastatic cancer (CA. Females were 90% in OMD group and 41% in CA. BP administration was 54% oral, 31% IV, and 11% IM; 89% of BPs were amino-BP and 11% non-amino-BP. Consistently with bone pathology (OMD/CA, alendronate appears to be prevalent for OMD (40% relative, while zoledronate was indicated in 92% of CA patients. Out of 502 cases collected, 28 BRONJ were detected: 17 of them were related to IV BP treatment. Preventive oral assessment was required for 50% of CA patients and by 4% of OMD patients. Conclusions. The proposed care pathway protocols for BP exposed patients appeared to be useful to meet treatment and preventive needs, in both oncological and osteometabolic diseases patients. Patients’ and physicians’ prevention awareness can be the starting point of a multilevel prevention system.

  5. The "CROMa" Project: A Care Pathway for Clinical Management of Patients with Bisphosphonate Exposure.

    Science.gov (United States)

    Capocci, Mauro; Romeo, Umberto; Cocco, Fabio; Bignozzi, Isabella; Annibali, Susanna; Ottolenghi, Livia

    2014-01-01

    Aim. To describe 7 years of activity of "CROMa" (Coordination of Research on Osteonecrosis of the Jaws) project of "Sapienza" University of Rome. Materials and Methods. A preventive and therapeutic care pathway was created for patients with bisphosphonates (BPs) exposure. Demographic, social, behavioural, pharmacological, and clinical variables were registered in a dedicated database. Results. In the project, 502 patients, 403 females and 99 males, were observed. Bone pathologies were 79% osteometabolic diseases (OMD) and 21% metastatic cancer (CA). Females were 90% in OMD group and 41% in CA. BP administration was 54% oral, 31% IV, and 11% IM; 89% of BPs were amino-BP and 11% non-amino-BP. Consistently with bone pathology (OMD/CA), alendronate appears to be prevalent for OMD (40% relative), while zoledronate was indicated in 92% of CA patients. Out of 502 cases collected, 28 BRONJ were detected: 17 of them were related to IV BP treatment. Preventive oral assessment was required for 50% of CA patients and by 4% of OMD patients. Conclusions. The proposed care pathway protocols for BP exposed patients appeared to be useful to meet treatment and preventive needs, in both oncological and osteometabolic diseases patients. Patients' and physicians' prevention awareness can be the starting point of a multilevel prevention system.

  6. Combination treatment with a selective androgen receptor modulator q(SARM) and a bisphosphonate has additive effects in osteopenic female rats.

    Science.gov (United States)

    Vajda, Eric G; Hogue, Aimee; Griffiths, Kimberly N; Chang, William Y; Burnett, Kelven; Chen, Yanling; Marschke, Keith; Mais, Dale E; Pedram, Bijan; Shen, Yixing; van Oeveren, Arjan; Zhi, Lin; López, Francisco J; Meglasson, Martin D

    2009-02-01

    Recent clinical trials with bisphosphonates and PTH have not supported the hypothesis that combination treatments with antiresorptive and anabolic agents would lead to synergistic activity. We hypothesized that combination treatment with a selective androgen receptor modulator (SARM), LGD-3303, and a bisphosphonate would be beneficial. In vitro competitive binding and transcriptional activity assays were used to characterize LGD-3303. LGD-3303 is a potent nonsteroidal androgen that shows little or no cross-reactivity with related nuclear receptors. Tissue selective activity of LGD-3303 was assessed in orchidectomized male rats orally administered LGD-3303 for 14 days. LGD-3303 increased the levator ani muscle weight above eugonadal levels but had greatly reduced activity on the prostate, never increasing the ventral prostate weight to >50% of eugonadal levels even at high doses. Ovariectomized female rats were treated with LGD-3303, alendronate, or combination treatment to study the effects on bone. DXA scans, histomorphometry, and biomechanics were performed. LGD-3303 increased muscle weight in females rats. In addition, LGD-3303 increased BMD and BMC at both cortical and cancellous bone sites. At cortical sites, the effects were caused in part by anabolic activity on the periosteal surface. At every measured site, combination treatment was as effective as either single agent and in some cases showed significant added benefit. LGD-3303 is a novel SARM with anabolic effects on muscle and cortical bone not observed with bisphosphonates. Combination therapy with LGD-3303 and alendronate had additive effects and may potentially be a useful therapy for osteoporosis and frailty.

  7. Studies of the Effectiveness of Bisphosphonate and Vanadium-Bisphosphonate Compounds In Vitro against Axenic Leishmania tarentolae

    Science.gov (United States)

    Christensen, Amy T.; McLauchlan, Craig C.; Dolbecq, Anne; Mialane, Pierre; Jones, Marjorie A.

    2016-01-01

    Leishmaniasis is a disease that is a significant problem for people, especially in tropical regions of the world. Current drug therapies to treat the disease are expensive, not very effective, and/or of significant side effects. A series of alkyl bisphosphonate compounds and one amino bisphosphonate compound, as well as alendronate and zoledronate, were tested as potential agents against Leishmania tarentolae. Also, two polyoxometalates (POMs) with nitrogen-containing bisphosphonate ligands, vanadium/alendronate (V5(Ale)2) and vanadium/zoledronate (V3(Zol)3), were tested against L. tarentolae and compared to the results of the alendronate and zoledronate ligands alone. Of the compounds evaluated in this study, the V5(Ale)2 and V3(Zol)3 complexes were most effective in inhibiting the growth of L. tarentolae. The V5(Ale)2 complex had a larger impact on cell growth than either alendronate or orthovanadate alone, whereas zoledronate itself has a significant effect on cell growth, which may contribute to the activity of the V3(Zol)3 complex. PMID:27034744

  8. Studies of the Effectiveness of Bisphosphonate and Vanadium-Bisphosphonate Compounds In Vitro against Axenic Leishmania tarentolae

    Directory of Open Access Journals (Sweden)

    Amy T. Christensen

    2016-01-01

    Full Text Available Leishmaniasis is a disease that is a significant problem for people, especially in tropical regions of the world. Current drug therapies to treat the disease are expensive, not very effective, and/or of significant side effects. A series of alkyl bisphosphonate compounds and one amino bisphosphonate compound, as well as alendronate and zoledronate, were tested as potential agents against Leishmania tarentolae. Also, two polyoxometalates (POMs with nitrogen-containing bisphosphonate ligands, vanadium/alendronate (V5(Ale2 and vanadium/zoledronate (V3(Zol3, were tested against L. tarentolae and compared to the results of the alendronate and zoledronate ligands alone. Of the compounds evaluated in this study, the V5(Ale2 and V3(Zol3 complexes were most effective in inhibiting the growth of L. tarentolae. The V5(Ale2 complex had a larger impact on cell growth than either alendronate or orthovanadate alone, whereas zoledronate itself has a significant effect on cell growth, which may contribute to the activity of the V3(Zol3 complex.

  9. Bisphosphonate associated osteomyelitis of the jaw in patients with bony exposure: prevention, a new way of thinking

    Directory of Open Access Journals (Sweden)

    Arezo TARDAST

    2015-06-01

    Full Text Available Objective There is strong evidence of a link between the use of systemic bisphosphonates (BPs and osteonecrosis of the jaw, especially in cancer patients. Among risk factors for BRONJ, tooth extraction and immune suppressive drugs seem to have significant role on bone healing. Therefore, the importance of these parameters in development of BRONJ was reviewed in this retrospective study in two maxillofacial surgery units. Material and Methods From 2007 to 2012, 46 patients on bisphosphonate who had developed oral bony lesions participated in this study. The pharmacological exposure, comorbidities, maxillofacial findings, types of treatment and outcome data were collected from clinical and radiological records. Results The most frequently used BP was alendronate (67%. Tooth extraction was reported in 61% of patients with BRONJ. Systemic corticosteroids were prescribed in 35 cases (76% as an adjuvant for BP. Patients on corticosteroids had a lower probability of bony lesion healing (p<0.05 than patients without corticosteroids. Of the 46 patients who underwent conservative treatments, only ten were completely healed (21%. Conclusions Beside tooth extraction, corticosteroids were shown to be an implant risk factor for low rate of bone healing and hence the development of BRONJ. The outcome of conservative treatment was uncertain and this emphasizes the importance of prevention.

  10. Use of bisphosphonates and raloxifene and risk of deep venous thromboembolism and pulmonary embolism

    DEFF Research Database (Denmark)

    Vestergaard, P; Schwartz, K; Pinholt, E M;

    2010-01-01

    Prior studies have associated raloxifene and strontium ranelate with deep venous thromboembolism and pulmonary embolism. In a cohort study, we observed an increased risk also with the bisphosphonates. However, the increase was present already before the start of bisphosphonates pointing at an eff...

  11. Risk of atrial fibrillation among bisphosphonate users: a multicenter, population-based, Italian study

    NARCIS (Netherlands)

    L. Herrera (Lizbeth); I. Leal (Ingrid); F. Lapi (Francesco); M.J. Schuemie (Martijn); V. Arcoraci (Vincenzo); F. Cipriani (Francesco); E. Sessa (E.); A. Vaccheri (Alberto); C. Piccinni (C.); T. Staniscia (Tommaso); A. Vestri (Annarita); M. Di Bari (M.); G. Corrao (Giovanni); A. Zambon (A.); D Gregori (Dario); F. Carle (F.); M.C.J.M. Sturkenboom (Miriam); G. Mazzaglia (Giampiero); G. Trifirò (Gianluca)

    2015-01-01

    textabstractSummary: Bisphosphonate treatment is used to prevent bone fractures. A controversial association of bisphosphonate use and risk of atrial fibrillation has been reported. In our study, current alendronate users were associated with a higher risk of atrial fibrillation as compared with tho

  12. Bilateral Maxillary Reconstruction Using Fibular Flap in Bisphosphonate-related Osteonecrosis

    Science.gov (United States)

    Fujiwara, Toshihiro; Kawai, Kenichiro; Nishimoto, Soh; Kakibuchi, Masao

    2016-01-01

    Summary: Recent reports have shown successful transfer of vascularized fibular flap in bisphosphonate-induced mandibular osteonecrosis. We present a case of a 50-year-old patient who presented with bisphosphonate-related osteonecrosis of bilateral maxilla, which is reconstructed using a fibular flap.

  13. Oral Histoplasmosis.

    Science.gov (United States)

    Folk, Gillian A; Nelson, Brenda L

    2017-02-20

    A 44-year-old female presented to her general dentist with the chief complaint of a painful mouth sore of 2 weeks duration. Clinical examination revealed an irregularly shaped ulcer of the buccal and lingual attached gingiva of the anterior mandible. A biopsy was performed and microscopic evaluation revealed histoplasmosis. Histoplasmosis, caused by Histoplasma capsulate, is the most common fungal infection in the United States. Oral lesions of histoplasmosis are generally associated with the disseminated form of histoplasmosis and may present as a fungating or ulcerative lesion of the oral mucosa. The histologic findings and differential diagnosis for oral histoplasmosis are discussed.

  14. Bisphosphonates: from preclinical evidence to survival data in the oncologic setting

    Directory of Open Access Journals (Sweden)

    Bruno Vincenzi

    2011-12-01

    Full Text Available Bisphosphonate therapy has become a standard of therapy for patients with malignant bone disease. In vivo pre-clinical data suggest that bisphosphonates may exert an antitumor effect and preliminary clinical data show promising activity on metastatic disease in cancer patients. This review will describe the pre-clinical evidence of action of bisphosphonates on osteoclasts and tumor cells, in both in vitro and animal models. In addition, the effects of principal bisphosphonates on skeletal disease progression in patients with cancers in different sites, including breast cancer, prostate cancer and non-small cell lung cancer will be reported. The preliminary clinical data from retrospective trials on the effect of bisphosphonates on survival will be described and the ongoing adjuvant phase III trial will be analyzed. This review will describe the preliminary clinical evidences from prospective studies on the effect of zoledronic acid treatment on the prevention of bone metastases.

  15. Vitamin D insufficiency reduces the protective effect of bisphosphonate on ovariectomy-induced bone loss in rats.

    Science.gov (United States)

    Mastaglia, Silvina R; Pellegrini, Gretel G; Mandalunis, Patricia M; Gonzales Chaves, Macarena M; Friedman, Silvia M; Zeni, Susana N

    2006-10-01

    The present study was carried out to obtain an experimental model of vitamin D (vit D) insufficiency and established osteopenia (experiment 1) to then investigate whether vit D status, i.e. normal or insufficient, interferes with bone mass recovery resulting from bisphosphonate therapy (experiment 2). Rats (n = 40) underwent OVX (n = 32) or a sham operation (n = 8). The first 15 days post-surgery, all groups were kept under fluorescent tube lighting and fed a diet containing 200 IU% vit D (+D). They were then assigned during an additional 45 days to receive either +D or a diet lacking vit D (-D) and kept under 12 h light/dark cycles using fluorescent or red lighting. Serum 25HOD was significantly lower in -D rats (P bone alkaline phosphatase (b-AL), CTX, bone density or histology. No osteoid was observed in undecalcified bone sections. Experiment 2 (105 days): rats were fed either +D or -D according to experiment 1 and were treated with either placebo or 16 mug olpadronate (OPD)/100 g rat/week during the last 45 days. Whereas 25HOD was significantly lower (P bone volume (BV/TV) (P bone. In summary, this is the first experimental study to provide evidence that differences in vit D status may affect the anticatabolic response to bisphosphonate treatment. However, the molecular mechanism through which vit D insufficiency reduces the effect of the aminobisphosphonate remains to be defined.

  16. Opsismodysplasia: Phosphate wasting osteodystrophy responds to bisphosphonate therapy

    Directory of Open Access Journals (Sweden)

    Ansab eKhwaja

    2015-06-01

    Full Text Available We present two siblings affected with opsismodysplasia, a rare skeletal dysplasia caused by mutations in the INPPL1 gene. The skeletal findings include short stature with postnatal onset micromelia, marked platyspondyly, squared metacarpals, delayed skeletal ossification, metaphyseal cupping and postnatal micromelia. Respiratory compromise, delayed ambulation, and progressive lower extremity deformities are described. The severity of findings is variable. Renal phosphate wasting is associated with severe bone demineralization and a more severe phenotype. This report represents the first described cases of opsismodysplasia treated with intravenous bisphosphonate (pamidronate. Surgical management for lower extremity deformities associated with OPS is also reviewed.

  17. Non-exposed variant of bisphosphonate-related osteonecrosis of the jaw (BRONJ with a plasmacytoma: A rare case report

    Directory of Open Access Journals (Sweden)

    Arvind Muthukrishnan

    2015-01-01

    Full Text Available Bisphoshonate-related osteonecrosis of the jaw (BRONJ is an avascular osteo-chemonecrosis of the jaw which results after administration of the group of drugs called as bisphosphonates. Bisphosphonates are given to prevent bone resorption in osteolytic diseases such as Paget′s, osteoporosis, osteogenic carcinoma, and other carcinomas where there could be metastasis and bone resorption. Incidence of BRONJ is reported to be high in western literature and is found to be more after intravenous route compared to oral route of administration. There are various clinical stages of BRONJ as per the American Association of Oral and Maxillofacial Surgeons (AAOMS. Here, we present a rare case of a 60-year-old lady who presented with a complaint of a painless swelling in the alveolus and gingiva in the left maxillary posterior region. This patient was on intravenous Zolendronate for more than 4 years. Thorough examination with detailed investigations revealed BRONJ along with a coexisting second primary tumor, plasmacytoma. Metastasis to distant site is a common feature of malignancy. A metastatic lesion usually occurs within 6 months to 1 year after treatment of a primary lesion. Any fresh neoplasm beyond 1 or 2 years after detection of a primary can be regarded as a second primary tumor. Solitary bone plasmacytoma is a localized form of plasma cell tumor. Diagnosis is based on the presence of the following: Malignant proliferation of plasma cells in biopsy, absence of osteolytic bone lesion, absence of Bence Jones proteins, low concentration of monoclonal proteins, elevated IgG and gamma globulin levels.

  18. Valores de PTH en pacientes bajo tratamiento con bifosfonatos PTH Levels in Patients Treated with Bisphosphonates

    Directory of Open Access Journals (Sweden)

    MS Saavedra

    2012-06-01

    . Los autores declaran no poseer conflictos de interés.PTH reference intervals (RI defined in subjects in which the causes of increased levels of PTH have not been fully excluded have been questioned; an optimal RI must coexist with adequate vitamin D levels. In this study we analyzed the RI in post-menopausal women with adequate levels of 25 (OH D, treated with oral bisphosphonates. Because of their mechanism of action, bisphosphonates may produce an asymptomatic decrease of serum calcium and an increase in PTH; therefore, the 15-65 pg/ml RI reported for intact PTH molecule measurement by electrochemiluminescence may not be suitable for this particular population. The mean and standard deviation age of the subjects was 71.4±8.55 years; mean for 25 (OH D3: 37.3 ng/ml; calcium ion: 4.9 mg/dl (RR 4.3-5.3; urinary calcium: 110 mg/24 hours (RR: 60-200; serum phosphorus: 3.6 mg% (RR: 2.5-4.5; urinary phosphorus: 0.61 g/24hs (RR:0.3-1.0; serum creatinine: 0.80 mg% (RR: 0.5-1.5 and eGFR of 74 min/ml/1.73m² (cut off > 60. BCTx for the average obtained was 212 pg/ml, reflecting the antirresorptive action of bisphosphonates. The RI calculated for PTH in this population, with the method recommended by the CLSI C28-A3, was 26.2 to 87.7 ng/ml. By multiple linear regression (r²= 0.14 of the dependent variable PTH with the predictors pCTx and creatinine, adjusted for age, PTH values depended on pCTx (P = - 0.024, p-value = 0.022 and creatinine (P = 22.294, p-value = 0.040. Our results demonstrate the increase in PTH levels would be due to the effect of antiresorptive therapy and the natural physiological aging process. Conclusion: The RI used for the general population would not be applicable to postmenopausal women with sufficient levels of 25OHD3, supplemented with calcium, treated with oral bisphosphonates. No financial conflicts of interest exist.

  19. [Therapeutic holidays in osteoporosis: Long-term strategy of treatment with bisphosphonates].

    Science.gov (United States)

    Moro Álvarez, María Jesús; Neyro, José Luis; Castañeda, Santos

    2016-01-01

    Oral bisphosphonates (BF) are drugs widely used in the treatment of osteoporosis and placed as first-line treatment for osteoporosis in most clinical guidelines. BF are effective drugs that reduce the incidence of fractures and even reduce mortality. Because of their great affinity for bone, BF have shown that even when they are discontinued still offer a latent protective effect on bone mineral density, maintaining their anti-fracture effect. However, prolonged use for years has been linked to the gradual emergence of complications such as osteonecrosis of the jaw or atypical femur fractures, which have raised questions as when to hold and when to make a final or temporary break, recognized as periods of rest or "therapeutic holidays" of these drugs. Thus, in patients treated with BF for a period of 3-5 years with a low risk of fracture, the drug should be discontinued and restarted when there is an indication for treatment. In contrast, in patients with moderate risk, therapeutic holidays are advised, while reassessing after 2-3 years for restarting purposes. Finally, in patients with high risk of fracture, treatment with BF should not be withdrawn. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  20. Conservative Surgical Management of Stage I Bisphosphonate-Related Osteonecrosis of the Jaw

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    Paolo Vescovi

    2014-01-01

    Full Text Available Purpose. To report the efficacy of conservative surgical treatment for stage I bisphosphonate-related osteonecrosis of the jaw (BRONJ. Materials and Methods. This study reports the clinical outcomes of 63 patients treated for BRONJ stage I (according to Ruggiero's staging system at the Oral Pathology and Laser-Assisted Surgery Unit of the University of Parma between January 2004 and January 2011. Surgical interventions were performed, under local analgesia, in patients unresponsive for a period of six months to noninvasive treatments such as cycles of local or systemic antibacterial therapy combined or not to low level laser therapy, ozone therapy, or Hyperbaric Oxygen Therapy. All interventions were performed after the consultation of oncologist or physician. Results. In our experience, conservative surgical treatment is associated with the highest number of BRONJ healed sites in stage I disease. Complete healing was observed in 92.6% of sites surgically treated. Conclusions. This study confirms that treatment of patients affected by minimal bone exposition, (stage I of BRONJ, through conservative surgical strategies, possibly with laser, may result in a high control of the disease in the long term.

  1. Randomized, 6-Week, Placebo-Controlled Study of Treatment for Adult Attention-Deficit/Hyperactivity Disorder: Individualized Dosing of Osmotic-Release Oral System (OROS) Methylphenidate With a Goal of Symptom Remission.

    Science.gov (United States)

    Goodman, David W; Starr, H Lynn; Ma, Yi-Wen; Rostain, Anthony L; Ascher, Steve; Armstrong, Robert B

    2017-01-01

    To evaluate the efficacy and safety of individualized dosing within the approved dose range for osmotic-release oral system (OROS) methylphenidate hydrochloride in adults with attention-deficit/hyperactivity disorder (ADHD). A double-blind, 6-week trial was conducted between July 2009 and February 2010 at 35 US sites. Adults with ADHD (DSM-IV diagnostic criteria) and a screening ADHD Investigator Symptom Rating Scale (AISRS) score > 24 were randomly assigned to OROS methylphenidate 18 mg or matching placebo. Treatment dose could be increased at 18 mg increments, up to 72 mg/d, until an optimal dose was achieved. AISRS score changes from baseline to end point (primary outcome) were analyzed using analysis of covariance. At baseline, the intent-to-treat population of 169 OROS methylphenidate and 172 placebo subjects (mean age = 35.8 years) had mean (standard deviation [SD]) AISRS scores of 37.8 (6.94) and 37.0 (7.51), respectively. OROS methylphenidate-treated subjects exhibited a significantly greater mean (SD) AISRS score improvement than placebo subjects (-17.1 [12.44] vs -11.7 [13.30]; P methylphenidate-treated subjects experienced greater improvements than placebo subjects in secondary measures of symptom frequency, cognitive function, work productivity, and quality-of-life. Little effect of OROS methylphenidate was observed in exploratory sleep assessments. The adverse event pattern was similar to previous reports of stimulants in adults with ADHD. OROS methylphenidate treatment with individualized doses titrated to achieve symptom remission demonstrated greater ADHD symptom reduction than placebo treatment. These data support the overall efficacy of OROS methylphenidate treatment in the management of adults with ADHD and provide new possibilities for additional intervention. ClinicalTrials.gov identifier: NCT00937040.

  2. Increased vascular eNOS and cystathionine-γ-lyase protein after 6 weeks oral administration of 3, 5, 7, 3', 4'-pentamethoxyflavone to middle-aged male rats.

    Science.gov (United States)

    Yorsin, Somruedee; Kanokwiroon, Kanyanatt; Radenahmad, Nisaudah; Jansakul, Chaweewan

    2016-11-01

    Effects of treatment of middle-aged male rats with 3, 5, 7, 3', 4'-pentamethoxyflavone (PMF) on vascular and perivascular adipose tissue (PVAT) functions and blood chemistry were investigated. Rats received PMF (22 mg/kg), orally or vehicle, twice a day for 6 weeks. The PMF-treated rats had lower serum glucose, higher HDL-C levels, but no change in other parameters. Thoracic aortic and mesenteric rings of PMF treated rats produced lower maximal contraction to phenylephrine that was normalized by N(G)-nitro-L-arginine (L-NA) or endothelial removal. The aortic- and mesenteric rings of the PMF treated rats showed improved relaxation to acetylcholine, but not to glyceryl trinitrate, and had higher eNOS protein. DL-propargylglycine (PAG) caused greater increase in the baseline tension of the PMF-treated aortic ring and higher contraction to low concentrations of phenylephrine. PVAT lowered the contractile response of the L-NA pretreated aortic rings to phenylephrine for both groups, but PAG had no effect. The cystathionine-γ-lyase (CSE) protein of the thoracic rings, but not of the PVAT, shows increased expression after PMF treatment. Overall, PMF treatment of middle aged rats appeared to increase production of NO and H2S from the blood vessels by upregulating the expression of eNOS and CSE. PMF also decreased fasting serum glucose and increased HDL-C levels, with no toxicity to liver and kidney functions. Thus, PMF is a novel compound for possible use as a health product to prevent and/or to reduce the development of diabetes type II and/or cardiovascular disease.

  3. Prophylactic bilateral intramedullary femoral nails for bisphosphonate-associated signs of impending subtrochanteric hip fracture.

    Science.gov (United States)

    Yoon, Richard S; Beebe, Kathleen S; Benevenia, Joseph

    2010-04-01

    In the short and midterm, bisphosphonates have proven highly efficacious in the prevention of low-energy fractures, but long-term results and adverse effects have yet to be definitively identified. Of particular concern are emerging reports of long-term bisphosphonate users presenting with unusual low-energy subtrochanteric femur fractures. Perhaps associated with hyperactive bone remodeling leading to an eventually weakened bony architecture, the efficacy of longer-term bisphosphonate use has come into question, especially in those with >5 years of therapy.This article describes a case of a 65-year-old woman with a 10-year history of bisphosphonate use who presented with prodromal thigh pain and characteristic radiographic findings indicative of potential impending subtrochanteric insufficiency fracture. Supported by reports in the literature, unique characteristics of a certain clinical picture warn of potential bisphosphonate-associated subtrochanteric hip fracture; to our knowledge, we present the first reported prophylactic bilateral femoral intramedullary nailing to prevent fragility fracture. A deeper look into the biochemistry behind associated bony weakness caused by long-term incorporation of bisphosphonates is needed, especially if an endpoint to the therapy is to be determined. However, with mounting clinical evidence supporting the risk of bisphosphonate-associated fragility fracture, a characteristic radiographic appearance and clinical presentation cannot be ignored. In the interim, elective surgery may be an efficacious alternative in the treatment of an expected, readily preventable fracture.

  4. Preventive effect of doxycycline sponge against bisphosphonate-related osteonecrosis of the jaws: an animal study

    Directory of Open Access Journals (Sweden)

    Gonca Duygu Çapar

    2016-07-01

    Full Text Available The aim of this study is to investigate the effect of doxycycline collagen sponge on bisphosphonate-related osteonecrosis of the jaw (BRONJ and the level of serum biomarkers as an indicator of osteonecrosis. Twenty-four rats were divided into four groups. Animals in the control group were injected with saline and animals in Groups I, II and III were injected with zoledronate three times a week for eight weeks. After eight weeks, the following procedures were performed in each group. In Group I: extraction of maxillary first molar, in Group II: extraction of maxillary first molar and mucoperiosteal coverage was performed and in Group III: extraction of maxillary first molar and mucoperiosteal coverage with doxycycline collagen sponges was performed. At the end of 16 weeks, all animals were sacrificed. Serum collagen type I C-telopeptide (CTx, tartrate-resistant acid phosphatase (TRACP 5b and alkaline phosphatase (ALP levels’ analysis, clinical examination, histological and histomorphometrical analysis were performed. As a result no significant difference in CTx, TRACP 5b and ALP levels was observed between groups. Complete mucosal healing was observed in all animals in the control group and 66.7% of animals in Group III. The necrotic bone area in Group III was significantly lower than the other groups (p < 0.01. Statistically significant difference was observed between groups in terms of detached osteoclast number (p < 0.01. In conclusion, local application of doxycycline could have a positive effect in reducing the risk of BRONJ in rats.

  5. Bisphosphonates and their clinical implications in endodontic therapy.

    Science.gov (United States)

    Moinzadeh, A-T; Shemesh, H; Neirynck, N A M; Aubert, C; Wesselink, P R

    2013-05-01

    This review gives an overview of the factors that may play a role in the development of osteonecrosis of the jaw in patients treated with bisphosphonates (BPs) and undergoing nonsurgical endodontic treatment as well as some recommendations for its prevention. BPs are a widely prescribed group of drugs for diverse bone diseases. The occasional but devastating adverse effect of these drugs has been described as bisphosphonate-related osteonecrosis of the jaw (BRONJ). As this condition is debilitating and difficult to treat, all efforts should be made to prevent its occurence in patients at risk. The main triggering event is considered to be dental extraction. Even though nonsurgical endodontic treatment appears to be a relatively safe procedure, care remains essential. After an overview of this class of drugs, the clinical presentation, epidemiology and pathogenesis of BRONJ, as well as the possible risk factors associated with its development after nonsurgical endodontic treatment will be described. Finally, several strategies will be proposed for the prevention of BRONJ during nonsurgical endodontic treatment.

  6. Cranial base pathology in pediatric osteogenesis imperfecta patients treated with bisphosphonates.

    Science.gov (United States)

    Arponen, Heidi; Vuorimies, Ilkka; Haukka, Jari; Valta, Helena; Waltimo-Sirén, Janna; Mäkitie, Outi

    2015-03-01

    Cranial base pathology is a serious complication of osteogenesis imperfecta (OI). Our aim was to analyze whether bisphosphonate treatment, used to improve bone strength, could also prevent the development of craniocervical junction pathology (basilar impression, basilar invagination, or platybasia) in children with OI. In this single-center retrospective study the authors analyzed the skull base morphology from lateral skull radiographs and midsagittal MR images (total of 94 images), obtained between the ages of 0 and 25 years in 39 bisphosphonate-treated OI patients. The results were compared with age-matched normative values and with findings in 70 OI patients who were not treated with bisphosphonates. In addition to cross-sectional data, longitudinal data were available from 22 patients with an average follow-up period of 7.6 years. The patients, who had OI types I, III, IV, VI, and VII, had been treated with zoledronic acid, pamidronate, or risedronate for 3.2 years on average. Altogether 33% of the 39 bisphosphonate-treated patients had at least 1 cranial base anomaly, platybasia being the most prevalent diagnosis (28%). Logistic regression analysis suggested a higher risk of basilar impression or invagination in patients with severe OI (OR 22.04) and/or older age at initiation of bisphosphonate treatment (OR 1.45), whereas a decreased risk was associated with longer duration of treatment (OR 0.28). No significant associations between age, height, or cumulative bisphosphonate dose and the risk for cranial base anomaly were detected. In longitudinal evaluation, Kaplan-Meier curves suggested delayed development of cranial base pathology in patients treated with bisphosphonates but the differences from the untreated group were not statistically significant. These findings indicate that cranial base pathology may develop despite bisphosphonate treatment. Early initiation of bisphosphonate treatment may delay development of craniocervical junction pathology

  7. Acute Nontraumatic Clavicle Fracture Associated with Long-Term Bisphosphonate Therapy

    Directory of Open Access Journals (Sweden)

    Shen Hwa Vun

    2014-01-01

    Full Text Available Cases of osteonecrosis of the jaw, insufficiency fractures and atypical low energy or atraumatic fractures of pelvis, femur (subtrochanteric/mid-shaft/distal-third, tibia, fibula, metatarsal, humerus, and ulna related to long-term bisphosphonate therapy have been reported in the literature. We present the case of an acute nontraumatic clavicle fracture, associated with long-term bisphosphonate therapy, which to our knowledge has not been reported previously. This case highlights the need of critical evaluation of patients with atypical fractures during long-term bisphosphonate therapy.

  8. Acute nontraumatic clavicle fracture associated with long-term bisphosphonate therapy.

    Science.gov (United States)

    Vun, Shen Hwa; Husami, Yahya; Shareef, Sajan; Bramley, Diane

    2014-01-01

    Cases of osteonecrosis of the jaw, insufficiency fractures and atypical low energy or atraumatic fractures of pelvis, femur (subtrochanteric/mid-shaft/distal-third), tibia, fibula, metatarsal, humerus, and ulna related to long-term bisphosphonate therapy have been reported in the literature. We present the case of an acute nontraumatic clavicle fracture, associated with long-term bisphosphonate therapy, which to our knowledge has not been reported previously. This case highlights the need of critical evaluation of patients with atypical fractures during long-term bisphosphonate therapy.

  9. Concurrent bisphosphonate-related bilateral atypical subtrochanteric fractures and osteonecrosis of the jaw on bone scintigraphy.

    Science.gov (United States)

    Kim, Jo Eun; Yun, Mijin; Lim, Sung-Kil; Rhee, Yumie

    2015-05-01

    An 82-year-old woman presented with bilateral thigh pain. She had pain in her right thigh operated for a low-trauma fracture 2 years earlier and newly developed pain in her left thigh without trauma. A whole-body bone scan revealed increased tracer uptake in her bilateral subtrochanteric femoral shafts and in the right mandible without evidence of metastatic bone disease. She had been taking bisphosphonates for 7 years to treat osteoporosis and was soon diagnosed with atypical subtrochanteric fractures and bisphosphonate-related osteonecrosis of the jaw. The bone scan simultaneously identified 2 serious adverse effects of long-term use of bisphosphonates.

  10. Catechol versus bisphosphonate ligand exchange at the surface of iron oxide nanoparticles: towards multi-functionalization

    Science.gov (United States)

    Guénin, Erwann; Lalatonne, Yoann; Bolley, Julie; Milosevic, Irena; Platas-Iglesias, Carlos; Motte, Laurence

    2014-11-01

    We report an investigation of the ligand exchange at the surface of iron oxide nanoparticles in water. For this purpose we compared two strong chelating agents on the iron oxide surface containing catechol and bisphosphonate moieties. Interactions between the coating agents (catechol/bisphosphonate) and the nanoparticle's surface were studied by FTIR and DFT calculations. Ligand exchange experiments were performed using sonication and the exchange yield was characterized by FTIR and EDX. This methodology allowed introducing bisphosphonates with various functionalities (alkyne or biotin) permitting multi-functionalization.

  11. Open, Prospective, Multi-Center, Two-Part Study of Patient Preference with Monthly Ibandronate Therapy in Women with Postmenopausal Osteoporosis Switched From Daily or Weekly Alendronate or Risendronate-BONCURE: Results of Turkish Sub-Study

    Directory of Open Access Journals (Sweden)

    Nurten Eskiyurt

    2012-04-01

    Full Text Available Aim: BONCURE (Bonviva for Current Bisphosphonate Users Regional European Trial, aimed to evaluate patient preference with monthly ibandronate in women with postmenopausal osteoporosis who previously received daily or weekly alendronate or risendronate. Materials and Methods: This prospective, open-label study consisted of two sequential stages, Part A (screening and Part B (treatment. Patients enrolled into Part A completed the Candidate Identification Questionnaire (CIQ. In Part B, after completing the Osteoporosis Patient Satisfaction Questionnaire (OPSATQ, patients received monthly oral ibandronate 150 mg for 6 months. Following treatment, patients completed the OPSAT-Q and Preference Questionnaire. Results: A total of 223 patients (mean age, 63.7±9.51 years were enrolled in Part A from Turkey. Among them, 103 (46.2% answered “YES” to at least one CIQ question. The mean composite OPSAT-Q domain scores increased for convenience (mean change, 15.3±17.7 points, quality of life (10.4±20.4 points, overall satisfaction (11.9±22.7 points, and side effects (3.3±18.8 points. At month 6, 177 subjects (92.7% preferred once-monthly dosing schedule and 99.0% were compliant (≥80% with study treatment. Thirty (15.6% subjects experienced mild to moderate adverse events, mostly gastrointestinal. Conclusion: Postmenopausal women with osteoporosis prefer and are more satisfied and compliant with monthly dosing of ibandronate than daily or weekly bisphosphonate treatment. (Turkish Journal of Osteoporosis 2012;18:1-7

  12. Tratamiento de osteogénesis imperfecta con bisfosfonatos Treatment of osteogenesis imperfecta with bisphosphonates

    Directory of Open Access Journals (Sweden)

    Cristina Tau

    2007-08-01

    Full Text Available El tratamiento con bisfosfonatos (BP, ha mejorado la calidad de vida de los pacientes con osteogénesis imperfecta (OI. Los efectos benéficos son el alivio del dolor, la reducción de la incidencia de fracturas, la mejor movilidad corporal y la recuperación en las formas vertebrales. El tratamiento es más efectivo durante el período de crecimiento. Se presenta una actualización del tema. De la lectura de los anales se destacan los siguientes interrogantes: ¿Por cuánto tiempo deberá instituirse el tratamiento? ¿Es la vía oral tan efectiva como la endovenosa? ¿Cuál es la mejor dosis? ¿Cuándo suspender el tratamiento? ¿Se conservará la integridad del tejido óseo después de un tratamiento prolongado? ¿Qué fenómenos ocurren en el tejido óseo después de la interrupción de la terapia?.Treatment with bisphosphonates (BP improves the quality of life of patients with osteogenesis imperfecta (OI. Beneficial effects are the relief of bone pain, a reduction of fracture incidence, improvement of corporal mobility and recovery of normal vertebral form. Treatment is less effective after completion of growth is here. An update of the literature is here presented. A number of important unsolved questions have been pointed out: for how long should treatment be instituted? Is the oral route as effective as the intravenous one? Which is the best dose? When treatment should be stopped? How well preserved is the longterm integrity of the bones? Which are the phenomena occurring in bone tissue after interruption of therapy?.

  13. Phase I and pharmacokinetic study of XR11576, an oral topoisomerase I and II inhibitor, administered on days 1-5 of a 3-weekly cycle in patients with advanced solid tumours

    NARCIS (Netherlands)

    M.J.A. de Jonge (Maja); S.B. Kaye (Stan); J. Verweij (Jaap); C. Brock (C.); S. Reade (Sarah); M. Scurr (M.); L. van Doorn (Leni); C. Verheij (Coleta); W.J. Loos (Walter); C. Brindley (C.); H.D. Mistry; M. Cooper (Meghan); I.R. Judson (Ian)

    2004-01-01

    textabstractXR11576 is an oral topoisomerase I and II inhibitor. The objectives of this phase I study were to assess the dose-limiting toxicities (DLTs), to determine the maximum tolerated dose (MTD) and to describe the pharmacokinetics (PKs) of XR11576 when administered orally on days 1-5 every 3 w

  14. Phase I and pharmacokinetic study of XR11576, an oral topoisomerase I and II inhibitor, administered on days 1-5 of a 3-weekly cycle in patients with advanced solid tumours

    NARCIS (Netherlands)

    M.J.A. de Jonge (Maja); S.B. Kaye (Stan); J. Verweij (Jaap); C. Brock (C.); S. Reade (Sarah); M. Scurr (M.); L. van Doorn (Leni); C. Verheij (Coleta); W.J. Loos (Walter); C. Brindley (C.); H.D. Mistry; M. Cooper (Meghan); I.R. Judson (Ian)

    2004-01-01

    textabstractXR11576 is an oral topoisomerase I and II inhibitor. The objectives of this phase I study were to assess the dose-limiting toxicities (DLTs), to determine the maximum tolerated dose (MTD) and to describe the pharmacokinetics (PKs) of XR11576 when administered orally on days 1-5 every 3 w

  15. Bilateral Incomplete Atypical Femoral Fracture due to Long-Term Bisphosphonate Use: A Case Report

    Directory of Open Access Journals (Sweden)

    Sibel Başaran

    2017-08-01

    Full Text Available Although the overall safety profile of bisphosphonates (BP is favorable, adverse effects associated with long-term use have came up during recent years. In this report, a case of bilateral incomplete atypical femoral fracture (AFF due to prolonged BP use was presented. A 69-year-old patient, who has been in surgical menopause for 20 years and was started on BP following vertebral fracture almost 10 years ago, was admitted with thigh pain, which was increased two weeks ago. On physical examination, she had antalgic gait, increased thoracic kyphosis and tenderness to percussion over the thoracolumbar region. Lateral cortical thickness in the subtrochanteric region of both femurs and cortical radiolucency on the left femur were observed on plain radiography. Loss of height in L3 and L4 vertebrae was detected on vertebral radiography. Serum 25-hydroxy vitamin D [25(OHD], parathyroid hormone, alkaline phosphatase and calcium levels, along with osteoporosis markers were all within the normal ranges. As the patient was diagnosed with AFF, BP therapy was terminated and vitamin D-calcium supplementation was continued. Since she did not have severe pain, conservative management (limited weight bearing, using a walking stick was recommended for 3 months. Teriparatide therapy was started and she was discharged with recommendations. AFF, which is a rare disorder, should be kept in mind in patients on long-term BP treatment who are admitted with thigh pain and, necessary interventions should be tailored before the occurrence of complete fracture.

  16. Oral Steroids for Dermatitis.

    Science.gov (United States)

    Fisher, Andrew D; Clarke, Jesse; Williams, Timothy K

    2015-01-01

    Contact/allergic dermatitis is frequently treated inappropriately with lower-than-recommended doses or inadequate duration of treatment with oral and intramuscular glucocorticoids. This article highlights a case of dermatitis in a Ranger Assessment and Selection Program student who was improperly treated over 2 weeks with oral steroids after being bit by Cimex lectularius, commonly known as bed bugs. The article also highlights the pitfalls of improper oral steroid dosing and provides reasoning for longer-duration oral steroid treatment.

  17. Dystrophic Cutaneous Calcification and Metaplastic Bone Formation due to Long Term Bisphosphonate Use in Breast Cancer

    Science.gov (United States)

    Tatlı, Ali Murat; Göksu, Sema Sezgin; Arslan, Deniz; Başsorgun, Cumhur İbrahim; Coşkun, Hasan Şenol

    2013-01-01

    Bisphosphonates are widely used in the treatment of breast cancer with bone metastases. We report a case of a female with breast cancer presented with a rash around a previous mastectomy site and a discharge lesion on her right chest wall in August 2010. Biopsy of the lesion showed dystrophic calcification and metaplastic bone formation. The patient's history revealed a long term use of zoledronic acid for the treatment of breast cancer with bone metastasis. We stopped the treatment since we believed that the cutaneous dystrophic calcification could be associated with her long term bisphosphonate therapy. Adverse cutaneous events with bisphosphonates are very rare, and dystrophic calcification has not been reported previously. The dystrophic calcification and metaplastic bone formation in this patient are thought to be due to long term bisphosphonate usage. PMID:23956898

  18. Dystrophic Cutaneous Calcification and Metaplastic Bone Formation due to Long Term Bisphosphonate Use in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ali Murat Tatlı

    2013-01-01

    Full Text Available Bisphosphonates are widely used in the treatment of breast cancer with bone metastases. We report a case of a female with breast cancer presented with a rash around a previous mastectomy site and a discharge lesion on her right chest wall in August 2010. Biopsy of the lesion showed dystrophic calcification and metaplastic bone formation. The patient’s history revealed a long term use of zoledronic acid for the treatment of breast cancer with bone metastasis. We stopped the treatment since we believed that the cutaneous dystrophic calcification could be associated with her long term bisphosphonate therapy. Adverse cutaneous events with bisphosphonates are very rare, and dystrophic calcification has not been reported previously. The dystrophic calcification and metaplastic bone formation in this patient are thought to be due to long term bisphosphonate usage.

