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Sample records for cancer-induced bone loss

  1. Mechanisms of cancer-induced bone pain

    OpenAIRE

    Lozano-Ondoua, AN; Symons-Liguori, AM; Vanderah, TW

    2013-01-01

    Cancerous cells can originate in a number of different tissues such as prostate, breast and lung, yet often go undetected and are non-painful. Many types of cancers will metastasize toward the bone microenvironment first. Tumor burden within the bone causes excruciating breakthrough pain with properties of continual pain inadequately managed with current analgesics. Part of this failure is due to the poor understanding of the etiology of cancer pain. Animal models of cancer-induced bone pain ...

  2. Acupuncture for Cancer-Induced Bone Pain?

    Directory of Open Access Journals (Sweden)

    Carole A. Paley

    2011-01-01

    Full Text Available Bone pain is the most common type of pain in cancer. Bony metastases are common in advanced cancers, particularly in multiple myeloma, breast, prostate or lung cancer. Current pain-relieving strategies include the use of opioid-based analgesia, bisphosphonates and radiotherapy. Although patients experience some pain relief, these interventions may produce unacceptable side-effects which inevitably affect the quality of life. Acupuncture may represent a potentially valuable adjunct to existing strategies for pain relief and it is known to be relatively free of harmful side-effects. Although acupuncture is used in palliative care settings for all types of cancer pain the evidence-base is sparse and inconclusive and there is very little evidence to show its effectiveness in relieving cancer-induced bone pain (CIBP. The aim of this critical review is to consider the known physiological effects of acupuncture and discuss these in the context of the pathophysiology of malignant bone pain. The aim of future research should be to produce an effective protocol for treating CIBP with acupuncture based on a sound, evidence-based rationale. The physiological mechanisms presented in this review suggest that this is a realistic objective.

  3. Cancer-induced bone loss and associated pain-related behavior is reduced by risedronate but not its phosphonocarboxylate analog NE-10790

    DEFF Research Database (Denmark)

    Hald, Andreas; Hansen, Rikke; THOMSEN, METTE;

    2009-01-01

    Prostate, breast and lung cancers readily develop bone metastases which lead to fractures, hypercalcemia and pain. Malignant growth in the bones depends on osteoclast-mediated bone resorption and in this regard bisphosphonate compounds, which have high-bone affinity and inhibit osteoclast activity......, have been found to alleviate bone cancer symptoms. In this study, the bisphosphonate risedronate and its phosphonocarboxylate derivative NE-10790 was tested in a murine bone cancer pain model. Risedronate decreased bone cancer-related bone destruction and pain-related behavior and decreased the spinal...... that a direct toxic effect on tumor cells may also be present in vivo and be related to the efficacy of bisphosphonate compounds. In conclusion, these results suggest that risedronate treatment may lead to an increased life quality, in patient suffering from bone cancer, in terms of decreased...

  4. Acupuncture for cancer-induced bone pain?

    OpenAIRE

    Mark I Johnson; Bennett, Michael I; Paley, Carole A.

    2011-01-01

    Bone pain is the most common type of pain in cancer. Bony metastases are common in advanced cancers, particularly in multiple myeloma, breast, prostate or lung cancer. Current pain-relieving strategies include the use of opioid-based analgesia, bisphosphonates and radiotherapy. Although patients experience some pain relief, these interventions may produce unacceptable side-effects which inevitably affect the quality of life. Acupuncture may represent a potentially valuable adjunct to existing...

  5. Menopause and Bone Loss

    Science.gov (United States)

    Fact Sheet & Menopause Bone Loss How are bone loss and menopause related? Throughout life your body keeps a balance between the loss ... The sooner you take steps to prevent bone loss, the lower your risk of osteoporosis later in life. If you are skipping menstrual periods, have had ...

  6. Bone Loss in IBD

    Science.gov (United States)

    ... DENSITY? Although bone seems as hard as a rock, it’s actually living tissue. Throughout your life, old ... available Bone Loss (.pdf) File: 290 KB 733 Third Avenue, Suite 510, New York, NY 10017 | 800- ...

  7. Use of Animal Models in Understanding Cancer-induced Bone Pain

    OpenAIRE

    Slosky, Lauren M.; Tally M. Largent-Milnes; Vanderah, Todd W

    2015-01-01

    Many common cancers have a propensity to metastasize to bone. Although malignancies often go undetected in their native tissues, bone metastases produce excruciating pain that severely compromises patient quality of life. Cancer-induced bone pain (CIBP) is poorly managed with existing medications, and its multifaceted etiology remains to be fully elucidated. Novel analgesic targets arise as more is learned about this complex and distinct pain state. Over the past two decades, multiple animal ...

  8. P2X7 receptor-mediated analgesia in cancer-induced bone pain

    DEFF Research Database (Denmark)

    Falk, Sarah; D. Schwab, Samantha; Frøsig-Jørgensen, Majbrit;

    2015-01-01

    Pain is a common and debilitating complication for cancer patients significantly compromising their quality of life. Cancer-induced bone pain involves a complex interplay of molecular events, including mechanisms observed in inflammatory and neuropathic pain states, but also changes unique for...... cancer-induced bone pain. The P2X7 receptor (P2X7R) is involved in a variety of cellular functions and has been linked to both inflammatory and neuropathic pain. Here we study the analgesic potential of P2X7 receptor antagonism in a rat model of cancer-induced bone pain. In cancer-bearing animals, the P2....... The results suggest that the P2X7R is involved in the mechanisms of cancer-induced bone pain, and that P2X7R antagonism might be a useful analgesic target. No effect was observed in sham or naïve animals, indicating that the P2X7R-mediated effect is state-dependent, and might therefore be an...

  9. Current Studies of Acupuncture in Cancer-Induced Bone Pain Animal Models

    OpenAIRE

    Hee Kyoung Ryu; Yong-Hyeon Baek; Yeon-Cheol Park; Byung-Kwan Seo

    2014-01-01

    Acupuncture is generally accepted as a safe and harmless treatment option for alleviating pain. To explore the pain mechanism, numerous animal models have been developed to simulate specific human pain conditions, including cancer-induced bone pain (CIBP). In this study, we analyzed the current research methodology of acupuncture for the treatment of CIBP. We electronically searched the PubMed database for animal studies published from 2000 onward using these search terms: (bone cancer OR can...

  10. Influence of sex differences on the progression of cancer-induced bone pain

    DEFF Research Database (Denmark)

    Falk, Sarah; Uldall, Maria; Appel, Camilla;

    2013-01-01

    on the progression of cancer-induced bone pain. Materials and Methods: 4T1-luc2 mammary cancer cells were introduced into the femoral cavity of female and male BALB/cJ mice. Bioluminescence tumor signal, pain-related behavior and bone degradation were monitored for 14 days. Results: Female mice demonstrated...... a significantly greater bioluminescence signal on day 2 compared to male mice and, in addition, a significant earlier onset of pain-related behavior was observed in the females. No sex difference was observed for bone degradation. Finally, a strong correlation between pain-related behavior and bone degradation...

  11. The role of purinergic receptors in cancer-induced bone pain

    DEFF Research Database (Denmark)

    Falk, Sarah; Uldall, Maria; Heegaard, Anne-Marie

    2012-01-01

    Cancer-induced bone pain severely compromises the quality of life of many patients suffering from bone metastasis, as current therapies leave some patients with inadequate pain relief. The recent development of specific animal models has increased the understanding of the molecular and cellular...... mechanisms underlying cancer-induced bone pain including the involvement of ATP and the purinergic receptors in the progression of the pain state. In nociception, ATP acts as an extracellular messenger to transmit sensory information both at the peripheral site of tissue damage and in the spinal cord....... Several of the purinergic receptors have been shown to be important for the development and maintenance of neuropathic and inflammatory pain, and studies have demonstrated the importance of both peripheral and central mechanisms. We here provide an overview of the current literature on the role of...

  12. Breast Cancer and Bone Loss

    Science.gov (United States)

    ... Balance › Breast Cancer and Bone Loss Fact Sheet Breast Cancer and Bone Loss July, 2010 Download PDFs English ... JoAnn Pinkerton, MD What is the link between breast cancer and bone loss? Certain treatments for breast cancer ...

  13. Use of Animal Models in Understanding Cancer-induced Bone Pain.

    Science.gov (United States)

    Slosky, Lauren M; Largent-Milnes, Tally M; Vanderah, Todd W

    2015-01-01

    Many common cancers have a propensity to metastasize to bone. Although malignancies often go undetected in their native tissues, bone metastases produce excruciating pain that severely compromises patient quality of life. Cancer-induced bone pain (CIBP) is poorly managed with existing medications, and its multifaceted etiology remains to be fully elucidated. Novel analgesic targets arise as more is learned about this complex and distinct pain state. Over the past two decades, multiple animal models have been developed to study CIBP's unique pathology and identify therapeutic targets. Here, we review animal models of CIBP and the mechanistic insights gained as these models evolve. Findings from immunocompromised and immunocompetent host systems are discussed separately to highlight the effect of model choice on outcome. Gaining an understanding of the unique neuromolecular profile of cancer pain through the use of appropriate animal models will aid in the development of more effective therapeutics for CIBP. PMID:26339191

  14. Calpain Inhibitor Reduces Cancer-induced Bone Pain Possibly Through Inhibition of Osteoclastogenesis in Rat Cancer-induced Bone Pain Model

    Directory of Open Access Journals (Sweden)

    Jia-Ying Xu

    2015-01-01

    Full Text Available Background: Calpain, a calcium-dependent cysteine protease, has been demonstrated to regulate osteoclastogenesis, which is considered one of the major reasons for cancer-induced bone pain (CIBP. In the present study, calpain inhibitor was applied in a rat CIBP model to determine whether it could reduce CIBP through regulation of osteoclastogenesis activity. Methods: A rat CIBP model was established with intratibial injection of Walker 256 cells. Then, the efficacy of intraperitoneal administered calpain inhibitor III (MDL28170, 1 mg/kg on mechanical withdrawal threshold (MWT of bilateral hind paws was examined on postoperative days (PODs 2, 5, 8, 11, and 14. On POD 14, the calpain inhibitor′s effect on tumor bone tartrate-resistant acid phosphatase (TRAP stain and radiology was also carefully investigated. Results: Pain behavioral tests in rats showed that the calpain inhibitor effectively attenuated MWTs of both the surgical side and contralateral side hind paws on POD 5, 8, and 11 (P < 0.05. TRAP-positive cell count of the surgical side bone was significantly decreased in the calpain inhibitor group compared with the vehicle group (P < 0.05. However, bone resorption and destruction measured by radiographs showed no difference between the two groups. Conclusions: Calpain inhibitor can effectively reduce CIBP of both the surgical side and nonsurgical side after tumor injection in a rat CIBP model. It may be due to the inhibition of receptor activator of nuclear factor-kappa B ligand-induced osteoclastogenesis. Whether a calpain inhibitor could be a novel therapeutic target to treat CIBP needs further investigation.

  15. Calpain Inhibitor Reduces Cancer-induced Bone Pain Possibly Through Inhibition of Osteoclastogenesis in Rat Cancer-induced Bone Pain Model

    Institute of Scientific and Technical Information of China (English)

    Jia-Ying Xu; Yu Jiang; Wei Liu; Yu-Guang Huang

    2015-01-01

    Background:Calpain,a calcium-dependent cysteine protease,has been demonstrated to regulate osteoclastogenesis,which is considered one of the major reasons for cancer-induced bone pain (CIBP).In the present study,calpain inhibitor was applied in a rat CIBP model to determine whether it could reduce CIBP through regulation of osteoclastogenesis activity.Methods:A rat CIBP model was established with intratibial injection of Walker 256 cells.Then,the efficacy of intraperitoneal administered calpain inhibitor Ⅲ (MDL28170,1 mg/kg) on mechanical withdrawal threshold (MWT) of bilateral hind paws was examined on postoperative days (PODs) 2,5,8,11,and 14.On POD 14,the calpain inhibitor's effect on tumor bone tartrate-resistant acid phosphatase (TRAP) stain and radiology was also carefully investigated.Results:Pain behavioral tests in rats showed that the calpain inhibitor effectively attenuated MWTs of both the surgical side and contralateral side hind paws on POD 5,8,and 11 (P < 0.05).TRAP-positive cell count of the surgical side bone was significantly decreased in the calpain inhibitor group compared with the vehicle group (P < 0.05).However,bone resorption and destruction measured by radiographs showed no difference between the two groups.Conclusions:Calpain inhibitor can effectively reduce CIBP of both the surgical side and nonsurgical side after tumor injection in a rat CIBP model.It may be due to the inhibition of receptor activator of nuclear factor-kappa B ligand-induced osteoclastogenesis.Whether a calpain inhibitor could be a novel therapeutic target to treat CIBP needs further investigation.

  16. Space Radiation and Bone Loss.

    Science.gov (United States)

    Willey, Jeffrey S; Lloyd, Shane A J; Nelson, Gregory A; Bateman, Ted A

    2011-01-01

    Exposure to ionizing radiation may negatively impact skeletal integrity during extended spaceflight missions to the moon, Mars, or near-Earth asteroids. However, our understanding of the effects of radiation on bone is limited when compared to the effects of weightlessness. In addition to microgravity, astronauts will be exposed to space radiation from solar and cosmic sources. Historically, radiation exposure has been shown to damage both osteoblast precursors and local vasculature within the irradiated volume. The resulting suppression of bone formation and a general state of low bone-turnover is thought to be the primary contributor to bone loss and eventual fracture. Recent investigations using mouse models have identified a rapid, but transient, increase in osteoclast activity immediately after irradiation with both spaceflight and clinically-relevant radiation qualities and doses. Together with a chronic suppression of bone formation after radiation exposure, this acute skeletal damage may contribute to long-term deterioration of bone quality, potentially increasing fracture risk. Direct evidence for the damaging effects of radiation on human bone are primarily demonstrated by the increased incidence of fractures at sites that absorb high doses of radiation during cancer therapy: exposures are considerably higher than what could be expected during spaceflight. However, both the rapidity of bone damage and the chronic nature of the changes appear similar between exposure scenarios. This review will outline our current knowledge of space and clinical exploration exposure to ionizing radiation on skeletal health. PMID:22826632

  17. Differences in electrophysiological properties of functionally identified nociceptive sensory neurons in an animal model of cancer-induced bone pain

    Science.gov (United States)

    Zhu, Yong Fang; Ungard, Robert; Seidlitz, Eric; Zacal, Natalie; Huizinga, Jan; Henry, James L

    2016-01-01

    Background Bone cancer pain is often severe, yet little is known about mechanisms generating this type of chronic pain. While previous studies have identified functional alterations in peripheral sensory neurons that correlate with bone tumours, none has provided direct evidence correlating behavioural nociceptive responses with properties of sensory neurons in an intact bone cancer model. Results In a rat model of prostate cancer-induced bone pain, we confirmed tactile hypersensitivity using the von Frey test. Subsequently, we recorded intracellularly from dorsal root ganglion neurons in vivo in anesthetized animals. Neurons remained connected to their peripheral receptive terminals and were classified on the basis of action potential properties, responses to dorsal root stimulation, and to mechanical stimulation of the respective peripheral receptive fields. Neurons included C-, Aδ-, and Aβ-fibre nociceptors, identified by their expression of substance P. We suggest that bone tumour may induce phenotypic changes in peripheral nociceptors and that these could contribute to bone cancer pain. Conclusions This work represents a significant technical and conceptual advance in the study of peripheral nociceptor functions in the development of cancer-induced bone pain. This is the first study to report that changes in sensitivity and excitability of dorsal root ganglion primary afferents directly correspond to mechanical allodynia and hyperalgesia behaviours following prostate cancer cell injection into the femur of rats. Furthermore, our unique combination of techniques has allowed us to follow, in a single neuron, mechanical pain-related behaviours, electrophysiological changes in action potential properties, and dorsal root substance P expression. These data provide a more complete understanding of this unique pain state at the cellular level that may allow for future development of mechanism-based treatments for cancer-induced bone pain. PMID:27030711

  18. The characteristics of physical activity and gait in patients receiving radiotherapy in cancer induced bone pain

    International Nuclear Information System (INIS)

    Background and purpose: An objective measure of pain relief may add important information to patients’ self assessment, particularly after a treatment. The study aims were to determine whether measures of physical activity and/or gait can be used in characterizing cancer-induced bone pain (CIBP) and whether these biomarkers are sensitive to treatment response, in patients receiving radiotherapy (XRT) for CIBP. Materials and methods: Patients were assessed before (baseline) and 6–8 weeks after XRT (follow up). The following assessments were done: Brief Pain Inventory (BPI), activPAL™ activity meter, and GAITRite® electronic walkway (measure of gait). Wilcoxon, Mann–Whitney and Pearson statistical analyses were done. Results: Sixty patients were assessed at baseline; median worst pain was 7 and walking interference was 5. At follow up 42 patients were assessed. BPI worst pain, average pain, walking interference and total functional interference all improved (p < 0.001). An improvement in functional interference correlated with aspects of physical activity (daily hours standing r = 0.469, p = 0.002) and gait (cadence r = 0.341, p = 0.03). The activPAL and GAITRite parameters did not change following XRT (p > 0.05). In responder analyses there were no differences in activPAL and GAITRite parameters (p > 0.05). Conclusion: Assessment of physical activity and gait allow a characterization of the functional aspects of CIBP, but not in the evaluation of XRT

  19. The Analgesic and Antineuroinflammatory Effect of Baicalein in Cancer-Induced Bone Pain.

    Science.gov (United States)

    Hu, Shan; Chen, Yu; Wang, Zhi-Fu; Mao-Ying, Qi-Liang; Mi, Wen-Li; Jiang, Jian-Wei; Wu, Gen-Cheng; Wang, Yan-Qing

    2015-01-01

    Cancer-induced bone pain (CIBP) is a severe type of chronic pain. It is imperative to explore safe and effective analgesic drugs for CIBP treatment. Baicalein (BE), isolated from the traditional Chinese herbal medicine Scutellaria baicalensis Georgi (or Huang Qin), has been demonstrated to have anti-inflammatory and neuroprotective effects. In this study, we examined the effect of BE on CIBP and the mechanism of this effect. Intrathecal and oral administration of BE at different doses could alleviate the mechanical allodynia in CIBP rats. Intrathecal 100 μg BE could inhibit the production of IL-6 and TNF-α in the spinal cord of CIBP rats. Moreover, intrathecal 100 μg BE could effectively inhibit the activation of p-p38 and p-JNK MAPK signals in CIBP rats. The analgesic effect of BE may be associated with the inhibition of the expression of the inflammatory cytokines IL-6 and TNF-α and through the activation of p-p38 and p-JNK MAPK signals in the spinal cord. These findings suggest that BE is a promising novel analgesic agent for CIBP. PMID:26649065

  20. Metaphyseal bone loss in revision knee arthroplasty.

    Science.gov (United States)

    Ponzio, Danielle Y; Austin, Matthew S

    2015-12-01

    The etiology of bone loss encountered during revision total knee arthroplasty (TKA) is often multifactorial and can include stress shielding, osteolysis, osteonecrosis, infection, mechanical loss due to a grossly loose implant, and iatrogenic loss at the time of implant resection. Selection of the reconstructive technique(s) to manage bone deficiency is determined by the location and magnitude of bone loss, ligament integrity, surgeon experience, and patient factors including the potential for additional revision, functional demand, and comorbidities. Smaller, contained defects are reliably managed with bone graft, cement augmented with screw fixation, or modular augments. Large metaphyseal defects require more extensive reconstruction such as impaction bone grafting with or without mesh augmentation, prosthetic augmentation, use of bulk structural allografts, or use of metaphyseal cones or sleeves. While each technique has advantages and disadvantages, the most optimal method for reconstruction of large metaphyseal bone defects during revision TKA is not clearly established. PMID:26362647

  1. Horizontal alveolar bone loss: A periodontal orphan

    Directory of Open Access Journals (Sweden)

    Jayakumar A

    2010-01-01

    Full Text Available Background: Attempts to successfully regenerate lost alveolar bone have always been a clinician′s dream. Angular defects, at least, have a fairer chance, but the same cannot be said about horizontal bone loss. The purpose of the present study was to evaluate the prevalence of horizontal alveolar bone loss and vertical bone defects in periodontal patients; and later, to correlate it with the treatment modalities available in the literature for horizontal and vertical bone defects. Materials and Methods: The study was conducted in two parts. Part I was the radiographic evaluation of 150 orthopantomographs (OPGs (of patients diagnosed with chronic periodontitis and seeking periodontal care, which were digitized and read using the AutoCAD 2006 software. All the periodontitis-affected teeth were categorized as teeth with vertical defects (if the defect angle was ≤45° and defect depth was ≥3 mm or as having horizontal bone loss. Part II of the study comprised search of the literature on treatment modalities for horizontal and vertical bone loss in four selected periodontal journals. Results: Out of the 150 OPGs studied, 54 (36% OPGs showed one or more vertical defects. Totally, 3,371 teeth were studied, out of which horizontal bone loss was found in 3,107 (92.2% teeth, and vertical defects were found only in 264 (7.8% of the teeth, which was statistically significant (P<.001. Search of the selected journals revealed 477 papers have addressed the treatment modalities for vertical and horizontal types of bone loss specifically. Out of the 477 papers, 461 (96.3% have addressed vertical bone loss, and 18 (3.7% have addressed treatment options for horizontal bone loss. Two papers have addressed both types of bone loss and are included in both categories. Conclusion: Horizontal bone loss is more prevalent than vertical bone loss but has been sidelined by researchers as very few papers have been published on the subject of regenerative treatment

  2. Regenerate augmentation with bone marrow concentrate after traumatic bone loss

    OpenAIRE

    Jan Gessmann; Manfred Köller; Holger Godry; Thomas Armin Schildhauer; Dominik Seybold

    2012-01-01

    Distraction osteogenesis after post-traumatic segmental bone loss of the tibia is a complex and time-consuming procedure that is often complicated due to prolonged consolidation or complete insufficiency of the regenerate. The aim of this feasibility study was to investigate the potential of bone marrow aspiration concentrate (BMAC) for percutaneous regenerate augmentation to accelerate bony consolidation of the regenerate. Eight patients (age 22-64) with an average posttraumatic bone defect ...

  3. Topical Treatment with Xiaozheng Zhitong Paste (XZP Alleviates Bone Destruction and Bone Cancer Pain in a Rat Model of Prostate Cancer-Induced Bone Pain by Modulating the RANKL/RANK/OPG Signaling

    Directory of Open Access Journals (Sweden)

    Yanju Bao

    2015-01-01

    Full Text Available To explore the effects and mechanisms of Xiaozheng Zhitong Paste (XZP on bone cancer pain, Wistar rats were inoculated with vehicle or prostate cancer PC-3 into the tibia bone and treated topically with inert paste, XZP at 15.75, 31.5, or 63 g/kg twice per day for 21 days. Their bone structural damage, nociceptive behaviors, bone osteoclast and osteoblast activity, and the levels of OPG, RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-α were examined. In comparison with that in the placebo group, significantly reduced numbers of invaded cancer cells, decreased levels of bone damage and mechanical threshold and paw withdrawal latency, lower levels of serum TRACP5b, ICTP, PINP, and BAP, and less levels of bone osteoblast and osteoclast activity were detected in the XZP-treated rats (P<0.05. Moreover, significantly increased levels of bone OPG but significantly decreased levels of RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-α were detected in the XZP-treated rats (P<0.05 for all. Together, XZP treatment significantly mitigated the cancer-induced bone damage and bone osteoclast and osteoblast activity and alleviated prostate cancer-induced bone pain by modulating the RANKL/RANK/OPG pathway and bone cancer-related inflammation in rats.

  4. Space Radiation and Bone Loss

    OpenAIRE

    Willey, Jeffrey S.; Lloyd, Shane A. J.; Nelson, Gregory A.; Bateman, Ted A.

    2011-01-01

    Exposure to ionizing radiation may negatively impact skeletal integrity during extended spaceflight missions to the moon, Mars, or near-Earth asteroids. However, our understanding of the effects of radiation on bone is limited when compared to the effects of weightlessness. In addition to microgravity, astronauts will be exposed to space radiation from solar and cosmic sources. Historically, radiation exposure has been shown to damage both osteoblast precursors and local vasculature within th...

  5. Bone loss without the loss of bone mineral material? A new perspective on anorexia nervosa.

    Science.gov (United States)

    Bolotin, H H

    2009-06-01

    Since the advent on non-invasive in vivo clinical bone densitometry, investigators have reported that regional bone mineral material loss accompanies the onset and continuance of anorexia nervosa (AN). Initial single-energy photon absorptiometric (SPA) studies were followed by a succession of dual-energy X-ray absorptiometric (DXA) investigations, and a few single-energy quantitative computer assisted tomographic (SEQCT) bone densitometry vertebral measurements. Although most all DXA studies found a relatively small diminution (approximately 3%) of bone mineral material at lumbar vertebral and proximal femoral bone-sites of AN-afflicted adolescent girls and young women, these findings have been consensually interpreted and near-universally accepted as losses of actual bone mineral material accompanying AN. It has also been claimed by some that about 50% of those beset by AN while still young adolescents were osteoporotic. Nonetheless, over the last intervening 2 decades of these studies, no specific underlying direct bone-biological causal link between AN and trabecular bone material loss has yet been uncovered. The present exposition shows that in vivo SPA, DXA, and SEQCT measurements of bone mineral material losses do not constitute evidence of actual loss of bone material, and that the attribution of osteopenia and osteoporosis to AN-afflicted younger adolescent girls is not sustainable. Rather, the full gamut of these reported bone material "losses" can be accounted for by the already well-documented AN-induced changes in the anthropometrics and compositional mixes of extra-osseous soft tissues (primarily in a very noticeable reduction of extra-skeletal fat) and intra-osseous bone marrow yellowing (marrow hypoplasia and marrow cell necrosis). These changes in soft tissue compositions and anthropometrics alone have been shown to be sufficient to cause in vivo SPA, DXA, and SEQCT to systematically mis-estimate true bone material density and erroneously register

  6. Effect of sex in the MRMT-1 model of cancer-induced bone pain

    DEFF Research Database (Denmark)

    Falk, Sarah; Al-Dihaissy, Tamara; Mezzanotte, Laura;

    2015-01-01

    An overwhelming amount of evidence demonstrates sex-induced variation in pain processing, and has thus increased the focus on sex as an essential parameter for optimization of in vivo models in pain research. Mammary cancer cells are often used to model metastatic bone pain in vivo, and are...

  7. Cancer-induced bone pain sequentially activates the ERK/MAPK pathway in different cell types in the rat spinal cord

    OpenAIRE

    Cheng Hao; Ji Fu-hai; Zhang Yan-bing; Li Cai-fang; Peng Yan; Peng Jun; Yang Jian-ping; Yao Ming; Wang Li-na; Xu Qi-nian; Wang Xiu-yun; Zuo Jian-ling

    2011-01-01

    Abstract Background Previous studies have demonstrates that, after nerve injury, extracellular signal-regulated protein kinase (ERK) activation in the spinal cord-initially in neurons, then microglia, and finally astrocytes. In addition, phosphorylation of ERK (p-ERK) contributes to nociceptive responses following inflammation and/or nerve injury. However, the role of spinal cells and the ERK/MAPK pathway in cancer-induced bone pain (CIBP) remains poorly understood. The present study analyzed...

  8. Inhibition of spinal UCHL1 attenuates pain facilitation in a cancer-induced bone pain model by inhibiting ubiquitin and glial activation

    Science.gov (United States)

    Cheng, Wei; Chen, Yuan-Li; Wu, Liang; Miao, Bei; Yin, Qin; Wang, Jin-Feng; Fu, Zhi-Jian

    2016-01-01

    The present study examined alterations of spinal ubiquitin C-terminal hydrolase L1 (UCHL1), ubiquitin expression and glial activation in the cancer-induced bone pain rats. Furthermore, whether inhibition of spinal UCHL1 could alleviate cancer-induced bone pain was observed. The CIBP model was established by intrathecal Walker 256 mammary gland carcinoma cells in SD rats. The rats of CIBP developed significant pain facilitation in the Von Frey test. Double immunofluorescence analyses revealed that in the spines of CIBP rats, ubiquitin co-localized with NeuN, Iba-1 or GFAP; UCHL1 and NeuN were co-expressed and UCHL1 also co-localized with ubiquitin. The CIBP model induced up-regulation of ubiquitin and UCHL1 in the spines, as well as glial activation. Inhibition of spinal UCHL1 attenuated pain facilitation by down-regulation of ubiquitin expression and glial activation. in the CIBP rats. Our data suggests that UCHL1/ubiquitin distributed and increased in the spines of CIBP rats, that glial activation also increased in the CIBP model and that inhibition of spinal UCHL1 may be an effective method to alleviate cancer-induced bone pain. PMID:27508024

  9. Regenerate augmentation with bone marrow concentrate after traumatic bone loss

    Directory of Open Access Journals (Sweden)

    Jan Gessmann

    2012-03-01

    Full Text Available Distraction osteogenesis after post-traumatic segmental bone loss of the tibia is a complex and time-consuming procedure that is often complicated due to prolonged consolidation or complete insufficiency of the regenerate. The aim of this feasibility study was to investigate the potential of bone marrow aspiration concentrate (BMAC for percutaneous regenerate augmentation to accelerate bony consolidation of the regenerate. Eight patients (age 22-64 with an average posttraumatic bone defect of 82.4 mm and concomitant risk factors (nicotine abuse, soft-tissue defects, obesity and/or circulatory disorders were treated with a modified Ilizarov external frame using an intramedullary cable transportation system. At the end of the distraction phase, each patient was treated with a percutaneously injection of autologous BMAC into the centre of the regenerate. The concentration factor was analysed using flow cytometry. The mean follow up after frame removal was 10 (4-15 months. With a mean healing index (HI of 36.9 d/cm, bony consolidation of the regenerate was achieved in all eight cases. The mean concentration factor of the bone marrow aspirate was 4.6 (SD 1.23. No further operations concerning the regenerate were needed and no adverse effects were observed with the BMAC procedure. This procedure can be used for augmentation of the regenerate in cases of segmental bone transport. Further studies with a larger number of patients and control groups are needed to evaluate a possible higher success rate and accelerating effects on regenerate healing.

  10. Postmenopausal bone loss and the risk of osteoporosis.

    Science.gov (United States)

    Christiansen, C

    1994-01-01

    The two most important risk factors for long-term skeletal health are the peak bone mass and the subsequent rate of bone loss. The rate of bone loss after skeletal maturity is determined by both genetic factors and environmental factors. Furthermore, all factors that impair estrogen production will increase bone loss. The present risk of developing osteoporosis and fractures may be assessed by bone mass measurements in the total skeleton, or in local parts of the skeleton such as the spine, hip and forearm, by single-photon/X-ray absorptiometry (SPA or SXA), dual-photon/energy X-ray absorptiometry (DPA or DXA), or quantitative computed tomography (QCT). Furthermore, the rate of bone loss in postmenopausal women may be assessed by means of a number of biochemical markers. The fútúre risk of developing osteoporosis may thus be determined by combining the values for bone mineral content and bone loss. PMID:8081059

  11. Assessment of bone loss with repeated bone mineral measurements: Application to measurements on the individual patient

    International Nuclear Information System (INIS)

    Longitudinal measurements on lumbar spine and mid-radius were made by bone absorptiometry techniques in 139 normal women. Bone mineral was measured every 6 months over an median interval of 2.1 years. The results revealed that bone loss at different skeletal sites is non-uniform with equal bone loss patterns in all patients and relatively small variations in bone loss rate between normal women. For achieving these results there is strong demand on high precision and properly spaced measuring intervals for long-term rate of loss measurements. For exclusion of progressive degenerative disease a radiographic evaluation of the spine in the beginning and at the end of the study is mandatory as compression fractures or trauma reveal bone mineral changes independent from the agerelated bone loss. These repeated bone mineral measurements are useful for monitoring and follow-up studies during different therapeutic regimens. (orig.)

  12. The molecular signature of the stroma response in prostate cancer-induced osteoblastic bone metastasis highlights expansion of hematopoietic and prostate epithelial stem cell niches.

    Science.gov (United States)

    Özdemir, Berna C; Hensel, Janine; Secondini, Chiara; Wetterwald, Antoinette; Schwaninger, Ruth; Fleischmann, Achim; Raffelsberger, Wolfgang; Poch, Olivier; Delorenzi, Mauro; Temanni, Ramzi; Mills, Ian G; van der Pluijm, Gabri; Thalmann, George N; Cecchini, Marco G

    2014-01-01

    The reciprocal interaction between cancer cells and the tissue-specific stroma is critical for primary and metastatic tumor growth progression. Prostate cancer cells colonize preferentially bone (osteotropism), where they alter the physiological balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, and elicit prevalently an osteoblastic response (osteoinduction). The molecular cues provided by osteoblasts for the survival and growth of bone metastatic prostate cancer cells are largely unknown. We exploited the sufficient divergence between human and mouse RNA sequences together with redefinition of highly species-specific gene arrays by computer-aided and experimental exclusion of cross-hybridizing oligonucleotide probes. This strategy allowed the dissection of the stroma (mouse) from the cancer cell (human) transcriptome in bone metastasis xenograft models of human osteoinductive prostate cancer cells (VCaP and C4-2B). As a result, we generated the osteoblastic bone metastasis-associated stroma transcriptome (OB-BMST). Subtraction of genes shared by inflammation, wound healing and desmoplastic responses, and by the tissue type-independent stroma responses to a variety of non-osteotropic and osteotropic primary cancers generated a curated gene signature ("Core" OB-BMST) putatively representing the bone marrow/bone-specific stroma response to prostate cancer-induced, osteoblastic bone metastasis. The expression pattern of three representative Core OB-BMST genes (PTN, EPHA3 and FSCN1) seems to confirm the bone specificity of this response. A robust induction of genes involved in osteogenesis and angiogenesis dominates both the OB-BMST and Core OB-BMST. This translates in an amplification of hematopoietic and, remarkably, prostate epithelial stem cell niche components that may function as a self-reinforcing bone metastatic niche providing a growth support specific for osteoinductive prostate cancer cells. The induction of this

  13. A radiographic study of alveolar bone loss in Irish schoolchildren

    International Nuclear Information System (INIS)

    Bitewing radiographs were used to assess evidence of alveolar bone loss in 1492 children in the age range 7-12 years. According to the method used in this study, alveolar bone loss was shown to occur in 1.7% of the children, and maxillary teeth were affected twice as frequently as mandibular teeth. (Author)

  14. Alveolar bone loss: mechanisms, potential therapeutic targets, and interventions.

    Science.gov (United States)

    Intini, G; Katsuragi, Y; Kirkwood, K L; Yang, S

    2014-05-01

    This article reviews recent research into mechanisms underlying bone resorption and highlights avenues of investigation that may generate new therapies to combat alveolar bone loss in periodontitis. Several proteins, signaling pathways, stem cells, and dietary supplements are discussed as they relate to periodontal bone loss and regeneration. RGS12 is a crucial protein that mediates osteoclastogenesis and bone destruction, and a potential therapeutic target. RGS12 likely regulates osteoclast differentiation through regulating calcium influx to control the calcium oscillation-NFATc1 pathway. A working model for RGS10 and RGS12 in the regulation of Ca(2+) oscillations during osteoclast differentiation is proposed. Initiation of inflammation depends on host cell-microbe interactions, including the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Oral p38 inhibitors reduced lipopolysaccharide (LPS)-induced bone destruction in a rat periodontitis model but showed unsatisfactory safety profiles. The p38 substrate MK2 is a more specific therapeutic target with potentially superior tolerability. Furthermore, MKP-1 shows anti-inflammatory activity, reducing inflammatory cytokine biosynthesis and bone resorption. Multipotent skeletal stem cell (SSC) populations exist within the bone marrow and periosteum of long bones. These bone-marrow-derived SSCs and periosteum-derived SSCs have shown therapeutic potential in several applications, including bone and periodontal regeneration. The existence of craniofacial bone-specific SSCs is suggested based on existing studies. The effects of calcium, vitamin D, and soy isoflavone supplementation on alveolar and skeletal bone loss in post-menopausal women were investigated. Supplementation resulted in stabilization of forearm bone mass density and a reduced rate of alveolar bone loss over 1 yr, compared with placebo. Periodontal attachment levels were also well-maintained and alveolar bone loss suppressed during 24 wk of

  15. Effects of Spaceflight on Bone: The Rat as an Animal Model for Human Bone Loss

    Science.gov (United States)

    Halloran, B.; Weider, T.; Morey-Holton, E.

    1999-01-01

    The loss of weight bearing during spaceflight results in osteopenia in humans. Decrements in bone mineral reach 3-10% after as little as 75-184 days in space. Loss of bone mineral during flight decreases bone strength and increases fracture risk. The mechanisms responsible for, and the factors contributing to, the changes in bone induced by spaceflight are poorly understood. The rat has been widely used as an animal model for human bone loss during spaceflight. Despite its potential usefulness, the results of bone studies performed in the rat in space have been inconsistent. In some flights bone formation is decreased and cancellous bone volume reduced, while in others no significant changes in bone occur. In June of 1996 Drs. T. Wronski, S. Miller and myself participated in a flight experiment (STS 78) to examine the effects of glucocorticoids on bone during weightlessness. Technically the 17 day flight experiment was flawless. The results, however, were surprising. Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis were the same in flight and ground-based control rats. Normal levels of cancellous bone mass and bone formation were also detected in the lumbar vertebrae and femoral neck of flight rats. Furthermore, periosteal bone formation rate was found to be identical in flight and ground-based control rats. Spaceflight had little or no effect on bone metabolism! These results prompted us to carefully review the changes in bone observed in, and the flight conditions of previous spaceflight missions.

  16. Chronic administration of the selective P2X3, P2X2/3 receptor antagonist, A-317491, transiently attenuates cancer-induced bone pain in mice

    DEFF Research Database (Denmark)

    Hansen, RR; Nasser, A; Falk, S;

    2012-01-01

    The purinergic P2X3 and P2X2/3 receptors are in the peripheral nervous system almost exclusively confined to afferent sensory neurons, where they are found both at peripheral and central synapses. The P2X3 receptor is implicated in both neuropathic and inflammatory pain. However, the role of the ......X3 receptor in chronic cancer-induced bone pain is less known. Here we investigated the effect of systemic acute and chronic administration of the selective P2X3, P2X2/3 receptor antagonist (5-[[[(3-Phenoxyphenyl)methyl][(1S)-1,2,3,4-tetrahydro-1-naphthalenyl]amino]carbonyl]-1...

  17. Role of Oxidative Damage in Radiation-Induced Bone Loss

    Science.gov (United States)

    Schreurs, Ann-Sofie; Alwood, Joshua S.; Limoli, Charles L.; Globus, Ruth K.

    2014-01-01

    During prolonged spaceflight, astronauts are exposed to both microgravity and space radiation, and are at risk for increased skeletal fragility due to bone loss. Evidence from rodent experiments demonstrates that both microgravity and ionizing radiation can cause bone loss due to increased bone-resorbing osteoclasts and decreased bone-forming osteoblasts, although the underlying molecular mechanisms for these changes are not fully understood. We hypothesized that excess reactive oxidative species (ROS), produced by conditions that simulate spaceflight, alter the tight balance between osteoclast and osteoblast activities, leading to accelerated skeletal remodeling and culminating in bone loss. To test this, we used the MCAT mouse model; these transgenic mice over-express the human catalase gene targeted to mitochondria, the major organelle contributing free radicals. Catalase is an anti-oxidant that converts reactive species, hydrogen peroxide into water and oxygen. This animal model was selected as it displays extended lifespan, reduced cardiovascular disease and reduced central nervous system radio-sensitivity, consistent with elevated anti-oxidant activity conferred by the transgene. We reasoned that mice overexpressing catalase in mitochondria of osteoblast and osteoclast lineage cells would be protected from the bone loss caused by simulated spaceflight. Over-expression of human catalase localized to mitochondria caused various skeletal phenotypic changes compared to WT mice; this includes greater bone length, decreased cortical bone area and moment of inertia, and indications of altered microarchitecture. These findings indicate mitochondrial ROS are important for normal bone-remodeling and skeletal integrity. Catalase over-expression did not fully protect skeletal tissue from structural decrements caused by simulated spaceflight; however there was significant protection in terms of cellular oxidative damage (MDA levels) to the skeletal tissue. Furthermore, we

  18. Probiotics protect mice from ovariectomy-induced cortical bone loss.

    Directory of Open Access Journals (Sweden)

    Claes Ohlsson

    Full Text Available The gut microbiota (GM modulates the hosts metabolism and immune system. Probiotic bacteria are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host and can alter the composition of the GM. Germ-free mice have increased bone mass associated with reduced bone resorption indicating that the GM also regulates bone mass. Ovariectomy (ovx results in bone loss associated with altered immune status. The purpose of this study was to determine if probiotic treatment protects mice from ovx-induced bone loss. Mice were treated with either a single Lactobacillus (L strain, L. paracasei DSM13434 (L. para or a mixture of three strains, L. paracasei DSM13434, L. plantarum DSM 15312 and DSM 15313 (L. mix given in the drinking water during 6 weeks, starting two weeks before ovx. Both the L. para and the L. mix treatment protected mice from ovx-induced cortical bone loss and bone resorption. Cortical bone mineral content was higher in both L. para and L. mix treated ovx mice compared to vehicle (veh treated ovx mice. Serum levels of the resorption marker C-terminal telopeptides and the urinary fractional excretion of calcium were increased by ovx in the veh treated but not in the L. para or the L. mix treated mice. Probiotic treatment reduced the expression of the two inflammatory cytokines, TNFα and IL-1β, and increased the expression of OPG, a potent inhibitor of osteoclastogenesis, in cortical bone of ovx mice. In addition, ovx decreased the frequency of regulatory T cells in bone marrow of veh treated but not probiotic treated mice. In conclusion, treatment with L. para or the L. mix prevents ovx-induced cortical bone loss. Our findings indicate that these probiotic treatments alter the immune status in bone resulting in attenuated bone resorption in ovx mice.

  19. Receptor tyrosine kinase inhibition causes simultaneous bone loss and excess bone formation within growing bone in rats

    International Nuclear Information System (INIS)

    During postnatal skeletal growth, adaptation to mechanical loading leads to cellular activities at the growth plate. It has recently become evident that bone forming and bone resorbing cells are affected by the receptor tyrosine kinase (RTK) inhibitor imatinib mesylate (STI571, Gleevec (registered) ). Imatinib targets PDGF, ABL-related gene, c-Abl, c-Kit and c-Fms receptors, many of which have multiple functions in the bone microenvironment. We therefore studied the effects of imatinib in growing bone. Young rats were exposed to imatinib (150 mg/kg on postnatal days 5-7, or 100 mg/kg on postnatal days 5-13), and the effects of RTK inhibition on bone physiology were studied after 8 and 70 days (3-day treatment), or after 14 days (9-day treatment). X-ray imaging, computer tomography, histomorphometry, RNA analysis and immunohistochemistry were used to evaluate bone modeling and remodeling in vivo. Imatinib treatment eliminated osteoclasts from the metaphyseal osteochondral junction at 8 and 14 days. This led to a resorption arrest at the growth plate, but also increased bone apposition by osteoblasts, thus resulting in local osteopetrosis at the osteochondral junction. The impaired bone remodelation observed on day 8 remained significant until adulthood. Within the same bone, increased osteoclast activity, leading to bone loss, was observed at distal bone trabeculae on days 8 and 14. Peripheral quantitative computer tomography (pQCT) and micro-CT analysis confirmed that, at the osteochondral junction, imatinib shifted the balance from bone resorption towards bone formation, thereby altering bone modeling. At distal trabecular bone, in turn, the balance was turned towards bone resorption, leading to bone loss. - Research highlights: → 3-Day imatinib treatment. → Causes growth plate anomalies in young rats. → Causes biomechanical changes and significant bone loss at distal trabecular bone. → Results in loss of osteoclasts at osteochondral junction.

  20. The Effect of Bone Loss Pattern on the Structural Capacity of the Proximal Femur

    Institute of Scientific and Technical Information of China (English)

    FAN Li-xia; Eric Wang

    2006-01-01

    The effect of age-related bone loss on the structural capacity of the proximal femur were investigated by Finite Element Analysis(FEA). Four bone loss patterns were considered. These were "uniform cortical bone loss", "neck cortical bone loss", "intertrochanteric cortical bone loss" and "uniform trabecular bone loss". The results show that the two "non-uniform cortical bone loss" patterns are more dangerous than the "uniform cortical bone loss" pattern, and that the cortical bone loss in intertrochanteric region is associated with a greater reduction in cortical failure load than the cortical bone loss in the femoral neck. The trabecular bone loss causes a limited decrease in both cortical failure and trabecular failure loads. This research should be helpful to the clinical assessment of femur fracture risk due to age-related bone loss.

  1. Periprosthetic bone loss: diagnostic and therapeutic approaches

    OpenAIRE

    Loredana Cavalli; Maria Luisa Brandi

    2014-01-01

    Total joint replacement surgery is being performed on an increasingly large part of the population. Clinical longevity of implants depends on their osseointegration, which is influenced by the load, the characteristics of the implant and the bone-implant interface, as well as by the quality and quantity of the surrounding bone. Aseptic loosening due to periprosthetic osteolysis is the most frequent known cause of implant failure. Wear of prosthetic materials results in the formation of numero...

  2. Biglycan deficiency interferes with ovariectomy-induced bone loss

    DEFF Research Database (Denmark)

    Nielsen, Karina L; Allen, Matthew R; Bloomfield, Susan A;

    2003-01-01

    Biglycan is a matrix proteoglycan with a possible role in bone turnover. In a 4-week study with sham-operated or OVX biglycan-deficient or wildtype mice, we show that biglycan-deficient mice are resistant to OVX-induced trabecular bone loss and that there is a gender difference in the response to...

  3. Pathophysiology of bone loss in the female athlete.

    Science.gov (United States)

    Lambrinoudaki, Irene; Papadimitriou, Dimitra

    2010-09-01

    Low bone mass is frequent among female athletes. The "female athlete triad" is a term that describes the interaction among energy availability, menstrual function, and bone metabolism that may lead to amenorrhea and osteopenia or osteoporosis. The main pathophysiologic mechanisms that lead to low bone mass in female athletes are low energy availability and functional hypothalamic amenorrhea. Increased energy expenditure and/or decreased energy intake, as well as the presence of eating disorders, are associated with low bone mass. In addition, menstrual dysfunction is quite common, especially among athletes competing in sports favoring leanness, and also associates with low bone mass. Screening for bone loss in female athletes should take place in the presence of amenorrhea or body mass index <18 kg/m(2) . Management of low bone mass aims to restore normal energy availability and nutritional habits. Hormone replacement therapy has no effect in abnormally underweight patients unless normal eating behaviors are restored. PMID:20840252

  4. Paradoxical Response to Mechanical Unloading in Bone Loss, Microarchitecture, and Bone Turnover Markers

    OpenAIRE

    Sun, Xiaodi; Kaiyun YANG; Wang, Chune; Cao, Sensen; Merritt, Mackenzie; Hu, Yingwei; Xu, Xin

    2015-01-01

    Background: Sclerostin, encoded by the SOST gene, has been implicated in the response to mechanical loading in bone. Some studies demonstrated that unloading leads to up-regulated SOST expression, which may induce bone loss. Purpose: Most reported studies regarding the changes caused by mechanical unloading were only based on a single site. Considering that the longitudinal bone growth leads to cells of different age with different sensitivity to unloading, we hypothesized that bone turnover ...

  5. Platform switching: A panacea for bone loss??

    OpenAIRE

    Desai, Manthan H.; Patil, Veena A.

    2013-01-01

    The goal of modern implant therapy entails more than just the successful osseointegration of the implant. A successful result must also include an esthetic and functional restoration surrounded by stable peri-implant tissue levels that are in harmony with the existing dentition. In an attempt to improve long-term bone maintenance around implants, a new implant-to abutment connection referred to as “platform switching” has been proposed. It refers to the use of an abutment of smaller diameter ...

  6. RANK, RANKL and osteoprotegerin in arthritic bone loss

    Directory of Open Access Journals (Sweden)

    M.C. Bezerra

    2005-02-01

    Full Text Available Rheumatoid arthritis is characterized by the presence of inflammatory synovitis and destruction of joint cartilage and bone. Tissue proteinases released by synovia, chondrocytes and pannus can cause cartilage destruction and cytokine-activated osteoclasts have been implicated in bone erosions. Rheumatoid arthritis synovial tissues produce a variety of cytokines and growth factors that induce monocyte differentiation to osteoclasts and their proliferation, activation and longer survival in tissues. More recently, a major role in bone erosion has been attributed to the receptor activator of nuclear factor kappa B ligand (RANKL released by activated lymphocytes and osteoblasts. In fact, osteoclasts are markedly activated after RANKL binding to the cognate RANK expressed on the surface of these cells. RANKL expression can be upregulated by bone-resorbing factors such as glucocorticoids, vitamin D3, interleukin 1 (IL-1, IL-6, IL-11, IL-17, tumor necrosis factor-alpha, prostaglandin E2, or parathyroid hormone-related peptide. Supporting this idea, inhibition of RANKL by osteoprotegerin, a natural soluble RANKL receptor, prevents bone loss in experimental models. Tumor growth factor-ß released from bone during active bone resorption has been suggested as one feedback mechanism for upregulating osteoprotegerin and estrogen can increase its production on osteoblasts. Modulation of these systems provides the opportunity to inhibit bone loss and deformity in chronic arthritis.