  19. Osteonecrosis of the jaw: a rare and devastating side effect of bisphosphonates.

    LENUS (Irish Health Repository)

    Ryan, P

    2009-12-01

    Evidence has emerged that bisphosphonate use in cancer patients is associated with osteonecrosis of the jaw. This form of osteonecrosis has been termed bisphosphonate induced osteonecrosis of the jaw (BIONJ). BIONJ is commonly precipitated by a tooth extraction in patients treated with long term, potent, high dose intravenous bisphosphonates for the management of myeloma, breast or prostate cancer. The overall prevalence of BIONJ is about 5% in patients with these malignancies. Current evidence shows that the risk of BIONJ in non-cancerous patients, such as those with osteoporosis, is very low and appears to be comparable with that of the general population. Prescribing physicians need to encourage cancer patients to see their dentists before the initiation of bisphosphonate treatment, and regularly thereafter.

  20. Long-term Treatment with Bisphosphonates and Their Side Effects in Postmenopausal Osteoporosis - Review

    Directory of Open Access Journals (Sweden)

    Merih Sarıdoğan

    2010-12-01

    Full Text Available Bisphosphonates are the most commonly used drugs for the prevention and treatment of osteoporosis. Bisphosphonates are generally well tolerated and safe. Nevertheless, adverse events have been noted. Effects on the gastrointestinal tract and kidney function are well recognized, as are transient acute-phase reactions. Atrial fibrillation was first identified as a potential adverse event in a zoledronate trial, but subsequent trials and analyses failed to substantiate an association with bisphosphonates. Likewise a possible association between bisphosphonate use and osteonecrosis of the jaw, esophageal cancer and subtrochanteric fractures has also been suggested. However, the risk appears to be low, with no evidence from prospective RCTs of a causal association. (From the World of Osteoporosis 2010;16:66-71

  1. Bisphosphonate-associated osteonecrosis of the jaw: a six-year history of a case.

    Science.gov (United States)

    Hewson, I D

    2011-09-01

    Patients with multiple myeloma are usually treated with IV bisphosphonates soon after diagnosis. Bisphosphonate administration has been associated with bisphosphonate-associated osteonecrosis of the jaw (BONJ). BONJ can occur spontaneously; the most common spontaneous site is at the lingual aspect of the posterior mandible. The condition can continue to expose more bone well after bisphosphonates have been discontinued. This report describes the development and progression of a spontaneous BONJ of the mandible in an individual with multiple myeloma. The area of exposed bone slowly increased in size and eventually became mobile. Removal of the sequestrum provided a temporary respite from exposed bone and resolution of symptoms, but there was a recurrence of exposed bone that required further sequestrum removal.

  2. Bisphosphonate treatment affects trabecular bone apparent modulus through micro-architecture rather than matrix properties

    DEFF Research Database (Denmark)

    Ding, Ming

    2004-01-01

    and trabecular architecture independently. Conventional histomorphometry and microdamage data were obtained from the second and third lumbar vertebrae of the same dogs [Bone 28 (2001) 524]. Bisphosphonate treatment resulted in an increased apparent Young's modulus, decreased bone turnover, increased calcified......Bisphosphonates are emerging as an important treatment for osteoporosis. But whether the reduced fracture risk associated with bisphosphonate treatment is due to increased bone mass, improved trabecular architecture and/or increased secondary mineralization of the calcified matrix remains unclear....... We examined the effects of bisphosphonates on both the trabecular architecture and matrix properties of canine trabecular bone. Thirty-six beagles were divided into a control group and two treatment groups, one receiving risedronate and the other alendronate at 5-6 times the clinical dose...

  3. Knowledge of bisphosphonate-related osteonecrosis of the Jaws among Mexican dentists

    Science.gov (United States)

    Ibáñez-Mancera, Norma-Guadalupe; Aguilar-Rojas, Ana-Martha; Álvarez-Jardón, Ana-Pilar

    2017-01-01

    Background Bisphosphonate-related osteonecrosis is an infrequent but potentially serious complication. Its treatment remains complex, and in some cases can be mutilating. Prevention, a correct diagnosis and opportune management are crucial. Material and Methods A cross-sectional study was made, interviewing 410 dentists with the aim of assessing their knowledge of the subject. Results Practically all of the dental professionals (99.7%) were found to lack sufficient knowledge of the prevention, diagnosis and management of bisphosphonate-related osteonecrosis. Conclusions Actions including increased diffusion in the professional media and inclusion of the subject in training programs are needed in order to enhance the knowledge of bisphosphonate-related osteonecrosis among dentists and thus prevent complications in this group of patients. Key words:Knowledge, mexico, osteonecrosis, bisphosphonates. PMID:27918741

  4. Eleven years of experience with bisphosphonate plus alfacalcidol treatment in a man with osteogenesis imperfecta type I

    Directory of Open Access Journals (Sweden)

    Iwamoto J

    2012-12-01

    Full Text Available Jun Iwamoto,1 Yoshihiro Sato,2 Mitsuyoshi Uzawa,3 Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, 2Department of Neurology, Mitate Hospital, Fukuoka, 3Department of Orthopaedic Surgery, Keiyu Orthopaedic Hospital, Gunma, JapanAbstract: We report the 11-year follow-up of a man with osteogenesis imperfecta type I who was treated with bisphosphonates and alfacalcidol. A 36-year-old Japanese man with osteogenesis imperfecta type I who had frequently experienced painful fragility fractures consulted our clinic because of chronic back pain. The patient had multiple morphometric vertebral fractures and a low bone mineral density (BMD at the lumbar spine. The patient was treated with cyclical etidronate 200 mg, for 2 weeks every 3 months, plus alfacalcidol 1 µg daily, for 2 years; and alendronate 5 mg daily or 35 mg weekly, plus alfacalcidol 1 µg daily for 9 years. After 11 years of treatment, BMD at the lumbar spine increased by 6.4%, following a 20.3% reduction in serum alkaline phosphatase. Serum calcium, phosphorus, and intact parathyroid hormone levels remained within the normal ranges. Three clinical fractures occurred at two ribs and the metacarpus, and two morphometric vertebral fractures occurred at the thoracic spine during the 11-year treatment period, but the patient experienced no adverse effects. Thus, the present case report shows the long-term outcome and safety of bisphosphonate plus alfacalcidol treatment in a man with osteogenesis imperfecta type I.Keywords: etidronate, alendronate, fragility fracture, bone mineral density, osteogenesis imperfecta

  5. Bisfosfonatos podem minimizar a fome óssea após paratireoidectomia em pacientes com hiperparatireoidismo primário e osteíte fibrosa cística Bisphosphonates can reduce bone hunger after parathyroidectomy in patients with primary hyperparathyroidism and osteitis fibrosa cystica

    Directory of Open Access Journals (Sweden)

    Tatiana Clementino Pinto Toscano de França

    2011-04-01

    . RESULTS: Mean age was 35.6 ± 10.5 years; serum calcium = 13.51 + 0.87 mg/dL; iPTH = 1,389 + 609 pg/mL. The mean value of urine deoxypyridinoline (UDPD of three patients was 131 ± 183 nmol/mmol Cr, and of C-telopeptide (CTX, 2,253 ± 1,587 pg/mL. The mean values of bone densitometry (T score were as follows: 0.673 ± 0.150 g/cm² (-4.42 ± 1.23 in lumbar spine (L2-L4; 0.456 ± 0.149 g/cm² (-5.58 ± 1.79 in the femoral neck; and 0.316 ± 0.055 g/cm² (-5.85 ± 0.53 in radius 33. Patient 1 received oral alendronate, 30 mg/day for four weeks; his calcium decreased from 14 to 11.6 mg/dL, and his UDPD from 342 to 160 nmol/mmol Cr. Patient 2 received oral alendronate, 20 mg/day for six weeks; his calcium decreased from 14 to 11.0 mg/dL and his UDPD from 28.8 to 14 nmol/mmol Cr. Patient 3 received intravenous pamidronate, 90 mg prior to surgery. Patient 4 received oral alendronate, 140 mg/week for six weeks; her calcium decreased from 13.7 to 12.3 mg/dL and her CTX from 2,160 to 1,340 pg/mL. Patient 5 received oral alendronate, 140 mg/ week for six weeks; her calcium levels dropped from 14.3 to 14.1 mg/dL; her CTX did not change. Patient 6 received ibandronate, 150 mg, ten days prior to surgery; his CTX reduced by 62%. No patient developed severe hypocalcemia in the first postoperative week. One year after surgery, the mean gain in bone mineral density was 40% ± 29% in L2-L4, 86 ± 39% in the femoral neck, and 22% ± 11% in radius 33. CONCLUSION: The preoperative use of bisphosphonates seems to attenuate bone hunger without preventing a significant increase in bone mass in the follow-up of parathyroidectomy.

  6. Methylene bisphosphonates as the inhibitors of HIV RT phosphorolytic activity.

    Science.gov (United States)

    Yanvarev, D V; Korovina, A N; Usanov, N N; Khomich, O A; Vepsäläinen, J; Puljula, E; Kukhanova, M K; Kochetkov, S N

    2016-08-01

    The structure-function analysis of 36 methylenebisphosphonates (BPs) as inhibitors of the phosphorolytic activity of native and drug-resistant forms of HIV-1 reverse transcriptase (RT) was performed. It was shown that with the increase of the inhibitory potential of BPs towards the phosphorolytic activity raises their ability to inhibit the RT-catalyzed DNA elongation. Herein, we report the impact of the thymidine analog mutations (TAM) on the activity of bisphosphonates, as well as some structural features of the BPs, allowing them to maintain the inhibitory activity on the enzyme resistant to nucleoside analog therapy. We estimated the Mg(2+)-coordinating group structure, the linker and the aromatic pharmacophore influence on the inhibitory potential of the BPs. Based on the 31 BPs SAR, several BPs with improved inhibitory properties were designed and synthesized.

  7. Bone metabolism and clinical study of 44 patients with bisphosphonate-related osteonecrosis of the jaws

    OpenAIRE

    Bocanegra Pérez, Sacramento; Vicente Barrero, Mario; Sosa Henríquez, Manuel; Rodríguez Bocanegra, Eduardo; Limiñana Cañal, José María; López Márquez, Ariadna; Pérez Plasencia, D.; Ramos Macías, Ángel

    2012-01-01

    Osteonecrosis of the jaws is a clinical entity described and linked to treatment with bisphosphonates in 2003. Its real incidence is unknown and it could increase due to the large number of patients treated with these drugs, and its cumulative effect on the bone. State of the art knowledge regarding its etiopathogeny, clinical course and suitable treatments is limited. Objectives: To study the clinical characteristics of 44 patients with bisphosphonate-related osteonecrosis of the jaws and th...

  8. Acute Nontraumatic Clavicle Fracture Associated with Long-Term Bisphosphonate Therapy

    OpenAIRE

    Shen Hwa Vun; Yahya Husami; Sajan Shareef; Diane Bramley

    2014-01-01

    Cases of osteonecrosis of the jaw, insufficiency fractures and atypical low energy or atraumatic fractures of pelvis, femur (subtrochanteric/mid-shaft/distal-third), tibia, fibula, metatarsal, humerus, and ulna related to long-term bisphosphonate therapy have been reported in the literature. We present the case of an acute nontraumatic clavicle fracture, associated with long-term bisphosphonate therapy, which to our knowledge has not been reported previously. This case highlights the need of ...

  9. Atypical femoral fractures bilaterally in a patient receiving bisphosphonate: a case report

    Science.gov (United States)

    Moghnie, Alessandro; Scamacca, Veronica; De Fabrizio, Giovanni; Valentini, Roberto

    2016-01-01

    Summary Atypical femoral fractures are often associated with prolonged bisphosphonate use. The American Society for Bone and Mineral Research (ASBMR) has set the diagnosis criteria for atypical subtrochanteric and diaphyseal femoral fractures by classifying them according to their major and minor criteria. Prolonged bisphosphonate use is correlated with AFF, but the pathogenetic mechanism that causes this kind of fracture has not been defined yet. We describe simultaneous bilaterally femoral fractures in a 76-year-old woman. PMID:27252749

  10. The chemistry of bisphosphonates: from antiscaling agents to clinical therapeutics.

    Science.gov (United States)

    Widler, Leo; Jahnke, Wolfgang; Green, Jonathan R

    2012-02-01

    In the early 1960s, inorganic pyrophosphate (PPi) was found to be present in body fluids and to act as a natural inhibitor of calcification by its interaction with hydroxyapatite. In addition to inhibiting the formation of calcium phosphate, PPi also inhibited dissolution of hydroxyapatite crystals, which made it interesting for pharmacologic applications in the treatment of diseases associated with excessive bone resorption. However, PPi is metabolically unstable because of rapid hydrolysis of the P-O-P backbone by hydrolytic enzymes in the gastrointestinal tract. In the search for more stable analogues of PPi, attention turned to the chemical class of bisphosphonates (BPs). The first BPs were synthesized in the 19th century and widely used for industrial applications. Bisphosphonates are formally derived from PPi by replacement of the bridging oxygen atom by a carbon atom, resulting in a P-C-P moiety that is resistant to hydrolysis. In addition to its decisive role in stability, the central carbon atom also provides an attachment point for 2 additional substituents (R¹ and R²). While R¹ is preferentially a hydroxy group, allowing such derivatives to act as powerful tridentate ligands for calcium (bone hook), R² is mainly responsible for antiresorptive potency. The clinically available BPs can be divided into 2 subclasses based on their structure and molecular mechanism of action. The simple, non-nitrogen-containing derivatives can be incorporated into non-hydrolyzable cytotoxic ATP analogues. The more potent nitrogen-containing BPs inhibit FPPS, a key enzyme in the mevalonate pathway. Details of this crucial molecular interaction have recently been elucidated. Members of this class have a wide therapeutic window between therapeutic inhibition of bone resorption and undesired inhibition of bone formation, and several have found widespread use for the treatment of benign and malignant bone disease.

  11. Bilateral distal fibula fractures in a woman on long-term bisphosphonate therapy.

    Science.gov (United States)

    Murray, J C; Audet, M C; Bédard, M; Michou, L

    2016-02-01

    We report the case of a 53-year-old female, treated by bisphosphonate for 12 years, who presented atraumatic fractures of both fibulas. Her X-rays showed bilateral distal fibula fractures with radiological features similar to atypical femur fractures. The distal fibula should be considered as a potential site for stress fractures in bisphosphonate users. Bisphosphonates are the most widely used drugs in the treatment of osteoporosis. During the last decade, the occurrence of atypical fractures, mostly subtrochanteric and diaphyseal femoral fractures, has been acknowledged in patients with long-term use of bisphosphonates. We report the case of a 53-year-old female on alendronate therapy for the past 12 years who presented with a few months history of atraumatic right, and subsequently left, lateral ankle pain. Her X-rays showed bilateral distal fibula fractures with radiological features similar to atypical femur fractures. She had been treated conservatively with walking boots and her treatment with bisphosphonate had been stopped 5 months prior to the fractures. Callus was progressively seen on serial follow-up X-rays, and both fractures healed completely within a reasonable period of 1 year. Investigations did not reveal any secondary causes of osteoporosis or metabolic bone disorders. To our knowledge, this is the first reported case of bilateral distal fibula fractures in a patient on long-term bisphosphonate therapy.

  12. Osteonecrosis de los maxilares asociada al uso de bifosfonatos: revisión de ocho casos Bisphosphonate-related jaw osteonecrosis: Review of eight cases

    Directory of Open Access Journals (Sweden)

    J. Joshi Otero

    2011-03-01

    Full Text Available Introducción: A finales de 2003 se comienzan a publicar en forma creciente los primeros casos de exposición ósea en los maxilares con evolución tórpida, asociados al uso de bifosfonatos por vía intravenosa. Estos fármacos son usados en pacientes con osteoporosis, mieloma múltiple, hipercalcemia maligna y cáncer de pulmón, mama y próstata, principalmente por su capacidad de inhibir la resorción ósea. Material y método: Estudio prospectivo de los pacientes en el Hospital Virgen Macarena que presentaban lesiones maxilares asociadas al uso de bifosfonatos desde el año 2006 hasta la actualidad. Las variables que valoramos en el paciente son: sexo, edad, tratamiento con bifosfonatos, inicio de la osteonecrosis, relación con tratamientos dentales, tratamiento realizado y evolución. Resultados: Se estudiaron 8 pacientes con osteonecrosis maxilar secundaria a tratamiento con bifosfonatos intravenosos u orales por su patología previa oncológica u osteoporótica que fueron tratados según su estadio clínico-radiológico con antibioterapia, legrado y/o exéresis del secuestro según el caso. Presentamos los resultados con un seguimiento mínimo de 15 meses. Conclusiones: El aumento en la incidencia de la osteomielitis maxilar en los pacientes asociados al uso de bifosfonatos y la dificultad para su tratamiento hacen necesario establecer pautas terapéuticas estandarizadas. En nuestra experiencia, el tratamiento conservador basado en la antibioterapia además del legrado de la zona bajo anestesia local permite el control y la curación del proceso en algunos de los pacientes con OMRB grado II.Background: In late 2003, an increasing number of case reports began to appear on bone exposure of the jaw with a torpid evolution in association with intravenous bisphosphonate use. Bisphosphonates are used to inhibit bone resorption in patients with osteoporosis, multiple myeloma, hypercalcemia of malignancy, lung cancer, breast cancer and prostate

  13. Case analysis of osteonecrosis of the jaw associated with bisphosphonates%双膦酸盐与下颌骨坏死病例分析

    Institute of Scientific and Technical Information of China (English)

    翟蕾; 王建伟

    2015-01-01

    Objective: To analyze the mechanism of osteonecrosis of the jaw and the causes of bisphosphonate associated osteonecrosis of the jaws.Methods:A retrospective analysis was made on the data of 1 patients.The patient was female breast cancer patients,received an IV infusion of zoledronie acid 4 mg dissolved in 0.9% sodium chloride 100 ml, 22 times.Then received an IV infusion of ibandronic acid 4 mg dissolved in 0.9% sodium chloride 500 ml,7 times.During this period, the patient received head radiotherapy for brain metastasis. During this period of the hospital,the Patient complain that their was a pain in the oral mucosa . Osteonecrosis of the jaw (ONJ) was diagnosed by dentists. ONJ was considered to be associated with pamidronate disodium, or both radiotherapy and bisphosphonates.Results:The patients were instructed by X-ray examination to confirm whether the osteonecrosis of the jaw, the patient refused. But with the wide application of bisphosphonates, containing nitrogen bisphosphonate associated osteonecrosis of the report is also increasing, patients with long-term use of bisphosphonates anti treatment of bone metastases, not to the exclusion of bisphosphonate induced osteonecrosis of the jaw.Conclusion:Bisphosphonate related osteonecrosis of the jaw is a very serious side effects.In the use of bisphosphonates, must carefully analyze the risk - benefit,explain to patients in advance, so that patients with psychological preparation.If patients need bisphosphonate therapy, should be given the strict oral hygiene measures,regular dental examination,guidance for patients with rational and scientific use of drugs,in order to reduce the side effects of bisphosphonates.%目的:分析颌骨坏死的原因和双膦酸盐相关性颌骨坏死的机制。方法采用回顾性分析法对1例患者的病例资料进行分析,该患者为女性乳腺癌患者,因骨转移,给予唑来膦酸4 mg,溶于0.9%氯化钠注射液100 mL,静脉滴注,共22

  14. Platelet-Rich Plasma in Treatment of Zoledronic Acid-Induced Bisphosphonate-related Osteonecrosis of the Jaws.

    Science.gov (United States)

    Sarkarat, Farzin; Kalantar Motamedi, Mohammad Hosein; Jahanbani, Jahanfar; Sepehri, Dena; Kahali, Roozbeh; Nematollahi, Zahra

    2014-04-01

    Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a well-known challenging entity warranting management. Platelet-Rich Plasma (PRP) plays an important role in bone biology by enhancing bone repair and regeneration. The aim of this animal study was to evaluate the effects of PRP on zoledronic acid-induced BRONJ. Seven rats were given 0.04 mg Zoledronic acid intravenously once a week for five weeks. Two weeks later, the animals underwent extraction of their first lower molars, bilaterally. After clinical confirmation of the osteonecrosis, PRP was injected randomly into one of the extraction sockets of each rat. Three weeks later, all rats were sacrificed in order to obtain histological sections. The analysis of epithelialization was performed by McNamar's test, and the analysis of osteogenesis and angiogenesis was performed by the Wilcoxon Sign Rank test. P value was set at 0.05. We found no significant differences between the two groups regarding the amount of epithelialization, angiogenesis or sequestrum formation (P > 0.05), but a significant difference was seen between the two groups regarding the amount of existing vital bone (P < 0.05). Our study demonstrates positive results (preservation or regeneration of bone) using PRP in treatment of BRONJ. Although PRP may enhance osseous regeneration, long-term follow-ups are required to confirm its benefits.

  15. Osteonecrosis de los maxilares inducida por bifosfonatos: prevención y actitud terapéutica Bisphosphonate induced osteonecrosis of the jaws: prevention and therapeutic approach

    Directory of Open Access Journals (Sweden)

    F.J. Barrientos Lezcano

    2007-10-01

    Full Text Available Introducción. La osteonecrosis maxilar o mandibular por bifosfonatos puede convertirse en una epidemia debido a la amplia difusión de estos fármacos entre la población. Material y método. Se muestra un protocolo para la prevención y el tratamiento de esta enfermedad. Se presentan tres casos de osteonecrosis maxilar/mandibular. Resultados. Es difícil lograr una curación completa; sin embargo es posible detener la progresión de la enfermedad. Discusión. La cirugía y la suspensión de la terapia con bifosfonatos han demostrado poca utilidad. Los antibióticos y los enjuagues con clorhexidina son las únicas medidas eficaces. Conclusiones. Es imprescindible una planificación adecuada previa a la instauración del tratamiento con bifosfonatos. Ante una osteonecrosis establecida, la actitud debe ser conservadora.Introduction. Bisphosphonate-induced osteonecrosis of the jaws might reach epidemic proportions due to the widespread use of this therapy. Materials and methods. A protocol for prevention and treatment of this pathology is shown. Three clinical cases are reported. Results. It is quite difficult to reach restitutio ad integrum, but stopping the progress of the disease is possible. Discussion. Surgical treatment and cessation of bisphosphonate therapy are of no use. Only antibiotics and oral chlorhexidine have shown some benefits. Conclusions. An accurate preventive attitude is mandatory prior to undergoing bisphosphonate therapy. If osteonecrosis of the jaws is present, management should be conservative.

  16. Bisphosphonate Induces Osteonecrosis of the Jaw in Diabetic Mice via NLRP3/Caspase-1-Dependent IL-1β Mechanism

    Science.gov (United States)

    Zhang, Qunzhou; Yu, Weihua; Lee, Sumin; Xu, Qilin; Naji, Ali; Le, Anh D.

    2016-01-01

    Diabetes mellitus is an established risk factor associated with bisphosphonate-related osteonecrosis of the jaw (BRONJ). Sustained activation of Nod-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome contributes to the persistent inflammation and impaired cutaneous wound healing in diabetic mice and human. We have recently demonstrated a compelling linkage between M1 macrophages and BRONJ conditions in both murine and human diseases. The aim of this study was to determine whether NLRP3 inflammasome activation is involved in BRONJ development in diabetic mice. We showed an increased incidence of delayed oral wound healing and bone necrosis of extraction sockets in db/db mice as compared to those in non-diabetic db/+ controls, which correlated with an elevated expression of NLRP3, caspase-1 and IL-1β in macrophages residing at local wounds. Constitutively, bone marrow-derived macrophages from db/db mice (db/db BMDMs) secrete a relatively higher level of IL-1β than those from db/+ mice (db/+ BMDMs). Upon stimulation by NLRP3 activators, the secretion of IL-1β by db/db BMDMs was 1.77-fold higher than that by db/+ BMDMs (p<0.001). Systemic treatment of mice with zoledronate (Zol), a nitrogen-containing bisphosphonate, resulted in a 1.86- and 1.63-fold increase in NLRP3/caspase-1-dependent IL-1β secretion by db/+ and db/db BMDMs, respectively, in comparison to BMDMs derived from non-treated mice (p<0.001). Importantly, systemic administration of pharmacological inhibitors of NLRP3 activation improved oral wound healing and suppressed BRONJ formation in db/db mice. Mechanistically, we showed that supplementation with intermediate metabolites of the mevalonate pathway, inhibitors of caspase-1 and NLRP3 activation, an antagonist for P2X7R, or a scavenger of reactive oxygen species (ROS), robustly abolished Zol-enhanced IL-1β release from macrophages in response to NLRP3 activation (p<0.001). Our findings suggest that diabetes

  17. Polyoxomolybdate Bisphosphonate Heterometallic Complexes: Synthesis, Structure, and Activity on a Breast Cancer Cell Line.

    Science.gov (United States)

    Saad, Ali; Zhu, Wei; Rousseau, Guillaume; Mialane, Pierre; Marrot, Jérôme; Haouas, Mohamed; Taulelle, Francis; Dessapt, Rémi; Serier-Brault, Hélène; Rivière, Eric; Kubo, Tadahiko; Oldfield, Eric; Dolbecq, Anne

    2015-07-13

    Six polyoxometalates containing Mn(II) , Mn(III) , or Fe(III) as the heteroelement were synthesized in water by treating Mo(VI) precursors with biologically active bisphosphonates (alendronate (Ale), zoledronate (Zol), an n-alkyl bisphosphonate (BPC9 ), an aminoalkyl bisphosphonate (BPC8 NH2 )) in the presence of additional metal ions. The Pt complex was synthesized from a polyoxomolybdate bisphosphonate precursor with Mo(VI) ions linked by the 2-pyridyl analogue of alendronate (AlePy). The complexes Mo4 Ale2 Mn, Mo4 Zol2 Mn, Mo4 Ale2 Fe, Mo4 Zol2 Fe, Mo4 (BPC8 NH2 )2 Fe, and Mo4 (BPC9 )2 Fe contain two dinuclear Mo(VI) cores bound to a central heterometallic ion. The oxidation state of manganese was determined by magnetic measurements. Complexes Mo12 (AlePy)4 and Mo12 (AlePy)4 Pt4 were studied by solid-state NMR spectroscopy and the photochromic properties were investigated in the solid state; both methods confirmed the complexation of Pt. Activity against the human breast adenocarcinoma cell line MCF-7 was determined and the most potent compound was Mn(III) -containing Mo4 Zol2 Mn (IC50 ≈1.3 μM). Unlike results obtained with vanadium-containing polyoxometalate bisphosphonates, cell growth inhibition was rescued by the addition of geranylgeraniol, which reverses the effects of bisphosphonates on isoprenoid biosynthesis/protein prenylation. The results indicate an important role for both the heterometallic element and the bisphosphonate ligand in the mechanism of action of the most active compounds.

  18. The impact of bisphosphonates on the osteoblast proliferation and Collagen gene expression in vitro

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    Ziebart Thomas

    2010-07-01

    Full Text Available Abstract Background Bisphosphonates are widely used in the clinical treatment of bone diseases with increased bone resorption. In terms of side effects, they are known to be associated with osteonecrosis of the jaw (BONJ. The objective of this study was to evaluate the effect of bisphosphonates on osteoblast proliferation by cell count and gene expression analysis of cyclin D1 in vitro. Furthermore, the gene expression of the extracellular matrix protein collagen type I was evaluated. Nitrogen-containing and non-nitrogen-containing bisphosphonates have been compared on gene expression levels. Methods Human osteoblast obtained from hip bone were stimulated with zoledronate, ibandronate and clodronate at concentrations of 5 × 10-5M over the experimental periods of 1, 2, 5, 10 and 14 days. At each point in time, the cells were dissolved, the mRNA extracted, and the gene expression level of cyclin D1 and collagen type I were quantified by Real-Time RT-PCR. The gene expression was compared to an unstimulated osteoblast cell culture for control. Results The proliferation appeared to have been influenced only to a small degree by bisphosphonates. Zolendronate led to a lower cyclin D1 gene expression after 10 days. The collagen gene expression was enhanced by nitrogen containing bisphosphonates, decreased however after day 10. The non-nitrogen-containing bisphosphonate clodronate, however, did not significantly influence cyclin D1 and collagen gene expression. Conclusions The above data suggest a limited influence of bisphosphonates on osteoblast proliferation, except for zoledronate. The extracellular matrix production seems to be initially advanced and inhibited after 10 days. Interestingly, clodronate has little influence on osteoblast proliferation and extracellular matrix production in terms of cyclin D1 and collagen gene expression.

  19. Bisphosphonate use and the risk of endometrial cancer: a meta-analysis of observational studies.

    Science.gov (United States)

    Ou, Ying-Ju; Chiu, Hui-Fen; Wong, Yun-Hong; Yang, Yi-Hsin

    2016-10-01

    The association of bisphosphonate use and the risk of endometrial cancer is still unclear. No meta-analysis was conducted to review the evidence concerning this topic. Relevant studies were identified through PubMed and EMBASE and the Cochrane Library databases. The adjusted relative risk (RR) or odds ratios were determined using a fixed effects or random effects model, depending on the overall heterogeneity. Seven studies, including four cohort studies and three case-control studies, met the method criteria and were included. The random effects model showed a significant reduction in the risk association between bisphosphonate use and endometrial cancer incidence (RR 0.75, 95%CI 0.60-0.94, p = 0.064, I(2)  = 49.6%). A significantly protective effect was observed with the use of bisphosphonate for more than 1 year, and we found a statistically significant risk reduction with the use of bisphosphonate for more than 1 to 3 years (RR 0.58, 95%CI 0.47-0.72) and for more than 3 years (RR 0.44, 95%CI 0.28-0.70). However, with the use of bisphosphonate for less than 1 year (RR 0.92, 95%CI 0.64-1.34), we found no protective effect against endometrial cancer. We found that the use of bisphosphonate was significantly associated with a 25% risk reduction in the incidence of endometrial cancer in the overall analysis. Furthermore, the use of bisphosphonate for more than 1 year but not less than 1 year may have a more beneficial effect on endometrial cancer risk. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  20. Pharmacist Theodor Salzer (1833-1900) and the discovery of bisphosphonates.

    Science.gov (United States)

    Petroianu, G A

    2011-10-01

    Herbert Fleisch, the father of the therapeutic use of bisphosphonates in modern medicine, repeatedly stated in his numerous reviews that bisphosphonates were first synthesized 1865 in Germany by the Russian chemist Menschutkin. He was wrong on two counts. Had Menschutkin synthesized bisphosphonates, as he was a student of Wurtz at the time of the "synthesis", the birthplace of the substances would have been France and not Germany; but he did not. By reacting phosphorous acid with acetyl-chloride he obtained derivatives of pyro-phosphorous and pyro-phosphoric acids (P-O-P backbone) and not bisphosphonates (P-C-P backbone). The discovery of the first bisphosphonate occurred indeed in Germany but some thirty years later and not without some drama. First 1894 the pharmacist Theodor Salzer (1833-1900) described an impurity contained in commercially available phosphoric acid but failed to identify it as acetodiphosphoric acid, a bisphosphonate. 1896, an undergraduate student, Hans von Baeyer working in Munich at the Royal Academy of Sciences in the chemical laboratory of his father Adolf (the 1905 Nobel Prize laureate and discoverer of the barbiturates) synthesized an unknown substance which his famous father summarily rejected as some "Dreck" or impurity. Only due to the tenacity of young Hans work on the matter was continued and the paper describing the synthesis published a year later. The correctness of the chemical structure of the compound as assumed by von Baeyer (and his Ph.D. supervisor Hofmann) was confirmed 1901 by Heidepriem, a Ph.D. student of Hofmann. This short report attempts to shed some light on the life of the lesser known pharmacists and chemists involved in the synthesis of the first bisphosphonate, focusing on Salzer, Heidepriem and von Baeyer.

  1. AB129. Osteogenesis imperfecta: clinical features and bisphosphonate treatment outcome

    Science.gov (United States)

    Can, Ngoc Thi Bich; Vu, Dung Chi; Bui, Thao Phuong; Nguyen, Khanh Ngoc

    2015-01-01

    Background and objective Osteogenesis imperfecta (OI) comprises a group of disorders principally affecting type I collagen which result in increased bone fragility. Children with severe OI suffer recurrent fractures, resulting in severe deformity and growth stunting in many cases, with loss of independent ambulation by the teenage years in over 50% of cases. Recently, cyclical intravenous treatment with pamidronate has proven of benefit to children with severe forms of OI. This article aims to describle clinical features and laboratory manifestations of patient with OI and evaluate outcome of bisphosphonate management. Methods Clinical features, biochemical finding, and management outcome of 104 cases were study. The patients were classified into four major subtypes of Sillience et al. 1979. Patients with severe types were treatment with pamidronate (Aredia) used Rauch protocol 2003. Results Now we have 196 patients (87 females and 109 males) but we studied focus on 104 patients from 98 families (60 males, 44 females) onset at 2.1±3.0 years (median 0.35) with the average fracture bone of 5.9±4.4 times. In there, 17% type I, 8% type II, 63% type III, and 12% type IV. Clinical features include of intrauterine fracture visible on ultrasound 35%, bone deformation after birth 68%, triangle face 76%, long bone deformation 91%, chest deformation 46%, scoliosis 27%, short status 90%, blue sclera 83%, dentinogenesis imperfecta 20%, hearing loss 6%. Thirty patients have been treated with pamidronate at 3.2±3.7 years (4 months to 8 years) during 13±0.8 months (6-30 months). Fourteen patients had fracture bone after 6 months of treatment but no patients had fracture bone after 12 months. Seven patients had been treatment after 1.6±0.5 years, BMD increase from 0.39±0.311 to 0.79±0.105 g/cm2 (P<0.05). One patient had fever reaction after first pamidronate infusion but controlled with standard antipyretic therapy, and do not recur in later treatments. Conclusions OI has

  2. Impact of bisphosphonate-related osteonecrosis of the jaw on osteoporotic patients after dental extraction: a population-based cohort study.

    Directory of Open Access Journals (Sweden)

    Yi Fang Huang

    Full Text Available Little is currently known about the risk of developing bisphosphonate-related osteonecrosis of the jaw (BRONJ. This study sought to determine the incidence of BRONJ in osteoporotic patients. We also sought to identify the nature and types of risk factors of osteonecrosis of jaw (ONJ related to the use of oral bisphosphonates (BPs.Data from the National Health Insurance system of Taiwan. This cohort study included 19,399 adult osteoporosis patients received dental extraction in 2000-2010 (osteoporosis cohort and 38,669 age and gender matched comparisons selected from dental extraction people without osteoporosis and osteonecrosis history (comparison cohort. All study subjects were followed from the date of their dental extraction (index date to the development of ONJ and were included in the study up to 2011 or were lost to the study, whichever occurred first. Cox proportional hazard regression was used to estimate the hazard ratio and 95% confidence intervals for the two cohorts.Patients with osteoporosis had a significantly higher risk to develop ONJ than healthy persons (adjusted HR, 2.05; 95% confidence interval, 1.58-2.65. The risk of ONJ increased with the severity of osteoporosis, no matter whether patient with cancer or not. A cumulative effect of dental extraction frequency may increase the risk of ONJ.We concluded that ONJ is caused by a number of factors. Osteoporosis and past dental history play the very important roles, while BPs play the synergistic effect.

  3. Bisphosphonate-related osteonecrosis of the jaw: from the sine qua non condition of bone exposure to a non-exposed BRONJ entity.

    Science.gov (United States)

    Koth, Valesca Sander; Figueiredo, Maria Antonia; Salum, Fernanda Gonçalves; Cherubini, Karen

    The present work aimed to review the literature focusing on the diagnostic criteria for bisphosphonate-related osteonecrosis of the jaw (BRONJ) and its implications regarding the management of the disease. Since the report of the first cases, BRONJ concepts, diagnostic criteria and guidelines have been changed. The presence of bone exposure in the oral cavity was at first a sine qua non condition for diagnosis. However, it seems that the great concern now is the possibility of occurrence of BRONJ without this feature. Some authors warn that the bone exposure criterion leads to late diagnosis and poor response to treatment. Meanwhile, some radiographic features, such as bone sclerosis, have been postulated as early signs of the disease. Criticisms have also been raised about the clinical staging system of BRONJ. While there is no consensus on the subject, common sense recommends treating symptomatic patients taking bisphosphonate as having BRONJ despite the absence of bone exposure; and asymptomatic patients must be kept under dental follow-up, since all of them are at risk for BRONJ.

  4. Factors associated with acute-phase response of bisphosphonate-naïve or pretreated women with osteoporosis receiving an intravenous first dose of zoledronate or ibandronate.

    Science.gov (United States)

    Popp, A W; Senn, R; Curkovic, I; Senn, C; Buffat, H; Popp, P F; Lippuner, K

    2017-03-15

    A first intravenous dose of bisphosphonates may be associated with an acute-phase response (APR). In bisphosphonate-naïve women with postmenopausal osteoporosis, the characteristics and frequency of APR may differ by compound. Prior bisphosphonate exposure was predictive of APR risk and severity.

  5. Bisphosphonate treatment affects trabecular bone apparent modulus through micro-architecture rather than matrix properties.

    Science.gov (United States)

    Day, J S; Ding, M; Bednarz, P; van der Linden, J C; Mashiba, T; Hirano, T; Johnston, C C; Burr, D B; Hvid, I; Sumner, D R; Weinans, H

    2004-05-01

    Bisphosphonates are emerging as an important treatment for osteoporosis. But whether the reduced fracture risk associated with bisphosphonate treatment is due to increased bone mass, improved trabecular architecture and/or increased secondary mineralization of the calcified matrix remains unclear. We examined the effects of bisphosphonates on both the trabecular architecture and matrix properties of canine trabecular bone. Thirty-six beagles were divided into a control group and two treatment groups, one receiving risedronate and the other alendronate at 5-6 times the clinical dose for osteoporosis treatment. After one year, the dogs were killed, and samples from the first lumbar vertebrae were examined using a combination of micro-computed tomography, finite element modeling, and mechanical testing. By combining these methods, we examined the treatment effects on the calcified matrix and trabecular architecture independently. Conventional histomorphometry and microdamage data were obtained from the second and third lumbar vertebrae of the same dogs [Bone 28 (2001) 524]. Bisphosphonate treatment resulted in an increased apparent Young's modulus, decreased bone turnover, increased calcified matrix density, and increased microdamage. We could not detect any change in the effective Young's modulus of the calcified matrix in the bisphosphonate treated groups. The observed increase in apparent Young's modulus was due to increased bone mass and altered trabecular architecture rather than changes in the calcified matrix modulus. We hypothesize that the expected increase in the Young's modulus of the calcified matrix due to the increased calcified matrix density was counteracted by the accumulation of microdamage.

  6. Dialkyl bisphosphonate platinum(II) complex as a potential drug for metastatic bone tumor.

    Science.gov (United States)

    Nakatake, Hidetoshi; Ekimoto, Hisao; Aso, Mariko; Ogawa, Atsushi; Yamaguchi, Asami; Suemune, Hiroshi

    2011-01-01

    Bisphosphonates have high affinity for hydroxyapatite (HA), which is abundantly present in bone. Also, platinum complexes are known that have a wide spectrum of antitumor activities. The conjugate of bisphosphonate and a platinum complex might have HA affinity and antitumor activity, and become a drug for metastatic bone tumor. In this study, the authors synthesized platinum complexes that had dialkyl bisphosphonic acid as a ligand, and evaluated the possibility of the synthesized complexes as a drug for metastatic bone tumor. The synthesized dialkyl bisphosphonate platinum(II) complex was characterized, and its stability in an aqueous solution was also confirmed. The synthesized platinum complex showed higher HA affinity than other platinum complexes such as cisplatin and carboplatin in an experiment of adsorption to HA. In vitro, the platinum complex showed tumor growth inhibitory effect stronger than or equal to cisplatin, which is the most commonly used antitumor agent. Moreover, the platinum complex showed a bone absorption inhibitory effect on the osteoclast. These results suggest potential of dialkyl bisphosphonate platinum(II) complexes as a drug for metastatic bone tumor.

  7. Interaction between a bisphosphonate, tiludronate, and biomimetic nanocrystalline apatites.

    Science.gov (United States)

    Pascaud, Patricia; Gras, Pierre; Coppel, Yannick; Rey, Christian; Sarda, Stéphanie

    2013-02-19

    Bisphosphonates (BPs) are well established as successful antiresorptive agents for the prevention and treatment of bone diseases such as osteoporosis and Paget's disease. The aim of this work was to clarify the reaction mechanisms between a BP molecule, tiludronate, and the nanocrystalline apatite surface. The adsorption of tiludronate on well-characterized synthetic biomimetic nanocrystalline apatites with homogeneous but different compositions and surface characteristics was investigated to determine the effect of the nanocrystalline apatite substrate on the adsorption behavior. The results show that the adsorption of tiludronate on nanocrystalline biomimetic apatite surfaces varies over a large range. The most immature apatitic samples exhibited the highest affinity and the greatest amount adsorbed at saturation. Maturation of the nanocrystals induces a decrease of these values. The amount of phosphate ion released per adsorbed BP molecule varied, depending on the nanocrystalline substrate considered. The adsorption mechanism, although associated with a release of phosphate ions, cannot be considered as a simple ion exchange process involving one or two phosphate ions on the surface. A two-step process is proposed consisting of a surface binding of BP groups to calcium ions associated with a proton release inducing the protonation of surface orthophosphate ions and their eventual solubilization.

  8. Risk of atrial fibrillation associated with use of bisphosphonates and other drugs against osteoporosis: a cohort study

    DEFF Research Database (Denmark)

    Vestergaard, Peter; Schwartz, Kristoffer; Pinholt, Else Marie;

    2010-01-01

    We studied the association between bisphosphonate use and risk of atrial fibrillation or flutter and the effect of confounders such as heart and lung disease in a nationwide retrospective cohort from Denmark. All users of bisphosphonates and other drugs against osteoporosis between 1996 and 2006 ...