  7. Bone cancer induces a unique central sensitization through synaptic changes in a wide area of the spinal cord

    Directory of Open Access Journals (Sweden)

    Uta Daisuke

    2010-07-01

    Full Text Available Abstract Background Chronic bone cancer pain is thought to be partly due to central sensitization. Although murine models of bone cancer pain revealed significant neurochemical changes in the spinal cord, it is not known whether this produces functional alterations in spinal sensory synaptic transmission. In this study, we examined excitatory synaptic responses evoked in substantia gelatinosa (SG, lamina II neurons in spinal cord slices of adult mice bearing bone cancer, using whole-cell voltage-clamp recording techniques. Results Mice at 14 to 21 days after sarcoma implantation into the femur exhibited hyperalgesia to mechanical stimuli applied to the skin of the ipsilateral hind paw, as well as showing spontaneous and movement evoked pain-related behaviors. SG neurons exhibited spontaneous excitatory postsynaptic currents (EPSCs. The amplitudes of spontaneous EPSCs were significantly larger in cancer-bearing than control mice without any changes in passive membrane properties of SG neurons. In the presence of TTX, the amplitude of miniature EPSCs in SG neurons was increased in cancer-bearing mice and this was observed for cells sampled across a wide range of lumbar segmental levels. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA receptor- and N-methyl-D-aspartate (NMDA receptor-mediated EPSCs evoked by focal stimulation were also enhanced in cancer-bearing mice. Dorsal root stimulation elicited mono- and/or polysynaptic EPSCs that were caused by the activation of Aδ and/or C afferent fibers in SG neurons from both groups of animals. The number of cells receiving monosynaptic inputs from Aδ and C fibers was not different between the two groups. However, the amplitude of the monosynaptic C fiber-evoked EPSCs and the number of SG neurons receiving polysynaptic inputs from Aδ and C fibers were increased in cancer-bearing mice. Conclusions These results show that spinal synaptic transmission mediated through Aδ and C fibers is

  8. Intermittent recombinant TSH injections prevent ovariectomy-induced bone loss

    OpenAIRE

    Sun, Li; Vukicevic, Slobodan; Baliram, Ramkumarie; Yang, Guozhe; Sendak, Rebecca; McPherson, John; Zhu, Ling-ling; Iqbal, Jameel; Latif, Rauf; Natrajan, Arjun; Arabi, Ario; Yamoah, Kosj; Moonga, Baljit S.; Gabet, Yankel; Davies, Terry F.

    2008-01-01

    We recently described the direct effects of thyroid-stimulating hormone (TSH) on bone and suggested that the bone loss in hyperthyroidism, hitherto attributed solely to elevated thyroid hormone levels, could at least in part arise from accompanying decrements in serum TSH. Recent studies on both mice and human subjects provide compelling evidence that thyroid hormones and TSH have the opposite effects on the skeleton. Here, we show that TSH, when injected intermittently into rodents, even at ...

  9. Anabolic Vitamin D Analogs as Countermeasures to Bone Loss

    Science.gov (United States)

    Li, Wei; Duncan, Randall L.; Karin, Norman J.; Farach-Carson, Mary C.

    1997-01-01

    We demonstrated for the first time that vitamin D3 influences the effect of PTH on bone cell calcium ion levels. This is a rapid effect, taking place within seconds/minutes. This may prove to be a critical contribution to our understanding of bone physiology in that these two hormones are among the most potent regulators of bone calcium content and of systemic calcium homeostasis. Together with the data gathered from the study of astronauts exposed to microgravity for extended periods, these observations suggest the interaction of vitamin D3 and PTH as a possible therapeutic target in the treatment of bone loss disorders such as osteoporosis and disuse atrophy. Chronic exposure of cultured osteoblasts to vitamin D, altered the number of voltage-sensitive Ca(+2) channels expressed. Estrogen treatment yielded a similar result, suggesting that there is overlap in the mechanism by which these hormones elicit long-term effects on bone cell calcium homeostasis.

  10. Predictors of bone loss in revision total knee arthroplasty.

    Science.gov (United States)

    Bloomfield, Michael R; Klika, Alison K; Lee, Ho H; Joyce, David M; Mehta, Priyesh; Barsoum, Wael K

    2010-03-01

    Revision total knee arthroplasty (RTKA) requires preoperative planning to enable the reconstruction of bony deficiencies. The objective of this project was to identify predictors of bone loss management at RTKA based on the preoperative failure mode and patient demographics known preoperatively. We retrospectively reviewed 245 consecutive RTKA procedures in which the same revision knee system was utilized. Patient demographic and treatment data were recorded, and locations of bone loss were identified based on the reconstructive management. We identified significant predictors for use of femoral augments at all four positions. Several predictors significantly predisposed to use of a thick (>19 mm) polyethylene; however, no predictors of tibial augments were significant. Although the reconstruction of bone loss is primarily based on the intraoperative assessment, these findings may provide additional information to help the surgeon prepare for difficult revision procedures. PMID:20812582

  11. Genistein supplementation increases bone turnover but does not prevent alcohol-induced bone loss in male mice

    Science.gov (United States)

    Chronic alcohol consumption results in bone loss through increased bone resorption and decreased bone formation. These effects can be reversed by estradiol (E2) supplementation. Soy diets are suggested to have protective effects on bone loss in men and women, as a result of the presence of soy prote...

  12. Dried plum's unique capacity to reverse bone loss and alter bone metabolism in postmenopausal osteoporosis model.

    Directory of Open Access Journals (Sweden)

    Elizabeth Rendina

    Full Text Available Interest in dried plum has increased over the past decade due to its promise in restoring bone and preventing bone loss in animal models of osteoporosis. This study compared the effects of dried plum on bone to other dried fruits and further explored the potential mechanisms of action through which dried plum may exert its osteoprotective effects. Adult osteopenic ovariectomized (OVX C57BL/6 mice were fed either a control diet or a diet supplemented with 25% (w/w dried plum, apple, apricot, grape or mango for 8 weeks. Whole body and spine bone mineral density improved in mice consuming the dried plum, apricot and grape diets compared to the OVX control mice, but dried plum was the only fruit to have an anabolic effect on trabecular bone in the vertebra and prevent bone loss in the tibia. Restoration of biomechanical properties occurred in conjunction with the changes in trabecular bone in the spine. Compared to other dried fruits in this study, dried plum was unique in its ability to down-regulate osteoclast differentiation coincident with up-regulating osteoblast and glutathione (GPx activity. These alterations in bone metabolism and antioxidant status compared to other dried fruits provide insight into dried plum's unique effects on bone.

  13. Soy Isoflavones and Osteoporotic Bone Loss: A Review with an Emphasis on Modulation of Bone Remodeling.

    Science.gov (United States)

    Zheng, Xi; Lee, Sun-Kyeong; Chun, Ock K

    2016-01-01

    Osteoporosis is an age-related disorder that affects both women and men, although estrogen deficiency induced by menopause accelerates bone loss in older women. As the demographic shifts to a more aged population, a growing number of men and women will be afflicted with osteoporosis. Since the current drug therapies available have multiple side effects, including increased risk of developing certain types of cancer or complications, a search for potential nonpharmacologic alternative therapies for osteoporosis is of prime interest. Soy isoflavones (SI) have demonstrated potential bone-specific effects in a number of studies. This article provides a systematic review of studies on osteoporotic bone loss in relation to SI intake from diet or supplements to comprehensively explain how SI affect the modulation of bone remodeling. Evidence from epidemiologic studies supports that dietary SI attenuate menopause-induced osteoporotic bone loss by decreasing bone resorption and stimulating bone formation. Other studies have also illustrated that bone site-specific trophic and synergistic effects combined with exercise intervention might contribute to improve the bioavailability of SI or strengthen the bone-specific effects. To date, however, the effects of dietary SI on osteoporotic bone loss remain inconclusive, and study results vary from study to study. The current review will discuss the potential factors that result in the conflicting outcomes of these studies, including dosages, intervention materials, study duration, race, and genetic differences. Further well-designed studies are needed to fully understand the underlying mechanism and evaluate the effects of SI on osteoporosis in humans. PMID:26670451

  14. Rate of bone loss in postmenopausal and osteoporotic women

    International Nuclear Information System (INIS)

    Regional and total bone mass were determined in three groups of women by photon absorptiometry of the distal radius [bone mineral content (BMC)] and total neutron activation analysis [total body calcium (TBCa)], respectively. There were three groups of patients: group A, osteoporotic women treated with a variety of pharmacologic agents; group B, osteoporotic women (controls) taking only calcium supplements; and group C, normal postmenopausal women. The mean TBCa and BMC were considerably higher in the postmenopausal women than in the osteoporotic women. The rate of change of bone mass in group C was -0.45%/yr and -0.9%/yr for the total skeleton and radius, respectively. Group B had no significant rate of loss, whereas group A demonstrated a significant increase in TBCa of 0.75%/yr with no change in the BMC of the radius. There were no significant between-subject correlations for the slopes (rates of change) of the two bone mineral measurements

  15. Is bone loss after gastric bypass surgery associated with the extent of weight loss?

    OpenAIRE

    Shapses, Sue A

    2009-01-01

    This Practice Point commentary discusses a prospective study by Fleisher et al. that showed bone loss in response to extreme weight loss in 23 patients following Roux-en-Y gastric bypass surgery. The decline in BMD at the hip, but not at the spine or distal radius, was found to be proportional to the extent of weight loss. Although dietary calcium and vitamin D intake markedly increased after surgery, serum 25 hydroxyvitamin D, serum parathyroid hormone and urinary calcium l...

  16. Modeling the Mechanical Consequences of Age-Related Trabecular Bone Loss by XFEM Simulation

    Science.gov (United States)

    Fan, Ruoxun; Zhang, Xianbin; Liu, Jun; Jia, Zhengbin; Zhu, Dong

    2016-01-01

    The elderly are more likely to suffer from fracture because of age-related trabecular bone loss. Different bone loss locations and patterns have different effects on bone mechanical properties. Extended finite element method (XFEM) can simulate fracture process and was suited to investigate the effects of bone loss on trabecular bone. Age-related bone loss is indicated by trabecular thinning and loss and may occur at low-strain locations or other random sites. Accordingly, several ideal normal and aged trabecular bone models were created based on different bone loss locations and patterns; then, fracture processes from crack initiation to complete failure of these models were observed by XFEM; finally, the effects of different locations and patterns on trabecular bone were compared. Results indicated that bone loss occurring at low-strain locations was more detrimental to trabecular bone than that occurring at other random sites; meanwhile, the decrease in bone strength caused by trabecular loss was higher than that caused by trabecular thinning, and the effects of vertical trabecular loss on mechanical properties were more severe than horizontal trabecular loss. This study provided a numerical method to simulate trabecular bone fracture and distinguished different effects of the possible occurrence of bone loss locations and patterns on trabecular bone.

  17. Cilostazol attenuates ovariectomy-induced bone loss by inhibiting osteoclastogenesis.

    Directory of Open Access Journals (Sweden)

    Ke Ke

    Full Text Available Cilostazol has been reported to alleviate the metabolic syndrome induced by increased intracellular adenosine 3',5'-cyclic monophosphate (cAMP levels, which is also associated with osteoclast (OC differentiation. We hypothesized that bone loss might be attenuated via an action on OC by cilostazol.To test this idea, we investigated the effect of cilostazol on ovariectomy (OVX-induced bone loss in mice and on OC differentiation in vitro, using μCT and tartrate-resistant acid phosphatase staining, respectively. Cilostazol prevented from OVX-induced bone loss and decreased oxidative stress in vivo. It also decreased the number and activity of OC in vitro. The effect of cilostazol on reactive oxygen species (ROS occurred via protein kinase A (PKA and cAMP-regulated guanine nucleotide exchange factor 1, two major effectors of cAMP. Knockdown of NADPH oxidase using siRNA of p47phox attenuated the inhibitory effect of cilostazol on OC formation, suggesting that decreased OC formation by cilostazol was partly due to impaired ROS generation. Cilostazol enhanced phosphorylation of nuclear factor of activated T cells, cytoplasmic 1 (NFAT2 at PKA phosphorylation sites, preventing its nuclear translocation to result in reduced receptor activator of nuclear factor-κB ligand-induced NFAT2 expression and decreased binding of nuclear factor-κB-DNA, finally leading to reduced levels of two transcription factors required for OC differentiation.Our data highlight the therapeutic potential of cilostazol for attenuating bone loss and oxidative stress caused by loss of ovarian function.

  18. Nutritional Interventions for Cancer-induced Cachexia

    OpenAIRE

    Gullett, Norleena P.; Mazurak, Vera; Hebbar, Gautam; Ziegler, Thomas R

    2011-01-01

    Cancer-induced cachexia remains a significant cause of morbidity and mortality in cancer treatment. Cancer research and development continues at an aggressive pace and yet a degree of cancer-induced cachexia is experienced by up to 80% of advanced stage cancer patients. Unfortunately, there are no established treatment regimens for this condition. Weight loss and fatigue consistently appear in patient oncologic histories and progress notes. However, few oncologists fully understand the pathol...

  19. Simulating Bone Loss in Microgravity Using Mathematical Formulations of Bone Remodeling

    Science.gov (United States)

    Pennline, James A.

    2009-01-01

    Most mathematical models of bone remodeling are used to simulate a specific bone disease, by disrupting the steady state or balance in the normal remodeling process, and to simulate a therapeutic strategy. In this work, the ability of a mathematical model of bone remodeling to simulate bone loss as a function of time under the conditions of microgravity is investigated. The model is formed by combining a previously developed set of biochemical, cellular dynamics, and mechanical stimulus equations in the literature with two newly proposed equations; one governing the rate of change of the area of cortical bone tissue in a cross section of a cylindrical section of bone and one governing the rate of change of calcium in the bone fluid. The mechanical stimulus comes from a simple model of stress due to a compressive force on a cylindrical section of bone which can be reduced to zero to mimic the effects of skeletal unloading in microgravity. The complete set of equations formed is a system of first order ordinary differential equations. The results of selected simulations are displayed and discussed. Limitations and deficiencies of the model are also discussed as well as suggestions for further research.

  20. Mast Cells Contribute to Porphyromonas gingivalis-induced Bone Loss.

    Science.gov (United States)

    Malcolm, J; Millington, O; Millhouse, E; Campbell, L; Adrados Planell, A; Butcher, J P; Lawrence, C; Ross, K; Ramage, G; McInnes, I B; Culshaw, S

    2016-06-01

    Periodontitis is a chronic inflammatory and bone-destructive disease. Development of periodontitis is associated with dysbiosis of the microbial community, which may be caused by periodontal bacteria, such as Porphyromonas gingivalis Mast cells are sentinels at mucosal surfaces and are a potent source of inflammatory mediators, including tumor necrosis factors (TNF), although their role in the pathogenesis of periodontitis remains to be elucidated. This study sought to determine the contribution of mast cells to local bone destruction following oral infection with P. gingivalis Mast cell-deficient mice (Kit(W-sh/W-sh)) were protected from P. gingivalis-induced alveolar bone loss, with a reduction in anti-P. gingivalis serum antibody titers compared with wild-type infected controls. Furthermore, mast cell-deficient mice had reduced expression of Tnf, Il6, and Il1b mRNA in gingival tissues compared with wild-type mice. Mast cell-engrafted Kit(W-sh/W-sh) mice infected with P. gingivalis demonstrated alveolar bone loss and serum anti-P. gingivalis antibody titers equivalent to wild-type infected mice. The expression of Tnf mRNA in gingival tissues of Kit(W-sh/W-sh) mice was elevated following the engraftment of mast cells, indicating that mast cells contributed to the Tnf transcript in gingival tissues. In vitro, mast cells degranulated and released significant TNF in response to oral bacteria, and neutralizing TNF in vivo abrogated alveolar bone loss following P. gingivalis infection. These data indicate that mast cells and TNF contribute to the immunopathogenesis of periodontitis and may offer therapeutic targets. PMID:26933137

  1. Bone loss in inflammatory Bowel disease: our multicentric study

    Directory of Open Access Journals (Sweden)

    Alessandro Geraci

    2011-05-01

    Full Text Available Patients with inflammatory bowel disease are at increased risk of developing disorder in bone and mineral metabolism The study was aimed to determine if inflammatory bowel disease (IBD is a risk factor for osteoporosis in 103 adult patients. We included 103 IBD patients, 67 patients with Crohn’s disease (CD and 36 with ulcerative colitis (UC. Bone mineral density was measured by dual-energy X-ray absorptiometry. We used T score to express bone loss (osteopenia: -2.5 SD <-1 SD, osteoporosis: T <-2.5 SD. Plain x-rays were examined to search for vertebral compression or spontaneous fractures before DEXA. Among the 103 patients, 47.7% exhibited osteopenia of the femoral neck and 62.3% of the lumbar spine, with no significant difference between CD and UC. The prevalence of osteoporosis of the lumbar spine was significantly higher in CD patients (41.2% versus 8.7%. Osteoporosis is frequent in IBD patients, especially in CD patients. Female gender, malnutrition (body mass index <20 kg/m2, disease course (>2 years and active disease would be risk factors of bone mineral loss in IBD.

  2. Bone loss and human adaptation to lunar gravity

    Science.gov (United States)

    Keller, T. S.; Strauss, A. M.

    1992-01-01

    Long-duration space missions and establishment of permanently manned bases on the Moon and Mars are currently being planned. The weightless environment of space and the low-gravity environments of the Moon and Mars pose an unknown challenge to human habitability and survivability. Of particular concern in the medical research community today is the effect of less than Earth gravity on the human skeleton, since the limits, if any, of human endurance in low-gravity environments are unknown. This paper provides theoretical predictions on bone loss and skeletal adaptation to lunar and other nonterrestrial-gravity environments based upon the experimentally derived relationship, density approximately (mass x gravity)(exp 1/8). The predictions are compared to skeletal changes reported during bed rest, immobilization, certrifugation, and spaceflight. Countermeasures to reduce bone losses in fractional gravity are also discussed.

  3. “Subcritical” Glenoid Bone Loss Increases Redislocation Rates in Primary Arthroscopic Bankart Repair

    OpenAIRE

    Shaha, James S.; Cook, Jay B.; Song, Daniel J.; Rowles, Douglas J.; Bottoni, Craig R.; Shaha, Steven H.; Tokish, John M.

    2014-01-01

    Objectives: While bone loss is increasingly recognized as a risk factor for failure after arthroscopic stabilization, the precise definition of critical bone loss has not been defined. Additionally, there is no clarity on the amount of bone loss routinely present in patients presenting for primary arthroscopic stabilization of anterior glenohumeral instability. The purpose of this study is to report on the average bone loss measured in primary isolated Bankart reconstructions of the shoulder ...

  4. Whey Protein Concentrate Hydrolysate Prevents Bone Loss in Ovariectomized Rats.

    Science.gov (United States)

    Kim, Jonggun; Kim, Hyung Kwan; Kim, Saehun; Imm, Ji-Young; Whang, Kwang-Youn

    2015-12-01

    Milk is known as a safe food and contains easily absorbable minerals and proteins, including whey protein, which has demonstrated antiosteoporotic effects on ovariectomized rats. This study evaluated the antiosteoporotic effect of whey protein concentrate hydrolysate (WPCH) digested with fungal protease and whey protein concentrate (WPC). Two experiments were conducted to determine (1) efficacy of WPCH and WPC and (2) dose-dependent impact of WPCH in ovariectomized rats (10 weeks old). In Experiment I, ovariectomized rats (n=45) were allotted into three dietary treatments of 10 g/kg diet of WPC, 10 g/kg diet of WPCH, and a control diet. In Experiment II, ovariectomized rats (n=60) were fed four different diets (0, 10, 20, and 40 g/kg of WPCH). In both experiments, sham-operated rats (n=15) were also fed a control diet containing the same amount of amino acids and minerals as dietary treatments. After 6 weeks, dietary WPCH prevented loss of bone, physical properties, mineral density, and mineral content, and improved breaking strength of femurs, with similar effect to WPC. The bone resorption enzyme activity (tartrate resistance acid phosphatase) in tibia epiphysis decreased in response to WPCH supplementation, while bone formation enzyme activity (alkaline phosphatase) was unaffected by ovariectomy and dietary treatment. Bone properties and strength increased as the dietary WPCH level increased (10 and 20 g/kg), but there was no difference between the 20 and 40 g/kg treatment. WPCH and WPC supplementation ameliorated bone loss induced by ovariectomy in rats. PMID:26367331

  5. Wnt16 Is Associated with Age-Related Bone Loss and Estrogen Withdrawal in Murine Bone.

    Science.gov (United States)

    Todd, Henry; Galea, Gabriel L; Meakin, Lee B; Delisser, Peter J; Lanyon, Lance E; Windahl, Sara H; Price, Joanna S

    2015-01-01

    Genome Wide Association Studies suggest that Wnt16 is an important contributor to the mechanisms controlling bone mineral density, cortical thickness, bone strength and ultimately fracture risk. Wnt16 acts on osteoblasts and osteoclasts and, in cortical bone, is predominantly derived from osteoblasts. This led us to hypothesize that low bone mass would be associated with low levels of Wnt16 expression and that Wnt16 expression would be increased by anabolic factors, including mechanical loading. We therefore investigated Wnt16 expression in the context of ageing, mechanical loading and unloading, estrogen deficiency and replacement, and estrogen receptor α (ERα) depletion. Quantitative real time PCR showed that Wnt16 mRNA expression was lower in cortical bone and marrow of aged compared to young female mice. Neither increased nor decreased (by disuse) mechanical loading altered Wnt16 expression in young female mice, although Wnt16 expression was decreased following ovariectomy. Both 17β-estradiol and the Selective Estrogen Receptor Modulator Tamoxifen increased Wnt16 expression relative to ovariectomy. Wnt16 and ERβ expression were increased in female ERα-/- mice when compared to Wild Type. We also addressed potential effects of gender on Wnt16 expression and while the expression was lower in the cortical bone of aged males as in females, it was higher in male bone marrow of aged mice compared to young. In the kidney, which we used as a non-bone reference tissue, Wnt16 expression was unaffected by age in either males or females. In summary, age, and its associated bone loss, is associated with low levels of Wnt16 expression whereas bone loss associated with disuse has no effect on Wnt16 expression. In the artificially loaded mouse tibia we observed no loading-related up-regulation of Wnt16 expression but provide evidence that its expression is influenced by estrogen receptor signaling. These findings suggest that while Wnt16 is not an obligatory contributor to

  6. Wnt16 Is Associated with Age-Related Bone Loss and Estrogen Withdrawal in Murine Bone.

    Directory of Open Access Journals (Sweden)

    Henry Todd

    Full Text Available Genome Wide Association Studies suggest that Wnt16 is an important contributor to the mechanisms controlling bone mineral density, cortical thickness, bone strength and ultimately fracture risk. Wnt16 acts on osteoblasts and osteoclasts and, in cortical bone, is predominantly derived from osteoblasts. This led us to hypothesize that low bone mass would be associated with low levels of Wnt16 expression and that Wnt16 expression would be increased by anabolic factors, including mechanical loading. We therefore investigated Wnt16 expression in the context of ageing, mechanical loading and unloading, estrogen deficiency and replacement, and estrogen receptor α (ERα depletion. Quantitative real time PCR showed that Wnt16 mRNA expression was lower in cortical bone and marrow of aged compared to young female mice. Neither increased nor decreased (by disuse mechanical loading altered Wnt16 expression in young female mice, although Wnt16 expression was decreased following ovariectomy. Both 17β-estradiol and the Selective Estrogen Receptor Modulator Tamoxifen increased Wnt16 expression relative to ovariectomy. Wnt16 and ERβ expression were increased in female ERα-/- mice when compared to Wild Type. We also addressed potential effects of gender on Wnt16 expression and while the expression was lower in the cortical bone of aged males as in females, it was higher in male bone marrow of aged mice compared to young. In the kidney, which we used as a non-bone reference tissue, Wnt16 expression was unaffected by age in either males or females. In summary, age, and its associated bone loss, is associated with low levels of Wnt16 expression whereas bone loss associated with disuse has no effect on Wnt16 expression. In the artificially loaded mouse tibia we observed no loading-related up-regulation of Wnt16 expression but provide evidence that its expression is influenced by estrogen receptor signaling. These findings suggest that while Wnt16 is not an

  7. A new concept of the pattern of structural changes with bone loss by histomorphometric analysis using bone slabs.

    Science.gov (United States)

    Hoshino, K; Naguro, T; Iino, A

    1999-01-01

    We examined naked bone slabs (1.2 mm thick) from iliac bone biopsied cores obtained from 33 women aged 33-89 years. The number, size, and shape of the pores in the bone slabs were analyzed. The results revealed that the % bone area (the percentage area occupied by bone in the slab) was linearly correlated with age and other parameters, such as the size of pores, irregularity of pores, and pore distance, but was not correlated to the number of pores. We found a second-degree polynomial relationship between the % bone area and the number of pores. Based on three parameters--% bone area, number of pores, and size of pores--cluster analysis was performed and the specimens divided into three groups. The group with sufficient bone mass showed few small round pores, and the group with severe bone loss revealed a few large pores that were caved in. The characteristics of these groups represented the relationship between bone mass and structural change. The remaining group with moderate bone loss was divided into two subgroups, one with an increased number of pores without expansion and one with expanded pores without an increase in number. We presumed that the variations between the groups were caused by differences between fine and rough structures in the trabeculae caused during the process of bone loss. We concluded that this analysis of bone slabs allowed the pattern of trabecular structural change that occurred with bone loss to be determined easily and visually. PMID:10757677

  8. Artificial Gravity as a Bone Loss Countermeasure in Simulated Weightlessness

    Science.gov (United States)

    Smith, S. M.; Zwart, S. R.; Crawford, G. E.; Gillman, P. L.; LeBlanc, A.; Shackelford, L. C.; Heer, M. A.

    2007-01-01

    The impact of microgravity on the human body is a significant concern for space travelers. We report here initial results from a pilot study designed to explore the utility of artificial gravity (AG) as a countermeasure to the effects of microgravity, specifically to bone loss. After an initial phase of adaptation and testing, 15 male subjects underwent 21 days of 6 head-down bed rest to simulate the deconditioning associated with space flight. Eight of the subjects underwent 1 h of centrifugation (AG, 1 gz at the heart, 2.5 gz at the feet) each day for 21 days, while 7 of the subjects served as untreated controls (CN). Blood and urine were collected before, during, and after bed rest for bone marker determinations. At this point, preliminary data are available on the first 8 subjects (6 AG, and 2 CN). Comparing the last week of bed rest to before bed rest, urinary excretion of the bone resorption marker n-telopeptide increased 95 plus or minus 59% (mean plus or minus SD) in CN but only 32 plus or minus 26% in the AG group. Similar results were found for another resorption marker, helical peptide (increased 57 plus or minus 0% and 35 plus or minus 13% in CN and AG respectively). Bone-specific alkaline phosphatase, a bone formation marker, did not change during bed rest. At this point, sample analyses are continuing, including calcium tracer kinetic studies. These initial data demonstrate the potential effectiveness of short-radius, intermittent AG as a countermeasure to the bone deconditioning that occurs during bed rest.

  9. CD38 is associated with premenopausal and postmenopausal bone mineral density and postmenopausal bone loss.

    LENUS (Irish Health Repository)

    Drummond, Frances J

    2012-02-03

    One goal of osteoporosis research is to identify the genes and environmental factors that contribute to low bone mineral density (BMD) and fracture. Linkage analyses have identified quantitative trait loci (QTLs), however, the genes contributing to low BMD are largely unknown. We examined the potential association of an intronic polymorphism in CD38 with BMD and postmenopausal bone loss. CD38 resides in 4p15, where a QTL for BMD has been described. CD38-\\/- mice display an osteoporotic phenotype at 3 months, with normalization of BMD by 5 months. The CD38 polymorphism was identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 457 postmenopausal and 173 premenopausal Caucasian women whose spine and hip BMD was measured by dual energy X-ray absorptiometry (DXA). Influence of the CD38 polymorphism on bone loss was analyzed in 273 postmenopausal women over a follow-up of 2.94 +\\/- 1.50 years. The CD38-PvuII polymorphism was significantly associated with premenopausal and postmenopausal (P = 0.001) lumbar spine BMD. Women homozygous for the G allele had >14% lower spinal BMD than women with GC\\/CC genotypes. An allele dose effect was observed at the spine in premenopausal (P = 0.002) and postmenopausal (P < 0.001) cohorts. The CD38-PvuII polymorphism was significantly associated with femoral neck BMD in pre- and postmenopausal women (P = 0.002 and P = 0.011, respectively). However, significance was lost following adjustment of hip BMD for covariates in the postmenopausal cohort (P = 0.081). The CD38-PvuII polymorphism was weakly associated with bone loss at the spine (P = 0.024), in postmenopausal women not taking hormone replacement therapy. We suggest that the CD38-PvuII polymorphism may influence the attainment and maintenance of peak BMD and postmenopausal bone loss.

  10. Rhus javanica Gall Extract Inhibits the Differentiation of Bone Marrow-Derived Osteoclasts and Ovariectomy-Induced Bone Loss

    Directory of Open Access Journals (Sweden)

    Tae-Ho Kim

    2016-01-01

    Full Text Available Inhibition of osteoclast differentiation and bone resorption is a therapeutic strategy for the management of postmenopausal bone loss. This study investigated the effects of Rhus javanica (R. javanica extracts on bone marrow cultures to develop agents from natural sources that may prevent osteoclastogenesis. Extracts of R. javanica (eGr cocoons spun by Rhus javanica (Bell. Baker inhibited the osteoclast differentiation and bone resorption. The effects of aqueous extract (aeGr or 100% ethanolic extract (eeGr on ovariectomy- (OVX- induced bone loss were investigated by various biochemical assays. Furthermore, microcomputed tomography (µCT was performed to study bone remodeling. Oral administration of eGr (30 mg or 100 mg/kg/day for 6 weeks augmented the inhibition of femoral bone mineral density (BMD, bone mineral content (BMC, and other factors involved in bone remodeling when compared to OVX controls. Additionally, eGr slightly decreased bone turnover markers that were increased by OVX. Therefore, it may be suggested that the protective effects of eGr could have originated from the suppression of OVX-induced increase in bone turnover. Collectively, the findings of this study indicate that eGr has potential to activate bone remodeling by inhibiting osteoclast differentiation and bone loss.

  11. Blueberry consumption prevents loss of collagen in bone matrix and inhibits senescence pathways in osteoblastic cells

    Science.gov (United States)

    Ovariectomy (OVX)-induced bone loss has been linked to increased bone turnover and higher bone matrix collagen degradation as the result of osteoclast activation. However, the role of degraded collagen matrix in the fate of resident bone-forming cells is unclear. In this report, we show that OVX-i...

  12. Phytoestrogens for menopausal bone loss and climacteric symptoms.

    Science.gov (United States)

    Lagari, Violet S; Levis, Silvina

    2014-01-01

    Women have always looked for non-hormonal options to alleviate menopausal vasomotor symptoms and prevent menopausal bone loss. The use of complementary and alternative medicine for these purposes has particularly increased after the publication of the Women's Health Initiative's results suggesting that there might be more risks than benefits with hormone replacement. Phytoestrogens are plant-derived estrogens that, although less potent than estradiol, bind to the estrogen receptor and can function as estrogen agonists or antagonists. Soy isoflavones extracted from soy are the phytoestrogens most commonly used by menopausal women. Because typical Western diets are low in phytoestrogens and taking into account the general difficulty in changing dietary habits, most clinical trials in Western women have used isoflavone-fortified foods or isoflavone tablets. Although some women might experience a reduction in the frequency or severity of hot flashes, most studies point towards the lack of effectiveness of isoflavones derived from soy or red clover, even in large doses, in the prevention of hot flashes and menopausal bone loss. This article is part of a Special Issue entitled 'Phytoestrogens'. PMID:23246986

  13. Alpha-1 antitrypsin gene therapy prevented bone loss in ovariectomy induced osteoporosis mouse model

    Science.gov (United States)

    Osteoporosis is a major healthcare burden affecting mostly postmenopausal women characterized by compromised bone strength and increased risk of fragility fracture. Although pathogenesis of this disease is complex, elevated proinflammatory cytokine production is clearly involved in bone loss at meno...

  14. DLK1 is a novel regulator of bone mass that mediates estrogen deficiency-induced bone loss in mice

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Ditzel, Nicholas; Mahmood, Amer;

    2011-01-01

    Delta-like 1/fetal antigen 1 (DLK1/FA-1) is a transmembrane protein belonging to the Notch/Delta family that acts as a membrane-associated or a soluble protein to regulate regeneration of a number of adult tissues. Here we examined the role of DLK1/FA-1 in bone biology using osteoblast-specific Dlk...... the bone marrow by activated T cells. Interestingly, Dlk1(-/-) mice were significantly protected from ovx-induced bone loss compared with wild-type mice. Thus we identified Dlk1 as a novel regulator of bone mass that functions to inhibit bone formation and to stimulate bone resorption. Increasing DLK1...... production by T cells under estrogen deficiency suggests its possible use as a therapeutic target for preventing postmenopausal bone loss....

  15. Bone Loss Triggered by the Cytokine Network in Inflammatory Autoimmune Diseases

    OpenAIRE

    Amarasekara, Dulshara Sachini; Yu, Jiyeon; Rho, Jaerang

    2015-01-01

    Bone remodeling is a lifelong process in vertebrates that relies on the correct balance between bone resorption by osteoclasts and bone formation by osteoblasts. Bone loss and fracture risk are implicated in inflammatory autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, and systemic lupus erythematosus. The network of inflammatory cytokines produced during chronic inflammation induces an uncoupling of bone formation and resorption, resulting...

  16. Topical Treatment with Xiaozheng Zhitong Paste (XZP) Alleviates Bone Destruction and Bone Cancer Pain in a Rat Model of Prostate Cancer-Induced Bone Pain by Modulating the RANKL/RANK/OPG Signaling

    OpenAIRE

    Yanju Bao; Yebo Gao; Maobo Du; Wei Hou; Liping Yang; Xiangying Kong; Honggang Zheng; Weidong Li; Baojin Hua

    2015-01-01

    To explore the effects and mechanisms of Xiaozheng Zhitong Paste (XZP) on bone cancer pain, Wistar rats were inoculated with vehicle or prostate cancer PC-3 into the tibia bone and treated topically with inert paste, XZP at 15.75, 31.5, or 63 g/kg twice per day for 21 days. Their bone structural damage, nociceptive behaviors, bone osteoclast and osteoblast activity, and the levels of OPG, RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-α were examined. In comparison with that in the placebo gr...

  17. Multi-slice CT evaluation of glenoid bone loss in patients with recurrent anterior shoulder dislocation

    International Nuclear Information System (INIS)

    Objective: To evaluate multi-slice CT (MSCT) in glenoid bone loss of patients with recurrent anterior shoulder dislocation. Methods: MSCT findings of 108 patients with recurrent anterior shoulder dislocation and 12 with single anterior shoulder dislocation were retrospectively studied. The incidence, degrees and locations of glenoid bone losses were recorded. The incidence was analyzed with Fisher exact test. The maximum length,depth and proportion were compared with Wilcoxon rank sum test. Results: Glenoid bone loss was detected in 91.7% (99/108) patients with recurrent anterior shoulder dislocation. The proportion of glenoid bone loss was (16.0 ± 6.0)%, and the central locations of glenoid bone loss were from 2: 20 to 4: 25 (mean 3: 20). Sixty-two percent (67/108) patients had bony Bankart lesions in which 58.2% (39/67) bony fragments were free and 41.8% (28/67) were adherent to the anterior border of the glenoid cavity. Seventy-five percent (9/12) patients with single shoulder dislocation had anterior glenoid bone loss,and the proportion of glenoid bone loss was (15.2 ± 7.1)%. There were no statistical differences of the incidence (P=0.100) and proportion of glenoid bone loss (P=0.453) between the recurrent and single anterior shoulder dislocation. Conclusions: Anterior glenoid bone loss is common in patients with recurrent anterior shoulder dislocation. (authors)

  18. Animal Models of Bone Loss in Inflammatory Arthritis: from Cytokines in the Bench to Novel Treatments for Bone Loss in the Bedside-a Comprehensive Review.

    Science.gov (United States)

    Alves, C Henrique; Farrell, Eric; Vis, Marijn; Colin, Edgar M; Lubberts, Erik

    2016-08-01

    Throughout life, bone is continuously remodelled. Bone is formed by osteoblasts, from mesenchymal origin, while osteoclasts induce bone resorption. This process is tightly regulated. During inflammation, several growth factors and cytokines are increased inducing osteoclast differentiation and activation, and chronic inflammation is a condition that initiates systemic bone loss. Rheumatoid arthritis (RA) is a chronic inflammatory auto-immune disease that is characterised by active synovitis and is associated with early peri-articular bone loss. Peri-articular bone loss precedes focal bone erosions, which may progress to bone destruction and disability. The incidence of generalised osteoporosis is associated with the severity of arthritis in RA and increased osteoporotic vertebral and hip fracture risk. In this review, we will give an overview of different animal models of inflammatory arthritis related to RA with focus on bone erosion and involvement of pro-inflammatory cytokines. In addition, a humanised endochondral ossification model will be discussed, which can be used in a translational approach to answer osteoimmunological questions. PMID:26634933

  19. Alendronate reduced peri-tunnel bone loss and enhanced tendon graft to bone tunnel healing in anterior cruciate ligament reconstruction

    Directory of Open Access Journals (Sweden)

    PPY Lui

    2013-01-01

    Full Text Available Peri-tunnel bone loss after anterior cruciate ligament (ACL reconstruction is commonly observed, both clinically and experimentally. We aimed to study the effect and mechanisms of different doses of alendronate in the reduction of peri-tunnel bone loss and promotion of graft-bone tunnel healing in ACL reconstruction. Eighty-four ACL-reconstructed rats were divided into 4 groups. Alendronate at different dosages, or saline, were injected subcutaneously weekly, for 2 or 6 weeks post-reconstruction, for vivaCT (computed tomography imaging, biomechanical tests, histology and immunohistochemistry. Alendronate significantly increased bone mass and density of tissue inside bone tunnels except at the epiphyseal region of tibial tunnel. The femoral tunnel diameter decreased significantly in the mid-dose and high-dose alendronate groups compared to that in the saline group at week 6. Alendronate significantly increased the peri-tunnel bone mass and density along all tunnel regions at week 6. Better graft-bone tunnel integration and intra-tunnel graft integrity were observed in the alendronate groups. The ultimate load was significantly higher in the mid-dose and high-dose alendronate groups at week 2, but not at week 6. There was a reduction in matrix metalloprotein (MMP1, MMP13 and CD68-positive cells at the peri-tunnel region and graft-bone interface in the alendronate-treated group compared to the saline group. Alendronate reduced peri-tunnel bone resorption, increased mineralised tissue inside bone tunnel as well as histologically and biomechanically promoted graft-bone tunnel healing, probably by reducing the expression of MMP1, MMP13 and CD68-positive cells. Alendronate might be used for reducing peri-tunnel bone loss and promoting graft-bone tunnel healing at early stage post-ACL reconstruction.

  20. Hypercortisolemia Is Associated with Severity of Bone Loss and Depression in Hypothalamic Amenorrhea and Anorexia Nervosa

    OpenAIRE

    Lawson, Elizabeth A; Donoho, Daniel; Miller, Karen K.; Misra, Madhusmita; Meenaghan, Erinne; Lydecker, Janet; Wexler, Tamara; Herzog, David B.; Klibanski, Anne

    2009-01-01

    Context: Anorexia nervosa (AN) and functional hypothalamic amenorrhea (HA) are associated with low bone density, anxiety, and depression. Women with AN and HA have elevated cortisol levels. Significant hypercortisolemia, as in Cushing’s disease, causes bone loss. It is unknown whether anxiety and depression and/or cortisol dysregulation contribute to low bone density in AN or HA.

  1. Blueberry consumption prevents loss of collagen in bone matrix and inhibits senescence pathways in osteoblastic cells

    OpenAIRE

    Zhang, Jian; Lazarenko, Oxana P.; Blackburn, Michael L.; Badger, Thomas M.; Ronis, Martin J. J.; Chen, Jin-Ran

    2012-01-01

    Ovariectomy (OVX)-induced bone loss has been linked to increased bone turnover and higher bone matrix collagen degradation as the result of osteoclast activation. However, the role of degraded collagen matrix in the fate of resident bone-forming cells is unclear. In this report, we show that OVX-induced bone loss is associated with profound decreases in collagen 1 and Sirt1. This was accompanied by increases in expression and activity of the senescence marker collagenase and expression of p16...

  2. S-Ketoprofen Inhibits Tenotomy-Induced Bone Loss and Dynamics in Weanling Rats

    Science.gov (United States)

    Zeng, Q. Q.; Jee, W. S. S.; Ke, H. Z.; Wechter, W. J.

    1993-01-01

    The objects of this study were to determine whether S-ketoprofen, a non-steroidal anti-inflammatory drug (NSAID), can prevent immobilization (tenotomy)-induced bone loss in weanling rats. Forty five 4 week-old Sprague-Dawley female rats were either sham-operated or subjected to knee tenotomy and treated simultaneously with 0, 0.02, 0.1, 0.5 or 2.5 mg of S-ketoprofen/kg per day for 21 days. We then studied double-fluorescent labeled proximal tibial longitudinal sections and tibial shaft cross sections using static and dynamic histomorphometry. Less cancellous bone mass in proximal tibial metaphyses was found in tenotomized controls than in basal (36%) and sham-operated (54%) controls. This was due to the inhibition of age-related bone gain and induced bone loss due to increased bone resorption and decreased bone formation. S-ketoprofen prevented both the inhibition of age-related bone gain and the stimulation of bone loss at the 2.5 mg/kg per day dose level, while it only prevented bone loss at the 0.5 mg/kg dose levels. In cancellous bone, dynamic histomorphometry showed that S-ketoprofen prevented the tenotomy induced decrease in bone formation and increase in bone resorption. In the tibial shaft, tenotomy inhibited the enlargement of total tissue area by depressing periosteal bone formation, and thus inhibited age-related cortical bone gain. S-ketoprofen treatment did not prevent this change at all dose levels, but reduced marrow cavity area to increase cortical bone area at the 0.1, 0.5 and 2.5 mg/kg per dose levels compared to tenotomy controls. However, the cortical bone area in the 0.1 and 0.5 mg dose-treated treated tenotomy rats was still lower than in the age-related controls. S-ketoprofen also prevented the increase in endocortical eroded perimeter induced by tenotomy. In summary, tenotomy inhibited age-related bone gain and stimulated bone loss in cancellous bone sites, and only inhibited age-related bone gain in cortical bone sites. S

  3. Probiotic L. reuteri treatment prevents bone loss in a menopausal ovariectomized mouse model

    OpenAIRE

    Britton, Robert A.; Irwin, Regina; Quach, Darin; Schaefer, Laura; Zhang, Jing; Lee, Taehyung; Parameswaran, Narayanan; McCabe, Laura R.

    2014-01-01

    Estrogen deficiency is a major risk factor for osteoporosis that is associated with bone inflammation and resorption. Half of women over the age of 50 will experience an osteoporosis related fracture in their lifetime, thus novel therapies are needed to combat post-menopausal bone loss. Recent studies suggest an important role for gut-bone signaling pathways and the microbiota in regulating bone health. Given that the bacterium Lactobacillus reuteri ATCC PTA 6475 (L. reuteri) secretes benefic...

  4. Depression induces bone loss through stimulation of the sympathetic nervous system

    OpenAIRE

    Yirmiya, Raz; Goshen, Inbal; Bajayo, Alon; Kreisel, Tirzah; Feldman, Sharon; Tam, Joseph; Trembovler, Victoria; Csernus, Valér; Shohami, Esther; Bab, Itai

    2006-01-01

    Major depression is associated with low bone mass and increased incidence of osteoporotic fractures. However, causality between depression and bone loss has not been established. Here, we show that mice subjected to chronic mild stress (CMS), an established model of depression in rodents, display behavioral depression accompanied by impaired bone mass and structure, as portrayed by decreases in trabecular bone volume density, trabecular number, and trabecular connectivity density assessed in ...

  5. Probiotic L. reuteri treatment prevents bone loss in a menopausal ovariectomized mouse model.

    Science.gov (United States)

    Britton, Robert A; Irwin, Regina; Quach, Darin; Schaefer, Laura; Zhang, Jing; Lee, Taehyung; Parameswaran, Narayanan; McCabe, Laura R

    2014-11-01

    Estrogen deficiency is a major risk factor for osteoporosis that is associated with bone inflammation and resorption. Half of women over the age of 50 will experience an osteoporosis related fracture in their lifetime, thus novel therapies are needed to combat post-menopausal bone loss. Recent studies suggest an important role for gut-bone signaling pathways and the microbiota in regulating bone health. Given that the bacterium Lactobacillus reuteri ATCC PTA 6475 (L. reuteri) secretes beneficial immunomodulatory factors, we examined if this candidate probiotic could reduce bone loss associated with estrogen deficiency in an ovariectomized (Ovx) mouse menopausal model. Strikingly, L. reuteri treatment significantly protected Ovx mice from bone loss. Osteoclast bone resorption markers and activators (Trap5 and RANKL) as well as osteoclastogenesis are significantly decreased in L. reuteri-treated mice. Consistent with this, L. reuteri suppressed Ovx-induced increases in bone marrow CD4+ T-lymphocytes (which promote osteoclastogenesis) and directly suppressed osteoclastogenesis in vitro. We also identified that L. reuteri treatment modifies microbial communities in the Ovx mouse gut. Together, our studies demonstrate that L. reuteri treatment suppresses bone resorption and loss associated with estrogen deficiency. Thus, L. reuteri treatment may be a straightforward and cost-effective approach to reduce post-menopausal bone loss. PMID:24677054

  6. Peptide-induced de novo bone formation after tooth extraction prevents alveolar bone loss in a murine tooth extraction model.

    Science.gov (United States)

    Arai, Yuki; Aoki, Kazuhiro; Shimizu, Yasuhiro; Tabata, Yasuhiko; Ono, Takashi; Murali, Ramachandran; Mise-Omata, Setsuko; Wakabayashi, Noriyuki

    2016-07-01

    Tooth extraction causes bone resorption of the alveolar bone volume. Although recombinant human bone morphogenetic protein 2 (rhBMP-2) markedly promotes de novo bone formation after tooth extraction, the application of high-dose rhBMP-2 may induce side effects, such as swelling, seroma, and an increased cancer risk. Therefore, reduction of the necessary dose of rhBMP-2 which can still obtain sufficient bone mass is necessary by developing a new osteogenic reagent. Recently, we showed that the systemic administration of OP3-4 peptide, which was originally designed as a bone resorption inhibitor, had osteogenic ability both in vitro and in vivo. This study evaluated the ability of the local application of OP3-4 peptide to promote bone formation in a murine tooth extraction model with a very low-dose of BMP. The mandibular incisor was extracted from 10-week-old C57BL6/J male mice and a gelatin hydrogel containing rhBMP-2 with or without OP3-4 peptide (BMP/OP3-4) was applied to the socket of the incisor. Bone formation inside the socket was examined radiologically and histologically at 21 days after the extraction. The BMP/OP3-4-group showed significant bone formation inside the mandibular extraction socket compared to the gelatin-hydrogel-carrier-control group or rhBMP-2-applied group. The BMP/OP3-4-applied mice showed a lower reduction of alveolar bone and fewer osteoclast numbers, suggesting that the newly formed bone inside the socket may prevent resorption of the cortical bone around the extraction socket. Our data revealed that OP3-4 peptide promotes BMP-mediated bone formation inside the extraction socket of mandibular bone, resulting in preservation from the loss of alveolar bone. PMID:27118173

  7. Alveolar bone loss in osteoporosis: a loaded and cellular affair?

    Science.gov (United States)

    Jonasson, Grethe; Rythén, Marianne

    2016-01-01

    Maxillary and mandibular bone mirror skeletal bone conditions. Bone remodeling happens at endosteal surfaces where the osteoclasts and osteoblasts are situated. More surfaces means more cells and remodeling. The bone turnover rate in the mandibular alveolar process is probably the fastest in the body; thus, the first signs of osteoporosis may be revealed here. Hormones, osteoporosis, and aging influence the alveolar process and the skeletal bones similarly, but differences in loading between loaded, half-loaded, and unloaded bones are important to consider. Bone mass is redistributed from one location to another where strength is needed. A sparse trabeculation in the mandibular premolar region (large intertrabecular spaces and thin trabeculae) is a reliable sign of osteopenia and a high skeletal fracture risk. Having dense trabeculation (small intertrabecular spaces and well-mineralized trabeculae) is generally advantageous to the individual because of the low fracture risk, but may imply some problems for the clinician. PMID:27471408

  8. Prostaglandin E2 Prevents Ovariectomy-Induced Cancellous Bone Loss in Rats

    Science.gov (United States)

    Ke, Hua Zhu; Li, Mei; Jee, Webster S. S.

    1992-01-01

    The object of this study was to determine whether prostaglandin E2, (PGE2) can prevent ovariectomy induced cancellous bone loss. Thirty-five 3-month-old female Sprague-Dawley rats were divided into two groups. The rats in the first group were ovariectomized (OVX) while the others received sham operation (sham-OVX). The OVX group was further divided into three treatment groups. The daily doses for the three groups were 0,1 and 6 mg PGE2/kg for 90 days. Bone histomorphometric analyses were performed on double-fluorescent-labeled undecalcified proximal tibial metaphysis (PTM). We confirmed that OVX induces massive cancellous bone loss (-80%) and a higher bone turnover (+143%). The new findings from the present study demonstrate that bone loss due to ovarian hormone deficiency can be prevented by a low-dose (1 mg) daily administration of PGE2. Furthermore, a higher-dose (6 mg) daily administration of PGE2 not only prevents bone loss but also adds extra bone to the proximal tibial metaphyses. PGE, at the 1-mg dose level significantly increased trabecular bone area, trabecular width, trabecular node density, density of node to node, ratio of node to free end, and thus significantly decreased trabecular separation from OVX controls. At this dose level, these same parameters did not differ significantly from sham-OVX controls. However, at the 6-mg dose level PGE2, there were significant increases in trabecular bone area, trabecular width, trabecular node density, density of node to node, and ratio of node to free end, while there was significant decrease in trabecular separation from both OVX and sham-operated controls. The changes in indices of trabecular bone microanatomical structure indicated that PGE2 prevented bone loss as well as the disconnection of existing trabeculae. In summary, PGE2, administration to OVX rats decreased bone turnover and increased bone formation parameters resulting in a positive bone balance that prevented bone loss (in both lower and higher

  9. AN APPROACH OF BONE LOSS ESTIMATION THROUGH DIGITAL RADIOGRAPHY

    Directory of Open Access Journals (Sweden)

    Anupam Maiti,

    2011-06-01

    Full Text Available Osteoporosis is a disease characterized by low bone mass or density. In osteoporosis, bone mineral density (BMD is reduced and bone micro-architecture is deteriorating. Bones are becomes brittle and subjected to breakage even at a normal load. Conventionally, bone mineral density is measured by dual-emission X-ray absorptiometery (DEXA to establish osteoporosis but is costly. In this study, images from digital X-ray have been used to measure bone mineral density. The selected radiograph is segmented to separate bone image frombackground and converted to a gray level intensity matrix. Each pixel value of the matrix is related to bone density. A set of gray level intensity matrix corresponds to a particular region is taken and perform the Tstatistics on those data sample. To detect osteoporosis, a comparative study between calculated T-score and standard T-score, maintained by WHO (World Health Organization is performed from the selected area. Tstatistics is also the measurement of probability of osteoporotic fracture risk.

  10. Using Natural Stable Calcium Isotopes to Rapidly Assess Changes in Bone Mineral Balance Using a Bed Rest Model to Induce Bone Loss

    Science.gov (United States)

    Morgan, J. L. L.; Skulan, J. L.; Gordon, G. E.; Smith, Scott M.; Romaniello, S. J.; Anbar, A. D.

    2012-01-01

    Metabolic bone diseases like osteoporosis result from the disruption of normal bone mineral balance (BMB) resulting in bone loss. During spaceflight astronauts lose substantial bone. Bed rest provides an analog to simulate some of the effects of spaceflight; including bone and calcium loss and provides the opportunity to evaluate new methods to monitor BMB in healthy individuals undergoing environmentally induced-bone loss. Previous research showed that natural variations in the Ca isotope ratio occur because bone formation depletes soft tissue of light Ca isotopes while bone resorption releases that isotopically light Ca back into soft tissue (Skulan et al, 2007). Using a bed rest model, we demonstrate that the Ca isotope ratio of urine shifts in a direction consistent with bone loss after just 7 days of bed rest, long before detectable changes in bone mineral density (BMD) occur. The Ca isotope variations tracks changes observed in urinary N-teleopeptide, a bone resorption biomarker. Bone specific alkaline phosphatase, a bone formation biomarker, is unchanged. The established relationship between Ca isotopes and BMB can be used to quantitatively translate the changes in the Ca isotope ratio to changes in BMD using a simple mathematical model. This model predicts that subjects lost 0.25 0.07% ( SD) of their bone mass from day 7 to day 30 of bed rest. Given the rapid signal observed using Ca isotope measurements and the potential to quantitatively assess bone loss; this technique is well suited to study the short-term dynamics of bone metabolism.

  11. Male Astronauts Have Greater Bone Loss and Risk of Hip Fracture Following Long Duration Spaceflights than Females

    Science.gov (United States)

    Ellman, Rachel; Sibonga, Jean; Bouxsein, Mary

    2010-01-01

    This slide presentation reviews bone loss in males and compares it to female bone loss during long duration spaceflight. The study indicates that males suffer greater bone loss than females and have a greater risk of hip fracture. Two possible reason for the greater male bone loss are that the pre-menopausal females have the estrogen protection and the greater strength of men max out the exercise equipment that provide a limited resistance to 135 kg.

  12. Aromatase inhibitor-associated bone loss and its management with bisphosphonates in patients with breast cancer

    OpenAIRE

    Bauer M; Bryce J; Hadji P

    2012-01-01

    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 th...

  13. Mechanism and Therapeutic Strategies of Ailamode in the Treatment of RA-induced Bone Loss

    Institute of Scientific and Technical Information of China (English)

    Wang Feng

    2013-01-01

    Rheumatoid arthritis (RA) caused by exceed bone absorption than osteogenesis and the subsequent osteoporosis (bone loss) around joints and in entire body, is the most commonly seen bone disease in clinic, which is induced by inlfammatory factors and corticosteroid therapies, while RA-induced bone loss is believed to be associated with the decreased osteogenesis because of the increased bone absorption and low osterix expression by reason of over-expressions of TNF-α, IL-1, Il-6 and RANKL, etc.. Ailamode (ALMD, T-614) is a new anti-RA agent (DMARDs) and a regulator for immunity and bone metabolism. Research showed that T-614 could eliminate bone absorption and up-regulate osterix expression to improve osteogenesis by inhibiting some inlfammatory factors (TNF-α, IL-1 and Il-6), so as to reduce bone and joint damages. And several clinical evidences have proved that T-614 is safe in treating RA and has synergistic effect with methotrexate (MTX), which could strengthen the efifcacy and decrease bone erosion. Therefore, it is considered to be the most valuable agent in the treatment of RA and RA-induced bone loss at present.

  14. Monoaxial distraction of ulna to second metacarpal followed by single bone forearm in massive post infective radial bone loss

    Directory of Open Access Journals (Sweden)

    Jitendra N Pal

    2012-01-01

    Full Text Available Introduction: Radial bone loss associated with gross manus valgus deformity can be managed by open reduction internal fixation using intervening strut bone graft, callus distraction using ring or monoaxial fixator, and achieving union by distraction histogenesis. These methods are particularly suitable when bone loss is small. Single or staged procedure is described for congenital as well as in acquired extensive bone loss of radius. Distraction through radial proximal to distal segments, to achieve reduction of distal radio-ulnar joint (DRUJ, is also described in acquired cases. In the present series, functional results of distraction through ulna to 2 nd metacarpal is studied alongwith, functional status of hand, stability of wrist, level of patient′s satisfaction are also studied. Materials and Methods: 7 unilateral cases of radial loss (M = 5, F = 2 affecting 4 right hands of mean age 17 years (range 9 to 24 years were included in this study. They were treated by distracting through ulna to 2 nd metacarpal to achieve DRUJ alignment in first stage. Subsequently ulna was osteotomised and translated to distal stump of radius. It was then fixed to the distal radial remnant in 30° pronation in dominant and 30° supination non dominant hands. Results: Union was achieved in all cases associated with beneficial cross union of distal ulna. Hand functions improved near to normal, with fully corrected stable wrist joint, hypertrophied ulna and without recurrence. All of them had practically complete loss of forearm rotations, however patients were fully satisfied. Conclusion: This method is particularly suitable when associated with 6 cm or more radial bone loss. But when loss is small, sacrifice of one bone may not be justifiable.

  15. Inhibitory effects of morinda officinalis extract on bone loss in ovariectomized rats.

    Science.gov (United States)

    Li, Nan; Qin, Lu-Ping; Han, Ting; Wu, Yan-Bin; Zhang, Qiao-Yan; Zhang, Hong

    2009-01-01

    The present study was undertaken to investigate the protective effects of ethanol extract from the root of Morinda Officinalis (RMO) on ovariectomy-induced bone loss. Administration of RMO extract increased trabecular bone mineral content and bone mineral density of tibia, improved the levels of phosphorus (P), calcium (Ca) and OPG, decreased the levels of DPD/Cr, TRAP, ACTH and corticosterone, but did not reverse the levels of ALP, TNF-alpha and IL-6 in serum of ovariectomized rats. These findings demonstrated that RMO extract reduced bone loss in ovariectomized rats, probably via the inhibition of bone resorption, but was not involved with bone formation. Anthraquinones and polysaccharides from Morinda officinals could be responsible for their antiosteoporotic activity, and the action mechanism of these constituents needs to be further studied. Therefore, RMO has the potential to develop a clinically useful antiosteoporotic agent. PMID:19513005

  16. Inhibitory Effects of Morinda officinalis Extract on Bone Loss in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Qiao-Yan Zhang

    2009-06-01

    Full Text Available The present study was undertaken to investigate the protective effects of ethanol extract from the root of Morinda Officinalis (RMO on ovariectomy-induced bone loss. Administration of RMO extract increased trabecular bone mineral content and bone mineral density of tibia, improved the levels of phosphorus (P, calcium (Ca and OPG, decreased the levels of DPD/Cr, TRAP, ACTH and corticosterone, but did not reverse the levels of ALP, TNF-α and IL-6 in serum of ovariectomized rats. These findings demonstrated that RMO extract reduced bone loss in ovariectomized rats, probably via the inhibition of bone resorption, but was not involved with bone formation. Anthraquinones and polysaccharides from Morinda officinals could be responsible for their antiosteoporotic activity, and the action mechanism of these constituents needs to be further studied. Therefore, RMO has the potential to develop a clinically useful antiosteoporotic agent.

  17. Bone-targeted therapy for metastatic breast cancer—Where do we go from here? A commentary from the BONUS 8 meeting

    Directory of Open Access Journals (Sweden)

    Xiaofu Zhu

    2014-03-01

    Full Text Available The annual Bone and The Oncologist New Updates (BONUS 8 conference focuses on the current understanding and dilemmas in the treatment and prevention of bone metastasis in cancer, as well as novel research on bone homeostasis and cancer-induced bone loss. We present commentaries from experts for their own take on where they feel the field of bone-targeted therapies for metastatic breast cancer is moving, or needs to move, if we are to make further progress.

  18. Sclerostin antibody prevented progressive bone loss in combined ovariectomized and concurrent functional disuse.

    Science.gov (United States)

    Zhang, Dongye; Hu, Minyi; Chu, Timothy; Lin, Liangjun; Wang, Jingyu; Li, Xiaodong; Ke, Hua Zhu; Qin, Yi-Xian

    2016-06-01

    Osteoporosis is characterized by low bone mass and compromised trabecular architecture, and is commonly occurred in post-menopausal women with estrogen deficiency. In addition, prolonged mechanical unloading, i.e., long term bed rest, can exaggerate the bone loss. Sclerostin is a Wnt signaling antagonist and acts as a negative regulator for bone formation. A sclerostin-neutralizing antibody (Scl-Ab) increased bone mineral density in women with postmenopausal osteoporosis and healthy men. The objective of this study was to characterize the condition of bone loss in ovariectomized (OVX) rats with concurrent mechanical unloading and evaluate the effect of sclerostin antibody treatment in mitigating the prospective severe bone loss conditions in this model. Four-month-old OVX- or sham-operated female SD rats were used in this study. They were subjected to functional disuse induced by hind-limb suspension (HLS) or free ambulance after 2days of arrival. Subcutaneous injections with either vehicle or Scl-Ab at 25mg/kg were made twice per week for 5weeks from the time of HLS. μCT analyses demonstrated a significant decrease in distal metaphyseal trabecular architecture integrity with HLS, OVX and HLS+OVX (bone volume fraction decreased by 29%, 71% and 87% respectively). The significant improvements of various trabecular bone parameters (bone volume fraction increased by 111%, 229% and 297% respectively as compared with placebo group) with the administration of Scl-Ab are associated with stronger mechanical property and increased bone formation by histomorphometry. These results together indicate that Scl-Ab prevented the loss of trabecular bone mass and cortical bone strength in OVX rat model with concurrent mechanical unloading. The data suggested that monoclonal sclerostin-neutralizing antibody represents a promising therapeutic approach for severe osteoporosis induced by estrogen deficiency with concurrent mechanical unloading. PMID:26868528

  19. Buccal bone loss after immediate implantation can be reduced by the flapless approach

    Directory of Open Access Journals (Sweden)

    ARTHUR BELÉM NOVAES JR

    2011-10-01

    Full Text Available Aim: The aim of this study was to evaluate the buccal bone remodeling after immediate implantation with flap or flapless approach. Material and Methods: The mandibular bilateral premolars of 3 dogs were extracted and immediately three implants were placed in both hemi-arches of each dog. Randomly, one hemi-arch was treated with the flapless approach, while in the contra lateral hemi-arch tooth extractions and implant placement were done after mucoperiosteal flap elevation. Non-submerged healing of 12 weeks was provided for both groups. Histomorphometric analysis was done to compare buccal and lingual bone height loss, bone density and bone-to-implant contact in the groups. Fluorescence analysis was performed to investigate the dynamic of bone remodeling in the different groups. Results: There was a significant association between the surgical flap and the extent of bone resorption around immediate implants. The loss of buccal bone height was significantly lower in the flapless group when compared to the flap group (0.98 mm x 2.14 mm, respectively, p<0.05. The coronal and apical buccal bone densities of the flap group were significantly higher when compared to the lingual components, showing anatomical differences between the bone plates. Fluorescence analysis showed no major differences in bone healing between the flap and flapless groups, supporting that the higher loss of buccal bone height is linked to the anatomic characteristics of this plate and to the negative influence of the detachment of the periosteum in immediate implant therapy. Conclusion: The flapless approach for immediate post-extraction implants reduces the buccal bone height loss.

  20. Inhibitory Effects of Morinda officinalis Extract on Bone Loss in Ovariectomized Rats

    OpenAIRE

    Qiao-Yan Zhang; Hong Zhang; Yan-Bin Wu; Ting Han; Lu-Ping Qin; Nan Li

    2009-01-01

    The present study was undertaken to investigate the protective effects of ethanol extract from the root of Morinda Officinalis (RMO) on ovariectomy-induced bone loss. Administration of RMO extract increased trabecular bone mineral content and bone mineral density of tibia, improved the levels of phosphorus (P), calcium (Ca) and OPG, decreased the levels of DPD/Cr, TRAP, ACTH and corticosterone, but did not reverse the levels of ALP, TNF-α and IL-6 in serum of ovariectomized rats. These findin...

  1. Is Opium Addiction a Risk Factor for Bone Loss?

    OpenAIRE

    Gozashti, M H; Shahesmaeili, A; Amini Zadeh, N

    2011-01-01

    Background Drug abuse is one of the most important public health problems worldwide as in Iran. The aim of present study was to determine whether opium addiction can affect bone mineral density or not. Methods Fifty opium addicted and 50 non-addicted volunteer men aged between 25-45 were enrolled. The subjects with positive history of other osteoporosis risk factors were excluded. The vertebral bone density and potential confounders (age, cigarette smoking and body mass index) were measured i...

  2. Metastasis and bone loss: Advancing treatment and prevention

    OpenAIRE

    Coleman, Robert E.; Lipton, Allan; Roodman, G. David; Guise, Theresa A.; Boyce, Brendon F.; Brufsky, Adam M.; Clézardin, Philippe; Peter I Croucher; Gralow, Julie R.; Hadji, Peyman; Holen, Ingunn; Mundy, Gregory R.; Smith, Matthew R.; Suva, Larry J.

    2010-01-01

    Tumor metastasis to the skeleton affects over 400,000 individuals in the United States annually, more than any other site of metastasis, including significant proportions of patients with breast, prostate, lung and other solid tumors. Research on the bone microenvironment and its role in metastasis suggests a complex role in tumor growth. Parallel preclinical and clinical investigations into the role of adjuvant bone-targeted agents in preventing metastasis and avoiding cancer therapy-induced...

  3. COMPARSION BETWEEN PANORAMIC PERIAPICAL AND VERTICAL BITEWING RADIOGRAPHY IN DIAGNOSIS OF PERIODONTAL BONE LOSS

    Directory of Open Access Journals (Sweden)

    M SHEIKHI

    2000-09-01

    Full Text Available Introduction. For diagnosis and treatment planing and detection the quality of remaining Alveolar bone the radiography is very useful so the type of radiography is very important. The purpose of this study is the comparison between panoramic, periapical (bisecting technique and vertical bitewing radiographs in diagnosis of periodontitis. Methods. Twelve patients (3 male and 9 female with a mean age of 35, with a moderate to advanced periodontitis were evaluated. At the time of periodontal surgery, in the posterior site of two jaws (in 6 and 7 teeth, the bone loss was measured from CEJ to the base of alveolar bone, and compared with the radiographic findings of proximal bone loss. Results. The average of distance between CEJ and alveolar bone in 48 surfaces were 4.27 in clinic, 4.80 in panoramic, 2.62 in periapical (bisecting technique, 2.98 in vertical bitewing and 4.05 in panoramic without magnification. Discussion. In this research we cancluded that both techniques (periapical and vertical bitewing are not accurate in detection of proximal bone loss and there was significant difference between quantity of proximal bone in clinical measurment than radiographic measurment and this study showed that the panoramic (specially panoramic without magnification is more careful than other radiographic techniques in detection of proximal bone loss.

  4. Effect of Vitamin K Supplementation on Bone Loss in Elderly Men and Women

    Science.gov (United States)

    Introduction: Vitamin K has been implicated in bone health, primarily in observational studies. However, little is known about the role of phylloquinone supplementation on prevention of bone loss in men and women. The objective of this study was to determine the effect of three-year phylloquinone ...

  5. Vitamin D receptor overexpression in osteoblasts and osteocytes prevents bone loss during vitamin D-deficiency.

    Science.gov (United States)

    Lam, Nga N; Triliana, Rahma; Sawyer, Rebecca K; Atkins, Gerald J; Morris, Howard A; O'Loughlin, Peter D; Anderson, Paul H

    2014-10-01

    There are several lines of evidence that demonstrate the ability of 1,25-dihydroxyvitamin D (1,25(OH)2D3), acting via the vitamin D receptor (VDR) to mediate negative or positive effects in bone. Transgenic over-expression of VDR in osteoblasts and osteocytes in a mouse model (OSVDR) has been previously shown to inhibit processes of bone resorption and enhance bone formation, under conditions of adequate calcium intake. While these findings suggest that vitamin D signalling in osteoblasts and osteocytes promotes bone mineral accrual, the vitamin D requirement for this action is not well understood. In this study, 4 week old female OSVDR and wild-type (WT) mice were fed either a vitamin D-replete (1000IU/kg diet, D+) or vitamin D-deficient (D-) diet for 4 months to observe changes to bone mineral homeostasis. Tibial bone mineral volume was analysed by micro-CT and changes to bone cell activities were measured using standard dynamic histomorphometric techniques. While vitamin D-deplete WT mice demonstrated a reduction in periosteal bone accrual and overall bone mineral volume, OSVDR mice, however, displayed increased cortical and cancellous bone volume in mice which remained higher during vitamin D-depletion due to a reduced osteoclast number and increased bone formation rate. These data suggest that increased VDR-mediated activity in osteoblast and osteocytes prevents bone loss due to vitamin D-deficiency. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. PMID:24434283

  6. Treatment of eggshell with casein phosphopeptide reduces the severity of ovariectomy-induced bone loss

    OpenAIRE

    Kim, Jung-Hoon; Kim, Min Seuk; Oh, Hong-Geun; Lee, Hak-Yong; Park, Jeong-Woo; Lee, Bong-Gun; Park, Sang-Hoon; Moon, Dae-In; Shin, Eun-Hye; Oh, Eun-Kyeong; Erkhembaatar, Munkhsoyol; Kim, Okjin; Lee, Yong-Rae; Chae, Han-Jung

    2013-01-01

    It has been generally accepted that calcium intake prevents bone loss, and frequent fracture resulted from osteoporosis. However, it is still elusive as to how effective sole calcium intake is in preventing or attenuating the severity of osteoporosis. Here, we demonstrate the effects of eggshell-casein phosphopeptide (ES-CPP), and compared these effects those of calcium supplement, for restoring ovariectomy-mediated bone loss. CPP, synthesized from the hydrolysis of casein (0.5%) using trypsi...

  7. Correlation of the interdental and the interradicular bone loss: A radiovisuographic analysis

    Science.gov (United States)

    Grover, Vishakha; Malhotra, Ranjan; Kapoor, Anoop; Mankotia, Chahat Singh; Bither, Rupika

    2014-01-01

    Background: Presence of furcation involvement indicates advanced periodontitis, and a potentially less-favorable prognosis, for the affected tooth and its diagnosis has always been an enigma. The present study was carried out to measure and correlate the interdental and interradicular bone loss in patients suffering from periodontitis using radiovisuography (RVG) for the purpose of early furcation diagnosis. Materials and Methods: A total of 50 patients suffering from chronic generalized periodontitis and with furcation involvement in mandibular molars were selected. Under standardized conditions, RVGs were taken and the morphologic measurements defining the furcation areas were recorded and analyzed. Result: Interradicular bone loss of about 0.8 mm or more, was observed in the study subjects only when the bone loss at the interdental area was minimal of 3.7 mm. The correlation between the interradicular and the interdental bone loss was statistically highly significant (T-test, P < 0.001). A stronger correlation was observed in subjects above 40 years of age as compared with the younger subjects. There was not much difference in the degree of correlation between the interradicular and the interdental bone loss when compared in the context of gender. Conclusion: The very first millimeter of interradicular bone loss was seen when the interdental bone loss was around 4 mm. Therefore, to detect the earliest lesions of furcations, the interdental bone loss can be kept as an approximate guide for the comprehensive diagnosis and management of such sites/patients. The current investigation paves the path for future longitudinal studies with larger samples to ascertain these findings. PMID:25210264

  8. Alendronate and estrogen-progestin in the long-term prevention of bone loss

    DEFF Research Database (Denmark)

    Ravn, Pernille; Bidstrup, M; Wasnich, R D;

    1999-01-01

    alendronate to placebo than in those who continuously received placebo. In years 3 and 4, bone loss in participants who switched from alendronate to placebo was similar to that seen during years 1 and 2 in those who continuously received placebo. Compared with 5 mg of alendronate per day, estrogen-medroxyprogesterone...... acetate produced similar increases in bone mineral density and estradiol-norethisterone acetate produced increases that were substantially greater. CONCLUSIONS: Four years of treatment with alendronate or estrogen-progestin prevented postmenopausal bone loss. A residual effect was seen 2 years after...

  9. Protective effect of Pycnogenol® on ovariectomy-induced bone loss in rats.

    Science.gov (United States)

    Mei, Lin; Mochizuki, Miyako; Hasegawa, Noboru

    2012-01-01

    Pycnogenol® (PYC) is a natural plant extract from the bark of Pinus pinaster and has potent antioxidant activities. The protective effect of PYC on bone loss was studied in multiparous ovariectomized (OVX) female rats. Pycnogenol® (30 or 15 mg/kg body weight/day) was administered orally to 8-month-old OVX rats for 3 months. At the end of the experiment, bone strength was measured by a three-point bending test and bone mineral density was estimated by peripheral quantitative computed tomography. Ovariectomy significantly decreased femur bone strength and bone density. Supplementation with PYC suppressed the bone loss induced by OVX. The OVX treatment significantly increased serum osteocalcin (OC) and C-terminal telopeptide of type I collagen (CTx). Supplementation with PYC reduced the serum OC and CTx in OVX rats to a level similar to that of the sham-operated group. The results indicated that orally administered PYC can decrease the bone turnover rate in OVX rats, resulting in positive effects on the biomechanical strength of bone and bone mineral density. PMID:21710590

  10. Establishment of age- and sex-adjusted reference data for hand bone mass and investigation of hand bone loss in patients with rheumatoid arthritis treated in clinical practice

    DEFF Research Database (Denmark)

    Ørnbjerg, Lykke Midtbøll; Østergaard, Mikkel; Jensen, Trine; Hyldstrup, Lars; Bach-Mortensen, Pernille; Bøyesen, Pernille; Thormann, Anja; Tarp, Ulrik; Bøhme, Wolfgang Peter; Lindegaard, Hanne; Poulsen, Uta Engling; Schlemmer, Annette; Graudal, Niels; Rødgaard, Anne; Espesen, Jakob; Kollerup, Gina Birgitte; Glintborg, Bente; Madsen, Ole Rintek; Jensen, Dorte Vendelbo; Hetland, Merete Lund

    2016-01-01

    BACKGROUND: Rheumatoid arthritis is characterised by progressive joint destruction and loss of periarticular bone mass. Hand bone loss (HBL) has therefore been proposed as an outcome measure for treatment efficacy. A definition of increased HBL adjusted for age- and sex-related bone loss is lacking....... In this study, we aimed to: 1) establish reference values for normal hand bone mass (bone mineral density measured by digital x-ray radiogrammetry (DXR-BMD)); and 2) examine whether HBL is normalised in rheumatoid arthritis patients during treatment with tumour necrosis factor alpha inhibitors (TNFI...

  11. Sex steroid deficiency-associated bone loss is microbiota dependent and prevented by probiotics.

    Science.gov (United States)

    Li, Jau-Yi; Chassaing, Benoit; Tyagi, Abdul Malik; Vaccaro, Chiara; Luo, Tao; Adams, Jonathan; Darby, Trevor M; Weitzmann, M Neale; Mulle, Jennifer G; Gewirtz, Andrew T; Jones, Rheinallt M; Pacifici, Roberto

    2016-06-01

    A eubiotic microbiota influences many physiological processes in the metazoan host, including development and intestinal homeostasis. Here, we have shown that the intestinal microbiota modulates inflammatory responses caused by sex steroid deficiency, leading to trabecular bone loss. In murine models, sex steroid deficiency increased gut permeability, expanded Th17 cells, and upregulated the osteoclastogenic cytokines TNFα (TNF), RANKL, and IL-17 in the small intestine and the BM. In germ-free (GF) mice, sex steroid deficiency failed to increase osteoclastogenic cytokine production, stimulate bone resorption, and cause trabecular bone loss, demonstrating that the gut microbiota is central in sex steroid deficiency-induced trabecular bone loss. Furthermore, we demonstrated that twice-weekly treatment of sex steroid-deficient mice with the probiotics Lactobacillus rhamnosus GG (LGG) or the commercially available probiotic supplement VSL#3 reduces gut permeability, dampens intestinal and BM inflammation, and completely protects against bone loss. In contrast, supplementation with a nonprobiotic strain of E. coli or a mutant LGG was not protective. Together, these data highlight the role that the gut luminal microbiota and increased gut permeability play in triggering inflammatory pathways that are critical for inducing bone loss in sex steroid-deficient mice. Our data further suggest that probiotics that decrease gut permeability have potential as a therapeutic strategy for postmenopausal osteoporosis. PMID:27111232

  12. Effects of chronic estrogen treatment on modulating age-related bone loss in female mice.

    Science.gov (United States)

    Syed, Farhan A; Mödder, Ulrike Il; Roforth, Matthew; Hensen, Ira; Fraser, Daniel G; Peterson, James M; Oursler, Merry Jo; Khosla, Sundeep

    2010-11-01

    While female mice do not have the equivalent of a menopause, they do undergo reproductive senescence. Thus, to dissociate the effects of aging versus estrogen deficiency on age-related bone loss, we sham-operated, ovariectomized, or ovariectomized and estrogen-replaced female C57/BL6 mice at 6 months of age and followed them to age 18 to 22 months. Lumbar spines and femurs were excised for analysis, and bone marrow hematopoietic lineage negative (lin-) cells (enriched for osteoprogenitor cells) were isolated for gene expression studies. Six-month-old intact control mice were euthanized to define baseline parameters. Compared with young mice, aged/sham-operated mice had a 42% reduction in lumbar spine bone volume/total volume (BV/TV), and maintaining constant estrogen levels over life in ovariectomized/estrogen-treated mice did not prevent age-related trabecular bone loss at this site. By contrast, lifelong estrogen treatment of ovariectomized mice completely prevented the age-related reduction in cortical volumetric bone mineral density (vBMD) and thickness at the tibial diaphysis present in the aged/sham-operated mice. As compared with cells from young mice, lin- cells from aged/sham-operated mice expressed significantly higher mRNA levels for osteoblast differentiation and proliferation marker genes. These data thus demonstrate that, in mice, age-related loss of cortical bone in the appendicular skeleton, but not loss of trabecular bone in the spine, can be prevented by maintaining constant estrogen levels over life. The observed increase in osteoblastic differentiation and proliferation marker gene expression in progenitor bone marrow cells from aged versus young mice may represent a compensatory mechanism in response to ongoing bone loss. PMID:20499336

  13. Interleukin-6 gene knockout antagonizes high-fat-induced trabecular bone loss.

    Science.gov (United States)

    Wang, Chunyu; Tian, Li; Zhang, Kun; Chen, Yaxi; Chen, Xiang; Xie, Ying; Zhao, Qian; Yu, Xijie

    2016-10-01

    The purpose of the study was to determine the roles of interleukin-6 (IL6) in fat and bone communication. Male wild-type (WT) mice and IL6 knockout (IL6(-/-)) mice were fed with either regular diet (RD) or high-fat diet (HFD) for 12 weeks. Bone mass and bone microstructure were evaluated by micro-computed tomography. Gene expression related to lipid and bone metabolisms was assayed with real-time quantitative polymerase chain reaction. Bone marrow cells from both genotypes were induced to differentiate into osteoblasts or osteoclasts, and treated with palmitic acid (PA). HFD increased the body weight and fat pad weight, and impaired lipid metabolism in both WT and IL6(-/-) mice. The dysregulation of lipid metabolism was more serious in IL6(-/-) mice. Trabecular bone volume fraction, trabecular bone number and trabecular bone thickness were significantly downregulated in WT mice after HFD than those in the RD (P < 0.05). However, these bone microstructural parameters were increased by 53%, 34% and 40%, respectively, in IL6(-/-) mice than those in WT mice on the HFD (P < 0.05). IL6(-/-) osteoblasts displayed higher alkaline phosphatase (ALP) activity and higher mRNA levels of Runx2 and Colla1 than those in WT osteoblasts both in the control and PA treatment group (P < 0.05). IL6(-/-) mice showed significantly lower mRNA levels of PPARγ and leptin and higher mRNA levels of adiponectin in comparison with WT mice on HFD. In conclusion, these findings suggested that IL6 gene deficiency antagonized HFD-induced bone loss. IL6 might bridge lipid and bone metabolisms and could be a new potential therapeutic target for lipid metabolism disturbance-related bone loss. PMID:27493246

  14. Time course of bone loss in patients with anorexia nervosa

    OpenAIRE

    Olmos Martínez, José Manuel; Valero Díaz de Lamadrid, Carmen; Gómez del Barrio, José Andrés; Amado Señarís, José Antonio; Hernández Hernández, José Luis; Menéndez Arango, José; González Macías, Jesús

    2010-01-01

    Objective: To evaluate the time course of bone mineral density (BMD) in women with anorexia nervosa (AN) during two years of follow-up. Methods: We prospectively studied 51 female with AN aged 18-38 years, and forty age-matched healthy women (19-34 years). BMD was measured in lumbar spine (LS), femoral neck (FN) and total hip (TH) by DXA. Results: At baseline, weight, body mass index, and lumbar and hip BMD were significantly (p

  15. The combined effects of X-ray radiation and hindlimb suspension on bone loss

    International Nuclear Information System (INIS)

    Outer space is a complex environment with various phenomena that negatively affect bone metabolism, including microgravity and highly energized ionizing radiation. In the present study, we used four groups of male Wistar rats treated with or without four-week hindlimb suspension after 4 Gy of X-rays to test whether there is a combined effect for hindlimb suspension and X-ray radiation. We tested trabecular parameters and some cytokines of the bone as leading indicators of bone metabolism. The results showed that hindlimb suspension and X-ray radiation could cause a significant increase in bone loss. Hindlimb suspension caused a 56.6% bone loss (P = 0.036), while X-ray radiation caused a 30.7% (P = 0.041) bone loss when compared with the control group. The combined factors of hindlimb suspension and X-rays exerted a combined effect on bone mass, with a reduction of 64.8% (P = 0.003). (author)

  16. A murine model for bone loss from therapeutic and space-relevant sources of radiation.

    Science.gov (United States)

    Hamilton, S A; Pecaut, M J; Gridley, D S; Travis, N D; Bandstra, E R; Willey, J S; Nelson, G A; Bateman, T A

    2006-09-01

    Cancer patients receiving radiation therapy are exposed to photon (gamma/X-ray), electron, and less commonly proton radiation. Similarly, astronauts on exploratory missions will be exposed to extended periods of lower-dose radiation from multiple sources and of multiple types, including heavy ions. Therapeutic doses of radiation have been shown to have deleterious consequences on bone health, occasionally causing osteoradionecrosis and spontaneous fractures. However, no animal model exists to study the cause of radiation-induced osteoporosis. Additionally, the effect of lower doses of ionizing radiation, including heavy ions, on general bone quality has not been investigated. This study presents data developing a murine model for radiation-induced bone loss. Female C57BL/6 mice were exposed to gamma, proton, carbon, or iron radiation at 2-Gray doses, representing both a clinical treatment fraction and spaceflight exposure for an exploratory mission. Mice were euthanized 110 days after irradiation. The proximal tibiae and femur diaphyses were analyzed using microcomputed tomography. Results demonstrate profound changes in trabecular architecture. Significant losses in trabecular bone volume fraction were observed for all radiation species: gamma, (-29%), proton (-35%), carbon (-39%), and iron (-34%). Trabecular connectivity density, thickness, spacing, and number were also affected. These data have clear implications for clinical radiotherapy in that bone loss in an animal model has been demonstrated at low doses. Additionally, these data suggest that space radiation has the potential to exacerbate the bone loss caused by microgravity, although lower doses and dose rates need to be studied. PMID:16741258

  17. Radiographic Vertical Bone Loss Evaluation around Dental Implants Following One Year of Functional Loading

    Directory of Open Access Journals (Sweden)

    A. Khorsand

    2010-06-01

    Full Text Available Objective: Vertical bone loss evaluations in the Nobel Biocare Replace® Select Tapered TM implant system in the human after one-year loading time.Materials and Methods: This retrospective cross-sectional study was performed on 31 patients (14 men, 17 women; mean age, 60.39 years receiving 170 implants (mean, 5.48 for each patient of Groovy and Non-groovy designs in the Nobel Biocare Replace® Select Tapered TM system. The marginal bone loss was measured at mesial and distal aspects of the implants on OPG x-rays after one-year follow-up. The data regarding the patient's gender, age, history of disease, smoking, bone type at implant location, loading time of prosthesis and implant, implant design, diameter and length were recorded by the patients'records and interview. The data were subjected to multiple linear regression and Pearson coefficient ratio regarding different factors.Results: The mean (standard deviation distal, mesial and overall bone loss was 0.688 mm (0.851, 0.665 mm (0.849 and 0.935 mm (0.905, respectively in the studied implants. No significant differences were found regarding implant location, bone quality at the implant region, implant design and bone graft reception. In addition, no significant correlation was found between the occurred bone loss and implant diameter, length and number of usedsplints.Conclusion: Due to the criteria mentioned for implant success in term of bone loss values after one-year loading time, Noble Biocare Replace® Select Tapered TM implant system is an acceptable treatment option for implant restorations in this regard.

  18. Average annual crestal bone loss of ITI implants following the first year of loading

    Directory of Open Access Journals (Sweden)

    A Hosseinzadeh

    2006-07-01

    Full Text Available BACKGROUND: Long term success of dental implants directly depends on marginal bone resorption. The aim of this study was to determine the annual average bone loss on the mesial and distal aspects of implants following the first year of implantation. METHODS: This was a descriptive analytical study of patients treated with ITI (International Team of Implantology implants at the Dental School of Isfahan University of Medical Sciences from 1998-2002 (1377-81. A total of 15 patients with 41 implants were selected by convenience sampling method. The height of the alveolar bone was measured using panoramic radiography before and after loading with calipers to determine the average bone loss. Other information such as pocket depth, bleeding index, plaque index, gingival recession, was obtained by clinical examinations. The mean bone loss on the mesial & distal sides was analyzed by ANOVA at 0.05 level of significance. RESULTS: The average bone loss on the proximal sides of ITI implants obtained annually after the first year of loading was 0.084 ± 0.035 mm with slight difference on the mesial (0.092 ± 0.035 and distal (0.072 ± 0.033 sides. There was negligible difference between male and female patients. The average survival rate for thirty three months was 95.1%. CONCLUSION: The average bone loss on the mesial and distal sides of ITI implants compared with other studies was satisfactory. Survival and success rates were acceptable. KEYWORDS: Dental implants, bone resorption, survival rate, dental plaque index.

  19. MicroCT evaluation of bone mineral density loss in human bones

    International Nuclear Information System (INIS)

    Bone is a connective tissue largely composed of an organic protein, collagen and the inorganic mineral hydroxyapatite [Ca10(PO4)6OH2], which combine to provide a mechanical and supportive role in the body. Depending on the orientation of collagen fibers, two types of bone can be distinguished: trabecular and cortical bone. Degree of mineralization is considered an important feature of bone quality. Changes in the degree of mineralization is generally due to osteoporosis, but many recent studies have already shown that alterations in degree of mineralization can occur due to a large variety of factors. The transmission X-ray microtomography is one of the most popular methods, which provides the spatial distribution of the total absorption coefficient inside the sample. The aim of this study was to investigate the suitability of using microCT as a supplementary tool for the diagnosis of the health status of human bones. Eleven samples were constructed simulating the physiological range of bone mineral density (BMD) found in cortical human bone. The samples represent healthy mixtures of swine compact bone dried at room temperature, powdered and mixed with fat (0 - 100 % by mass). The samples were imaged by a microfocus tube (Fein-Focus) with focal size of about 60 μm (±5%), and a CCD camera (0.143 mm pixel size) coupled with an intensifier tube with fluoroscope screen at the Nuclear Instrumentation Laboratory (COPPE/UFRJ), Brazil. The images were reconstructed and treated with suitable software developed at the Nuclear Instrumentation Laboratory. The mineral content in cortical bone is defined by the volume of dry, fat-free bone per unit bulk volume of the bone. The volumes were calculated from the bone density using the relationship between volume and density. The densities of fat and bone were taken to be 0.95 g.cm-3 and 1.92 g.cm-3 respectively. The correlation of the measured absorption coefficient with the mineral content in the samples was then investigated

  20. Modeling of Blood Lead Levels in Astronauts Exposed to Lead from Microgravity-Accelerated Bone Loss

    Science.gov (United States)

    Garcia, H.; James, J.; Tsuji, J.

    2014-01-01

    Human exposure to lead has been associated with toxicity to multiple organ systems. Studies of various population groups with relatively low blood lead concentrations (lead level with lower cognitive test scores in children, later onset of puberty in girls, and increased blood pressure and cardiovascular mortality rates in adults. Cognitive effects are considered by regulatory agencies to be the most sensitive endpoint at low doses. Although 95% of the body burden of lead is stored in the bones, the adverse effects of lead correlate with the concentration of lead in the blood better than with that in the bones. NASA has found that prolonged exposure to microgravity during spaceflight results in a significant loss of bone minerals, the extent of which varies from individual to individual and from bone to bone, but generally averages about 0.5% per month. During such bone loss, lead that had been stored in bones would be released along with calcium. The effects on the concentration of lead in the blood (PbB) of various concentrations of lead in drinking water (PbW) and of lead released from bones due to accelerated osteoporosis in microgravity, as well as changes in exposure to environmental lead before, during, and after spaceflight were evaluated using a physiologically based pharmacokinetic (PBPK) model that incorporated exposure to environmental lead both on earth and in flight and included temporarily increased rates of osteoporosis during spaceflight.

  1. Recurrent anterior glenohumeral instability: the quantification of glenoid bone loss using magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Martins e Souza, Patricia [Fleury Medicina e Saude and Instituto Nacional de Traumatologia e Ortopedia, Rio de Janeiro, RJ (Brazil); Brandao, Bruno Lobo; Motta, Geraldo; Monteiro, Martim [Instituto Nacional de Traumatologia e Ortopedia, Rio de Janeiro, RJ (Brazil); Brown, Eduardo [Grupo Fleury Medicina Diagnostica, Rio de Janeiro, RJ (Brazil); Marchiori, Edson [Universidade Federal do Rio de Janeiro, Petropolis, RJ (Brazil)

    2014-08-15

    To investigate the accuracy of conventional magnetic resonance imaging (MRI) in determining the severity of glenoid bone loss in patients with anterior shoulder dislocation by comparing the results with arthroscopic measurements. Institutional review board approval and written consent from all patients were obtained. Thirty-six consecutive patients (29 men, seven women; mean age, 34.5 [range, 18-55] years) with recurrent anterior shoulder dislocation (≥3 dislocations; mean, 37.9; range, 3-200) and suspected glenoid bone loss underwent shoulder MRI before arthroscopy (mean interval, 28.5 [range, 9-73] days). Assessments of glenoid bone loss by MRI (using the best-fit circle area method) and arthroscopy were compared. Inter- and intrareader reproducibility of MRI-derived measurements was evaluated using arthroscopy as a comparative standard. Glenoid bone loss was evident on MRI and during arthroscopy in all patients. Inter- and intrareader correlations of MRI-derived measurements were excellent (intraclass correlation coefficient = 0.80-0.82; r = 0.81-0.86). The first and second observers' measurements showed strong (r = 0.76) and moderate (r = 0.69) interreader correlation, respectively, with arthroscopic measurements. Conventional MRI can be used to measure glenoid bone loss, particularly when employed by an experienced musculoskeletal radiologist. (orig.)

  2. Recurrent anterior glenohumeral instability: the quantification of glenoid bone loss using magnetic resonance imaging

    International Nuclear Information System (INIS)

    To investigate the accuracy of conventional magnetic resonance imaging (MRI) in determining the severity of glenoid bone loss in patients with anterior shoulder dislocation by comparing the results with arthroscopic measurements. Institutional review board approval and written consent from all patients were obtained. Thirty-six consecutive patients (29 men, seven women; mean age, 34.5 [range, 18-55] years) with recurrent anterior shoulder dislocation (≥3 dislocations; mean, 37.9; range, 3-200) and suspected glenoid bone loss underwent shoulder MRI before arthroscopy (mean interval, 28.5 [range, 9-73] days). Assessments of glenoid bone loss by MRI (using the best-fit circle area method) and arthroscopy were compared. Inter- and intrareader reproducibility of MRI-derived measurements was evaluated using arthroscopy as a comparative standard. Glenoid bone loss was evident on MRI and during arthroscopy in all patients. Inter- and intrareader correlations of MRI-derived measurements were excellent (intraclass correlation coefficient = 0.80-0.82; r = 0.81-0.86). The first and second observers' measurements showed strong (r = 0.76) and moderate (r = 0.69) interreader correlation, respectively, with arthroscopic measurements. Conventional MRI can be used to measure glenoid bone loss, particularly when employed by an experienced musculoskeletal radiologist. (orig.)

  3. TEI-3313, a novel prostaglandin A1 derivative, prevents bone loss and enhances bone formation in immobilized male rats.

    Science.gov (United States)

    Ohta, T; Azuma, Y; Kanatani, H; Kiyoki, M; Koshihara, Y

    1995-10-01

    The effect of a novel prostaglandin A1 derivative, TEI-3313, with the chemical structure 5-[(Z,2E)-4,7-dihydroxy-2-heptenyridene]-4-hydroxy- 2-methylthio-4-(4-phenoxybutyl)-2-cyclopentenone, on bone mineral content was investigated. Seven-week-old Sprague-Dawley rats in which the right hindlimbs were immobilized by sciatic nerve dissection received 1, 10, 100 or 500 micrograms of TEI-3313/kg/day, i.p., for 6 weeks. Control animals were operated on but received vehicle only. Bone mineral content of the femur was measured by single-photon absorptiometry, and biochemical parameters were analyzed. Histomorphometric observations were performed on the proximal metaphysial sections of the tibiae. The administration of up to 500 micrograms/kg of TEI-3313 to rats had no effect on body weight or on serum calcium, inorganic phosphorus and 1 alpha,25 dihydroxy vitamin D3 levels. Immobilization decreased the ash content, calcium content and total bone mineral content of the femur compared with nonimmobilization (unoperated femur). With TEI-3313 administration, changes in these parameters in the immobilized femur were prevented almost to the levels of the nonimmobilized femur, in a dose-dependent manner. The enhancement of bone mineral content was remarkable in the midshaft of the femur. TEI-3313 enhanced ash and calcium content and total bone mineral content in nonimmobilized femurs. Microradiograms showed that TEI-3313, unlike pamidronate and 17 beta-estradiol, had little inhibitory effect on trabecular bone resorption in the proximal portion of the tibia. TEI-3313 not only prevented the bone loss induced by immobilization but also increased bone mass in the nonimmobilized femurs without affecting the levels of 1 alpha,25 dihydroxy vitamin D3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7562584

  4. Single-Limb Irradiation Induces Local and Systemic Bone Loss in a Murine Model.

    Science.gov (United States)

    Wright, Laura E; Buijs, Jeroen T; Kim, Hun-Soo; Coats, Laura E; Scheidler, Anne M; John, Sutha K; She, Yun; Murthy, Sreemala; Ma, Ning; Chin-Sinex, Helen J; Bellido, Teresita M; Bateman, Ted A; Mendonca, Marc S; Mohammad, Khalid S; Guise, Theresa A

    2015-07-01

    Increased fracture risk is commonly reported in cancer patients receiving radiotherapy, particularly at sites within the field of treatment. The direct and systemic effects of ionizing radiation on bone at a therapeutic dose are not well-characterized in clinically relevant animal models. Using 20-week-old male C57Bl/6 mice, effects of irradiation (right hindlimb; 2 Gy) on bone volume and microarchitecture were evaluated prospectively by microcomputed tomography and histomorphometry and compared to contralateral-shielded bone (left hindlimb) and non-irradiated control bone. One week postirradiation, trabecular bone volume declined in irradiated tibias (-22%; p MLO-Y4 cell apoptosis was induced as early as 48 hours postirradiation (4 Gy). In osteoclastogenesis assays, radiation exposure (8 Gy) stimulated murine macrophage RAW264.7 cell differentiation, and coculture of irradiated RAW264.7 cells with MLO-Y4 or murine bone marrow cells enhanced this effect. These studies highlight the multifaceted nature of radiation-induced bone loss by demonstrating direct and systemic effects on bone and its many cell types using clinically relevant doses; they have important implications for bone health in patients treated with radiation therapy. PMID:25588731

  5. Simvastatin prevents alveolar bone loss in an experimental rat model of periodontitis after ovariectomy

    OpenAIRE

    XU, XIN-CHEN; Chen, Hui; Zhang, Xi; ZHAI, ZAN-JING; Liu, Xu-qiang; Qin, An; Lu, Er-yi

    2014-01-01

    Background Periodontitis is an inflammatory disease characterized by the loss of connective tissue and alveolar bone. There is an increasing evidence that periodontitis is associated with a number of chronic disease, including osteoporosis. Periodontitis and osteoporosis are both bone destructive diseases and of high prevalence in adult population. Osteoporosis could increase some inflammatory factors that also participate in the progression of periodontitis, so as to facilitate the alveolar ...

  6. Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice

    OpenAIRE

    Azuma, Kagaku; Furuzawa, Manabu; Fujiwara, Shu; YAMADA, Kumiko; Kubo, Kin-Ya

    2015-01-01

    Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a woode...

  7. Potential role of proinflammatory cytokines in nerve damage related bone loss.

    Science.gov (United States)

    Miesse, Andrew M; Willey, Jeffrey S; Bateman, Ted A

    2004-01-01

    An estimated 375,000 people are currently suffering from spinal cord injuries and another 1.5 million are afflicted by peripheral nerve damage in the United States. Wolf's Law states that a bone grows or remodels in response to the stresses that are placed on it. Forces applied to bones that occur due to normal daily activity allow for healthy resorption and formation of bones. Periods of immobilization caused by nerve damage have a profound effect on the integrity of bone, causing an increased risk of bone fracture. The need for investigating ways of combating this secondary effect of nerve damage is imperative to the long-term health of spinal cord injury and peripheral nerve damage patients. Our lab uses two sciatic nerve damage models in mice to mimic the bone loss caused by recoverable, sciatic nerve crush (NC), and non-recoverable, sciatic neurectomy (NX), injuries. We are examining the hypothesis that recoverable damage actually causes an accelerated loss of bone mass compared to the permanently damaged nerve because of the transport of proinflammatory cytokines from the site of the nerve damage to the locally affected bone. This inflammatory response, and the hypothesized differences between the two models, will be examined via ELISA of the quadriceps to investigate the relative degree of proinflammatory cytokines local to the damage site. Understanding the cellular mechanisms that occur at nerve injury sites will allow for improved care and long-term treatment of patients. A preliminary analysis of the bone loss associate with these two nerve injury models indicate approximately a 50% greater decline in femoral mass of the NC femur compared to the NX limb, supporting the proinflammatory hypothesis. PMID:15133969

  8. Staged Custom, Intramedullary Antibiotic Spacers for Severe Segmental Bone Loss in Infected Total Hip Arthroplasty

    Directory of Open Access Journals (Sweden)

    Atul F. Kamath

    2011-01-01

    Full Text Available Introduction. Total hip arthroplasty (THA infections with severe bone loss pose significant reconstructive challenges. We present our experience with two-stage hip reimplantation using an intramedullary, antibiotic-impregnated nail. Methods. Three patients with infected THA with severe proximal femoral bone loss (Mallory type IIIB or greater were treated using a custom antibiotic spacer. Clinical outcomes and any complications were recorded. Average followup was 49 months from final reimplantation. Results. Mean age at spacer placement (stage 1 was 53 years. The mean Harris Hip Score at final followup was 80. Two patients had asymptomatic heterotopic ossification, and one patient had a 2 cm leg-length discrepancy. Conclusions. A custom intramedullary nail antibiotic spacer is a reliable option in the staged management of the infected THA with severe proximal femoral bone loss. Benefits of this technique include limb salvage with maintenance of leg length, soft tissue tension, and functional status.

  9. Blueberry consumption prevents loss of collagen in bone matrix and inhibits senescence pathways in osteoblastic cells.

    Science.gov (United States)

    Zhang, Jian; Lazarenko, Oxana P; Blackburn, Michael L; Badger, Thomas M; Ronis, Martin J J; Chen, Jin-Ran

    2013-06-01

    Ovariectomy (OVX)-induced bone loss has been linked to increased bone turnover and higher bone matrix collagen degradation as the result of osteoclast activation. However, the role of degraded collagen matrix in the fate of resident bone-forming cells is unclear. In this report, we show that OVX-induced bone loss is associated with profound decreases in collagen 1 and Sirt1. This was accompanied by increases in expression and activity of the senescence marker collagenase and expression of p16/p21 in bone. Feeding a diet supplemented with blueberries (BB) to pre-pubertal rats throughout development or only prior to puberty [postnatal day 21 (PND21) to PND34] prevents OVX-induced effects on expression of these molecules at PND68. In order to provide more evidence and gain a better understanding on the association between bone collagen matrix and resident bone cell fate, in vitro studies on the cellular senescence pathway using primary calvarial cells and three cell lines (ST2 cells, OB6, and MLO-Y4) were conducted. We found that senescence was inhibited by collagen in a dose-response manner. Treatment of cells with serum from OVX rats accelerated osteoblastic cell senescence pathways, but serum from BB-fed OVX rats had no effect. In the presence of low collagen or treatment with OVX rat serum, ST2 cells exhibited higher potential to differentiate into adipocytes. Finally, we demonstrated that bone cell senescence is associated with decreased Sirt1 expression and activated p53, p16, and p21. These results suggest that (1) a significant prevention of OVX-induced bone cell senescence from adult rats can occur after only 14 days consumption of a BB-containing diet immediately prior to puberty, and (2) the molecular mechanisms underlying this effect involves, at least in part, prevention of collagen degradation. PMID:22555620

  10. Cordycepin Prevents Bone Loss through Inhibiting Osteoclastogenesis by Scavenging ROS Generation

    Science.gov (United States)

    Dou, Ce; Cao, Zhen; Ding, Ning; Hou, Tianyong; Luo, Fei; Kang, Fei; Yang, Xiaochao; Jiang, Hong; Xie, Zhao; Hu, Min; Xu, Jianzhong; Dong, Shiwu

    2016-01-01

    Cordycepin was previously reported to have anti-tumor, anti-inflammatory and anti-oxidant activity. However, the potential role of cordycepin in bone metabolism and cell biology of osteoclasts remains unclear. In our study, we focused on the in vitro effects of cordycepin on osteoclastogenesis and its in vivo effects in ovariectomized (OVX) mice. Osteoclast differentiation, formation and fusion were evaluated by Tartrate-resistant acid phosphatase (TRAP) stain, focal adhesion stain and fusion assay, respectively. Osteoclastic bone resorption was evaluated by pit formation assay. Reactive oxygen species (ROS) generation and removal were detected by the ROS assay. OVX mice were orally administered with 10 mg/kg of cordycepin daily for four weeks. In vitro results revealed that cordycepin inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation, formation, fusion and bone resorption activity. We further proved that cordycepin treatments scavenged the generation of ROS, upregulated interferon regulatory factor 8 (IRF-8) and suppressed the activity of nuclear factor of activated T cells c1 (NFATc1) during osteoclastogenesis. In vivo results indicated cordycepin prevents bone loss, rescues bone microarchitecture, and restores bone mineralization in OVX mice. Our observations strongly suggested that cordycepin is an efficient osteoclast inhibitor and hold potential therapeutic value in preventing bone loss among postmenopausal osteoporosis patients. PMID:27104563

  11. [Transitory bone loss during substitution treatment for hypothyroidism. Results of a two year prospective study].