  9. A novel soft-tissue in vitro model for bisphosphonate-associated osteonecrosis

    Directory of Open Access Journals (Sweden)

    Scheper MA

    2010-04-01

    Full Text Available Abstract Background Bisphosphonate (BP-associated osteonecrosis of the jaw (ONJ has been reported in patients receiving intravenous BP, particularly zoledronic acid (ZA. The purpose of this study was to develop an in vitro model representative of the effects BP has on soft tissue secondary to its release from bone. Human gingival fibroblasts and oral epithelial cell lines were exposed to various concentrations (0-10 μM of ZA using dentine discs (DDs as a direct carrier of BP, which were exposed for 24 hours to ZA in normal medium (NM, washed in phosphate-buffered saline (PBS and placed in a new co-culture with the cells. The cells were allowed to proliferate until they grew over the bone discs and then the discs either were left unchelated, or were chelated using 0.001% EDTA or EGTA to release BP from the discs and to observe the cellular effects. Direct effects were determined using direct and fluorescent imaging. Apoptotic effects were determined by vital stain, terminal dUTP nick-end labeling, and annexin V studies. The effect on cell proliferation was determined by mitochondrial tetrazolium salt assay. The level of BP release was determined based on the effect of BP directly on cells, using the DDs or the supernatant fluids resulting from chelation. Results A dose-response effect was seen on imaging, and effects on apoptosis and cell proliferation were observed with increasing ZA concentrations liberated from the DDs, particularly after calcium cleavage and release of ZA from the DDs with a variety of chelating agents. Apoptotic effects were observed microscopically after chelation at 24 hours. Release of ZA was confirmed by extracting medium from non-chelated and chelated cell culture models with DDs and applying this medium to untreated fresh cell cultures, providing appropriate controls. Conclusions The results from this study demonstrate that low concentrations of ZA released from bone can rapidly and directly affect the oral mucosal

  10. Sol-gel derived titania coating with immobilized bisphosphonate enhances screw fixation in rat tibia.

    Science.gov (United States)

    Linderbäck, Paula; Areva, Sami; Aspenberg, Per; Tengvall, Pentti

    2010-08-01

    A variety of surface modifications have been tested for the enhancement of screw fixation in bone, and locally delivered anti-osteoporosis drugs such as bisphosphonates (BP) are then of interest. In this in vivo study, the impact of surface immobilized BP was compared with systemic BP delivery and screws with no BP. After due in vitro characterization, differently treated stainless steel (SS) screws were divided into four groups with 10 rats each. Three of the groups received screws coated with sol-gel derived TiO(2) and calcium phosphate (SS+TiO(2)+CaP). One of these had no further treatment, one had alendronate (BP) adsorbed to calcium phosphate mineral, and one received systemic BP treatment. The fourth group received uncoated SS screws and no BP (control). The screw pullout force was measured after 4 weeks of implantation in rat tibiae. The immobilized amount and release rate of alendronate could be controlled by different immersion times. The SS+TiO(2)+CaP coating did not increase the pullout force compared to SS alone. Surface delivered alendronate enhanced the pullout force by 93% [p = 0.000; 95% Confidence Interval (CI): 67-118%] compared to SS, and by 39% (p = 0.044; 95% CI: 7-71%) compared to systemic alendronate delivery. Both surface immobilized and systemically delivered alendronate improved implant fixation. Also, locally delivered, that is, surface immobilized alendronate showed a better fixation than systemically delivered. Using sol-gel derived TiO(2) as a platform, it is possible to administer controllable amounts of a variety of BPs.

  11. [Bisphosphonate-associated osteonecrosis of the jaws in lung cancer patients].

    Science.gov (United States)

    Neves, Inês; Morais, António; Magalhães, Adriana

    2013-01-01

    Osteonecrosis of the jaw (ONJ) can occur as a complication of bisphosphonate therapy. This condition has been described in cancer patients and its development has been associated with prolonged exposure to high doses of bisphosphonates. Bad dental hygiene, a history of prosthesis or dental extraction, chemotherapy, corticosteroids, and radiation therapy of the head and neck are risk factors reported. In the initial stages it may be asymptomatic, but the patient subsequently develops severe pain and progressive exposed bone. The authors describe three cases of ONJ in lung cancer patients after prolonged exposure to bisphosphonates and there were known risk factors. ONJ can seriously affect the quality of life of cancer patients. An early diagnosis may reduce or avoid the consequences of progressive bone lesion. Copyright © 2013 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

  12. Canine cancellous bone microarchitecture after one year of high-dose bisphosphonates

    DEFF Research Database (Denmark)

    Ding, Ming; Day, JS; Burr, DB

    2003-01-01

    that was typically plate-like, denser, with thicker and more trabeculae compared with those of the controls. Consistent with architectural changes, the Young's moduli of cancellous bone increased in all three directions with the greatest increase in primary axial loading (cephalo-caudal) direction after treatment....... Our results suggest a bone remodeling-adaptation mechanism stimulated by bisphosphonates that increases bone volume fraction, thickens trabeculae, changes trabeculae towards more plate-like, and increases mechanical properties. The secondary degree of anisotropy contributed significantly...... improvements of cancellous bone architecture provide a rationale for the clinical observation that fracture risk decreased by 50% in the first year of bisphosphonate therapy with only a 5% increase in bone mineral density. We conclude that bisphosphonates enhance mechanical properties and reduce fracture risk...

  13. Bisphosphonates in multicentric osteolysis, nodulosis and arthropathy (MONA) spectrum disorder – an alternative therapeutic approach

    Science.gov (United States)

    Pichler, Karin; Karall, Daniela; Kotzot, Dieter; Steichen-Gersdorf, Elisabeth; Rümmele-Waibel, Alexandra; Mittaz-Crettol, Laureane; Wanschitz, Julia; Bonafé, Luisa; Maurer, Kathrin; Superti-Furga, Andrea; Scholl-Bürgi, Sabine

    2016-01-01

    Multicentric osteolysis, nodulosis and arthropathy (MONA) spectrum disorder is a rare inherited progressive skeletal disorder caused by mutations in the matrix metalloproteinase 2 (MMP2) gene. Treatment options are limited. Herein we present successful bisphosphonate therapy in three affected patients. Patients were treated with bisphosphonates (either pamidronate or zoledronate) for different time periods. The following outcome variables were assessed: skeletal pain, range of motion, bone densitometry, internal medical problems as well as neurocognitive function. Skeletal pain was dramatically reduced in all patients soon after initiation of therapy and bone mineral density increased. Range of motion did not significantly improve. One patient is still able to walk with aids at the age of 14 years. Neurocognitive development was normal in all patients. Bisphosphonate therapy was effective especially in controlling skeletal pain in MONA spectrum disorder. Early initiation of treatment seems to be particularly important in order to achieve the best possible outcome. PMID:27687687

  14. Mode of administration-dependent pharmacokinetics of bisphosphonates and bioavailability determination.

    Science.gov (United States)

    Hoffman, A; Stepensky, D; Ezra, A; Van Gelder, J M; Golomb, G

    2001-06-04

    We investigated the influence of mode of administration on the pharmacokinetics of a clinically used bisphosphonate, pamidronate, and of suberoylbisphosphonate (SuBP), a novel bisacylphosphonate of the P-CO-(C)(n)-CO-P type, in rats. Serum drug levels and tissue disposition were determined following administration of the drugs by different modes: intravenous bolus (iso-osmotic and hypo-osmotic solutions), continuous intravenous infusion, and peroral administration. Results of the study indicate that the disposition of the bisphosphonates in soft tissue (liver, kidney and spleen) was dependent on route and rate of drug administration, and on the osmoticity of the vehicle. Consequently, main pharmacokinetic parameters (AUC, CL, and V(ss)) were influenced by the mode of drug administration, precluding accurate determination of bioavailability from AUC values. On the other hand, bone and urine bisphosphonate accumulation were considerably less dependent on mode of administration, and, therefore, are recommended for bioavailability calculation.

  15. Atraumatic intracapsular neck of femur fractures after prolonged bisphosphonate treatment: a new atypical variant?

    Science.gov (United States)

    Khan, Sameer Khalid; Savaridas, Terence; Hemers, Jennifer S.; Maarouf, Zouheir; Orgee, Jane M.; Orr, Michael M.

    2016-01-01

    Summary We present 2 cases of elderly females presenting with atraumatic, near-vertical (Pauwells grade 3), intracapsular neck of femur fractures. Following diagnosis of osteoporosis on DEXA scans, they had received alendronic acid for 7 and 10 years respectively. Routine blood tests and serum estimations of calcium, vitamin-D and thyroid-stimulating hormone, done at admission, were within the normal ranges. These patients were managed with a hemiarthroplasty and a dynamic hip screw (DHS) respectively, following discontinuation of bisphosphonates. We present these 2 cases in light of emerging evidence that associates long-term bisphosphonate use with atypical low energy femoral fractures. Only subtrochanteric/diaphyseal fractures have been reported to date. We present a new variant of atypical femoral neck fractures in metaphyseal bone related to prolonged bisphosphonate therapy. PMID:27252743

  16. Bisphosphonate long-term treatment related bilateral subtrochanteric femoral fracture. Can teriparatide be useful?

    Science.gov (United States)

    Tarazona-Santabalbina, Francisco José; Aguilella-Fernández, Luis

    2013-10-01

    Long-term treatment with bisphosphonates has been related to atypical femoral fractures. We report the clinical case of a woman who suffered a proximal diaphyseal oblique fracture of the left femur after uninterrupted 13-year treatment with alendronate. Shortly after surgery, a painful lytic image in the external cortex of her right femur diaphysis was detected. Some papers have suggested surgical treatment to repair femur fractures after long-term treatment with bisphosphonates. Otherwise, two studies have shown healing acceleration of bone fractures with teriparatide. A lytic lesion was treated with teriparatide obtaining progressive disappearance of symptoms as well as bone healing. This outcome may suggest a way of prevention of complete fractures in symptomatic patients with long-term treatment with bisphosphonates.

  17. Bisphosphonate-related osteonecrosis of jaw (BRONJ: an anti-angiogenic side-effect?

    Directory of Open Access Journals (Sweden)

    Petcu Eugen B

    2012-07-01

    Full Text Available Abstract Bisphosphonates are recommended in the treatment of osteoporosis and some cancers, in which case they prevent the appearance of bone metastasis. The patients taking bisphosphonates are at increased risk of developing bisphosphonate-related osteonecrosis of jaw (BRONJ which is characterised by the presence of an un-healing wound after dental surgery. BRONJ might represent an anti-angiogenic side effect. However, the real number of patients with BRONJ might be higher than currently recorded. Considering the differential diagnosis which includes various primary and secondary cancers, a correct histopathological diagnosis is very important. The morphological criteria for diagnosis of BRONJ are highlighted in this material. Virtual Slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1813972972323288

  18. Reduced cortical bone compositional heterogeneity with bisphosphonate treatment in postmenopausal women with intertrochanteric and subtrochanteric fractures.

    Science.gov (United States)

    Donnelly, Eve; Meredith, Dennis S; Nguyen, Joseph T; Gladnick, Brian P; Rebolledo, Brian J; Shaffer, Andre D; Lorich, Dean G; Lane, Joseph M; Boskey, Adele L

    2012-03-01

    Reduction of bone turnover with bisphosphonate treatment alters bone mineral and matrix properties. Our objective was to investigate the effect of bisphosphonate treatment on bone tissue properties near fragility fracture sites in the proximal femur in postmenopausal women with osteoporosis. The mineral and collagen properties of corticocancellous biopsies from the proximal femur were compared in bisphosphonate-naive (-BIS, n = 20) and bisphosphonate-treated (+BIS, n = 20, duration 7 ± 5 years) patients with intertrochanteric (IT) and subtrochanteric (ST) fractures using Fourier transform infrared imaging (FTIRI). The mean values of the FTIRI parameter distributions were similar across groups, but the widths of the parameter distributions tended to be reduced in the +BIS group relative to the -BIS group. Specifically, the widths of the cortical collagen maturity and crystallinity were reduced in the +BIS group relative to those of the -BIS group by 28% (+BIS 0.45 ± 0.18 versus -BIS 0.63 ± 0.28, p = 0.03) and 17% (+BIS 0.087 ± 0.012 versus -BIS 0.104 ± 0.036, p = 0.05), respectively. When the tissue properties were examined as a function of fracture morphology within the +BIS group, the FTIR parameters were generally similar regardless of fracture morphology. However, the cortical mineral:matrix ratio was 8% greater in tissue from patients with atypical ST fractures (n = 6) than that of patients with typical (IT or spiral ST) fractures (n = 14) (Atypical 5.6 ± 0.3 versus Typical 5.2 ± 0.5, p = 0.03). Thus, although the mean values of the FTIR properties were similar in both groups, the tissue in bisphosphonate-treated patients had a more uniform composition than that of bisphosphonate-naive patients. The observed reductions in mineral and matrix heterogeneity may diminish tissue-level toughening mechanisms.

  19. Rhemium-186-monoaminemonoamidedithiol-conjugated bisphosphonate derivatives for bone pain palliation

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Kazuma [Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501 (Japan); Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640 (Japan); Mukai, Takahiro [Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501 (Japan); Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582 (Japan); Arano, Yasushi [Graduate School of Pharmaceutical Sciences, Chiba University, Chuo-ku, Chiba 260-8675 (Japan); Otaka, Akira [Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501 (Japan); Ueda, Masashi [Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501 (Japan); Uehara, Tomoya [Graduate School of Pharmaceutical Sciences, Chiba University, Chuo-ku, Chiba 260-8675 (Japan); Magata, Yasuhiro [Photon Medical Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Hashimoto, Kazuyuki [Japan Atomic Energy Research Institute, Tokai-mura, Ibaraki 319-1195 (Japan); Saji, Hideo [Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501 (Japan)]. E-mail: hsaji@pharm.kyoto-u.ac.jp

    2006-05-15

    To develop a radiopharmaceutical for the palliation of painful bone metastases based on the concept of bifunctional radiopharmaceuticals, we synthesized a bisphosphonate derivative labeled with rhenium-186 ({sup 186}Re) that contains a hydroxyl group at the central carbon of its bisphosphonate structure, we attached a stable {sup 186}Re-MAMA chelate to the amino group of a 4-amino butylidene-bisphosphonate derivative [N-[2-[[4-[(4-hydroxy-4,4-diphosphonobutyl)amino]-4-oxobutyl] -2-thioethylamino]acetyl]-2-aminoethanethiolate] oxorhenium (V) ({sup 186}Re-MAMA-HBP) and we investigated the effect of a hydroxyl group at the central carbon of its bisphosphonate structure on affinity for hydroxyapatite and on biodistribution by conducting a comparative study with [N-[2-[[3-(3,3-diphosphonopropylcarbamoyl)propyl]-2-thioethylamino]acetyl] -2-a minoethanethiolate] oxorhenium (V) ({sup 186}Re-MAMA-BP). The precursor of {sup 186}Re-MAMA-HBP, trityl (Tr)-MAMA-HBP, was obtained by coupling a Tr-MAMA derivative to 4-amino-1-hydroxybutylidene-1,1-bisphosphonate. {sup 186}Re-MAMA-HBP was prepared by a reaction with {sup 186}ReO{sub 4} {sup -} and SnCl{sub 2} in citrate buffer after the deprotection of the Tr groups of Tr-MAMA-HBP. After reversed-phase high-performance liquid chromatography, {sup 186}Re-MAMA-HBP had a radiochemical purity of over 95%. Compared with {sup 186}Re-MAMA-BP, {sup 186}Re-MAMA-HBP showed a greater affinity for hydroxyapatite beads in vitro and accumulated a significantly higher level in the femur in vivo. Thus, the introduction of a hydroxyl group into {sup 186}Re complex-conjugated bisphosphonates would be effective in enhancing accumulation in bones. These findings provide useful information on the design of bone-seeking therapeutic radiopharmaceuticals.

  20. Safety and effectiveness of 24-week treatment with iguratimod, a new oral disease-modifying antirheumatic drug, for patients with rheumatoid arthritis: interim analysis of a post-marketing surveillance study of 2679 patients in Japan.

    Science.gov (United States)

    Mimori, Tsuneyo; Harigai, Masayoshi; Atsumi, Tatsuya; Fujii, Takao; Kuwana, Masataka; Matsuno, Hiroaki; Momohara, Shigeki; Takei, Syuji; Tamura, Naoto; Takasaki, Yoshinari; Ikeuchi, Satoshi; Kushimoto, Satoru; Koike, Takao

    2017-09-01

    To determine the real-world safety and effectiveness of iguratimod (IGU) for rheumatoid arthritis (RA), a 52-week, Japanese, post-marketing surveillance study was conducted. An interim analysis at week 24 was performed. This study included all RA patients who received IGU following its introduction to the market. All adverse events (AEs) and adverse drug reactions (ADRs) were collected. Effectiveness was evaluated by the change in Disease Activity Score 28-C-reactive protein (DAS28-CRP) from baseline to week 24. Safety was analyzed in 2679 patients. The overall incidences of AEs, ADRs, and serious ADRs were 38.41, 31.65, and 3.21%, respectively; the most commonly reported serious ADRs were pneumonia/bacterial pneumonia, interstitial lung disease, and Pneumocystis jiroveci pneumonia. Concomitant glucocorticoid use and comorbid conditions associated with respiratory disease were identified as risk factors for serious infections. Pulmonary alveolar hemorrhage and increased international normalized ratio of prothrombin time were observed with concomitant use of IGU and warfarin. The DAS28-CRP decreased from baseline to week 24. Although a safety concern was identified with concomitant use of IGU and warfarin, this real-world study showed no other new safety concerns and similar effectiveness to clinical trials. IGU is a new therapeutic option for RA patients.

  1. Atypical bisphosphonate-associated subtrochanteric and femoral shaft stress fractures: diagnostic features on bone scan.

    Science.gov (United States)

    Probst, Stephan; Rakheja, Rajan; Stern, Jerry

    2013-05-01

    A 69-year-old woman presented with a spontaneous right subtrochanteric hip fracture. Pan-imaging following orthopedic repair failed to identify a primary malignancy to explain the presumed pathologic basis for this fracture. The patient then underwent bone scintigraphy and SPECT/CT which showed mild uptake in multifocal endosteal thickening of the lateral left femoral diaphysis, diagnostic of bisphosphonate-associated femoral shaft stress fractures, but no evidence of metastatic bone disease. Atypical bisphosphonate-associated subtrochanteric and femoral shaft stress fractures have a fairly specific appearance on bone scintigraphy, and nuclear medicine physicians should be aware of this relatively infrequent emerging pathology.

  2. Structural, densitometric and biomechanical evaluations of Chinese patients with long-term bisphosphonate treatment

    Institute of Scientific and Technical Information of China (English)

    LEUNG Kwok-sui; TANG Ning; James Griffith; CHOY Tak-Kee; HUNG Vivian Wing-Yin; MOK Hoi-Wa; SHI Lin

    2013-01-01

    Background The association of long-term bisphosphonate treatment for osteoporosis and related safety problems such as atypical fractures were not clearly defined.This study was to evaluate the structural,densitometric and biomechanical properties of the prolonged bisphosphonate-loaded bones.Methods Bone mineral density (BMD) at hip and femoral midshaft,bone cross-sectional area,moment of inertia of both femurs,bone formation and resorption biochemical markers were compared between 28 elderly with at least 4 years of bisphosphonate treatment from 2002 through 2006 and age-matched group of 37 elderly.Results The total hip BMD and t-score were found not different between two groups.However,bisphosphonate treated patients were found to have significantly lower bone mineral content in the femoral shaft (P <0.05); morphological study showed lower cross-sectional area in subtrochanteric and mid-diaphyseal region and thus significantly lower moment of inertia (P <0.01).High resolution-peripheral quantitative computed tomography showed significantly decreased trabecular density,bone volume ratio,trabecular number but increased trabecular spacing in tibia and distal radius.Finite element analysis further confirmed significantly lower stiffness and failure load in tibia.Biochemical studies also showed lower bone resorption and severely suppressed bone formation activity (P <0.001).Conclusions The unchanged total hip BMD between two groups confirmed the beneficial effects of bisphosphonate on trabecular bone,thus preventing osteoporotic fractures at large in previous studies.However,the inferior structural,densitometric and biomechanical properties at cortical bones,especially femur midshaft,need a special attention to look into the association between long-term bisphosphonate intake and the occurrence of stress fractures.When patients taking bisphosphonate complain of proximal thigh pain or discomfort,plain X-ray film can be the first line screening.All patients

  3. Current perspectives on bisphosphonate treatment in Paget’s disease of bone

    Directory of Open Access Journals (Sweden)

    Wat WZM

    2014-11-01

    Full Text Available Winnie Zee Man Wat Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong Abstract: Paget’s disease of bone is a chronic metabolic bone disease with focal increase in bone turnover. The exact etiology of the disease is uncertain, although genetic and environmental factors are believed to be important. Bisphosphonate is the main class of medication being used to control disease activity via its antiresorptive effect. This review discusses the controversies concerning the use of bisphosphonates in the treatment of Paget’s disease of bone, the efficacy of different bisphosphonates in controlling disease activity, and the possible rare side effects of bisphosphonates. Symptoms are the main indication for treatment in Paget’s disease of bone. As treatment benefits in asymptomatic individuals remain controversial and nonevidence based, the decision to treat these patients should be individualized to their risk and benefit profiles. There are several trials conducted to evaluate and compare the efficacy of different regimes of bisphosphonates for treating Paget’s disease of bone. Most trials used biochemical markers rather than clinical symptoms or outcomes as parameters for comparison. Zoledronate is an attractive option as it can achieve high rates of biochemical remission and sustain long duration of suppression by a single dose. Atypical femoral fracture and osteonecrosis of the jaw are two rare and severe side effects reported, possibly related to the use of bisphosphonates in patients with osteoporosis and malignancy-induced hypercalcemia. As the regimes of bisphosphonates used for treating Paget’s disease of bone are different from those two diseases, the risks of developing these two possible side effects are expected to be very low, although this remains unknown. Vitamin D and calcium supplement should be given to patients at risk of vitamin D insufficiency when given zoledronate, as symptomatic

  4. Biodegradable bisphosphonate nanoparticles for imaging and therapeutic applications in osteosarcoma

    Science.gov (United States)

    Rudnick-Glick, S.; Corem-Salkmon, E.; Grinberg, I.; Gluz, E.; Margel, S.

    2015-08-01

    Osteosarcoma (OS) is amongst the most commonly diagnosed bone tumors occurring in adolescence, young adults and adults over the age of 65. Current treatment is based on a combination of surgery and chemotherapy. Chemotherapy has improved the survival rate, however it is associated with severe side effects due to the use of high dosages, nonspecific uptake and poor bone blood supply. At present bisphosphonates (BP) are widely used in the treatment of bone disorders including OS. We have engineered a unique biodegradable BP nanoparticle that possesses a dual functionality: 1) covalent attachment of a dye (e.g., NIR dye) or drug to the nanoparticles through the primary amine groups on the surface of the nanoparticle; 2) chelation to the bone mineral hydroxyapatite through the BP on the surface of the nanoparticle. Due to a high concentration of PEG in the BP nanoparticles they possess a relatively long plasma half-life time. Therefore, the nanoparticle has potential for use both in diagnosis and therapy of OS. Doxorubicin was conjugated to the free amine on the surface of the BP nanoparticles. In vitro experiments on osteosarcoma cells demonstrated that the doxorubicin-conjugated BP nanoparticles possess a higher efficacy than the free doxorubicin. Further investigation in vivo in a chicken embryo model confirmed that the doxorubicin-conjugated nanoparticle was significantly more effective in inhibiting tumor growth compared to free doxorubicin at a similar concentration. Additionally, we have shown that these BP nanoparticles preferentially target OS tumor tissue, thus increasing anti-cancer drug bioavailability at targeted site.

  5. Oral Bisphosphonate Use Increases the Risk for Inflammatory Jaw Disease: A Cohort Study

    DEFF Research Database (Denmark)

    Vestergaard, Peter; Schwartz, Kristoffer; Rejnmark, Lars;

    2011-01-01

    PURPOSE: The objective of this study was to address whether among people living in Denmark, those treated with medications to prevent osteoporosis have an increased risk for inflammatory jaw disease compared with those not treated. PATIENTS AND METHODS: A historical cohort study was designed to c...

  6. Treatment of bisphosphonate-related osteonecrosis of the jaws – a report of seven cases

    Science.gov (United States)

    Rahnama, Mansur; Szczerba-Gwóźdź, Joanna

    2017-01-01

    Aim of the study The aim of the study was to report on seven cases of BRONJ treated with surgical debridement, oral antibiotics and gentamicin-collagen sponge (Collatamp EG) placed in the bone wound. Material and methods Seven patients with 9 sites of BRONJ stage 2 were included in the study. Perioperative oral antibiotics, surgical debridement and/or sequestrotomy and gentamicin-collagen sponge (Collatamp EG) were used. Postoperative monitoring was carried out for the next 3 months. Results Three weeks after the surgery, six sites of BRONJ in five patients were treated successfully. In two patients on three sites BRONJ stage 1 was observed. Three months after surgery another two sites healed fully. In one patient there was still BRONJ stage 1, however, the area of exposed bone was visibly reduced. Conclusions The use of surgical debridement together with oral antibiotic therapy and collagen-gentamycin sponge indicates positive results regarding the surgical treatment of BRONJ. PMID:28239288

  7. Incidence of bisphosphonate-related osteonecrosis of the jaw in high-risk patients undergoing surgical tooth extraction.

    Science.gov (United States)

    Bodem, Jens Philipp; Kargus, Steffen; Eckstein, Stefanie; Saure, Daniel; Engel, Michael; Hoffmann, Jürgen; Freudlsperger, Christian

    2015-05-01

    As the most suitable approach for preventing bisphosphonate-related osteonecrosis of the jaw (BRONJ) in patients undergoing surgical tooth extraction is still under discussion, the present study evaluates the incidence of BRONJ after surgical tooth extraction using a standardized surgical protocol in combination with an adjuvant perioperative treatment setting in patients who are at high-risk for developing BRONJ. High-risk patients were defined as patients who received intravenous bisphosphonate (BP) due to a malignant disease. All teeth were removed using a standardized surgical protocol. The perioperative adjuvant treatment included intravenous antibiotic prophylaxis starting at least 24 h before surgery, a gastric feeding tube and mouth rinses with chlorhexidine (0.12%) three times a day. In the follow-up period patients were examined every 4 weeks for the development of BRONJ. Minimum follow-up was 12 weeks. In 61 patients a total number of 184 teeth were removed from 102 separate extraction sites. In eight patients (13.1%) BRONJ developed during the follow-up. A higher risk for developing BRONJ was found in patients where an additional osteotomy was necessary (21.4% vs. 8.0%; p = 0.0577), especially for an osteotomy of the mandible (33.3% vs. 7.3%; p = 0.0268). Parameters including duration of intravenous antibiotic prophylaxis, the use of a gastric feeding tube and the duration of intravenous BP therapy showed no statistical impact on the development of BRONJ. Furthermore, patients currently undergoing intravenous BP therapy showed no higher risk for BRONJ compared with patients who have paused or completed their intravenous BP therapy (p = 0.4232). This study presents a protocol for surgical tooth extraction in high-risk BP patients in combination with a perioperative adjuvant treatment setting, which reduced the risk for postoperative BRONJ to a minimum. However, the risk for BRONJ increases significantly if an additional osteotomy is necessary

  8. Golden Week, Golden Effect

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ The Golden Week Holiday System was established in 1999. Bv adding legal holidays and the time off from the previous and following weekends, China made three Golden Weeks (7-day holidays), for the Spring Festival, May Labor Day and National Day in October.Since it was introduced eight years ago,the Golden Weeks have added considerably to China's economic development.The significant role they have played in promoting economic development and changing the Chinese people's concept of consumption and way of living has been witnessed by everyone.

  9. A randomised comparison of increase in serum 25-hydroxyvitamin D concentration after 4 weeks of daily oral intake of 10 microg cholecalciferol from multivitamin tablets or fish oil capsules in healthy young adults.

    Science.gov (United States)

    Holvik, Kristin; Madar, Ahmed A; Meyer, Haakon E; Lofthus, Cathrine M; Stene, Lars C

    2007-09-01

    Many types of vitamin supplements are available on the market, but little is known about whether cholecalciferol obtained from fat-containing capsules differs in bioavailability from that of solid tablets. Our objective was to test whether 4 weeks of daily supplementation with 10 mug cholecalciferol given as a fish oil capsule produces a larger increase in serum 25-hydroxyvitamin D (s-25(OH)D) concentration compared with the same dose of cholecalciferol given as a multivitamin tablet. A total of seventy-four healthy subjects aged 19-49 years were initially included and fifty-five of these completed the study and fulfilled the inclusion criteria. After completing a self-administered questionnaire about diet and sunshine exposure and having a non-fasting venous blood sample drawn, participants were randomised to receive daily multivitamin tablets (n 28) or fish oil capsules (n 27), each containing equal doses of cholecalciferol. A second blood sample was drawn after 28 d. Mean baseline s-25(OH)D was 40.3 (sd 22.0) nmol/l in the multivitamin group and 48.5 (24.8) nmol/l in the fish oil group. When controlling for baseline s-25(OH)D, mean 4-week increase in s-25(OH)D was 35.8 (95 % CI 30.9, 40.8) nmol/l in the multivitamin group and 32.3 (95 % CI 27.3, 37.4) nmol/l in the fish oil group; the mean difference was 3.5 (95 % CI - 3.6, 10.6) nmol/l (P = 0.33). The results were unaltered by statistical adjustment for BMI, ethnic background, age and sex. We conclude that fish oil capsules and multivitamin tablets containing 10 microg cholecalciferol administered over a 4-week period produced a similar mean increase in s-25(OH)D concentration.

  10. Statin and Bisphosphonate Induce Starvation in Fast-Growing Cancer Cell Lines.

    Science.gov (United States)

    Karlic, Heidrun; Haider, Florian; Thaler, Roman; Spitzer, Silvia; Klaushofer, Klaus; Varga, Franz

    2017-09-15

    Statins and bisphosphonates are increasingly recognized as anti-cancer drugs, especially because of their cholesterol-lowering properties. However, these drugs act differently on various types of cancers. Thus, the aim of this study was to compare the effects of statins and bisphosphonates on the metabolism (NADP⁺/NADPH-relation) of highly proliferative tumor cell lines from different origins (PC-3 prostate carcinoma, MDA-MB-231 breast cancer, U-2 OS osteosarcoma) versus cells with a slower proliferation rate like MG-63 osteosarcoma cells. Global gene expression analysis revealed that after 6 days of treatment with pharmacologic doses of the statin simvastatin and of the bisphosphonate ibandronate, simvastatin regulated more than twice as many genes as ibandronate, including many genes associated with cell cycle progression. Upregulation of starvation-markers and a reduction of metabolism and associated NADPH production, an increase in autophagy, and a concomitant downregulation of H3K27 methylation was most significant in the fast-growing cancer cell lines. This study provides possible explanations for clinical observations indicating a higher sensitivity of rapidly proliferating tumors to statins and bisphosphonates.

  11. Graft polymerization of styryl bisphosphonate monomer onto polypropylene films for inhibition of biofilm formation.

    Science.gov (United States)

    Steinmetz, Hanna P; Rudnick-Glick, Safra; Natan, Michal; Banin, Ehud; Margel, Shlomo

    2016-11-01

    There has been increased concern during the past few decades over the role bacterial biofilms play in causing a variety of health problems, especially since they exhibit a high degree of resistance to antibiotics and are able to survive in hostile environments. Biofilms consist of bacterial aggregates enveloped by a self-produced matrix attached to the surface. Ca(2+) ions promote the formation of biofilms, and enhance their stability, viscosity, and strength. Bisphosphonates exhibit a high affinity for Ca(2+) ions, and may inhibit the formation of biofilms by acting as sequestering agents for Ca(2+) ions. Although the antibacterial activity of bisphosphonates is well known, research into their anti-biofilm behavior is still in its early stages. In this study, we describe the synthesis of a new thin coating composed of poly(styryl bisphosphonate) grafted onto oxidized polypropylene films for anti-biofilm applications. This grafting process was performed by graft polymerization of styryl bisphosphonate vinylic monomer onto O2 plasma-treated polypropylene films. The surface modification of the polypropylene films was confirmed using surface measurements, including X-ray photoelectron spectroscopy, atomic force microscopy, and water contact angle goniometry. Significant inhibition of biofilm formation was achieved for both Gram-negative and Gram-positive bacteria.

  12. Time to onset of bisphosphonate-related osteonecrosis of the jaws

    DEFF Research Database (Denmark)

    Fung, Ppl; Bedogni, G; Bedogni, A

    2017-01-01

    OBJECTIVES: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to esti...

  13. Novel Radiolabeled Bisphosphonates for PET Diagnosis and Endoradiotherapy of Bone Metastases

    Science.gov (United States)

    Pfannkuchen, Nina; Meckel, Marian; Bergmann, Ralf; Bachmann, Michael; Bal, Chandrasekhar; Sathekge, Mike; Mohnike, Wolfgang; Baum, Richard P.; Rösch, Frank

    2017-01-01

    Bone metastases, often a consequence of breast, prostate, and lung carcinomas, are characterized by an increased bone turnover, which can be visualized by positron emission tomography (PET), as well as single-photon emission computed tomography (SPECT). Bisphosphonate complexes of 99mTc are predominantly used as SPECT tracers. In contrast to SPECT, PET offers a higher spatial resolution and, owing to the 68Ge/68Ga generator, an analog to the established 99mTc generator exists. Complexation of Ga(III) requires the use of chelators. Therefore, DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), NOTA (1,4,7-triazacyclododecane-1,4,7-triacetic acid), and their derivatives, are often used. The combination of these macrocyclic chelators and bisphosphonates is currently studied worldwide. The use of DOTA offers the possibility of a therapeutic application by complexing the β-emitter 177Lu. This overview describes the possibility of diagnosing bone metastases using [68Ga]Ga-BPAMD (68Ga-labeled (4-{[bis-(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl)acetic acid) as well as the successful application of [177Lu]Lu-BPAMD for therapy and the development of new diagnostic and therapeutic tools based on this structure. Improvements concerning both the chelator and the bisphosphonate structure are illustrated providing new 68Ga- and 177Lu-labeled bisphosphonates offering improved pharmacological properties. PMID:28524118

  14. Bisphosphonate therapy and osteogenesis imperfecta: The lived experience of children and their mothers.

    Science.gov (United States)

    Wiggins, Shirley; Kreikemeier, Rose

    2017-09-06

    Osteogenesis imperfecta (OI) is a chronic, genetic condition frequently described as "brittle bones." This condition is expressed by low bone density and characterized by frequent fractures with and without trauma. Additional symptoms include pain, altered growth, and challenges with mobility. This experience has a great impact on the daily life of the child diagnosed with OI and their family. With the introduction of bisphosphonate therapy children diagnosed with OI experienced an increase in bone density that included a change in symptoms and improvement in daily functioning. The purpose of this study was to describe the lived experience of children receiving bisphosphonate therapy for osteogenesis imperfecta (OI) and their mothers. A phenomenological study was conducted using interviews with a purposive sample of six children diagnosed with OI and their six mothers (N = 12). Children ranged in age from 6 to 18 years. The Giorgi (2009) methodology was used to discover the meaning of living day to day since initiating the bisphosphonate infusion therapy. Four themes emerged from the synthesis of the meaning units that reflected the experience that bisphosphonate therapy had on daily life with OI. These four themes explicitly described the phenomena being studied and included living daily life in stride; normalcy is living with uncertainty; renewal with infusions; and making choices and living with the consequences. Nurses must take an active role in developing and promoting family-centered interventions for transition and support. © 2017 Wiley Periodicals, Inc.

  15. Implant failure caused by non-union of bisphosphonate-associated subtrochanteric femur fracture.

    LENUS (Irish Health Repository)

    O'Neill, Barry James

    2014-04-03

    Bisphosphonate use has been identified as a contributory factor in atypical subtrochanteric fracture of the femur. These fractures are commonly treated with an intramedullary device. We present a case of implant failure of an intrameduallary device caused by non-union of an atypical subtrochanteric fracture.

  16. Comparison of nonexposed and exposed bisphosphonate-induced osteonecrosis of the jaws

    DEFF Research Database (Denmark)

    Schiodt, Morten; Reibel, Jesper; Oturai, Peter

    2014-01-01

    Nonexposed osteonecrosis of the jaws (NE-ONJ) does not fit into the current definition of osteonecrosis, which requires exposed bone. A modification of the classification of bisphosphonate-induced osteonecrosis of the jaws (ONJ) is proposed. This study aimed to test proposed criteria for NE-ONJ a...

  17. Ab initio Investigation of Adsorption Characteristics of Bisphosphonates on Hydroxyapatite (001) Surface

    CERN Document Server

    Ri, Mun-Hyok; Yu, Chol-Jun; Kim, Song-Un

    2016-01-01

    The structures of some bisphosphonates (clodronate, etidronate, pamidronate, alendronate, risedronate, zoledronate, minodronate) were obtained and analyzed, and their adsorption energies onto hydroxyapatite (001) surface were compared to find out ranking order of binding affinity, which shows that the adsorption energy is the largest for pamidronate, followed by alendronate, zoledronate, clodronate, ibandronate, the lowest for minodronate and etidronate.

  18. Implant failure caused by non-union of bisphosphonate-associated subtrochanteric femur fracture

    OpenAIRE

    2014-01-01

    Bisphosphonate use has been identified as a contributory factor in atypical subtrochanteric fracture of the femur. These fractures are commonly treated with an intramedullary device. We present a case of implant failure of an intrameduallary device caused by non-union of an atypical subtrochanteric fracture.

  19. Catechol-Bisphosphonate Conjugates:New Potential Chelating Agents for Metal Intoxication Therapy

    Institute of Scientific and Technical Information of China (English)

    Guang Yu XU; Chun Hao YANG; Bo LIU; Xi Han WU; Yu Yuan XIE

    2004-01-01

    In a quest for better chelating therapy drugs for the treatment of intoxication by Fe, Al, or actinides, two new series of mixed catechol-bisphosphonate through amide linkage were synthesized.Benzyl group was used as protecting group to avoid the breakage of amide by acid hydrolysis or imcomplete reaction in silylation-dealkylation using bromotrimethylsilane.

  20. Osteonecrosis of the jaw-a bone site - specific effect of bisphosphonates

    NARCIS (Netherlands)

    Vermeer, J.A.F.; Renders, G.A.P.; Everts, V.

    2016-01-01

    A known complication that can occur in patients using bisphosphonates (BPs) is osteonecrosis of the jaw (ONJ). ONJ features bone exposure that may be associated with severe pain, swelling, local infection, and pathological fracture of the jaw. Current literature indicates that a complex combination

  1. Bisphosphonate related osteonecrosis of the jaw; a literature review and a new hypothesis

    NARCIS (Netherlands)

    Helsloot, R.S.J.; van den Berg, T.; Frank, M.H.; Everts, V.

    2011-01-01

    Bisphosphonates are drugs used to reduce normal bone turnover. These medicines are prescribed to patients with diseases like bone malignancies, osteoporosis and Paget’s disease. Since a decade it has been recognized that osteonecrosis of the jaws occurs relatively frequent as a side-effect of the us

  2. Sinusitis and oroantral fistula in patients with bisphosphonate-associated necrosis of the maxilla.

    Science.gov (United States)

    Voss, Pit Jacob; Vargas Soto, Gustavo; Schmelzeisen, Rainer; Izumi, Kiwako; Stricker, Andres; Bittermann, Gido; Poxleitner, Philipp

    2016-01-06

    The management of bisphosphonate related necrosis of the jaw has become clinical routine. While approximately two thirds of the lesions are in the mandible, one third is located in the maxilla. In 40-50 % of maxillary necrosis the maxillary sinus is involved, leading to maxillary sinusitis and oro-antral communications. This retrospective single center study includes all patients with diagnosis of BP-ONJ of the maxilla and concomitant maxillary sinusitis. The information collected includes age, gender, primary disease, bisphosphonate intake, involving type of bisphosphonate, route of administration and duration of BP treatment previous to surgical treatment and treatment outcome. A total of 12 patients fulfill the criteria of the diagnosis of maxillary sinusitis associated to maxillary necrosis, of which 6 Patients showed purulent sinusitis. All patients underwent surgical treatment with complete resection of the affected bone and a multilayer wound closure. A recurrence appeared in one patient with open bone and no sign of sinusitis and was treated conservatively. Purulent maxillary Sinusitis is a common complication of bisphosphonate-related necrosis of the maxilla. The surgical technique described can be suggested for the treatment of these patients.

  3. A New Epoxy Bis-Phosphonate Crosslinker for Durable Fire Retardancy on Cotton

    Science.gov (United States)

    A new epoxy bis-phosphonate crosslinker for cotton [2-(dimethoxy-phosphorylmethyl)-oxiranylmethyl]-phosphonic acid dimethyl ester was prepared in two steps from 3-chloro-2-chloromethylpropene in 55% yield. The new monomer was characterized by proton and carbon NMR and GC-mass spectrometry. This cro...

  4. Improved efficacy of intramuscular weekly administration of clodronate 200 mg (100 mg twice weekly) compared with 100 mg (once weekly) for increasing bone mineral density in postmenopausal osteoporosis.

    Science.gov (United States)

    Frediani, Bruno; Bertoldi, Ilaria; Pierguidi, Serena; Nicosia, Antonella; Picerno, Valentina; Filippou, Georgios; Cantarini, Luca; Galeazzi, Mauro

    2013-03-01

    Clodronate is a bisphosphonate used for the treatment of postmenopausal osteoporosis and all conditions characterized by excess bone resorption. We have previously reported that intramuscular (IM) therapy with clodronate at a dose of 100 mg/week displays significant effects on bone mineral density (BMD) although a plateau effect is observed after 1 year of treatment. Previous reports indicate that the densitometric effects of bisphosphonates directly correlate with the drug dosage and suggest that using IM clodronate at doses higher than 100 mg/week may result in improved efficacy. However, to the best of our knowledge, this has never been proved. The primary endpoint of the study was the effect on BMD of IM clodronate 100 mg once weekly or 100 mg twice weekly in patients with postmenopausal osteoporosis. The incidence of non-traumatic vertebral fractures and adverse events was also reported. The present study was a randomized, open-label, parallel-group trial conducted between January 2007 and December 2009 in the Osteoporosis and Osteoarticular Instrumental Diagnosis Centre (University of Siena, Siena, Italy). The study involved 60 women, aged 57-78 years, with a history of postmenopausal osteoporosis for more than 5 years. Patients were randomized to receive IM clodronate 100 mg once weekly (Group A, 30 patients) or 100 mg twice weekly (Group B, 30 patients), for 2 years. Significant increases compared with baseline in BMD were observed for both groups at 1 and 2 years, with significantly higher increases for Group B compared with Group A. Group B displayed a BMD increase (± SD) at the lumbar spine of +4.0 % (± 2.1) and +5.9 % (± 2.0) at 1 and 2 year(s), respectively, compared with +2.8 % (± 1.7) and +3.5 % (± 2.2), respectively, observed for Group A. Similarly, Group B showed better performance compared with Group A for BMD increase at the femoral neck, with an observed increase of +3.5 % (± 1.7) and +5.4 % (± 1.8) at 1 and 2 year(s), respectively

  5. Examining the association between oral health and oral HPV infection.

    Science.gov (United States)

    Bui, Thanh Cong; Markham, Christine M; Ross, Michael Wallis; Mullen, Patricia Dolan

    2013-09-01

    Oral human papillomavirus (HPV) infection is the cause of 40% to 80% of oropharyngeal cancers; yet, no published study has examined the role of oral health in oral HPV infection, either independently or in conjunction with other risk factors. This study examined the relation between oral health and oral HPV infection and the interactive effects of oral health, smoking, and oral sex on oral HPV infection. Our analyses comprised 3,439 participants ages 30 to 69 years for whom data on oral HPV and oral health were available from the nationally representative 2009-2010 National Health and Nutrition Examination Survey. Results showed that higher unadjusted prevalence of oral HPV infection was associated with four measures of oral health, including self-rated oral health as poor-to-fair [prevalence ratio (PR) = 1.56; 95% confidence interval (CI), 1.25-1.95], indicated the possibility of gum disease (PR = 1.51; 95% CI, 1.13-2.01), reported use of mouthwash to treat dental problems in the past week (PR = 1.28; 95% CI, 1.07-1.52), and higher number of teeth lost (Ptrend = 0.035). In multivariable logistic regression models, oral HPV infection had a statistically significant association with self-rated overall oral health (OR = 1.55; 95% CI, 1.15-2.09), independent of smoking and oral sex. In conclusion, poor oral health was an independent risk factor of oral HPV infection, irrespective of smoking and oral sex practices. Public health interventions may aim to promote oral hygiene and oral health as an additional measure to prevent HPV-related oral cancers.