    Science.gov (United States)

    Trémollières, F; Pouillès, J M; Louvet, J P; Ribot, C

    1991-12-01

    The authors report the results of a prospective study designed to assess changes in vertebral and femoral bone density during the first two years of replacement therapy in 10 patients with hypothyroidism (4 men, 6 women). During the first year, bone density measured by dual photon absorptiometry fell significantly in the lumbar vertebrae (-5.4%), neck of the femur (-7%) and the trochanteric region (-7.3%). This bone loss was accompanied by an early increase in serum osteocalcin levels, urinary calcium/urinary creatinine ratio and in Sex Hormone Binding Globulin. During the second year, there was complete recovery of values of vertebral and trochanteric bone density, while density of the neck of the femur remained significantly lower than initial values. None of the patients showed any evidence of overdose during the period of monitoring of clinical and laboratory (free T4, total and free T3, ultra-sensitive TSH) parameters. This transitory bone loss could be indicative of a state of tissue hyperthyroidism and/or "hypersensitivity" of hypothyroid bone to the action of thyroid hormones. Its influence on the subsequent risk of fracture remains unclear. In the current state of knowledge, measurement of vertebral and femoral bone density appears to be indicated in patients given long term treatment which suppresses TSH, or requiring replacement therapy for severe hypothyroidism. Any demineralisation prior to treatment could justify the temporary prescription of an antiosteoclastic agent. PMID:1780668

  12. [Prostate cancer and Cancer Treatment-Induced Bone Loss(CTIBL)].

    Science.gov (United States)

    Matsushima, Hisashi

    2016-07-01

    Osteopenia and osteoporosis often become the long term complications in cancer treatment and is defined as cancer treatment-induced bone loss(CTIBL). Hormonal therapy is the main factor for CTIBL in both men and women. Androgen deprivation therapy(ADT)is a mainstay in the systemic therapy for prostate cancer(PC)and often persists for a long term. ADT induces bone loss and increases the risk of osteoporosis and bone fractures, which reduces QOL of the patients, results in the need of nursing care state and a serious adverse event to be connected for shortening of the overall survival. It is important that we prevent a fracture above all in the bone management of patients with PC. According to the results of overseas large-scale clinical trials, denosumab is a drug having the highest evidence level. And it is necessary to set a clear treatment objective depending on the clinical condition of the PC patients, and to use it. In the non-bone metastatic, castration-sensitive PC patients, we do it with a dose for the purpose of the prevention of osteoporosis and bone fractures, and it is demanded what a dose for the purpose of prevention and in bone metastatic, castration resistant PC patients, the reduction of symptomatic skeletal events. However, There is no benefit in prolongation of overall survival by addition of denosumab or zoledronic acid. Care for oral hygiene should be considered to avoid osteonecrosis of the jaw, oral infection and hypocalcemia. PMID:27346316

  13. Use of 3D MR reconstructions in the evaluation of glenoid bone loss: a clinical study

    International Nuclear Information System (INIS)

    To assess the ability of 3D MR shoulder reconstructions to accurately quantify glenoid bone loss in the clinical setting using findings at the time of arthroscopy as the gold standard. Retrospective review of patients with MR shoulder studies that included 3D MR reconstructions (3D MR) produced using an axial Dixon 3D-T1W-FLASH sequence at our institution was conducted with the following inclusion criteria: history of anterior shoulder dislocation, arthroscopy (OR) performed within 6 months of the MRI, and an estimate of glenoid bone loss made in the OR using the bare-spot method. Two musculoskeletal radiologists produced estimates of bone loss along the glenoid width, measured in mm and %, on 3D MR using the best-fit circle method, which were then compared to the OR measurements. There were a total of 15 patients (13 men, two women; mean age, 28, range, 19-51 years). There was no significant difference, on average, between the MRI (mean 3.4 mm/12.6 %; range, 0-30 %) and OR (mean, 12.7 %; range, 0-30 %) measurements of glenoid bone loss (p = 0.767). A 95 % confidence interval for the mean absolute error extended from 0.45-2.21 %, implying that, when averaged over all patients, the true mean absolute error of the MRI measurements relative to the OR measurements is expected to be less than 2.21 %. Inter-reader agreement between the two readers had an IC of 0.92 and CC of 0.90 in terms of percentage of bone loss. 3D MR reconstructions of the shoulder can be used to accurately measure glenoid bone loss. (orig.)

  14. Use of 3D MR reconstructions in the evaluation of glenoid bone loss: a clinical study

    Energy Technology Data Exchange (ETDEWEB)

    Gyftopoulos, Soterios; Beltran, Luis S.; Yemin, Avner; Recht, Michael P. [NYU Langone Medical Center, Department of Radiology, New York, NY (United States); Strauss, Eric; Meislin, Robert; Jazrawi, Laith [NYU Langone Medical Center, Center for Musculoskeletal Care, Department of Orthopaedic Surgery, New York, NY (United States)

    2014-02-15

    To assess the ability of 3D MR shoulder reconstructions to accurately quantify glenoid bone loss in the clinical setting using findings at the time of arthroscopy as the gold standard. Retrospective review of patients with MR shoulder studies that included 3D MR reconstructions (3D MR) produced using an axial Dixon 3D-T1W-FLASH sequence at our institution was conducted with the following inclusion criteria: history of anterior shoulder dislocation, arthroscopy (OR) performed within 6 months of the MRI, and an estimate of glenoid bone loss made in the OR using the bare-spot method. Two musculoskeletal radiologists produced estimates of bone loss along the glenoid width, measured in mm and %, on 3D MR using the best-fit circle method, which were then compared to the OR measurements. There were a total of 15 patients (13 men, two women; mean age, 28, range, 19-51 years). There was no significant difference, on average, between the MRI (mean 3.4 mm/12.6 %; range, 0-30 %) and OR (mean, 12.7 %; range, 0-30 %) measurements of glenoid bone loss (p = 0.767). A 95 % confidence interval for the mean absolute error extended from 0.45-2.21 %, implying that, when averaged over all patients, the true mean absolute error of the MRI measurements relative to the OR measurements is expected to be less than 2.21 %. Inter-reader agreement between the two readers had an IC of 0.92 and CC of 0.90 in terms of percentage of bone loss. 3D MR reconstructions of the shoulder can be used to accurately measure glenoid bone loss. (orig.)

  15. Growth hormone mitigates loss of periosteal bone formation and muscle mass in disuse osteopenic rats

    DEFF Research Database (Denmark)

    Grubbe, M.-C.; Thomsen, J. S.; Nyengaard, J. R.;

    2014-01-01

    Growth hormone (GH) is a potent anabolic agent capable of increasing both bone and muscle mass. The aim was to investigate whether GH could counteract disuse-induced loss of bone and muscle mass in a rat model. Paralysis was induced by injecting 4 IU Botox (BTX) into the muscles of the right hind......BMD, -13%, P<0.001), trabecular bone volume (BV/TV, -26%, P<0.05), and mid-femoral bone strength (-12%, P<0.05). In addition, BTX reduced rectus femoris muscle mass (-69%, P<0.001) and muscle cell cross sectional area (CSA) (-73%, P<0.001) compared with controls. GH counteracted disuse-induced losses of...... periosteal BFR/BS (2-fold increase vs. BTX, P<0.001), whereas no effect on aBMD, trabecular BV/TV, or bone strength was found. In addition, GH partly prevented loss of muscle mass (+29% vs. BTX, P<0.001), and tended to prevent loss of muscle CSA (+11%, P=0.064). In conclusion, GH mitigates disuse...

  16. Effects of COLIA1 polymorphisms and haplotypes on perimenopausal bone mass, postmenopausal bone loss and fracture risk

    DEFF Research Database (Denmark)

    González-Bofill, N; Husted, L B; Harsløf, T; Tofteng, C L; Abrahamsen, B; Eiken, P; Vestergaard, Peter; Langdahl, B L

    2011-01-01

    total hip by 0.016 +/- 0.007 g/cm(2), 0.015 +/- 0.006 g/cm(2) and 0.017 +/- 0.006 g/cm(2), respectively (p < 0.05-0.005). No association with postmenopausal changes in bone mass and fracture risk and no overall interaction with the effects of hormone therapy could be demonstrated for any of the......One thousand seven hundred seventeen perimenopausal women from the Danish Osteoporosis Prevention Study were genotyped for the -1997G/T, -1663indelT and +1245G/T polymorphisms in the COLIA1 gen. We found that the -1997T allele and a haplotype containing it were associated with reduced bone mineral...... density (BMD) and increased bone turnover at menopause and after 10 years of follow-up. INTRODUCTION: We wanted to investigate whether the -1997G/T, -1663indelT and +1245G/T polymorphisms in the COLIA1 gene are associated with perimenopausal bone mass, early postmenopausal bone loss and interact with...

  17. Hyperactive lesions of gingiva associated with severe alveolar bone loss: A rare finding

    Directory of Open Access Journals (Sweden)

    Amitandra Kumar Tripathi

    2015-01-01

    Full Text Available Pyogenic granuloma (PG is an inflammatory reactive hyperplasia of connective tissue. It usually arises in response to various stimuli such as low-grade local irritation, traumatic injury, hormonal factors or certain kinds of drugs. It predominantly occurs in the second decade of life in young females and rarely may cause significantly alveolar bone loss. It managed by conservative surgical excision and removal of causative irritants. This paper presents the case of a PG in a 55-year-old male with severe alveolar bone loss in the affected site, managed by surgical intervention.

  18. Hyperactive lesions of gingiva associated with severe alveolar bone loss: A rare finding.

    Science.gov (United States)

    Tripathi, Amitandra Kumar; Upadhaya, Vinod; Kumar, Vivek; Saimbi, C S

    2015-01-01

    Pyogenic granuloma (PG) is an inflammatory reactive hyperplasia of connective tissue. It usually arises in response to various stimuli such as low-grade local irritation, traumatic injury, hormonal factors or certain kinds of drugs. It predominantly occurs in the second decade of life in young females and rarely may cause significantly alveolar bone loss. It managed by conservative surgical excision and removal of causative irritants. This paper presents the case of a PG in a 55-year-old male with severe alveolar bone loss in the affected site, managed by surgical intervention. PMID:26097359

  19. Premature loss of bone remodeling compartment canopies is associated with deficient bone formation

    DEFF Research Database (Denmark)

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Søe, Kent; Hauge, Ellen Margrethe; Bollerslev, Jens; Amling, Michael; Barvencik, Florian; Delaissé, Jean-Marie

    2011-01-01

    support to this hypothesis by analyzing the changes in prevalence of BRC canopies during the progress of the remodeling cycle in a cohort of healthy individuals and in patients with endogenous Cushing's syndrome (CS), and by relating these changes in prevalence with the extent of bone forming surfaces...

  20. Trabecular Plate Loss and Deteriorating Elastic Modulus of Femoral Trabecular Bone in Intertrochanteric Hip Fractures

    Institute of Scientific and Technical Information of China (English)

    Ji Wang; Bin Zhou; Ian Parkinson; C. David L. Thomas; John G. Clement; Nick Fazzalari; X. Edward Guo

    2013-01-01

    Osteoporotic hip fracture is associated with significant trabecular bone loss, which is typically characterized as low bone density by dual-energy X-ray absorptiometry (DXA) and altered microstructure by micro-computed tomography (µCT). Emerging morphological analysis techniques, e.g. individual trabecula segmentation (ITS), can provide additional insights into changes in plate-like and rod-like trabeculae, two major micro-structural types serving different roles in determining bone strength. Using ITS, we evaluated trabecular microstructure of intertrochanteric bone cores obtained from 23 patients undergoing hip replacement surgery for intertrochanteric fracture and 22 cadaveric controls. Micro-finite element (µFE) analyses were performed to further understand how the abnormalities seen by ITS might translate into effects on bone strength. ITS analyses revealed that, near fracture site, plate-like trabeculae were seriously depleted in fracture patients, but trabecular rod volume was maintained. Besides, decreased plate area and rod length were observed in fracture patients. Fracture patients also showed decreased elastic moduli and shear moduli of trabecular bone. These results provided evidence that in intertrochanteric hip fracture, preferential loss of plate-like trabeculae led to more rod-like microstructure and deteriorated mechanical competence adjacent to the fracture site, which increased our understanding of the biomechanical pathogenesis of hip fracture in osteoporosis.

  1. Dried plum diet protects from bone loss caused by ionizing radiation

    International Nuclear Information System (INIS)

    Bone loss caused by ionizing radiation is a potential health concern for radiotherapy patients, radiation workers and astronauts. In animal studies, exposure to ionizing radiation increases oxidative damage in skeletal tissues, and results in an imbalance in bone remodeling initiated by increased bone-resorbing osteoclasts. Therefore, we evaluated various candidate interventions with antioxidant or antiinflammatory activities (antioxidant cocktail, dihydrolipoic acid, ibuprofen, dried plum) both for their ability to blunt the expression of resorption-related genes in marrow cells after irradiation with either gamma rays (photons, 2 Gy) or simulated space radiation (protons and heavy ions, 1 Gy) and to prevent bone loss. Dried plum was most effective in reducing the expression of genes related to bone resorption (Nfe2l2, Rankl, Mcp1, Opg, TNF-α) and also preventing later cancellous bone decrements caused by irradiation with either photons or heavy ions. Furthermore, dietary supplementation with DP may prevent the skeletal effects of radiation exposures either in space or on Earth

  2. Novel Receptor-Based Countermeasures to Microgravity-Induced Bone Loss

    Science.gov (United States)

    OMalley, Bert W.

    1999-01-01

    The biological actions mediated by the estrogen receptor (ER), vitamin D receptor (VDR) and Ca(sup 2+) (sub o) -sensing receptor (CaR) play key roles in the normal control of bone growth and skeletal turnover that is necessary for skeletal health. These receptors act by controlling the differentiation and/or function of osteoblasts and osteoclasts, and other cell types within the bone and bone marrow microenvironment. The appropriate use of selective ER modulators (SERMS) which target bone, vitamin D analogs that favor bone formation relative to resorption, and CaR agonists may both stimulate osteoblastogenesis and inhibit osteoclastogenesis and the function of mature osteoclasts, should make it possible to prevent the reduction in bone formation and increase in bone resorption that normally contribute to the bone loss induced by weightlessness. Indeed, there may be synergistic interactions among these receptors that enhance the actions of any one used alone. Therefore, we proposed to: 1) assess the in vitro ability of novel ER, VDR and CaR agonists, alone or in combination, to modulate osteoblastogenesis and mature osteoblast function under conditions of 1g and simulated microgravity; 2) assess the in vitro ability of novel ER, VDR and CaR agonists, alone or in combination, to modulate osteoclastogenesis and bone resorption under conditions of lg and simulated microgravity; and 3) carry out baseline studies on the skeletal localization of the CaR in normal rat bone as well as the in vivo actions of our novel ER- and VDR-based therapeutics in the rat in preparation for their use, alone or in combination, in well-established ground-based models of microgravity and eventually in space flight.

  3. The management of bone loss in revision total knee arthroplasty: rebuild, reinforce, and augment.

    Science.gov (United States)

    Sculco, P K; Abdel, M P; Hanssen, A D; Lewallen, D G

    2016-01-01

    The treatment of bone loss in revision total knee arthroplasty has evolved over the past decade. While the management of small to moderate sized defects has demonstrated good results with a variety of traditional techniques (cement and screws, small metal augments, impaction bone grafting or modular stems), the treatment of severe defects continues to be problematic. The use of a structural allograft has declined in recent years due to an increased failure rate with long-term follow-up and with the introduction of highly porous metal augments that emphasise biological metaphyseal fixation. Recently published mid-term results on the use of tantalum cones in patients with severe bone loss has reaffirmed the success of this treatment strategy. PMID:26733657

  4. Aging of marrow stromal (skeletal) stem cells and their contribution to age-related bone loss

    DEFF Research Database (Denmark)

    Bellantuono, Ilaria; Aldahmash, Abdullah; Kassem, Moustapha

    2009-01-01

    Marrow stromal cells (MSC) are thought to be stem cells with osteogenic potential and therefore responsible for the repair and maintenance of the skeleton. Age related bone loss is one of the most prevalent diseases in the elder population. It is controversial whether MSC undergo a process of aging...

  5. Coincidence of calcified carotid atheromatous plaque, osteoporosis, and periodontal bone loss in dental panoramic radiographs

    Energy Technology Data Exchange (ETDEWEB)

    Ramesh, Aruna; Ganguly, Rumpa [Dept. of Diagnosis and Health Promotion, Division of Oral and Maxillofacial Radiology, Tufts University School of Dental Medicine, Boston (United States); Soroushian, Sheila [Dept. of Orthodontics, Howard University College of Dentistry, Washington, DC(United States)

    2013-12-15

    This study was performed to assess the correlation of calcified carotid atheromatous plaque (CCAP), the mandibular cortical index, and periodontal bone loss in panoramic radiographs. One hundred eighty-five panoramic radiographs with CCAP and 234 without this finding were evaluated by 3 observers for the presence of osseous changes related to osteoporosis and periodontal bone loss. Chi-squared and Mann-Whitney U tests were used to compare the two groups for an association of CCAP with the mandibular cortical index and periodontal bone loss, respectively. There was a statistically significant coincidence of CCAP and osseous changes related to osteopenia/osteoporosis, with a p-value <0.001. There was no statistically significant coincidence of CCAP and periodontal bone loss. When comparing the 2 groups, 'With CCAP' and 'Without CCAP', there was a statistically significant association with the mean body mass index (BMI), number of remaining teeth, positive history of diabetes mellitus, and vascular accidents. There was no statistically significant association with gender or a history of smoking. This study identified a possible concurrence of CCAP and mandibular cortical changes secondary to osteopenia/osteoporosis in panoramic radiographs. This could demonstrate the important role of dental professionals in screening for these systemic conditions, leading to timely and appropriate referrals resulting in early interventions and thus improving overall health.

  6. Phyto-oestrogen excretion and rate of bone loss in postmenopausal women

    NARCIS (Netherlands)

    Kardinaal, A.F.M.; Morton, M.S.; Brüggemann-Rotgans, I.E.M.; Beresteijn, E.C.H. van

    1998-01-01

    Objective: The hypothesis was tested that the rate of postmenopausal bone loss is inversely associated with long-term urinary excretion of phyto-oestrogens, as a marker of habitual dietary intake. Design: Secondary analysis of a 10-year follow-up study (1979-1989) among postmenopausal women in the N

  7. Coincidence of calcified carotid atheromatous plaque, osteoporosis, and periodontal bone loss in dental panoramic radiographs

    International Nuclear Information System (INIS)

    This study was performed to assess the correlation of calcified carotid atheromatous plaque (CCAP), the mandibular cortical index, and periodontal bone loss in panoramic radiographs. One hundred eighty-five panoramic radiographs with CCAP and 234 without this finding were evaluated by 3 observers for the presence of osseous changes related to osteoporosis and periodontal bone loss. Chi-squared and Mann-Whitney U tests were used to compare the two groups for an association of CCAP with the mandibular cortical index and periodontal bone loss, respectively. There was a statistically significant coincidence of CCAP and osseous changes related to osteopenia/osteoporosis, with a p-value <0.001. There was no statistically significant coincidence of CCAP and periodontal bone loss. When comparing the 2 groups, 'With CCAP' and 'Without CCAP', there was a statistically significant association with the mean body mass index (BMI), number of remaining teeth, positive history of diabetes mellitus, and vascular accidents. There was no statistically significant association with gender or a history of smoking. This study identified a possible concurrence of CCAP and mandibular cortical changes secondary to osteopenia/osteoporosis in panoramic radiographs. This could demonstrate the important role of dental professionals in screening for these systemic conditions, leading to timely and appropriate referrals resulting in early interventions and thus improving overall health.

  8. The role of osteocyte apoptosis in cancer chemotherapy-induced bone loss.

    Science.gov (United States)

    Shandala, Tetyana; Shen Ng, Yeap; Hopwood, Blair; Yip, Yuen-Ching; Foster, Bruce K; Xian, Cory J

    2012-07-01

    Intensive cancer chemotherapy leads to significant bone loss, the underlying mechanism of which remains unclear. The objective of this study was to elucidate mechanisms for effect of the commonly used anti-metabolite methotrexate (MTX) on osteocytes and on general bone homeostasis. The current study in juvenile rats showed that MTX chemotherapy caused a 4.3-fold increase in the number of apoptotic osteocytes in tibial metaphysis, which was accompanied by a 1.8-fold increase in the number of tartrate-resistant acid phosphatase-positive bone resorbing osteoclasts, and a 35% loss of trabecular bone. This was associated with an increase in transcription of the osteoclastogenic cytokines IL-6 (10-fold) and IL-11 (2-fold). Moreover, the metaphyseal bone of MTX-treated animals exhibited a 37.6% increase in the total number of osteocytes, along with 4.9-fold higher expression of the DMP-1 transcript. In cultured osteocyte-like MLO-Y4 cells, MTX treatment significantly increased caspase-3-mediated apoptosis, which was accompanied by the formation of plasma membrane-born apoptotic bodies and an increase in IL-6 (24-fold) and IL-11 (29-fold) mRNA expression. Conditioned media derived from MTX-treated MLO-Y4 cells was twice as strong as untreated media in its capacity to induce osteoclast formation in primary bone marrow osteoclast precursors. Thus, our in vivo and in vitro data suggested that MTX-induced apoptosis of osteocytes caused higher recruitment of DMP-1 positive osteocytes and increased osteoclast formation, which could contribute towards the loss of bone homeostasis in vivo. PMID:21938727

  9. Changes in bone turnover and bone loss in HIV-infected patients changing treatment to tenofovir-emtricitabine or abacavir-lamivudine.

    Directory of Open Access Journals (Sweden)

    Hila Haskelberg

    Full Text Available BACKGROUND: Those receiving tenofovir/emtricitabine (TDF-FTC had greater bone loss compared with abacavir/lamivudine (ABC-3TC in a randomized simplification trial (STEAL study. Previous studies associated increased bone turnover and bone loss with initiation of antiretroviral treatment, however it is unclear whether change in bone mineral density (BMD was a result of specific drugs, from immune reconstitution or from suppression of HIV replication. This analysis determined predictors of BMD change in the hip and spine by dual-energy x-ray absorptiometry in virologically suppressed participants through week 96. METHODOLOGY/PRINCIPAL FINDINGS: Bone turnover markers (BTMS tested were: formation [bone alkaline phosphatase, procollagen type 1 N-terminal propeptide (P1NP]; resorption (C-terminal cross-linking telopeptide of type 1 collagen [CTx]; and bone cytokine-signalling (osteoprotegerin, RANK ligand. Independent predictors of BMD change were determined using forward, stepwise, linear regression. BTM changes and fracture risk (FRAX® at week 96 were compared by t-test. Baseline characteristics (n = 301 were: 98% male, mean age 45 years, current protease-inhibitor (PI 23%, tenofovir/abacavir-naïve 52%. Independent baseline predictors of greater hip and spine bone loss were TDF-FTC randomisation (p ≤ 0.013, lower fat mass (p-trend ≤ 0.009, lower P1NP (p = 0.015, and higher hip T score/spine BMD (p-trend ≤ 0.006. Baseline PI use was associated with greater spine bone loss (p = 0.004. TDF-FTC increased P1NP and CTx through Wk96 (p<0.01. Early changes in BTM did not predict bone loss at week 96. No significant between-group difference was found in fracture risk. CONCLUSIONS/SIGNIFICANCE: Tenofovir/emtricitabine treatment, lower bone formation and lower fat mass predicted subsequent bone loss. There was no association between TDF-FTC and fracture risk.

  10. Black Lucques olives prevented bone loss caused by ovariectomy and talc granulomatosis in rats.

    Science.gov (United States)

    Puel, Caroline; Mardon, Julie; Kati-Coulibaly, Séraphin; Davicco, Marie-Jeanne; Lebecque, Patrice; Obled, Christiane; Rock, Edmond; Horcajada, Marie-Noelle; Agalias, Apostolos; Skaltsounis, Leandros A; Coxam, Véronique

    2007-05-01

    This study was conducted to determine whether olive fruits, rich in micronutrients, might improve bone loss in ovariectomized (OVX) rats (an experimental model of postmenopausal osteoporosis) and in OVX rats with granulomatosis inflammation (a model of senile osteoporosis). Six-month-old Wistar female rats underwent ovariectomy and were then immediately treated orally by substituting oil in the diet by 10 g/d green Lucques olives or 6 g/d black Lucques olives for each rat for 84 days. OVX rats and sham-operated controls received the same diet with oil. Three weeks before the end of the experiment, subcutaneous inflammation was provoked by injections of sterile magnesium silicate in half the animals in each group. In OVX rats, granulomatosis inflammation, characterized by a rise in inflammatory parameters such as fibrinogen, alpha1-acid glycoprotein, spleen weight and granulocyte level, and an impairment of oxidative status (as shown by a decrease in plasma antioxidant capacity, a higher rate of isoprostane excretion) elicited a bone loss in the whole femur and in the metaphyseal areas considered on their own. Whereas green olives had no effect on osteopenia, consumption of the black variety prevented bone loss in the whole femur and at cortical sites in those oestrogen-deficient animals with talc inflammation (diaphyseal bone mineral density: black olives and inflammation 0-2323 (SE 0.0026) v. ovariectomy and inflammation 0.2117 (SE 0.0030); P=0.027). This bone-sparing effect seemed to result from an improvement in the inflammatory and oxidative status. The present data show that black olives are able to prevent bone loss in an experimental model of senile osteoporosis (oestrogen-deficient rats in which a low-grade inflammation was induced by talc injection). PMID:17408530

  11. Decreased bone formation and increased osteoclastogenesis cause bone loss in mucolipidosis II

    OpenAIRE

    Kollmann, Katrin; Pestka, Jan Malte; Kühn, Sonja Christin; Schöne, Elisabeth; Schweizer, Michaela; Karkmann, Kathrin; Otomo, Takanobu; Catala-Lehnen, Philip; Failla, Antonio Virgilio; Marshall, Robert Percy; Krause, Matthias; Santer, Rene; Amling, Michael; Braulke, Thomas; Schinke, Thorsten

    2013-01-01

    Mucolipidosis type II (MLII) is a severe multi-systemic genetic disorder caused by missorting of lysosomal proteins and the subsequent lysosomal storage of undegraded macromolecules. Although affected children develop disabling skeletal abnormalities, their pathogenesis is not understood. Here we report that MLII knock-in mice, recapitulating the human storage disease, are runted with accompanying growth plate widening, low trabecular bone mass and cortical porosity. Intralysosomal deficiency...

  12. Comparative Evaluation of the Prevalence of Maxillary Sinus Mucosal Thickening in the Patients with Periodontal Bone Loss: A Digital Panoramic Study

    Directory of Open Access Journals (Sweden)

    S Mirbeigi

    2015-07-01

    Results: Mucosal thickening was significantly correlated with the bone loss and pattern type of the bone loss. Moreover, the prevalence of sinus mucosal thickening was 12.10% in patients with mild bone loss, 27.45% in patients with moderate bone loss, 63.15% in patients with severe bone loss. No statistically significant relationship was detected between Maxillary sinus mucositis with patients’ age and sex (p =0.05. Conclusion: In patients suffering from the bone loss, increased severity of the bone loss can lead to an increase in the prevalence of sinus mucosal thickening. The maxillary sinus mucositis was reported to be more prevalent in the bone loss with a vertical pattern rather than the bone loss with a horizontal pattern. Moreover, based on the results of the present study, the periodontal disease may increase the risk of sinus mucosal thickening.

  13. Bone Grafts

    Science.gov (United States)

    A bone graft transplants bone tissue. Surgeons use bone grafts to repair and rebuild diseased bones in your hips, knees, spine, and sometimes other bones and joints. Grafts can also repair bone loss caused by some ...

  14. Correlation analysis of alveolar bone loss in buccal/palatal and proximal surfaces in rats

    Directory of Open Access Journals (Sweden)

    Carolina Barrera de Azambuja

    2012-12-01

    Full Text Available The aim was to correlate alveolar bone loss in the buccal/palatal and the mesial/distal surfaces of upper molars in rats. Thirty-three, 60-day-old, male Wistar rats were divided in two groups, one treated with alcohol and the other not treated with alcohol. All rats received silk ligatures on the right upper second molars for 4 weeks. The rats were then euthanized and their maxillae were split and defleshed with sodium hypochlorite (9%. The cemento-enamel junction (CEJ was stained with 1% methylene blue and the alveolar bone loss in the buccal/palatal surfaces was measured linearly in 5 points on standardized digital photographs. Measurement of the proximal sites was performed by sectioning the hemimaxillae, restaining the CEJ and measuring the alveolar bone loss linearly in 3 points. A calibrated and blinded examiner performed all the measurements. Intraclass Correlation Coefficient revealed values of 0.96 and 0.89 for buccal/lingual and proximal surfaces, respectively. The Pearson Correlation Coefficient (r between measurements in buccal/palatal and proximal surfaces was 0.35 and 0.05 for the group treated with alcohol, with and without ligatures, respectively. The best correlations between buccal/palatal and proximal surfaces were observed in animals not treated with alcohol, in sites both with and without ligatures (r = 0.59 and 0.65, respectively. A positive correlation was found between alveolar bone loss in buccal/palatal and proximal surfaces. The correlation is stronger in animals that were not treated with alcohol, in sites without ligatures. Areas with and without ligature-induced periodontal destruction allow detection of alveolar bone loss in buccal/palatal and proximal surfaces.

  15. Toll-Like Receptor 4 Signaling Pathway Mediates Inhalant Organic Dust-Induced Bone Loss.

    Science.gov (United States)

    Staab, Elizabeth; Thiele, Geoffrey M; Clarey, Dillon; Wyatt, Todd A; Romberger, Debra J; Wells, Adam D; Dusad, Anand; Wang, Dong; Klassen, Lynell W; Mikuls, Ted R; Duryee, Michael J; Poole, Jill A

    2016-01-01

    Agriculture workers have increased rates of airway and skeletal disease. Inhalant exposure to agricultural organic dust extract (ODE) induces bone deterioration in mice; yet, mechanisms underlying lung-bone crosstalk remain unclear. Because Toll-like receptor 2 (TLR2) and TLR4 are important in mediating the airway consequences of ODE, this study investigated their role in regulating bone responses. First, swine facility ODE stimulated wild-type (WT) bone marrow macrophages to form osteoclasts, and this finding was inhibited in TLR4 knock-out (KO), but not TLR2 KO cells. Next, using an established intranasal inhalation exposure model, WT, TLR2 KO and TLR4 KO mice were treated daily with ODE or saline for 3 weeks. ODE-induced airway neutrophil influx and cytokine/chemokine release were similarly reduced in TLR2 and TLR4 KO animals as compared to WT mice. Utilizing micro-computed tomography (CT), analysis of tibia showed loss of bone mineral density, volume and deterioration of bone micro-architecture and mechanical strength induced by ODE in WT mice were significantly reduced in TLR4 but not TLR2 KO animals. Bone marrow osteoclast precursor cell populations were analyzed by flow cytometry from exposed animals. In WT animals, exposure to inhalant ODE increased osteoclast precursor cell populations as compared to saline, an effect that was reduced in TLR4 but not TLR2 KO mice. These results show that TLR2 and TLR4 pathways mediate ODE-induced airway inflammation, but bone deterioration consequences following inhalant ODE treatment is strongly dependent upon TLR4. Thus, the TLR4 signaling pathway appears critical in regulating the lung-bone inflammatory axis to microbial component-enriched organic dust exposures. PMID:27479208

  16. Lactobacillus fermentation enhances the inhibitory effect of Hwangryun-haedok-tang in an ovariectomy-induced bone loss

    OpenAIRE

    Shim, Ki-Shuk; Kim, Taesoo; Ha, Hyunil; Lee, Kwang Jin; Cho, Chang-Won; Kim, Han Sung; Seo, Dong-Hyun; Ma, Jin Yeul

    2013-01-01

    Background Hwangryun-haedok-tang (HRT) is traditional herbal medicine used to treat inflammatory-related diseases in Asia. However, its effect on osteoclastogenesis and bone loss is still unknown. In this study, we evaluated the effect of HRT and its fermented product (fHRT) on the receptor activator for the nuclear factor-κB ligand-induced osteoclastogenesis using murine bone marrow-derived macrophages and postmenopausal bone loss using an ovariectomy (OVX) rat model. Methods Tartrate resist...

  17. Loss of the PGE2 receptor EP1 enhances bone acquisition, which protects against age and ovariectomy-induced impairments in bone strength.

    Science.gov (United States)

    Zhang, Minjie; Feigenson, Marina; Sheu, Tzong-jen; Awad, Hani A; Schwarz, Edward M; Jonason, Jennifer H; Loiselle, Alayna E; O'Keefe, Regis J

    2015-03-01

    PGE2 exerts anabolic and catabolic effects on bone through the discrete actions of four prostanoid receptors (EP1-4). We have previously demonstrated that loss EP1 accelerates fracture repair by enhancing bone formation. In the present study we defined the role of EP1 in bone maintenance and homeostasis during aging and in response to ovariectomy. The femur and L4 vertebrae of wild type (WT) and EP1(-/-) mice were examined at 2-months, 6-months, and 1-year of age, and in WT and EP1(-/-) mice following ovariectomy (OVX) or sham surgery. Bone volume fraction, trabecular architecture and mechanical properties were maintained during aging in EP1(-/-) mice to a greater degree than age-matched WT mice. Moreover, significant increases in bone formation rate (BFR) (+60%) and mineral apposition rate (MAR) (+50%) were observed in EP1(-/-), relative to WT, while no change in osteoclast number and osteoclast surface were observed. Following OVX, loss of EP1 was protective against bone loss in both femur and L4 vertebrae, with increased bone volume/total volume (BV/TV) (+32% in femur) and max load at failure (+10% in femur) relative to WT OVX, likely resulting from the increased bone formation rate that was observed in these mice. Taken together these studies identify inhibition of EP1 as a potential therapeutic approach to suppress bone loss in aged or post-menopausal patients. PMID:25446888

  18. Evaluation of the Stress Induced in Tooth, Periodontal Ligament & Alveolar Bone with Varying Degrees of Bone Loss During Various Types of Orthodontic Tooth Movements

    Science.gov (United States)

    Mahajan, Shalu; Verma, Santosh; Bhardwaj, Preeti; Sharma, Geeta

    2016-01-01

    Introduction The force applied on to a tooth with periodontal bone loss may generate different magnitude and pattern of stresses in the periodontium when compared to a tooth with no bone loss & under the same force system. The intensity of the forces and moment to force ratios needed to be applied during an Orthodontic treatment must be adapted to obtain the same movement as in a tooth with a healthy periodontal support. Aim Evaluation and assessment of the stress distribution during various types of Orthodontic tooth movement on application of Orthodontic force, at various levels of alveolar bone loss; & determination of the most ideal force system producing the Optimum Stress (i.e., stress within optimum range), uniformly (conducive to bodily movement of maxillary canine with varying degrees of bone loss). Materials and Methods A human maxillary canine tooth of right side was simulated by means of Finite Element Method (FEM). Five different models were constructed with bone loss ranging from 0mm in model 1, to 8mm in model 5 (progressing at 2mm per model). Ten different loading conditions were applied on these models and the stress generated was charted at various occluso-gingival levels and surfaces around the tooth. The evaluation and assessment of the stress distribution during various types of Orthodontic tooth movement on application of Orthodontic force, at various levels of alveolar bone loss was done. Results The results showed that there was a high positive correlation between the increase in bone loss & the stress generated, suggesting an elevation in the stress with advancing bone loss. Additionally, the type of tooth movement was found to be changed with bone loss. During the determination of ideal force system it was found that the centre of resistance of the canine migrated apically with bone loss and an increase in the moment to force ratio (Mc:F) was required to control the root position in these cases. Conclusion A high positive correlation

  19. Current concepts in the management of recurrent anterior gleno-humeral joint instability with bone loss

    Science.gov (United States)

    Ramhamadany, Eamon; Modi, Chetan S

    2016-01-01

    The management of recurrent anterior gleno-humeral joint instability is challenging in the presence of bone loss. It is often seen in young athletic patients and dislocations related to epileptic seizures and may involve glenoid bone deficiency, humeral bone deficiency or combined bipolar lesions. It is critical to accurately identify and assess the amount and position of bone loss in order to select the most appropriate treatment and reduce the risk of recurrent instability after surgery. The current literature suggests that coracoid and iliac crest bone block transfers are reliable for treating glenoid defects. The treatment of humeral defects is more controversial, however, although good early results have been reported after arthroscopic Remplissage for small defects. Larger humeral defects may require complex reconstruction or partial resurfacing. There is currently very limited evidence to support treatment strategies when dealing with bipolar lesions. The aim of this review is to summarise the current evidence regarding the best imaging modalities and treatment strategies in managing this complex problem relating particularly to contact athletes and dislocations related to epileptic seizures. PMID:27335809

  20. Chronic skin inflammation leads to bone loss by IL-17-mediated inhibition of Wnt signaling in osteoblasts.

    Science.gov (United States)

    Uluçkan, Özge; Jimenez, Maria; Karbach, Susanne; Jeschke, Anke; Graña, Osvaldo; Keller, Johannes; Busse, Björn; Croxford, Andrew L; Finzel, Stephanie; Koenders, Marije; van den Berg, Wim; Schinke, Thorsten; Amling, Michael; Waisman, Ari; Schett, Georg; Wagner, Erwin F

    2016-03-16

    Inflammation has important roles in tissue regeneration, autoimmunity, and cancer. Different inflammatory stimuli can lead to bone loss by mechanisms that are not well understood. We show that skin inflammation induces bone loss in mice and humans. In psoriasis, one of the prototypic IL-17A-mediated inflammatory human skin diseases, low bone formation and bone loss correlated with increased serum IL-17A levels. Similarly, in two mouse models with chronic IL-17A-mediated skin inflammation,K14-IL17A(ind)andJunB(Δep), strong inhibition of bone formation was observed, different from classical inflammatory bone loss where osteoclast activation leads to bone degradation. We show that under inflammatory conditions, skin-resident cells such as keratinocytes, γδ T cells, and innate lymphoid cells were able to express IL-17A, which acted systemically to inhibit osteoblast and osteocyte function by a mechanism involving Wnt signaling. IL-17A led to decreased Wnt signaling in vitro, and importantly, pharmacological blockade of IL-17A rescued Wnt target gene expression and bone formation in vivo. These data provide a mechanism where IL-17A affects bone formation by regulating Wnt signaling in osteoblasts and osteocytes. This study suggests that using IL-17A blocking agents in psoriasis could be beneficial against bone loss in these patients. PMID:27089206

  1. Hypercortisolemia Is Associated with Severity of Bone Loss and Depression in Hypothalamic Amenorrhea and Anorexia Nervosa

    Science.gov (United States)

    Lawson, Elizabeth A.; Donoho, Daniel; Miller, Karen K.; Misra, Madhusmita; Meenaghan, Erinne; Lydecker, Janet; Wexler, Tamara; Herzog, David B.; Klibanski, Anne

    2009-01-01

    Context: Anorexia nervosa (AN) and functional hypothalamic amenorrhea (HA) are associated with low bone density, anxiety, and depression. Women with AN and HA have elevated cortisol levels. Significant hypercortisolemia, as in Cushing’s disease, causes bone loss. It is unknown whether anxiety and depression and/or cortisol dysregulation contribute to low bone density in AN or HA. Objective: Our objective was to investigate whether hypercortisolemia is associated with bone loss and mood disturbance in women with HA and AN. Design and Setting: We conducted a cross-sectional study in a clinical research center. Participants: We studied 52 women [21 healthy controls (HC), 13 normal-weight women with functional HA, and 18 amenorrheic women with AN]. Outcome Measures: Serum samples were measured every 20 min for 12 h overnight and pooled for average cortisol levels. Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry (DXA) at anteroposterior and lateral spine and hip. Hamilton Rating Scales for Anxiety (HAM-A) and Depression (HAM-D) were administered. Results: BMD was lower in AN and HA than HC at all sites and lower in AN than HA at the spine. On the HAM-D and HAM-A, AN scored higher than HA, and HA scored higher than HC. Cortisol levels were highest in AN, intermediate in HA, and lowest in HC. HAM-A and HAM-D scores were associated with decreased BMD. Cortisol levels were positively associated with HAM-A and HAM-D scores and negatively associated with BMD. Conclusions: Hypercortisolemia is a potential mediator of bone loss and mood disturbance in these disorders. PMID:19837921

  2. Bone loss and fractures in multiple sclerosis: focus on epidemiologic and physiopathological features

    Directory of Open Access Journals (Sweden)

    Dionyssiotis Y

    2011-07-01

    Full Text Available Yannis DionyssiotisRehabilitation Department, Physical and Social Rehabilitation Center, Amyntæo, Florina, GreeceAbstract: Multiple sclerosis (MS affects the central nervous system leading to disability and is complicated by bone loss and fractures. Despite the acceptance of osteoporosis and fractures as two major public health problems, in people with MS the mechanisms have not been investigated adequately. Physicians and patients usually focus on the major cause of disability and neglect the multiple risk factors for osteoporosis and fractures in this specific population. This review updates the epidemiology and physiopathological mechanisms in MS.Keywords: multiple sclerosis, bone, fractures, osteoporosis, osteopenia

  3. ITI implants with overdentures: a prevention of bone loss in edentulous mandibles?

    DEFF Research Database (Denmark)

    von Wowern, N; Harder, F; Hjørting-Hansen, E;

    1990-01-01

    Changes in the bone mineral content (BMC) of edentulous mandibles with osseointegrated ITI implants supporting overdentures were measured in vivo by dual-photon absorptiometry. The BMC measurements were performed 3 weeks postoperatively and at the 2-year follow-up visit. Measurements were made...... in the ITI site (anteriorly), the premolar region just behind the fixtures, and the standard site of the mandible for obtaining reference values of the age-related MBC loss. The increased function of the mandible after this treatment seems to cause a load-related bone formation that minimizes, or in some...

  4. Methanol Extract of the Fruits of Morinda citrifolia Linn., Restores Bone Loss in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    V. Parmar

    2011-01-01

    Full Text Available The objective of this study was to evaluate the effect of methanol extract of the fruits of Morinda citrifolia Linn., on osteoporosis induced by ovariectomy in female albino rats at two different dose levels of 500 and 750 mg/kg/day. Healthy female albino rats in the age group of 90 days were selected and randomized into five groups of six animals each. Group 1 was sham operated and served as control while all the remaining groups were ovariectomized. Group 2 was fed with an equivolume of saline and served as ovariectomized control. Group 3 was orally treated with standard Raloxifene (5.4 mg kg-1 whereas the methanol extract of Morinda citrifolia (500 and 750 mg kg-1 was administered to the groups 4 and 5. The findings assessed on the basis of biomechanical, biochemical and histopathological parameters, showed that the methanol extract significantly reduced bone loss, as evidenced by a reduction in Tartrate Resistant Acid Phosphatase (TRAP and urine Hydroxyproline (Hp levels while simultaneously increasing bone formation [high serum Alkaline Phosphatase (ALP levels], thereby restoring bone mineralization. The restoration of bone strength was confirmed by biomechanical parameters viz., the three point bending of tibia, load testing of femoral head and compression of IV lumbar vertebra and it was further endorsed by histopathological findings i.e., bone microarchitecture. The extract significantly increased the osteoblastic activity on one hand while on the other it retarded the osteoclastic function thereby contributing to a positive bone balance and hence enhanced mineralization.

  5. Ionizing Radiation and Bone Loss: Space Exploration and Clinical Therapy Applications.

    Science.gov (United States)

    Willey, Jeffrey S; Lloyd, Shane A J; Nelson, Gregory A; Bateman, Ted A

    2011-03-01

    Damage to normal, nontumor bone tissue following therapeutic irradiation increases the risk of fracture among cancer patients. For example, women treated for various pelvic tumors have been shown to have a greater than 65% increased incidence of hip fracture by 5 years postradiotherapy. Another practical situation in which exposure to ionizing radiation may negatively impact skeletal integrity is during extended spaceflight missions. There is a limited understanding of how spaceflight-relevant doses and types of radiation can influence astronaut bone health, particularly when combined with the significant effects of mechanical unloading experienced in microgravity. Historically, negative effects on osteoblasts have been studied. Radiation exposure has been shown to damage osteoblast precursors. Damage to local vasculature has been observed, ranging from decreased lumen diameter to complete ablation within the irradiated volume, causing a state of hypoxia. These effects result in suppression of bone formation and a general state of low bone turnover. More recently, however, we have demonstrated in pre-clinical mouse models, a very rapid but transient increase in osteoclast activity after exposure to spaceflight and clinically relevant radiation doses. Combined with long-term suppression of bone formation, this skeletal damage may cause long-term deficits. This review will present a broad set of literature outlining our current set knowledge of both clinical therapy and space exploration exposure to ionizing radiation. Additionally, we will discuss prevention of the initial osteoclast-mediated bone loss, the need to promote normal bone turnover and long-term quality of bone tissue, and our hypothesized molecular mechanisms. PMID:22826690

  6. Severe Bone Loss as Part of the Life History Strategy of Bowhead Whales.

    Science.gov (United States)

    George, John C; Stimmelmayr, Raphaela; Suydam, Robert; Usip, Sharon; Givens, Geof; Sformo, Todd; Thewissen, J G M

    2016-01-01

    The evolution of baleen constituted a major evolutionary change that made it possible for baleen whales to reach enormous body sizes while filter feeding on tiny organisms and migrating over tremendous distances. Bowhead whales (Balaena mysticetus) live in the Arctic where the annual cycle of increasing and decreasing ice cover affects their habitat, prey, and migration. During the nursing period, bowheads grow rapidly; but between weaning and approximately year 5, bowhead whales display sustained baleen and head growth while limiting growth in the rest of their bodies. During this period, they withdraw resources from the skeleton, in particular the ribs, which may lose 40% of bone mass. Such dramatic changes in bones of immature mammals are rare, although fossil cetaceans between 40 and 50 million years ago show an array of rib specializations that include bone loss and are usually interpreted as related to buoyancy control. PMID:27333180

  7. Increased periodontal bone loss in temporarily B lymphocyte-deficient rats

    DEFF Research Database (Denmark)

    Klausen, B; Hougen, H P; Fiehn, N E

    1989-01-01

    In order to study the role of T lymphocytes and B lymphocytes in the development of marginal periodontitis, experiments were performed on specific-pathogen-free (SPF) rats with various immunologic profiles. The study comprised nude (congenitally T lymphocyte-deficient), thymus-grafted nude (T...... had significantly less periodontal bone support than controls. Anti-mu treated inoculated rats had significantly less periodontal bone support than nude and normal rats, whereas no difference was found between normal, nude, and thymus-grafted rats. It is concluded that permanent T......-lymphocyte deficiency did not interfere with the development of periodontal disease in this model, whereas a temporary and moderate reduction in B-lymphocyte numbers seemed to predispose for aggravation of periodontal bone loss....

  8. Severe Bone Loss as Part of the Life History Strategy of Bowhead Whales.

    Directory of Open Access Journals (Sweden)

    John C George

    Full Text Available The evolution of baleen constituted a major evolutionary change that made it possible for baleen whales to reach enormous body sizes while filter feeding on tiny organisms and migrating over tremendous distances. Bowhead whales (Balaena mysticetus live in the Arctic where the annual cycle of increasing and decreasing ice cover affects their habitat, prey, and migration. During the nursing period, bowheads grow rapidly; but between weaning and approximately year 5, bowhead whales display sustained baleen and head growth while limiting growth in the rest of their bodies. During this period, they withdraw resources from the skeleton, in particular the ribs, which may lose 40% of bone mass. Such dramatic changes in bones of immature mammals are rare, although fossil cetaceans between 40 and 50 million years ago show an array of rib specializations that include bone loss and are usually interpreted as related to buoyancy control.

  9. Aerobic Exercise and Whole-Body Vibration in Offsetting Bone Loss in Older Adults

    Directory of Open Access Journals (Sweden)

    Pei-Yang Liu

    2011-01-01

    Full Text Available Osteoporosis and its associated fractures are common complications of aging and most strategies to prevent and/or treat bone loss focused on antiresorptive medications. However, aerobic exercise (AEX and/or whole-body vibration (WBV might have beneficial effect on bone mass and provide an alternative approach to increase or maintain bone mineral density (BMD and reduce the risk of fractures. The purpose of this paper was to investigate the potential benefits of AEX and WBV on BMD in older population and discuss the possible mechanisms of action. Several online databases were utilized and based on the available literature the consensus is that both AEX and WBV may increase spine and femoral BMD in older adults. Therefore, AEX and WBV could serve as nonpharmacological and complementary approaches to increasing/maintaining BMD. However, it is uncertain if noted effects could be permanent and further studies are needed to investigate sustainability of either type of the exercise.

  10. Severe Bone Loss as Part of the Life History Strategy of Bowhead Whales

    Science.gov (United States)

    George, John C.; Stimmelmayr, Raphaela; Suydam, Robert; Usip, Sharon; Givens, Geof; Sformo, Todd; Thewissen, J. G. M.

    2016-01-01

    The evolution of baleen constituted a major evolutionary change that made it possible for baleen whales to reach enormous body sizes while filter feeding on tiny organisms and migrating over tremendous distances. Bowhead whales (Balaena mysticetus) live in the Arctic where the annual cycle of increasing and decreasing ice cover affects their habitat, prey, and migration. During the nursing period, bowheads grow rapidly; but between weaning and approximately year 5, bowhead whales display sustained baleen and head growth while limiting growth in the rest of their bodies. During this period, they withdraw resources from the skeleton, in particular the ribs, which may lose 40% of bone mass. Such dramatic changes in bones of immature mammals are rare, although fossil cetaceans between 40 and 50 million years ago show an array of rib specializations that include bone loss and are usually interpreted as related to buoyancy control. PMID:27333180

  11. Bone Loss in the Acute Stage Following Burn Injury - Original Investigation

    Directory of Open Access Journals (Sweden)

    Berrin Leblebici

    2007-06-01

    Full Text Available Aim: The purpose of this study was to determine whether a bone loss occurs during acute period following burn injury or not, and to investigate the effects of various parameters on it. Materials and Methods: This study was conducted on 19 patients, ages between 20 and 50, who had a burn injury with more than %20 of Total Body Surface Area (TBSA. We recorded the patients’ burn cause, localization, percantage, ambulation and functional status. At the end of the first month, we measured bone mıneral densıty of total L1-L4 vertebrae, left distal forearm, left total femur, in all patients. A Z score less than –1 was accepted to be the indicator of bone loss. Results: The mean age of the patients (14 male and 5 female was 33.09±11.61. We found a Z score less then -1 in 68.4% of left distal forearm, 21.1% of left total femur and 36.8% of total L1-L4 vertabrae measurements. There were no significant correlations between TBSA, Functional Ambulatıon Scale and Functional Independence Measure, and Z scores. Conclusion: There is a reduction in Bone Mineral Density in patıents wıth moderate/severe burn ınjuries in the acute period which is not correlated wıth neither TBSA nor functional status. (From the World of Osteoporosis 2007;13:33-6

  12. Ethanol Extract of Atractylodes macrocephala Protects Bone Loss by Inhibiting Osteoclast Differentiation

    Directory of Open Access Journals (Sweden)

    Youn-Hwan Hwang

    2013-06-01

    Full Text Available The rhizome of Atractylodes macrocephala has been used mainly in Traditional Chinese Medicine for invigorating the functions of the stomach and spleen. In the present study, we investigated the inhibitory effect of the 70% ethanol extract of the rhizome of Atractylodes macrocephala (AMEE on osteoclast differentiation. We found that AMEE inhibits osteoclast differentiation from its precursors induced by receptor activator of nuclear factor-κB ligand (RANKL, an essential cytokine required for osteoclast differentiation. AMEE attenuated RANKL-induced activation of NF-κB signaling pathway, subsequently inhibiting the induction of osteoclastogenic transcription factors, c-Fos and nuclear factor of activated T cells cytoplasmic 1. Consistent with the in vitro results, administration of AMEE protected RANKL-induced bone loss in mice. We also identified atractylenolide I and II as active constituents contributing to the anti-osteoclastogenic effect of AMEE. Taken together, our results demonstrate that AMEE has a protective effect on bone loss via inhibiting osteoclast differentiation and suggest that AMEE may be useful in preventing and treating various bone diseases associated with excessive bone resorption.

  13. Pyogenic granuloma associated with periodontal abscess and bone loss - A rare case report

    Directory of Open Access Journals (Sweden)

    Bhrugesh J Panseriya

    2011-01-01

    Full Text Available A diverse group of the pathologic process can produce the enlargement of soft tissues in the oral cavity and often present a diagnostic challenge. This soft tissue enlargement may represent a variation of the normal anatomic structure, inflammatory reaction, cyst, neoplasm, and developmental anomalies. A group of reactive hyperplasias, which develop in response to chronic recurring tissue injury that stimulates an excessive tissue repair response. The pyogenic granuloma (PG is a reactive enlargement that is an inflammatory response to local irritation such as calculus, a fractured tooth, rough dental restoration, and foreign materials or hormonal (pregnancy tumor and rarely associated with bone loss. This paper presents a rare case of PG associated with periodontal abscess and bone loss in a 30-year-old male.

  14. Pyogenic granuloma associated with periodontal abscess and bone loss - A rare case report.

    Science.gov (United States)

    Panseriya, Bhrugesh J; Hungund, Shital

    2011-07-01

    A diverse group of the pathologic process can produce the enlargement of soft tissues in the oral cavity and often present a diagnostic challenge. This soft tissue enlargement may represent a variation of the normal anatomic structure, inflammatory reaction, cyst, neoplasm, and developmental anomalies. A group of reactive hyperplasias, which develop in response to chronic recurring tissue injury that stimulates an excessive tissue repair response. The pyogenic granuloma (PG) is a reactive enlargement that is an inflammatory response to local irritation such as calculus, a fractured tooth, rough dental restoration, and foreign materials or hormonal (pregnancy tumor) and rarely associated with bone loss. This paper presents a rare case of PG associated with periodontal abscess and bone loss in a 30-year-old male. PMID:22090773

  15. Mitochondria related peptide MOTS-c suppresses ovariectomy-induced bone loss via AMPK activation.

    Science.gov (United States)

    Ming, Wei; Lu, Gan; Xin, Sha; Huanyu, Lu; Yinghao, Jiang; Xiaoying, Lei; Chengming, Xu; Banjun, Ruan; Li, Wang; Zifan, Lu

    2016-08-01

    Therapeutic targeting bone loss has been the focus of the study in osteoporosis. The present study is intended to evaluate whether MOTS-c, a novel mitochondria related 16 aa peptide, can protect mice from ovariectomy-induced osteoporosis. After ovary removal, the mice were injected with MOTS-c at a dose of 5 mg/kg once a day for 12 weeks. Our results showed that MOTS-c treatment significantly alleviated bone loss, as determined by micro-CT examination. Mechanistically, we found that the receptor activator of nuclear factor-κB ligand (RANKL) induced osteoclast differentiation was remarkably inhibited by MOTS-c. Moreover, MOTS-c increased phosphorylated AMPK levels, and compound C, an AMPK inhibitor, could partially abrogate the effects of the MOTS-c on osteoclastogenesis. Thus, our findings provide evidence that MOTS-c may exert as an inhibitor of osteoporosis via AMPK dependent inhibition of osteoclastogenesis. PMID:27237975

  16. Denosumab, a RANK ligand inhibitor, for the management of bone loss in cancer patients

    OpenAIRE

    Yee AJ; Raje NS

    2012-01-01

    Andrew J Yee, Noopur S RajeDivision of Hematology-Oncology, Massachusetts General Hospital Cancer Center, Boston, MA, USAAbstract: Bone loss is a common side effect of cancer treatments, especially antihormonal treatments used in the treatment of breast and prostate cancer. Denosumab is a monoclonal antibody given subcutaneously that inhibits osteoclast activity by targeting the RANK ligand. It is effective in settings ranging from preventing skeletal-related complications in cancer patients ...

  17. Hyperactive lesions of gingiva associated with severe alveolar bone loss: A rare finding

    OpenAIRE

    Amitandra Kumar Tripathi; Vinod Upadhaya; Vivek Kumar; Saimbi, C. S.

    2015-01-01

    Pyogenic granuloma (PG) is an inflammatory reactive hyperplasia of connective tissue. It usually arises in response to various stimuli such as low-grade local irritation, traumatic injury, hormonal factors or certain kinds of drugs. It predominantly occurs in the second decade of life in young females and rarely may cause significantly alveolar bone loss. It managed by conservative surgical excision and removal of causative irritants. This paper presents the case of a PG in a 55-year-old male...

  18. Evaluation of the Survival Rate and Bone Loss of Implants with Various Lengths

    OpenAIRE

    Rokn AR.; H Noorani; R. Afzalifar

    2006-01-01

    Statement of Problem: The replacement of missing teeth with implant-associated restorations has become a widely used treatment modality in recent years. The length of dental implants may be a critical factor in achieving and maintaining osseointegration.Purpose: The aim of this study was to evaluate the survival rate and bone loss of dental implants with different lengthsMaterials and Methods: A retrospective cohort study was performed on 60 ITI-system implants, evenly distributed into three ...

  19. Correlation of the interdental and the interradicular bone loss: A radiovisuographic analysis

    OpenAIRE

    Grover, Vishakha; Malhotra, Ranjan; Kapoor, Anoop; Mankotia, Chahat Singh; Bither, Rupika

    2014-01-01

    Background: Presence of furcation involvement indicates advanced periodontitis, and a potentially less-favorable prognosis, for the affected tooth and its diagnosis has always been an enigma. The present study was carried out to measure and correlate the interdental and interradicular bone loss in patients suffering from periodontitis using radiovisuography (RVG) for the purpose of early furcation diagnosis. Materials and Methods: A total of 50 patients suffering from chronic generalized peri...

  20. Evaluation of the Survival Rate and Bone Loss of Implants with Various Lengths

    Directory of Open Access Journals (Sweden)

    AR. Rokn

    2006-12-01

    Full Text Available Statement of Problem: The replacement of missing teeth with implant-associated restorations has become a widely used treatment modality in recent years. The length of dental implants may be a critical factor in achieving and maintaining osseointegration.Purpose: The aim of this study was to evaluate the survival rate and bone loss of dental implants with different lengthsMaterials and Methods: A retrospective cohort study was performed on 60 ITI-system implants, evenly distributed into three groups including 8, 10 and 12 mm high implants in the posterior segments of both jaws. Demographic information, oral hygiene,cigarette smoking, implant length, duration of implant placement (at least 24 months,bleeding on probing index and pocket probing depth were recorded for all participants.Bone loss was calculated using pre- and post-operative panoramic radiographs.Results: The mean rate of bone loss was different among the three groups and were found to be 0.21 (0.45, 0.3 (0.41 and 0.43 (0.55 mm in the 8, 10, and 12 mm high implants, respectively. Neither mean bone loss nor bleeding on probing index showed significant differences with implant length. A significant correlation was found between implant length and pocket probing depth (P<0.0001.Conclusion: The results of this study suggest that both short (8 mm high and long (10 or 12 mm high implants may be used with nearly equal success rates in the posterior segments of the jaws.

  1. Erythropoietin treatment in murine multiple myeloma: immune gain and bone loss.

    Science.gov (United States)

    Deshet-Unger, Naamit; Hiram-Bab, Sahar; Haim-Ohana, Yasmin; Mittelman, Moshe; Gabet, Yankel; Neumann, Drorit

    2016-01-01

    Multiple myeloma (MM) is a plasma cell malignancy, characterized by osteolytic lesions and monoclonal immunoglobulins. The anemia, accompanying the disease is often treated with recombinant human EPO. Diverse non-erythropoietic effects of EPO have led us to question its combined action on the immune system and bone in the 5T33MM mouse model. EPO administration to MM mice attenuated disease progression as demonstrated by a decrease in serum MM IgG2b, splenic CD138 expressing cells, IL-6 and RORγτ transcripts in bone marrow (BM). IFN-γ transcript levels and macrophages (F4/80(+)CD11b(+)) in the BM both increased ~1.5 fold in the EPO-treated MM mice. In-vitro, EPO stimulated phagocytosis of 5T33MM cells (+30%) by BM-derived macrophages. In contrast, high-resolution microCT analysis of distal femurs revealed EPO-associated bone loss in both healthy and 5T33MM mice. EPO significantly increased expression of the osteoclastogenic nuclear factor-kappa B ligand (RANKL) in healthy mice, but not in MM mice, likely due to antagonizing effects on MM progression. Thus, in MM, EPO may act as a double-edged-sword stimulating immune response, while accelerating bone resorption, possibly via direct action on BM macrophages. This study supports a prudent approach of treating anemia in MM patients, aiming to maintain EPO-associated anti-MM effects, while considering bone damage. PMID:27481313

  2. Inactivity-induced bone loss is not exacerbated by moderate energy restriction

    Science.gov (United States)

    Heer, M.; Boese, A.; Baecker, N.; Zittermann, A.; Smith, S. M.

    Severe energy restriction leads to decreased bone mineral density (BMD) in postmenopausal women, adolescent females, and in male athletes. Astronauts in space also lose bone mass, and most of them have reduced energy intake (about 25 % below requirements). The aim of our study was to examine if bone loss in space is partly induced by moderate energy restriction. Physiological changes of space flight were simulated by 6 head-down tilt bed rest (HDBR). Nine healthy male subjects (age: 23.6 ± 3.0 years; BMI: 23.0 ± 2.9 kg/m2, mean ± SD) finished four study phases, two of normocaloric nutrition, either ambulatory or HDBR, and two of hypocaloric nutrition, either ambulatory or HDBR. Urine samples (24 h) were analyzed for calcium excretion (UCaV) and bone resorption markers (C-Telopeptide, CTX, and N-Telopeptide, NTX). Serum calcium, parathyroid hormone (PTH) and bone formation markers (Procollagen-I-C-terminal-Peptide, PICP, Procollagen-I-N-terminal-Peptide, PINP, and bone-specific alkaline phosphatase, bAP) were analyzed. No significant changes in serum calcium or PTH were noted either during HDBR or during hypocaloric nutrition. PICP, but not PINP or bAP, decreased significantly during HDBR (normocaloric: p<0.02; hypocaloric: p<0.005). UCaV increased significantly over time (p<0.01) but no difference between HDBR or hypocaloric nutrition or both (p<0.26) occurred. Both CTX and NTX excretion significantly increased with HDBR (CTX: p<0.05; NTX: p<0.05), but were unaffected by hypocaloric nutrition in ambulatory and HDBR phases. In conclusion, moderate energy restriction did not exaggerate bone resorption during HDBR.

  3. Dietary Polyphenols, Berries, and Age-Related Bone Loss: A Review Based on Human, Animal, and Cell Studies

    Directory of Open Access Journals (Sweden)

    Patrice A. Hubert

    2014-03-01

    Full Text Available Bone loss during aging has become an increasing public health concern as average life expectancy has increased. One of the most prevalent forms of age-related bone disease today is osteoporosis in which the body slows down bone formation and existing bone is increasingly being resorbed by the body to maintain the calcium balance. Some causes of this bone loss can be attributed to dysregulation of osteoblast and osteoclast activity mediated by increased oxidative stress through the aging process. Due to certain serious adverse effects of the currently available therapeutic agents that limit their efficacy, complementary and alternative medicine (CAM has garnered interest as a natural means for the prevention of this debilitating disease. Natural antioxidant supplementation, a type of CAM, has been researched to aid in reducing bone loss caused by oxidative stress. Naturally occurring polyphenols, such as anthocyanins rich in berries, are known to have anti-oxidative properties. Several studies have been reviewed to determine the impact polyphenol intake—particularly that of berries—has on bone health. Studies reveal a positive association of high berry intake and higher bone mass, implicating berries as possible inexpensive alternatives in reducing the risk of age related bone loss.

  4. Inhibition of bone loss with surface-modulated, drug-loaded nanoparticles in an intraosseous model of prostate cancer.

    Science.gov (United States)

    Adjei, Isaac M; Sharma, Blanka; Peetla, Chiranjeevi; Labhasetwar, Vinod

    2016-06-28

    Advanced-stage prostate cancer usually metastasizes to bone and is untreatable due to poor biodistribution of intravenously administered anticancer drugs to bone. In this study, we modulated the surface charge/composition of biodegradable nanoparticles (NPs) to sustain their blood circulation time and made them small enough to extravasate through the openings of the bone's sinusoidal capillaries and thus localize into marrow. NPs with a neutral surface charge, achieved by modulating the NP surface-associated emulsifier composition, were more effective at localizing to bone marrow than NPs with a cationic or anionic surface charge. These small neutral NPs (~150nm vs. the more usual ~320nm) were also ~7-fold more effective in localizing in bone marrow than large NPs. We hypothesized that NPs that effectively localize to marrow could improve NP-mediated anticancer drug delivery to sites of bone metastasis, thereby inhibiting cancer progression and preventing bone loss. In a PC-3M-luc cell-induced osteolytic intraosseous model of prostate cancer, these small neutral NPs demonstrated greater accumulation in bone within metastatic sites than in normal contralateral bone as well as co-localization with the tumor mass in marrow. Significantly, a single-dose intravenous administration of these small neutral NPs loaded with paclitaxel (PTX-NPs), but not anionic PTX-NPs, slowed the progression of bone metastasis. In addition, neutral PTX-NPs prevented bone loss, whereas animals treated with the rapid-release drug formulation Cremophor EL (PTX-CrEL) or saline (control) showed >50% bone loss. Neutral PTX-NPs did not cause acute toxicity, whereas animals treated with PTX-CrEL experienced weight loss. These results indicate that NPs with appropriate physical and sustained drug-release characteristics could be explored to treat bone metastasis, a significant clinical issue in prostate and other cancers. PMID:27090164

  5. Hwangryun-Haedok-Tang Fermented with Lactobacillus casei Suppresses Ovariectomy-Induced Bone Loss

    Directory of Open Access Journals (Sweden)

    Ki-Shuk Shim

    2012-01-01

    Full Text Available Hwangryun-haedok-tang (HRT is the common recipe in traditional Asian medicine, and microbial fermentation is used for the conventional methods for processing traditional medicine. We investigated the inhibitory effect of the n-butanol fraction of HRT (HRT-BU and fHRT (fHRT-BU on the RANKL-induced osteoclastogenesis in bone-marrow-derived macrophages. mRNA expression of osteoclastogenesis-related genes were evaluated by real-time QPCR. The activation of signaling pathways was determined by western blot analysis. The marker compounds of HRT-BU and fHRT-BU were analyzed by HPLC. The inhibitory effect of HRT or fHRT on ovariectomy-induced bone loss were evaluated using OVX rats with orally administered HRT, fHRT (300, 1000 mg/kg, or its vehicle for 12 weeks. fHRT-BU significantly inhibited RANKL-induced osteoclastogenesis, and phosphorylation of p38, IKKα/β, and NF-κBp65 compared to HRT-BU. In addition, fHRT-BU also significantly inhibited the mRNA expression of Nfκb2, TNF-α, NFATc1, TRAP, ATPv0d2, and cathepsin K. Furthermore, administration of fHRT had a greater effect on the increase of BMD, and greater improved bone microstructure of the femora than that of HRT in ovariectomy rats. This study demonstrated that bacterial fermentation enhances the inhibitory effect of HRT on osteoclastogenesis and bone loss. These results suggest that fermented HRT might have the beneficial effects on bone disease by inhibiting osteoclastogenesis.

  6. Dietary emu oil supplementation suppresses 5-fluorouracil chemotherapy-induced inflammation, osteoclast formation, and bone loss.

    Science.gov (United States)

    Raghu Nadhanan, Rethi; Abimosleh, Suzanne M; Su, Yu-Wen; Scherer, Michaela A; Howarth, Gordon S; Xian, Cory J

    2012-06-01

    Cancer chemotherapy can cause osteopenia or osteoporosis, and yet the underlying mechanisms remain unclear, and currently, no preventative treatments are available. This study investigated damaging effects of 5-fluorouracil (5-FU) on histological, cellular, and molecular changes in the tibial metaphysis and potential protective benefits of emu oil (EO), which is known to possess a potent anti-inflammatory property. Female dark agouti rats were gavaged orally with EO or water (1 ml·day(-1)·rat(-1)) for 1 wk before a single ip injection of 5-FU (150 mg/kg) or saline (Sal) was given. The treatment groups were H(2)O + Sal, H(2)O + 5-FU, EO + 5-FU, and EO + Sal. Oral gavage was given throughout the whole period up to 1 day before euthanasia (days 3, 4, and 5 post-5-FU). Histological analysis showed that H(2)O + 5-FU significantly reduced heights of primary spongiosa on days 3 and 5 and trabecular bone volume of secondary spongiosa on days 3 and 4. It reduced density of osteoblasts slightly and caused an increase in the density of osteoclasts on trabecular bone surface on day 4. EO supplementation prevented reduction of osteoblasts and induction of osteoclasts and bone loss caused by 5-FU. Gene expression studies confirmed an inhibitory effect of EO on osteoclasts since it suppressed 5-FU-induced expression of proinflammatory and osteoclastogenic cytokine TNFα, osteoclast marker receptor activator of nuclear factor-κB, and osteoclast-associated receptor. Therefore, this study demonstrated that EO can counter 5-FU chemotherapy-induced inflammation in bone, preserve osteoblasts, suppress osteoclast formation, and potentially be useful in preventing 5-FU chemotherapy-induced bone loss. PMID:22436700

  7. Suppression of Experimental Arthritis and Associated Bone Loss by a Tissue-Selective Estrogen Complex.

    Science.gov (United States)

    Andersson, Annica; Bernardi, Angelina I; Nurkkala-Karlsson, Merja; Stubelius, Alexandra; Grahnemo, Louise; Ohlsson, Claes; Carlsten, Hans; Islander, Ulrika

    2016-03-01

    In addition to the systemic inflammation present in rheumatoid arthritis (RA), decreased estradiol levels in postmenopausal RA patients further accelerate bone loss in these patients. The tissue-selective estrogen complex (TSEC), an estrogen combined with a selective estrogen receptor modulator, is a new hormone replacement therapy option. The first approved TSEC, containing conjugated estrogens and bazedoxifene (BZA), reduces menopausal symptoms and prevents osteoporosis with an improved safety profile compared with conventional hormone replacement therapy. Previous studies have shown that estrogens strongly inhibit experimental arthritis whereas BZA is mildly suppressive. In this study the antiarthritic potential of combined BZA and estradiol is explored for the first time. Female ovariectomized DBA/1 mice were subjected to collagen-induced arthritis, an experimental postmenopausal RA model, and treated with BZA, 17β-estradiol (E2), combined BZA and E2 (BZA/E2), or vehicle. BZA/E2 suppressed arthritis severity and frequency, synovitis, and joint destruction, equally efficient as E2 alone. Unwanted estrogenic proliferative effects on the endometrium were blocked by the addition of BZA, determined by collecting uterine weights. Bone mineral density was measured by peripheral quantitative computed tomography, and all treatments protected collagen-induced arthritis mice from both trabecular and cortical bone loss. Moreover, BZA/E2, but not E2 alone, inhibited preosteoclast formation and reduced serum anticollagen type II antibodies. In conclusion, a TSEC, herein combined BZA/E2, suppresses experimental arthritis and prevents associated bone loss as efficiently as E2 alone but with minimal uterine effects, highlighting the need for clinical trials that evaluate the addition of a TSEC to conventional postmenopausal RA treatment. PMID:26745543

  8. Telomerase-Deficient Mice Exhibit Bone Loss Owing to Defects in Osteoblasts and Increased Osteoclastogenesis by Inflammatory Microenvironment

    DEFF Research Database (Denmark)

    Saeed, H.; Abdallah, B. M.; Ditzel, N.;

    2011-01-01

    Telomere shortening owing to telomerase deficiency leads to accelerated senescence of human skeletal (mesenchymal) stem cells (MSCs) in vitro, whereas overexpression leads to telomere elongation, extended life span, and enhanced bone formation. To study the role of telomere shortening in vivo, we...... osteoblastic defects and creation of a proinflammatory osteoclast-activating microenvironment. Thus telonnerization of MSCs may provide a novel approach for abolishing age-related bone loss. (C) 2011 American Society for Bone and Mineral Research....

  9. Receptor activator of nuclear factor-κB ligand and osteoprotegerin: maintaining the balance to prevent bone loss

    OpenAIRE

    Trouvin, Anne-Priscille; Goëb, Vincent

    2010-01-01

    Bone remodeling requires a precise balance between resorption and formation. It is a complex process that involves numerous factors: hormones, growth factors, vitamins, and cytokines, and notably osteoprotegerin (OPG) and receptor activator for nuclear factor-κB (RANK) ligand. The signaling pathway OPG/RANK/RANKL is key to regulation for maintaining the balance between the activity of osteoblasts and osteoclasts in order to prevent bone loss and ensure a normal bone turnover. In this review, ...

  10. The effect of chronic mild hyponatremia on bone mineral loss evaluated by retrospective national Danish patient data

    DEFF Research Database (Denmark)

    Kruse, Christian; Eiken, Pia; Verbalis, Joseph;

    2016-01-01

    PURPOSE: To evaluate the effect of chronic mild hyponatremia ([Na+]=130-137mmol/L) on bone mineral content (BMC) and bone mineral density (BMD) loss through multiple, serial dual-energy X-ray absorptiometry (DXA) scans. METHODS: Utilizing biochemical and DXA scan data from two Danish regions...

  11. Prediction of bone loss in elderly female subjects by MR perfusion imaging and spectroscopy

    International Nuclear Information System (INIS)

    To determine whether MR perfusion indices or marrow fat content at baseline can predict areal bone mineral density (BMDa) loss. Repeat dual x-ray absorptiometry (DXA) of the hip was performed in female subjects at 2 years (n = 52) and 4 years (n = 45) following baseline MR perfusion imaging and spectroscopy of the hip. Percentage reduction in femoral neck BMDa at 4 years post-baseline was greater in subjects with below median acetabulum enhancement slope (Eslope) (-5.6 ± 1.2 Vs -1.1 ± 1.2 (mean ± standard error) p = 0.014) or muscle maximum enhancement (Emax) (-5.7 ± 1.2 Vs -0.23 ± 1.2, p = 0.009) after adjusting for baseline co-variables. Baseline MR parameters correlated with reduction in BMDa at 4 years (acetabulum Eslope r = 0.517, p = 0.0003; muscle Emax r = 0.306, p = 0.043) as well as traditionally applied clinical risk factors. Acetabulum Eslope, femoral neck Emax and marrow fat content at baseline had sensitivities of 89%, 81% and 72% respectively at distinguishing between fast (>1%/annum) (n = 18) and slow (<1%/annum) (n = 27) BMD losers. Elderly female subjects with reduced perfusion indices at baseline had increased femoral neck bone loss at 4 years. Selected perfusion indices and marrow fat content have a moderate to high sensitivity in discriminating between fast and slow bone losers. (orig.)

  12. DEL-1 restrains osteoclastogenesis and inhibits inflammatory bone loss in nonhuman primates.

    Science.gov (United States)

    Shin, Jieun; Maekawa, Tomoki; Abe, Toshiharu; Hajishengallis, Evlambia; Hosur, Kavita; Pyaram, Kalyani; Mitroulis, Ioannis; Chavakis, Triantafyllos; Hajishengallis, George

    2015-09-30

    DEL-1 (developmental endothelial locus-1) is an endothelial cell-secreted protein that regulates LFA-1 (lymphocyte function-associated antigen-1) integrin-dependent leukocyte recruitment and inflammation in various tissues. We identified a novel regulatory mechanism of DEL-1 in osteoclast biology. Specifically, we showed that DEL-1 is expressed by human and mouse osteoclasts and regulates their differentiation and resorptive function. Mechanistically, DEL-1 inhibited the expression of NFATc1, a master regulator of osteoclastogenesis, in a Mac-1 integrin-dependent manner. In vivo mechanistic analysis has dissociated the anti-inflammatory from the anti-bone-resorptive action of DEL-1 and identified structural components thereof mediating these distinct functions. Locally administered human DEL-1 blocked inflammatory periodontal bone loss in nonhuman primates-a relevant model of human periodontitis. The ability of DEL-1 to regulate both upstream (inflammatory cell recruitment) and downstream (osteoclastogenesis) events that lead to inflammatory bone loss paves the way to a new class of endogenous therapeutics for treating periodontitis and perhaps other inflammatory disorders. PMID:26424570

  13. Micromolar sodium fluoride mediates anti-osteoclastogenesis in Porphyromonas gingivalis-induced alveolar bone loss

    Institute of Scientific and Technical Information of China (English)

    Ujjal K Bhawal; Nobushiro Hamada; Ikuo Nasu; Hirohisa Arakawa; Koh Shibutani; Hye-Jin Lee; Kazumune Arikawa; Michiharu Shimosaka; Masatoshi Suzuki; Toshizo Toyama; Takenori Sato; Ryota Kawamata; Chieko Taguchi

    2015-01-01

    Osteoclasts are bone-specific multinucleated cells generated by the differentiation of monocyte/macrophage lineage precursors. Regulation of osteoclast differentiation is considered an effective therapeutic approach to the treatment of bone-lytic diseases. Periodontitis is an inflammatory disease characterized by extensive bone resorption. In this study, we investigated the effects of sodium fluoride (NaF) on osteoclastogenesis induced by Porphyromonas gingivalis, an important colonizer of the oral cavity that has been implicated in periodontitis. NaF strongly inhibited the P. gingivalis-induced alveolar bone loss. That effect was accompanied by decreased levels of cathepsin K, interleukin (IL)-1b, matrix metalloproteinase 9 (MMP9), and tartrate-resistant acid phosphatase, which were up-regulated during P. gingivalis-induced osteoclastogenesis. Consistent with the in vivo anti-osteoclastogenic effect, NaF inhibited osteoclast formation caused by the differentiation factor RANKL (receptor activator of nuclear factor kB ligand) and macrophage colony-stimulating factor (M-CSF). The RANKL-stimulated induction of the transcription factor nuclear factor of activated T cells (NFAT) c1 was also abrogated by NaF. Taken together, our data demonstrate that NaF inhibits RANKL-induced osteoclastogenesis by reducing the induction of NFATc1, ultimately leading to the suppressed expression of cathepsin K and MMP9. The in vivo effect of NaF on the inhibition of P. gingivalis-induced osteoclastogenesis strengthens the potential usefulness of NaF for treating periodontal diseases.

  14. Long-term physical exercise retards trabecular bone loss in lumbar vertebrae of aging female mice

    Energy Technology Data Exchange (ETDEWEB)

    Silbermann, M.; Bar-Shira-Maymon, B.; Coleman, R.; Reznick, A.; Weisman, Y.; Steinhagen-Thiessen, E.; von der Mark, H.; von der Mark, K. (Rappaport Family Institute for Research in the Medical Sciences, Technion, Haifa (Israel))

    1990-02-01

    The present study examined the effect of long-term, moderate physical exercise on trabecular bone volume (TBV), calcium content, 3H-proline uptake, and the activities of alkaline and acid phosphatases in lumbar vertebrae of aging and senescent mice. It became apparent that if physical activity starts at an early stage of life, i.e., prior to middle age and is extended until old age, it exerts beneficial effects on trabecular bone mass and mineralization. Such a positive effect is not obtained if the training program is initiated after middle age. The training-induced reduction in bone loss was accompanied by a significant decrease in acid phosphatase activity whereas no changes took place with regard to the activity of alkaline phosphatase. Long-term physical exercise also enhanced the uptake of 3H-proline by lining cells along the bone trabecules. In spite of its moderate nature, the endured training program served as a stress factor for the involved animals, a fact that was manifested by an increase in the serum levels of corticosterone. Thus, it seems that whereas young animals respond favorably to such a stimulatory stress, older animals lose this ability of adaptation.

  15. The effects of different exercise modes for preventing endothelial dysfunction of arteries and bone loss in ovariectomized rats

    OpenAIRE

    Park, Jonghoon; Omi, Naomi

    2014-01-01

    [Purpose] Several epidemiological studies have demonstrated that there are positive correlations between vascular disorders and bone loss in postmenopausal women. The aim of the present study was to examine the effect of different types of exercise (e.g., climbing and swimming) for preventing endothelial dysfunction of arteries and bone loss in ovariectomized rats. [Methods] Twenty Sprague-Dawley female rats were randomly divided into three groups: ovariectomy (OVX) plus treatment with vitami...

  16. Doxorubicin-mediated bone loss in breast cancer bone metastases is driven by an interplay between oxidative stress and induction of TGFβ.

    Directory of Open Access Journals (Sweden)

    Tapasi Rana

    Full Text Available Breast cancer patients, who are already at increased risk of developing bone metastases and osteolytic bone damage, are often treated with doxorubicin. Unfortunately, doxorubicin has been reported to induce damage to bone. Moreover, we have previously reported that doxorubicin treatment increases circulating levels of TGFβ in murine pre-clinical models. TGFβ has been implicated in promoting osteolytic bone damage, a consequence of increased osteoclast-mediated resorption and suppression of osteoblast differentiation. Therefore, we hypothesized that in a preclinical breast cancer bone metastasis model, administration of doxorubicin would accelerate bone loss in a TGFβ-mediated manner. Administration of doxorubicin to 4T1 tumor-bearing mice produced an eightfold increase in osteolytic lesion areas compared untreated tumor-bearing mice (P = 0.002 and an almost 50% decrease in trabecular bone volume expressed in BV/TV (P = 0.0005, both of which were rescued by anti-TGFβ antibody (1D11. Doxorubicin, which is a known inducer of oxidative stress, decreased osteoblast survival and differentiation, which was rescued by N-acetyl cysteine (NAC. Furthermore, doxorubicin treatment decreased Cu-ZnSOD (SOD1 expression and enzyme activity in vitro, and treatment with anti-TGFβ antibody was able to rescue both. In conclusion, a combination therapy using doxorubicin and anti-TGFβ antibody might be beneficial for preventing therapy-related bone loss in cancer patients.

  17. A full-mouth radiographic survey of periodontal bone loss in dogs

    International Nuclear Information System (INIS)

    The objective of this study was to evaluate the relationship between clinically observed periodontal disease indicators and radiographic findings using fullmouth radiographs in poodles. The dogs were divided into three groups according to their age. Upper and lower incisors, canines and premolars/molars were used for clinical and radiographic analyses. The prevalence and severity of periodontal disease increased with age. In addition, the deepest pockets and most severe bone loss were found around the canine teeth. The values obtained from radiographic analysis correlated well with clinical measurements. Fullmouth radiographic surveys show clearly the alveolar bone level around the whole dentition of dogs. It should be performed prior to the institution of any treatment

  18. CD147 deficiency blocks IL-8 secretion and inhibits lung cancer-induced osteoclastogenesis

    International Nuclear Information System (INIS)

    Bone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and poor prognosis; however, the molecular basis of this process is still unknown. This study investigated the role of extracellular matrix metalloproteinase inducer (also known as cluster of differentiation (CD)147) in osteoclastogenesis resulting from bone metastasis, based on the enrichment of this glycoprotein on the surface of many malignant bone tumors. RNA interference was used to silence CD147 expression in A549 human lung cancer cells. Compared with conditioned medium (CM) from control cells (A549-CM), CM from CD147-deficient cells (A549-si-CM) suppressed receptor activator of nuclear factor κB ligand-stimulated osteoclastogenesis in RAW 264.7 cells and bone marrow-derived macrophages. The mRNA levels of osteoclast-specific genes such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K were also reduced in the presence of A549-si-CM. CD147 knockdown in A549 cells decreased interleukin (IL)-8mRNA and protein expression. IL-8 is present in large amounts in A549-CM and mimicked its inductive effect on osteoclastogenesis; this was reversed by depletion of IL-8 from the medium. Taken together, these results indicate that CD147 promotes lung cancer-induced osteoclastogenesis by modulating IL-8 secretion, and suggest that CD147 is a potential therapeutic target for cancer-associated bone resorption in lung cancer patients. - Highlights: • Bone loss frequently results from lung cancer metastasis. • Cluster of differentiation (CD)147 was depleted in A549 lung adenocarcinoma cells. • RAW 264.7 cell osteoclastogenesis was blocked by medium from CD147-deficient cells. • Interleukin (IL)-8 level was reduced in the conditioned medium. • Osteoclastogenesis induced by lung tumor cells requires CD147-mediated IL-8 release

  19. CD147 deficiency blocks IL-8 secretion and inhibits lung cancer-induced osteoclastogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hongkai; Zhuo, Yunyun; Hu, Xu; Shen, Weiwei; Zhang, Ying; Chu, Tongwei, E-mail: chtw@sina.com

    2015-03-06

    Bone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and poor prognosis; however, the molecular basis of this process is still unknown. This study investigated the role of extracellular matrix metalloproteinase inducer (also known as cluster of differentiation (CD)147) in osteoclastogenesis resulting from bone metastasis, based on the enrichment of this glycoprotein on the surface of many malignant bone tumors. RNA interference was used to silence CD147 expression in A549 human lung cancer cells. Compared with conditioned medium (CM) from control cells (A549-CM), CM from CD147-deficient cells (A549-si-CM) suppressed receptor activator of nuclear factor κB ligand-stimulated osteoclastogenesis in RAW 264.7 cells and bone marrow-derived macrophages. The mRNA levels of osteoclast-specific genes such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K were also reduced in the presence of A549-si-CM. CD147 knockdown in A549 cells decreased interleukin (IL)-8mRNA and protein expression. IL-8 is present in large amounts in A549-CM and mimicked its inductive effect on osteoclastogenesis; this was reversed by depletion of IL-8 from the medium. Taken together, these results indicate that CD147 promotes lung cancer-induced osteoclastogenesis by modulating IL-8 secretion, and suggest that CD147 is a potential therapeutic target for cancer-associated bone resorption in lung cancer patients. - Highlights: • Bone loss frequently results from lung cancer metastasis. • Cluster of differentiation (CD)147 was depleted in A549 lung adenocarcinoma cells. • RAW 264.7 cell osteoclastogenesis was blocked by medium from CD147-deficient cells. • Interleukin (IL)-8 level was reduced in the conditioned medium. • Osteoclastogenesis induced by lung tumor cells requires CD147-mediated IL-8 release.

  20. Longitudinal HR-pQCT and image registration detects endocortical bone loss in kidney transplantation patients.

    Science.gov (United States)

    Nishiyama, Kyle K; Pauchard, Yves; Nikkel, Lucas E; Iyer, Sapna; Zhang, Chiyuan; McMahon, Donald J; Cohen, David; Boyd, Steven K; Shane, Elizabeth; Nickolas, Thomas L

    2015-03-01

    Patients with chronic kidney disease (CKD) who undergo kidney transplantation experience bone loss and increased risk of fracture. However, the mechanisms of this bone loss are unclear. Our objective was to use image registration to define the cortex to assess changes in cortical porosity (Ct.Po) in patients undergoing first-time kidney transplantation. We obtained serial measurements of parathyroid hormone (PTH) and bone turnover markers and used high-resolution peripheral quantitative computed tomography (HR-pQCT) to scan the distal radius and tibia in 31 patients (21 men, 10 women; aged 51.9 ± 13.4 years) at transplant and after 1 year. Baseline and 1-year images were aligned using a fully automated, intensity-based image registration framework. We compared three methods to define the cortical region of interest (ROI) and quantify the changes: 1) cortical bone was independently defined in baseline and follow-up scans; 2) cortical bone was defined as the common cortical ROI; and 3) the cortical ROI at baseline was carried forward to 1-year follow-up (baseline-indexed). By the independently defined ROI, Ct.Po increased 11.7% at the radius and 9.1% at the tibia, whereas by the common ROI, Ct.Po increased 14.6% at the radius and 9.1% at the tibia. By the baseline-indexed ROI, which provides insight into changes at the endocortical region, Ct.Po increased 63.4% at the radius and 17.6% at the tibia. We found significant relationships between changes in Ct.Po and bone formation and resorption markers at the radius. The strongest associations were found between markers and Ct.Po using the baseline-index method. We conclude that Ct.Po increases throughout the cortex after kidney transplant, and this increase is particularly marked at the endocortical surface. These methods may prove useful for all HR-pQCT longitudinal studies, particularly when changes are expected at the endocortical region. PMID:25213758

  1. Long-term bone loss after renal transportation. Comparison of immunosuppressive regimens

    International Nuclear Information System (INIS)

    Serial measurements of serum and urine markers of bone metabolism and of forearm bone density (BMD) by dual photon absorptiometry were performed in 22 patients undergoing renal transplantation in 1986. Patients were randomised to immunosuppression with (1) cyclosporin alone (CsA group, n = 10), (2) cyclosporin for 3 months followed by azathioprine-prednisone (CsA/AzP group, n = 3) or (3) long-term azathioprine-prednisone (LT AzP group, n = 9). As no reduction in bone mineral density (BMD) was noted in the first 6 months, groups 2 and 3 were considered together (AzP group, n = 12). Mean±SEM BMD fell by 19±2% at 36 months (n = 19,m p<0.01), with similar reductions seen in the CsA and AzP groups. At 60 months, BMD of the AzP group was 25±3% below baseline (p<0.01), while the CsA group were only 5±4% belov baseline (p = NS vs baseline, p<0.05 vs AzP group). The degree of reduction in BMD over 5 years correlated with total glucocorticoid dose (r = 0.63, p<0.05), but not with biochemical markers of bone turnover. Serum alkaline phosphatase fell post-transplant in patients treated with AzP, but not in the CsA group. These results demonstrate significant loss of forearm bone mineral with long-term follow-up after renal transplantation, but suggest that patients treated with cyclosporin monotherapy may be at lower risk of this complication. (au) (15 refs.)

  2. Long-term bone loss after renal transportation. Comparison of immunosuppressive regimens

    Energy Technology Data Exchange (ETDEWEB)

    Menzies, B.; Rigby, R.; Hawley, CJ.M.; Hardie, I.R. [Princess Alexandra Hospital, Renal Transplant Unit, Woolloongabba (Australia); McIntyre, H.D. [Mater Adult Hospital, Department of Medicine, South Brisbane (Australia); Perry-Keene, D.A. [Royal Brisbane Hospital, Department of Endocrinology, Herston, Queensland (Australia)

    1995-02-01

    Serial measurements of serum and urine markers of bone metabolism and of forearm bone density (BMD) by dual photon absorptiometry were performed in 22 patients undergoing renal transplantation in 1986. Patients were randomised to immunosuppression with (1) cyclosporin alone (CsA group, n = 10), (2) cyclosporin for 3 months followed by azathioprine-prednisone (CsA/AzP group, n = 3) or (3) long-term azathioprine-prednisone (LT AzP group, n = 9). As no reduction in bone mineral density (BMD) was noted in the first 6 months, groups 2 and 3 were considered together (AzP group, n = 12). Mean{+-}SEM BMD fell by 19{+-}2% at 36 months (n = 19,m p<0.01), with similar reductions seen in the CsA and AzP groups. At 60 months, BMD of the AzP group was 25{+-}3% below baseline (p<0.01), while the CsA group were only 5{+-}4% belov baseline (p = NS vs baseline, p<0.05 vs AzP group). The degree of reduction in BMD over 5 years correlated with total glucocorticoid dose (r = 0.63, p<0.05), but not with biochemical markers of bone turnover. Serum alkaline phosphatase fell post-transplant in patients treated with AzP, but not in the CsA group. These results demonstrate significant loss of forearm bone mineral with long-term follow-up after renal transplantation, but suggest that patients treated with cyclosporin monotherapy may be at lower risk of this complication. (au) (15 refs.).

  3. Rates of Bone Loss Among Women Initiating Antidepressant Medication Use in Midlife

    Science.gov (United States)

    Ruppert, Kristine; Cauley, Jane A.; Lian, YinJuan; Bromberger, Joyce T.; Finkelstein, Joel S.; Greendale, Gail A.; Solomon, Daniel H.

    2013-01-01

    Context: Concern has been raised that medications that block serotonin reuptake may affect bone metabolism, resulting in bone loss. Objective: The aim of the study was to compare annual bone mineral density (BMD) changes among new users of selective serotonin reuptake inhibitors (SSRIs), new users of tricyclic antidepressants (TCAs), and nonusers of antidepressant medications. Design and Setting: We conducted a prospective cohort study at five clinical centers in the United States. Participants: The study included 1972 community-dwelling women, aged 42 years and older, enrolled in the Study of Women's Health Across the Nation (SWAN). Exposure: The use of antidepressant medications was assessed by interview and verified from medication containers at annual visits. Subjects were categorized as nonusers (no SSRI or TCA use at any examination), SSRI users (initiated SSRI use after the baseline SWAN visit), or TCA users (initiated TCA use after the baseline visit), using a computerized dictionary to categorize type of medication. Main Outcome Measures: BMD at the lumbar spine, total hip, and femoral neck was measured using dual-energy x-ray absorptiometry at annual visits. Results: BMD was compared among 311 new users of SSRIs, 71 new users of TCAs, and 1590 nonusers. After adjustment for potential confounders, including age, race, body mass index, menopausal status, and hormone therapy use, mean lumbar spine BMD decreased on average 0.68% per year in nonusers, 0.63% per year in SSRI users (P = .37 for comparison to nonusers), and 0.40% per year in TCA users (P = .16 for comparison to nonusers). At the total hip and femoral neck, there was also no evidence that SSRI or TCA users had an increased rate of bone loss compared with nonusers. Results were similar in subgroups of women stratified by the Center for Epidemiologic Studies Depression Scale (<16 vs ≥16). Conclusions: In this cohort of middle-aged women, use of SSRIs and TCAs was not associated with an increased

  4. Improving Distal Fixation with Total Shoulder Arthroplasty in Cases of Severe Humeral Bone Loss.

    Science.gov (United States)

    Jacobson, Amanda; Stroud, Nick; Roche, Christopher P

    2015-12-01

    The usage of and indications for total shoulder arthroplasty have grown in recent years. Certain aspects of these arthro - plasty procedures can be very complex, especially in revi - sion and fracture cases, often leading to proximal humerus bone loss. For cases with significant bone loss, there is a need for improved devices with additional options to treat a wider range of deformities while also mitigating existing complications and rates, such as poor distal fixation, inad - equate soft tissue reattachment options, and joint instability. To that end, a fatigue and torsional test was conducted on two different devices to assess the ability of each to survive an extreme fatigue and torsional load when assembled in worst-case configurations. Evaluation of the Equinoxe ® humeral reconstruction prosthesis demonstrated superior fixation in both the fatigue loading scenario and also the torsional loading scenario as compared to the 8 mm x 215 mm cemented humeral long stem, where each had only 80 mm of cemented fixation. The results of the fatigue test demonstrated that despite the humeral reconstruction pros - thesis being subjected to a 960 N force and 45 Nm bending moment (which was significantly more challenging than the 576 N force and 24.2 Nm bending moment subjected to the cemented humeral long stem), the humeral reconstruction prosthesis completed 1 M cycles without fracture or failure. Additionally, the Equinoxe ® humeral reconstruction pros - thesis was associated with a significantly greater torsional resistance in both the torque to initial slip (29.4 Nm versus 8.2 Nm; p = 0.0002) and also the maximum torque to failure (44.3 Nm versus 12.1 Nm; p fer the potential for the Equinoxe ® humeral reconstruction prosthesis to be an improved treatment option for patients with proximal humeral bone loss, though clinical follow-up is necessary to confirm these positive biomechanical results. PMID:26631195

  5. Soy isoflavones avert chronic inflammation-induced bone loss and vascular disease

    Directory of Open Access Journals (Sweden)

    Lightfoot Stan A

    2007-09-01

    metaphysis and down-regulated by IF. Conclusion These results suggest IF may attenuate the negative effects of chronic inflammation on bone and cardiovascular health. Additional research is warranted to examine the anti-inflammatory properties of the soy isoflavones and the mechanisms underlying their prevention of chronic inflammation-induced bone loss.

  6. Adseverin plays a role in osteoclast differentiation and periodontal disease-mediated bone loss.

    Science.gov (United States)

    Jiang, Hongwei; Wang, Yongqiang; Viniegra, Ana; Sima, Corneliu; McCulloch, Christopher A; Glogauer, Michael

    2015-06-01

    Osteoclast differentiation and function are highly dependent on the assembly and turnover of actin filaments, but little is known about the roles of actin binding proteins in these processes. Adseverin (Ads), a member of the gelsolin superfamily of actin capping and severing proteins, regulates actin filament turnover and can regulate the turnover of cortical actin filaments of chromaffin cells during exocytosis. Using a conditional Ads knockout mouse model, we confirmed our previous finding in cultured cells that Ads plays a role in osteoclastogenesis (OCG) and actin cytoskeletal organization in osteoclasts. Here we show that Ads is required for osteoclast formation and that when alveolar bone resorption is experimentally induced in mice, genetic deletion of Ads prevents osteoclast-mediated bone loss. Further, when Ads-null osteoclasts are cultured, they exhibit defective OCG, disorganized podosome-based actin filament superstructures, and decreased bone resorption. Reintroduction of Ads into Ads-null osteoclast precursor cells restored these osteoclast defects. Collectively, these data demonstrate a unique and osteoclast-specific role for Ads in OCG and osteoclast function. PMID:25681458

  7. Pycnogenol® treatment inhibits bone mineral density loss and trabecular deterioration in ovariectomized rats

    Science.gov (United States)

    Huang, Gangyong; Wu, Jianguo; Wang, Siqun; Wei, Yibing; Chen, Feiyan; Chen, Jie; Shi, Jingsheng; Xia, Jun

    2015-01-01

    Context: Pycnogenol® extracted from French maritime pine bark (Pinus pinaster Ait. subsp. atlantica) is functional for its antioxidant activity. Objective: To investigate the effects of Pycnogenol® on bone mineral density (BMD), trabecular microarchitecture and bone metabolism in ovariectomized (OVX) rats. Materials and methods: Thirty Sprague-Dawley rats were randomized into 3 groups: SHAM group (sham-operated rats), OVX group (OVX rats), and treatment group (OVX rats supplemented with 40 mg/kg Pycnogenol® by oral gavage). Serum levels of procollagen type I N-terminal propeptide (PINP), alkaline phosphatase (ALP) and minerals were detected at the end of 9 weeks of gavage. Deoxypyridinoline/creatinine (DPYD/Cr) and N-telopeptide of type I collagen/creatinine (NTX/Cr) rate in urine were also calculated. Left femora were collected for BMD determination, and the right distal femora were made into undecalcified specimens for histomorphometry analysis. Results: At the end of study, PINP level, DPYD/Cr and NTX/Cr rate were significantly increased, and femoral BMD were dramatically decreased in OVX group compared with SHAM group (P Pycnogenol® (40 mg/kg) can inhibit aggravated bone resorption, prevent BMD loss, and restore the impaired trabecular microarchitecture in OVX rats after 9-week-intervention. PMID:26379883

  8. Does increasing the number of short implants reduce marginal bone loss in the posterior mandible? A prospective study.