  6. Trabecular reorganization in consecutive iliac crest biopsies when switching from bisphosphonate to strontium ranelate treatment.

    Directory of Open Access Journals (Sweden)

    Björn Jobke

    Full Text Available BACKGROUND: Several agents are available to treat osteoporosis while addressing patient-specific medical needs. Individuals' residual risk to severe fracture may require changes in treatment strategy. Data at osseous cellular and microstructural levels due to a therapy switch between agents with different modes of action are rare. Our study on a series of five consecutively taken bone biopsies from an osteoporotic individual over a six-year period analyzes changes in cellular characteristics, bone microstructure and mineralization caused by a therapy switch from an antiresorptive (bisphosphonate to a dual action bone agent (strontium ranelate. METHODOLOGY/PRINCIPAL FINDINGS: Biopsies were progressively taken from the iliac crest of a female patient. Four biopsies were taken during bisphosphonate therapy and one biopsy was taken after one year of strontium ranelate (SR treatment. Furthermore, serum bone markers and dual x-ray absorptiometry measurements were acquired. Undecalcified histology was used to assess osteoid parameters and bone turnover. Structural indices and degree of mineralization were determined using microcomputed tomography, quantitative backscattered electron imaging, and combined energy dispersive x-ray/µ-x-ray-fluorescence microanalysis. CONCLUSIONS/SIGNIFICANCE: Microstructural data revealed a notable increase in bone volume fraction after one year of SR treatment compared to the bisphosphonate treatment period. Indices of connectivity density, structure model index and trabecular bone pattern factor were predominantly enhanced indicating that the architectural transformation from trabecular rods to plates was responsible for the bone volume increase and less due to changes in trabecular thickness and number. Administration of SR following bisphosphonates led to a maintained mineralization profile with an uptake of strontium on the bone surface level. Reactivated osteoclasts designed tunneling, hook-like intratrabecular

  7. Subtrochanteric fractures in bisphosphonate-naive patients: results from the HORIZON-recurrent fracture trial.

    Science.gov (United States)

    Adachi, Jonathan D; Lyles, Kenneth; Boonen, Steven; Colón-Emeric, Cathleen; Hyldstrup, Lars; Nordsletten, Lars; Pieper, Carl; Recknor, Chris; Su, Guoqin; Bucci-Rechtweg, Christina; Magaziner, Jay

    2011-12-01

    Our purpose was to characterize the risks of osteoporosis-related subtrochanteric fractures in bisphosphonate-naive individuals. Baseline characteristics of patients enrolled in the HORIZON-Recurrent Fracture Trial with a study-qualifying hip fracture were examined, comparing those who sustained incident subtrochanteric fractures with those sustaining other hip fractures. Subjects were bisphosphonate-naive or had a bisphosphonate washout period of 6-24 months and subsequently received an annual infusion of zoledronic acid 5 mg or placebo after low-trauma hip-fracture repair. In total, 2,127 men and women were included. Of the qualifying hip fractures, 5.2% were subtrochanteric, 54.8% femoral neck, 33.0% intertrochanteric, and 7.1% other (generally complex fractures of mixed type). Significant baseline (pre-hip fracture) differences were seen between index hip-fracture types, with the percentage of patients with extreme mobility problems being twofold higher in patients with index subtrochanteric fracture (9.9%) compared to other patients. The distribution of hip-fracture types was similar between the treatment groups at baseline. No patients with index subtrochanteric fractures and six patients with other qualifying hip fractures reported prior bisphosphonate use. Only one further subtrochanteric fracture occurred in each treatment group over an average 2-year patient follow-up. Subtrochanteric fractures are not uncommon in bisphosphonate-naive patients. Extreme difficulties with mobility may be a unique risk factor predisposing to development of incident subtrochanteric fractures rather than other types of hip fracture. In patients with recent hip fracture who received zoledronic acid therapy, the incidence of new subtrochanteric fractures was too small to draw any meaningful conclusions.

  8. Psychometric evaluation of the Osteoporosis Patient Treatment Satisfaction Questionnaire (OPSAT-Q™, a novel measure to assess satisfaction with bisphosphonate treatment in postmenopausal women

    Directory of Open Access Journals (Sweden)

    Shikiar Richard

    2006-07-01

    Full Text Available Abstract Background The Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q is a new measure of patient satisfaction with bisphosphonate treatment for osteoporosis. The objective of this study was to evaluate the psychometric characteristics of the OPSAT-Q. Methods The OPSAT-Q contains 16 items in four subscales: Convenience, Confidence with Daily Activities, Side Effects, and Overall Satisfaction. All four subscale scores and an overall composite satisfaction score (CSS can be computed. The OPSAT-Q, Osteoporosis Targeted Quality of Life (OPTQoL, and sociodemographic/clinical questionnaires, including 3 global items on convenience, functioning and side effects, were self-administered to women with osteoporosis or osteopenia recruited from four US clinics. Analyses included item and scale performance, internal consistency reliability, reproducibility, and construct validity. Reproducibility was measured using the intraclass correlation coefficient (ICC via a follow-up questionnaire completed by participants 2 weeks post baseline. Results 104 women with a mean age of 65.1 years participated. The majority were Caucasian (64.4%, living with someone (74%, and not currently employed (58.7%. 73% had osteoporosis and 27% had osteopenia. 80% were taking weekly bisphosphonates and 18% were taking daily medication (2% missing data. On a scale of 0–100, individual patient subscale scores ranged from 17 to 100 and CSS scores ranged from 44 to 100. All scores showed acceptable internal consistency reliability (Cronbach's alpha > 0.70 (range 0.72 to 0.89. Reproducibility ranged from 0.62 (Daily Activities to 0.79 (Side Effects for the subscales; reproducibility for the CSS was 0.81. Significant correlations were found between the OPSAT-Q subscales and conceptually similar global measures (p Conclusion The findings from this study confirm the validity and reliability of the OPSAT-Q and support the proposed composition of four subscales and a composite

  9. The bisphosphonate zoledronate prevents vertebral bone loss in mature estrogen-deficient rats as assessed by micro-computed tomography

    Directory of Open Access Journals (Sweden)

    Glatt M.

    2001-01-01

    Full Text Available The effect of long-term treatment with the bisphosphonate zoledronate on vertebral bone architecture was investigated in estrogen-deficient mature rats. 4-month-old rats were ovariectomized and development of cancellous osteopenia was assessed after 1 year. The change of bone architectural parameters was determined with a microtomographic instrument of high resolution. After 1 year of estrogen-deficiency, animals lost 55% of vertebral trabecular bone in comparison to sham operated control animals. Trabecular number (Tb.N and trabecular thickness (Tb.Th were significantly reduced in ovariectomized animals, whereas trabecular separation (Tb.Sp, bone surface to volume fraction (BS/BV and trabecular bone pattern factor (TBPf were significantly increased, indicating a loss of architectural integrity throughout the vertebral body. 3 groups of animals were treated subcutaneously with zoledronate for 1 year with 0.3, 1.5 and 7.5 microgram/kg/week to inhibit osteoclastic bone degradation. Administration started immediately after ovariectomy and treatment dose-dependently prevented the architectural bone deterioration and completely suppressed the effects of estrogen deficiency at the higher doses. The results show that microtomographic determination of static morphometric parameters can be used to quantitate the effects of drugs on vertebral bone architecture in small laboratory animals and that zoledronate is highly effective in this rat model.

  10. Effect of Long-Term Use of Bisphosphonates on Forearm Bone: Atypical Ulna Fractures in Elderly Woman with Osteoporosis

    Directory of Open Access Journals (Sweden)

    Yusuf Erdem

    2016-01-01

    Full Text Available Osteoporosis is a common musculoskeletal disease of the elderly population characterized by decreased bone mineral density and subsequent fractures. Bisphosphonates are a widely accepted drug therapy which act through inhibition of bone resorption and prevent fractures. However, in long-term use, atypical bisphosphonate induced fractures may occur, particularly involving the lower weight bearing extremity. Atypical ulna fracture associated with long-term bisphosphonate use is rarely reported in current literature. We present a 62-year-old woman with atypical ulna due to long-term alendronate therapy without a history of trauma or fall. Clinicians should be aware of stress fracture in a patient who has complaints of upper extremity pain and history of long-term bisphosphonate therapy.

  11. A randomized controlled trial to compare the efficacy of bisphosphonates in the management of painful bone metastasis

    Directory of Open Access Journals (Sweden)

    Krishnangshu Bhanja Choudhury

    2011-01-01

    Conclusion: The use of bisphosphonates for 6 months or more results in a statistical significant improvement in bone pain, more so with zoledronic acid. Hypercalcemia, an SRE, was significantly less in the zoledronic acid arm.

  12. [Inorganic pyrophosphatase activity of the mouse spleen in the immune response and after treatment with bis-phosphonates].

    Science.gov (United States)

    Komissarenko, S V; Gulaia, N M; Gaĭvoronskaia, G G; Karlova, N P; Tarusova, N B

    1986-01-01

    The inorganic pyrophosphatase activity was determined in different tissues of mice. The immunization of mice by sheep erythrocytes increased the inorganic pyrophosphatase activity of the spleen. The in vivo administration of bisphosphonates (40 mg per 1 g of mass), which are structural analogs of inorganic pyrophosphate (methylene bisphosphonic acid--MBPA, hydroxyethylidene bisphosphonic acid--HEBPA and aminomethylene bisphosphonic acid--AMBPA), inhibited the inorganic pyrophosphatase activity only by MBPA in the thymus and spleen but not in liver. The addition of MBPA, HEBPA as well as of phosphonoacetic acid, imidobisphosphate, bis(phosphonomethyl)-phosphonic acid, MBPA and phosphoric acid monoanhydride to cytosol from the mouse spleen led to the competitive (relative to the [Mg (PPi)2-] complex) inhibition of the inorganic pyrophosphatase activity. AMBPA didn't possess the analogous effect.

  13. Bone mineral density testing, and bisphosphonate and oestrogen prescribing associated with depot medroxyprogesterone acetate utilization-The impact of the boxed warning.

    Science.gov (United States)

    Eworuke, E; Popat, V; Moeny, D G

    2017-08-01

    Depot medroxyprogesterone acetate (DMPA) prevents follicular maturation and ovulation, resulting in oestrogen deficiency. Oestrogen deficiency is particularly concerning as it is associated with decreases in bone mineral density (BMD) or bone mass. Widespread use of concurrent oestrogen or bisphosphonates with DMPA has been observed in a previous single-centre US study. The authors also reported that more than half of obstetrician-gynaecologists ordered BMD testing solely due to DMPA. The small sample size of the survey, potential for volunteer bias and recall bias limit the utility of this study. Given the study limitations, we sought to examine the trends of concurrent bone mineral density (BMD) testing, and bisphosphonate (BPA) and oral oestrogen-only (EST) prescribing during depot medroxyprogesterone (DMPA) use in a large administrative database. From IMS Health LifeLink™ database (2001-2013), we identified DMPA and combined hormonal contraceptive (CHC) users as women with no contraceptive claim 6 months before and after the defined episode. We examined concurrent use as the proportion of BPA or EST claims and concurrent therapy days during contraception use. We also determined the proportion of users who had a concurrent BMD test by calendar year. We identified 203 477 DMPA episodes associated with 600 BPA and 7060 EST claims and 1 297 806 CHC episodes associated with 2792 BPA and 145 600 EST claims. Most concurrent BPA use overlapped with 10% or less of the DMPA episode, whereas most concurrent BPA use overlapped with >90%-100% of CHC episode. No difference was noted with concurrent EST use. Concurrent BMD testing was higher among DMPA users (0.68%) compared to CHC users (0.11%). Across calendar year, BMD testing peaked in 2004 and declined steadily to the baseline. Most DMPA concurrent BPA (69.3%) users had a BMD test. Our findings indicate the absence of BST or EST use solely due to DMPA initiation and present alternative explanations. Published

  14. Phun Week: Understanding Physiology

    Science.gov (United States)

    Limson, Mel; Matyas, Marsha Lakes

    2009-01-01

    Topics such as sports, exercise, health, and nutrition can make the science of physiology relevant and engaging for students. In addition, many lessons on these topics, such as those on the cardiovascular, respiratory, and digestive systems, align with national and state life science education standards. Physiology Understanding Week (PhUn…

  15. A Week for Space

    Science.gov (United States)

    Comstock, Diane

    2008-01-01

    Space Week focuses on concepts that enable students to make concrete observations in the early grades (K-2) and move to concepts that help students develop their internet research and writing skills in middle and upper grades (Grades 3-5), and culminates with the development of science investigation design skills (Grade 6). To help launch your…

  16. An Evaluative History of Bisphosphonate Drugs: Dual Physiologic Effects of Pyrophosphate as Inspiration for a Novel Pharmaceutical Class

    Science.gov (United States)

    2016-01-01

    The documented history of the development of the bisphosphonate drugs is reviewed in sufficient detail to permit independent evaluation of the consistency of the conclusions reached from the available data. The evidence developed during the early interval of these studies 1960–1975 was sufficient to establish that pyrophosphate shares the subsequently established dual bisphosphonate characteristics of bone resorption inhibition and prevention of tissue mineralization. PMID:27800209

  17. Effects of bisphosphonates on the growth of Entamoeba histolytica and Plasmodium species in vitro and in vivo.

    Science.gov (United States)

    Ghosh, Subhash; Chan, Julian M W; Lea, Christopher R; Meints, Gary A; Lewis, Jared C; Tovian, Zev S; Flessner, Ryan M; Loftus, Timothy C; Bruchhaus, Iris; Kendrick, Howard; Croft, Simon L; Kemp, Robert G; Kobayashi, Seiki; Nozaki, Tomoyoshi; Oldfield, Eric

    2004-01-01

    The effects of a series of 102 bisphosphonates on the inhibition of growth of Entamoeba histolytica and Plasmodium falciparum in vitro have been determined, and selected compounds were further investigated for their in vivo activity. Forty-seven compounds tested were active (IC(50) histolytica growth in vitro. The most active compounds (IC(50) approximately 4-9 microM) were nitrogen-containing bisphosphonates with relatively large aromatic side chains. Simple n-alkyl-1-hydroxy-1,1-bisphosphonates, known inhibitors of the enzyme farnesylpyrophosphate (FPP) synthase, were also active, with optimal activity being found with C9-C10 side chains. However, numerous other nitrogen-containing bisphosphonates known to be potent FPP synthase inhibitors, such as risedronate or pamidronate, had little or no activity. Several pyridine-derived bisphosphonates were quite active (IC(50) approximately 10-20 microM), and this activity was shown to correlate with the basicity of the aromatic group, with activity decreasing with increasing pK(a) values. The activities of all compounds were tested versus a human nasopharyngeal carcinoma (KB) cell line to enable an estimate of the therapeutic index (TI). Five bisphosphonates were selected and then screened for their ability to delay the development of amebic liver abscess formation in an E. histolytica infected hamster model. Two compounds were found to decrease liver abscess formation at 10 mg/kg ip with little or no effect on normal liver mass. With P. falciparum, 35 compounds had IC(50) values vivo investigation in a Plasmodium berghei ANKA BALB/c mouse suppressive test. The most active compound, a C9 n-alkyl side chain containing bisphosphonate, caused an 80% reduction in parasitemia with no overt toxicity. Taken together, these results show that bisphosphonates appear to be useful lead compounds for the development of novel antiamebic and antimalarial drugs.

  18. Bisphosphonates and risk of subtrochanteric, femoral shaft, and atypical femur fracture: a systematic review and meta-analysis.

    Science.gov (United States)

    Gedmintas, Lydia; Solomon, Daniel H; Kim, Seoyoung C

    2013-08-01

    Although there is strong evidence that bisphosphonates prevent certain types of osteoporotic fractures, there are concerns that these medications may be associated with rare atypical femoral fractures (AFF). Recent published studies examining this potential association are conflicting regarding the existence and strength of this association. We conducted a systematic review and meta-analysis of published studies examining the association of bisphosphonates with subtrochanteric, femoral shaft, and AFF. The random-effects model was used to calculate the pooled estimates of adjusted risk ratios (RR). Subgroup analysis was performed by study design, for studies that used validated outcome definitions for AFF, and for studies reporting on duration of bisphosphonate use. Eleven studies were included in the meta-analysis: five case-control and six cohort studies. Bisphosphonate exposure was associated with an increased risk of subtrochanteric, femoral shaft, and AFF, with adjusted RR of 1.70 (95% confidence interval [CI], 1.22-2.37). Subgroup analysis of studies using the American Society for Bone and Mineral Research criteria to define AFF suggests a higher risk of AFF, with bisphosphonate use with RR of 11.78 (95% CI, 0.39-359.69) as compared to studies using mainly diagnosis codes (RR, 1.62; 95% CI, 1.18-2.22), although there is a wide confidence interval and severe heterogeneity (I(2)  = 96.15%) in this subgroup analysis. Subgroup analysis of studies examining at least 5 years of bisphosphonate use showed adjusted RR of 1.62 (95% CI, 1.29-2.04). This meta-analysis suggests there is an increased risk of subtrochanteric, femoral shaft, and AFF among bisphosphonate users. Further research examining the risk of AFF with long-term use of bisphosphonates is indicated as there was limited data in this subgroup. The public health implication of this observed increase in AFF risk is not clear.

  19. Combined zoledronic acid and meloxicam reduced bone loss and tumour growth in an orthotopic mouse model of bone-invasive oral squamous cell carcinoma.

    Science.gov (United States)

    Martin, C K; Dirksen, W P; Carlton, M M; Lanigan, L G; Pillai, S P; Werbeck, J L; Simmons, J K; Hildreth, B E; London, C A; Toribio, R E; Rosol, T J

    2015-09-01

    Oral squamous cell carcinoma (OSCC) is common in cats and humans and invades oral bone. We hypothesized that the cyclooxygenase (COX)-2 inhibitor, meloxicam, with the bisphosphonate, zoledronic acid (ZOL), would inhibit tumour growth, osteolysis and invasion in feline OSCC xenografts in mice. Human and feline OSCC cell lines expressed COX-1 and COX-2 and the SCCF2 cells had increased COX-2 mRNA expression with bone conditioned medium. Luciferase-expressing feline SCCF2Luc cells were injected beneath the perimaxillary gingiva and mice were treated with 0.1 mg kg(-1) ZOL twice weekly, 0.3 mg kg(-1) meloxicam daily, combined ZOL and meloxicam, or vehicle. ZOL inhibited osteoclastic bone resorption at the tumour-bone interface. Meloxicam was more effective than ZOL at reducing xenograft growth but did not affect osteoclastic bone resorption. Although a synergistic effect of combined ZOL and meloxicam was not observed, combination therapy was well-tolerated and may be useful in the clinical management of bone-invasive feline OSCC.

  20. Low Bone Density and Bisphosphonate Use and the Risk of Kidney Stones.

    Science.gov (United States)

    Prochaska, Megan; Taylor, Eric; Vaidya, Anand; Curhan, Gary

    2017-08-07

    Previous studies have demonstrated lower bone density in patients with kidney stones, but no longitudinal studies have evaluated kidney stone risk in individuals with low bone density. Small studies with short follow-up reported reduced 24-hour urine calcium excretion with bisphosphonate use. We examined history of low bone density and bisphosphonate use and the risk of incident kidney stone as well as the association with 24-hour calcium excretion. We conducted a prospective analysis of 96,092 women in the Nurses' Health Study II. We used Cox proportional hazards models to adjust for age, body mass index, thiazide use, fluid intake, supplemental calcium use, and dietary factors. We also conducted a cross-sectional analysis of 2294 participants using multivariable linear regression to compare 24-hour urinary calcium excretion between participants with and without a history of low bone density, and among 458 participants with low bone density, with and without bisphosphonate use. We identified 2564 incident stones during 1,179,860 person-years of follow-up. The multivariable adjusted relative risk for an incident kidney stone for participants with history of low bone density compared with participants without was 1.39 (95% confidence interval [95% CI], 1.20 to 1.62). Among participants with low bone density, the multivariable adjusted relative risk for an incident kidney stone for bisphosphonate users was 0.68 (95% CI, 0.48 to 0.98). In the cross-sectional analysis of 24-hour urine calcium excretion, the multivariable adjusted mean difference in 24-hour calcium was 10 mg/d (95% CI, 1 to 19) higher for participants with history of low bone density. However, among participants with history of low bone density, there was no association between bisphosphonate use and 24-hour calcium with multivariable adjusted mean difference in 24-hour calcium of -2 mg/d (95% CI, -25 to 20). Low bone density is an independent risk factor for incident kidney stone and is associated with

  1. Bisphosphonates and Nonhealing Femoral Fractures: Analysis of the FDA Adverse Event Reporting System (FAERS) and International Safety Efforts

    Science.gov (United States)

    Edwards, Beatrice J.; Bunta, Andrew D.; Lane, Joseph; Odvina, Clarita; Rao, D. Sudhaker; Raisch, Dennis W.; McKoy, June M.; Omar, Imran; Belknap, Steven M.; Garg, Vishvas; Hahr, Allison J.; Samaras, Athena T.; Fisher, Matthew J.; West, Dennis P.; Langman, Craig B.; Stern, Paula H.

    2013-01-01

    Background: In the United States, hip fracture rates have declined by 30% coincident with bisphosphonate use. However, bisphosphonates are associated with sporadic cases of atypical femoral fracture. Atypical femoral fractures are usually atraumatic, may be bilateral, are occasionally preceded by prodromal thigh pain, and may have delayed fracture-healing. This study assessed the occurrence of bisphosphonate-associated nonhealing femoral fractures through a review of data from the U.S. FDA (Food and Drug Administration) Adverse Event Reporting System (FAERS) (1996 to 2011), published case reports, and international safety efforts. Methods: We analyzed the FAERS database with use of the proportional reporting ratio (PRR) and empiric Bayesian geometric mean (EBGM) techniques to assess whether a safety signal existed. Additionally, we conducted a systematic literature review (1990 to February 2012). Results: The analysis of the FAERS database indicated a PRR of 4.51 (95% confidence interval [CI], 3.44 to 5.92) for bisphosphonate use and nonhealing femoral fractures. Most cases (n = 317) were attributed to use of alendronate (PRR = 3.32; 95% CI, 2.71 to 4.17). In 2008, international safety agencies issued warnings and required label changes. In 2010, the FDA issued a safety notification, and the American Society for Bone and Mineral Research (ASBMR) issued recommendations about bisphosphonate-associated atypical femoral fractures. Conclusions: Nonhealing femoral fractures are unusual adverse drug reactions associated with bisphosphonate use, as up to 26% of published cases of atypical femoral fractures exhibited delayed healing or nonhealing. PMID:23426763

  2. Ab initio DFT study of bisphosphonate derivatives as a drug for inhibition of cancer: NMR and NQR parameters.

    Science.gov (United States)

    Aghabozorg, Hussein; Sohrabi, Beheshteh; Mashkouri, Sara; Aghabozorg, Hamid Reza

    2012-03-01

    DFT computations were carried out to characterize the (17)Oand (2)H electric field gradient, EFG, in various bisphosphonate derivatives. The computations were performed at the B3LYP level with 6-311++G (d,P) standard basis set. Calculated EFG tensors were used to determine the (17)O and (2)H nuclear quadrupole coupling constant, χ and asymmetry parameter, η. For better understanding of the bonding and electronic structure of bisphosphonates, isotropic and anisotropic NMR chemical shieldings were calculated for the (13)C, (17)O and (31)P nuclei using GIAO method for the optimized structure of intermediate bisphosphonates at B3LYP level of theory using 6-311++G (d, p) basis set. The results showed that various substituents have a strong effect on the nuclear quadrupole resonance (NQR) parameters (χ, η) of (17)O in contrast with (2)H NQR parameters. The NMR and NQR parameters were studied in order to find the correlation between electronic structure and the activity of the desired bisphosphonates. In addition, the effect of substitutions on the bisphosphonates polarity was investigated. Molecular polarity was determined via the DFT calculated dipole moment vectors and the results showed that substitution of bromine atom on the ring would increase the activity of bisphosphonates.

  3. Oral and written instruction of oral hygiene: a randomized trial.

    Science.gov (United States)

    Harnacke, Daniela; Beldoch, Magdalena; Bohn, Gertrude-Heidi; Seghaoui, Ouarda; Hegel, Nicole; Deinzer, Renate

    2012-10-01

    This randomized, evaluator-masked, controlled study evaluates the effectiveness of oral in contrast to written instruction of oral hygiene. Eighty-three students without clinical signs of periodontitis were randomly assigned to either a control group or one of three experimental conditions: 1) written instruction, 2) standardized oral instruction, or 3) individualized oral instruction. Plaque and bleeding indices were assessed to analyze intervention effects on oral health and oral hygiene skills. Measurements took place at baseline and 4 weeks after intervention. Groups differed significantly with respect to gingival bleeding and were tentatively significant with respect to oral hygiene skills. Participants who had received oral individualized instructions showed the best results. A gradient of effectiveness of the instruction methods was observed with most favorable results for the individualized instruction.

  4. Impending Atypical Femoral Fracture in Patients With Medullary Thyroid Cancer With Skeletal Metastasis Treated With Long-term Bisphosphonate and Denosumab.

    Science.gov (United States)

    Koizumi, Mitsuru; Gokita, Tabu; Toda, Kazuhisa

    2017-02-24

    Atypical femoral fractures (AFFs) occur in osteoporosis patients receiving long-term bisphosphonate. Atypical femoral fractures also occur in cancer patients receiving long-term bisphosphonate or denosumab, but the prevalence is low. We describe a 53-year-old woman with a history of medullary thyroid cancer and skull metastasis who was prescribed bisphosphonate for 6 years and denosumab for 1.5 years, consecutively. Bone scintigraphy performed because of spontaneous groin pain showed uptake in the lateral aspect of the left femur, which was confirmed as impending AFF. In oncological patients receiving long-term bisphosphonate or denosumab, AFF should be included as a differential diagnosis with focal femoral findings.

  5. Towards potential nanoparticle contrast agents: Synthesis of new functionalized PEG bisphosphonates

    Science.gov (United States)

    Kachbi-Khelfallah, Souad; Monteil, Maelle; Cortes-Clerget, Margery; Migianu-Griffoni, Evelyne; Pirat, Jean-Luc; Gager, Olivier; Deschamp, Julia

    2016-01-01

    Summary The use of nanotechnologies for biomedical applications took a real development during these last years. To allow an effective targeting for biomedical imaging applications, the adsorption of plasmatic proteins on the surface of nanoparticles must be prevented to reduce the hepatic capture and increase the plasmatic time life. In biologic media, metal oxide nanoparticles are not stable and must be coated by biocompatible organic ligands. The use of phosphonate ligands to modify the nanoparticle surface drew a lot of attention in the last years for the design of highly functional hybrid materials. Here, we report a methodology to synthesize bisphosphonates having functionalized PEG side chains with different lengths. The key step is a procedure developed in our laboratory to introduce the bisphosphonate from acyl chloride and tris(trimethylsilyl)phosphite in one step. PMID:27559386

  6. Atypical femoral fracture due to chronic use of bisphosphonates: case report☆

    Science.gov (United States)

    Temponi, Eduardo Frois; de Carvalho Junior, Lúcio Honório; Costa, Lincoln Paiva

    2015-01-01

    The causal relationship between chronic use of bisphosphonates and occurrences of atypical femoral fractures has not yet been established. Nonetheless, it is known that their chronic use is more related to fractures with a pattern differing from that of classical osteoporotic fractures. Atypical fractures are still rare events and the benefit from using bisphosphonates remains greater for prevention and treatment of osteoporosis. There are few studies guiding the diagnosis and management of these fractures, thus making it difficult to achieve better results. In this report, we present the case of an elderly patient with an atypical femoral fracture that was managed in accordance with guidance from the American Society for Bone and Mineral Research. PMID:26401508

  7. Mandibular Inferior Cortical Bone Thickness on Panoramic Radiographs in Patients using Bisphosphonates

    Science.gov (United States)

    Torres, Sandra R.; Chen, Curtis S. K.; Leroux, Brian G.; Lee, Peggy P.; Hollender, Lars G.; Lloid, Michelle; Drew, Shane Patrick; Schubert, Mark M.

    2015-01-01

    Objective To detect dimensional changes in the mandibular cortical bone associated with bisphosphonate (BP) use and to correlate the measurements of the cortical bone with the cumulative dose of BP therapy. Methods Mandibular inferior cortical bone thickness (MICBT) was measured under the mental foramen from panoramic radiographs of subjects using BP with and without bisphosphonate related osteonecrosis of the jaws (BRONJ) and controls. Results The highest mean MICBT was observed in BRONJ subjects 6.81 (± 1.35 mm), when compared to subjects using BP 5.44 (± 1.09 mm) and controls 4.79 (± 0.85 mm; p<0.01). The mean MICBT of BRONJ subjects was significantly higher than that of subjects using BP without BRONJ. There was a correlation between MICBT and cumulative dose of zolendronate. Conclusion The MICBT on panoramic radiograph is a potentially useful tool for the detection of dimensional changes associated with BP therapy. PMID:25864820

  8. Nitrogen containing bisphosphonates associated osteonecrosis of the jaws: A review for past 10 year literature

    Directory of Open Access Journals (Sweden)

    Vijay Kumar

    2014-01-01

    Full Text Available Nitrogen containing bisphosphonate (N-BP therapy is used extensively to treat osteoporosis and osteolytic bone lesions. Recently, a special form of osteonecrosis limited to the maxillofacial skeleton has been discovered especially within those patients who are receiving either long-term N-BP therapy alone and/or associated with invasive dental procedure. Bisphosphonates accumulate almost exclusively in maxillofacial skeleton owing to high bone turn over remodeling to maintain the mechanical competence. The pathogenesis and why it commonly appears in maxillofacial skeleton and the fixed treatment strategies remains unknown. The aim of this study was to improve the clinician understanding of N-BPs associated osteonecrosis of maxillofacial skeleton by reviewing the past 10 year literature.

  9. Nitrogen containing bisphosphonates associated osteonecrosis of the jaws: A review for past 10 year literature

    Science.gov (United States)

    Kumar, Vijay; Shahi, Ashish Kumar

    2014-01-01

    Nitrogen containing bisphosphonate (N-BP) therapy is used extensively to treat osteoporosis and osteolytic bone lesions. Recently, a special form of osteonecrosis limited to the maxillofacial skeleton has been discovered especially within those patients who are receiving either long-term N-BP therapy alone and/or associated with invasive dental procedure. Bisphosphonates accumulate almost exclusively in maxillofacial skeleton owing to high bone turn over remodeling to maintain the mechanical competence. The pathogenesis and why it commonly appears in maxillofacial skeleton and the fixed treatment strategies remains unknown. The aim of this study was to improve the clinician understanding of N-BPs associated osteonecrosis of maxillofacial skeleton by reviewing the past 10 year literature. PMID:24932183

  10. Bisphosphonate Treatment in a Patient Affected by MPS IVA with Osteoporotic Phenotype.

    Science.gov (United States)

    Tummolo, Albina; Gabrielli, Orazio; Gaeta, Alberto; Masciopinto, Maristella; Zampini, Lucia; Pavone, Luigi Michele; Di Natale, Paola; Papadia, Francesco

    2013-01-01

    Morquio A syndrome (Mucopolysaccharidosis type IVA) (MPS IVA) is a rare inherited metabolic disorder characterized by the defective degradation of keratan sulfate and chondroitin-6-sulfate. Classically, MPS IVA patients present with severe multisystemic involvement and have a short life expectancy. Attenuated forms with clinical features limited to minor skeletal abnormalities and short stature have also been described, sometimes associated to an early-onset osteoporotic phenotype. No treatment with allogenic bone marrow transplantation or gene therapy is currently available for Morquio A syndrome, and enzyme replacement therapy is under evaluation. We report a case of MPS IVA, who manifested tardily attenuated phenotype and significant bone mass reduction, which was treated with a bisphosphonate (BPN), resulting in an improvement of X-ray skeletal aspects and functional bone performance. We suggest that the use of bisphosphonates may be an interesting supportive therapeutic option for Morquio A patients with osteoporotic phenotype, but further studies involving more patients are necessary to confirm our findings.

  11. Oral Medication

    Science.gov (United States)

    ... Size: A A A Listen En Español Oral Medication The first treatment for type 2 diabetes blood ... new — even over-the-counter items. Explore: Oral Medication How Much Do Oral Medications Cost? Save money ...

  12. Prevention of vascular calcification with bisphosphonates without affecting bone mineralization: a new challenge?

    Science.gov (United States)

    Neven, Ellen G; De Broe, Marc E; D'Haese, Patrick C

    2009-03-01

    Arterial calcification has been found to coexist with bone loss. Bisphosphonates, used as standard therapy for osteoporosis, inhibit experimentally induced vascular calcification, offering perspectives for the treatment of vascular calcification in renal failure patients. However, Lomashvili et al. report that the doses of etidronate and pamidronate that are effective in attenuating aortic calcification also decrease bone formation and mineralization in uremic rats, limiting their therapeutic use as anticalcifying agents.

  13. Bisphosphonates improve trabecular bone mass and normalize cortical thickness in ovariectomized, osteoblast connexin43 deficient mice.

    Science.gov (United States)

    Watkins, Marcus P; Norris, Jin Yi; Grimston, Susan K; Zhang, Xiaowen; Phipps, Roger J; Ebetino, Frank H; Civitelli, Roberto

    2012-10-01

    The gap junction protein, connexin43 (Cx43) controls both bone formation and osteoclastogenesis via osteoblasts and/or osteocytes. Cx43 has also been proposed to mediate an anti-apoptotic effect of bisphosphonates, potent inhibitors of bone resorption. We studied whether bisphosphonates are effective in protecting mice with a conditional Cx43 gene deletion in osteoblasts and osteocytes (cKO) from the consequences of ovariectomy on bone mass and strength. Ovariectomy resulted in rapid loss of trabecular bone followed by a slight recovery in wild type (WT) mice, and a similar degree of trabecular bone loss, albeit slightly delayed, occurred in cKO mice. Treatment with either risedronate (20 μg/kg) or alendronate (40 μg/kg) prevented ovariectomy-induced bone loss in both genotypes. In basal conditions, bones of cKO mice have larger marrow area, higher endocortical osteoclast number, and lower cortical thickness and strength relative to WT. Ovariectomy increased endocortical osteoclast number in WT but not in cKO mice. Both bisphosphonates prevented these increases in WT mice, and normalized endocortical osteoclast number, cortical thickness and bone strength in cKO mice. Thus, lack of osteoblast/osteocyte Cx43 does not alter bisphosphonate action on bone mass and strength in estrogen deficiency. These results support the notion that one of the main functions of Cx43 in cortical bone is to restrain osteoblast and/or osteocytes from inducing osteoclastogenesis at the endocortical surface. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Synthesis and antiproliferative activity of aromatic and aliphatic bis[aminomethylidene(bisphosphonic)] acids.

    Science.gov (United States)

    Goldeman, Waldemar; Nasulewicz-Goldeman, Anna

    2014-08-01

    A series of aromatic and aliphatic bis[aminomethylidene(bisphosphonic)] acids was synthesized in the reaction of triethylphosphite with isonitriles followed by hydrolysis or dealkylation. The in vitro anti-proliferative effect of all synthesized tetraphosphonic acids against MCF-7 breast cancer cells, J774E macrophages and HL-60 promyelocytic leukemia cells was determined. Three aromatic derivatives (5a, 5f and 5j) showed a similar or higher anti-proliferative activity than zoledronic acid.

  15. Atypical metatarsal fracture in a patient on long term bisphosphonate therapy

    Directory of Open Access Journals (Sweden)

    Pavan Pradhan

    2012-01-01

    Full Text Available A 24 years old female of cushing disease had undergone adrenelectomy. She was put on alendronate and steroid. After six and a half years she developed pathological fracture subtrochanteric femur. The patient was treated with proximal femoral nailing and the fracture united. 2 years later she developed pain right foot. She was diagnosed as transverse fracture of fifth metatarsal. We report this rare case of atypical metatarsal fracture in a patient on long term bisphosphonate therapy.

  16. Eldecalcitol improves chair-rising time in postmenopausal osteoporotic women treated with bisphosphonates

    Directory of Open Access Journals (Sweden)

    Iwamoto J

    2014-01-01

    Full Text Available Jun Iwamoto,1 Yoshihiro Sato21Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Neurology, Mitate Hospital, Fukuoka, JapanAbstract: An open-label randomized controlled trial was conducted to clarify the effect of eldecalcitol (ED on body balance and muscle power in postmenopausal osteoporotic women treated with bisphosphonates. A total of 106 postmenopausal women with osteoporosis (mean age 70.8 years were randomly divided into two groups (n=53 in each group: a bisphosphonate group (control group and a bisphosphonate plus ED group (ED group. Biochemical markers, unipedal standing time (body balance, and five-repetition chair-rising time (muscle power were evaluated. The duration of the study was 6 months. Ninety-six women who completed the trial were included in the subsequent analyses. At baseline, the age, body mass index, bone mass indices, bone turnover markers, unipedal standing time, and chair-rising time did not differ significantly between the two groups. During the 6-month treatment period, bone turnover markers decreased significantly from the baseline values similarly in the two groups. Although no significant improvement in the unipedal standing time was seen in the ED group, compared with the control group, the chair-rising time decreased significantly in the ED group compared with the control group. The present study showed that ED improved the chair-rising time in terms of muscle power in postmenopausal osteoporotic women treated with bisphosphonates.Keywords: osteoporosis, fall, vitamin D, muscle power, body balance

  17. Development of [{sup 90}Y]DOTA-conjugated bisphosphonate for treatment of painful bone metastases

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Kazuma [Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640 (Japan)], E-mail: kogawa@med.kanazawa-u.ac.jp; Kawashima, Hidekazu [Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Graduate School of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Shiba, Kazuhiro [Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640 (Japan); Washiyama, Kohshin; Yoshimoto, Mitsuyoshi [Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-0942 (Japan); Kiyono, Yasushi [Biomedical Imaging Research Center, University of Fukui, Yoshida-gun 910-1193 (Japan); Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Ueda, Masashi [Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Mori, Hirofumi [Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640 (Japan); Saji, Hideo [Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan)

    2009-02-15

    Introduction: Based on the concept of bifunctional radiopharmaceuticals, we have previously developed {sup 186}Re-complex-conjugated bisphosphonate analogs for palliation of painful bone metastases and have demonstrated the utility of these compounds. By applying a similar concept, we hypothesized that a bone-specific directed {sup 90}Y-labeled radiopharmaceutical could be developed. Methods: In this study, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was chosen as the chelating site, and DOTA was conjugated with 4-amino-1-hydroxybutylidene-1,1-bisphosphonate. [{sup 90}Y]DOTA-complex-conjugated bisphosphonate ([{sup 90}Y]DOTA-HBP) was prepared by coordination with {sup 90}Y, and its biodistribution was studied in comparison to [{sup 90}Y]citrate. Results: In biodistribution experiments, [{sup 90}Y]DOTA-HBP and [{sup 90}Y]citrate rapidly accumulated and resided in the bone. Although [{sup 90}Y]citrate showed a higher level of accumulation in the bone than [{sup 90}Y]DOTA-HBP, the clearances of [{sup 90}Y]DOTA-HBP from the blood and from almost all soft tissues were much faster than those of [{sup 90}Y]citrate. As a result, the estimated absorbed dose ratios of soft tissues to osteogenic cells (target organ) of [{sup 90}Y]DOTA-HBP were lower than those of [{sup 90}Y]citrate. Conclusions: [{sup 90}Y]DOTA-HBP showed superior biodistribution characteristics as a bone-seeking agent and led to a decrease in the level of unnecessary radiation compared to [{sup 90}Y]citrate. Since the DOTA ligand forms a stable complex not only with {sup 90}Y but also with lutetium ({sup 177}Lu), indium ({sup 111}In), gallium ({sup 67/68}Ga), gadolinium (Gd) and so on, complexes of DOTA-conjugated bisphosphonate with various metals could be useful as agents for palliation of metastatic bone pain, bone scintigraphy and magnetic resonance imaging.

  18. Oral myiasis

    OpenAIRE

    Thalaimalai Saravanan; Mathan A Mohan; Meera Thinakaran; Saneem Ahammed

    2015-01-01

    Myiasis is a pathologic condition in humans occurring because of parasitic infestation. Parasites causing myiasis belong to the order Diptera. Oral myiasis is seen secondary to oral wounds, suppurative lesions, and extraction wounds, especially in individuals with neurological deficit. In such cases, neglected oral hygiene and halitosis attracts the flies to lay eggs in oral wounds resulting in oral myiasis. We present a case of oral myiasis in 40-year-old male patient with mental disability ...

  19. Soft Robotics Week

    CERN Document Server

    Rossiter, Jonathan; Iida, Fumiya; Cianchetti, Matteo; Margheri, Laura

    2017-01-01

    This book offers a comprehensive, timely snapshot of current research, technologies and applications of soft robotics. The different chapters, written by international experts across multiple fields of soft robotics, cover innovative systems and technologies for soft robot legged locomotion, soft robot manipulation, underwater soft robotics, biomimetic soft robotic platforms, plant-inspired soft robots, flying soft robots, soft robotics in surgery, as well as methods for their modeling and control. Based on the results of the second edition of the Soft Robotics Week, held on April 25 – 30, 2016, in Livorno, Italy, the book reports on the major research lines and novel technologies presented and discussed during the event.

  20. CERN safety week

    CERN Multimedia

    DG Unit

    2009-01-01

    Following an increase in the number of accidents in 2008, the Safety Commission is organising a CERN safety week from 8 to 12 June for riders of bicycles, scooters and motorbikes. We invite you to take part in the programme, which will be held in the Main Building (Bldg. 500) and will consist of an exhibition, organised events and hands-on activities, including demonstrations of emergency braking, a driving simulator, simulation of what it feels like to drive under the influence of alcohol, demonstrations by the Fire Brigade, video projections, etc. There will also be a number of prizes to be won. Please sign up via your DSO.

  1. CERN safety week

    CERN Multimedia

    DG Unit

    2009-01-01

    Following an increase in the number of accidents in 2008, the Safety Commission is organising a CERN safety week from 8 to 12 June for riders of bicycles, scooters and motorbikes. We invite you to take part in the programme, which will be held in the Main Building (Bldg. 500) and will consist of an exhibition, organised events and hands-on activities, including demonstrations of emergency braking, a driving simulator, simulation of what it feels like to drive under the influence of alcohol, demonstrations by the Fire Brigade, video projections, etc. There will also be a number of prizes to be won. Please sign up via your DSO.

  2. Predictors of atypical femoral fractures during long term bisphosphonate therapy: A case series & review of literature

    Directory of Open Access Journals (Sweden)

    Sanjay Kumar Bhadada

    2014-01-01

    Full Text Available Background & objectives: Bisphosphonates (BPs are the most widely prescribed medicines for the treatment of osteoporosis because of their efficacy and favourable safety profile. There have been, several reports on an increased incidence of atypical femoral fractures after long term treatment with BPs. The objective of this study was to evaluate the clinical presentation including prodromal symptoms, skeletal radiograph findings, type and duration of BPs received and treatment outcome of patients who developed atypical femoral fractures during bisphosphonate therapy. Methods: In this retrospective study, eight patients with atypical femoral fractures were analysed based on clinical features, biochemical and radiological investigations. Results: Of the eight patients, who sustained atypical femoral fractures, six were on alendronate and two were on zoledronate therapy before the fractures. In addition to BPs, two patients were on long term corticosteroid therapy for rheumatoid arthritis and Addison′s disease. Three patients had bilateral atypical femoral fractures. Except one, all of them had prodromal symptoms prior to fracture. Skeletal radiograph showed cortical thickening, pointed (beaking of cortical margin and transverse fracture in meta-diaphyseal location. Serum calcium, phosphate, alkaline phosphatase (ALP and intact parathyroid hormone (iPTH concentrations were within the reference range in all patients. Interpretation & conclusions: Long term bisphosphonate therapy may increase the risk of atypical femoral fractures. Presence of prodromal pain, thickened cortex with cortical beaking may be an early clue for predicting the atypical fractures. High risk patients need periodical skeletal survey and a close follow up for early detection of cases.

  3. Optimising bisphosphonate treatment outcomes in postmenopausal osteoporosis: review and Italian experience.

    Science.gov (United States)

    Rossini, M; Di Munno, O; Gatti, D; Giannini, S; Minisola, S; Varenna, M; Adami, S

    2011-01-01

    This review aims to investigate ways to optimise treatment outcomes with bisphosphonate therapy of osteoporosis in general, and in Italian clinical practice specifically. Overall, poor adherence to bisphosphonate therapy is a major limiting factor in the treatment of osteoporosis, and is associated to a large extent with gastrointestinal adverse events. An improved patient-doctor relationship and patient motivation are critical factors to improving adherence. However, other medical interventions also play a significant role. Intermittent dosing regimens decrease gastrointestinal adverse events and improve adherence, and demonstrate at least equivalent efficacy to daily regimens. Intravenous formulations also improve gastrointestinal tolerability, and are recommended in Italy for patients at high risk of this adverse event. Other recommendations in Italy to improve treatment outcomes include a case-finding approach to identify patients most suitable for bisphosphonate therapy, thus reducing the numbers needed to treat to avoid fractures. To facilitate this, a comprehensive assessment is advocated which incorporates bone mineral density, previous fractures, parental history of fractures, corticosteroid use and the presence of other diseases associated with secondary osteoporosis.

  4. Atypical subtrochanteric and femoral shaft fractures and possible association with bisphosphonates.

    Science.gov (United States)

    Nieves, Jeri W; Cosman, Felicia

    2010-03-01

    Several case series and multiple individual case reports suggest that some subtrochanteric and femoral shaft fractures might occur in patients who have been treated with long-term bisphosphonates. Several unique clinical and radiographic features are emerging: prodromal thigh pain prior to the fracture, complete absence of trauma precipitating the fracture, and bilateral fractures in some patients. Radiographic features include presence of stress reaction, transverse or short oblique fractures, and thick femoral cortices. The overall incidence of subtrochanteric and shaft fractures combined is below 30 per 100,000 person-years, so this type of fracture is much less common than proximal femur (hip) fracture. Furthermore, the unique "atypical" fracture type is a subset of all subtrochanteric and femoral shaft fractures. The putative mechanism is unknown, and more research is needed to identify distinctive characteristics and the pathophysiology of these atypical fractures. There is no rationale to withhold bisphosphonate therapy from patients with osteoporosis, although continued use of bisphosphonate therapy beyond a treatment period of 3 to 5 years should be re-evaluated annually.

  5. a week in space

    Science.gov (United States)

    collette, christian

    2016-04-01

    COLLETTE Christian Institut Saint Laurent Liège Belgium. I am a science teacher at a technical high school. Generally, my students don't come from a privileged social background and are not particularly motivated for studies. For 10 years, I organize, for one of my sections, a spatial (and special) school year that ends in a spatial week. Throughout this year, with the help of my colleagues, I will introduce into all themes a lot of concepts relating to space. French, history, geography, English, mathematics, technical courses, sciences, and even gymnastics will be training actors in space culture. In spring, I will accompany my class in the Euro Space Center (Redu- Belgium) where we will live one week 24 hours on "like astronauts" One third of the time is dedicated to astronaut training (moonwalk, remote manipulator system, mission simulation, weightless wall, building rockets, satellites, etc.), One third to more intellectual activities on space (lectures, research, discovery of the outside run) the last one third of time in outside visits (museums, site of ESA-Redu) or in movies about space (October sky, Apollo 13, etc.) During this year, the profits, so educational as human, are considerable!

  6. ATLAS overview week highlights

    CERN Multimedia

    D. Froidevaux

    2005-01-01

    A warm and early October afternoon saw the beginning of the 2005 ATLAS overview week, which took place Rue de La Montagne Sainte-Geneviève in the heart of the Quartier Latin in Paris. All visitors had been warned many times by the ATLAS management and the organisers that the premises would be the subject of strict security clearance because of the "plan Vigipirate", which remains at some level of alert in all public buildings across France. The public building in question is now part of the Ministère de La Recherche, but used to host one of the so-called French "Grandes Ecoles", called l'Ecole Polytechnique (in France there is only one Ecole Polytechnique, whereas there are two in Switzerland) until the end of the seventies, a little while after it opened its doors also to women. In fact, the setting chosen for this ATLAS overview week by our hosts from LPNHE Paris has turned out to be ideal and the security was never an ordeal. For those seeing Paris for the first time, there we...

  7. Influence of bisphosphonates on dental implants%二膦酸盐对口腔种植的影响

    Institute of Scientific and Technical Information of China (English)

    苏美莹(综述); 施斌(审校); 张玉峰(审校)

    2013-01-01

    二膦酸盐药物是治疗骨质疏松的药物,而骨质疏松与牙体脱落在老年人群中普遍存在,故骨质疏松与牙体脱落的种植牙治疗可能同期进行,但是同时进行这两种治疗的患者却出现了大量的二膦酸盐药物相关性颌骨坏死(BRONJ)。研究显示,二膦酸盐诱导BRONJ的风险可能与用药方法、药物效力、治疗时间及其他局部或系统性因素有关。本文就二膦酸盐影响骨内种植体的危险因素、二膦酸盐的药理作用及导致种植体失败的原因、控制BRONJ的方法等研究进展作一综述。%Both?osteoporosis?and?tooth?loss?are?prevalent?in?the?elderly?population.?Thus,?implant?use?is?essential?in?solving?the?problem?of?missing?teeth?in?osteoporotic?patients?undergoing?bisphosphonate?treatment.?Incidents?of?osteonecrosis?of?the?jaw,?known?as?bisphosphonate-related?osteonecrosis?of?the?jaw(BRONJ),?have?been?reported?in?persons?using?bisphosphonates?and?undergoing?invasive?dental?implants.?Many?studies?show?that?the?risk?for?bisphosphonate-induced?osteonecrosis?may?be?influenced?by?the?route?of?drug?administration,?the?potency?and?duration?of?use,?as?well?as?other?local?and?systematic?factors.?This?study?reviews?the?risk?factors?of?bisphosphonates?that?affect?bone?implants,?the?pharmacological?effects?of?bisphosphonates,?how?bisphosphonates?lead?to?implant?failure,?and?how?to?control?BRONJ.

  8. 降钙素及二膦酸盐治疗血液透析患者肾性骨病的长期疗效%Long-term efficacy of calcitonin and bisphosphonates on renal osteopathy in maintenance hemodialysis patients

    Institute of Scientific and Technical Information of China (English)

    石书梅; 赵学智; 陆烈; 卜磊; 陈意志

    2009-01-01

    Objective To observe the efficacy of ealcitonin and bisphosphonates on renal osteopathy of maintenance hemodialysis (MHD)patients. Methods Forty-three MHD patients were raindomly divided into two groups: A group and B group. All the patients were routinely received oral calcium carbonate 1.0 g tid and calcitriol 0.25 μg qd. Calcitonin (20U) hypodermic injection was given three times a week additionally during hemodialysis in A group. Patients in B group received bisphosphonates 70 mg once a week based on the therapy of A group. Serum levels of intact parathyroid hormone (iPTH), calcium, phosphorus, alkaline phosphatase (AKP), bone mass density (BMD) of lumbar spine and femoral neck, and the degree of bone ache (visual analogue scale, VAS) were assessed before the therapy and 3, 6 and 12 months after treatment. The adverse reactions were recorded during treatment. Results The levels of AKP and iPTH in both two groups decreased significantly after treatment. The above values of pre-treatment and 12 months after treatment were as follows: AKP(U/L)of A group 244.05±41.99 and 148.35±27.71,of B group 245.60±40.86 and 143.40±28.03;PTH(ng/L) of A group 697.5±119.7 and 267.4±45.9,of B group 708.2±120.3 and 277.6±41.9 (all P0.05). BMD was not improved at 3, 6 mouths and became better at 12 mouths after treatment. As compared to pre-treatment, BMD of lumbar spine(g/cm2) in A group was 1.062±0.223 vs 1.202±0.251 ,in B group 1.033±0.152 vs 1.189±0.225; BMD of femoral neck (g/cm2)in A group was 0.993±0.108 vs 1.067±0.095,in B group 0.947±0.083 vs 1.018 ±0.217 (all P<0.05). The scores of VAS also decreased significantly at 3, 6, 12 months after treatment(P<0.05). No severe adverse reaction was found during the treatment. Conclusions Utilization of calcitonin and combination with bisphosphonates during bemodialysis can effectively preserve the BMD and prevent bone loss in MHD patients and is well tolerated. No significant difference of therapeutic effect is

  9. Bisphosphonate effects in cancer and inflammatory diseases: in vitro and in vivo modulation of cytokine activities.

    Science.gov (United States)

    Santini, Daniele; Fratto, Maria E; Vincenzi, Bruno; La Cesa, Annalisa; Dianzani, Caterina; Tonini, Giuseppe

    2004-01-01

    Bisphosphonates are endogenous pyrophosphate analogs in which a carbon atom replaces the central atom of oxygen. They are indicated in non-neoplastic diseases including osteoporosis, corticosteroid-induced bone loss, Paget disease, and in cancer-related diseases such as neoplastic hypercalcemia, multiple myeloma and bone metastases secondary to breast and prostate cancer. There is now extensive in vitro evidence suggesting a direct antitumor effect of bisphosphonates at different levels of action. Some new in vitro and in vivo studies support the cytostatic effects of bisphosphonates on tumor cells, and the effects on the regulation of cell growth, apoptosis, angiogenesis, cell adhesion, and invasion, with particular attention to biological properties. Well designed clinical trials are necessary to investigate whether the antitumor potential of bisphosphonates may be clinically relevant. On the basis of their effects on macrophages, we may divide bisphosphonates into two distinct categories: aminobisphosphonates, which sensitize macrophages to an inflammatory stimulus inducing an acute-phase response, and non-aminobisphosphonates that can be metabolized into macrophages and that may inhibit the inflammatory response of macrophages. There is evidence of aminobisphosphonate-induced pro-inflammatory response, in particular, related to modifications of the cytokine network. Several in vivo studies have demonstrated an acute-phase reaction after the first administration of aminobisphosphonates, with a significant increase in the main pro-inflammatory cytokines. However, a peculiar aspect concerning the action of non-aminobisphosphonates seems to be an anti-inflammatory activity caused by the inhibition of the release of inflammatory mediators from activated macrophages, such as interleukin (IL)-6, tumor necrosis factor-alpha and IL-1. The inhibition of inflammatory responses is demonstrated in both in vivo and in vitro models. This activity suggests the use of non

  10. Local Administration of Bisphosphonate-soaked Hydroxyapatite for the Treatment of Osteonecrosis of the Femoral Head in Rabbit

    Institute of Scientific and Technical Information of China (English)

    Jin-Hui Ma; Wan-Shou Guo; Zi-Rong Li; Bai-Liang Wang

    2016-01-01

    Background:Systemic administration ofbisphosphonates has shown promising results in the treatment ofosteonecrosis of the femoral head (ONFH).However,few studies have evaluated the efficacy of local zoledronate (ZOL) administration in the treatment of ONFH.The purpose of this study was to investigate whether local administration of bisphosphonate-soaked hydroxyapatite (HA) could improve bone healing in an experimental rabbit model of ONFH.Methods:This experimental study was conducted between October 2014 and June 2015.Forty-five rabbits underwent simulated ONFH surgery.Immediately following surgery,they were divided into three groups:model (untreated,n =15),HA (treated with HA alone,n =15),and HA + ZOL (treated with HA soaked in a low-dose ZOL solution,n =15).Histological,immunohistochemical,and quantitative analyses were performed to evaluate bone formation and resorption 2,4,and 8 weeks after surgery.Results:Gross bone matrix and hematopoietic tissue formation were observed in the HA + ZOL group 4 weeks after surgery.The immunohistochemical staining intensities for 5-bromodeoxyuridine,runt-related transcription factor 2,osteocalcin,osteopontin,and osteoprotegerin were significantly higher in the HA + ZOL group than that in the model (P < 0.001,P < 0.001,P < 0.001,P < 0.001,and P =0.018,respectively) and HA groups (P =0.003,P =0.049,P < 0.00l,P =0.020,and P =0.019,respectively),whereas receptor activator of the nuclear factor-κB ligand staining intensity was significantly lower in the HA + ZOL group than that in the model and HA groups (P =0.029 and P =0.015,respectively) 4 weeks after surgery.No significant differences in bone formation or bone resorption marker expression were found between the three groups 2 or 8 weeks after surgery (P > 0.05).Conclusions:Local administration of HA soaked in a low-dose ZOL solution increased new bone formation while inhibiting bone resorption in an animal model of ONFH,which might provide new evidence for joint

  11. Bisphosphonates for the prevention of fractures in osteogenesis imperfecta: meta-analysis of placebo-controlled trials.

    Science.gov (United States)

    Hald, Jannie D; Evangelou, Evangelos; Langdahl, Bente L; Ralston, Stuart H

    2015-05-01

    Bisphosphonates are widely used off-label in the treatment of patients with osteogenesis imperfecta (OI) with the intention of reducing the risk of fracture. Although there is strong evidence that bisphosphonates increase bone mineral density in osteogenesis imperfecta, the effects on fracture occurrence have been inconsistent. The aim of this study was to gain a better insight into the effects of bisphosphonate therapy on fracture risk in patients with osteogenesis imperfecta by conducting a meta-analysis of randomized controlled trials in which fractures were a reported endpoint. We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials in which the effects of bisphosphonates on fracture risk in osteogenesis imperfecta were compared with placebo and conducted a meta-analysis of these studies using standard methods. Heterogeneity was assessed using the I2 statistic. Six eligible studies were identified involving 424 subjects with 751 patient-years of follow-up. The proportion of patients who experienced a fracture was not significantly reduced by bisphosphonate therapy (Relative Risk [RR] = 0.83 [95% confidence interval 0.69-1.01], p = 0.06) with no heterogeneity between studies (I2  = 0). The fracture rate was reduced by bisphosphonate treatment when all studies were considered (RR = 0.71 [0.52-0.96], p = 0.02), but with considerable heterogeneity (I2  = 36%) explained by one study where a small number of patients in the placebo group experienced a large number of fractures. When this study was excluded, the effects of bisphosphonates on fracture rate was not significant (RR = 0.79 [0.61-1.02], p = 0.07, I2  = 0%). We conclude that the effects of bisphosphonates on fracture prevention in osteogenesis imperfecta are inconclusive. Adequately powered trials with a fracture endpoint are needed to further investigate the risks and benefits of bisphosphonates in this condition.

  12. Bone Loss Prevention of Bisphosphonates in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yan Hu

    2017-01-01

    Full Text Available Objective. The purpose of this study was to evaluate the effect of bisphosphonates in improving bone mineral density (BMD and decreasing the occurrence rate of fractures and adverse events in patients with inflammatory bowel disease (IBD. Methods. Randomized controlled trials (RCTs which use bisphosphonates in IBD patients were identified in PubMed, MEDLINE database, EMBASE database, Web of Knowledge, and the Cochrane Databases between 1990 and June 2016. People received bisphosphonate or placebos with a follow-up of at least one year were also considered. STATA 12.0 software was used for the meta-analysis. Results. Eleven randomized clinical trials were included in the meta-analysis. The data indicated that the percentage change in the increased BMD in the bisphosphonates groups was superior to that of the control groups at the lumbar spine and total hip. At the femoral neck, there was no significant difference between the two groups. The incidence of new fractures during follow-up showed significant reduction. The adverse event analysis revealed no significant difference between the two groups. Conclusion. Our results demonstrate that bisphosphonates therapy has an effect on bone loss in patients with IBD but show no evident efficiency at increasing the incidence of adverse events.

  13. 13-week oral toxicity study with stanol esters in rats

    NARCIS (Netherlands)

    Turnbull, D.; Whittaker, M.H.; Frankos, V.H.; Jonker, D.

    1999-01-01

    Plant sterols and their saturated derivatives, known as stanols, reduce serum cholesterol when consumed in amounts of approximately 2 g per day. Stanol fatty acid esters have been developed as a highly fat-soluble form that may lower cholesterol more effectively than stanols. Stanol esters occur nat

  14. Subchronic (13-week) oral toxicity of neohesperidin dihydrochalcone in rats.

    Science.gov (United States)

    Lina, B A; Dreef-van der Meulen, H C; Leegwater, D C

    1990-07-01

    Neohesperidin dihydrochalcone was administered to groups of 20 male and 20 female Wistar rats at dietary levels of 0, 0.2, 1.0 and 5.0% for 91 days. No treatment-related ophthalmoscopical, haematological or histopathological effects were observed. In the high-dose group, a marked caecal enlargement occurred in both sexes, accompanied by soft stools in the early stages of the study, somewhat lower plasma urea concentrations and increased plasma alkaline phosphatase activity and a decreased urinary pH. This group also showed slight growth depression accompanied by transient reduction in food intake; in males the body weights remained relatively low throughout the experimental period. Furthermore, bilirubin level was increased in females and total protein level was decreased in males of the high-dose group. The above changes were considered adaptive responses or chance effects rather than manifestations of clear toxicity. The low-and intermediate- dose groups did not show any compound-related untoward effect. It was concluded that the intermediate dose, providing an overall intake of about 750 mg neohesperidin dihydrochalcone per kg body weight per day, was the no-effect level.

  15. Dyskinesias evoked in monkeys by weekly administration of haloperidol

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, B.; Santelli, S.

    1978-05-19

    In two cebus (Cebus albifrons) monkeys given weekly oral doses of 0.25 milligram of haloperidol per kilogram, movement disorders appeared 1 to 8 hours after drug administration following the tenth weekly dose. These disorders included oral movements, peculiar postures, writhing, and stretching. Such reactions faded in intensity after the next two doses. Increasing the dose to 0.5 milligram per kilogram has elicited the disorders reliably after each weekly dose for almost 2 years. Similar reactions also developed in a squirrel monkey (Saimiri sciurea) treated weekly with haloperidol and in a third cebus monkey previously maintained for a year on a regimen of 0.25 milligram of haloperidol per kilogram on 5 days per week. These findings suggest an experimental model for determining the etiology of drug-induced movement disorders. They also suggest an unrecognized clinical problem.

  16. Dyskinesias evoked in monkeys by weekly administration of haloperidol.

    Science.gov (United States)

    Weiss, B; Santelli, S

    1978-05-19

    In two cebus (Cebus albifrons) monkeys given weekly oral doses of 0.25 milligram of haloperidol per kilogram, movement disorders appeared 1 to 8 hours after drug administration following the tenth weekly dose. These disorders included oral movements, peculiar postures, writhing, and stretching. Such reactions faded in intensity after the next two doses. Increasing the dose to 0.5 milligram per kilogram has elicited the disorders reliably after each weekly dose for almost 2 years. Similar reactions also developed in a squirrel monkey (Saimiri sciurea) treated weekly with haloperidol and in a third cebus monkey previously maintained for a year on a regimen of 0.25 milligram of haloperidol per kilogram on 5 days per week. These findings suggest an experimental model for determining the etiology of drug-induced movement disorders. They also suggest an unrecognized clinical problem.

  17. A memorable week

    CERN Document Server

    2012-01-01

    This has been a memorable week for CERN, starting with the award of a Special Fundamental Physics Prize and ending with the handover of the CERN Council Presidency from Michel Spiro to Agnieszka Zalewska. In between, the LHC team demonstrated its expertise with a successful pilot run with 25 nanosecond bunch spacing, a new application for Associate Membership was received, and we had good news on the budget.   The award of the Fundamental Physics Prize, and the manner in which it was divided between ATLAS, CMS and the LHC, is fitting recognition of the efforts of the thousands of people who have contributed over many years to the success of our flagship scientific endeavour. In making the award, the Milner Foundation aims to raise the profile of fundamental physics and its value to society. The Fundamental Physics Prize comes hot on the heels of the European Physical Society’s first Edison Volta Prize, which Sergio Bertolucci, Steve Myers and I were honoured to accept on behalf of t...

  18. Alternativas de tratamiento para la osteonecrosis de los maxilares asociada a bisfosfonatos Treatment alternatives for bisphosphonate associated osteonecrosis of the jaw

    Directory of Open Access Journals (Sweden)

    C.M. Ardila Medina

    2010-06-01

    Full Text Available Se ha notificado recientemente un incremento de la osteonecrosis en los pacientes que reciben bisfosfonatos que contienen nitrógeno. Clínicamente, la necrosis ósea maxilar o mandibular puede ocurrir de forma espontánea o aparecer secundariamente a una exodoncia o trauma que afecte los maxilares. La necrosis se manifiesta por exposición del hueso en el sitio afectado, inflamación de los tejidos blandos adyacentes, halitosis, dolor y fiebre; puede producir fístula mucosa o cutánea. También se observa que los pacientes tratados con administración intravenosa de bisfosfonatos se encuentran en alto riesgo de desarrollar focos osteonecróticos únicos o múltiples, situación advertida esporádicamente en los sujetos tratados con administración oral. Se han indicado diferentes recomendaciones con el fin de establecer los procedimientos efectivos para tratar la osteonecrosis asociada a bisfosfonatos. Los tratamientos comprenden alternativas no quirúrgicas, antibióticos, terapia hiperbárica, cirugía convencional o mediante láser. Adicionalmente, las medidas preventivas son un aspecto importante que debe tenerse en cuenta.A relative increase in osteonecrosis has been reported in recent years particularly among patients receiving nitrogen-containing bisphosphonates. Clinically, mandibular or maxillary necrosis may occur spontaneously or be secondary to tooth extraction or trauma affecting the jaws. Necrosis typically manifests itself with exposure of the bone at the site involved and swelling of the adjacent soft tissues, halitosis, pain and fever, and may produce cutaneous or mucosal fistulae. It has also been observed that patients who have taken bisphosphonates by intravenous administration appear to be at a higher risk of developing single or multiple osteonecrotic foci of the jaw bones, whereas this has only been reported sporadically in patients with oral administration Several recommendations have been made to establish effective

  19. Bisphosphonate-related osteonecrosis of the jaw in a multiple myeloma patient: A case report with characteristic radiographic features

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Byung Do; Kwon, Kyung Hwan [College of Dentistry, Wonkwang University, Iksan (Korea, Republic of); Park, Moo Rim [Dept. of Internal Medicine, School of Medicine, Wonkwang University, Iksan (Korea, Republic of)

    2015-09-15

    A 59-year-old male who had suffered from multiple myeloma for nine years and had been administered bisphosphonates for seven years visited a dental hospital for pain relief due to extensive caries in his left maxillary molars. The molars were extracted, leaving an exposed wound for three months. The radiograph showed sequestra formation and irregular bone destruction in the left maxilla. Sudden pain and gingival swelling in the right mandibular molar area occurred six months later. The interseptum of the right lower second molar was observed to be necrotic during surgery. These findings coincided with the features of bisphosphonate-related osteonecrosis of the jaw (BRONJ). In this case, the long intravenous administration of bisphosphonates and tooth extraction were likely the etiologic factors of BRONJ in a patient with multiple myeloma; moreover, the bilateral occurrence of BRONJ is a characteristic feature.

  20. Sequential subtrochanteric femoral fracture after atypical diaphyseal fracture in a long-term bisphosphonate user: a case report.

    Science.gov (United States)

    Park, K-T; Lee, K-B

    2015-01-01

    Recent reports have found a relationship between long-term bisphosphonate therapy and the occurrence of low-energy subtrochanteric or diaphyseal atypical femoral fractures. These fractures usually occur at only one site in the same bone. We report a rare case of a patient with sequential atypical femoral fractures (first, a diaphyseal fracture, and second, an ipsilateral subtrochanteric fracture) after low-energy trauma. We present the clinical and operative findings and discuss how to prevent subsequent atypical femoral fractures. This case indicates that an atypical subtrochanteric femoral fracture can occur after an atypical diaphyseal fracture in a long-term bisphosphonate user. Doctors should be aware of the possibility of a second fracture and explain the risk to the patient. Key words: bisphosphonate, atypical femoral fracture, low-energy trauma, subtrochanteric and diaphyseal femoral fractures.

  1. Oral myiasis

    Directory of Open Access Journals (Sweden)

    Thalaimalai Saravanan

    2015-01-01

    Full Text Available Myiasis is a pathologic condition in humans occurring because of parasitic infestation. Parasites causing myiasis belong to the order Diptera. Oral myiasis is seen secondary to oral wounds, suppurative lesions, and extraction wounds, especially in individuals with neurological deficit. In such cases, neglected oral hygiene and halitosis attracts the flies to lay eggs in oral wounds resulting in oral myiasis. We present a case of oral myiasis in 40-year-old male patient with mental disability and history of epilepsy.

  2. Efficacy of laser therapy in the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ): a systematic review.

    Science.gov (United States)

    Weber, João Batista Blessmann; Camilotti, Renata Stifelman; Ponte, Monique Estér

    2016-08-01

    Bisphosphonate-related osteonecrosis of the jaw is a well-known potential side effect of long-term bisphosphonate therapy; the primary objective of the treatment should be to improve patient quality of life through pain and infection management, to prevent the development of new lesions, and to slow disease progression. In recent years, the use of laser for bisphosphonate-related osteonecrosis of the jaw has become more widespread, due to its use of administration and widely reported beneficial effects on tissue healing. The present systematic review of the literature sought to elucidate whether low-level laser therapy has positive effects on the treatment of bisphosphonate-related osteonecrosis of the jaw. We conducted a systematic search of the PubMed, EMBASE, and Cochrane Library electronic databases, with no restrictions on language or year of publication. Search strategies were formulated using keywords and Boolean operators. The electronic search strategy retrieved 55 records. From 55 articles, 16 were selected for full-text review, and of these, 10 were ultimately included for data analysis in this review. Our findings show that treatment modalities including laser were associated with superior outcomes in terms of cure or improvement of bisphosphonate-related osteonecrosis of the jaw lesions as compared with conventional surgical and/or conservative drug therapy. It can be concluded that combined treatment with antibiotics, minimally invasive surgery (including Er:YAG laser surgery), and low-level laser therapy in the early stages of the disease should be the gold standard for bisphosphonate-related osteonecrosis of the jaw management.

  3. Fluorescent Risedronate Analogues Reveal Bisphosphonate Uptake by Bone Marrow Monocytes and Localization Around Osteocytes In Vivo

    Science.gov (United States)

    Roelofs, Anke J; Coxon, Fraser P; Ebetino, Frank H; Lundy, Mark W; Henneman, Zachary J; Nancollas, George H; Sun, Shuting; Blazewska, Katarzyna M; Bala, Joy Lynn F; Kashemirov, Boris A; Khalid, Aysha B; McKenna, Charles E; Rogers, Michael J

    2010-01-01

    Bisphosphonates are effective antiresorptive agents owing to their bone-targeting property and ability to inhibit osteoclasts. It remains unclear, however, whether any non-osteoclast cells are directly affected by these drugs in vivo. Two fluorescent risedronate analogues, carboxyfluorescein-labeled risedronate (FAM-RIS) and Alexa Fluor 647–labeled risedronate (AF647-RIS), were used to address this question. Twenty-four hours after injection into 3-month-old mice, fluorescent risedronate analogues were bound to bone surfaces. More detailed analysis revealed labeling of vascular channel walls within cortical bone. Furthermore, fluorescent risedronate analogues were present in osteocytic lacunae in close proximity to vascular channels and localized to the lacunae of newly embedded osteocytes close to the bone surface. Following injection into newborn rabbits, intracellular uptake of fluorescently labeled risedronate was detected in osteoclasts, and the active analogue FAM-RIS caused accumulation of unprenylated Rap1A in these cells. In addition, CD14high bone marrow monocytes showed relatively high levels of uptake of fluorescently labeled risedronate, which correlated with selective accumulation of unprenylated Rap1A in CD14+ cells, as well as osteoclasts, following treatment with risedronate in vivo. Similar results were obtained when either rabbit or human bone marrow cells were treated with fluorescent risedronate analogues in vitro. These findings suggest that the capacity of different cell types to endocytose bisphosphonate is a major determinant for the degree of cellular drug uptake in vitro as well as in vivo. In conclusion, this study shows that in addition to bone-resorbing osteoclasts, bisphosphonates may exert direct effects on bone marrow monocytes in vivo. © 2010 American Society for Bone and Mineral Research PMID:20422624

  4. Vitamin K nutritional status and undercarboxylated osteocalcin in postmenopausal osteoporotic women treated with bisphosphonates.

    Science.gov (United States)

    Iwamoto, Jun; Takada, Tetsuya; Sato, Yoshihiro

    2014-01-01

    Serum undercarboxylated osteocalcin (ucOC) is an index of vitamin K nutritional status in treatment-naive postmenopausal osteoporotic women. The purpose of the present study was to reveal the association between vitamin K nutritional status and serum ucOC concentrations in postmenopausal osteoporotic women taking bisphosphonates. Eighty-six postmenopausal women with osteoporosis (age range: 47-90 years) initiated bisphosphonate treatment. Vitamin K nutritional status was evaluated using a simple vitamin K-intake questionnaire and serum ucOC concentrations were measured after 6 months of treatment. The patients were divided into two groups according to the simple vitamin K-intake questionnaire score: a low vitamin K-intake (score =40) group (n=19). There were no significant differences between the groups in baseline parameters including age, height, body weight, body mass index, serum alkaline phosphatase (ALP), urinary cross-linked N-terminal telopeptides of type I collagen (NTX), and changes in serum ALP and urinary NTX concentrations during the 6-month treatment period. However, the mean serum ucOC concentration after 6 months of treatment was significantly higher in the low vitamin K-intake group (2.79 ng/mL) than in the normal vitamin K-intake group (2.20 ng/mL). These results suggest that 78% of postmenopausal osteoporotic women treated with bisphosphonates may have vitamin K deficiency as indicated by low vitamin K-intake and high serum ucOC concentrations, despite having a similar reduction in bone turnover to women who have normal vitamin K-intake.

  5. A sensitive post-column photochemical derivatization/fluorimetric detection system for HPLC determination of bisphosphonates.

    Science.gov (United States)

    Pérez-Ruiz, Tomás; Martínez-Lozano, Carmen; García-Martínez, María Dolores

    2009-02-27

    A new reversed-phase ion-pair high-performance liquid chromatographic (HPLC) method has been developed for the determination of the following bisphosphonic acids: alendronic acid (ALEN), etidronic acid (ETID), ibandronic acid (IBAN) and risedronic acid (RISE). Separation was achieved on a C(18) column using a mixture of 50 mmol L(-1) borate buffer pH 9.0 containing 0.25 mmol L(-1) tetrabutylammonium chloride and 0.5 mmol L(-1) EDTA and acetonitrile (97:3) as the mobile phase. The sensitive detection of the above bisphosphonic acids was based on their oxidation to orthophosphate by the on-line peroxydisulfate-assisted photolysis followed by post-column reaction with molybdate to yield phosphomolybdate. This subsequently reacted with thiamine to generate thiochrome and, finally, the fluorescence of thiochrome was measured at 440 nm with excitation at 375 nm. The developed method is precise with a mean relative standard deviation of 1.3%, sensitive (with a detection limit at the nmol L(-1) level), accurate, specific, rapid (analysis time approximately 13 min) and inexpensive because to the low cost of the reagents. The assay was applied to the analysis of the four bisphosphonic acids in commercial dosage formulations, in which the excipients did not interfere with the determination. The method was also applied to the determination of etidronate, risedronate and ibandronate in human urine. Sample preparation involves precipitation of the analytes from urine along with endogenous phosphates such as calcium salts by addition of calcium chloride at alkaline pH and dissolution of the precipitate in 0.05 mol L(-1) ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid.

  6. Preparation and evaluation of a radiogallium complex-conjugated bisphosphonate as a bone scintigraphy agent

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Kazuma, E-mail: kogawa@p.kanazawa-u.ac.jp [Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa 920-1192 (Japan); Takai, Kenichiro; Kanbara, Hiroya; Kiwada, Tatsuto [Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa 920-1192 (Japan); Kitamura, Yoji; Shiba, Kazuhiro [Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640 (Japan); Odani, Akira [Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa 920-1192 (Japan)

    2011-07-15

    Introduction: {sup 68}Ga is a radionuclide of great interest as a positron emitter for positron emission tomography (PET). To develop a new bone-imaging agent with radiogallium, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was chosen as a chelating site and Ga-DOTA complex-conjugated bisphosphonate, which has a high affinity for bone, was prepared and evaluated. Although we are interested in developing {sup 68}Ga-labeled bone imaging agents for PET, in these initial studies {sup 67}Ga was used because of its longer half-life. Methods: DOTA-conjugated bisphosphonate (DOTA-Bn-SCN-HBP) was synthesized by conjugation of 2-(4-isothiocyanatebenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7, 10-tetraacetic acid to 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (alendronate). {sup 67}Ga-DOTA-Bn-SCN-HBP was prepared by coordination with {sup 67}Ga, and its in vitro and in vivo evaluations were performed. Results: {sup 67}Ga-DOTA-Bn-SCN-HBP was prepared with a radiochemical purity of over 95% without purification. {sup 67}Ga-DOTA-Bn-SCN-HBP had great affinity for hydroxyapatite in binding assay. In biodistribution experiments, {sup 67}Ga-DOTA-Bn-SCN-HBP accumulated in bone rapidly but was hardly observed in tissues other than bone. Pretreatment of an excess amount of alendronate inhibited the bone accumulation of {sup 67}Ga-DOTA-Bn-SCN-HBP. Conclusions: {sup 67}Ga-DOTA-Bn-SCN-HBP showed ideal biodistribution characteristics as a bone-imaging agent. These findings should provide useful information on the drug design of bone imaging agents for PET with {sup 68}Ga.

  7. Treatment of bisphosphonate related osteonecrosis following root canal therapy at the 1-year follow-up: report of two cases

    Directory of Open Access Journals (Sweden)

    Kaptan F

    2013-12-01

    Full Text Available Figen Kaptan,1 Meric Karapinar Kazandag,1 Ufuk Iseri21Yeditepe University, Faculty of Dentistry, Department of Endodontics, 2Department of Prosthodontics, Istanbul, TurkeyAbstract: The objective of this report was to use topical gaseous ozone as an adjunct to conventional treatment methods and to describe the multidisciplinary management of bisphosphonate associated bone necrosis, which developed following endodontic treatment. No complaints were noted by the patients at their 1-year follow-up and the treatment showed favorable prognosis.Keywords: bisphosphonate, osteonecrosis, BRONJ, endodontics, oxygen, ozone

  8. Osteonecrosis de los maxilares asociada al empleo de bifosfonatos Bisphosphonate-associated osteonecrosis of the jaw

    Directory of Open Access Journals (Sweden)

    J.L. del Castillo Pardo de Vera

    2007-10-01

    Full Text Available Los bifosfonatos constituyen un grupo de fármacos inhibidores de la resorción ósea, utilizados en el tratamiento de numerosas patologías como la osteoporosis, la enfermedad de Paget, el mieloma múltiple, la hipercalcemia maligna y las metástasis óseas asociadas al cáncer de mama o de próstata. El principal efecto farmacológico de los bifosfonatos es la inhibición de la resorción ósea, mediante una disminución de la actividad de los osteoclastos, sin intervenir en la formación y mineralización del hueso. Son fármacos utilizados a nivel mundial con unos claros beneficios contrastados clínicamente. Numerosas publicaciones durante los últimos tres años, y debido a su utilización masiva, consideran que la osteonecrosis de los maxilares está asociada al tratamiento con bifosfonatos. Es importante que los pacientes sean informados del riesgo de presentarse esta complicación, para tener la oportunidad de someterse a procedimientos dentales previos al inicio del tratamiento. Las medidas preventivas deben realizarse antes, durante y después del tratamiento con bifosfonatos. El tratamiento quirúrgico debe reservarse para aquellos pacientes que presenten síntomas. Son necesarias nuevas investigaciones que clarifiquen esta complicación.Bisphosphonates constitute a group of inhibitors of bone resorption that are used for treating many disor-ders such as osteoporosis, Paget´s disease, multiple myeloma, malignant hypercalcemia and bone metas-tases associated with breast and prostate cancer. The main pharmacological effect of bisphosphonates is the inhibition of bone resorption, mediated by a decreased function of osteoclasts without interfering in bone formation and mineralization. These drugs are used worldwide, with clear and clinically proven benefits. Several publications within the last three years consider osteonecrosis of the jaw to be associated with bisphosphonate therapy as a result of their extensive use. It is important

  9. Transient osteoporosis associated with pregnancy: use of bisphosphonate in treating a lactating mother.

    Science.gov (United States)

    Shenker, N G; Shaikh, M F; Jawad, A S M

    2010-12-14

    Transient osteoporosis is a rare condition causing regional pain, immobility and functional compromise. The authors present the case of a pregnant lady with multiple sites of transient osteoporosis, including a stress fracture, successfully treated with intravenous pamidronate and a physical rehabilitation programme. The authors discuss the mechanisms for the syndrome and its overlap with complex regional pain syndrome type I; as well as the implications of bisphosphonate administration to a nursing mother. The authors also highlight the advantages of MRI over standard radiography when investigating unexplained foot pain.

  10. Design, synthesis, and biological evaluation of novel estradiol-bisphosphonate conjugates as bone-specific estrogens.

    Science.gov (United States)

    Morioka, Masahiko; Kamizono, Akihito; Takikawa, Hirosato; Mori, Akihisa; Ueno, Hiroaki; Kadowaki, Shu-ichiro; Nakao, Yoshihide; Kato, Kuniki; Umezawa, Kazuo

    2010-02-01

    Bone deficiency causes osteoporosis and often decreases quality of life in patients with rheumatoid arthritis. Estrogens are known to protect elderly women from bone loss. Synthesis of new estradiol-bisphosphonate conjugates (E(2)-BPs) was accomplished and their in vivo activity as bone-specific estrogens were examined. Among them, MCC-565 showed selective estrogenic activity in bones; but it showed little estrogenic activity in the uterus. We also found that the linker moiety in E(2)-BPs was essential for the absorption and specificity of the conjugates.

  11. The effect on implant fixation of soaking tricalcium phosphate granules in bisphosphonate

    DEFF Research Database (Denmark)

    Jakobsen, Thomas; Baas, Jørgen; Bechtold, Joan E;

    2012-01-01

    biomechanical implant fixation and osseointegration of experimental implant grafted with β-TCP granules (Conduit) could be improved by soaking the β-TCP granules in bisphosphonate (zoledronate). In 10 dogs, a pair of titanium coated implants surrounded by a 2.5 mm gap was inserted into the proximal part of each......The use of bone grafting is a well-established way to enhance initial implant fixation in situations with reduced bone stock. Ceramic bone substitutes are inferior alternatives to autogenous or allogeneic bone graft. Improvement of bone graft substitutes is needed. We investigated whether...

  12. Oral Thrush

    Science.gov (United States)

    ... feeding mothers In addition to the distinctive white mouth lesions, infants may have trouble feeding or be fussy ... candidiasis (yeast infection) patient information. American Academy of Oral & Maxillofacial Pathology. http://www.aaomp.org/public/oral-candidiasis.php. ...

  13. Oral Dysfunction

    OpenAIRE

    鈴木, 規子; スズキ, ノリコ; Noriko, SUZUKI

    2004-01-01

    The major oral functions can be categorized as mastication, swallowing, speech and respiratory functions. Dysfunction of these results in dysphagia, speech disorders and abnormal respiration (such as Sleep Apnea). These functions relate to dentistry in the occurrence of : (1) oral preparatory and oral phases, (2) articulation disorders and velopharyngeal incompetence (VPI), and (3) mouth breathing, respiratory and blowing disorders. These disorders are related to oral and maxillofacial diseas...

  14. Oral fluconazole in tinea versicolor

    Directory of Open Access Journals (Sweden)

    Sankara Rao I

    1997-01-01

    Full Text Available 25 patients with extensive tinea versicolor were treated with single oral dose of 400 mg of fluconazole. 25 patients returned for follow-up. Follow-up at 3 weeks, 6 weeks and 8 weeks showed 100% clinical cure rate and 92% mycological cure rate. No significant side effects were noticed. The majority of patients found the treatment effective, safe and convenient.