    Science.gov (United States)

    Tabrizi, Reza; Arabion, Hamidreza; Aliabadi, Ehsan; Hasanzadeh, Farzaneh

    2016-09-01

    Marginal bone loss is a concern in the long-term prognosis of short dental implants. The aim of this prospective cohort study was to evaluate the loss when variable numbers of short implants were used in the posterior mandible. The subjects were allocated into three groups according to the number of short implants. The first group was given two, the second three, and the third four. Each patient had radiographs taken immediately after loading and repeated 36 months later. Twenty- three subjects with 65 implants were entered in the three groups. The mean (SD) marginal bone loss was 0.49 (0.04) mm in the two implant group, 0.41 (0.25) mm in the three implant group, and 0.35 (0.25) mm in the four implant group. There were significant differences in marginal bone loss among the three groups (p=0.001), in that the fewer the number of short implant-supported fixed prostheses in the posterior mandible, the greater the marginal bone loss. When we used more short implants the amount of marginal bone loss decreased. PMID:27131984

  9. Brief Report: Macrophage Activation in HIV-Infected Adolescent Males Contributes to Differential Bone Loss by Sex: Adolescent Trials Network Study 021.

    Science.gov (United States)

    Ruan, Alexandra; Tobin, Nicole H; Mulligan, Kathleen; Rollie, Adrienne; Li, Fan; Sleasman, John; Aldrovandi, Grace M

    2016-08-01

    Accumulating evidence suggests that rates of low bone mass are greater in HIV-infected males than females. Of 11 biomarkers assessed by sex and HIV-status, HIV-infected males had increased levels of soluble CD14 which inversely correlated with bone mineral content and bone mineral density measures, suggesting macrophage activation as a possible mechanism of differential bone loss. PMID:26885808

  10. Risk factors for bone loss with prostate cancer in Korean men not receiving androgen deprivation therapy

    Directory of Open Access Journals (Sweden)

    Sun-Ouck Kim

    2009-04-01

    Full Text Available PURPOSE: Preexisting bone loss in men with prostate cancer is an important issue due to the accelerated bone loss during androgen deprivation therapy (ADT. In addition, a high prostate-specific antigen (PSA level has been reported to be related to bone metabolism. This study assessed the factors associated with osteoporosis in Korean men with non-metastatic prostate cancer before undergoing ADT. MATERIAL AND METHODS: The study enrolled patients admitted for a prostate biopsy because of a high PSA or palpable nodule on a digital rectal examination. We divided the patients (n = 172 according to the results of the biopsy: group I, non-metastatic prostate cancer (n = 42 and group II, benign prostatic hypertrophy (BPH; n = 130. The lumbar bone mineral density (BMD was evaluated using quantitative computed tomography. The demographic, health status, lifestyle, body mass index (BMI, serum testosterone concentration, and disease variables in prostate cancer (Gleason score, clinical stage, and PSA were analyzed prospectively to determine their effect on the BMD. RESULTS: The estimated mean T-score was higher in group I than in group II (-1.96 ± 3.35 vs. -2.66 ± 3.20, but without statistic significance (p = 0.235. The significant factors correlated with BMD in group I were a high serum PSA (ß = -0.346, p = 0.010 and low BMI (ß = 0.345, p = 0.014 in the multiple linear regression model. Also old age (r = -0.481, p = 0.001, a high serum PSA (r = -0.571, p < 0.001, low BMI (r = 0.598, p < 0.001, and a high Gleason’s score (r = -0.319, p = 0.040 were the factors related to BMD in the correlation. The significant factors correlated with BMD in group II were old age (ß = -0.324, p = 0.001 and BMI (ß = 0.143, p = 0.014 in the multiple linear regression model. CONCLUSIONS: The risk factors for osteoporosis in men with prostate cancer include a low BMI, and elevated serum PSA. Monitoring BMD from the outset of ADT is a logical first step in the clinical

  11. Implant and root supported overdentures - a literature review and some data on bone loss in edentulous jaws

    Science.gov (United States)

    2014-01-01

    PURPOSE To present a literature review on implant overdentures after a brief survey of bone loss after extraction of all teeth. MATERIALS AND METHODS Papers on alveolar bone loss and implant overdentures have been studied for a narrative review. RESULTS Bone loss of the alveolar process after tooth extraction occurs with great individual variation, impossible to predict at the time of extraction. The simplest way to prevent bone loss is to avoid extraction of all teeth. To keep a few teeth and use them or their roots for a tooth or root-supported overdenture substantially reduces bone loss. Jaws with implant-supported prostheses show less bone loss than jaws with conventional dentures. Mandibular 2-implant overdentures provide patients with better outcomes than do conventional dentures, regarding satisfaction, chewing ability and oral-health-related quality of life. There is no strong evidence for the superiority of one overdenture retention-system over the others regarding patient satisfaction, survival, peri-implant bone loss and relevant clinical factors. Mandibular single midline implant overdentures have shown promising results but long-term results are not yet available. For a maxillary overdenture 4 to 6 implants splinted with a bar provide high survival both for implants and overdenture. CONCLUSION In edentulous mandibles, 2-implant overdentures provide excellent long-term success and survival, including patient satisfaction and improved oral functions. To further reduce the costs a single midline implant overdenture can be a promising option. In the maxilla, overdentures supported on 4 to 6 implants splinted with a bar have demonstrated good functional results. PMID:25177466

  12. Possible Role of Garlic Oil and Parsley Extract in Ameliorating Radiation-Induced Bone Loss in Female Rats

    International Nuclear Information System (INIS)

    To Investigate the possible protective effect of garlic oil and parsley extract against bone loss resulted in female virgin rats exposed to fractionated doses of gamma-radiation (1 Gy 3 times weekly for 5 weeks). Urinary calcium (U Ca), calcium to creatinine ratio (Ca/Cr), hydroxyproline and serum phosphorus were measured as bone resorption bio markers, while serum osteocalcine (OST) and serum alkaline phosphatase (ALP) were measured as bone formation bio markers. Furthermore, nitric oxide (NO) which represents the balance in bone remodeling was measured. Malondiadehyde level (MDA) as well as superoxide dismutase activity (SOD) was measured as oxidative stress bio markers. Female irradiated rats in the present study had significant increases in both bone resorption and bone formation bio markers after 6 weeks from the last exposure to gamma-radiation. Irradiated rats also had significant decreases in plasma NO indicating imbalance in bone remodeling as well as significant increase in oxidative stress bio markers. Daily treatment with garlic oil extracted in olive oil improved all measured parameters except OST level, while the vehicle used for garlic oil (extra virgin olive oil) significantly decreased bone resorption bio markers. Parsley extract induced normalization to all bone resorption and formation parameters measured in irradiated rats. Daily administration of garlic oil and parsley extract protected the bone from degeneration induced by exposure to fractionated doses of gamma radiation.

  13. Preventive effects of bee pollen Cistus ladaniferus extract on bone loss in ovariectomized rats in vivo

    International Nuclear Information System (INIS)

    The effect of bee pollen Cistus ladaniferus extract on ovariectomy (OVX)-induced bone loss in vivo was investigated. The water-solubilized extracts were obtained from the bee pollen of Cistus ladaniferus. Cistus extract (5.0 or 10.0 mg/100 g body weight) was orally administered once daily for 30 days to OVX rats. The analysis using a peripheral quantitative computed tomography (pQCT) showed that OVX-induced a significant decrease in mineral content, mineral density, and polar strength strain index in the femoral-metaphyseal tissues. These decreases were significantly prevented after the administration of Cistus extract (10.0 mg/100 g). Moreover, OVX-induced a significant decrease in calcium content in the femoral-diaphyseal and -metaphyseal tissues. This decrease was significantly prevented after the administration of cistus extract (5.0 or 10.0 mg/100 g). This study demonstrates that cistus extract has a preventive effect on OVX-induced bone loss in vivo. (author)

  14. Combination chemotherapy with cyclophosphamide, epirubicin and 5-fluorouracil causes trabecular bone loss, bone marrow cell depletion and marrow adiposity in female rats.

    Science.gov (United States)

    Fan, Chiaming; Georgiou, Kristen R; McKinnon, Ross A; Keefe, Dorothy M K; Howe, Peter R C; Xian, Cory J

    2016-05-01

    The introduction of anthracyclines to adjuvant chemotherapy has increased survival rates among breast cancer patients. Cyclophosphamide, epirubicin and 5-fluorouracil (CEF) combination therapy is now one of the preferred regimens for treating node-positive breast cancer due to better survival with less toxicity involved. Despite the increasing use of CEF, its potential in causing adverse skeletal effects remains unclear. Using a mature female rat model mimicking the clinical setting, this study examined the effects of CEF treatment on bone and bone marrow in long bones. Following six cycles of CEF treatment (weekly intravenous injections of cyclophosphamide at 10 mg/kg, epirubicin at 2.5 mg/kg and 5-flurouracil at 10 mg/kg), a significant reduction in trabecular bone volume was observed at the metaphysis, which was associated with a reduced serum level of bone formation marker alkaline phosphatase (ALP), increased trends of osteoclast density and osteoclast area at the metaphysis, as well as an increased size of osteoclasts being formed from the bone marrow cells ex vivo. Moreover, a severe reduction of bone marrow cellularity was observed following CEF treatment, which was accompanied by an increase in marrow adipose tissue volume. This increase in marrow adiposity was associated with an expansion in adipocyte size but not in marrow adipocyte density. Overall, this study indicates that six cycles of CEF chemotherapy may induce some bone loss and severe bone marrow damage. Mechanisms for CEF-induced bone/bone marrow pathologies and potential preventive strategies warrant further investigation. PMID:26056019

  15. High-fat Diet Causes Bone Loss in Young Mice by Promoting Osteoclastogenesis through Alteration of the Bone Marrow Environment

    OpenAIRE

    Shu, Lei; Beier, Eric; Sheu, Tzong; Zhang, Hengwei; Zuscik, Michael; Puzas, J. Edward; Boyce, F. Brendan; Mooney, A. Robert; Xing, Lianping

    2015-01-01

    Obesity is a severe health problem in children, afflicting several organ systems including bone. However, the role of obesity on bone homeostasis and bone cell function in children has not been studied in detail. Here we used young mice fed a high-fat diet (HFD) to model childhood obesity and investigate the effect of HFD on the phenotype of cells within the bone marrow environment. Five-week-old male mice were fed a HFD for 3, 6, and 12 weeks. Decreased bone volume was detected after 3 weeks...

  16. Treatment for Progressive Hearing Loss Due to Paget's Disease of Bone - A Case Report and Literature Review.

    Science.gov (United States)

    Aoki, Mitsuhiro; Tanahashi, Shigeaki; Mizuta, Keisuke; Kato, Hiroki

    2015-12-01

    Paget's disease is a common bone remodeling disorder that typically begins with excessive bone resorption in the elderly. Bilateral progressive hearing loss is the most frequently encountered complication of Paget's disease. The types of hearing loss identified by audiometry are conductive, sensorineural, or both. However, the precise mechanism of hearing loss remains unclear, and the treatment has been controversial. We present a 73-year-old man who suffered from bilateral progressive hearing loss due to Paget's disease. Potent bisphosphonates, oral risedronate in daily adjusted dosages for 6 months, did not decrease or suppress the worsening of the hearing loss. The Nucleus CI24 Contour electrode array was successfully inserted on the left side without surgical and postoperative complications. The Japanese open set monosyllable word recognition test in a sound field at 65 dB had a result of 74%. This cochlear implantation can be an indication for cases of profound hearing loss due to Paget's disease. PMID:26915163

  17. Increased activity of osteocyte autophagy in ovariectomized rats and its correlation with oxidative stress status and bone loss

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yuehua, E-mail: yuesjtu@126.com; Zheng, Xinfeng, E-mail: zxf272@126.com; Li, Bo, E-mail: libo@126.com; Jiang, Shengdan, E-mail: jiangsd@126.com; Jiang, Leisheng, E-mail: leisheng_jiang@126.com

    2014-08-15

    Highlights: • Examine autophagy level in the proximal tibia of ovariectomized rats. • Investigate whether autophagy level is associated with bone loss. • Investigate whether autophagy level is associated with oxidative stress status. - Abstract: Objectives: The objectives of the present study were to investigate ovariectomy on autophagy level in the bone and to examine whether autophagy level is associated with bone loss and oxidative stress status. Methods: 36 female Sprague–Dawley rats were randomly divided into sham-operated (Sham), and ovariectomized (OVX) rats treated either with vehicle or 17-β-estradiol. At the end of the six-week treatment, bone mineral density (BMD) and bone micro-architecture in proximal tibias were assessed by micro-CT. Serum 17β-estradiol (E2) level were measured. Total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, catalase (CAT) activity in proximal tibia was also determined. The osteocyte autophagy in proximal tibias was detected respectively by Transmission Electron Microscopy (TEM), immunofluorescent histochemistry (IH), realtime-PCR and Western blot. In addition, the spearman correlation between bone mass, oxidative stress status, serum E2 and autophagy were analyzed. Results: Ovariectomy increased Atg5, LC3, and Beclin1 mRNA and proteins expressions while decreased p62 expression. Ovariectomy also declined the activities of T-AOC, CAT, and SOD. Treatment with E2 prevented the reduction in bone mass as well as restored the autophagy level. Furthermore, LC3-II expression was inversely correlated with T-AOC, CAT, and SOD activities. A significant inverse correlation between LC3-II expression and BV/TV, Tb.N, BMD in proximal tibias was found. Conclusions: Ovariectomy induced oxidative stress, autophagy and bone loss. Autophagy of osteocyte was inversely correlated with oxidative stress status and bone loss.

  18. Increased activity of osteocyte autophagy in ovariectomized rats and its correlation with oxidative stress status and bone loss

    International Nuclear Information System (INIS)

    Highlights: • Examine autophagy level in the proximal tibia of ovariectomized rats. • Investigate whether autophagy level is associated with bone loss. • Investigate whether autophagy level is associated with oxidative stress status. - Abstract: Objectives: The objectives of the present study were to investigate ovariectomy on autophagy level in the bone and to examine whether autophagy level is associated with bone loss and oxidative stress status. Methods: 36 female Sprague–Dawley rats were randomly divided into sham-operated (Sham), and ovariectomized (OVX) rats treated either with vehicle or 17-β-estradiol. At the end of the six-week treatment, bone mineral density (BMD) and bone micro-architecture in proximal tibias were assessed by micro-CT. Serum 17β-estradiol (E2) level were measured. Total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, catalase (CAT) activity in proximal tibia was also determined. The osteocyte autophagy in proximal tibias was detected respectively by Transmission Electron Microscopy (TEM), immunofluorescent histochemistry (IH), realtime-PCR and Western blot. In addition, the spearman correlation between bone mass, oxidative stress status, serum E2 and autophagy were analyzed. Results: Ovariectomy increased Atg5, LC3, and Beclin1 mRNA and proteins expressions while decreased p62 expression. Ovariectomy also declined the activities of T-AOC, CAT, and SOD. Treatment with E2 prevented the reduction in bone mass as well as restored the autophagy level. Furthermore, LC3-II expression was inversely correlated with T-AOC, CAT, and SOD activities. A significant inverse correlation between LC3-II expression and BV/TV, Tb.N, BMD in proximal tibias was found. Conclusions: Ovariectomy induced oxidative stress, autophagy and bone loss. Autophagy of osteocyte was inversely correlated with oxidative stress status and bone loss

  19. Delayed loss of hearing after hearing preservation cochlear implantation: Human temporal bone pathology and implications for etiology.

    Science.gov (United States)

    Quesnel, Alicia M; Nakajima, Hideko Heidi; Rosowski, John J; Hansen, Marlan R; Gantz, Bruce J; Nadol, Joseph B

    2016-03-01

    After initially successful preservation of residual hearing with cochlear implantation, some patients experience subsequent delayed hearing loss. The etiology of such delayed hearing loss is unknown. Human temporal bone pathology is critically important in investigating the etiology, and directing future efforts to maximize long term hearing preservation in cochlear implant patients. Here we present the temporal bone pathology from a patient implanted during life with an Iowa/Nucleus Hybrid S8 implant, with initially preserved residual hearing and subsequent hearing loss. Both temporal bones were removed for histologic processing and evaluated. Complete clinical and audiologic records were available. He had bilateral symmetric high frequency severe to profound hearing loss prior to implantation. Since he was implanted unilaterally, the unimplanted ear was presumed to be representative of the pre-implantation pathology related to his hearing loss. The implanted and contralateral unimplanted temporal bones both showed complete degeneration of inner hair cells and outer hair cells in the basal half of the cochleae, and only mild patchy loss of inner hair cells and outer hair cells in the apical half. The total spiral ganglion neuron counts were similar in both ears: 15,138 (56% of normal for age) in the unimplanted right ear and 13,722 (51% of normal for age) in the implanted left ear. In the basal turn of the implanted left cochlea, loose fibrous tissue and new bone formation filled the scala tympani, and part of the scala vestibuli. Delayed loss of initially preserved hearing after cochlear implantation was not explained by additional post-implantation degeneration of hair cells or spiral ganglion neurons in this patient. Decreased compliance at the round window and increased damping in the scala tympani due to intracochlear fibrosis and new bone formation might explain part of the post-implantation hearing loss. Reduction of the inflammatory and immune response to

  20. Prophylactic pamidronate partially protects from glucocorticoid-induced bone loss in the mdx mouse model of Duchenne muscular dystrophy.

    Science.gov (United States)

    Yoon, Sung-Hee; Chen, Jinghan; Grynpas, Marc D; Mitchell, Jane

    2016-09-01

    Glucocorticoids are extensively used to treat patients with Duchenne muscular dystrophy because of their ability to delay muscle damage, prolong ambulation and extend life. However, use of glucocorticoids significantly increases bone loss, fragility and fractures. To determine if antiresorptive bisphosphonates could prevent the effects of glucocorticoids on bone quality, we used dystrophic mdx mice treated with the glucocorticoid prednisone during 8weeks of rapid bone growth from 5 to 13weeks of age and treated some mice with the bisphosphonate pamidronate during the first two weeks of prednisone administration. Prednisone reduced long bone growth, decreased cortical bone thickness and area and decreased the strength of the femurs. Pamidronate treatment protected mice from cortical bone loss but did not increase bone strength. The combination of prednisone and pamidronate inhibited remodeling of metaphyseal trabecular bone with large numbers of trabeculae containing remnants of calcified cartilage. Prednisone improved muscle strength in the mdx mice and decreased serum creatine kinase with evidence of improved muscle histology and these effects were maintained in mice treated with pamidronate. PMID:27373502

  1. Men and Women in Space: Bone Loss and Kidney Stone Risk after Long-Duration Space Flight

    Science.gov (United States)

    Smith, Scott M.; Zwart, Sara R.; Heer, Martina; Hudson, Edgar, K.; Shackelford, Linda; Morgan, Jennifer L. L.

    2014-01-01

    Bone loss on Earth is more prevalent in women than men, leading to the assumption that women may be at greater risk from bone loss during flight. Until recently, the number of women having flown long-duration missions was too small to allow any type of statistical analysis. We report here data from 42 astronauts on long-duration missions to the International Space Station, 33 men and 9 women. Bone mineral density (dual-energy X-ray absorptiometry), bone biochemistry (from blood and urine samples), and renal stone risk factors were evaluated before and after flight. Data were analyzed in two groups, based on available resistance exercise equipment. The response of bone mineral density to flight was the same for men and women, and the typical decrease in bone mineral density (whole body and/or regional) after flight was not observed for either sex for those using an Advanced Resistive Exercise Device. Bone biochemistry, specifically markers of formation and resorption, generally responded similarly in male and female astronauts. The response of urinary supersaturation risk to space flight was not significantly different between men and women, although risks were typically increased after flight in both groups and risks were generally greater in men than in women before and after flight. Overall, the bone and renal stone responses of men and women to space flight were not different.

  2. Analysis of Bone Density in Patients with Urolithiasis; Role of Hypercalciuria in Bone Loss: Do These Patients Need a Low-Calcium Diet?

    Directory of Open Access Journals (Sweden)

    Ali-Asghar Yarmohammadi

    2008-01-01

    Full Text Available Introduction: Kidney stone is a common urologic complaint. In this study, bone density in stone formers was compared with that of a control group; bone density of stone formers was also analyzed based on age, sex and stone configuration. Methods: In a group of 85 patients with upper urinary calcium stones and 85 healthy people, variables such as age, height, weight, BMI, T-score and Z-score results of bone densitometry of lumbar vertebrae (L2-L4 and femoral neck were recorded. The serum levels of uric acid, calcium, potassium, sodium, phosphor, alkaline phosphates and parathyroid hormone were also analyzed and recorded. Furthermore, all patients, 24-hour urine was studied for levels of cr, oxalate, citrate, uric acid calcium, urea and the total volume. Results: Lumbar and femoral bone mineral density (BMD was significantly lower in patients suffering from renal stone. This difference was also significant when the study and control groups were classified into hypercalciuric and normocalciuric ones. Based on the densimetric results of lumbar vertebrae and femoral neck, BMD reduction among menopause women was significantly greater. Conclusion: Noting the lack of relationship between hypercalciuria and bone loss, and noting that a low-calcium diet not only has no proved role in renal stone prevention, but also it leads to calcium imbalance and finally bone loss, low-calcium diets are not suggested for renal stone formers

  3. Low body mass index is an important risk factor for low bone mass and increased bone loss in early postmenopausal women. Early Postmenopausal Intervention Cohort (EPIC) study group

    DEFF Research Database (Denmark)

    Ravn, Pernille; Cizza, G; Bjarnason, N H;

    1999-01-01

    Thinness (low percentage of body fat, low body mass index [BMI], or low body weight) was evaluated as a risk factor for low bone mineral density (BMD) or increased bone loss in a randomized trial of alendronate for prevention of osteoporosis in recently postmenopausal women with normal bone mass (n...... = 1609). The 2-year data from the placebo group were used (n = 417). Percentage of body fat, BMI, and body weight were correlated with baseline BMD (r = -0. 13 to -0.43, p < 0.01) and 2-year bone loss (r = -0.14 to -0.19, p < 0.01). Women in the lowest tertiles of percentage of body fat or BMI had up to...... 12% lower BMD at baseline and a more than 2-fold higher 2-year bone loss as compared with women in the highest tertiles (p

  4. The Preventive Effect of Biochanin A on Bone Loss in Ovariectomized Rats: Involvement in Regulation of Growth and Activity of Osteoblasts and Osteoclasts

    OpenAIRE

    Shu-Jem Su; Yao-Tsung Yeh; Huey-Wen Shyu

    2013-01-01

    Biochanin A (BCA) is a major isoflavone abundant in red clover (Trifolium pretense). The protective effect of BCA on bone loss in an ovariectomized (OVX) animal model has never been clarified. The objective of this study was to investigate the biological effects of BCA on bone loss in OVX rats in vivo and on the development of osteoblasts and osteoclasts in vitro. Ovariectomy resulted in a marked increase in body weight and a decrease in femoral bone mineral density and trabecular bone volume...

  5. Conjugated linoleic acid prevents ovariectomy-induced bone loss in mice by modulating both osteoclastogenesis and osteoblastogenesis

    OpenAIRE

    Rahman, Md Mizanur; Fernandes, Gabriel; Williams, Paul

    2013-01-01

    Postmenopausal osteoporosis due to estrogen deficiency is associated with severe morbidity and mortality. Beneficial effects of conjugated linoleic acid (CLA) on bone mineral density (BMD) have been reported in mice, rats and humans, but the effect of long term CLA supplementation against ovariectomy-induced bone loss in mice and the mechanisms underlying this effect have not been studied yet. Eight weeks old ovariectomized (Ovx) and sham operated C57BL/6 mice were fed either a diet containin...

  6. Naringin ameliorates bone loss induced by sciatic neurectomy and increases Semaphorin 3A expression in denervated bone

    OpenAIRE

    Xinlong Ma; Jianwei Lv; Xiaolei Sun; Jianxiong Ma; Guosheng Xing; Ying Wang; Lei Sun; Jianbao Wang; Fengbo Li; Yanjun Li; Zhihu Zhao

    2016-01-01

    Naringin maintains bone mass in various osteoporosis models, while its effect on bone in disuse osteoporosis has not been reported. The present study explores whether naringin can prevent disuse osteoporosis induced by unilateral sciatic neurectomy (USN) and whether the Semaphorin 3A-induced Wnt/β-catenin signalling pathway is involved in the osteoprotection of naringin. Naringin dose-dependently prevented the deterioration of bone mineral density (BMD), trabecular structure and biomechanical...

  7. Bone Grafts

    Science.gov (United States)

    ... repair and rebuild diseased bones in your hips, knees, spine, and sometimes other bones and joints. Grafts can also repair bone loss caused by some types of fractures or cancers. Once your body accepts the bone ...

  8. Andrographolide Inhibits Ovariectomy-Induced Bone Loss via the Suppression of RANKL Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Tao Wang

    2015-11-01

    Full Text Available Osteoporosis is a debilitating skeletal disorder with an increased risk of low-energy fracture, which commonly occurs among postmenopausal women. Andrographolide (AP, a natural product isolated from Andrographis paniculata, has been found to have anti-inflammatory, anti-cancer, anti-asthmatic, and neuro-protective properties. However, its therapeutic effect on osteoporosis is unknown. In this study, an ovariectomy (OVX mouse model was used to evaluate the therapeutic effects of AP on post-menopausal osteoporosis by using micro-computed tomography (micro-CT. Bone marrow-derived osteoclast culture was used to examine the inhibitory effect of AP on osteoclastogenesis. Real time PCR was employed to examine the effect of AP on the expression of osteoclast marker genes. The activities of transcriptional factors NF-κB and NFATc1 were evaluated using a luciferase reporter assay, and the IκBα protein level was analyzed by Western blot. We found that OVX mice treated with AP have greater bone volume (BV/TV, trabecular thickness (Tb.Th, and trabecular number (Tb.N compared to vehicle-treated OVX mice. AP inhibited RANKL-induced osteoclastogenesis, the expression of osteoclast marker genes including cathepsin K (Ctsk, TRACP (Acp5, and NFATc1, as well as the transcriptional activities of NF-κB and NFATc1. In conclusion, our results suggest that AP inhibits estrogen deficiency-induced bone loss in mice via the suppression of RANKL-induced osteoclastogensis and NF-κB and NFATc1 activities and, thus, might have therapeutic potential for osteoporosis.

  9. Andrographolide Inhibits Ovariectomy-Induced Bone Loss via the Suppression of RANKL Signaling Pathways.

    Science.gov (United States)

    Wang, Tao; Liu, Qian; Zhou, Lin; Yuan, Jin Bo; Lin, Xixi; Zeng, Rong; Liang, Xiaonan; Zhao, Jinmin; Xu, Jiake

    2015-01-01

    Osteoporosis is a debilitating skeletal disorder with an increased risk of low-energy fracture, which commonly occurs among postmenopausal women. Andrographolide (AP), a natural product isolated from Andrographis paniculata, has been found to have anti-inflammatory, anti-cancer, anti-asthmatic, and neuro-protective properties. However, its therapeutic effect on osteoporosis is unknown. In this study, an ovariectomy (OVX) mouse model was used to evaluate the therapeutic effects of AP on post-menopausal osteoporosis by using micro-computed tomography (micro-CT). Bone marrow-derived osteoclast culture was used to examine the inhibitory effect of AP on osteoclastogenesis. Real time PCR was employed to examine the effect of AP on the expression of osteoclast marker genes. The activities of transcriptional factors NF-κB and NFATc1 were evaluated using a luciferase reporter assay, and the IκBα protein level was analyzed by Western blot. We found that OVX mice treated with AP have greater bone volume (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) compared to vehicle-treated OVX mice. AP inhibited RANKL-induced osteoclastogenesis, the expression of osteoclast marker genes including cathepsin K (Ctsk), TRACP (Acp5), and NFATc1, as well as the transcriptional activities of NF-κB and NFATc1. In conclusion, our results suggest that AP inhibits estrogen deficiency-induced bone loss in mice via the suppression of RANKL-induced osteoclastogensis and NF-κB and NFATc1 activities and, thus, might have therapeutic potential for osteoporosis. PMID:26593901

  10. Endogenous n-3 fatty acids protect ovariectomy induced bone loss by attenuating osteoclastogenesis.

    Science.gov (United States)

    Rahman, Md Mizanur; Bhattacharya, Arunabh; Banu, Jameela; Kang, Jing X; Fernandes, Gabriel

    2009-08-01

    Beneficial effects of n-3 fatty acids (FA) on bone mineral density (BMD) have been reported in mice, rats and human beings, but the precise mechanisms involved have not been described. This study used the Fat-1 mouse, a transgenic model that synthesizes n-3 FA from n-6 FA to directly determine if outcome of bone health were correlated with n-3 FA. Ovariectomized (Ovx) and sham operated wild-type (WT) and Fat-1 mice were fed an AIN-93M diet containing 10% corn oil for 24 weeks. BMD was analysed by dual energy x-ray absorptiometry. Fat-1 Ovx mice exhibited significantly lower level of osteotropic factors like receptor activator of NF-kappaB ligand and tartrate-resistant acid phosphatase (TRAP)5b in serum and higher BMD in distal femoral metaphysis, proximal tibial metaphysis, femoral diaphysis and lumbar vertebra as compared to WT Ovx mice. LPS-stimulated bone marrow (BM) cells from Fat-1 Ovx mice produced significantly lower level of pro-inflammatory cytokines like tumour necrosis factor-alpha, interleukin (IL)-1-beta, IL-6 and higher level of anti-inflammatory cytokines like IL-10, IFN-gamma and higher level of nitric oxide as compared to BM cells from WT Ovx mice. LPS-stimulated COX-II activity as well as NF-kappaB activation in BM cells from Fat-1 Ovx mice was significantly less as compared to BM cells from WT Ovx mice. Furthermore, Fat-1 BM cells generated significantly less number of TRAP osteoclast-like cells as compared to WT BM cells. In conclusion, we offer further insight into the mechanisms involved in preventing the BMD loss in Ovx mice by n-3 FA using a Fat-1 transgenic mouse model. PMID:20141608

  11. The effects of IL-6 and its receptors on bone loss in postmenopausal women

    International Nuclear Information System (INIS)

    Objective: To investigate the effects of IL-6 and its receptors on bone loss in healthy women, and to assess the pathogenesis of the postmenopausal osteoporosis in women. Methods: One hundred and thirty one healthy women aged 31-72 including 64 sexual maturity women aged 31-52 were enrolled in four groups and 67 postmenopausal women, the years of menopause from 1 month to 23 years, were also enrolled in four groups. The bone mass of the lumbar-spine and femur were measured using dual-energy X-rays absorptiometry; the serum E2, FSH, BGP by radioimmunoassay (RIA); the serum IL-6, sIL-6R, sgp 130 by ELISA; the serum AKP, calcium, phosphate by auto-biochemistry instrument. Results: The BMD of lumbar-spine and right femur decreased following increase of age and the duration of menopause. Significant positive correlation was observed between BMD and E2. The serum IL-6, sIL-6R, sgp 130 level was low, and stable before menopause. The level of IL-6, sIL-6R, sgp 130 increased with variation of age and the duration of menopause. Significant negative correlation was observed between IL-6, sIL-6R, sgp 130 and E2, BMD. Serum AKP and BGP level was higher in postmenopausal women than that in sexual maturity women. The serum calcium level increased significantly soon after menopausal, then decreased to the normal level. The serum phosphate level had no difference in these groups. Conclusion: The main cause of postmenopausal osteoporosis is the unbalance of the bone formation and resorption

  12. Bone marrow mesenchymal stem cells protect against retinal ganglion cell loss in aged rats with glaucoma

    Directory of Open Access Journals (Sweden)

    Hu Y

    2013-10-01

    Full Text Available Ying Hu,1,2 Hai Bo Tan,1 Xin Mei Wang,3 Hua Rong,1 Hong Ping Cui,1 Hao Cui2 Departments of Ophthalmology, 1Shanghai East Hospital of Tongji University, Shanghai, 2First Affiliated Hospital, 3Fourth Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China Abstract: Glaucoma is a common eye disease in the aged population and has severe consequences. The present study examined the therapeutic effects of bone marrow mesenchymal stem cell (BMSC transplantation in preventing loss of visual function in aged rats with glaucoma caused by laser-induced ocular hypertension. We found that BMSCs promoted survival of retinal ganglion cells in the transplanted eye as compared with the control eye. Further, in swimming tests guided by visual cues, the rats with a BMSC transplant performed significantly better. We believe that BMSC transplantation therapy is effective in treating aged rats with glaucoma. Keywords: glaucoma, stem cell, transplantation, cell therapy, aging

  13. 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.

  14. Comparison of Peri-Implant Bone Loss and Survival of Maxillary Intrasinus and Extrasinus Implants After 2 Years

    Directory of Open Access Journals (Sweden)

    S. Hemati

    2011-09-01

    Full Text Available Objective: Low quality of the bone and insufficient bone due to the size of the sinus and resorption of the alveolar ridge decrease the long-term survival of implants in the posterior maxilla compared to other regions of the jaws. Surgical procedures to increase bone volume make it possible to place implants longer than 8 mm. In this situation sinus elevation makes it possible to place implants. We intend to evaluate peri-implant bone loss and survivalof implants placed in elevated sinuses after 2 years and to compare with implants placed in the native posterior maxilla.Materials and Methods:Twenty-five implants placed in sinuses that had been reconstructed with Bio-Oss and healed after 9 months were compared with 30 implants placed in the posterior maxilla without any surgery. The groups were compared using probing pocket depth, bleeding on probing, Plaque Index and bone loss immediately after implant placement surgery and 2 years postoperatively. The criterion for implant survival was presence or absence of the implant in the oral cavity, which was recorded in relevant forms in both groups.Results: Three implants were lost; one in control and two in grafted sinuses. No significant differences were observed in the survival rates. In general, the mean bone loss around intrasinus and extrasinus implants was not significantly different. In the same context, no differences were observed between bleeding on probing, Plaque Index and probing pocket depths of two groups (P=0.397, P=0.637 and P=0.224, respectively.Conclusion: The survival and bone loss around intrasinus and extrasinus implants are similar.

  15. Pomegranate Peel Extract Prevents Bone Loss in a Preclinical Model of Osteoporosis and Stimulates Osteoblastic Differentiation in Vitro

    Directory of Open Access Journals (Sweden)

    Mélanie Spilmont

    2015-11-01

    Full Text Available The nutritional benefits of pomegranate have attracted great scientific interest. The pomegranate, including the pomegranate peel, has been used worldwide for many years as a fruit with medicinal activity, mostly antioxidant properties. Among chronic diseases, osteoporosis, which is associated with bone remodelling impairment leading to progressive bone loss, could eventually benefit from antioxidant compounds because of the involvement of oxidative stress in the pathogenesis of osteopenia. In this study, with in vivo and ex vivo experiments, we investigated whether the consumption of pomegranate peel extract (PGPE could limit the process of osteopenia. We demonstrated that in ovariectomized (OVX C57BL/6J mice, PGPE consumption was able to significantly prevent the decrease in bone mineral density (−31.9%; p < 0.001 vs. OVX mice and bone microarchitecture impairment. Moreover, the exposure of RAW264.7 cells to serum harvested from mice that had been given a PGPE-enriched diet elicited reduced osteoclast differentiation and bone resorption, as shown by the inhibition of the major osteoclast markers. In addition, PGPE appeared to substantially stimulate osteoblastic MC3T3-E1 alkaline phosphatase (ALP activity at day 7, mineralization at day 21 and the transcription level of osteogenic markers. PGPE may be effective in preventing the bone loss associated with ovariectomy in mice, and offers a promising alternative for the nutritional management of this disease.

  16. Comparison of two methods for alveolar bone loss measurement in an experimental periodontal disease model in rats

    Directory of Open Access Journals (Sweden)

    Diego Nique Liberman

    2011-02-01

    Full Text Available There are many studies that evaluate possible risk factors for periodontal diseases in animals. Most of them have focused only on the biological aspects of disease occurrence; therefore, it has been difficult to compare studies of the different methodological approaches. The aim of the present study was to compare different methods - linear and area - of the evaluation of morphometrical alveolar bone loss. Sixty hemimaxillae, defleshed and stained with 1% methylene blue to delineate the cementoenamel junction and alveolar bone crest, were obtained from a previous study that induced periodontal disease by means of ligatures in two groups of fifteen Wistar rats during 9 weeks. Ligatures were placed around the right upper second molars, and the contra-lateral teeth remained as intra-group controls. Digital photographs were taken from the specimens and submitted to a single, calibrated, blind examiner who performed the morphometrical evaluation of alveolar bone loss using both linear and area methods. Mean values of linear and area measurements were obtained from each side - buccal and palatal - of the specimens. The degree of association between the two methods was determined by Pearson's Correlation Coefficient. An almost perfect association (0.98 was determined between the linear and area evaluations. A mathematical formula was subsequently created to estimate the total area of alveolar bone loss, from linear mean measurements. Both methods were suitable for detecting bone level alterations. The results of the present study allow for the transformation of data and better compilation of results from different studies.

  17. Uncemented hip arthroplasty in primary and revision surgery : patterns of bone remodelling and options to influence periprosthetic bone loss

    OpenAIRE

    Salemyr, Mats

    2013-01-01

    Introduction The incidence of hip arthroplasty surgery in young and active patients is increasing. Consequently, an increasing number of patients will live with hip prostheses for longer periods of time in the future. The mismatch in modulus of elasticity between the stiffer metal components and the surrounding bone will induce periprosthetic adaptive bone remodelling. The clinical importance of this is still uncertain but the risk of late occuring complications, secondary to periprosthet...

  18. Naringin ameliorates bone loss induced by sciatic neurectomy and increases Semaphorin 3A expression in denervated bone.

    Science.gov (United States)

    Ma, Xinlong; Lv, Jianwei; Sun, Xiaolei; Ma, Jianxiong; Xing, Guosheng; Wang, Ying; Sun, Lei; Wang, Jianbao; Li, Fengbo; Li, Yanjun; Zhao, Zhihu

    2016-01-01

    Naringin maintains bone mass in various osteoporosis models, while its effect on bone in disuse osteoporosis has not been reported. The present study explores whether naringin can prevent disuse osteoporosis induced by unilateral sciatic neurectomy (USN) and whether the Semaphorin 3A-induced Wnt/β-catenin signalling pathway is involved in the osteoprotection of naringin. Naringin dose-dependently prevented the deterioration of bone mineral density (BMD), trabecular structure and biomechanical strength in femur due to USN. Naringin increased bone formation but inhibited resorption, as indicated by bone-turnover markers in blood and urine and the histological staining of Osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP) in femur. Semaphorin 3A (Sema3A) and active β-catenin protein decreased after USN and could be restored by naringin to the levels of the sham-operated rats. In addition, naringin in vitro promoted the differentiation of osteoblasts and inhibited osteoclastic differentiation. Our studies suggest that the down-regulation of Sema3A and the subsequent inactivation of Wnt/β-catenin signalling may be some of the mechanisms involved in USN-induced osteoporosis. Naringin could increase the expression of Sema3A and the activation of Wnt/β-catenin signalling to prevent disuse osteoporosis induced by denervation. Thus, naringin functions in bone maintenance and could be a promising therapeutic alternative in preventing disuse osteoporosis. PMID:27109829

  19. Anti-epileptic drugs and bone loss: Phenytoin reduces pro-collagen I and alters the electrophoretic mobility of osteonectin in cultured bone cells.

    Science.gov (United States)

    Wilson, Emma L; Garton, Mark; Fuller, Heidi R

    2016-05-01

    Phenytoin is an antiepileptic drug used in the management of partial and tonic-clonic seizures. In previous studies we have shown that valproate, another antiepileptic drug, reduced the amount of two key bone proteins, pro-collagen I and osteonectin (SPARC, BM-40), in both skin fibroblasts and cultured osteoblast-like cells. Here we show that phenytoin also reduces pro-collagen I production in osteoblast-like cells, but does not appear to cause a decrease in osteonectin message or protein production. Instead, a 24h exposure to a clinically relevant concentration of phenytoin resulted in a dose-dependent change in electrophoretic mobility of osteonectin, which was suggestive of a change in post-translational modification status. The perturbation of these important bone proteins could be one of the mechanisms to explain the bone loss that has been reported following long-term treatment with phenytoin. PMID:26999801

  20. Denosumab--a powerful RANKL inhibitor to stop lytic metastases and other bone loss actions by osteoclasts.

    Science.gov (United States)

    Kopper, László

    2012-10-01

    Denosumab is a perfect example on the targeted anticancer therapy. The inhibition of RANKL activity suppressed the osteoclasts' resorptive function and so prevented skeletal related events. This effect is useful not only against bone metastases, but also in the treatment of other diseases caused by bone loss. In different solid tumors with bone metastasis the quality of life also improved, although the overall survival usually showed no change. On the market the main competitors for denosumab are still the bisphosphonates (questions of costs and reimbursement are not discussed) and some potential new agents e.g. Src kinases (as dasatinib, saracatinib, bosutinib), cathepsin K inhibitors, (e.g. odanacatib), and new selective estrogen receptor modulators (e.g. bazedoxifene, lasofoxifene). Nevertheless, today denosumab is one of the most powerful agents in bone-saving area. PMID:22588706

  1. Low Baseline CD4+ Count Is Associated With Greater Bone Mineral Density Loss After Antiretroviral Therapy Initiation

    OpenAIRE

    Grant, Philip M.; Kitch, Douglas; McComsey, Grace A; Dube, Michael P.; Haubrich, Richard; Huang, Jeannie; Riddler, Sharon; Tebas, Pablo; Zolopa, Andrew R.; Collier, Ann C; Brown, Todd T.

    2013-01-01

    Low pretreatment CD4+ cell count is an independent risk factor for bone loss after antiretroviral therapy (ART) initiation, providing further evidence for the benefits of early ART. Initiation of ART at higher CD4+ counts may reduce the burden of osteoporosis and fragility fracture.

  2. Radiologic evaluation of bone loss at implants with biocide coated titanium abutments: a study in the dog.

    Directory of Open Access Journals (Sweden)

    Roberto López-Píriz

    Full Text Available The objective of the present study is to evaluate bone loss at implant abutments coated with a soda-lime glass containing silver nanoparticles subjected to experimental peri-implantitis. Five beagle dogs were used in the experiments, 3 implants were installed in each quadrant of the mandibles. Glass/n-Ag coted abutments were connected to implant platform. Cotton floss ligatures were placed in a submarginal position around the abutment necks and the animals were subject to a diet which allowed plaque accumulation, and after 15 weeks the dogs were sacrificed. Radiographs of all implant sites were obtained at the beginning and at the end of the experimentally induced peri-implantitis. The radiographic examination indicated that significant amounts of additional bone loss occurred in implants without biocide coating, considering both absolute and relative values of bone loss. Percentages of additional bone loss observed in implants dressed with a biocide coated abutment were about 3 times lower (p<0.006 distal aspect; and p<0.031 at mesial aspect than the control ones. Within the limits of the present study it seems promising the use of soda-lime glass/nAg coatings on abutments to prevent peri-implant diseases.

  3. Plasma B vitamins, homocysteine and their relation with bone loss and hip fracture in elderly men and women

    Science.gov (United States)

    Elevated homocysteine is a strong risk factor for osteoporotic fractures among elders, yet it may be a marker for low B vitamin status. Objective: To examine the associations of plasma concentrations of folate, vitamin B12, vitamin B6 and homocysteine with bone loss and hip fracture risk in elderly...

  4. Muscular strength measurements indicate bone mineral density loss in postmenopausal women

    Directory of Open Access Journals (Sweden)

    Zhou Z

    2013-10-01

    measurements were identified for different age groups. Age-appropriate testing mode can improve detection of osteoporotic fracture risk in early menopause by determining muscular strength reduction related to BMD loss. This may enable early initiation of preventative therapies. Keywords: osteoporosis, fracture, bone mineral density, postmenopausal, menopause, muscle strength, isokinetic, isometric

  5. Plasma sodium level is associated with bone loss severity in women with anorexia nervosa

    Science.gov (United States)

    Lawson, Elizabeth A.; Fazeli, Pouneh K.; Calder, Genevieve; Putnam, Hannah; Misra, Madhusmita; Meenaghan, Erinne; Miller, Karen K.; Klibanski, Anne

    2013-01-01

    Purpose Anorexia nervosa (AN) is a psychiatric disorder characterized by restrictive eating, low body weight, and severe bone loss. Recent data show a deleterious relationship between low circulating sodium levels and bone mass, and relative or absolute hyponatremia is a known complication of AN. Clinical studies of other medical conditions associated with hyponatremia suggest that detrimental effects of low sodium levels on health are seen even within the normal range. We hypothesized that women with AN and relatively low sodium levels would have lower bone mineral density (BMD) than those with higher sodium levels. Methods In a cross-sectional study (1997–2009) of 404 women ages 17–54 (mean±SEM age 25.6±0.3 years) who met DSM-IV criteria for AN, we measured BMD using dual energy x-ray absorptiometry (DXA). BMD was compared in women with sodium levels <140 mmol/L (midpoint of normal range) vs. those with sodium levels ≥140 mmol/L, and in women with hyponatremia (sodium <135 mmol/L) vs. those without. Results Women with sodium levels <140 mmol/L had lower BMD, T- and Z-scores at the AP spine (Z-scores −1.6±0.1 vs. −1.3±0.1, p=0.004) and total hip (−1.2±0.1 vs. −0.9±0.1, p=0.029) vs. those with sodium levels ≥140 mmol/L. In a model including age, BMI, psychiatric drug use, and disease duration, differences remained significant at the AP spine. Hyponatremic women had lower BMD, T- and Z-scores at the AP spine (Z-scores −2.2±0.3 vs. −1.3±0.1, p=0.009), lateral spine (−2.4±0.4 vs. −1.5±0.1, p=0.031) and total hip (−2.5±0.5 vs. −1.0±0.1, p<0.0001) vs. those without. In a model including age, BMI, psychiatric drug use, and disease duration, differences remained significant at all sites. Conclusions These data suggest that relative sodium deficiency may contribute to AN-related osteopenia. PMID:23218167

  6. Single-nucleotide polymorphisms in the P2X7 receptor gene are associated with post-menopausal bone loss and vertebral fractures

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye; Husted, Lise Bjerre; Skarratt, Kristen K; Stokes, Leanne; Tofteng, Charlotte L.; Kvist, Torben; Jensen, Jens-Erik Beck; Eiken, Pia Agnete; Brixen, Kim; Fuller, Stephen; Clifton-Bligh, Rory; Gartland, Alison; Schwarz, Peter; Langdahl, Bente Lomholt; Wiley, James S

    2012-01-01

    , vertebral fracture incidence was documented at 10 years. We found that the rate of bone loss was clearly associated with the Arg307Gln amino acid substitution such that individuals heterozygous for this polymorphism had a 40% increased rate of bone loss. Furthermore, individuals carrying the Ile568Asn...... variant allele had increased bone loss. In contrast, the Gln460Arg polymorphism was associated with protection against bone loss. The Ala348Thr polymorphism was associated with a lower vertebral fracture incidence 10 years after menopause. Finally, we developed a risk model, which integrated P2RX7...... to bone mass and fracture incidence in post-menopausal women. A total of 1694 women (aged 45-58) participating in the Danish Osteoporosis Prevention Study were genotyped for 12 functional P2X7 receptor variants. Bone mineral density was determined at baseline and after 10 years. In addition...

  7. The role of alpha 6 integrin in prostate cancer migration and bone pain in a novel xenograft model.

    Directory of Open Access Journals (Sweden)

    Tamara E King

    Full Text Available Of the estimated 565,650 people in the U.S. who will die of cancer in 2008, almost all will have metastasis. Breast, prostate, kidney, thyroid and lung cancers metastasize to the bone. Tumor cells reside within the bone using integrin type cell adhesion receptors and elicit incapacitating bone pain and fractures. In particular, metastatic human prostate tumors express and cleave the integrin A6, a receptor for extracellular matrix components of the bone, i.e., laminin 332 and laminin 511. More than 50% of all prostate cancer patients develop severe bone pain during their remaining lifetime. One major goal is to prevent or delay cancer induced bone pain. We used a novel xenograft mouse model to directly determine if bone pain could be prevented by blocking the known cleavage of the A6 integrin adhesion receptor. Human tumor cells expressing either the wildtype or mutated A6 integrin were placed within the living bone matrix and 21 days later, integrin expression was confirmed by RT-PCR, radiographs were collected and behavioral measurements of spontaneous and evoked pain performed. All animals independent of integrin status had indistinguishable tumor burden and developed bone loss 21 days after surgery. A comparison of animals containing the wild type or mutated integrin revealed that tumor cells expressing the mutated integrin resulted in a dramatic decrease in bone loss, unicortical or bicortical fractures and a decrease in the ability of tumor cells to reach the epiphyseal plate of the bone. Further, tumor cells within the bone expressing the integrin mutation prevented cancer induced spontaneous flinching, tactile allodynia, and movement evoked pain. Preventing A6 integrin cleavage on the prostate tumor cell surface decreased the migration of tumor cells within the bone and the onset and degree of bone pain and fractures. These results suggest that strategies for blocking the cleavage of the adhesion receptors on the tumor cell surface can

  8. Myeloid-derived suppressor cells function as novel osteoclast progenitors enhancing bone loss in breast cancer

    OpenAIRE

    Sawant, Anandi; Deshane, Jessy; Jules, Joel; Lee, Carnella M.; Harris, Brittney A.; Feng, Xu; Ponnazhagan, Selvarangan

    2012-01-01

    Enhanced bone destruction is a hallmark of various carcinomas such as breast cancer, where osteolytic bone metastasis is associated with increased morbidity and mortality. Immune cells contribute to osteolysis in cancer growth but the factors contributing to aggressive bone destruction are not well understood. In this study, we demonstrate the importance of myeloid-derived suppressor cells (MDSC) in this process at bone metastatic sites. Since MDSC originate from the same myeloid lineage as m...

  9. Implant-supported overdentures, a prevention of bone loss in edentulous mandibles? A 5-year follow-up study

    DEFF Research Database (Denmark)

    von Wowern, N; Gotfredsen, K

    2001-01-01

    minimizes the physiologic age-related mandibular BMC loss, 2) this effect seems to be independent of attachment system and 3) mandibular osteoporosis prior to implant treatment may be a risk factor for bone loss around implants. However, this treatment can be recommended also in osteoporotic persons.......The purpose of this study were to analyse 1) the changes in the bone mineral content (BMC) in mandibles with implant-supported overdentures when compared with the physiologic age-related mandibular BMC loss, 2) whether the BMC changes were different in groups without or with a bar connecting the...... in half of the patients. BMC measurements were performed in vivo by dual-photon scanner at baseline, just after attachment insertion, at 2-year and 5-year visits. Mandibular osteoporosis was estimated by comparing baseline BMC values with normal mandibular BMC values for young adults of same gender...