  15. Bifunctional bisphosphonates for delivering PTH (1-34) to bone mineral with enhanced bioactivity.

    Science.gov (United States)

    Yewle, Jivan N; Puleo, David A; Bachas, Leonidas G

    2013-04-01

    The objective of this work was to demonstrate the bioactivity of parathyroid hormone (1-34) (PTH) delivered through a single molecule of bisphosphonate to improve tissue/cell interactions. Bifunctional hydrazine-bisphosphonates (HBPs) with varying length and lipophilicity were used as a drug delivery vehicle. PTH was oxidized with periodate treatment to obtain an N-terminal aldehyde that was then conjugated to HBPs. The toxicity and apoptotic properties of HBPs and HBP-PTH conjugates were studied with macrophages (RAW 264.7). It was found that one of the HBPs had significant apoptotic characteristics similar to alendronate, which is a widely prescribed drug in the treatment of osteoporosis. The improved binding affinity of PTH following conjugation to HBP was determined using a hydroxyapatite binding assay. The amount of PTH delivered to bone through HBPs was not affected by the length or lipophilicity of the HBPs. Furthermore, the improved bioactivity of PTH delivered to bone through HBPs, in comparison to adsorbed PTH, was demonstrated by quantifying the cAMP produced by pre-osteoblastic (MC3T3-E1) cells in response to PTH. The delivery of bioactive PTH to bone tissue by HBP conjugation demonstrates the potential use of HBPs in delivering therapeutic macromolecules to bone for the treatment of several skeletal diseases. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Inherited multicentric osteolysis: case report of three siblings treated with bisphosphonate

    Directory of Open Access Journals (Sweden)

    Whitewood Colin

    2010-04-01

    Full Text Available Abstract Inherited Multicentric Osteolysis (IMO is an uncommon familial condition of idiopathic pathophysiology causing bone osteolysis and dysplasia. These patients present with common rheumatologic complaints of pain, dysfunction and disability, and are often initially misdiagnosed as a chronic rheumatic disease of childhood such as juvenile idiopathic arthritis. We report a case of three siblings diagnosed with IMO. Diagnosis was made during childhood, with each sibling having different manifestations and course of disease. One had a previous history of bilateral hip dysplasia. Two had osteolysis of the foot, distal tibia and femur (lower limb bones, whilst one had osteolysis of the rib and unusual clavicular fractures. Unusually, all siblings appear to experience decreased pain sensation compared to norms. All siblings were treated with bisphosphonates and experienced a rapid improvement in pain symptoms, decreased analgesic requirements. Two had bone mineral density testing performed and both had increases post-bisphosphonate. In all three, there was subjective evidence of stabilisation of bone disease. Testing for matrix metalloproteinase-2 (MMP2 gene was negative.

  17. Bisphosphonate Treatment in a Patient Affected by MPS IVA with Osteoporotic Phenotype

    Directory of Open Access Journals (Sweden)

    Albina Tummolo

    2013-01-01

    Full Text Available Morquio A syndrome (Mucopolysaccharidosis type IVA (MPS IVA is a rare inherited metabolic disorder characterized by the defective degradation of keratan sulfate and chondroitin-6-sulfate. Classically, MPS IVA patients present with severe multisystemic involvement and have a short life expectancy. Attenuated forms with clinical features limited to minor skeletal abnormalities and short stature have also been described, sometimes associated to an early-onset osteoporotic phenotype. No treatment with allogenic bone marrow transplantation or gene therapy is currently available for Morquio A syndrome, and enzyme replacement therapy is under evaluation. We report a case of MPS IVA, who manifested tardily attenuated phenotype and significant bone mass reduction, which was treated with a bisphosphonate (BPN, resulting in an improvement of X-ray skeletal aspects and functional bone performance. We suggest that the use of bisphosphonates may be an interesting supportive therapeutic option for Morquio A patients with osteoporotic phenotype, but further studies involving more patients are necessary to confirm our findings.

  18. Aromatase inhibitor-associated bone loss and its management with bisphosphonates in patients with breast cancer

    Directory of Open Access Journals (Sweden)

    Bauer M

    2012-06-01

    Full Text Available M Bauer,1 J Bryce,2 P Hadji11University of Marburg, Marburg, Germany; 2National Cancer Institute, Naples, ItalyAbstract: Postmenopausal women have an increased risk of osteopenia and osteoporosis due to loss of the bone-protective effects of estrogen. Disease-related processes may also contribute to the risk of bone loss in postmenopausal women with breast cancer. One of the most common and severe safety issues associated with cancer therapy for patients with breast cancer is bone loss and the associated increase in risk of fractures. This paper reviews the recent literature pertaining to aromatase inhibitor (AI-associated bone loss, and discusses suggested management and preventative approaches that may help patients remain on therapy to derive maximum clinical benefit. A case study is presented to illustrate the discussion. We observed that AIs are in widespread use for women with hormone receptor-positive breast cancer and are now recommended as adjuvant therapy, either as primary therapy or sequential to tamoxifen, for postmenopausal women. AIs target the estrogen biosynthetic pathway and deprive tumor cells of the growth-promoting effects of estrogen, and AI therapies provide benefits to patients in terms of improved disease-free survival. However, there is a concern regarding the increased risk of bone loss with prolonged AI therapy, which can be managed in many cases with the use of bisphosphonates and other interventions (eg, calcium, vitamin D supplementation, exercise.Keywords: aromatase inhibitors, bisphosphonates, bone loss, breast cancer, estrogen

  19. The effect of bisphosphonates on the endothelial differentiation of mesenchymal stem cells.

    Science.gov (United States)

    Sharma, Dileep; Hamlet, Stephen Mark; Petcu, Eugen Bogdan; Ivanovski, Saso

    2016-02-09

    The contribution of the local stem cell niche to providing an adequate vascular framework during healing cannot be overemphasized. Bisphosphonates (BPs) are known to have a direct effect on the local vasculature, but their effect on progenitor cell differentiation is unknown. This in vitro study evaluated the effect(s) of various BPs on the differentiation of human placental mesenchymal stem cells (pMSCs) along the endothelial lineage and their subsequent functional and morphogenic capabilities. pMSC multipotency was confirmed by successful differentiation into cells of both the osteogenic and endothelial lineages, as demonstrated by positive Alizarin Red S staining and Ac-LDL uptake. pMSC differentiation in the presence of non-cytotoxic BP concentrations showed that nitrogen containing BPs had a significant inhibitory effect on cell migration and endothelial marker gene expression, as well as compromised endothelial differentiation as demonstrated using von Willebrand factor immunofluorescence staining and tube formation assay. This in vitro study demonstrated that at non-cytotoxic levels, nitrogen-containing BPs inhibit differentiation of pMSCs into cells of an endothelial lineage and affect the downstream functional capability of these cells supporting a multi-modal effect of BPs on angiogenesis as pathogenic mechanism contributing to bone healing disorders such as bisphosphonate related osteonecrosis of the jaws (BRONJ).

  20. The critical role of bisphosphonates to target bone cancer metastasis: an overview.

    Science.gov (United States)

    Singh, Tejinder; Kaur, Veerpal; Kumar, Manish; Kaur, Prabhjot; Murthy, R S R; Rawal, Ravindra K

    2015-01-01

    Cancer becomes the leading cause of deaths worldwide, including breast cancer, prostate cancer and lung cancer that preferentially metastasize to bone and bone marrow. Bisphosphonates (BPs) have been used successfully for many years to reduce the skeletal complications related with the benign and malignant bone diseases that are characterized by enhanced osteoclastic bone resorption. Nitrogen-containing bisphosphonates (N-BPs) have also been demonstrated to exhibit direct anti-tumour effects. BPs binds avidly to the bone matrix, and released from matrix during bone resorption process, BPs are internalized by the osteoclasts where they interfere with biochemical pathways and induce osteoclast apoptosis. BPs also antagonizes the production of osteoclast and promotes the osteoblasts proliferation. Currently, Zoledronic acid is widely used as one of the BP having high bone specificity and potential to inhibit the osteoclast-mediated bone resorption. In addition to inhibition of cell multiplication and initiation of apoptosis in cultured cancer cells, they also interfere with adhesion of cancer cells to the bone matrix and inhibit cell migration and invasion. Pathophysiology and current target therapies like conjugate of BPs with liposomes, nanoparticle used for the treatment of bone cancer is reviewed in this article along with the use of different BPs.

  1. Osteonecrose maxilar associada ao uso de bisfosfonatos Bisphosphonate-related osteonecrosis of the jaw

    Directory of Open Access Journals (Sweden)

    Mariana Aparecida Brozoski

    2012-04-01

    Full Text Available Os bisfosfonatos (BFs têm sido indicados para o tratamento de doenças do metabolismo ósseo. Atualmente, seu emprego terapêutico aumentou e, com ele, os efeitos adversos, dos quais um dos mais importantes é a indução da osteonecrose dos maxilares, uma complicação de difíceis tratamento e solução. Até o presente, não se sabe ao certo qual é o mecanismo de desenvolvimento da osteonecrose dos maxilares induzida por bisfosfonatos (ONMB, nem qual deve ser o tratamento estabelecido perante essa manifestação. Apesar de a literatura apresentar formas variadas de tratamento, não existe um protocolo definido. Apresentamos uma revisão sobre a ONMB, enfocando sua etiopatogenia e as formas reportadas de tratamento.Bisphosphonates (BPs have been used for the management of bone metabolic diseases. Currently their therapeutic use has increased, as also have their adverse effects, one of the most important being the bisphosphonate-related osteonecrosis of the jaw (BRONJ, a complication of difficult treatment and solution. Until now, the physiopathology of BRONJ remains unclear, and its treatment is uncertain. Although the literature provides several treatment options, there is no defined protocol. We present a review about BRONJ, focusing on its pathogenesis and its reported forms of treatment.

  2. Bisphosphonate treatment for osteolysis in total hip arthroplasty. A report of four cases

    Science.gov (United States)

    Trevisan, Carlo; Nava, Veronica; Mattavelli, Marta; Parra, Cleber Garcia

    2013-01-01

    Summary Aseptic loosening due to wear debris is the most frequent modality of failure in total hip arthroplasty. Bisphosphonates, a class of molecules which inhibit bone resorption showed an inhibitory effects on particles-induced osteolysis in vitro and in animal models. We report the clinical, radiographic and densitometric outcome of four postmenopausal women with total hip arthroplasty affected by peri-prosthetic osteolysis treated with neridronate due to their unwillingness to be operated. After neridronate treatment, there was general improvement in pain and function: VAS decrease 13 points (15%), the Harris Hip Score increase 9 points (15%). An average number of 3.3 x-ray per patients with an average follow-up of 23 months (range 12–34) were collected and evaluated. In all the patients except one, serial radiographs didn’t show any progression of radioluciencies lines or periprosthetic osteolysis. Bone density was evaluated by Dual energy X-ray absorptiometry after an average follow-up of 21 months (range 6–46 mo): periprosthetic BMD around the whole stem and the cup increased respectively 2.4% and 7.1%. Treatment was well tolerated and no significant side effects were registered. This retrospective collection of a small group of patients suggest that bisphosphonates should be clinically useful in preventing periprosthetic wear debris mediated osteolysis and claim for dedicated clinical trials. PMID:23858314

  3. Modulating P2X7 Receptor Signaling during Rheumatoid Arthritis: New Therapeutic Approaches for Bisphosphonates

    Directory of Open Access Journals (Sweden)

    Alberto Baroja-Mazo

    2012-01-01

    Full Text Available P2X7 receptor-mediated purinergic signaling is a well-known mechanism involved in bone remodeling. The P2X7 receptor has been implicated in the pathophysiology of various bone and cartilage diseases, including rheumatoid arthritis (RA, a widespread and complex chronic inflammatory disorder. The P2X7 receptor induces the release into the synovial fluid of the proinflammatory factors (e.g., interleukin-1β, prostaglandins, and proteases responsible for the clinical symptoms of RA. Thus, the P2X7 receptor is emerging as a novel anti-inflammatory therapeutic target, and various selective P2X7 receptor antagonists are under clinical trials. Extracellular ATP signaling acting through the P2X7 receptor is a complex and dynamic scenario, which varies over the course of inflammation. This signaling is partially modulated by the activity of ectonucleotidases, which degrade extracellular ATP to generate other active molecules such as adenosine or pyrophosphates. Recent evidence suggests differential extracellular metabolism of ATP during the resolution of inflammation to generate pyrophosphates. Extracellular pyrophosphate dampens proinflammatory signaling by promoting alternative macrophage activation. Our paper shows that bisphosphonates are metabolically stable pyrophosphate analogues that are able to mimic the anti-inflammatory function of pyrophosphates. Bisphosphonates are arising per se as promising anti-inflammatory drugs to treat RA, and this therapy could be improved when administrated in combination with P2X7 receptor antagonists.

  4. Genetic investigation of bisphosphonate-related osteonecrosis of jaw (BRONJ via whole exome sequencing and bioinformatics.

    Directory of Open Access Journals (Sweden)

    Jee-Hwan Kim

    Full Text Available Complications associated with the use of bisphosphonate (BP have risen over the years due to an increase in the prescription of BP. BP-related osteonecrosis of jaw (BRONJ, one of the complications linked to the consumption of BP, greatly affects patients with minor dental trauma, incurring a long healing period. While BRONJ afflicts only a minority of patients prescribed with BP, BRONJ is a multigenic disease affected both by environmental and genetic factors having a distinctive phenotype. This study aims to discover genetic biomarkers associated with BRONJ via whole exome sequencing (WES followed by statistical analysis. Sixteen individuals who had been prescribed with bisphosphonate medication and diagnosed as BRONJ were chosen and each individual's saliva sample was collected for WES. 126 randomized subsamples from the GSK project representing 109 male and 17 female Koreans were used as a control data set. Fisher's exact test was carried out to assess the significance of genetic variants in BRONJ patients. Gene set enrichment analysis (GSEA (DAVID Bioinformatics Resource 6.7 was used to perform a cluster analysis of variants found from Fisher's exact test. The results from this study suggest that BRONJ-inducing factors are genetically associated and BRONJ occurs due to the malfunctioning of post-translational modification in osteoclast leading to the impairment of cell morphology and adhesion.

  5. Farnesyl pyrophosphate synthase is the molecular target of nitrogen-containing bisphosphonates.

    Science.gov (United States)

    van Beek, E; Pieterman, E; Cohen, L; Löwik, C; Papapoulos, S

    1999-10-14

    Bisphosphonates (Bps), inhibitors of osteoclastic bone resorption, are used in the treatment of skeletal disorders. Recent evidence indicated that farnesyl pyrophosphate (FPP) synthase and/or isopentenyl pyrophosphate (IPP) isomerase is the intracellular target(s) of bisphosphonate action. To examine which enzyme is specifically affected, we determined the effect of different Bps on incorporation of [(14)C]mevalonate (MVA), [(14)C]IPP, and [(14)C]dimethylallyl pyrophosphate (DMAPP) into polyisoprenyl pyrophosphates in a homogenate of bovine brain. HPLC analysis revealed that the three intermediates were incorporated into FPP and geranylgeranyl pyrophosphate (GGPP). In contrast to clodronate, the nitrogen-containing Bps (NBps), alendronate, risedronate, olpadronate, and ibandronate, completely blocked FPP and GGPP formation and induced in incubations with [(14)C]MVA a 3- to 5-fold increase in incorporation of label into IPP and/or DMAPP. Using a method that could distinguish DMAPP from IPP on basis of their difference in stability in acid, we found that none of the NBps affected the conversion of [(14)C]IPP into DMAPP, catalyzed by IPP isomerase, excluding this enzyme as target of NBp action. On the basis of these and our previous findings, we conclude that none of the enzymes up- or downstream of FPP synthase are affected by NBps, and FPP synthase is, therefore, the exclusive molecular target of NBp action.

  6. Kinetic release studies of nitrogen-containing bisphosphonate from gum acacia crosslinked hydrogels.

    Science.gov (United States)

    Aderibigbe, B A; Varaprasad, K; Sadiku, E R; Ray, S S; Mbianda, X Y; Fotsing, M C; Owonubi, S J; Agwuncha, S C

    2015-02-01

    Natural polymer hydrogels are useful for controlling release of drugs. In this study, hydrogels containing gum acacia were synthesized by free-radical polymerization of acrylamide with gum acacia. The effect of gum acacia in the hydrogels on the release mechanism of nitrogen-containing bisphosphonate (BP) was studied at pH 1.2 and 7.4. The hydrogels exhibited high swelling ratios at pH 7.4 and low swelling ratios at pH 1.2. The release study was performed using UV-Visible spectroscopy via complex formation with Fe(III) ions. At pH 1.2, the release profile was found to be anomalous while at pH 7.4, the release kinetic of BP was a perfect zero-order release mechanism. The hydrogels were found to be pH-sensitive and the release profiles of the BP were found to be influenced by the degree of crosslinking of the hydrogel network with gum acacia. The preliminary results suggest that these hydrogels are promising devices for controlled delivery of bisphosphonate to the gastrointestinal region.

  7. Hydrogen bonding motifs in a hydroxy-bisphosphonate moiety: revisiting the problem of hydrogen bond identification.

    Science.gov (United States)

    Ashouri, Mitra; Maghari, Ali; Karimi-Jafari, M H

    2015-05-28

    Bisphosphonates are important therapeutic agents in bone-related diseases and exhibit complex H-bonding networks. To assess the role of H-bonds in biophosphonate stability, a full conformational search was performed for methylenebisphosphonate (MBP) and 1-hydroxyethylidene-1,1-diphosphonate (HEDP) using the MP2 method in conjunction with the continuum solvation model. The most stable structures and their equilibrium populations were analyzed at two protonation states via assignment of H-bonding motifs to each conformer. Geometrical and topological approaches for the identification and characterization of H-bonds were compared with each other, and some of the important correlations between H-bond features were described over the entire conformational space of a hydroxy-bisphosphonate moiety. The topologically derived H-bond energy obtained from the local density of potential energy at bond critical points shows consistent correlations with other measures such as H-bond frequency shift. An inverse power form without an intercept predicts topological H-bond energies from hydrogen-acceptor distances with an RMS error of less than 1 kcal mol(-1). The consistency of this measure was further checked by building a model that reasonably reproduces the relative stabilities of different conformers from their hydrogen-acceptor distances. In all systems, the predictions of this model are improved by the consideration of weak H-bonds that have no bond critical point.

  8. Scoliosis in osteogenesis imperfecta caused by COL1A1/COL1A2 mutations - genotype-phenotype correlations and effect of bisphosphonate treatment.

    Science.gov (United States)

    Sato, Atsuko; Ouellet, Jean; Muneta, Takeshi; Glorieux, Francis H; Rauch, Frank

    2016-05-01

    Bisphosphonates are widely used to treat children with osteogenesis imperfecta (OI), a bone fragility disorder that is most often caused by mutations in COL1A1 or COL1A2. However, it is unclear whether this treatment decreases the risk of developing scoliosis. We retrospectively evaluated spine radiographs and charts of 437 patients (227 female) with OI caused by mutations in COL1A1 or COL1A2 and compared the relationship between scoliosis, genotype and bisphosphonate treatment history. At the last follow-up (mean age 11.9 [SD: 5.9] years), 242 (55%) patients had scoliosis. The prevalence of scoliosis was highest in OI type III (89%), followed by OI type IV (61%) and OI type I (36%). Moderate to severe scoliosis (Cobb angle ≥25°) was rare in individuals with COL1A1 haploinsufficiency mutations but was present in about two fifth of patients with triple helical glycine substitutions or C-propeptide mutations. During the first 2 to 4years of bisphosphonate therapy, patients with OI type III had lower Cobb angle progression rates than before bisphosphonate treatment, whereas in OI types I and IV bisphosphonate treatment was not associated with a change in Cobb angle progression rates. At skeletal maturity, the prevalence of scoliosis (Cobb angle >10°) was similar in patients who had started bisphosphonate treatment early in life (before 5.0years of age) and in patients who had started therapy later (after the age of 10.0years) or had never received bisphosphonate therapy. Bisphosphonate treatment decreased progression rate of scoliosis in OI type III but there was no evidence of a positive effect on scoliosis in OI types I and IV. The prevalence of scoliosis at maturity was not influenced by the bisphosphonate treatment history in any OI type.

  9. Platelet-Rich Plasma in Treatment of Zoledronic Acid-Induced Bisphosphonate-related Osteonecrosis of the Jaws

    OpenAIRE

    Sarkarat; Kalantar Motamedi; Jahanbani; Sepehri; Kahali; Nematollahi

    2014-01-01

    Background Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a well-known challenging entity warranting management. Platelet-Rich Plasma (PRP) plays an important role in bone biology by enhancing bone repair and regeneration. Objectives The aim of this animal study was to evaluate the effects of PRP on zoledronic acid-induced BRONJ. Materials and Methods Seven rats were g...

  10. Risk of cardiac valvulopathy with use of bisphosphonates: a population-based, multi-country case-control study

    NARCIS (Netherlands)

    P.M. Coloma (Preciosa); M.A.J. de Ridder (Maria); I. Bezemer (Irene); R.M.C. Herings (Ron); R. Gini (Rosa); S. Pecchioli (Serena); L. Scotti (Lorenza); P.R. Rijnbeek (Peter); M. Mosseveld (Mees); J. van der Lei; G. Trifirò (Gianluca); M.C.J.M. Sturkenboom (Miriam)

    2016-01-01

    textabstractSummary: Analyses of healthcare data from 30 million individuals in three countries showed that current use of bisphosphonates may be associated with a small increased risk of cardiac valvulopathy (vs. those not exposed within the previous year), although confounding cannot be entirely r

  11. Comparison of serum Dkk1 (Dickkopf-1) and bone mineral density in patients on bisphosphonate treatment vs no treatment.

    LENUS (Irish Health Repository)

    Memon, Adeel R

    2013-05-17

    Complex pathways affect bone metabolism at the cellular level, and a balance between osteoblast and osteoclast activity is critical to bone remodeling. One of the major pathways affecting bone metabolism is Wnt\\/β-catenin signaling, and its disturbances lead to a wide range of bone abnormalities. An important antagonist of this pathway is Dickkopf-1 (Dkk1). Higher Dkk1 levels have been associated with increased bone loss due to inhibition of Wnt pathway. Currently, bisphosphonates are the most commonly used agents to treat primary osteoporotic patients. This study demonstrates the effect of bisphosphonates on Dkk1 levels and its correlation with bone mineral density (BMD). Eighty patients with low BMD were recruited and divided into 2 groups of 40 each (bisphosphonate treatment group and control group). The mean Dkk1 level in the treatment group was significantly reduced to 2358.18 vs 3749.80 pg\\/mL in the control group (p<0.001). Pearson correlation coefficient showed negative correlation between Dkk1 and BMD at lumbar spine (r=-0.55) and femoral neck in the control group; however, no such correlation was found in the treatment group (r=-0.05). Hence, bisphosphonate therapy leads to reduction in Dkk1 levels, but it does not correlate with BMD in such patients.

  12. Bisphosphonate-related osteonecrosis of jaws in advanced stage breast cancer was detected from bone scan: a case report

    Science.gov (United States)

    Chirappapha, Prakasit; Thongjood, Thanaporn; Aroonroch, Rangsima

    2017-01-01

    Bisphosphonates (BPs) are indicated to treat skeletal-related events (SREs) for cancer patients with bone metastasis. We report a 79-year-old woman with advanced stage breast cancer with bone metastasis who was prescribed BPs (zoledronate), then developed osteonecrosis of jaw. We provide a brief review of the pathogenesis, diagnosis and treatment of this complication. PMID:28210558

  13. Comparative study of effectiveness of oral acyclovir with oral erythromycin in the treatment of Pityriasis rosea.

    Science.gov (United States)

    Amatya, A; Rajouria, E A; Karn, D K

    2012-01-01

    Pityriasis rosea is an acute, self-limiting disease, probably infective in origin, affecting mainly children and young adults, characterized by distinctive skin eruptions and minimal constitutional symptoms. Both oral Erythromycin and oral Acyclovir have been used in its management. To compare the effectiveness of oral Erythromycin and oral Acyclovir in the treatment of Pityriasis rosea. Forty two patients with clinical diagnosis of Pityriasis rosea were enrolled. They were randomized into two groups. One group was given high-dose oral Acyclovir and another group oral Erythromycin in standard dose. The participants were evaluated one, two, four, six and eight weeks and six months after commencement of the study. Forty two patients including 26 males and 16 females completed the study. After 8th week, all patients showed complete response in both the groups. The response to oral Acyclovir compared with that to oral Erythromycin was better and was statistically significant in 1st, 2nd, 4th and 6th weeks. Although it is a self-limiting disease which resolves within three weeks to three months, this study reveals that both oral Acyclovir and oral Erythromycin are helpful in decreasing the severity and duration of Pityriasis rosea. Moreover, the study also indicates that oral Acyclovir is more effective than oral Erythromycin in reducing the severity and duration of Pityriasis rosea.

  14. Synthesis of triple-bond-containing 1-hydroxy-1,1-bisphosphonic acid derivatives to be used as precursors in "click" chemistry: two examples.

    Science.gov (United States)

    Turhanen, Petri A

    2014-07-03

    The synthesis of novel (ω-alkynyl-1-hydroxy-1,1-diyl)bisphosphonic acid tetramethyl esters (1a-c), their P,P'-dimethyl esters (2a-c), and two trimethyl ester derivatives (3a and 3b) is reported. The prepared compounds can be attached to many kinds of molecules containing azide (-N3) functionalities using a "click" chemistry approach. As an example, bisphosphonate trimethyl ester 3a and P,P'-dimethyl ester 2b were attached to triethylene glycol to form triethylene glycol-bisphosphonate conjugates 4 and 5 as model compounds for further studies in, for example, nanoparticle targeting.

  15. Parathyroid hormone versus bisphosphonate treatment on bone mineral density in osteoporosis therapy: a meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Longxiang Shen

    Full Text Available BACKGROUND: Bisphosphonates and parathyroid hormone (PTH represent the antiresorptive and anabolic classes of drugs for osteoporosis treatment. Bone mineral density (BMD is an essential parameter for the evaluation of anti-osteoporotic drugs. The aim of this study was to evaluate the effects of PTH versus bisphosphonates on BMD for the treatment of osteoporosis. METHODS/PRINCIPAL FINDINGS: We performed a literature search to identify studies that investigated the effects of PTH versus bisphosphonates treatment on BMD. A total of 7 articles were included in this study, representing data on 944 subjects. The pooled data showed that the percent change of increased BMD in the spine is higher with PTH compared to bisphosphonates (WMD = 5.90, 95% CI: 3.69-8.10, p<0.01,. In the hip, high dose (40 µg PTH (1-34 showed significantly higher increments of BMD compared to alendronate (femoral neck: WMD = 5.67, 95% CI: 3.47-7.87, p<0.01; total hip: WMD = 2.40, 95%CI: 0.49-4.31, p<0.05. PTH treatment has yielded significantly higher increments than bisphosphonates with a duration of over 12 months (femoral neck: WMD = 5.67, 95% CI: 3.47-7.86, p<0.01; total hip: WMD = 2.40, 95% CI: 0.49-4.31, P<0.05 and significantly lower increments at 12 months (femoral neck: WMD = -1.05, 95% CI: -2.26-0.16, p<0.01; total hip: WMD: -1.69, 95% CI: -3.05-0.34, p<0.05. In the distal radius, a reduction in BMD was significant between PTH and alendronate treatment. (WMD = -3.68, 95% CI: -5.57-1.79, p<0.01. DISCUSSION: Our results demonstrated that PTH significantly increased lumbar spine BMD as compared to treatment with bisphosphonates and PTH treatment induced duration- and dose-dependent increases in hip BMD as compared to bisphosphonates treatment. This study has also disclosed that for the distal radius, BMD was significantly lower from PTH treatment than alendronate treatment.

  16. Bisphosphonate-associated osteonecrosis of the jaw is linked to suppressed TGFβ1-signaling and increased Galectin-3 expression: A histological study on biopsies

    Directory of Open Access Journals (Sweden)

    Schlegel Karl A

    2011-07-01

    Full Text Available Abstract Background Bisphosphonate associated osteonecrosis of the jaw (BRONJ implies an impairment in oral hard- and soft tissue repair. An understanding of the signal transduction alterations involved can inform therapeutic strategies. Transforming growth factor β1 (TGFβ1 is a critical regulator of tissue repair; galectin-3 mediates tissue differentiation and specifically modulates periodontopathic bacterial infection. The aim of this study was to compare the expression of TGFβ1-related signaling molecules and Galectin-3 in BRONJ-affected and healthy mucosal tissues. To discriminate between BRONJ-specific impairments in TGFβ1 signaling and secondary inflammatory changes, the results were compared to the expression of TGFβ1 and Galectin-3 in mucosal tissues with osteoradionecrosis. Methods Oral mucosal tissue samples with histologically-confirmed BRONJ (n = 20, osteoradionecrosis (n = 20, and no lesions (normal, n = 20 were processed for immunohistochemistry. Automated staining with an alkaline phosphatase-anti-alkaline phosphatase kit was used to detect TGFβ1, Smad-2/3, Smad-7, and Galectin-3. We semiquantitatively assessed the ratio of stained cells/total number of cells (labeling index, Bonferroni-adjustment. Results TGFβ1 and Smad-2/3 were significantly decreased (p Conclusion Our results showed that disrupted TGFβ1 signaling was associated with delayed periodontal repair in BRONJ samples. The findings also indicated that impairments in TGFβ1-signaling were different in BRONJ compared to osteoradionecrosis. BRONJ appeared to be associated with increased terminal osseous differentiation and decreased soft tissue proliferation. The increase in Galectin-3 reflected the increase in osseous differentiation of mucoperiosteal progenitors, and this might explain the inflammatory anergy observed in BRONJ-affected soft tissues. The results substantiated the clinical success of treating BRONJ with sequestrectomy, followed by strict mucosa

  17. Elective caesarean section at 38 weeks versus 39 weeks

    DEFF Research Database (Denmark)

    Glavind, Julie; Kindberg, S F; Uldbjerg, N;

    2013-01-01

    To investigate whether elective caesarean section before 39 completed weeks of gestation increases the risk of adverse neonatal or maternal outcomes.......To investigate whether elective caesarean section before 39 completed weeks of gestation increases the risk of adverse neonatal or maternal outcomes....

  18. Evaluation of fracture risk and potential drug holidays for postmenopausal women on long-term bisphosphonate therapy

    Directory of Open Access Journals (Sweden)

    Kostoff MD

    2014-04-01

    Full Text Available Matthew D Kostoff, Joseph J Saseen, Laura M BorgeltDepartments of Clinical Pharmacy and Family Medicine, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences and School of Medicine, Aurora, CO, USAStudy objective: To describe characteristics of postmenopausal women on long-term bisphosphonate therapy who fall into one of four fracture risk categories (low, mild, moderate, high, and to determine the prevalence of women eligible for a drug holiday.Design: Retrospective electronic health record review.Setting: Eight primary care clinics within a university-based health care system.Patients: A total of 201 postmenopausal women of ages 55–89 years, with osteopenia or osteoporosis, prescribed bisphosphonate therapy for >4 years, between October 10, 2002 and September 9, 2012.Main results: The patients' mean age was 71.4 (±8.2 years; their mean body mass index was 25.3 (±5.6 kg/m2; and 73.1% were white. Seventy-four out of 201 patients (36.8% were low-risk; 10/201 (5.0% were mild-risk; 72/201 (35.8% were moderate-risk; and 45/201 (22.4% were high-risk. Eighty-one women (40.3% were eligible for a drug holiday or discontinuation. The estimated drug cost avoided per eligible patient was $574.80. Calcium and/or vitamin D supplementation was documented in 52.7% of women.Conclusion: More than one-third of postmenopausal women taking long-term bisphosphonate therapy had low fracture risk, and over 40% of our patients were eligble for a drug holiday or discontinuation. These data emphasize the need to accurately assess risk and benefit in patients treated with bisphosphonate therapy.Keywords: postmenopausal osteoporosis, bisphosphonates, drug holiday, fracture

  19. WBDOC Weekly Workload Status Report

    Data.gov (United States)

    Social Security Administration — Weekly reports of workloads processed in the Wilkes Barre Data Operation Center. Reports on quantities of work received, processed, pending and average processing...

  20. Oral Alendronate Treatment for Severe Polyostotic Fibrous Dysplasia due to McCune-Albright Syndrome in a Child: A Case Report

    Directory of Open Access Journals (Sweden)

    Silva IvaniNovato

    2010-09-01

    Full Text Available Polyostotic fibrous dysplasia (FD associated to McCune-Albright Syndrome (MAS often leads to fractures, deformities, and bone pain resulting in bad quality of life. Parenteral bisphosphonates have been used in children and adolescents to improve these symptoms with few adverse effects. We evaluated the response to oral Alendronate in a girl with severe MAS FD and observed improved quality of life with reduction of bone pain.

  1. Oral histoplasmosis

    Directory of Open Access Journals (Sweden)

    Patil Karthikeya

    2009-01-01

    Full Text Available Histoplasmosis is a systemic fungal disease that takes various clinical forms, among which oral lesions are rare. The disseminated form of the disease that usually occurs in association with Human Immunodeficiency Virus (HIV is one of the AIDS-defining diseases. Isolated oral histoplasmosis, without systemic involvement, with underlying immunosuppression due to AIDS is very rare. We report one such case of isolated oral histoplasmosis in a HIV-infected patient.

  2. Partial oral treatment of endocarditis

    DEFF Research Database (Denmark)

    Iversen, Kasper; Høst, Nis Baun; Bruun, Niels Eske;

    2013-01-01

    Guidelines for the treatment of left-sided infective endocarditis (IE) recommend 4 to 6 weeks of intravenous antibiotics. Conversion from intravenous to oral antibiotics in clinically stabilized patients could reduce the side effects associated with intravenous treatment and shorten the length...... of hospital stay. Evidence supporting partial oral therapy as an alternative to the routinely recommended continued parenteral therapy is scarce, although observational data suggest that this strategy may be safe and effective....

  3. Golden Week: A Holiday Revolution

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ As one of the most important and far-reaching focal points in people's lives, the Golden-Week holiday, is much more than a year 21-day vacation. How did the Golden Week take shape over the past few years, gradually attracting people's attention, and having an increasingly important impact in China each year?

  4. Bisphosphonates inhibit the growth of Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum: a potential route to chemotherapy.

    Science.gov (United States)

    Martin, M B; Grimley, J S; Lewis, J C; Heath, H T; Bailey, B N; Kendrick, H; Yardley, V; Caldera, A; Lira, R; Urbina, J A; Moreno, S N; Docampo, R; Croft, S L; Oldfield, E

    2001-03-15

    We have investigated the effects in vitro of a series of bisphosphonates on the proliferation of Trypanosoma cruzi, Trypanosoma brucei rhodesiense, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum. The results show that nitrogen-containing bisphosphonates of the type used in bone resorption therapy have significant activity against parasites, with the aromatic species having in some cases nanomolar or low-micromolar IC(50) activity values against parasite replication (e.g. o-risedronate, IC(50) = 220 nM for T. brucei rhodesiense; risedronate, IC(50) = 490 nM for T. gondii). In T. cruzi, the nitrogen-containing bisphosphonate risedronate is shown to inhibit sterol biosynthesis at a pre-squalene level, most likely by inhibiting farnesylpyrophosphate synthase. Bisphosphonates therefore appear to have potential in treating parasitic protozoan diseases.

  5. Randomized Phase II Trial of Denosumab in Patients With Bone Metastases From Prostate Cancer, Breast Cancer, or Other Neoplasms After Intravenous Bisphosphonates

    National Research Council Canada - National Science Library

    Karim Fizazi; Allan Lipton; Xavier Mariette; Jean-Jacques Body; Yasmin Rahim; Julie R. Gralow; Guozhi Gao; Ling Wu; Winnie Sohn; Susie Jun

    2009-01-01

    .... We evaluated the effect of denosumab, a fully human monoclonal antibody against RANKL, in patients with bone metastases and elevated uNTx levels despite ongoing intravenous (IV) bisphosphonate (BP) therapy...

  6. Study of bisphosphonates by matrix-assisted laser desorption/ionization mass spectrometry--influence of alkali atoms on fragmentation patterns.

    Science.gov (United States)

    Guénin, Erwann; Lecouvey, Marc; Hardouin, Julie

    2009-05-01

    1-hydroxymethylene-1,1-bisphosphonic acids (or bisphosphonates) are compounds that have interesting pharmacological applications. However, few mass spectrometric investigations have been carried out to determine their fragmentation patterns. Herein, we evaluated different matrices for the study by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) of the formation and fragmentation of the protonated, the cationized (MNa+ and MK+) and the deprotonated bisphosphonates. Some in-source fragmentations were observed both in positive and in negative ion modes. The fragmentation patterns obtained in post-source decay mode are also discussed. In contrast to previous electrospray ionization/multi-stage mass spectrometry (ESI-MSn) studies, some new fragmentation pathways were deduced and the effects of alkali ions on the fragmentation patterns were shown. The results summarized here completed the data previously recorded by ESI-MSn and could be used for the characterization of bisphosphonates as alkali complexes in biological mixtures.

  7. Maintaining Restored Bone with Bisphosphonate in the Ovariectomized Rat Skeleton: Dynamic Histomorphometry of Changes in Bone Mass

    Science.gov (United States)

    Jee, W. S. S.; Tang, L.; Ke, H. Z.; Setterberg, R. B.; Kimmel, D. B.

    1993-01-01

    This experiment contains the crucial data for the Lose, Restore and Maintain (LRM) concept, a practical approach for reversing existing osteoporosis. The LRM concept uses ovariectomy (ox) to lose bone, an anabolic agent to restore bone mass and then switches to an antiresorptive agent to maintain bone mass. We ox'd or sham-ox'd rats for 150 days (Loss Phase), treated them with 6 mg PGE(sub 2)kg/d for 75 days to restore lost cancellous bone mass (Restore Phase) and then stopped PGE(sub 2) treatment and began treatment with 1 or 5 micrograms/kg Risedronate, a bisphosphonate twice a week for 60 days (Maintain Phase). During the Loss Phase, cancellous bone volumes of the Proximal Tibial Metaphysis (PTM) in the ox'd rat fell to 19% of initial controls. During the Restore Phase, the PTM bone volume in ox'd rats doubled. However, when PGE(sub 2) treatment was stopped, the PGE(sub 2)-induced cancellous bone disappeared. In contrast, 5 miligrams of Risedronate inhibited the bone loss and maintained it at the PGE(sub 2) treatment level. The key dynamic histomorphometry value for the Restore (R) and Maintenance (M) phases was the ratio of bone formation to resorption rates. The ratio was elevated to 5.8 in the R phase and depressed to 0.4 for no and 1 miligram Risedronate treated M phase and to a ratio of near unity of 1.1 for the 5miligrams Risedronate treatment. These findings indicate that we were successful in maintaining the new PTM bone induced by PGE(sub 2) after discontinuing PGE(sub 2) by administering enough Risedronate, a resorption inhibitor. We concluded that the LRM concept is correct and such an approach should be considered when employing anabolic agents or growth factors in the treatment of osteoporosis. Continued use of an anabolic agent may not be appropriate because of cost, potential adverse side effects and a loss of efficacy.

  8. Osteonecrose dos maxilares associada ao uso de bisfosfonatos: importante complicação do tratamento oncológico Bisphosphonate-associated jaws osteonecrosis: an important complication of oncology treatment

    Directory of Open Access Journals (Sweden)

    Marco Antonio T. Martins

    2009-02-01

    ideal therapy being the elimination of oral infections before treatment with bisphosphonates is initiated thereby attempting to minimize possible traumas to the mouth with the use of these medications.

  9. Imaging in Patients with Bisphosphonate-Associated Osteonecrosis of the Jaws (MRONJ

    Directory of Open Access Journals (Sweden)

    Britt-Isabelle Berg

    2016-09-01

    Full Text Available Background: Bisphosphonate-associated osteonecrosis of the jaws (MRONJ/BP-ONJ/BRONJ is a commonly seen disease. During recent decades, major advances in diagnostics have occurred. Once the clinical picture shows typical MRONJ features, imaging is necessary to determine the size of the lesion. Exposed bone is not always painful, therefore a thorough clinical examination and radiological imaging are essential when MRONJ is suspected. Methods: In this paper we will present the latest clinical update on the imaging options in regard to MRONJ: X-ray/Panoramic Radiograph, Cone Beam Computed Tomography (CBCT and Computed Tomography (CT, Magnetic Resonance Imaging (MRI, Nuclear Imaging, Fluorescence-Guided Bone Resection. Conclusion: Which image modality is chosen depends not only on the surgeon’s/practitioner’s preference but also on the available imaging modalities. A three-dimensional imaging modality is desirable, and in severe cases necessary, for extended resections and planning of reconstruction.

  10. Bone turnover in elderly females and males using bisphosphonate treatment-A pilot study

    Science.gov (United States)

    Gulson, B. L.; Mizon, K. J.; Smith, H.; Eisman, J.; Palmer, J. M.; Korsch, M. J.; Donnelly, J.; Waite, K.

    2003-05-01

    We undertook a 2 year pilot study in premenopausal and postmenopausal females and male partners in which the subjects were administered a bisphosphonate, alendronate, for 6 months. The aim ot the study was to determine how lead isotopes and lead concentrations changed in relation to bone remodelling processes. Each subject had blood and urine samples collected for markers of bone turnover and for lead isotope studies monthly for 7-9 months before and then 3 monthly during and for up to 6 months after treatment with alendronate as an agent for inhibiting bone resorption. There were significant decreases in the lead isotope ratio, ^{206}Pb/^{204}Pb, for the migrant subjects cluring treatment compared with thepre-treatment period (plead isotopic composition and lead concentration are consistent with a decrease m bone résorption and associated mobilisation of lead during alendronate therapy.

  11. Self-healing hybrid nanocomposites consisting of bisphosphonated hyaluronan and calcium phosphate nanoparticles.

    Science.gov (United States)

    Nejadnik, M Reza; Yang, Xia; Bongio, Matilde; Alghamdi, Hamdan S; van den Beucken, Jeroen J J P; Huysmans, Marie C; Jansen, John A; Hilborn, Jöns; Ossipov, Dmitri; Leeuwenburgh, Sander C G

    2014-08-01

    Non-covalent interactions are often regarded as insufficient to construct macroscopic materials of substantial integrity and cohesion. However, the low binding energy of such reversible interactions can be compensated by increasing their number to work in concert to create strong materials. Here we present the successful development of an injectable, cohesive nanocomposite hydrogel based on reversible bonds between calcium phosphate nanoparticles and bisphosphonate-functionalized hyaluronic acid. These nanocomposites display a capacity for self-healing as well as adhesiveness to mineral surfaces such as enamel and hydroxyapatite. Most importantly, these non-covalently cross-linked composites are surprisingly robust yet biodegradable upon extensive in vitro and in vivo testing and show bone interactive capacity evidenced by bone ingrowth into material remnants. The herein presented method provides a new methodology for constructing nanoscale composites for biomedical applications, which owe their integrity to reversible bonds.

  12. Esclerite associada ao uso de bisfosfonatos Scleritis related to the use of bisphosphonates

    Directory of Open Access Journals (Sweden)

    Ângelo Ferreira Passos

    2006-10-01

    Full Text Available Alertar para o fato de que os bisfosfonatos, importante classe de drogas utilizada no tratamento da osteoporose, podem causar esclerite. Relatamos caso de uma paciente que apresentou episódio de esclerite durante o uso de alendronato e que recidivou com o uso de outra droga da mesma classe, o risedronato, um ano depois. Os bisfosfonatos constituem uma classe de drogas que tem sido, frequentemente, utilizada no tratamento da osteoporose. No entanto, boa parte da classe médica pode não estar alerta para os efeitos colaterais oculares, tendo em vista que não se encontrou relato desses efeitos na literatura nacional. Este trabalho mostra dois episódios de esclerite, ocorridos em uma mesma paciente, com intervalo de, aproximadamente, um ano, possivelmente, provocados pelo uso de dois tipos de bisfosfonatos. Nas duas ocasiões, houve resposta favorável à suspensão da droga, com a utilização de um tratamento pouco agressivo. Esse fato justificou a não realização da pesquisa de doenças consideradas causas de esclerite, das quais a paciente não apresentava sinais, sintomas, assim como qualquer história pregressa. Tudo isso, associado à existência, na literatura internacional, de relatos de casos de inflamação ocular, inclusive de esclerite, relacionados com o uso dos bisfosfonatos, reforça a hipótese de que os episódios, realmente, tenham sido provocados pelo uso da droga.To alert to the fact that bisphosphonates, important class of drugs used in the treatment of osteoporosis, can cause scleritis. Report of a female patient’s case, who presented an episode of scleritis while using alendronate, and who had one year later another episode during the use of a drug from the same class, risedronate. The bisphosphonates are a class of drugs, which have been used very often in the treatment of osteoporosis. However, a great part of the physicians can not be alert for its ocular side effects, considering that in the national literature

  13. Bisphosphonate use in patients with lung cancer and bone metastases: recommendations of a European expert panel

    DEFF Research Database (Denmark)

    De Marinis, Filippo; Eberhardt, Wilfried; Harper, Peter G

    2009-01-01

    INTRODUCTION: Bisphosphonates (BPs) are effective in preventing, reducing the incidence, and delaying the onset of skeletal-related events in patients with bone metastases in a variety of solid tumors, including lung cancer. The purpose of this article is to review the current evidence for the use...... of BPs in lung cancer and to provide specific European recommendations to support the clinical practice of using BPs to treat patients with lung cancer with bone metastases. METHODS: An expert panel of European clinical oncologists and lung cancer specialists convened for two face-to-face meetings...... designed to review available evidence on the efficacy of BPs in lung cancer and to develop recommendations based on published literature and clinical practice experiences. RESULTS: The panel recommends screening patients with lung cancer for bone metastases at the initial staging of disease to assess...

  14. A Case of Autoimmune Hepatitis and Bisphosphonate-Related Osteonecrosis of the Jaw

    Directory of Open Access Journals (Sweden)

    Y.S. de Boer

    2012-05-01

    Full Text Available Autoimmune hepatitis (AIH is a chronic inflammatory liver disease of unknown aetiology usually requiring long-term immunosuppressive therapy. We present the case of an AIH patient who received long-term corticosteroids and azathioprine. As treatment for concomitant osteoporosis she was also treated with potent intravenous bisphosphonate (BP. This treatment was complicated by the development of BP-related osteonecrosis of the jaw (BRONJ. BRONJ is an uncommon complication of BP treatment regimes that occurs at increased frequency in the presence of other risk factors, including chronic inflammatory conditions. Our patient suffered from a severe and complicated clinical course of BRONJ which, despite adequate therapy, resulted in death of the patient. Here we discuss the risk factors for the development and clinical course of BRONJ in AIH and the implications for management of these patients.

  15. Utilization of bone densitometry for prediction and administration of bisphosphonates to prevent osteoporosis in patients with prostate cancer without bone metastases receiving antiandrogen therapy

    Directory of Open Access Journals (Sweden)

    Holt A

    2014-12-01

    Full Text Available Abby Holt,1 Muhammad A Khan,2 Swetha Gujja,3 Rangaswmy Govindarajan31Arkansas Department of Health, Little Rock, 2White River Health System, Batesville, 3Division of Hematology/Oncology, University of Arkansas for Medical Sciences, Little Rock, AR, USABackground: Prostate cancer subjects with prostate-specific antigen (PSA relapse who are treated with androgen deprivation therapy (ADT are recommended to have baseline and serial bone densitometry and receive bisphosphonates. The purpose of this community population study was to assess the utilization of bone densitometry and bisphosphonate therapy in men receiving ADT for non-metastatic prostate cancer.Methods: A cohort study of men aged 65 years or older with non-metastatic incident diagnoses of prostate cancer was obtained from the Surveillance Epidemiology End Results (SEER-linked Medicare claims between 2004 and 2008. Claims were used to assess prescribed treatment of ADT, bone densitometry, and bisphosphonates.Results: A total of 30,846 incident prostate cancer cases receiving ADT and aged 65 years or older had no bone metastases; 87.3% (n=26,935 on ADT did not receive either bone densitometry or bisphosphonate therapy. Three percent (n=931 of the cases on ADT received bisphosphonate therapy without ever receiving bone densitometry, 8.8% (n=2,702 of the cases on ADT received bone densitometry without receiving intravenous bisphosphonates, while nearly 1% (0.90%, n=278 of the cases on ADT received both bone densitometry and bisphosphonates. Analysis showed treatment differed by patient characteristics.Conclusion: Contrary to the recommendations, bone densitometry and bisphosphonate therapy are underutilized in men receiving ADT for non-metastatic prostate cancer.Keywords: prostatic neoplasms, androgen antagonists, bone densitometry, gonadotropin-releasing hormone, osteoporosis

  16. Bone turnover is adequately suppressed in osteoporotic patients treated with bisphosphonates in daily practice

    Directory of Open Access Journals (Sweden)

    Dijkmans Ben AC

    2011-07-01

    Full Text Available Abstract Background Monitoring osteoporosis therapy by measurement of bone turnover markers (BTMs might detect non-compliance in an earlier stage of anti-osteoporosis treatment and improve persistence. Methods BTMs were measured in two groups. The first group consisted of patients newly diagnosed with osteoporosis and starting treatment. We observed which proportion of patients had a decrease of serum levels of procollagen type 1 N-terminal propeptide (P1NP and C-terminal crosslinking telopeptide (CTX greater than the least significant change (LSC after 3 months of treatment. Secondly, we determined which proportion of patients who were treated with bisphosphonates for ≥ 3 months reached the biological goal of therapy, BTMs in the lower half of the normal premenopausal range. P1NP and CTX were also measured in a reference population of 34 healthy premenopausal women. Results In the first group 31 patients were included, in 25 patients (81% levels of both markers decreased with ≥ LSC, in the other patients a possible explanation was found. In the second group 95 patients were included, in 95% the serum P1NP levels and CTX levels were in the lower half of the premenopausal range. In 6 of the 7 patients with a level above the premenopausal range a possible explanation was found. Conclusion A decrease in bone turnover ≥ LSC can be observed in the majority of newly treated patients. In chronically treated patients, 95% have a bone turnover in the premenopausal range. In most patients with inadequate suppression of BTMs during bisphosphonate treatment, an explanation was found. Monitoring treatment effect with BTMs in daily practice is feasible, and might be an additive tool in improving therapy compliance.

  17. Effects of bisphosphonate treatment on DNA methylation in osteonecrosis of the jaw.

    Science.gov (United States)

    Polidoro, Silvia; Broccoletti, Roberto; Campanella, Gianluca; Di Gaetano, Cornelia; Menegatti, Elisa; Scoletta, Matteo; Lerda, Ennio; Matullo, Giuseppe; Vineis, Paolo; Berardi, Daniela; Scully, Crispian; Arduino, Paolo G

    2013-10-09

    Bisphosphonates are used in the treatment of hypocalcaemia, mainly in cancer and osteoporosis. Some patients experience adverse events, such as BP-related osteonecrosis of the jaw (BRONJ). DNA methylation plays a key role in gene regulation in many tissues, but its involvement in bone homeostasis is not well characterized, and no information is available regarding altered methylation in BRONJ. Using the Illumina Infinium HumanMethylation27 BeadChip assay, we performed an epigenome-wide association study in peripheral blood samples from 68 patients treated with nitrogenous BP, including 35 with BRONJ. Analysis of the estimated cumulative BP exposure distribution indicated that the exposure of the case group to BP was slightly higher than that of the control group; more severely affected cases (i.e., with BRONJ in both mandible and maxilla) were significantly more exposed to BP than were those with BRONJ only in the mandible or maxilla (one-sided Wilcoxon rank sum test, p=0.002). Logistic regression analysis confirmed the positive association between cumulative bisphosphonates exposure and risk of BRONJ (OR 1.015 per mg of cumulative exposure, 95% CI 1.004-1.032, p=0.036). Although no statistically significant differences were observed between case and control groups, methylation levels of probes mapping on three genes, ERCC8, LEPREL1 and SDC2, were strongly associated with cumulative BP exposure levels (p<1.31E-007). Enrichment analysis, combining differentially methylated genes with genes involved in the mevalonate pathway, showed that BP treatment can affect the methylation pattern of genes involved in extracellular matrix organization and inflammatory responses, leading to more frequent adverse effects such as BRONJ. Differences in DNA methylation induced by BP treatment could be involved in the pathogenesis of the bone lesion.

  18. Once weekly azithromycin in secondary prevention of rheumatic fever.

    Science.gov (United States)

    Gopal, Rakesh; Harikrishnan, S; Sivasankaran, S; Ajithkumar, V K; Titus, T; Tharakan, J M

    2012-01-01

    Rheumatic fever and rheumatic heart disease (RHD) are still important problems in developing countries. Secondary prophylaxis which is the most cost-effective method in preventing recurrences of rheumatic fever is fraught with problems of drug compliance. The utility of 500 mg once weekly azithromycin (AZT), an orally effective long-acting antibiotic was evaluated against oral penicillin (phenoxy methyl penicillin 250 mg twice daily) in this study. Forty-eight consecutive patients (44% males, mean age 29.4 years) with established RHD were randomised into two groups-26 patients received AZT and 22 received oral penicillin. Patients were evaluated at randomisation, at 1 month, 3 months, and 6 months, clinically, serologically and by throat swab culture. End points were absence of streptococcal colonisation, infection or fever at the end of 6 months. During the study, 4 patients (15.4%) in the AZT group developed sore throat and fever, had positive throat culture and positive serology indicating streptococcal infection. None satisfied the criteria for rheumatic fever reactivation. None in the oral penicillin group developed streptococcal infection. In conclusion, weekly 500 mg of AZT is not effective in the prevention of streptococcal throat infection compared to oral penicillin therapy in adult patients with established RHD.

  19. Oral leukoplakia

    DEFF Research Database (Denmark)

    Holmstrup, Palle; Dabelsteen, Erik

    2016-01-01

    The idea of identifying oral lesions with a precancerous nature, i.e. in the sense of pertaining to a pathologic process with an increased risk for future malignant development, of course is to prevent frank malignancy to occur in the affected area. The most common oral lesion with a precancerous...... nature is oral leukoplakia, and for decades it has been discussed how to treat these lesions. Various treatment modalities, such as systemic therapies and surgical removal, have been suggested. The systemic therapies tested so far include retinoids, extracts of green tea, inhibitors of cyclooxygenase-2...

  20. Short-term bisphosphonate treatment reduces serum 25(OH) vitamin D3 and alters values of parathyroid hormone, pentosidine, and bone metabolic markers

    Science.gov (United States)

    Kamimura, Mikio; Uchiyama, Shigeharu; Nakamura, Yukio; Ikegami, Shota; Mukaiyama, Keijiro; Kato, Hiroyuki

    2017-01-01

    This study aimed to clarify the effects of short-term bisphosphonate (BP) administration in Japanese osteoporotic patients retrospectively. Daily minodronate (MIN) at 1 mg/day (MIN group) or weekly risedronate (RIS) at 17.5 mg/week (RIS group) was primarily prescribed for each patient. We analyzed the laboratory data of 35 cases (18 of MIN and 17 of RIS) before the start of treatment and at 4 months afterward. The changes in 25(OH)D3, whole parathyroid hormone (PTH), serum pentosidine, and the bone turnover markers urinary cross-linked N-telopeptide of type I collagen (NTX), serum tartrate-resistant acid phosphatase (TRACP)-5b, bone-specific alkaline phosphatase (BAP), and undercarboxylated osteocalcin were evaluated. Overall, serum 25(OH)D3 was significantly decreased from 21.8 to 18.4 ng/mL at 4 months, with a percent change of −14.7%. Whole PTH increased significantly from 23.4 to 30.0 pg/mL, with a percent change of 32.1%. Serum pentosidine rose from 0.0306 to 0.0337 μg/mL, with a percent change of 15.2%. In group comparisons, 25(OH)D3 and pentosidine showed comparable changes in both groups after 4 months of treatment, whereas whole PTH became significantly more increased in the MIN group. All bone turnover markers were significantly decreased at 4 months in both groups. Compared with the RIS group, the MIN group exhibited significantly larger value changes for urinary NTX, serum TRACP-5b, and BAP at the study end point. This study demonstrated that serum 25(OH)D3 became significantly decreased after only 4 months of BP treatment in Japanese osteoporotic patients and confirmed that MIN more strongly inhibited bone turnover as compared with RIS.

  1. Modulation of murine bone marrow-derived CFU-F and CFU-OB by in vivo bisphosphonate and fluoride treatments.

    Science.gov (United States)

    Chou, M-Y; Yan, D; Jafarov, T; Everett, E T

    2009-05-01

    Bisphosphonates (BPN) have actions on a variety of cell types including: osteoclasts, osteoblasts, osteocytes, and endothelial cells. The objectives of this report are to review the current state of understanding of the effects of BPNs on orthodontic tooth movement and to provide evidence on BPN's in vivo effects on bone marrow-derived osteoprogenitor cells. Mice from the C3H/HeJ (C3H), C57BL/6J (B6), FVB/NJ (FVB), and BALB/cByJ (BALB) strains were treated for 3 weeks with 0, 3, 30, or 150 mcg/kg/week alendronate (ALN) administered subcutaneous alone or in combination with 50 ppm fluoride (F). Bone marrow cells were harvested and subjected to in vitro colony-forming unit fibroblast (CFU-F) and colony-forming unit osteoblasts (CFU-OB) assays. Baseline differences in CFU-F, CFU-OB/ALP+, and CFU-OB/total were observed among the four strains. Strain-specific responses to ALN and F treatments were observed for CFU-F, CFU-OB/ALP+, and CFU-OB/total. F treatment alone resulted in decreases in CFU-F (p = 0.013), CFU-OB/ALP+ (p = 0.005), and CFU-OB/total (p = 0.003) in the C3H strain. CFU-F (p = 0.036) were decreased by F in the B6 strain. No significant (NS) effects of F were observed for FVB and BALB. ALN treatment resulted in a significant decrease in CFU-F (p = 0.0014) and CFU-OB/total (p = 0.028) in C3H only. ALN treatment had NS effect on CFU-OB/ALP+ in all four strains. Genetic factors appear to play a role in ALN's effects on CFU-F and CFU-OB/total but not on CFU-OB/ALP+.

  2. PHOSPHONYLATION DES COMPOSES A LIAISONS C=X : ACCES AUX Bis-PHOSPHONATES ET ETUDES DE LEURS DE LEURS FONCTIONNALISATIOS.

    OpenAIRE

    EPENIT, MONDJO RODY-DAVY

    2014-01-01

    Dans ce travail, consacré aux bis-phosphonates et iminophosphonates, nous avons tout d'abord, commencé par reproduire un travail sur les bis-phosphonates. Cette opération est bien réussie. Nous avons amélioré cette méthode, en utilisant un processus avec un minimum d'étape. Elle consiste à utiliser les ?-aminoacides sans recours à la protection. Ceci nous fait gagner deux étapes, puisque nous n'aurons pas à débloquer en fin de réaction. C'est à partir de cette méthode que la suite de nos trav...

  3. Topical erythropoietin as a novel preventive and therapeutic agent in bisphosphonate-related osteonecrosis of the jaw

    Directory of Open Access Journals (Sweden)

    Pantea Nazeman

    2016-01-01

    Full Text Available Introduction: One of the most common side effects of bisphosphonate intake is osteonecrosis of the jaw (ONJ which may develop following dentoalveolar interventions. Despite the vast available protocols, there is no clear guideline in the management of this condition. In osteonecrosis, the number and proliferation of bone-forming cells as well as vascularity are disturbed. Erythropoietin (EPO is a hematopoietic hormone with angiogenic, osteogenic, and antiapoptotic properties. The Hypothesis: It is suggested to utilize poly lactic-co-glycolic acid hydrogel containing 1500-3000 IU/kg EPO following dentoalveolar surgery in samples receiving bisphosphonates as a preventive or therapeutic agent. Evaluation of the Hypothesis: Considering the pathophysiology of ONJ and therapeutic properties of EPO, it is assumed that EPO may be effective in treatment of ONJ. Furthermore, as a preventive measure, utilizing EPO following dentoalveolar surgery may be beneficial in the patients at risk of ONJ.

  4. Synthesis and preliminary pharmacological characterisation of a new class of nitrogen-containing bisphosphonates (N-BPs).

    Science.gov (United States)

    Lolli, Marco L; Rolando, Barbara; Tosco, Paolo; Chaurasia, Shilpi; Di Stilo, Antonella; Lazzarato, Loretta; Gorassini, Eva; Ferracini, Riccardo; Oliaro-Bosso, Simonetta; Fruttero, Roberta; Gasco, Alberto

    2010-04-01

    A new series of bisphosphonates bearing either the nitrogen-containing NO-donor furoxan (1,2,5-oxadiazole 2-oxide) system or the related furazan (1,2,5-oxadiazole) in lateral chain has been developed. pK(a) values and affinity for hydroxyapatite were determined for all the compounds. The products were able to inhibit osteoclastogenesis on RAW 246.7 cells at 10microM concentration. The most active compounds were further assayed on human PBMC cells and on rat microsomes. Unlike most nitrogen-containing bisphosphonates which target farnesyl pyrophosphate synthase, experimental and theoretical investigations suggest that the activity of our derivatives may be related to different mechanisms. The furoxan derivatives were also tested for their ability to relax rat aorta strips in view of their potential NO-dependent vasodilator properties.

  5. Oral pathology.

    Science.gov (United States)

    Niemiec, Brook A

    2008-05-01

    Oral disease is exceedingly common in small animal patients. In addition, there is a very wide variety of pathologies that are encountered within the oral cavity. These conditions often cause significant pain and/or localized and systemic infection; however, the majority of these conditions have little to no obvious clinical signs. Therefore, diagnosis is not typically made until late in the disease course. Knowledge of these diseases will better equip the practitioner to effectively treat them. This article covers the more common forms of oral pathology in the dog and cat, excluding periodontal disease, which is covered in its own chapter. The various pathologies are presented in graphic form, and the etiology, clinical signs, recommended diagnostic tests, and treatment options are discussed. Pathologies that are covered include: persistent deciduous teeth, fractured teeth, intrinsically stained teeth, feline tooth resorption, caries, oral neoplasia, eosinophilic granuloma complex, lymphoplasmacytic gingivostomatitis, enamel hypoplasia, and "missing" teeth.

  6. Herpes - oral

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000606.htm Herpes - oral To use the sharing features on this page, ... 374. Read More Atopic dermatitis Cancer Fever Genital herpes Mouth ulcers Vesicles Review Date 8/14/2015 Updated ...

  7. Structural and thermodynamic basis of the inhibition of Leishmania major farnesyl diphosphate synthase by nitrogen-containing bisphosphonates

    Energy Technology Data Exchange (ETDEWEB)

    Aripirala, Srinivas [Johns Hopkins University, 725 North Wolfe Street WBSB 605, Baltimore, MD 21210 (United States); Gonzalez-Pacanowska, Dolores [López-Neyra Institute of Parasitology and Biomedicine, 18001 Granada (Spain); Oldfield, Eric [University of Illinois at Urbana-Champaign, Urbana, IL 61801 (United States); Kaiser, Marcel [University of Basel, Petersplatz 1, CH-4003 Basel (Switzerland); Amzel, L. Mario, E-mail: mamzel@jhmi.edu [Johns Hopkins University School of Medicine, 725 N. Wolfe Street WBSB 604, Baltimore, MD 21205 (United States); Gabelli, Sandra B., E-mail: mamzel@jhmi.edu [Johns Hopkins University School of Medicine, 725 N. Wolfe Street WBSB 604, Baltimore, MD 21205 (United States); Johns Hopkins University School of Medicine, Baltimore, MD 21205 (United States); Johns Hopkins University, 725 North Wolfe Street WBSB 605, Baltimore, MD 21210 (United States)

    2014-03-01

    Structural insights into L. major farnesyl diphosphate synthase, a key enzyme in the mevalonate pathway, are described. Farnesyl diphosphate synthase (FPPS) is an essential enzyme involved in the biosynthesis of sterols (cholesterol in humans and ergosterol in yeasts, fungi and trypanosomatid parasites) as well as in protein prenylation. It is inhibited by bisphosphonates, a class of drugs used in humans to treat diverse bone-related diseases. The development of bisphosphonates as antiparasitic compounds targeting ergosterol biosynthesis has become an important route for therapeutic intervention. Here, the X-ray crystallographic structures of complexes of FPPS from Leishmania major (the causative agent of cutaneous leishmaniasis) with three bisphosphonates determined at resolutions of 1.8, 1.9 and 2.3 Å are reported. Two of the inhibitors, 1-(2-hydroxy-2,2-diphosphonoethyl)-3-phenylpyridinium (300B) and 3-butyl-1-(2,2-diphosphonoethyl)pyridinium (476A), co-crystallize with the homoallylic substrate isopentenyl diphosphate (IPP) and three Ca{sup 2+} ions. A third inhibitor, 3-fluoro-1-(2-hydroxy-2,2-diphosphonoethyl)pyridinium (46I), was found to bind two Mg{sup 2+} ions but not IPP. Calorimetric studies showed that binding of the inhibitors is entropically driven. Comparison of the structures of L. major FPPS (LmFPPS) and human FPPS provides new information for the design of bisphosphonates that will be more specific for inhibition of LmFPPS. The asymmetric structure of the LmFPPS–46I homodimer indicates that binding of the allylic substrate to both monomers of the dimer results in an asymmetric dimer with one open and one closed homoallylic site. It is proposed that IPP first binds to the open site, which then closes, opening the site on the other monomer, which closes after binding the second IPP, leading to the symmetric fully occupied FPPS dimer observed in other structures.

  8. Bisphosphonate inhibitors reveal a large elasticity of plastidic isoprenoid synthesis pathway in isoprene-emitting hybrid aspen.

    Science.gov (United States)

    Rasulov, Bahtijor; Talts, Eero; Kännaste, Astrid; Niinemets, Ülo

    2015-06-01

    Recently, a feedback inhibition of the chloroplastic 1-deoxy-D-xylulose 5-phosphate (DXP)/2-C-methyl-D-erythritol 4-phosphate (MEP) pathway of isoprenoid synthesis by end products dimethylallyl diphosphate (DMADP) and isopentenyl diphosphate (IDP) was postulated, but the extent to which DMADP and IDP can build up is not known. We used bisphosphonate inhibitors, alendronate and zoledronate, that inhibit the consumption of DMADP and IDP by prenyltransferases to gain insight into the extent of end product accumulation and possible feedback inhibition in isoprene-emitting hybrid aspen (Populus tremula × Populus tremuloides). A kinetic method based on dark release of isoprene emission at the expense of substrate pools accumulated in light was used to estimate the in vivo pool sizes of DMADP and upstream metabolites. Feeding with fosmidomycin, an inhibitor of DXP reductoisomerase, alone or in combination with bisphosphonates was used to inhibit carbon input into DXP/MEP pathway or both input and output. We observed a major increase in pathway intermediates, 3- to 4-fold, upstream of DMADP in bisphosphonate-inhibited leaves, but the DMADP pool was enhanced much less, 1.3- to 1.5-fold. In combined fosmidomycin/bisphosphonate treatment, pathway intermediates accumulated, reflecting cytosolic flux of intermediates that can be important under strong metabolic pull in physiological conditions. The data suggested that metabolites accumulated upstream of DMADP consist of phosphorylated intermediates and IDP. Slow conversion of the huge pools of intermediates to DMADP was limited by reductive energy supply. These data indicate that the DXP/MEP pathway is extremely elastic, and the presence of a significant pool of phosphorylated intermediates provides an important valve for fine tuning the pathway flux.

  9. Bisphosphonates in the adjuvant treatment of young women with breast cancer: the estrogen rich is a poor candidate!

    OpenAIRE

    Azim, Hamdy A.; Kamal, Nermine S.; Malak, Rafaat A.

    2013-01-01

    During the last 2 decades the role of bisphosphonates (BPs) to reduce skeletal-related events from bone metastases in breast cancer has been well defined. Several preclinical studies have strongly suggested that BPs may also provide an anti-cancer effect in early breast cancer. Indeed, the use of adjuvant BPs represents a unique approach that attempts at eradicating occult tumor micro-metastases residing in the bone marrow via targeting the bone microenvironment to render it less favorable fo...

  10. Disparities in Oral Health

    Science.gov (United States)

    ... 2020: Oral Health Objectives Site Map Disparities in Oral Health Recommend on Facebook Tweet Share Compartir Oral health ... to get and keep dental insurance. Disparities in Oral Health Some of the oral health disparities that exist ...

  11. The ATLAS Glasgow Overview Week

    CERN Multimedia

    Richard Hawkings

    2007-01-01

    The ATLAS Overview Weeks always provide a good opportunity to see the status and progress throughout the experiment, and the July week at Glasgow University was no exception. The setting, amidst the traditional buildings of one of the UK's oldest universities, provided a nice counterpoint to all the cutting-edge research and technology being discussed. And despite predictions to the contrary, the weather at these northern latitudes was actually a great improvement on the previous few weeks in Geneva. The meeting sessions comprehensively covered the whole ATLAS project, from the subdetector and TDAQ systems and their commissioning, through to offline computing, analysis and physics. As a long-time ATLAS member who remembers plenary meetings in 1991 with 30 people drawing detector layouts on a whiteboard, the hardware and installation sessions were particularly impressive - to see how these dreams have been translated into 7000 tons of reality (and with attendant cabling, supports and services, which certainly...

  12. Clinical Aspects, Imaging Features, and Considerations on Bisphosphonate-Related Osteonecrosis Risk in a Pediatric Patient with Osteogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Fábio Wildson Gurgel Costa

    2014-01-01

    Full Text Available Osteogenesis imperfecta (OI is a rare hereditary condition caused by changes in collagen metabolism. It is classified into four types according to clinical, genetic, and radiological criteria. Clinically, bone fragility, short stature, blue sclerae, and locomotion difficulties may be observed in this disease. OI is often associated to severe dental problems, such as dentinogenesis imperfecta (DI and malocclusions. Radiographically, affected teeth may have crowns with bulbous appearance, accentuated constriction in the cementoenamel junction, narrowed roots, large root canals due to defective dentin formation, and taurodontism (enlarged pulp chambers. There is no definitive cure, but bisphosphonate therapy is reported to improve bone quality; however, there is a potential risk of bisphosphonate-related osteonecrosis of the jaw. In this study we report a case of OI in a male pediatric patient with no family history of OI who was receiving ongoing treatment with intravenous perfusion of bisphosphonate and who required dental surgery. In addition, we discussed the clinical and imaging findings and briefly reviewed the literature.

  13. Impact of Soft Tissue Pathophysiology in the Development and Maintenance of Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ

    Directory of Open Access Journals (Sweden)

    Thomas Ziebart

    2016-10-01

    Full Text Available Since the first description of bisphosphonate-related osteonecrosis of the jaw (BRONJ, numerous research groups have focused on possible pathological mechanisms including the suppression of the bone turnover of the jaw, antiangiogenic effects and soft tissue toxicity. In our review we focused on summarizing the role of the soft tissues in the development and progression of BRONJ. The biological behavior of fibroblasts can be significantly influenced by bisphosphonates (BP such as a concentration dependent reduction of cell viability. High concentrations of BP can induce apoptosis and necrosis of the cells. Comparable effects could be detected for keratinocytes. Compared to non-nitrogen containing bisphosphonates, nitrogen-containing BP have worse effects on cell biology by blocking the mevalonate pathway. Further, the cell architecture and expression levels of several genes and proteins are significantly disturbed by BP. These inhibitory effects of BP are in accordance with BP-related reduced angiogenesis and neovascularization and could underline the hypothesis that inhibition of fibroblasts and keratinocytes results in delayed wound healing and can induce and trigger BRONJ.

  14. Bones, breasts, and bisphosphonates: rationale for the use of zoledronic acid in advanced and early breast cancer

    Directory of Open Access Journals (Sweden)

    Allan Lipton

    2011-03-01

    Full Text Available Allan LiptonMilton S. Hershey Medical Center, Pennsylvania State University, Hershey, PA, USAAbstract: Bisphosphonates inhibit osteoclast-mediated bone resorption, thereby inhibiting the release of growth factors necessary to promote cancer cell growth, differentiation, and tumor formation in bone. These agents have demonstrated efficacy for delaying the onset and reducing the incidence of skeletal-related events in the advanced breast cancer setting, and have been shown to prevent cancer therapy-induced bone loss in the early breast cancer setting. Emerging clinical data indicate that the role of bisphosphonates in advanced and early breast cancer is evolving. Retrospective analyses and recent clinical trial data show that zoledronic acid may improve outcomes in some patients with breast cancer. Data from ABCSG-12 and ZO-FAST suggest that zoledronic acid may improve disease-free survival in the adjuvant breast cancer setting in postmenopausal women or women with endocrine therapy-induced menopause, and recent data from a predefined subset of the AZURE trial added to the anticancer story. However, the overall negative AZURE trial also raises questions about the role of bisphosphonates as an anticancer agent in patients with breast cancer. Overall, these data suggest that the addition of zoledronic acid to established anticancer regimens may have potential anticancer benefits in specific patient populations, although more studies are required to define its role.Keywords: anticancer, adjuvant therapy, bone metastasis, skeletal, zoledronic acid

  15. Progestin-Only Oral Contraceptives

    Science.gov (United States)

    Nor-Q.D.® ... only oral contraceptives are safe for use by breast-feeding mothers. If you are fully breastfeeding (not ... 6 weeks after delivery. If you are partially breast-feeding (giving your baby some food or formula), ...

  16. Fashion Week Illumes Fashion Life

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Nine days, 46 domestic and overseas brands, 30 designers from China and abroad, 41 fashion shows, six professional fashion design competitions, as well as ten press conferences and fashion forums, this is the menu of Mercedes-Benz China Fashion Week (A/W 2012/2013) this March.

  17. Structure of human farnesyl pyrophosphate synthase in complex with an aminopyridine bisphosphonate and two molecules of inorganic phosphate

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jaeok [McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1Y6 (Canada); Lin, Yih-Shyan [McGill University, 801 Rue Sherbrooke Ouest, Montreal, QC H3A 0B8 (Canada); Tsantrizos, Youla S. [McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1Y6 (Canada); McGill University, 801 Rue Sherbrooke Ouest, Montreal, QC H3A 0B8 (Canada); McGill University, 3649 Promenade Sir William Osler, Montreal, QC H3G 0B1 (Canada); Berghuis, Albert M., E-mail: albert.berghuis@mcgill.ca [McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1Y6 (Canada); McGill University, 3649 Promenade Sir William Osler, Montreal, QC H3G 0B1 (Canada); McGill University, 3775 Rue University, Montreal, QC H3A 2B4 (Canada)

    2014-02-19

    A co-crystal structure of human farnesyl pyrophosphate synthase in complex with an aminopyridine bisphosphonate, YS0470, and two molecules of inorganic phosphate has been determined. The identity of the phosphate ligands was confirmed by anomalous diffraction data. Human farnesyl pyrophosphate synthase (hFPPS) produces farnesyl pyrophos@@phate, an isoprenoid essential for a variety of cellular processes. The enzyme has been well established as the molecular target of the nitrogen-containing bisphosphonates (N-BPs), which are best known for their antiresorptive effects in bone but are also known for their anticancer properties. Crystal structures of hFPPS in ternary complexes with a novel bisphosphonate, YS0470, and the secondary ligands inorganic phosphate (P{sub i}), inorganic pyrophosphate (PP{sub i}) and isopentenyl pyrophosphate (IPP) have recently been reported. Only the co-binding of the bisphosphonate with either PP{sub i} or IPP resulted in the full closure of the C-@@terminal tail of the enzyme, a conformational change that is required for catalysis and that is also responsible for the potent in vivo efficacy of N-BPs. In the present communication, a co-crystal structure of hFPPS in complex with YS0470 and two molecules of P{sub i} is reported. The unusually close proximity between these ligands, which was confirmed by anomalous diffraction data, suggests that they interact with one another, with their anionic charges neutralized in their bound state. The structure also showed the tail of the enzyme to be fully disordered, indicating that simultaneous binding of two P{sub i} molecules with a bisphosphonate cannot induce the tail-closing conformational change in hFPPS. Examination of homologous FPPSs suggested that this ligand-dependent tail closure is only conserved in the mammalian proteins. The prevalence of P{sub i}-bound hFPPS structures in the PDB raises a question regarding the in vivo relevance of P{sub i} binding to the function of the enzyme.

  18. Outcome of Long-Term Bisphosphonate Therapy in McCune-Albright Syndrome and Polyostotic Fibrous Dysplasia.

    Science.gov (United States)

    Majoor, Bas Cj; Appelman-Dijkstra, Natasha M; Fiocco, Martha; van de Sande, Michiel Aj; Dijkstra, Pd Sander; Hamdy, Neveen At

    2017-02-01

    McCune-Albright syndrome (MAS) is a rare bone disorder characterized by fibrous dysplasia (FD), endocrinopathies, and café-au-lait patches. FD patients have been shown to respond favorably to treatment with bisphosphonates, but data are scarce in the more severe polyostotic form (PFD), including MAS, and factors determining treatment outcome are not known, particularly in the long-term. We evaluated the biochemical (bone turnover markers [BTMs]) and clinical (pain reduction) outcome of bisphosphonate therapy in 11 patients with MAS and 30 patients with PFD: median duration of treatment 6 years (range, 2 to 25 years). Prognostic factors for treatment outcome were identified in both groups. Patients with MAS were younger at diagnosis (p = 0.001), all had precocious puberty, and four (36%) had additional growth hormone (GH) excess associated with severe craniofacial FD. Extent of skeletal disease was more severe in MAS compared to PFD. MAS patients had higher serum alkaline phosphatase (ALP) concentrations (p = 0.005), higher skeletal burden scores (p < 0.001), and more fractures (p = 0.021). MAS patients had also higher levels of FGF-23 (p = 0.008) and higher prevalence of hypophosphatemia (p = 0.013). Twenty-four of 30 PFD patients (80%) demonstrated a complete clinical and biochemical response within a year of starting treatment (p = 0.015), compared to only four of 11 MAS patients (36%). There were no nonresponders. In the whole group, FGF-23, total ALP, P1NP, and CTX positively correlated with skeletal burden scores (all p ≤ 0.001), which was the only significant risk factor for an incomplete response to bisphosphonate therapy (p < 0.01). Our data suggest a beneficial and safe outcome of long-term bisphosphonate therapy in the majority of patients with PFD, although response to therapy was limited by the higher skeletal disease burden in MAS patients. In the PFD/MAS population studied, the only identified prognostic factor

  19. Oral manifestations of McCune-Albright syndrome.

    Science.gov (United States)

    Aravinda, Konidena; Ratnakar, Pamula; Srinivas, Kandakurti

    2013-01-01

    McCune- Albright Syndrome (MAS) is a rare fibrosseous lesion, characterized by a classic triad of polyostotic fibrous dysplasia (PFD), café -au-lait macules (CALM) and underlying endocrinopathies. We present the oral findings of an interesting case of MAS with relevant review of literature. A 30-year-old male presented to us with swelling of both jaws over a period of two years. Cutaneous examination revealed café - au - lait macule over the back, crossing the midline. Skeletal survey showed expansile, osteolytic, mixed radiolucent- radiopaque lesions in skull and jaw bones. Serum alkaline phosphatase was elevated (388 IU/L), with normal calcium, phosphorus, parathyroid hormone and 25 hydroxy vitamin D levels. Diagnosis of McCune- Albright syndrome was made and he was treated with parenteral bisphosphonates (intravenous Zoledronate 4 mg) and is under follow up for surgical recontouring of the jaws. Early recognition facilitates better treatment and improves prognosis by reducing the morbidity.

  20. Oral candidiasis.

    Science.gov (United States)

    Millsop, Jillian W; Fazel, Nasim

    2016-01-01

    Oral candidiasis (OC) is a common fungal disease encountered in dermatology, most commonly caused by an overgrowth of Candida albicans in the mouth. Although thrush is a well-recognized presentation of OC, it behooves clinicians to be aware of the many other presentations of this disease and how to accurately diagnose and manage these cases. The clinical presentations of OC can be broadly classified as white or erythematous candidiasis, with various subtypes in each category. The treatments include appropriate oral hygiene, topical agents, and systemic medications. This review focuses on the various clinical presentations of OC and treatment options.

  1. Oral myiasis

    Directory of Open Access Journals (Sweden)

    Treville Pereira

    2010-01-01

    Full Text Available Myiasis is a relatively rare condition arising from the invasion of body tissues or cavities of living animals or humans by maggots or larvae of certain species of flies. It is an uncommon clinical condition, being more frequent in underdeveloped countries and hot climate regions, and is associated with poor hygiene, suppurative oral lesions; alcoholism and senility. Its diagnosis is made basically by the presence of larvae. The present article reports a case of oral myiasis involving 20 larvae in a patient with neurological deficiency.

  2. ATLAS Overview Week at Brookhaven

    CERN Multimedia

    Pilcher, J

    Over 200 ATLAS participants gathered at Brookhaven National Laboratory during the first week of June for our annual overview week. Some system communities arrived early and held meetings on Saturday and Sunday, and the detector interface group (DIG) and Technical Coordination also took advantage of the time to discuss issues of interest for all detector systems. Sunday was also marked by a workshop on the possibilities for heavy ion physics with ATLAS. Beginning on Monday, and for the rest of the week, sessions were held in common in the well equipped Berkner Hall auditorium complex. Laptop computers became the norm for presentations and a wireless network kept laptop owners well connected. Most lunches and dinners were held on the lawn outside Berkner Hall. The weather was very cooperative and it was an extremely pleasant setting. This picture shows most of the participants from a view on the roof of Berkner Hall. Technical Coordination and Integration issues started the reports on Monday and became a...

  3. Bisphosphonate binding affinity as assessed by inhibition of carbonated apatite dissolution in vitro

    Science.gov (United States)

    Henneman, Zachary J.; Nancollas, George H.; Ebetino, F. Hal; Russell, R. Graham G.; Phipps, Roger J.

    2009-01-01

    Bisphosphonates (BPs), which display a high affinity for calcium phosphate surfaces, are able to selectively target bone mineral, where they are potent inhibitors of osteoclast-mediated bone resorption. The dissolution of synthetic hydroxyapatite (HAP) has been used previously as a model for BP effects on natural bone mineral. The present work examines the influence of BPs on carbonated apatite (CAP), which mimics natural bone more closely than does HAP. Constant composition dissolution experiments were performed at pH 5.50, physiological ionic strength (0.15M) and temperature (37°C). Selected BPs were added at (0.5 × 10−6) to (50.0 × 10−6)M, and adsorption affinity constants, KL, were calculated from the kinetics data. The BPs showed concentration-dependent inhibition of CAP dissolution, with significant differences in rank order zoledronate > alendronate > risedronate. In contrast, for HAP dissolution at pH 5.50, the differences between the individual BPs were considerably smaller. The extent of CAP dissolution was also dependent on the relative undersaturation, σ, and CAP dissolution rates increased with increasing carbonate content. These results demonstrate the importance of the presence of carbonate in mediating the dissolution of CAP, and the possible involvement of bone mineral carbonate in observed differences in bone affinities of BPs in clinical use. PMID:17907244

  4. Aspects of osseous, peritoneal and renal handling of bisphosphonate during peritoneal dialysis: a methodological study

    DEFF Research Database (Denmark)

    Joffe, P; Henriksen, Jens Henrik

    1996-01-01

    to continuous ambulatory peritoneal dialysis (CAPD). The aims were: to assess the kinetics of 99m-technetium MBP (99mTc-MBP) in CAPD, and to evaluate the correctness of the assumption that the peritoneal and renal clearances of 99mTc-MBP equal the total plasma clearance of 51-chromium ethylenediamine tetra......-acetic acid (51Cr-EDTA). Eight patients on CAPD were studied cross-sectionally. The mean plasma clearances of 99mTc-MBP and 51Cr-EDTA in the steady state (4h) were 38.2 and 12.2 ml min-1 (p peritoneal clearances (0-4 h) were 5.2 and 7.2 ml min-1 (p ....5 and 2.8 ml min-1 (not significant), respectively. The bone bisphosphonate clearance (BBC) at steady state was 26.0 ml min-1, a value which was significantly higher than that at infinity (16.5 ml min-1, p peritoneal and renal clearances of 99m...

  5. Ozone therapy in the treatment of avascular bisphosphonate-related jaw osteonecrosis.

    Science.gov (United States)

    Agrillo, Allesandro; Ungari, Claudio; Filiaci, Fabio; Priore, Paolo; Iannetti, Giorgio

    2007-09-01

    Avascular osteonecrosis of the jaw (ONJ) may occur as a consequence of several conditions, even including chemotherapy treatment in patients affected by tumors or osteoporosis. We report our clinical experience in treating bisphosphonate-induced ONJ with a therapeutic methodology that includes ozone therapy as a new and original approach for the clinical management of maxillary necrotic lesions. Of 58 patients with ONJ observed at our department, 33 gave their informed consent to be part of the research and were treated according to a therapeutic approach, which included noninvasive surgery associated with pre- and postsurgical cycles of ozone therapy consisting of eight sessions lasting 3 minutes each besides antibiotic and antifungal therapies. Outcomes showed how ozone therapy increases the benefits of surgical and pharmacologic treatments, increasing the complete healing of the lesions with the disappearance of symptoms and brings cases of lesion progression down to zero. In conclusion, ozone therapy is a reliable presidium in treatment of ONJ; its benefits are remarkable and improve significantly the outcomes of the surgical approach.