  10. Short-term, daily exposure to cold temperature may be an efficient way to prevent muscle atrophy and bone loss in a microgravity environment

    OpenAIRE

    Deng, Claudia; Wang, Ping; Zhang, Xiangming; Wang, Ya

    2015-01-01

    Microgravity induces less pressure on muscle/bone, which is a major reason for muscle atrophy as well as bone loss. Currently, physical exercise is the only countermeasure used consistently in the U.S. human space program to counteract the microgravity-induced skeletal muscle atrophy and bone loss. However, the routinely almost daily time commitment is significant and represents a potential risk to the accomplishment of other mission operational tasks. Therefore, development of more efficient...

  11. Weight loss on stimulant medication: how does it affect body composition and bone metabolism? – A prospective longitudinal study

    Directory of Open Access Journals (Sweden)

    Poulton Alison

    2012-12-01

    Full Text Available Abstract Objective Children treated with stimulant medication for attention deficit hyperactivity disorder (ADHD often lose weight. It is important to understand the implications of this during growth. This prospective study was designed to quantify the changes in body composition and markers of bone metabolism on starting treatment. Methods 34 children (29 boys aged 4.7 to 9.1 years newly diagnosed with ADHD were treated with dexamphetamine or methylphenidate, titrating the dose to optimise the therapeutic response. Medication was continued for as long as clinically indicated. Body composition and bone density (dual-energy X-ray absorptiometry were measured at baseline, 6 months and 3 years; changes were analysed in Z-scores based on data from 241 healthy, local children. Markers of bone turnover were measured at baseline, 3 months and 3 years. Results Fat loss of 1.4±0.96kg (total fat 5.7±3.6 to 4.3±3.1kg, p Conclusions Stimulant medication was associated with early fat loss and reduced bone turnover. Lean tissue including bone increased more slowly over 3 years of continuous treatment than would be expected for growth in height. There was long-term improvement in the proportion of central fat for height. This study shows that relatively minor reductions in weight on stimulant medication can be associated with long-term changes in body composition. Further study is required to determine the effects of these changes on adult health.

  12. Previous exposure to simulated microgravity does not exacerbate bone loss during subsequent exposure in the proximal tibia of adult rats.

    Science.gov (United States)

    Shirazi-Fard, Yasaman; Anthony, Rachel A; Kwaczala, Andrea T; Judex, Stefan; Bloomfield, Susan A; Hogan, Harry A

    2013-10-01

    Extended periods of inactivity cause severe bone loss and concomitant deterioration of the musculoskeletal system. Considerable research has been aimed at better understanding the mechanisms and consequences of bone loss due to unloading and the associated effects on strength and fracture risk. One factor that has not been studied extensively but is of great interest, particularly for human spaceflight, is how multiple or repeated exposures to unloading and reloading affect the skeleton. Space agencies worldwide anticipate increased usage of repeat-flier crewmembers, and major thrust of research has focused on better understanding of microgravity effects on loss of bone density at weightbearing skeletal sites; however there is limited data available on repeat microgravity exposure. The adult hindlimb unloaded (HU) rat model was used to determine how an initial unloading cycle will affect a subsequent exposure to disuse and recovery thereafter. Animals underwent 28 days of HU starting at 6 months of age followed by 56 days of recovery, and then another 28 days of HU with 56 days of recovery. In vivo longitudinal pQCT was used to quantify bone morphological changes, and ex vivo μCT was used to quantify trabecular microarchitecture and cortical shell geometry at the proximal tibia metaphysis (PTM). The mechanical properties of trabecular bone were examined by the reduced platen compression mechanical test. The hypothesis that the initial HU exposure will mitigate decrements in bone mass and density for the second HU exposure was supported as pre- to post-HU declines in total BMC, total vBMD, and cortical area by in vivo pQCT at the proximal tibia metaphysis were milder for the second HU (and not significant) compared to an age-matched single HU (3% vs. 6%, 2% vs. 6%, and 2% vs. 6%, respectively). In contrast, the hypothesis was not supported at the microarchitectural level as losses in BV/TV and Tb.Th. were similar during 2nd HU exposure and age-matched single HU

  13. Immunization with FSHβ fusion protein antigen prevents bone loss in a rat ovariectomy-induced osteoporosis model

    International Nuclear Information System (INIS)

    Highlights: •A GST-FSH fusion protein was successfully expressed in E. coli. •Immunization with GST-FSH antigen can raise high-titer anti-FSH polyclonal sera. •Anti-FSH polyclonal sera can neutralize osteoclastogenic effect of FSH in vitro. •FSH immunization can prevent bone loss in a rat osteoporosis model. -- Abstract: Osteoporosis, a metabolic bone disease, threatens postmenopausal women globally. Hormone replacement therapy (HTR), especially estrogen replacement therapy (ERT), is used widely in the clinic because it has been generally accepted that postmenopausal osteoporosis is caused by estrogen deficiency. However, hypogonadal α and β estrogen receptor null mice were only mildly osteopenic, and mice with either receptor deleted had normal bone mass, indicating that estrogen may not be the only mediator that induces osteoporosis. Recently, follicle-stimulating hormone (FSH), the serum concentration of which increases from the very beginning of menopause, has been found to play a key role in postmenopausal osteoporosis by promoting osteoclastogenesis. In this article, we confirmed that exogenous FSH can enhance osteoclast differentiation in vitro and that this effect can be neutralized by either an anti-FSH monoclonal antibody or anti-FSH polyclonal sera raised by immunizing animals with a recombinant GST-FSHβ fusion protein antigen. Moreover, immunizing ovariectomized rats with the GST-FSHβ antigen does significantly prevent trabecular bone loss and thereby enhance the bone strength, indicating that a FSH-based vaccine may be a promising therapeutic strategy to slow down bone loss in postmenopausal women

  14. Pharmacological study of the possible protective effect of certain natural products against irradiation-induced bone loss in female rats

    International Nuclear Information System (INIS)

    osteoporosis is a common human bone disease characterized by decreased bone mass and increased risk of fractures . it is associated with numerous risk factors; post menopausal oestrogen loss is the major factor. on another hand, exposure to γ -radiation may be responsible for the late reduction in bone mass following radiotherapy. research in nutrition suggests that diet can help to achieve optimal health specifically that human diet that contain macro nutrients and phytochemicals which have antioxidant and anti-inflammatory properties. the present study has been constructed to identify the effect of radiation exposure on bone, and to investigate the possible protective effect of garlic oil and parsley extract against bone loss induced in female virgin rats(180-200 g) either by ovariectomization or by exposure to γ -radiation. a pilot lest was carried first in this study on 2 groups of female virgin rats to estimate the degree of bone loss induced by exposure to fractionated doses of γ -radiation . the 1st group's rats were normal non-irradiated and served as control normal group. in the 2nd group, female rats were exposed to total dose of 15 Gy fractionated over 5 weeks (1 Gy 3 times weekly for 5 weeks), and measurements of urinary calcium and urinary hydroxyproline were carried out periodically after 4,8,11 and 15 weeks from the 1st day of exposure to γ -radiation doses . the highest values were detected after 11 weeks i.e. after 6 weeks from the last exposure to γ -radiation

  15. Immunization with FSHβ fusion protein antigen prevents bone loss in a rat ovariectomy-induced osteoporosis model

    Energy Technology Data Exchange (ETDEWEB)

    Geng, Wenxin; Yan, Xingrong; Du, Huicong; Cui, Jihong; Li, Liwen, E-mail: liven@nwu.edu.cn; Chen, Fulin, E-mail: chenfl@nwu.edu.cn

    2013-05-03

    Highlights: •A GST-FSH fusion protein was successfully expressed in E. coli. •Immunization with GST-FSH antigen can raise high-titer anti-FSH polyclonal sera. •Anti-FSH polyclonal sera can neutralize osteoclastogenic effect of FSH in vitro. •FSH immunization can prevent bone loss in a rat osteoporosis model. -- Abstract: Osteoporosis, a metabolic bone disease, threatens postmenopausal women globally. Hormone replacement therapy (HTR), especially estrogen replacement therapy (ERT), is used widely in the clinic because it has been generally accepted that postmenopausal osteoporosis is caused by estrogen deficiency. However, hypogonadal α and β estrogen receptor null mice were only mildly osteopenic, and mice with either receptor deleted had normal bone mass, indicating that estrogen may not be the only mediator that induces osteoporosis. Recently, follicle-stimulating hormone (FSH), the serum concentration of which increases from the very beginning of menopause, has been found to play a key role in postmenopausal osteoporosis by promoting osteoclastogenesis. In this article, we confirmed that exogenous FSH can enhance osteoclast differentiation in vitro and that this effect can be neutralized by either an anti-FSH monoclonal antibody or anti-FSH polyclonal sera raised by immunizing animals with a recombinant GST-FSHβ fusion protein antigen. Moreover, immunizing ovariectomized rats with the GST-FSHβ antigen does significantly prevent trabecular bone loss and thereby enhance the bone strength, indicating that a FSH-based vaccine may be a promising therapeutic strategy to slow down bone loss in postmenopausal women.

  16. Parameters Associated with Marginal Bone Loss around Implant after Prosthetic Loading.

    Science.gov (United States)

    Koller, Clarissa D; Pereira-Cenci, Tatiana; Boscato, Noéli

    2016-01-01

    This study evaluated retrospectively the association among occlusal, periodontal and implant-prosthetic parameters and marginal bone loss (MBL) around implants and survival rate at 5.7 ±3.2 years of follow-up after prosthetic loading. Eighty-two patients received 164 external hexagon implants. After the standard healing period (3 to 6 months), the implants were restored with single-tooth or up to three splinted crowns. All patients were followed according to a strict maintenance program with regular recalls and clinically evaluated by a calibrated examiner. The MBL measurements taken from standardized radiographs made at permanent crown placement (baseline) and after the last evaluation were calculated considering occlusal, periodontal and implant-prosthetic parameters. Veneer fractures and abutment loosening were not considered failure. Two implants failed during the follow-up period, resulting in a survival rate of 98.8%. Cox regression analyses showed MBL associated with non-working side contacts (p=0.047), inadequate anterior guidance (p=0.001), lateral group guidance involving teeth and implants (p=0.015), periimplant plaque index (p=0.035), prosthetic design (p=0.030) and retention (p=0.006). Inadequate occlusal pattern guide, presence of visible plaque, and cemented and splinted implant-supported restoration were associated with greater MBL around the implant. PMID:27224562

  17. Physical therapy resources in prevention of bone mineral density loss in patients with spinal cord injury – literature review

    Directory of Open Access Journals (Sweden)

    Daniele Rodrigues

    2004-03-01

    Full Text Available This paper comprises a literature review on physical therapytreatment on prevention, stabilization or slowing down the processof bone mineral density loss in patients with spinal cord injury.There are few studies in the literature on the efficiency of physicaltherapy treatment for bone demineralization. There are reports offour types of treatment for demineralization: functional electricalstimulation, functional electrical stimulation-induced cycling,standing and ambulation. These treatments are rather questionableand controversial in relation to efficacy and there is no consensuson their methodologies.

  18. Monotropein isolated from the roots of Morinda officinalis increases osteoblastic bone formation and prevents bone loss in ovariectomized mice.

    Science.gov (United States)

    Zhang, Zhiguo; Zhang, Qiaoyan; Yang, Hua; Liu, Wei; Zhang, Naidan; Qin, Luping; Xin, Hailiang

    2016-04-01

    Monotropein is a natural iridoid glycoside enriched in Morinda officinalis and has been used for medicinal purposes in China. In the present study, we systematically examined its effects on ovariectomy (OVX)-induced osteoporosis in mice and osteoblastic MC3T3-E1 cells for the first time. Eight-week-old female C57/BL6 mice were used to evaluate the osteoprotective effect of monotropein. Results showed that administration of monotropein (40 or 80mg/kg/day) for four weeks exerted good bone protective effects as evidenced by the increase of bone mineral content (BMC), bone mineral density (BMD), bone volume fraction (BVF) and improvement of bone microstructure. Monotropein also enhanced the parameters of biomechanical properties, including maximum load, maximum stress and elastic modulus of femur in OVX mice. In addition, monotropein treatment decreased the serum levels of interleukin 1 (IL-1), interleukin 6 (IL-6) and soluble receptor activator of NF-κB ligand (sRANKL) in OVX mice. In this study, we also assessed the effects of monotropein on the proliferation and differentiation of osteoblastic MC3T3-E1 cells in vitro. After incubation for 48h, the cell proliferation was increased at the concentration of 10μM, 25μM, 50μM and 100μM. ALP activities were significantly increased after treatment with monotropein for 72h. Quantitative analyses with alizarin red staining showed significantly increased mineralization of MC3T3-E1 cells after treatment with monotropein for 28days. Based on these results, monotropein may serve as a new candidate or a leading compound for antiosteoporosis. PMID:26996879

  19. High Prevalence of Low Bone Mineral Density and Substantial Bone Loss over 4 Years Among HIV-Infected Persons in the Era of Modern Antiretroviral Therapy.

    Science.gov (United States)

    Escota, Gerome V; Mondy, Kristin; Bush, Tim; Conley, Lois; Brooks, John T; Önen, Nur; Patel, Pragna; Kojic, Erna Milunka; Henry, Keith; Hammer, John; Wood, K C; Lichtenstein, Kenneth A; Overton, Edgar T

    2016-01-01

    HIV-infected persons are living longer on combination antiretroviral therapy (cART) but experiencing more comorbidities including low bone mineral density (BMD). Using data from the Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN Study), we determined the prevalence of low BMD (T-score below one standard deviation of the reference mean) and compared it with matched controls from the National Health and Nutrition Examination Survey (NHANES). We also assessed 4-year longitudinal BMD changes among participants virologically suppressed on cART. Of 653 participants included in this analysis (77% male, 29% black, median age 41 years, median CD4(+) cell count 464 cells/mm(3), 89% with HIV RNA <400 copies/ml), 51% and 10% had baseline osteopenia and osteoporosis, respectively. Low BMD at the femoral neck was significantly more prevalent than for the NHANES controls (47% versus 29%, p<0.001). Lower body mass index, nonwhite race, longer tenofovir exposure, older age, being unemployed or retired, and lower apolipoprotein E were independently associated with baseline osteoporosis. Among 170 participants virologically suppressed on cART and with longitudinal BMD data, 31% experienced substantial bone loss (≥5% BMD decline from baseline) over 4 years. Female sex, current smoking, and longer stavudine use were more common among participants who had substantial bone loss, although these variables failed to reach statistical significance. Low BMD was highly prevalent among HIV-infected persons. One-third of participants experienced substantial bone loss despite cART, suggesting the need for monitoring and potential clinical interventions. PMID:26366785

  20. Changes in bone mineral density and bone turnover markers in obese women after short -term weight loss therapy during a 5-year follow-up

    Directory of Open Access Journals (Sweden)

    Jerzy Chudek

    2010-07-01

    Full Text Available INTRODUCTION: The protective effect of adipocity on bone metabolism has not been confirmed during long-term follow-up. It is not known whether the rate of bone turnover and changes in mineral metabolism in obese people result from endocrine properties of the adipose tissue or merely the mechanical load. OBJECTIVES: The aim of the study was to evaluate bone and calcium-phosphorus metabolism in obese women during a 5-year follow-up. PATIENTS AND METHODS: The study involved 47 obese women who underwent a 3-month weight loss therapy. We evaluated changes in the serum levels of parathormone (PTH, calcidiol (25(OHD3, collagen type I crosslinked C-telopeptide (CTx-I, osteocalcin, total calcium, inorganic phosphates, and in bone mineral density. The control group consisted of 17 healthy women with proper body weight. RESULTS: We observed a similar decrease in bone mineral density (BMD in the lumbar spine and femoral neck, and a comparable decrease in the serum levels of CTx-I and osteocalcin in both groups during the 5-year follow-up. Changes in serum PTH levels were not statistically significant. In obese women, a nonsignificant increase in the serum level of 25(OHD3 was observed as early as after a 3-month weight loss therapy and during follow-up. In controls, serum 25(OHD3 levels tended to decrease. During follow-up, the number of obese patients with disturbances in vitamin D metabolism decreased from 78.7% to 53.2% (P = 0.01. Such disturbances were observed in 35.3% of the control group. In obese patients, there was a positive correlation between the change in body mass and BMD in the proximal femur (r = 0.279, P = 0.04. In controls, there was a positive correlation between the change in body mass and BMD in the lumbar spine (r = 0.477, P = 0.05. CONCLUSIONS: In obese women who underwent weight loss therapy, the levels of bone turnover markers decreased and abnormal vitamin D metabolism was still observed during the 5-year follow-up.

  1. Receptor activator of nuclear factor-κB ligand and osteoprotegerin: maintaining the balance to prevent bone loss

    Directory of Open Access Journals (Sweden)

    Anne-Priscille Trouvin

    2010-11-01

    Full Text Available Anne-Priscille Trouvin, Vincent GoëbDepartment of Rheumatology, Rouen University Hospital, Rouen, FranceAbstract: Bone remodeling requires a precise balance between resorption and formation. It is a complex process that involves numerous factors: hormones, growth factors, vitamins, and cytokines, and notably osteoprotegerin (OPG and receptor activator for nuclear factor-κB (RANK ligand. The signaling pathway OPG/RANK/RANKL is key to regulation for maintaining the balance between the activity of osteoblasts and osteoclasts in order to prevent bone loss and ensure a normal bone turnover. In this review, the RANK/RANKL/OPG pathway is described. The multiple interactions of various factors (hormones, cytokines, growth factors, and vitamins with the OPG/RANK/RANKL pathway are also commented on. Finally, the effects of denosumab, a human monoclonal antibody that binds to RANKL and thereby inhibits the activation of osteoclasts, and of strontium ranelate are also described. Indeed, these two new drugs afford appreciable assistance in daily care practice, helping to prevent bone loss in patients with osteoporosis.Keywords: osteoprotegerin, OPG, RANK, RANKL, denosumab, strontium ranelate, osteoporosis

  2. Neutrophil mobilization by surface-glycan altered Th17-skewing bacteria mitigates periodontal pathogen persistence and associated alveolar bone loss.

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    Rajendra P Settem

    Full Text Available Alveolar bone (tooth-supporting bone erosion is a hallmark of periodontitis, an inflammatory disease that often leads to tooth loss. Periodontitis is caused by a select group of pathogens that form biofilms in subgingival crevices between the gums and teeth. It is well-recognized that the periodontal pathogen Porphyromonas gingivalis in these biofilms is responsible for modeling a microbial dysbiotic state, which then initiates an inflammatory response destructive to the periodontal tissues and bone. Eradication of this pathogen is thus critical for the treatment of periodontitis. Previous studies have shown that oral inoculation in mice with an attenuated strain of the periodontal pathogen Tannerella forsythia altered in O-glycan surface composition induces a Th17-linked mobilization of neutrophils to the gingival tissues. In this study, we sought to determine if immune priming with such a Th17-biasing strain would elicit a productive neutrophil response against P. gingivalis. Our data show that inoculation with a Th17-biasing T. forsythia strain is effective in blocking P. gingivalis-persistence and associated alveolar bone loss in mice. This work demonstrates the potential of O-glycan modified Tannerella strains or their O-glycan components for harnessing Th17-mediated immunity against periodontal and other mucosal pathogens.

  3. A reversal phase arrest uncoupling the bone formation and resorption contributes to the bone loss in glucocorticoid treated ovariectomised aged sheep

    DEFF Research Database (Denmark)

    Andreasen, Christina Møller; Ding, Ming; Overgaard, Søren;

    2015-01-01

    had a complete absence of osteoid surfaces, and a 5-fold increase in the extent of eroded/reversal surfaces after 7months. Most of these reversal surfaces were actually arrested reversal surfaces, defined as reversal surfaces without the presence of neighbouring osteoid surfaces or osteoclasts, which...... is classically observed next to active reversal surfaces. As in humans, these arrested reversal surfaces had compared to active reversal surfaces a reduced canopy coverage, a significantly decreased cell density, and a decreased immunoreactivity for the osteoblastic markers osterix, runx2 and smooth...... muscle actin in the mononuclear reversal cells colonising the surfaces. In conclusion, glucocorticoid treatment of ovariectomised sheep induced a significant bone loss, caused by an arrest of the reversal phase, resulting in an uncoupling of the bone formation and resorption during the reversal phase, as...

  4. Radiologic Evaluation of Bone Loss at Implants with Biocide Coated Titanium Abutments: A Study in the Dog

    OpenAIRE

    López-Píriz, R.; Bartolomé, J. F.; Cabal, B.; Esteban-Tejeda, L.; Torrecillas, Ramón; J. S. Moya

    2012-01-01

    The objective of the present study is to evaluate bone loss at implant abutments coated with a soda-lime glass containing silver nanoparticles subjected to experimental peri-implantitis. Five beagle dogs were used in the experiments, 3 implants were installed in each quadrant of the mandibles. Glass/n-Ag coted abutments were connected to implant platform. Cotton floss ligatures were placed in a submarginal position around the abutment necks and the animals were subject to a diet which allowed...

  5. Bone resorption following weight loss surgery is associated with treatment procedure and changes in secreted Wnt antagonists.

    Science.gov (United States)

    Hofsø, Dag; Bollerslev, Jens; Sandbu, Rune; Jørgensen, Anders; Godang, Kristin; Hjelmesæth, Jøran; Ueland, Thor

    2016-07-01

    To assess if altered bone turnover following bariatric surgery is related to metabolic consequences of the surgical procedure or weight loss. We evaluated serum markers reflecting bone turnover and metabolic pathways at baseline and after 1-year in a controlled non-randomized clinical trial comparing Roux-en-Y gastric bypass surgery (n = 74) with lifestyle intervention (n = 63) on obesity-related comorbidities. The decrease in body mass index (BMI) was larger in the surgery (-14.0 kg/m(2)) compared to lifestyle (-3.7 kg/m(2)). Markedly increased bone turnover was observed following surgery compared to lifestyle intervention and was correlated with change in BMI. Stepwise multivariable regression analysis revealed that group (β = 0.31, p < 0.01), and changes in BMI (β = -0.28, p < 0.01), dickkopf-1 (β = 0.20, p < 0.001) and sclerostin (β = 0.11, p < 0.05) were predictors of change in the bone resorption marker N-terminal telopeptide. Our data support that mechanisms related to the procedure itself and changes in secreted Wnt antagonists may contribute to increased bone turnover following bariatric surgery. PMID:26956843

  6. Designation of a Novel DKK1 Multiepitope DNA Vaccine and Inhibition of Bone Loss in Collagen-Induced Arthritic Mice

    Science.gov (United States)

    Zhang, Xiaoqing; Liu, Sibo; Li, Shentao; Du, Yuxuan; Dou, Yunpeng; Li, Zhanguo; Yuan, Huihui; Zhao, Wenming

    2015-01-01

    Dickkopf-1 (DKK1), a secretory inhibitor of canonical Wnt signaling, plays a critical role in certain bone loss diseases. Studies have shown that serum levels of DKK1 are significantly higher in rheumatoid arthritis (RA) patients and are correlated with the severity of the disease, which indicates the possibility that bone erosion in RA may be inhibited by neutralizing the biological activity of DKK1. In this study, we selected a panel of twelve peptides using the software DNASTAR 7.1 and screened high affinity and immunogenicity epitopes in vitro and in vivo assays. Furthermore, we optimized four B cell epitopes to design a novel DKK1 multiepitope DNA vaccine and evaluated its bone protective effects in collagen-induced arthritis (CIA), a mouse model of RA. High level expression of the designed vaccine was measured in supernatant of COS7 cells. In addition, intramuscular immunization of BALB/c mice with this vaccine was also highly expressed and sufficient to induce the production of long-term IgG, which neutralized natural DKK1 in vivo. Importantly, this vaccine significantly attenuated bone erosion in CIA mice compared with positive control mice. These results provide evidence for the development of a DNA vaccine targeted against DKK1 to attenuate bone erosion. PMID:26075259

  7. A Comparison of Panoramic, Periapical and Bite Wing Radiographies in Evaluation of Alveolar Bone Loss in Periodiontitis

    Directory of Open Access Journals (Sweden)

    A Haerian Ardakani

    2007-07-01

    Full Text Available Introduction: The height of the alveolar bone, is normally maintained by equilibrium between bone formation and bone resorption, but in periodontal disease more destruction or lack of bone formation will reduce the alveolar bone height. However the radiography is important in diagnosis, treatment plan and detection of quality and quantity of the alveolar bone; although the type of radiography is more important. The purpose of this study is the comparison between panaromic, P.A (Parallel, Bite Wing radiographs in diagnosis of periodontitis. Methods: This study was descriptive cross-Sectional study Periapical (PA, Bitewing (B.W & Panoramic radiographic images in 32 pationent 13 male and 19 female with moderate to advanced periodontitis (mean age 38 year were taken before surgical treatment. Actual hight of defect were measured by a William's probe during surgery, the distance between cemento enamel junction (CEJ and alveolar crest were measured on radiographs using a digital vernie scale as will as. Actual measurements were compared with values taken from panoramic PA, B.W radiographs. For Data analysis Paired t test was used. Results: A total of 314 linear distances from the panoramic PA , B.W, and CEJ/BL were measured. The mean difference between panoramic and actual Measurements (0.115 and 0.28 P=(0.24-0.07, were not satistically significant (P> 0.05. The mean difference between P.A and actual measurements (0.279-0.498 P=(0.0001-0.004 showed a satistically significant difference (P< 0.05. The mean deference between BW and actual Measurements (0.576-0.613 P=(0.24-0.07 were satistically significant (P<0.05. Conclusion: Although, all forms of radiographic images showed agreement in detection of periodontal bone loss, the accuracy of panoramic radiographs was more than PA & BW radiographs'. Specially when the magnification was adjusted in panoramic radiography.

  8. Prevention of bone loss by injection of insulin-like growth factor-1 after sciatic neurectomy in rats

    Institute of Scientific and Technical Information of China (English)

    SUN Hai-biao; CHEN Jun-chang

    2013-01-01

    Injection of insulin-like growth factor-1 (IGF-1) can prevent bone loss in sciatic nerve transaction rats.We try to investigate the action mechanism of IGF-1 on bone formation.Methods:A total of 40 adult male Spragne-Dawley rats were divided into two groups (experimental group and control group) with 20 animals in each.Sciatic neurectomy was performed to model disuse osteoporosis in all rats.IGF-1was administered in experimental group with the dose of 100 μg/kg per day for 3 days.Meanwhile,the rats in control group were treated with saline.Bone mineral density was measured by dual-energy X-ray absorptiometry 4 and 6 weeks after neurectomy respectively.Expression of Osterix and Runx2 was determined by reverse transcription-polymerase chain reaction (RT-PCR) assay.Results:There was a significant increase in the bone mineral density of experimental group compared with control group.There was a significant decrease in the level of receptor activator of nuclear factor-κ B-ligand but an increase in the level of osteoprotegerin 4 and 6 weeks after neurectomy in the experimental group compared with control one.The expression of Osterix and Runx2 was up-regulated in the bone marrow of experimental group compared with control group.Conclusion:IGF-1 can increase bone formation by stimulation of osteoblast number and activity,and reduce bone resorption by restriction of differentiation of osteoclast,suggesting that IGF-1 may improve the therapeutic efficacy for disuse osteoporosis.

  9. Changes in bone marrow lesions in response to weight-loss in obese knee osteoarthritis patients

    DEFF Research Database (Denmark)

    Gudbergsen, Henrik; Boesen, Mikael; Christensen, Robin;

    2013-01-01

    Patients are susceptible for knee osteoarthritis (KOA) with increasing age and obesity and KOA is expected to become a major disabling disease in the future. An important feature of KOA on magnetic resonance imaging (MRI) is changes in the subchondral bone, bone marrow lesions (BMLs), which are...

  10. Is Serum Serotonin Involved in the Bone Loss of Young Females with Anorexia Nervosa?

    Science.gov (United States)

    Maïmoun, L; Guillaume, S; Lefebvre, P; Philibert, P; Bertet, H; Picot, M-C; Courtet, P; Mariano-Goulart, D; Renard, E; Sultan, C

    2016-03-01

    Recent experimental data suggest that circulating serotonin interacts with bone metabolism, although this is less clear in humans. This study investigated whether serum serotonin interferes with bone metabolism in young women with anorexia nervosa (AN), a clinical model of energy deprivation. Serum serotonin, markers of bone turnover [osteocalcin (OC), procollagen type I N-terminal propeptide (PINP), type I-C telopeptide breakdown products (CTX)], leptin, soluble leptin receptor (sOB-R), and insulin-like growth factor-1 (IGF-1) and its binding protein (IGFBP-3) were assessed. Whole body, spine, hip, and radius areal bone mineral density BMD (aBMD) were assessed by dual-energy X-ray absorptiometry in 21 patients with AN and 19 age-matched controls. Serum serotonin, leptin, IGF-1, IGFBP-3, OC, PINP, and aBMD at all sites, radius excepted, were significantly reduced in AN whereas CTX and sOB-R were increased compared with controls. Serum serotonin levels were positively correlated with weight, body mass index, whole body fat mass, leptin, and IGF-1, and negatively with CTX for the entire population. Low serum serotonin levels are observed in patients with AN. Although no direct link between low serum serotonin levels and bone mass was identified in these patients, the negative relationship between serotonin and markers of bone resorption found in all population nevertheless suggests the implication of serotonin in bone metabolism. Impact of low serum serotonin on bone in AN warrants further studies. PMID:26418163

  11. Olive oil and vitamin D synergistically prevent bone loss in mice.

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    Camille Tagliaferri

    Full Text Available As the Mediterranean diet (and particularly olive oil has been associated with bone health, we investigated the impact of extra virgin oil as a source of polyphenols on bone metabolism. In that purpose sham-operated (SH or ovariectomized (OVX mice were subjected to refined or virgin olive oil. Two supplementary OVX groups were given either refined or virgin olive oil fortified with vitamin D3, to assess the possible synergistic effects with another liposoluble nutrient. After 30 days of exposure, bone mineral density and gene expression were evaluated. Consistent with previous data, ovariectomy was associated with increased bone turnover and led to impaired bone mass and micro-architecture. The expression of oxidative stress markers were enhanced as well. Virgin olive oil fortified with vitamin D3 prevented such changes in terms of both bone remodeling and bone mineral density. The expression of inflammation and oxidative stress mRNA was also lower in this group. Overall, our data suggest a protective impact of virgin olive oil as a source of polyphenols in addition to vitamin D3 on bone metabolism through improvement of oxidative stress and inflammation.

  12. Evidence that increased calcium intake does not prevent early postmenopausal bone loss

    DEFF Research Database (Denmark)

    Hosking, D J; Ross, P D; Thompson, D E; Wasnich, R D; McClung, M; Bjarnason, N H; Ravn, Pernille; Cizza, G; Daley, M; Yates, A J

    1998-01-01

    intake was recorded, and bone mineral density (BMD) (in the lumbar spine, total body, forearm, and hip) and biochemical markers of bone turnover (serum total alkaline phosphatase, serum osteocalcin, and urinary N-telopeptide crosslink levels) were measured at baseline and annually thereafter. Women whose...

  13. High Vitamin C intake is associated with lower 4-year bone loss in elderly men

    Science.gov (United States)

    Vitamin C is essential for collagen formation and normal bone development. Therefore, we evaluated associations of total, supplemental and dietary vitamin C intake with bone mineral density (BMD) at the hip (femoral neck and trochanter), spine and radial shaft and 4 y change in BMD, in elderly men a...

  14. Vitamin D supplementation prevents hypocalcemia and cortical bone loss associated with chronic feeding in female mice

    Science.gov (United States)

    Dietary cholecalciferol supplementation alone or combined with calcium has shown great promise in improving bone health, which has been attributed to endocrine actions involved in calcium regulation and/or paracrine/autocrine actions within bone. Indeed, we and others have suggested that dietary su...

  15. The love hormone Oxytocin regulates the loss and gain of the Fat-Bone relationship.

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    Graziana eColaianni

    2015-05-01

    Full Text Available The involvement of Oxytocin (OT in bone metabolism is an interesting area of research that recently achieved remarkable results. Moreover, several lines of evidence have largely demonstrated that OT also participates in the regulation of energy metabolism. Hence, it has recently been determined that the posterior pituitary hormone OT directly regulates bone mass: mice lacking OT or OT receptor (OTR display severe osteopenia, caused by impaired bone formation. OT administration normalizes ovariectomy-induced osteopenia, bone marrow adiposity, body weight and intra-abdominal fat depots in mice. This effect is mediated through inhibition of adipocyte precursor differentiation and reduction of adipocyte size. The exquisite role of OT in regulating the bone-fat connection adds another milestone to the biological evidence supporting the existence of a tight relationship between the adipose tissue and the skeleton.

  16. Bone

    International Nuclear Information System (INIS)

    Bone scanning provides information on the extent of primary bone tumors, on possible metastatic disease, on the presence of osteomyelitis prior to observation of roentgenographic changes so that earlier therapy is possible, on the presence of collagen diseases, on the presence of fractures not disclosed by x-ray films, and on the evaluation of aseptic necrosis. However, the total effect and contribution of bone scanning to the diagnosis, treatment, and ultimate prognosis of pediatric skeletal diseases is, as yet, unknown. (auth)

  17. Effect of recent spinal cord injury on wnt signaling antagonists (sclerostin and dkk-1) and their relationship with bone loss. A 12-month prospective study.

    Science.gov (United States)

    Gifre, Laia; Vidal, Joan; Carrasco, Josep L; Filella, Xavier; Ruiz-Gaspà, Silvia; Muxi, Africa; Portell, Enric; Monegal, Ana; Guañabens, Nuria; Peris, Pilar

    2015-06-01

    Spinal cord injury (SCI) has been associated with a marked increase in bone loss and bone remodeling, especially short-term after injury. The absence of mechanical load, mediated by osteocyte mechanosensory function, seems to be a causative factor related to bone loss in this condition. However, the pathogenesis and clinical management of this process remain unclear. Therefore, the aim of the study was to analyze the effect of recent SCI on the Wnt pathway antagonists, sclerostin and Dickkopf (Dkk-1), and their relationship with bone turnover and bone mineral density (BMD) evolution. Forty-two patients (aged 35 ± 14yrs) with a recent (58 pmol/L) at baseline showed higher sublesional BMD loss. In conclusion, this study shows that short-term after SCI there is a marked increase in bone turnover and bone loss, the latter associated with an increase in Dkk-1 serum levels. The persistence of increased levels of this Wnt antagonist throughout the study and their relationship with the magnitude of bone loss suggests a contributory role of this mediator in this process. PMID:25484108

  18. Preventive Effects of Flaxseed and Sesame Oil on Bone Loss in Ovariectomized Rats

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    S. Boulbaroud

    2008-01-01

    Full Text Available A study was designed to examine the effects of dietary flaxseed oil (FO and sesame oil (SO which are rich successively in n-3 and (n-9 and n-6 on biochemical parameters and histological status of bone. Sixty-four 90-day-old female wistar rats were randomly assigned to 6 groups: sham-operated rat (sham+ control diets, ovariectomized rat (OVX+ control diets, OVX+ 7% FO, OVX+ 7% SO, OVX+ 10% FO, OVX+ 10% SO. After 4 weeks of treatments, rats were euthanized; blood and tissues were collected for analyses. Markers of bone formation which is alkaline phosphatase activity and markers of bone resorption which is tartrate resistant acid phosphatase activity were measured. Present results showed that OVX increased significantly ALP and TRAP activity and the examination of bone tissue showed disruptive and lytic bone trabeculae. Animals fed 10% FO and 10% SO of fat reduced these parameters and improved bone microarchitecture. Whereas, there was no improvement in biochemical and histological states in OVX rats that received 7% of PUFAs successively provided from FO and SO diets. In conclusion, our results are encouraging because they suggest that PUFAs intake may help to prevent osteoporosis associated with estrogens deficiency. However, further studies are needed to determine the mechanism by which a diet rich in n-3 or lignans modulate bone tissue.

  19. Does dermatitis herpetiformis result in bone loss as coeliac disease does?: a cross sectional study

    Directory of Open Access Journals (Sweden)

    Katalin Lorinczy

    2013-04-01

    Full Text Available Introduction and objectives: coeliac disease (CD and its cutaneous manifestation, dermatitis herpetiformis are both (DH gluten-sensitive diseases. Metabolic bone disease is common among patients with CD, even in asymptomatic forms. Data are scarce about bone density in patients with dermatitis herpetiformis. The aim of our study was to compare bone mineral density (BMD of celiac and dermatitis herpetiformis patients. Methods: 34 coeliac patients, 53 with dermatitis herpetiformis and 42 healthy controls were studied. The mean age was 38.0 ± 12.1, 32.18 ± 14.95, 35.33 ± 10.41 years in CD, dermatitis herpetiformis, and healthy controls, respectively. Bone mineral density of the lumbar spine, the left femoral neck and radius were measured by dual-energy X-ray absorptiometry. Low bone density, osteopenia and osteoporosis were defined as a body mass density (BMD T-score between 0 and -1, between -1 and -2.5, and under -2.5, respectively. Results: at lumbar region, consisting of dominantly trabecular compartment, a decreased BMD was detected in 49 % (n = 26 patients with dermatitis herpetiformis, 62 % (n = 21 of CD patients, and 29 % (n = 12 of healthy controls, respectively. Lower BMD were measured at the lumbar region in dermatitis herpetiformis and CD compared to healthy subjects (0.993 ± 0.136 g/cm² and 0.880 ± 0.155 g/cm² vs. 1.056 ± 0.126 g/cm²; p < 0.01. Density of bones consisting of dominantly cortical compartment (femoral neck did not differ in dermatitis herpetiformis and healthy subjects. Conclusions: our results show that a low bone mass is also frequent among patients with dermatitis herpetiformis. Bone mineral content in these patients is significantly lower in those parts of the skeleton which contain more trabecular than cortical bone.

  20. Protective effect of polysaccharides from morinda officinalis on bone loss in ovariectomized rats.

    Science.gov (United States)

    MengYong, Zhu; CaiJiao, Wang; HuSheng, Zhang; XianWu, Pei; JianMin, Fen

    2008-10-01

    In order to examine the effect of polysaccharides from morinda officinalis (MOP) on bone quality of osteoporosis rats. The osteoporosis in rats was induced by ovariectomy, and MOP (100 or 300 mg/kg) was orally administrated once daily. The animals were assessed 30 days after the operation for bone mineral density, serum cytokines level and mineral element concentration. MOP administration in rats resulted in an increase in bone mineral density and mineral element concentration, a decrease in serum cytokines level, which indicated that MOP administration may play an important role in the development of osteoporosis. PMID:18638500

  1. The Effectiveness of Crataegus orientalis M Bieber. (Hawthorn) Extract Administration in Preventing Alveolar Bone Loss in Rats with Experimental Periodontitis.

    Science.gov (United States)

    Hatipoğlu, Mükerrem; Sağlam, Mehmet; Köseoğlu, Serhat; Köksal, Ekrem; Keleş, Ali; Esen, Hacı Hasan

    2015-01-01

    The purpose of this animal study was to evaluate the effects of hawthorn (Crataeus orientalis M Bieber.) extract on serum oxidative status and alveolar bone loss in experimental periodontitis. Twenty-seven Wistar rats were assigned to one of the following groups: non- ligated+placebo (saline) (NL, n = 9), ligature only+placebo (saline) (LO, n = 9), and ligature and treated with hawthorn extract in saline (H, n = 9) (100 mg/kg orogastrically, once a day for 11 days). Periodontitis was induced by submerging a 4/0 silk ligature in the sulcus of the mandibular right first molars of rats, and the animals were sacrificed after 11 days. Micro-CT examinations were performed for linear and volumetric parameter assessment of alveolar bone. Periodontal tissues were histopathologically examined to assess the differences among the study groups. Levels of serum total antioxidant status (TAS)/total oxidant status (TOS), and oxidative stress index (OSI) were also analyzed. Alveolar bone loss was significantly reduced by hawthorn administration compared to LO group (p<0.05). The number of inflammatory cells and osteoclasts in the LO group was significantly higher than that of the NL and H groups (p< 0.05). The number of osteoblasts in the LO and H groups was significantly higher than that of the NL group (p<0.05). TOS and OSI levels were significantly reduced in H group compared to LO group (P <0.05) and TAS levels were similar in H and NL group (p< 0.05). Hawthorn extract showed inhibitory effect on periodontal inflammation and alveolar bone loss by regulating TAS, TOS and OSI levels in periodontal disease in rats when administered systemically. PMID:26030160

  2. Aqueous extract of pomegranate seed attenuates glucocorticoid-induced bone loss and hypercalciuria in mice: A comparative study with alendronate.

    Science.gov (United States)

    Zhang, Yan; Shao, Jin; Wang, Zhi; Yang, Tieyi; Liu, Shuyi; Liu, Yue; Fan, Xinbing; Ye, Weiguang

    2016-08-01

    The present study was performed in order to examine bone loss and calcium homeostasis in mice with glucocorticoid (GC)-induced osteoporosis (GIOP) following treatment with the aqueous extract of pomegranate seed (AE-PS). In addition, a comparative study with alendronate was performed. Biomarkers in the serum and the urine were measured. The tibias, kidney and duodenum were removed in order to measure the levels of bone calcium, protein expression as well as to perform histomorphological analysis of the bone. GC treatment facilitated the induction of hypercalciuria in the mice, and the AE-PS‑treated mice exhibited a greater increase in serum calcium and a decrease in urine calcium. The AE-PS reversed the deleterious effects on the trabecular bone induced by DXM and stimulated bone remodeling, including an increase in bone calcium and alkaline phosphatase‑b (ALP-b) and a decrease in a the critical bone resorption markers C-terminal telopeptide of type I collagen (CTX) and tartrate‑resistant acid phosphatase-5b (TRAP-5b). Hematoxylin and eosin (H&E) staining revealed the increased disconnections and separation between the growth plate and the trabecular bone network as well as the reduction in the trabecular bone mass of the primary and secondary spongiosa throughout the proximal metaphysis of the tibia in the DXM group. Moreover, the decreased protein expression of transient receptor potential vanilloid (TRPV)5, TRPV6 and calbindin‑D9k (CaBP‑9k) was reversed by the AE-PS or alendronate supplementation in the kidneys and the duodenum as well as plasma membrane Ca2+‑ATPase1 (PMCA1) expression in the kidneys of mice with GIOP. There was no marked difference in pharmacological effectiveness between alendronate and the AE-PS. Taken together, these findings suggest that the AE-PS may be an alternative therapy suitable for use in the management of secondary osteoporosis. PMID:27278225

  3. Trabecular bone loss after administration of the second-generation antipsychotic risperidone is independent of weight gain.

    Science.gov (United States)

    Motyl, Katherine J; Dick-de-Paula, Ingrid; Maloney, Ann E; Lotinun, Sutada; Bornstein, Sheila; de Paula, Francisco J A; Baron, Roland; Houseknecht, Karen L; Rosen, Clifford J

    2012-02-01

    Second generation antipsychotics (SGAs) have been linked to metabolic and bone disorders in clinical studies, but the mechanisms of these side effects remain unclear. Additionally, no studies have examined whether SGAs cause bone loss in mice. Using in vivo and in vitro modeling we examined the effects of risperidone, the most commonly prescribed SGA, on bone in C57BL6/J (B6) mice. Mice were treated with risperidone orally by food supplementation at a dose of 1.25 mg/kg daily for 5 and 8 weeks, starting at 3.5 weeks of age. Risperidone reduced trabecular BV/TV, trabecular number and percent cortical area. Trabecular histomorphometry demonstrated increased resorption parameters, with no change in osteoblast number or function. Risperidone also altered adipose tissue distribution such that white adipose tissue mass was reduced and liver had significantly higher lipid infiltration. Next, in order to tightly control risperidone exposure, we administered risperidone by chronic subcutaneous infusion with osmotic minipumps (0.5 mg/kg daily for 4 weeks) in 7 week old female B6 mice. Similar trabecular and cortical bone differences were observed compared to the orally treated groups (reduced trabecular BV/TV, and connectivity density, and reduced percent cortical area) with no change in body mass, percent body fat, glucose tolerance or insulin sensitivity. Unlike in orally treated mice, risperidone infusion reduced bone formation parameters (serum P1NP, MAR and BFR/BV). Resorption parameters were elevated, but this increase did not reach statistical significance. To determine if risperidone could directly affect bone cells, primary bone marrow cells were cultured with osteoclast or osteoblast differentiation media. Risperidone was added to culture medium in clinically relevant doses of 0, 2.5 or 25 ng/ml. The number of osteoclasts was significantly increased by addition in vitro of risperidone while osteoblast differentiation was not altered. These studies indicate that

  4. Pycnogenol® treatment inhibits bone mineral density loss and trabecular deterioration in ovariectomized rats

    OpenAIRE

    Huang, Gangyong; Wu, Jianguo; Wang, Siqun; Wei, Yibing; Chen, FeiYan; Chen, Jie; Shi, JingSheng; Xia, Jun

    2015-01-01

    Context: Pycnogenol® extracted from French maritime pine bark (Pinus pinaster Ait. subsp. atlantica) is functional for its antioxidant activity. Objective: To investigate the effects of Pycnogenol® on bone mineral density (BMD), trabecular microarchitecture and bone metabolism in ovariectomized (OVX) rats. Materials and methods: Thirty Sprague-Dawley rats were randomized into 3 groups: SHAM group (sham-operated rats), OVX group (OVX rats), and treatment group (OVX rats supplemented with 40 mg...

  5. Bone loss in thyroid disease: role of low TSH and high thyroid hormone.

    Science.gov (United States)

    Abe, Etsuko; Sun, Li; Mechanick, Jeffrey; Iqbal, Jameel; Yamoah, Kosj; Baliram, Ramkumarie; Arabi, Ario; Moonga, Baljit S; Davies, Terry F; Zaidi, Mone

    2007-11-01

    More than 10% of postmenopausal women in the United States receive thyroid hormone replacement therapy and up to 20% of these women are over-replaced inducing subclinical hyperthyroidism. Because hyperthyroidism and post menopausal osteoporosis overlap in women of advancing age, it is urgent to understand the effect of thyroid hormone excess on bone. We can now provide results that not thyroid hormones but also TSH itself has an equally important role to play in bone remodeling. PMID:18083940

  6. Single-Limb Irradiation Induces Local and Systemic Bone Loss in a Murine Model

    OpenAIRE

    Wright, Laura E; Buijs, Jeroen T.; Kim, Hun-Soo; Coats, Laura E.; Scheidler, Anne M.; John, Sutha K.; She, Yun; Murthy, Sreemala; Ma, Ning; Chin-Sinex, Helen J.; Bellido, Teresita M; Bateman, Ted A.; Mendonca, Marc S.; Mohammad, Khalid S; Guise, Theresa A.

    2015-01-01

    Increased fracture risk is commonly reported in cancer patients receiving radiotherapy, particularly at sites within the field of treatment. The direct and systemic effects of ionizing radiation on bone at a therapeutic dose are not well characterized in clinically relevant animal models. Using twenty-week male C57Bl/6 mice, effects of irradiation (right hindlimb; 2 Gy) on bone volume and microarchitecture were evaluated prospectively by microcomputed tomography and histomorphometry and compa...

  7. Atorvastatin Attenuates Bone Loss and Aortic Valve Atheroma in LDLR Mice.

    Science.gov (United States)

    Rajamannan, Nalini M

    2015-01-01

    Atherosclerosis and osteoporosis are the leading causes of mortality and morbidity. The objective of this study was to test this hypothesis in experimental hypercholesterolemia to determine whether statins play a protective role in this process. LDLR(-/-) mice (n = 60) were allocated to the following groups: group I (n = 20), normal diet; group II (n = 20), 0.25% (w/w) cholesterol diet (w/w), and group III (n = 20), 0.25% (w/w) cholesterol diet + atorvastatin for 48 weeks. Examination of aortic valves (AVA) and femurs for atherosclerosis and calcification markers included micro-CT, special stains, and calcein incorporation. The cholesterol diet induced bone formation in calcified AVA and an increase in macrophage infiltration. Hyperlipidemic bones expressed an increase in osteoclast cells and a decrease in bone formation. Atorvastatin reduced atherosclerosis and bone mineralization in AVA and increased mineralization within femur bones (p < 0.05). Atherosclerosis is present in hyperlipidemic bones and valves as characterized by macrophage and osteoclast infiltration, and it is attenuated by atorvastatin, which may have implications for therapy in the future. PMID:25997922

  8. Nanogel-crosslinked nanoparticles increase the inhibitory effects of W9 synthetic peptide on bone loss in a murine bone resorption model

    Directory of Open Access Journals (Sweden)

    Sato T

    2015-05-01

    induced by a low calcium diet, which was confirmed by measurement of serum bone resorption markers. These data suggest that NanoClik nanoparticles could be a useful carrier for peptide therapeutics, and also demonstrate that daily subcutaneous injections of the W9 peptide with the nanoparticles were able to inhibit bone loss in vivo. An osteoclastogenesis inhibition assay performed in vitro confirmed a slower release profile of W9 from NanoClik nanoparticles compared with conventional CHP nanogels. Keywords: nanocarrier, peptide drug, injectable drug carrier, polyethylene glycol crosslinking, cholesterol-bearing pullulan, controlled release

  9. The Protective Effects of Alisol A 24-Acetate from Alisma canaliculatum on Ovariectomy Induced Bone Loss in Vivo.

    Science.gov (United States)

    Hwang, Yun-Ho; Kang, Kyung-Yun; Lee, Sung-Ju; Nam, Sang-Jip; Son, Young-Jin; Yee, Sung-Tae

    2016-01-01

    Alisma canaliculatum is a herb commonly used in traditional Korean medicine, and has been shown in scientific studies to have antitumor, diuretic hepatoprotective, and antibacterial effects. Recently, the anti-osteoclastogenesis of alisol A 24-acetate from Alisma canaliculatum was investigated in vitro. However, the influence of alisol A 24-acetate on osteoporosis in animals has not been investigated. The present study was undertaken to investigate the anti-osteoporotic effect of alisol A 24-acetate on bone mass in ovariectomized (OVX) mice and to identify the mechanism responsible for its effects. OVX mice were treated daily with 0.5 or 2 μg/g of alisol A 24-acetate for a period of six weeks. It was found that these administrations significantly suppressed osteoporosis in OVX mice and improved bone morphometric parameters. The serum estradiol, bone alkaline phosphatase levels, regulatory T/Th17 cell numbers were significantly increased by alisol A 24-acetate as compared with untreated OVX mice. In addition, TRAP activity was inhibited by alisol A 24-acetate in OVX mice. These results suggest alisol A 24-acetate effectively prevents bone loss in OVX mice, and that it can be considered a potential therapeutic for the treatment of postmenopausal osteoporosis. PMID:26760992

  10. Monitoring Bone Health after Spaceflight: Data Mining to Support an Epidemiological Analysis of Age-related Bone Loss in Astronauts

    Science.gov (United States)

    Baker, K. S,; Amin, S.; Sibonga, Jean D.