  6. Perspectives in the elderly patient: benefits and limits of bisphosphonates and denosumab.

    Science.gov (United States)

    Santini, Daniele; Fratto, Maria Elisabetta; Aapro, Matti

    2012-01-01

    Skeletal metastases affect a large percentage of the cancer population and contribute to a marked decrease in their quality of life and survival, in particular in elderly population. A future end-point of bone-protecting therapy is the demonstration of its ability to prevent or improve results in the treatment of metastatic disease, enlarging their clinical indications in metastatic and osteoporotic setting with different schedules. In this chapter we will discuss on pharmacokinetic and pharmacodynamic interactions of bisphosphonates in elderly, and the preclinical and clinical evidences of anticancer activity of bone-targeted therapies will be critically described. The clinical results of new targeted therapies (such as rank/rankl/OPG inhibition) will be reported both in bone metastatic and in adjuvant settings. Finally, the prevention of cancer treatment-induced bone loss (CTIBL) represents both in young and more in old patients an emerging issue in the bone health care. For this reason, this chapter will discuss the results of current therapies in this clinical setting.

  7. Medical treatment of breast cancer bone metastasis: from bisphosphonates to targeted drugs.

    Science.gov (United States)

    Erdogan, Bulent; Cicin, Irfan

    2014-01-01

    Breast cancer bone metastasis causing severe morbidity is commonly encountered in daily clinical practice. It causes pain, pathologic fractures, spinal cord and other nerve compression syndromes and life threatening hypercalcemia. Breast cancer metastasizes to bone through complicated steps in which numerous molecules play roles. Metastatic cells disrupt normal bone turnover and create a vicious cycle to which treatment efforts should be directed. Bisphosphonates have been used safely for more than two decades. As a group they delay time to first skeletal related event and reduce pain, but do not prevent development of bone metastasis in patients with no bone metastasis, and also do not prolong survival. The receptor activator for nuclear factor κB ligand inhibitor denosumab delays time to first skeletal related event and reduces the skeletal morbidity rate. Radionuclides are another treatment option for bone pain. New targeted therapies and radionuclides are still under investigation. In this review we will focus on mechanisms of bone metastasis and its medical treatment in breast cancer patients.

  8. Aspects of osseous, peritoneal and renal handling of bisphosphonate during peritoneal dialysis: a methodological study

    DEFF Research Database (Denmark)

    Joffe, P; Henriksen, Jens Henrik Sahl

    1996-01-01

    to continuous ambulatory peritoneal dialysis (CAPD). The aims were: to assess the kinetics of 99m-technetium MBP (99mTc-MBP) in CAPD, and to evaluate the correctness of the assumption that the peritoneal and renal clearances of 99mTc-MBP equal the total plasma clearance of 51-chromium ethylenediamine tetra......-acetic acid (51Cr-EDTA). Eight patients on CAPD were studied cross-sectionally. The mean plasma clearances of 99mTc-MBP and 51Cr-EDTA in the steady state (4h) were 38.2 and 12.2 ml min-1 (p peritoneal clearances (0-4 h) were 5.2 and 7.2 ml min-1 (p ....5 and 2.8 ml min-1 (not significant), respectively. The bone bisphosphonate clearance (BBC) at steady state was 26.0 ml min-1, a value which was significantly higher than that at infinity (16.5 ml min-1, p peritoneal and renal clearances of 99m...

  9. Antiresorptive drugs beyond bisphosphonates and selective oestrogen receptor modulators for the management of postmenopausal osteoporosis.

    Science.gov (United States)

    Reginster, J Y; Neuprez, A; Beaudart, C; Lecart, M P; Sarlet, N; Bernard, D; Disteche, S; Bruyere, O

    2014-06-01

    Osteoporotic fractures are a major cause of morbidity in the elderly population. Since postmenopausal osteoporosis is related to an increase in osteoclastic activity at the time of menopause, inhibitors of bone resorption have genuinely been considered an adequate strategy for prevention and treatment of osteoporosis. Bisphosphonates and selective oestrogen receptor modulators are widely prescribed to treat osteoporosis. However, other antiresorptive drugs have been developed for the management of osteoporosis, with the objective of providing a substantial reduction in osteoporotic fractures at all skeletal sites, combined with an acceptable long-term skeletal and systemic safety profile. Denosumab, a human monoclonal antibody to receptor activator for nuclear factor kappa B ligand, has shown efficacy against vertebral, nonvertebral and hip fractures. Its administration every 6 months as a subcutaneous formulation might significantly influence compliance and persistence to therapy. Additional results regarding long-term skeletal safety (i.e. osteonecrosis of the jaw and atypical diaphyseal femoral fracture) are needed. Odanacatib, a selective cathepsin K inhibitor, is a promising new approach to the inhibition of osteoclastic resorption, with the potential to uncouple bone formation from bone resorption. Results regarding its anti-fracture efficacy are expected in the coming months.

  10. Clinical Analysis of Bisphosphonates Treatment on Bone Metastases and Hypercalcemia of Malignancy in Advanced Solid Tumor

    Institute of Scientific and Technical Information of China (English)

    MING Shu-hong; SUN Tie-ying

    2007-01-01

    Objective: To evaluate the efficacy and toleration of bisphosphonates therapy in patients with bone metastases and hypercalcemia of malignancy in advanced solid tumor. Methods: Patients with histologically or cytologically confirmed cancer and hypercalcemia with bone metastases were designed to open treatment with either 4mg zoledronic acid or 90mg pamidronate. The primary efficacy parameters were pain scores(NRS), Corrected serum calcium(CSC) and CSC effective rate. The vital signs, biochemical and hematological parameters were determined. Results: Twenty patients were enrolled in this study, twelve patients in zoledronic acid group and eight in pamidronate group. Zoledronic acid and pamidronate significantly palliated pain. Pain scores were significantly lower at end-point after Zoledronic acid or pamidronate infusion(5.92 vs 3.25,P<0.01;6.13 vs 4.38, P<0.01, respectively). The mean CSC level decreased significantly after Zoledronic acid or pamidronate infusion from 12.86 to 10.28mg/dl and 13.19 to 10.36mg/dl respectively. The CSC effective rate was about 90% at 14 days after infusion in two groups. There was no statistical significance for all primary efficacy parameters in zoledronic acid group compared with pamidronate group. An adverse reaction was mild fever after pamidronate infusion and then completely reversible. Conclusion: Zoledronic acid and pamidronate disodium were well tolerated and effective for bone metastases and hypercalcemia of malignancy in advanced solid tumor.

  11. Post-operative outcomes of atypical femoral subtrochanteric fracture in patients on bisphosphonate therapy.

    Science.gov (United States)

    Teo, B J X; Koh, J S B; Goh, S K; Png, M A; Chua, D T C; Howe, T S

    2014-05-01

    Management of bisphosphonate-associated subtrochanteric fractures remains opinion- or consensus-based. There are limited data regarding the outcomes of this fracture. We retrospectively reviewed 33 consecutive female patients with a mean age of 67.5 years (47 to 91) who were treated surgically between May 2004 and October 2009. The mean follow-up was 21.7 months (0 to 53). Medical records and radiographs were reviewed to determine the post-operative ambulatory status, time to clinical and radiological union and post-fixation complications such as implant failure and need for second surgery. The predominant fixation method was with an extramedullary device in 23 patients. 25 (75%) patients were placed on wheelchair mobilisation or no weight-bearing initially. The mean time to full weight-bearing was 7.1 months (2.2 to 29.7). The mean time for fracture site pain to cease was 6.2 months (1.2 to 17.1). The mean time to radiological union was 10.0 months (2.2 to 27.5). Implant failure was seen in seven patients (23%, 95 confidence interval (CI) 11.8 to 40.9). Revision surgery was required in ten patients (33%, 95 CI 19.2 to 51.2). A large proportion of the patients required revision surgery and suffered implant failure. This fracture is associated with slow healing and prolonged post-operative immobility.

  12. Combined local application of tetracycline and bisphosphonate reduces alveolar bone resorption in rats.

    Science.gov (United States)

    Yaffe, A; Herman, A; Bahar, H; Binderman, I

    2003-07-01

    Recent animal studies have shown that a combination of chemically-modified tetracyclines together with bisphosphonates, when delivered systemically, are synergistically effective in suppressing periodontal bone loss. In the present study, we explored the combined efficacy of local delivery of alendronate and tetracyclines in reducing alveolar bone loss. Eighty-six (86) male Wistar rats were used in these experiments. The flap was elevated using a special periosteal elevator, on both sides of the mandible, as described previously. A gelfoam pellet containing the drugs was applied between the alveolar bone and the mucoperiosteal flap, according to the experimental protocol. The rats were divided into 5 treatment groups: 1) alendronate; 2) doxycycline hyclate 10% (DOXY); 3) tetracycline hydrochloride 1% (TET); 4) alendronate + DOXY; and 5) alendronate + TET. In the operated control sites (C), saline was applied. The rats were sacrificed 21 days following the flap procedure. Sections of the mandibles (1.5 mm), in a buccal-lingual direction, underwent microradiography and were analyzed for bone loss. DOXY alone was most effective in reducing bone loss. Alendronate was also effective in reducing bone loss as shown in previous reports. TET did not reduce bone loss significantly when used alone. In combination with alendronate TET was synergistically effective. The combined local treatment of alendronate + DOXY showed no additive effect. In the present study, we found that tetracyclines can be most effective in reducing alveolar bone loss when applied locally. The combined local treatment of alendronate and tetracycline may have a synergistic effect.

  13. Metagenomic investigation of microbes and viruses in patients with jaw osteonecrosis associated with bisphosphonate therapy

    Science.gov (United States)

    Sedghizadeh, Parish P.; Yooseph, Shibu; Fadrosh, Douglas W.; Zeigler-Allen, Lisa; Thiagarajan, Mathangi; Salek, Hamid; Farahnik, Farid; Williamson, Shannon J.

    2013-01-01

    Objective The goal of this preliminary study was to use metagenomic approaches to investigate the taxonomic diversity of microorganisms in patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ). Study Design Samples of saliva for planktonic microbial analysis and biofilm cultivation were collected from 10 patients (5 with BRONJ and 5 non-BRONJ control subjects) who met all ascertainment criteria. Prophage induction experiments—16S rRNA polymerase chain reaction and 454 pyrosequencing—and epifluorescent microscopy were performed for characterization and enumeration of microbes and viruses. Results Three phyla of microbes—Proteobacteria (70%), Firmicutes (26.9%), and Actinobacteria (1.95%)—dominated all BRONJ samples and accounted for almost 99% of the total data. Viral abundance was ~1 order of magnitude greater than microbial cell abundance and comprised mainly phage viruses. Conclusions Individuals with jaw osteonecrosis harbored different microbial assemblages than nonaffected patients, and in general viral abundance and prophage induction increased with biofilm formation, suggesting that biofilm formation encouraged lysogenic interactions between viruses and microbial hosts and may contribute to pathogenicity. PMID:23159114

  14. Population pharmacokinetic and pharmacodynamic modeling for assessing risk of bisphosphonate-related osteonecrosis of the jaw

    Science.gov (United States)

    Sedghizadeh, Parish P.; Jones, Allan C.; LaVallee, Chris; Jelliffe, Roger W.; Le, Anh D.; Lee, Peter; Kiss, Andrew; Neely, Michael

    2012-01-01

    Objective We hypothesized that patients with bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) accumulate higher levels of BP in bone than those without BRONJ. Study Design Using the Pmetrics® package and published data, we designed a population pharmacokinetic model of pamidronate concentration in plasma and bone and derived a toxic bone BP threshold of 0.2 mM. With the model, and using patient individual BP duration and bone mineral content estimated from lean body weight, we calculated bone BP levels in 153 subjects. Results Mean bone BP in 69 BRONJ cases was higher than in 84 controls (0.20 vs. 0.10 mM, P<0.001) consistent with the toxic bone threshold of 0.2 mM. BRONJ was also associated with longer duration BP therapy (5.3 vs. 2.7 years, P<0.001), older age (76 vs. 70 years, P<0.001), and Asian race (49% vs. 14%, P<0.001). Conclusions Our model accurately discriminated BRONJ cases from controls, among patients on BP therapy. PMID:23246224

  15. Oral calcitonin

    Directory of Open Access Journals (Sweden)

    Hamdy RC

    2012-09-01

    Full Text Available Ronald C Hamdy,1,2 Dane N Daley11Osteoporosis Center, College of Medicine, East Tennessee State University, 2Veterans Affairs Medical Center, Johnson City, TN, USAAbstract: Calcitonin is a hormone secreted by the C-cells of the thyroid gland in response to elevations of the plasma calcium level. It reduces bone resorption by inhibiting mature active osteoclasts and increases renal calcium excretion. It is used in the management of postmenopausal osteoporosis, Paget's disease of bone, and malignancy-associated hypercalcemia. Synthetic and recombinant calcitonin preparations are available; both have similar pharmacokinetic and pharmacodynamic profiles. As calcitonin is a peptide, the traditional method of administration has been parenteral or intranasal. This hinders its clinical use: adherence with therapy is notoriously low, and withdrawal from clinical trials has been problematic. An oral formulation would be more attractive, practical, and convenient to patients. In addition to its effect on active osteoclasts and renal tubules, calcitonin has an analgesic action, possibly mediated through β-endorphins and the central modulation of pain perception. It also exerts a protective action on cartilage and may be useful in the management of osteoarthritis and possibly rheumatoid arthritis. Oral formulations of calcitonin have been developed using different techniques. The most studied involves drug-delivery carriers such as Eligen® 8-(N-2hydroxy-5-chloro-benzoyl-amino-caprylic acid (5-CNAC (Emisphere Technologies, Cedar Knolls, NJ. Several factors affect the bioavailability and efficacy of orally administered calcitonin, including amount of water used to take the tablet, time of day the tablet is taken, and proximity to intake of a meal. Preliminary results looked promising. Unfortunately, in two Phase III studies, oral calcitonin (0.8 mg with 200 mg 5-CNAC, once a day for postmenopausal osteoporosis and twice a day for osteoarthritis failed to

  16. Oral Cancer Exam

    Medline Plus

    Full Text Available ... Topics > Oral Cancer > Oral Cancer Exam Video Oral Cancer Exam Video This video shows what happens during an oral cancer examination. Quick and painless, the exam can detect ...

  17. Oral Cancer Exam

    Medline Plus

    Full Text Available ... Topics > Oral Cancer > Oral Cancer Exam Video Oral Cancer Exam Video This video shows what happens during an oral cancer examination. Quick and painless, the exam can detect ...

  18. Enteric-coated tablet of risedronate sodium in combination with phytic acid, a natural chelating agent, for improved oral bioavailability.

    Science.gov (United States)

    Kim, Jeong S; Jang, Sun W; Son, Miwon; Kim, Byoung M; Kang, Myung J

    2016-01-20

    The oral bioavailability (BA) of risedronate sodium (RS), an antiresorptive agent, is less than 1% due to its low membrane permeability as well as the formation of non-absorbable complexes with multivalent cations such as calcium ion (Ca(2+)) in the gastrointestinal tract. In the present study, to increase oral BA of the bisphosphonate, a novel enteric-coated tablet (ECT) dosage form of RS in combination with phytic acid (IP6), a natural chelating agent recognized as safe, was formulated. The chelating behavior of IP6 against Ca(2+), including a stability constant for complex formulation was characterized using the continuous variation method. Subsequently, in vitro dissolution profile and in vivo pharmacokinetic profile of the novel ECT were evaluated comparatively with that of the marketed product (Altevia, Sanofi, US), an ECT containing ethylenediaminetetraacetic acid (EDTA) as a chelating agent, in beagle dogs. The logarithm of stability constant for Ca(2+)-IP6 complex, an equilibrium constant approximating the strength of the interaction between two chemicals to form complex, was 19.05, which was 3.9-fold (pIP6-containing ECT were approximately 7.9- (pIP6 for an oral therapy with the bisphosphonate for improved BA. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Oral dirofilariasis

    Directory of Open Access Journals (Sweden)

    R S Desai

    2015-01-01

    Full Text Available Dirofilaria is parasitic nematodes of domestic and wild animals that can infect humans accidentally via vectors. Its occurrence in the oral cavity is extremely rare. The most frequent presentation of human dirofilariasis is a single submucosal nodule without signs of inflammation. We hereby, report a case of human dirofilariasis affecting the buccal mucosa in a 32-year-old farmer caused by D. repens.

  20. Oral leiomyomas.

    Science.gov (United States)

    Damm, D D; Neville, B W

    1979-04-01

    Oral leiomyomas are considered to be rare neoplasms, but they may be encountered more frequently than generally believed. Three types of leiomyomas are commonly described: solid leiomyomas, angiomyomas, and epithelioid leiomyomas. Three cases of solid leiomyoma are presented, all of which occurred in the anterior mandibular mucobuccal fold. Leiomyomas can be easily confused with other spindle-cell tumors. The necessity of using special stains, especially Mallory's phosphotungstic acid hematoxylin, is discussed.

  1. Alveolar bone grafting in association with polyostotic fibrous dysplasia and bisphosphonate-induced abnormal bone turnover in a bilateral cleft lip and palate patient: a case report.

    Science.gov (United States)

    Kodama, Yasumitsu; Ogose, Akira; Oguri, Yoshimitsu; Ubaidus, Sobhan; Iizuka, Tateyuki; Takagi, Ritsuo

    2012-09-01

    A case is presented of extensive alveolar bone grafting in a patient with bilateral cleft lip and palate and polyostotic fibrous dysplasia. The patient previously underwent bisphosphonate therapy. Because of an abnormal and often decreased bone turnover caused by the fibrous dysplasia and the bisphosphonate therapy, bone grafting in such a patient poses several potential difficulties. In addition, the histomorphometric analysis of the bone grafts showed markedly decreased bone turnover. However, alveolar bone grafting using the iliac crest was performed successfully. Sufficient occlusion was achieved by postoperative low-loading orthodontic treatment.

  2. Microwave-assisted synthesis of (aminomethylene)bisphosphine oxides and (aminomethylene)bisphosphonates by a three-component condensation

    Science.gov (United States)

    Tajti, Ádám; Dzielak, Anna; Hägele, Gerhard

    2016-01-01

    Summary A practical method was elaborated for the synthesis of (aminomethylene)bisphosphine oxides comprising the catalyst- and solvent-free microwave-assisted three-component condensation of primary amines, triethyl orthoformate and two equivalents of diphenylphosphine oxide. The method is also suitable for the preparation of (aminomethylene)bisphosphonates using (MeO)2P(O)H/(MeO)3CH or (EtO)2P(O)H/(EtO)3CH reactant pairs and even secondary amines. Several intermediates referring to the reaction mechanism together with a few by-products could also be identified. PMID:27559402

  3. Clinical and histopathological studies using fibrin-rich plasma in the treatment of bisphosphonate-related osteonecrosis of the jaw.

    Science.gov (United States)

    Dincă, Octavian; Zurac, Sabina; Stăniceanu, Florica; Bucur, Mihai Bogdan; Bodnar, Dana Cristina; Vlădan, Cristian; Bucur, Alexandru

    2014-01-01

    The authors report their experience using platelet-rich fibrin (PRF) therapy for the treatment of ten patients presenting bisphosphonate-related osteonecrosis of the jaw (BRONJ). The aim of our study was to evaluate the effect of this therapy on recurrent BRONJ and to describe the clinical and histopathological/immunohistochemical staining features of PRF treatment. As such, we describe the method we used and report the results observed in the areas treated as well as side effects. The reported results recommend the safety and efficacy of PRF in treatment of BRONJ.

  4. School based oral health promotional intervention: Effect on knowledge, practices and clinical oral health related parameters

    Directory of Open Access Journals (Sweden)

    Arjun Gauba

    2013-01-01

    Full Text Available Background: No organized school oral health program is existent in India. Aim: The aim of this study is to test the feasibility and efficacy of an economical school oral health promotional intervention with educational and preventive components. Settings and Design: School oral health promotional intervention carried out in one of the randomly selected school and evaluated through short duration prospective model. Materials and Methods: A total of 100 children with an age range of 10-12 years with no previous history of dental intervention were enrolled. Interventions comprised of oral health education (delivered through lecture and demonstrations by an undergraduate dental student and topical antibacterial therapy (fluoride varnish and povidone iodine. Outcomes consisted of Knowledge and practices (KAP regarding oral health, clinical oral health related parameters such as plaque index (PI, gingival index (GI and caries activity as per Modified Snyder′s test. These were reported at baseline, 3 weeks and 6 months follow-up examination by a calibrated examiner. Statistical Analysis: McNemar Bowker′s test, Student′s t-test, Pearson Chi-square tests were used. Results: Highly significant (P < 0.001 improvements in KAP scores, PI scores, GI scores and caries activity were reported at 3 weeks and 6 months follow-up examination. Conclusion: This small economical school oral health program positively influenced oral health related practices and parameters of oral health such as oral cleanliness, gingival health and caries activity.

  5. Live imaging of osteoclast inhibition by bisphosphonates in a medaka osteoporosis model

    Directory of Open Access Journals (Sweden)

    Tingsheng Yu

    2016-02-01

    Full Text Available Osteoclasts are bone-resorbing cells derived from the monocyte/macrophage lineage. Excess osteoclast activity leads to reduced bone mineral density, a hallmark of diseases such as osteoporosis. Processes that regulate osteoclast activity are therefore targeted in current osteoporosis therapies. To identify and characterize drugs for treatment of bone diseases, suitable in vivo models are needed to complement cell-culture assays. We have previously reported transgenic medaka lines expressing the osteoclast-inducing factor receptor activator of nuclear factor κB ligand (Rankl under control of a heat shock-inducible promoter. Forced Rankl expression resulted in ectopic osteoclast formation, as visualized by live imaging in fluorescent reporter lines. This led to increased bone resorption and a dramatic reduction of mineralized matrix similar to the situation in humans with osteoporosis. In an attempt to establish the medaka as an in vivo model for osteoporosis drug screening, we treated Rankl-expressing larvae with etidronate and alendronate, two bisphosphonates commonly used in human osteoporosis therapy. Using live imaging, we observed an efficient, dose-dependent inhibition of osteoclast activity, which resulted in the maintenance of bone integrity despite an excess of osteoclast formation. Strikingly, we also found that bone recovery was efficiently promoted after inhibition of osteoclast activity and that osteoblast distribution was altered, suggesting effects on osteoblast-osteoclast coupling. Our data show that transgenic medaka lines are suitable in vivo models for the characterization of antiresorptive or bone-anabolic compounds by live imaging and for screening of novel osteoporosis drugs.

  6. Use of disodium pamidronate bisphosphonate in patients with bone metastases of lung cancer

    Directory of Open Access Journals (Sweden)

    Ranković Boško

    2002-01-01

    Full Text Available Disodium pamidronate (Aredia®, a drug of the bisphosphonate group, was administered to 20 patients with pains in the bones due to secondary deposits of lung cancer. The aim of the study was to investigate the analgesic effect of pamidronate to osteolytic metastases of lung cancer in the bone. In 16 (80% patients non-small-cell lung cancer was diagnosed, and in 4 (20% patients small-cell-lung cancer was confirmed. Intensive disseminated pains in the bones were present in all the patients. Metastases in the skeleton were confirmed by radiography and scintigraphy of the bones. Initial values of calcium in the plasma were determined in those patients. In 11 (55% patients, initial values of calcium in the serum were normal, and in 9 (45% patients, they were elevated. Patients with normal calcium values received 30 mg of pamidronate in 250 ml of normal saline, and patients with hypercalcaemia received 45-60 mg in 500 ml of normal saline. Analgesic effect of pamidronate was present in 12 (60% patients, and the completely painless state was achieved in 4 out of 12 patients. Evaluation of the pain was done by questionnaire, using a simple, descriptive scale. In all 9 (100% patients with hypercalcaemia, values of calcium in plasma were normalized. Pamidronate exerted favorable analgesic effect in the case of metastases of lung cancer in the bones in more than 50% patients. Satisfactory results were also achieved in the patients non-responsive to palliative therapy by irradiation This enables the use of opiates in lower doses.

  7. Prolonged bisphosphonate release after treatment in women with osteoporosis. Relationship with bone turnover.

    Science.gov (United States)

    Peris, P; Torra, M; Olivares, V; Reyes, R; Monegal, A; Martínez-Ferrer, A; Guañabens, N

    2011-10-01

    Bisphosphonates (BP), especially alendronate and risedronate, are the drugs most commonly used for osteoporosis treatment, being incorporated into the skeleton where they inhibit bone resorption and are thereafter slowly released during bone turnover. However, there are few data on the release of BP in patients who have received treatment with these drugs for osteoporosis. This information is essential for evaluating the possibility of BP cyclic therapy in these patients and for controlling their long-term presence in bone tissue. This study evaluated the urinary excretion of alendronate and risedronate in patients treated with these drugs for osteoporosis and analysed its relationship with bone turnover, time of previous drug exposure and time of treatment discontinuation. We included 43 women (aged 65±9.4 years) previously treated with alendronate (36) or risedronate (7) during a mean of 51±3 and 53±3 months, respectively, who had not been treated with other antiosteoporotic treatment and with a median time of discontinuation of 13.5 and 14 months, respectively. Both BP were detected in 24-hour urine by HPLC. In addition, bone formation (PINP) and resorption (NTx) markers were analysed. Both BP were also determined in a control group of women during treatment. Alendronate was detected in 41% of women previously treated with this drug whereas no patient previously treated with risedronate showed detectable urinary values. All control patients showed detectable values of both BP. In patients with detectable alendronate levels, the time of drug cessation was shorter than in patients with undetectable values (12 [6-19] versus 31 [7-72] months, prisedronate, which was not detected in patients after cessation of treatment, alendronate was frequently detected in women previously treated with this agent up to 19 months after discontinuation of therapy. The relationship between alendronate levels and both bone resorption and time of treatment cessation further

  8. Implications of three phase bone scintigraphy for the diagnosis of bisphosphonate related osteonecrosis of the jaw

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Chae Moon; Ahn, Byeong Cheol; Choi, So Young; Kim, Do Hoon; Lee, Sang Woo; Kwon, Tae Geon; Lee, Jaetae [Kyungpook National Univ., Daegu (Korea, Republic of)

    2012-09-15

    Bisphosphonate (BP) related osteonecrosis of the jaw (BRONJ) is a well known serious complication of BP treatment. This study was undertaken to evaluate the diagnostic usefulness of three phase bone scintigraphy in patients with BRONJ. Forty one patients (48 lesions)with clinically proven BRONJ (2 males, 39 females, age 74.3{+-}6.7 years)under went Tc 99m HDP bone scintigraphy. Visual interpretation and semiquantitative analysis of uptakes using lesion to contralateral uptake ratios during the blood pool phase (BUR)and during the osseous phase (OUR)were performed, and relations were sought between these and various clinical parameters. Three phase bone scintigraphy showed increased perfusion and blood pooling in 21 (63.6%)and 27 (81.8%)of 33 lesions, respectively. The osseous phase was positive for 45 (93.8%)of the 48 lesions. Of the four inflammatory clinical parameters of BRONJ [pus discharge, pain, swelling, and erythrocyte sedimentation rate (ESR)], patients with three or more parameters had more positive findings in vascular and blood pool phase images (p=0.033, p=0.027). By semiquantitative analysis, patients with a positive ESR had statistically higher BUR and OUR (both p<0.001). Higher stage BRONJ lesions had higher OUR than lower stage lesions (p=0.003). In addition, bone scintigraphy revealed three clinically covert BRONJ lesions without bone exposure, and four patients were up staged based on bone scintigraphy. Bone scintigraphy provides a relatively sensitive means of detecting BRONJ, so it was helpful for accurate BRONJ staging. Furthermore, Increased uptakes in vascular and blood pool phases of three phase bone scintigraphy were related to the inflammatory activity of BRONJ.

  9. Surgical treatment vs. conservative treatment in intravenous bisphosphonate-related osteonecrosis of the jaws. Systematic review

    Science.gov (United States)

    Comas-Calonge, Aida; Figueiredo, Rui

    2017-01-01

    Aims To determine the success rates of the surgical and non-surgical treatments in the management of bisphosphonate-related osteonecrosis of the jaws (BRONJ). Material and Methods A systematic review of the literature was made. A PubMed Medline database search was performed in order to include clinical studies published in English,between2004 and 2014 with the following key-words: “BRONJ AND treatment” and “NOT osteoporosis”. The following data was gathered: authors, title, year of publication, aim of study, level of evidence, sample size, treatment performed, treatment outcomes and follow-up. Studies including more than 20 patients with at least 6 months of follow-up, and that specify the different treatment approaches and their outcomes were included. Systematic reviews were excluded.All studies were classified according to the SORT criteria (Strength of Recommendation Taxonomy). Results The initial electronic search yielded 169 papers, and 13 studies were added after a manual search (total of 182 studies). After analysing the title and abstract and removing duplicates, 31 full-texts were obtained. A total of 12 papers were finally included. Two were classified as level 3 evidence and 9 as level 2. The quality of the selected studies and the risk of bias were also reported. Conclusions Surgical treatments like sequestrectomy, surgical debridement and bone osteotomies provide successful treatment outcomes, with success rates ranging from 58 to 100%. Controlled randomized clinical trials with larger samples and longer follow-up are needed to support these findings. Key words:BRONJ, treatment. PMID:28210453

  10. Dinuclear Pt(II)-bisphosphonate complexes: a scaffold for multinuclear or different oxidation state platinum drugs.

    Science.gov (United States)

    Piccinonna, Sara; Margiotta, Nicola; Pacifico, Concetta; Lopalco, Antonio; Denora, Nunzio; Fedi, Serena; Corsini, Maddalena; Natile, Giovanni

    2012-08-28

    Geminal bisphosphonates (BPs), used in the clinic for the treatment of hypercalcaemia and skeletal metastases, have been also exploited for promoting the specific accumulation of platinum antitumor drugs in bone tissue. In this work, the platinum dinuclear complex [{Pt(en)}(2)(μ-AHBP-H(2))](+) (1) (the carbon atom bridging the two phosphorous atoms carrying a 2-ammonioethyl and a hydroxyl group, AHBP-H(2)) has been used as scaffold for the synthesis of a Pt(II) trinuclear complex, [{Pt(en)}(3)(μ-AHBP)](+) (2), and a Pt(IV) adamantane-shaped dinuclear complex featuring an oxo-bridge, [{Pt(IV)(en)Cl}(2)(μ-O)(μ-AHBP-H(2))](+) (3) (X-ray structure). Compound 2 undergoes a reversible, pH dependent, rearrangement with a neat switch point around pH = 5.4. Compound 3 undergoes a one-step electrochemical reduction at E(pc) = -0.84 V affording compound 1. Such a potential is far lower than that of glutathione (-0.24 V), nevertheless compound 3 can undergo chemical reduction to 1 by GSH, most probably through a different (inner-sphere) mechanism. In vitro cytotoxicity of the new compounds, tested against murine glioma (C6) and human cervix (HeLa) and hepatoma (HepG2) cell lines, has shown that, while the Pt(IV) dimer 3 is inactive up to a concentration of 50 μM, the two Pt(II) polynuclear compounds 1 and 2 have a cytotoxicity comparable to that of cisplatin with the trinuclear complex 2 generally more active than the dinuclear complex 1.

  11. The efficacy and tolerability of once-weekly alendronate 70 mg on bone mineral density and bone turnover markers in postmenopausal Chinese women with osteoporosis.

    Science.gov (United States)

    Yan, Yuxiang; Wang, Wei; Zhu, Hanmin; Li, Mei; Liu, Jianli; Luo, Bangyao; Xie, Haibao; Zhang, Guangjian; Li, Fuobao

    2009-01-01

    Osteoporosis has become an important health problem in postmenopausal Chinese women. Bisphosphonates currently are the preferred therapy for treating osteoporosis. However, the use of daily regimen of alendronate in women at risk for osteoporosis has been relatively low in China because of its dosing inconvenience. To determine the efficacy and tolerability of once-weekly alendronate 70 mg in Chinese, a multicenter, randomized, double blind, placebo controlled study was performed in China. Five hundred and sixty postmenopausal women (osteoporosis were randomly assigned to receive either alendronate 70 mg or placebo once-weekly for 12 months. All women received calcium 500 mg daily and vitamin D 200 IU daily. A significant increase in lumbar spine BMD was already evident at 6 months of alendronate treatment (P or =0% and > or =3% BMD increase in lumbar spine was significantly greater in women with alendronate than placebo (P osteoporosis in Chinese women.

  12. A busy week for Council

    CERN Multimedia

    2009-01-01

    This has been a busy week for the CERN Council, and there is much to report. Firstly, I’m pleased to say that Council approved the Organization’s Medium Term Plan, and with it the budget for financial year 2010. In a time of global recession, this is a strong vote of confidence from the Member States. This meeting of Council provided an opportunity for the working group on the scientific and geographical enlargement of CERN to set out a roadmap towards its final report, which is to be made at Council’s December session this year. One part of the process over the coming months is to bring the major players in particle physics from beyond the European region into the discussion, ensuring that the working group’s recommendations lead to an optimum position for CERN and European particle physics in the global context. An indicator of the continuing attractiveness of CERN is the fact that Council has received four new applications...

  13. Web Lectures - ATLAS Overview Week

    CERN Multimedia

    Tushar Bhatnagar; Jeremy Herr; Mitch McLachlan; Homer A. Neal

    2007-01-01

    ATLAS Web Archives Web Archives of the ATLAS Overview Week in Glasgow are now available from the University of Michigan portal here. Archives of ATLAS Plenary Sessions, Workshops, Meetings, and Tutorials recorded over the past two years are available via the University of Michigan Lecture Portal. Other recent additions include the ROOT Workshop held at CERN on March 26-27, the Physics Analysis Tools Workshop held in Bergen, Norway on April 23-27, and the CTEQ Workshop: "Physics at the LHC: Early Challenges" held at Michigan State University on May 14-15. Viewing requires a standard Web browser with RealPlayer plug-in (included in most browsers automatically) and works on any major platform. Lectures can be viewed directly over the Web or downloaded locally. In addition, you will find access to a variety of general tutorials and events via the portal. Feedback & Suggestions Welcome Suggestions for events or tutorials to record in 2007, as well as feedback on existing archives, is always welcome...

  14. Erythema multiforme limited to the oral mucosa in a teenager on oral contraceptive therapy.

    Science.gov (United States)

    Jawetz, Robert E; Elkin, Avigayil; Michael, Lisa; Jawetz, Sheryl A; Shin, Helen T

    2007-10-01

    Erythema multiforme has been linked to numerous drugs and infectious agents. A link to oral contraceptive use has been reported in the past in the adult population but thus far has not been reported in children or adolescents. We report the case of an 18-yr-old female who developed oral erosions consistent with erythema multiforme two and a half weeks after initiating therapy with an oral contraceptive agent. A thorough examination for other inciting factors was negative, and the lesions slowly resolved over the course of 3 weeks. This case illustrates that erythema multiforme should be considered in the differential diagnosis of adolescents with oral erosions who have been prescribed oral contraceptives.

  15. Short-term bisphosphonate treatment reduces serum 25(OH vitamin D3 and alters values of parathyroid hormone, pentosidine, and bone metabolic markers

    Directory of Open Access Journals (Sweden)

    Kamimura M

    2017-02-01

    Full Text Available Mikio Kamimura,1 Shigeharu Uchiyama,2 Yukio Nakamura,2,3 Shota Ikegami,2 Keijiro Mukaiyama,2 Hiroyuki Kato2 1Center for Osteoporosis and Spinal Disorders, Kamimura Orthopaedic Clinic, Matsumoto, Japan; 2Department of Orthopaedic Surgery, Shinshu University School of Medicine, Matsumoto, Japan; 3Department of Orthopedic Surgery, Showa-Inan General Hospital, Komagane, Japan Abstract: This study aimed to clarify the effects of short-term bisphosphonate (BP administration in Japanese osteoporotic patients retrospectively. Daily minodronate (MIN at 1 mg/day (MIN group or weekly risedronate (RIS at 17.5 mg/week (RIS group was primarily prescribed for each patient. We analyzed the laboratory data of 35 cases (18 of MIN and 17 of RIS before the start of treatment and at 4 months afterward. The changes in 25(OHD3, whole parathyroid hormone (PTH, serum pentosidine, and the bone turnover markers urinary cross-linked N-telopeptide of type I collagen (NTX, serum tartrate-resistant acid phosphatase (TRACP-5b, bone-specific alkaline phosphatase (BAP, and undercarboxylated osteocalcin were evaluated. Overall, serum 25(OHD3 was significantly decreased from 21.8 to 18.4 ng/mL at 4 months, with a percent change of –14.7%. Whole PTH increased significantly from 23.4 to 30.0 pg/mL, with a percent change of 32.1%. Serum pentosidine rose from 0.0306 to 0.0337 µg/mL, with a percent change of 15.2%. In group comparisons, 25(OHD3 and pentosidine showed comparable changes in both groups after 4 months of treatment, whereas whole PTH became significantly more increased in the MIN group. All bone turnover markers were significantly decreased at 4 months in both groups. Compared with the RIS group, the MIN group exhibited significantly larger value changes for urinary NTX, serum TRACP-5b, and BAP at the study end point. This study demonstrated that serum 25(OHD3 became significantly decreased after only 4 months of BP treatment in Japanese osteoporotic patients and

  16. Oral contraceptives.

    Science.gov (United States)

    Maclennan, A H

    1987-12-01

    Over 60 million women use highly efficient and safe modern combined oral contraceptives (OCs) every day. A women who takes the oral contraceptive for 5 years before the age of 30 will actually live 12 days longer, although a woman taking the pill for the 1st time for 5 years after the age of 30 will have her life span reduced on the average by 80 days. OC related morbidity and mortality mostly occur in women over 35 who smoke. Combined low dose OCs are safe for women who do not smoke, at least to 45 years of age and probably to the menopause. The prescription of OCs is also safe to the young adolescent. The pill does not interfere with maturation of the hypothalamic-pituitary ovarian axis and does not increase the incidence of amenorrhoea, oligomenorrhoea or infertility in later life. Patients with contraindications to estrogen therapy are excluded from OC use (history of thromboembolism, major heart disease, liver disease, breast cancer). Low-dose (30-35 mcg estrogen-containing monophasic or triphasic) pills are recommended. Combined oral contraceptives contain either ethinyl estradiol (1.7 to 2 times more potent) or mestranol. After absorption the progestagens, norethisterone acetate, ethynodiol diacetate and lynoestrenol are all metabolized to norethisterone. The progestagen-only pill has about a 2% failure rate and poorer cycle control than the combined pill, but it lacks estrogenic, progestagenic and androgenic side effects. This pill is suitable for the lactating mother, for smokers over 35, for hypertensive patients, and for those with a history of thrombosis. The efficacy of the progestagen-only pill is restored in 3 days of pill taking. Postcoital contraception is an alternative: treatment can be given for at least 72 hours after intercourse. The Yuzpe method calls for the patient to take 2 combined oral contraceptive tablets containing levonorgestrel and ethinyl estradiol (Eugynon or Ovral) followed by a further 2 tablets 12 hours later. This regimen

  17. Summer Oral Expression English Course

    CERN Multimedia

    HR Department

    2011-01-01

    An English Oral Expression course will take place between 15 August and 30 September 2011. Schedule: to be determined (2 sessions of 2 hours per week). Please note that this course is for learners who have a good knowledge of English (CERN level 7 upwards). If you are interested in following this course, please enrol here. Or contact: Kerstin FUHRMEISTER (70896) Tessa OSBORNE (72957)  

  18. Subchronic oral toxicity studies with y-cyclodextrin in rats

    NARCIS (Netherlands)

    Lina, B.A.R.; Bär, A.

    1998-01-01

    The toxicity of γ-cyclodextrin (γ-CD), a cyclic polymer of eight α-1,4-linked glucopyranosyl units with potential applications as a food ingredient, was examined in a 2-week pilot study followed by a 13-week oral toxicity study in Wistar rats. In the 2-week study, the test substance was administered

  19. Premature: growth and its relation to oral skills.

    Science.gov (United States)

    Vargas, Camila Lehnhart; Berwig, Luana Cristina; Steidl, Eduardo Matias dos Santos; Prade, Leila Sauer; Bolzan, Geovana; Keske-Soares, Márcia; Weinmann, Angela Regina Maciel

    2015-01-01

    To evaluate the influence of oral motor skills of premature infants on their oral feeding performance and growth, during neonatal hospitalization. Fifty-one newborns hospitalized in the neonatal intensive care unit of a hospital in Southern Brazil, between July 2012 and March 2013, were evaluated. The evaluation of oral feeding skills, according to Lau and Smith, was applied after prescription for starting oral feeding. The oral feeding performance was analyzed using the following variables: days taken to start independent oral feeding and hospital discharge. Growth was measured by weight, length, and head circumference, using the curves of Fenton, at birth, first and independent oral feeding, and hospital discharge. At birth, 71% preterm infants were proper for gestational age, most of them were males (53%), with average of 33.6 (±1.5) weeks of gestational age. The gestational age in the assessment did not influence the oral feeding performance of the premature infant and did not differ between levels. Time of transition from tube feeding to oral feeding and hospital stay was shorter when the oral skills were higher. At birth, there was a tendency of low weight and low oral feeding performance. Level IV premature infants in the release of oral feeding presented higher weights. The level of oral skills of the premature infant interfered positively on time of feeding transition from tube to independent oral feeding and hospital stay. Growth, represented by weight gain, was not affected by the level of oral skill.

  20. Binding of nitrogen-containing bisphosphonates (N-BPs) to the Trypanosoma cruzi farnesyl diphosphate synthase homodimer

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chuan-Hsiang; Gabelli, Sandra B.; Oldfield, Eric; Amzel, L. Mario (UIUC); (JHU-MED)

    2010-11-15

    Bisphosphonates (BPs) are a class of compounds that have been used extensively in the treatment of osteoporosis and malignancy-related hypercalcemia. Some of these compounds act through inhibition of farnesyl diphosphate synthase (FPPS), a key enzyme in the synthesis of isoprenoids. Recently, nitrogen-containing bisphosphonates (N-BPs) used in bone resorption therapy have been shown to be active against Trypanosoma cruzi, the parasite that causes American trypanosomiasis (Chagas disease), suggesting that they may be used as anti-trypanosomal agents. The crystal structures of TcFPPS in complex with substrate (isopentenyl diphosphate, IPP) and five N-BP inhibitors show that the C-1 hydroxyl and the nitrogen-containing groups of the inhibitors alter the binding of IPP and the conformation of two TcFPPS residues, Tyr94 and Gln167. Isothermal titration calorimetry experiments suggest that binding of the first N-BPs to the homodimeric TcFPPS changes the binding properties of the second site. This mechanism of binding of N-BPs to TcFPPS is different to that reported for the binding of the same compounds to human FPPS.