    2009-01-01

    Through the epidemiological analysis of bone data, HRP is seeking evidence as to whether the prolonged exposure to microgravity of low earth orbit predisposes crewmembers to an earlier onset of osteoporosis. While this collaborative Epidemiological Project may be currently limited by the number of ISS persons providing relevant spaceflight medical data, a positive note is that it compares medical data of astronauts to data of an age-matched (not elderly) population that is followed longitudinally with similar technologies. The inclusion of data from non-ISS and non-NASA crewmembers is also being pursued. The ultimate goal of this study is to provide critical information for NASA to understand the impact of low physical or minimal weight-bearing activity on the aging process as well as to direct its development of countermeasures and rehabilitation programs to influence skeletal recovery. However, in order to optimize these results NASA needs to better define the requirements for long term monitoring and encourage both active and retired astronauts to contribute to a legacy of data that will define human health risks in space.

  11. Vibrotactile threshold for hairy skin and its transformation into equivalent bone-conduction loss for the mastoid.

    Science.gov (United States)

    Lamoré, P J

    1984-01-01

    Vibrotactile thresholds for the glabrous skin of the hand and for the hairy skin of the arm are investigated as a function of frequency in the range from 40 to 2 000 Hz, using a heavy vibrator. These thresholds are expressed as equivalent bone-conduction loss and compared with vibrotactile thresholds determined with bone vibrators on the arm and mastoid for normally hearing and severely hearing-impaired subjects. The results are used to predict the vibrotactile threshold of the hairy skin of the mastoid under conditions of severe hearing impairment and deafness. The frequency characteristics of a number of vibrators are discussed with respect to their suitability for skin stimulation. PMID:6517747

  12. Applications of Anabolic Vitamin D Analogs as Countermeasures to Bone Loss

    Science.gov (United States)

    Karin, Norman J.

    1998-01-01

    The experiments in Round 2 were designed to extend the results of our efforts in Round 1 which led us to hypothesize that the seco-steroid, 1,25-dihydroxyvitamin D3[1,25(OH)2D3], acts in synergy with parathyroid hormone (PTH) to regulate bone calcium homeostasis. Our work centered on one particular target of 1,25(OH)2D3 action, the voltage-sensitive calcium channels (VSCC's), which are activated acutely by this steroid within milliseconds of exposure . A second area of research focused on the effects of mechanical strain on VSCC expression in bone. These experiments were performed in collaboration with Dr. Steven Goldstein (Univ. Michigan), who generously provided RNA extracted from dog bones that had been exposed to mechanical strain in vivo. Our results suggest that mechanical loading elevated VSCC expression in the long bones from 3 of the 6 animals tested. A second line of experimentation, carried out in collaboration with Dr. Randall Duncan, a NASA-funded investigator in Indianapolis, centered on RT-PCR analysis of effects of mechanical strain on Ca2(+) channel expression in cultured bone cells. Compared to unstrained controls, the expression of vitamin-D-sensidve Ca2(+) channels is elevated 3- to 5-fold over a 24 hr period.

  13. Gelatinous bone marrow transformation secondary to unusual eating habits and drastic weight loss.

    Science.gov (United States)

    Rafiullah; Islam, Rezwan; Mahmood, Ruth; Sitwala, Kajal V

    2013-01-01

    Gelatinous bone marrow transformation (GMT), also known as starvation bone marrow, has been reported in a number of chronic illnesses, eating disorders (anorexia nervosa) and malignancies. We report the case of a 37-year-old man with a history of bipolar disorder and obesity (weighing >300 pounds) who presented due to recently developing a deep yellow colour to his skin. Over the past 2 years, through diet and exercise, he lost over 150 pounds. He reported running 6-8 miles per day and eating 'lots of squash'. We made the diagnosis of starvation hepatitis and bone marrow degeneration, and referred the patient to a dietician and haematologist/oncologist, where improvements were observed at 4 weeks follow-up. PMID:23861277

  14. MicroRNAs: Potential Biomarkers and Therapeutic Targets for Alveolar Bone Loss in Periodontal Disease

    Science.gov (United States)

    Kagiya, Tadayoshi

    2016-01-01

    Periodontal disease is an inflammatory disease caused by bacterial infection of tooth-supporting structures, which results in the destruction of alveolar bone. Osteoclasts play a central role in bone destruction. Osteoclasts are tartrate-resistant acid phosphatase (TRAP)-positive multinucleated giant cells derived from hematopoietic stem cells. Recently, we and other researchers revealed that microRNAs are involved in osteoclast differentiation. MicroRNAs are novel, single-stranded, non-coding, small (20–22 nucleotides) RNAs that act in a sequence-specific manner to regulate gene expression at the post-transcriptional level through cleavage or translational repression of their target mRNAs. They regulate various biological activities such as cellular differentiation, apoptosis, cancer development, and inflammatory responses. In this review, the roles of microRNAs in osteoclast differentiation and function during alveolar bone destruction in periodontal disease are described. PMID:27529224

  15. MicroRNAs: Potential Biomarkers and Therapeutic Targets for Alveolar Bone Loss in Periodontal Disease

    Directory of Open Access Journals (Sweden)

    Tadayoshi Kagiya

    2016-08-01

    Full Text Available Periodontal disease is an inflammatory disease caused by bacterial infection of tooth-supporting structures, which results in the destruction of alveolar bone. Osteoclasts play a central role in bone destruction. Osteoclasts are tartrate-resistant acid phosphatase (TRAP-positive multinucleated giant cells derived from hematopoietic stem cells. Recently, we and other researchers revealed that microRNAs are involved in osteoclast differentiation. MicroRNAs are novel, single-stranded, non-coding, small (20–22 nucleotides RNAs that act in a sequence-specific manner to regulate gene expression at the post-transcriptional level through cleavage or translational repression of their target mRNAs. They regulate various biological activities such as cellular differentiation, apoptosis, cancer development, and inflammatory responses. In this review, the roles of microRNAs in osteoclast differentiation and function during alveolar bone destruction in periodontal disease are described.

  16. Protocatechuic Acid Attenuates Osteoclastogenesis by Downregulating JNK/c-Fos/NFATc1 Signaling and Prevents Inflammatory Bone Loss in Mice.

    Science.gov (United States)

    Park, Sun-Hyang; Kim, Ju-Young; Cheon, Yoon-Hee; Baek, Jong Min; Ahn, Sung-Jun; Yoon, Kwon-Ha; Lee, Myeung Su; Oh, Jaemin

    2016-04-01

    Protocatechuic acid (PCA) plays a critical role in nutritional metabolism; it is a major metabolite of anthocyanins, which are flavonoids with a range of health benefits. PCA has a variety of biological activities including anti-oxidant, antiinflammatory, anti-apoptosis, and anti-microbial activities. However, the pharmacological effect of PCA, especially on osteoclastogenesis, remains unknown. We examined the effect of PCA on receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation and bone resorption. PCA dose-dependently inhibited RANKL-induced osteoclast differentiation in mouse bone marrow macrophages (BMMs) and suppressed the bone-resorbing activity of mature osteoclasts. At the molecular level, PCA suppressed RANKL-induced phosphorylation of JNK among MAPKs only, without significantly affecting the early signaling pathway. PCA also suppressed RANKL-stimulated expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1) at the mRNA and protein levels, without altering c-Fos mRNA expression. Additionally, PCA down-regulated the expression of downstream osteoclastogenesis-related genes including β3-integrin, DC-STAMP, OC-STAMP, Atp6v0d2, CTR, and CtsK. Mice treated with PCA efficiently recovered from lipopolysaccharide-induced bone loss in vivo. Thus, PCA inhibits RANKL-induced osteoclast differentiation and function by suppressing JNK signaling, c-Fos stability, and expression of osteoclastic marker genes. These results suggest that PCA could be useful in treatment of inflammatory bone disorders. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26792397

  17. Addition of Fructooligosaccharides and Dried Plum to Soy-Based Diets Reverses Bone Loss in the Ovariectomized Rat

    Directory of Open Access Journals (Sweden)

    Catherine D. Johnson

    2011-01-01

    Full Text Available Dietary bioactive components that play a role in improving skeletal health have received considerable attention in complementary and alternative medicine practices as a result of their increased efficacy to combat chronic diseases. The objectives of this study were to evaluate the additive or synergistic effects of dried plum and fructooligosaccharides (FOS and to determine whether dried plum and FOS or their combination in a soy protein-based diet can restore bone mass in ovarian hormone deficient rats. For this purpose, 72 3-month-old female Sprague-Dawley rats were divided into six groups (n = 12 and either ovariectomized (Ovx, five groups or sham-operated (sham, one group. The rats were maintained on a semipurified standard diet for 45 days after surgery to establish bone loss. Thereafter, the rats were placed on one of the following dietary treatments for 60 days: casein-based diet (Sham and Ovx, soy-based diet (Ovx + soy or soy-based diet with dried plum (Ovx + soy + plum, FOS (Ovx + soy + FOS and combination of dried plum and FOS (Ovx + soy + plum + FOS. Soy protein in combination with the test compounds significantly improved whole-body bone mineral density (BMD. All test compounds in combination with soy protein significantly increased femoral BMD but the combination of soy protein, dried plum and FOS had the most pronounced effect in increasing lumbar BMD. Similarly, all of the test compounds increased ultimate load, indicating improved biomechanical properties. The positive effects of these test compounds on bone may be due to their ability to modulate bone resorption and formation, as shown by suppressed urinary deoxypyridinoline excretion and enhanced alkaline phosphatase activity.

  18. Endogenous n-3 fatty acids protect ovariectomy induced bone loss by attenuating osteoclastogenesis

    OpenAIRE

    Rahman, Md. Mizanur; Bhattacharya, Arunabh; Banu, Jameela; Kang, Jing X.; Fernandes, Gabriel

    2009-01-01

    Beneficial effects of n-3 fatty acids (FA) on bone mineral density (BMD) have been reported in mice, rats and humans, but the precise mechanisms involved have not been described. This study used the Fat-1 mouse, a transgenic model that synthesizes n-3 FA from n-6 FA to directly determine if outcomes of bone health were correlated with n-3 FA. Ovariectomized (Ovx) and sham operated wild type (WT) and Fat-1 mice were fed an AIN-93M diet containing 10% corn oil for 24 weeks. BMD was analyzed by ...

  19. Can vitamin D3 supplementation prevent bone loss in persons with MS?

    OpenAIRE

    Steffensen, Linn Hofsøy

    2012-01-01

    In persons with Multiple sclerosis (MS) low bone mineral density (BMD) is more prevalent when compared with healthy controls and MS may be a possible cause of secondary osteoporosis. BMD is primarily determined by genetic and hormonal factors, body mass index, physical activity and intake of calcium and vitamin D. Vitamin D level at 50 nmol/L or higher is classified as sufficient, however, optimal vitamin D level for bone health is according to many experts at least 75 nmol/L. In this 96 week...

  20. Regulation of osteoclast homeostasis and inflammatory bone loss by MFG-E81

    OpenAIRE

    Abe, T.; Shin, J.; Hosur, K.; Udey, M C; Chavakis, T.; Hajishengallis, G

    2014-01-01

    The glycoprotein milk fat globule-EGF factor 8 (MFG-E8) is expressed in several tissues and mediates diverse homeostatic functions. However, whether MFG-E8 plays a role in bone homeostasis has not been established. Here we show for the first time that osteoclasts express and are regulated by MFG-E8. Bone marrow-derived osteoclast precursors (OCPs) from MFG-E8–deficient (Mfge8−/−) mice underwent increased RANKL-induced osteoclastogenesis leading to enhanced resorption pit formation as compared...

  1. Theories and Practice in Prevention and Treatment Principles in Relation to Chinese Herbal Medicine and Bone Loss

    Institute of Scientific and Technical Information of China (English)

    Hong Xu 徐红; David LAWSON

    2004-01-01

    Osteoporosis is a world wide problem that is increasing in significance as the global population both increases and ages. While osteoporosis has been extensively studied in recent years, the utilization of Traditional Chinese Herbal Medicine for the prevention and treatment of this condition have seldom been examined in the Western world. This paper reviews the theories and the literature that relate to prevention and treatment of bone loss at the time of menopause according to the principles of Traditional Chinese Herbal Medicine. Practical developments in these areas are also illustrated in this paper based on the authors' research findings in recent studies.

  2. Defective Neutrophil Recruitment in Leukocyte Adhesion Deficiency Type I Disease Causes Local IL-17-Driven Inflammatory Bone Loss.

    OpenAIRE

    Moutsopoulos, N. M.; Konkel, J.; Sarmadi, M.; Eskan, M. A.; Wild, T.; N Dutzan; L Abusleme; Zenobia, C; Hosur, K. B.; Abe, T.; Uzel, G.; Chen, W.; Chavakis, T.; Holland, S.M.; Hajishengallis, G

    2014-01-01

    Leukocyte adhesion deficiency Type I (LAD-I), a disease syndrome associated with frequent microbial infections, is caused by mutations on the CD18 subunit of β2 integrins. LAD-I is invariably associated with severe periodontal bone loss, historically attributed to lack of neutrophil surveillance of the periodontal infection. Here, we challenge this dogma by showing that the cytokine IL-17 plays a major role in the oral pathology of LAD-I. Defective neutrophil recruitment in LAD-I patients, or...

  3. St. John's Wort (Hypericum perforatum) stimulates human osteoblastic MG-63 cell proliferation and attenuates trabecular bone loss induced by ovariectomy

    OpenAIRE

    You, Mi-Kyoung; Kim, Du-Woon; Jeong, Kyu-Shik; Bang, Mi-Ae; Kim, Hwan-Seon; Rhuy, Jin; Kim, Hyeon-A

    2015-01-01

    BACKGROUND/OBJECFTIVES The effect of St. John's Wort extract (SJW) on MG-63 cell proliferation and trabecular bone loss induced by ovariectomy was examined. MATERIALS/METHODS Proliferation, expression of estrogen receptor (ER) α and ER β, and gene expressions of osteoprotegerin (OPG), osteocalcin (OC) and alkaline phosphatase (ALP) were examined in MG-63 cells treated with or without SJW. Ovariectomized rats were treated with SJW at the dose of 100 or 200 mg/kg/day, β-estradiol-3-benzoate (E2...

  4. Periarticular and generalised bone loss in patients with early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Jensen, T W; Hansen, M S; Hørslev-Petersen, Kim; Hyldstrup, L; Abrahamsen, B; Langdahl, Bente Lomholt; Zerahn, Bo; Pødenphant, J; Stengaard-Petersen, K; Junker, P; Ostergaard, M; Lottenburger, Tine; Ellingsen, Torkell Juulsgaad; Andersen, L S; Hansen, I; Skjødt, H; Pedersen, J K; Lauridsen, U B; Svendsen, A J; Tarp, U; Lindegaard, Hanne; Jurik, Anne Grethe; Vestergaard, Aage; Hetland, M L; group, the Cimestra study

    2013-01-01

    OBJECTIVES: The aims of this study were to investigate the influence of alendronate and intra-articular betamethasone treatment on bone mineral density (BMD) changes in hand, lumbar spine and femoral neck during 1 year of a treat-to-target study (Cyclosporine, Methotrexate, Steroid in RA (CIMESTR...

  5. Non-pharmacological treatment and prevention of bone loss after spinal cord injury: a systematic review

    DEFF Research Database (Denmark)

    Biering-Sørensen, F; Hansen, B; Lee, B S B

    2009-01-01

    longer period of training, or higher frequency or stimulus intensity. Improvements correspond to trabecular bone in the distal femur or proximal tibia. Impact vibration and pulsed electromagnetic fields may have some positive effects, whereas pulsed ultrasound does not. Six studies on the influence of...

  6. Defective bone repair in mast cell deficient mice with c-Kit loss of function.

    Science.gov (United States)

    Behrends, D A; Cheng, L; Sullivan, M B; Wang, M H; Roby, G B; Zayed, N; Gao, C; Henderson, J E; Martineau, P A

    2014-01-01

    KitW-sh mice carry an inactivating mutation in the gene encoding the receptor for stem cell factor, which is expressed at high levels on the surface of haematopoietic precursor cells. The mutation results in mast cell deficiency, a variety of defects in innate immunity and poorly defined abnormalities in bone. The present study was designed to characterise healing of a cortical window defect in skeletally mature KitW-sh mice using high-resolution micro computed tomographic imaging and histological analyses. The cortical bone defect healed completely in all wild type mice but failed to heal in about half of the KitW-sh mice by 12 weeks post-operative. Defective healing was associated with premature and excessive expression of TRAP positive cells embedded in fibrous marrow but with little change in ALP activity. Immuno-histochemical analyses revealed reduced CD34 positive vascular endothelial cells and F4/80 positive macrophages at 1 and 2 weeks post-operative. Impaired bone healing in the KitW-sh mice was therefore attributed to altered catabolic activity, impaired re-vascularisation and compromised replacement of woven with compact bone. PMID:25284141

  7. Defective bone repair in mast cell deficient mice with c-Kit loss of function

    Directory of Open Access Journals (Sweden)

    DA Behrends

    2014-10-01

    Full Text Available KitW-sh mice carry an inactivating mutation in the gene encoding the receptor for stem cell factor, which is expressed at high levels on the surface of haematopoietic precursor cells. The mutation results in mast cell deficiency, a variety of defects in innate immunity and poorly defined abnormalities in bone. The present study was designed to characterise healing of a cortical window defect in skeletally mature KitW-sh mice using high-resolution micro computed tomographic imaging and histological analyses. The cortical bone defect healed completely in all wild type mice but failed to heal in about half of the KitW-sh mice by 12 weeks post-operative. Defective healing was associated with premature and excessive expression of TRAP positive cells embedded in fibrous marrow but with little change in ALP activity. Immuno-histochemical analyses revealed reduced CD34 positive vascular endothelial cells and F4/80 positive macrophages at 1 and 2 weeks post-operative. Impaired bone healing in the KitW-sh mice was therefore attributed to altered catabolic activity, impaired re-vascularisation and compromised replacement of woven with compact bone.

  8. Recurrent anterior shoulder instability: accuracy of estimations of glenoid bone loss with computed tomography is insufficient for therapeutic decision-making

    International Nuclear Information System (INIS)

    To evaluate the reliability of glenoid bone loss estimations based on either axial computed tomography (CT) series or single sagittal (''en face'' to glenoid) CT reconstructions, and to assess their accuracy by comparing with actual CT-based bone loss measurements, in patients with anterior glenohumeral instability. In two separate series of patients diagnosed with recurrent anterior glenohumeral instability, glenoid bone loss was estimated on axial CT series and on the most lateral sagittal (en face) glenoid view by two blinded radiologists. Additionally, in the second series of patients, glenoid defects were measured on sagittal CT reconstructions by an independent observer. In both series, larger defects were estimated when based on sagittal CT images compared to axial views. In the second series, mean measured bone loss was 11.5% (SD = 6.0) of the total original glenoid area, with estimations of 9.6% (SD = 7.2) and 7.8% (SD = 4.2) for sagittal and axial views, respectively. Correlations of defect estimations with actual measurements were fair to poor; glenoid defects tended to be underestimated, especially when based on axial views. CT-based estimations of glenoid bone defects are inaccurate. Especially for axial views, there is a high chance of glenoid defect underestimation. When using glenoid bone loss quantification in therapeutic decision-making, measuring the defect instead of estimating is strongly advised. (orig.)

  9. Prevention of postmenopausal bone loss - effects of alternative administration forms of estrogens, alternative gestagens and calcium addition

    International Nuclear Information System (INIS)

    Calcium metabolism was examined in 133 healthy postmenopausal women every three months during two years of treatment with oral or percutaneous 17β-estradiol combined with different doses of calcium supplementation and/or different gestagens. Bone mineral content measured in the forearm (single photon absorptiometry), in the spine and in the total skeleton (dual photon absorptiometry) was unchanged in all estrogen-treated groups during the two years of treatment, and the responses in the groups with and without calcium supplementation and with different gestagens were not significantly different. Furthermore, the responses were independent of route of administration of the estrogen. Biochemical indices of bone turnover (serum alkaline phosphatase and fasting urinary hydroxyproline/creatinine) decreased highly significantly during estrogen treatment (p<0.001) independent of route of administration of the estrogen, of calcium supplementation, and of gestagen agent. We conclude that estrogen treatment independently of route of administration, prevents postmenopausal bone loss. The gestagen agents used here do not affect calcium metabolism, and calcium supplementation has no additive effect to estrogen therapy. (orig.)

  10. Prevention of postmenopausal bone loss - effects of alternative administration forms of estrogens, alternative gestagens and calcium addition

    Energy Technology Data Exchange (ETDEWEB)

    Riis, B.J.; Christiansen, C.

    1987-02-01

    Calcium metabolism was examined in 133 healthy postmenopausal women every three months during two years of treatment with oral or percutaneous 17..beta..-estradiol combined with different doses of calcium supplementation and/or different gestagens. Bone mineral content measured in the forearm (single photon absorptiometry), in the spine and in the total skeleton (dual photon absorptiometry) was unchanged in all estrogen-treated groups during the two years of treatment, and the responses in the groups with and without calcium supplementation and with different gestagens were not significantly different. Furthermore, the responses were independent of route of administration of the estrogen. Biochemical indices of bone turnover (serum alkaline phosphatase and fasting urinary hydroxyproline/creatinine) decreased highly significantly during estrogen treatment (p<0.001) independent of route of administration of the estrogen, of calcium supplementation, and of gestagen agent. We conclude that estrogen treatment independently of route of administration, prevents postmenopausal bone loss. The gestagen agents used here do not affect calcium metabolism, and calcium supplementation has no additive effect to estrogen therapy.

  11. Effect of 1 year of an intentional weight loss intervention on bone mineral density in type 2 diabetes: Results from the Look AHEAD randomized trial

    Science.gov (United States)

    Intentional weight loss is an important component of treatment for overweight patients with type 2 diabetes, but the effects on bone density are not known. We used data from the Look AHEAD trial to determine the impact of an intensive lifestyle weight loss intervention (ILI) compared with diabetes s...

  12. Inhibition of reactive oxygen species generation and downstream activation of the ERK/STAT3/RANKL signaling cascade in osteoblasts accounts for the protective effects of estradiol on ethanol-induced bone loss

    Science.gov (United States)

    Bone loss occurs with chronic ethanol (EtOH) consumption in males and cycling females as a result of increased bone resorption. We have demonstrated that in vivo estradiol treatment can reverse this effect. However, the molecular mechanisms of EtOH-induced bone loss and of estrogen protection are la...

  13. Photothermal tomography for the functional and structural evaluation, and early mineral loss monitoring in bones.

    Science.gov (United States)

    Kaiplavil, Sreekumar; Mandelis, Andreas; Wang, Xueding; Feng, Ting

    2014-08-01

    Salient features of a new non-ionizing bone diagnostics technique, truncated-correlation photothermal coherence tomography (TC-PCT), exhibiting optical-grade contrast and capable of resolving the trabecular network in three dimensions through the cortical region with and without a soft-tissue overlayer are presented. The absolute nature and early demineralization-detection capability of a marker called thermal wave occupation index, estimated using the proposed modality, have been established. Selective imaging of regions of a specific mineral density range has been demonstrated in a mouse femur. The method is maximum-permissible-exposure compatible. In a matrix of bone and soft-tissue a depth range of ~3.8 mm has been achieved, which can be increased through instrumental and modulation waveform optimization. Furthermore, photoacoustic microscopy, a comparable modality with TC-PCT, has been used to resolve the trabecular structure and for comparison with the photothermal tomography. PMID:25136480

  14. Bone marrow mesenchymal stem cells protect against retinal ganglion cell loss in aged rats with glaucoma

    OpenAIRE

    Hu Y; Tan HB; Wang XM; Rong H; Cui HP; Cui H

    2013-01-01

    Ying Hu,1,2 Hai Bo Tan,1 Xin Mei Wang,3 Hua Rong,1 Hong Ping Cui,1 Hao Cui2 Departments of Ophthalmology, 1Shanghai East Hospital of Tongji University, Shanghai, 2First Affiliated Hospital, 3Fourth Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China Abstract: Glaucoma is a common eye disease in the aged population and has severe consequences. The present study examined the therapeutic effects of bone marrow mesenchymal stem cell (BMSC) transplantation i...

  15. Photothermal tomography for the functional and structural evaluation, and early mineral loss monitoring in bones

    OpenAIRE

    Kaiplavil, Sreekumar; Mandelis, Andreas; Wang, Xueding; Feng, Ting

    2014-01-01

    Salient features of a new non-ionizing bone diagnostics technique, truncated-correlation photothermal coherence tomography (TC-PCT), exhibiting optical-grade contrast and capable of resolving the trabecular network in three dimensions through the cortical region with and without a soft-tissue overlayer are presented. The absolute nature and early demineralization-detection capability of a marker called thermal wave occupation index, estimated using the proposed modality, have been established...

  16. Fermented soybeans by Rhizopus oligosporus reduce femoral bone loss in ovariectomized rats

    OpenAIRE

    Yoo, Hyun-Wook; Chang, Moon-Jeong; Kim, Sun-Hee

    2014-01-01

    BACKGROUND/OBJECTIVES Soy isoflavones are structurally similar to estrogen and bind to estrogen receptors, suggesting that they exhibit estrogenic activities; therefore, they are referred to as phytoestrogens. Fermentation may affect the bioavailability of isoflavones altering soy isoflavone glycosides in the form of aglycones. Thus, this study investigated the effects of fermented soybeans by Rhizopus oligosporus on bone metabolism in both young rats as a pilot test and in ovariectomized (ov...

  17. Ionizing Radiation and Bone Loss: Space Exploration and Clinical Therapy Applications

    OpenAIRE

    Willey, Jeffrey S.; Lloyd, Shane A. J.; Nelson, Gregory A.; Bateman, Ted A.

    2011-01-01

    Damage to normal, nontumor bone tissue following therapeutic irradiation increases the risk of fracture among cancer patients. For example, women treated for various pelvic tumors have been shown to have a greater than 65% increased incidence of hip fracture by 5 years postradiotherapy. Another practical situation in which exposure to ionizing radiation may negatively impact skeletal integrity is during extended spaceflight missions. There is a limited understanding of how spaceflight-relevan...

  18. A small molecule, odanacatib, inhibits inflammation and bone loss caused by endodontic disease.

    Science.gov (United States)

    Hao, Liang; Chen, Wei; McConnell, Matthew; Zhu, Zheng; Li, Sheng; Reddy, Michael; Eleazer, Paul D; Wang, Min; Li, Yi-Ping

    2015-04-01

    Periapical disease, an inflammatory disease mainly caused by dental caries, is one of the most prevalent infectious diseases of humans, affecting both children and adults. The infection travels through the root, leading to inflammation, bone destruction, and severe pain for the patient. Therefore, the development of a new class of anti-periapical disease therapies is necessary and critical for treatment and prevention. A small molecule, odanacatib (ODN), which is a cathepsin K (Ctsk) inhibitor, was investigated to determine its ability to treat this disease in a mouse model of periapical disease. While Ctsk was originally found in osteoclasts as an osteoclast-specific lysosomal protease, we were surprised to find that ODN can suppress the bacterium-induced immune response as well as bone destruction in the lesion area. X rays and microcomputed tomography (micro-CT) showed that ODN treatment had significant bone protection effects at different time points. Immunohistochemical and immunofluorescent staining show that ODN treatment dramatically decreased F4/80+ macrophages and CD3+ T cells in the lesion areas 42 days after infection. Consistent with these findings, quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) analysis showed low levels of proinflammatory mRNAs (for tumor necrosis factor alpha, interleukin 6, and interleukin 23α) and corresponding cytokine expression in the ODN-treated disease group. The levels of mRNA for Toll-like receptors 4, 5, and 9 also largely decreased in the ODN-treated disease group. Our results demonstrated that ODN can inhibit endodontic disease development, bone erosion, and immune response. These results indicate that application of this small molecule offers a new opportunity to design effective therapies that could prevent periapical inflammation and revolutionize current treatment options. PMID:25583522

  19. A Small Molecule, Odanacatib, Inhibits Inflammation and Bone Loss Caused by Endodontic Disease

    OpenAIRE

    Hao, Liang; Chen, Wei; McConnell, Matthew; Zhu, Zheng; Li, Sheng; Reddy, Michael; Eleazer, Paul D; Wang, Min; Li, Yi-Ping

    2015-01-01

    Periapical disease, an inflammatory disease mainly caused by dental caries, is one of the most prevalent infectious diseases of humans, affecting both children and adults. The infection travels through the root, leading to inflammation, bone destruction, and severe pain for the patient. Therefore, the development of a new class of anti-periapical disease therapies is necessary and critical for treatment and prevention. A small molecule, odanacatib (ODN), which is a cathepsin K (Ctsk) inhibito...

  20. Can bone loss be reversed by antithyroid drug therapy in premenopausal women with Graves' disease?

    Directory of Open Access Journals (Sweden)

    Belsing Tina Z

    2010-09-01

    Full Text Available Abstract Context Hyperthyroidism can lead to reduced bone mineral density (BMD and increased fracture risk particularly in postmenopausal women, but the mechanism behind is still unclear. Objective Prospective examination of the influence of thyroid hormones and/or thyroid autoantibodies on BMD in premenopause. Design We have examined 32 premenopausal women with untreated active Graves' disease from time of diagnosis, during 18 months of antithyroid drug therapy (ATD and additionally 18 months after discontinuing ATD. Variables of thyroid metabolism, calcium homeostasis and body composition were measured every 3 months. BMD of lumbar spine and femoral neck were measured at baseline, 18 ± 3 and 36 ± 3 months. Data were compared to base line, a sex- and age matched control group and a group of patients with Hashimoto's thyroiditis treated with non-suppressive doses of levothyroxine. Results The study showed significantly (p Conclusion The results indicated a clinically relevant impact of thyroid function on bone modulation also in premenopausal women with Graves' disease, and further indicated the possibility for a direct action of TRAb on bones.

  1. Evaluation of Treadmill Exercise in a Lower Body Negative Pressure Chamber as a Countermeasure for Weightlessness-Induced Bone Loss: a Bed Rest Study with Identical Twins

    Science.gov (United States)

    Smith, Scott M.; Davis-Street, Janis E.; Fesperman, J. Vernell; Calkins, D. S.; Bawa, Maneesh; Macias, Brandon R.; Meyer, R. Scott; Hargens, Alan R.

    2003-01-01

    Counteracting bone loss is required for future space exploration. We evaluated the ability of treadmill exercise in a LBNP chamber to counteract bone loss in a 30-day bed rest study. Eight pairs of identical twins were randomly assigned to sedentary control or exercise groups. Exercise within LBNP decreased the bone resorption caused by bed rest and may provide a countermeasure for spaceflight. INTRODUCTION: Bone loss is one of the greatest physiological challenges for extended-duration space missions. The ability of exercise to counteract weightlessness-induced bone loss has been studied extensively, but to date, it has proven ineffective. We evaluated the effectiveness of a combination of two countermeasures-treadmill exercise while inside a lower body negative pressure (LBNP) chamber-on bone loss during a 30-day bed rest study. MATERIALS AND METHODS: Eight pairs of identical twins were randomized into sedentary (SED) or exercise/LBNP (EX/LBNP) groups. Blood and urine samples were collected before, several times during, and after the 30-day bed rest period. These samples were analyzed for markers of bone and calcium metabolism. Repeated measures ANOVA was used to determine statistical significance. Because identical twins were used, both time and group were treated as repeated variables. RESULTS: Markers of bone resorption were increased during bed rest in samples from sedentary subjects, including the collagen cross-links and serum and urinary calcium concentrations. For N-telopeptide and deoxypyridinoline, there were significant (p < 0.05) interactions between group (SED versus EX/LBNP) and phase of the study (sample collection point). Pyridinium cross-links were increased above pre-bed rest levels in both groups, but the EX/LBNP group had a smaller increase than the SED group. Markers of bone formation were unchanged by bed rest in both groups. CONCLUSIONS: These data show that this weight-bearing exercise combined with LBNP ameliorates some of the negative

  2. Estrogen-mimicking isoflavone genistein prevents bone loss in a rat model of obstructive sleep apnea-hypopnea syndrome

    OpenAIRE

    Song, Lige; Liang, Xiao; Zhou, Yun

    2014-01-01

    Objective: Intermittent hypoxia was introduced to mimic obstructive sleep apnea-hypopnea syndrome (OSAHS) in rats. Then, bone mass, bone strength and bone turnover were evaluated, and the influence of genistein on bone mass reduction was investigated in these rats. Methods: OSAHS animal model was established via chronic intermittent hypoxia, and genistein (2.5 mg/kg/day) was used to treat OSAHS rats. The bone mineral density (BMD), bone Histomorphometric indicators, bone biomechanics and expr...

  3. Effect of bar cross-section geometry on stress distribution in overdenture-retaining system simulating horizontal misfit and bone loss.

    Science.gov (United States)

    Spazzin, Aloísio Oro; Costa, Ana Rosa; Correr, Américo Bortolazzo; Consani, Rafael Leonardo Xediek; Correr-Sobrinho, Lourenço; dos Santos, Mateus Bertolini Fernandes

    2013-08-01

    This study evaluated the influence of cross-section geometry of the bar framework on the distribution of static stresses in an overdenture-retaining bar system simulating horizontal misfit and bone loss. Three-dimensional FE models were created including two titanium implants and three cross-section geometries (circular, ovoid or Hader) of bar framework placed in the anterior part of a severely resorbed jaw. One model with 1.4-mm vertical loss of the peri-implant tissue was also created. The models set were exported to mechanical simulation software, where horizontal displacement (10, 50 or 100 μm) was applied simulating the settling of the framework, which suffered shrinkage during the laboratory procedures. The bar material used for the bar framework was a cobalt--chromium alloy. For evaluation of bone loss effect, only the 50-μm horizontal misfit was simulated. Data were qualitatively and quantitatively evaluated using von Mises stress for the mechanical part and maximum principal stress and μ-strain for peri-implant bone tissue given by the software. Stresses were concentrated along the bar and in the join between the bar and cylinder. In the peri-implant bone tissue, the μ-strain was higher in the cervical third. Higher stress levels and μ-strain were found for the models using the Hader bar. The bone loss simulated presented considerable increase on maximum principal stresses and μ-strain in the peri-implant bone tissue. In addition, for the amplification of the horizontal misfit, the higher complexity of the bar cross-section geometry and bone loss increases the levels of static stresses in the peri-implant bone tissue. PMID:23791086

  4. Alendronate prevents postmenopausal bone loss in women without osteoporosis. A double-blind, randomized, controlled trial. Alendronate Osteoporosis Prevention Study Group

    DEFF Research Database (Denmark)

    McClung, M; Clemmesen, B; Daifotis, A;

    1998-01-01

    to one of five regimens: oral placebo; oral alendronate, 1, 5, or 10 mg/d; or oral alendronate, 20 mg/d for 2 years followed by placebo during the third year (20/0 mg/d). MEASUREMENTS: Bone mineral density was measured by dual-energy x-ray absorptiometry. Bone turnover and bone quality were assessed...... with biochemical markers and bone histomorphometry. RESULTS: Alendronate at 5, 10, and 20/0 mg/d increased bone mineral density from baseline at the lumbar spine, femoral neck, and trochanter by 1% to 4% and in the total body by 0.3% to 1.0%; placebo led to losses of 2% to 4% at these sites....... Alendronate, 1 mg/d, attenuated losses relative to those seen with placebo. Alendronate decreased markers of bone resorption to a new steady state by 3 months and decreased markers of bone formation by 6 to 12 months. Bone quality remained normal. At all dosages studied, alendronate had a safety and...

  5. Effect of labiolingual inclination of a maxillary central incisor and surrounding alveolar bone loss on periodontal stress: A finite element analysis

    Science.gov (United States)

    Choi, Sung-Hwan; Kim, Young-Hoon; Lee, Kee-Joon

    2016-01-01

    Objective The aim of this study was to investigate whether labial tooth inclination and alveolar bone loss affect the moment per unit of force (Mt/F) in controlled tipping and consequent stresses on the periodontal ligament (PDL). Methods Three-dimensional models (n = 20) of maxillary central incisors were created with different labial inclinations (5°, 10°, 15°, and 20°) and different amounts of alveolar bone loss (0, 2, 4, and 6 mm). The Mt/F necessary for controlled tipping (Mt/Fcont) and the principal stresses on the PDL were calculated for each model separately in a finite element analysis. Results As labial inclination increased, Mt/Fcont and the length of the moment arm decreased. In contrast, increased alveolar bone loss caused increases in Mt/Fcont and the length of the moment arm. When Mt/F was near Mt/Fcont, increases in Mt/F caused compressive stresses to move from a predominantly labial apical region to a palatal apical position, and tensile stresses in the labial area moved from a cervical position to a mid-root position. Although controlled tipping was applied to the incisors, increases in alveolar bone loss and labial tooth inclination caused increases in maximum compressive and tensile stresses at the root apices. Conclusions Increases in alveolar bone loss and labial tooth inclination caused increases in stresses that might cause root resorption at the root apex, despite the application of controlled tipping to the incisors. PMID:27226961

  6. Preventive Effects of Flaxseed and Sesame Oil on Bone Loss in Ovariectomized Rats

    OpenAIRE

    S. Boulbaroud; Mesfioui, A.; A. Arfaoui; A. Ouichou; A. El Hessni

    2008-01-01

    A study was designed to examine the effects of dietary flaxseed oil (FO) and sesame oil (SO) which are rich successively in n-3 and (n-9 and n-6) on biochemical parameters and histological status of bone. Sixty-four 90-day-old female wistar rats were randomly assigned to 6 groups: sham-operated rat (sham)+ control diets, ovariectomized rat (OVX))+ control diets, OVX+ 7% FO, OVX+ 7% SO, OVX+ 10% FO, OVX+ 10% SO. After 4 weeks of treatments, rats were euthanized; blood and tissues were c...

  7. Periprosthetic bone loss: diagnostic and therapeutic approaches [v2; ref status: indexed, http://f1000r.es/3pz

    Directory of Open Access Journals (Sweden)

    Loredana Cavalli

    2014-06-01

    Full Text Available Total joint replacement surgery is being performed on an increasingly large part of the population. Clinical longevity of implants depends on their osseointegration, which is influenced by the load, the characteristics of the implant and the bone-implant interface, as well as by the quality and quantity of the surrounding bone. Aseptic loosening due to periprosthetic osteolysis is the most frequent known cause of implant failure. Wear of prosthetic materials results in the formation of numerous particles of debris that cause a complex biological response. Dual-energy X-ray Absorptiometry (DXA is regarded as an accurate method to evaluate Bone Mineral Density (BMD around hip or knee prostheses. Further data may be provided by a new device, the Bone Microarchitecture Analysis (BMA, which combines bone microarchitecture quantification and ultra high resolution osteo-articular imaging. Pharmacological strategies have been developed to prevent bone mass loss and to extend implant survival. Numerous trials with bisphosphonates show a protective effect on periprosthetic bone mass, up to 72 months after arthroplasty. Strontium ranelate has been demonstrated to increase the osseointegration of titanium implants in treated animals with improvement of bone microarchitecture and bone biomaterial properties.

  8. Clinical and hormonal variables related to bone mass loss in anorexia nervosa patients.

    Science.gov (United States)

    Fernández-Soto, María Luisa; González-Jiménez, Amalia; Chamorro-Fernández, Marta; Leyva-Martínez, Socorro

    2013-01-01

    A better understanding of the prognostic factors of low bone mass in anorexia nervosa (AN) and development of effective therapeutic strategies is critical. In order to determine which clinical, biochemical, and/or hormonal parameters could be related to bone mineral density (BMD), 47 female AN patients were classified according to the WHO osteoporosis criteria at lumbar spine (LS). This was a cross-sectional study of 16 AN women with osteoporosis criteria and 31without. Control group was 25 healthy, normal-weight, age-matched women. We assessed BMD using dual-energy X-ray absorptiometry at the LS and body composition. We measured serum fasting cortisol, estradiol, insulin-like growth factor-1 (IGF-1), leptin, sex hormone-binding globulin, albumin and retinol binding protein levels. The prevalence of osteoporosis was 34% and osteopenia 19% at the LS. The AN group with osteoporosis had lower IGF-1 and estradiol levels (both posteoporosis. The BMD and T-score at LS was inversely related to the duration of amenorrhea (posteoporosis. A low BMD is a consequence of hormonal alterations which include hypoestrogenism, hypoleptinemia, hypercortisolism, and decreases in IGF-1 levels, as well as a low BMI and fat mass. PMID:23601428

  9. Short-term, daily exposure to cold temperature may be an efficient way to prevent muscle atrophy and bone loss in a microgravity environment

    Science.gov (United States)

    Deng, Claudia; Wang, Ping; Zhang, Xiangming; Wang, Ya

    2015-04-01

    Microgravity induces less pressure on muscle/bone, which is a major reason for muscle atrophy as well as bone loss. Currently, physical exercise is the only countermeasure used consistently in the U.S. human space program to counteract the microgravity-induced skeletal muscle atrophy and bone loss. However, the routinely almost daily time commitment is significant and represents a potential risk to the accomplishment of other mission operational tasks. Therefore, development of more efficient exercise programs (with less time) to prevent astronauts from muscle atrophy and bone loss are needed. Consider the two types of muscle contraction: exercising forces muscle contraction and prevents microgravity-induced muscle atrophy/bone loss, which is a voluntary response through the motor nervous system; and cold temperature exposure-induced muscle contraction is an involuntary response through the vegetative nervous system, we formed a new hypothesis. The main purpose of this pilot study was to test our hypothesis that exercise at 4 °C is more efficient than at room temperature to prevent microgravity-induced muscle atrophy/bone loss and, consequently reduces physical exercise time. Twenty mice were divided into two groups with or without daily short-term (10 min × 2, at 12 h interval) cold temperature (4 °C) exposure for 30 days. The whole bodyweight, muscle strength and bone density were measured after terminating the experiments. The results from the one-month pilot study support our hypothesis and suggest that it would be reasonable to use more mice, in a microgravity environment and observe for a longer period to obtain a conclusion. We believe that the results from such a study will help to develop efficient exercise, which will finally benefit astronauts' heath and NASA's missions.

  10. Pyogenic granuloma associated with bone loss in an eight year old child: A case report

    Directory of Open Access Journals (Sweden)

    Shenoy S

    2006-01-01

    Full Text Available Soft tissue enlargements of the oral cavity often present a diagnostic challenge because a diverse group of pathologic processes can produce such lesions. An enlargement may represent a variation of normal anatomic structures, inflammation, cysts, developmental anomalies and neoplasm. Within these lesions is a group of reactive hyperplasias, which develop in response to a chronic, recurring tissue injury that stimulates an exuberant or excessive tissue repair response. The pyogenic granuloma is a reactive enlargement that is an inflammatory response to local irritation such as calculus, a fractured tooth, rough dental restoration and foreign materials. This article aims to present a case of pyogenic granuloma in 8 year old child patient associated with resorption of bone in relation to the tooth.

  11. The gap between calculated and actual calcium substitution during citrate anticoagulation in an immobilised patient on renal replacement therapy reflects the extent of bone loss – a case report

    OpenAIRE

    Klingele, Matthias; Seiler, Sarah; Poppleton, Aaron; Lepper, Philip; Fliser, Danilo; Seidel, Roland

    2014-01-01

    Background Demineralisation and bone density loss during immobilisation are known phenomena. However information concerning the extent of calcium loss during immobilisation remains inconsistent within literature. This may explain why treatment of bone loss and prevention of further demineralisation is often initiated only when spontaneous bone fracture occurred. Continuous renal replacement therapy is commonly utilised in critically ill patients with acute kidney injury requiring RRT. Regiona...

  12. The treatment of femoral bone loss by axial external fixation and susbequent locking plate application: a case report.

    Science.gov (United States)

    Boero, Emanuele; Mogollo, Maria del Amparo Paredes

    2015-12-01

    A 20-year-old man was admitted to our hospital having sustianed bilateral high-energy femoral fractures. The right femoral fracture was an open grade 3B with OTA grade 3 bone loss. The patient had also a brain contusion with a subdural haematoma and a closed fracture of the left clavicle. Initial management included temporarily stabilisation of the femoral fractures wth external fixators and prompt transfer to the intensive care unit. Three weeks later the external fixator of the right femur was converted to an hybrid system, and the fixator of the left side was removed and a reamed intramedullary locking nail was applied. Two months after the accident the patient underwent bone transport (11 cm long) of the right femur with an monolateral external fixation. When the final length was achieved there were knee stiffness (ROM 0° to 30°) and non-union of the docking site. Therefore, the patient underwent a Judet's procedure to treat the knee stiffness and stabilisation of the non united femur with a locking plate (LISS). After the operation the patient started progressive weight bearing. A year after trauma and following union of the femur, the patient underwent soft tissue reconstruction of the anterior side of the thigh with a free vascularised flap. At final follow upo the patient had a good functional recovery with return to his previous occupation. PMID:26738458

  13. The use of the Ilizarov method as a salvage procedure in infected nonunion of the distal femur with bone loss.

    Science.gov (United States)

    Saridis, A; Panagiotopoulos, E; Tyllianakis, M; Matzaroglou, C; Vandoros, N; Lambiris, E

    2006-02-01

    We reviewed 13 patients with infected nonunion of the distal femur and bone loss, who had been treated by radical surgical debridement and the application of an Ilizarov external fixator. All had severely restricted movement of the knee and a mean of 3.1 previous operations. The mean length of the bony defect was 8.3 cm and no patient was able to bear weight. The mean external fixation time was 309.8 days. According to Paley's grading system, eight patients had an excellent clinical and radiological result and seven excellent and good functional results. Bony union, the ability to bear weight fully, and resolution of the infection were achieved in all the patients. The external fixation time was increased when the definitive treatment started six months or more after the initial trauma, the patient had been subjected to more than four previous operations and the initial operation had been open reduction and internal fixation. PMID:16434530

  14. Association between alveolar bone loss and serum C-reactive protein levels in aggressive and chronic periodontitis patients

    Directory of Open Access Journals (Sweden)

    Rahul Chopra

    2012-01-01

    Full Text Available Background: C-reactive protein (CRP is an acute phase reactant that is produced in response to diverse inflammatory stimuli, and is known predictor of cardiovascular disease risk. Aggressive and chronic periodontitis are two main forms of periodontal disease, which differ mainly in the method of disease progression. This study aims at determining and comparing the relative levels of serum CRP and alveolar bone loss in aggressive and chronic periodontitis patients. Materials and Methods: A total of 45 subjects, which were divided into 3 groups diagnosed as having generalized aggressive periodontitis (GAP, chronic generalized periodontitis (CGP and non-periodontitis controls (NP, were selected for the study. Venous blood samples were collected for quantitative CRP analysis using Turbidimetric immunoassay. Alveolar bone loss (ABL was measured at proximal sites of posterior teeth on a panoramic radiograph. The relationship between the mean ratio of ABL to root length and serum CRP levels was statistically analyzed using Student unpaired t-test, analysis of variance (ANOVA and Pearson′s correlation coefficient. Results: Mean CRP levels were significantly greater in both GAP (7.49±2.31 mg/l and CGP (4.88±1.80 mg/l groups as compared to NP (0.68±0.23 mg/l with P value <0.0001. The mean value of ABL (% was 31.58 in CGP group and 36.77 in the GAP group, the difference being statistically significant (P=0.0079. Correlation coefficient between CRP and ABL is 0.9310 in CGP, and 0.9252 in GAP, which indicates a positive correlation between both variables. Conclusion: Both forms of periodontitis are associated with increased systemic inflammatory response with aggressiveness of disease progression determining the degree of response.

  15. Botulinum toxin in masticatory muscles of the adult rat induces bone loss at the condyle and alveolar regions of the mandible associated with a bone proliferation at a muscle enthesis.

    Science.gov (United States)

    Kün-Darbois, Jean-Daniel; Libouban, Hélène; Chappard, Daniel

    2015-08-01

    In man, botulinum toxin type A (BTX) is injected in masticatory muscles for several indications such as trismus, bruxism, or masseter hypertrophy. Bone changes in the mandible following BTX injections in adult animal have therefore became a subject of interest. The aim of this study was to analyze condylar and alveolar bone changes following BTX unilateral injections in masseter and temporal muscles in adult rats. Mature male rats (n = 15) were randomized into 2 groups: control (CTRL; n = 6) and BTX group (n= 9). Rats of the BTX group received a single injection of BTX into right masseter and temporal muscles. Rats of the CTRL group were similarly injected with saline solution. Rats were sacrificed 4 weeks after injections. Masticatory muscles examination and microcomputed tomography (microCT) were performed. A significant difference of weight was found between the 2 groups at weeks 2, 3 and 4 (p muscles was observed in all BTX rats. MicroCT analysis showed significant bone loss in the right alveolar and condylar areas in BTX rats. Decrease in bone volume reached -20% for right alveolar bone and -35% for right condylar bone. A hypertrophic bone metaplasia at the digastric muscle enthesis was found on every right hemimandible in the BTX group and none in the CTRL group. BTX injection in masticatory muscles leads to a significant and major mandible bone loss. These alterations can represent a risk factor for fractures in human. The occurrence of a hypertrophic bone metaplasia at the Mus Digastricus enthesis may constitute an etiological factor for tori. PMID:25857689

  16. The emerging role of skeletal muscle oxidative metabolism as a biological target and cellular regulator of cancer-induced muscle wasting.

    Science.gov (United States)

    Carson, James A; Hardee, Justin P; VanderVeen, Brandon N

    2016-06-01

    While skeletal muscle mass is an established primary outcome related to understanding cancer cachexia mechanisms, considerable gaps exist in our understanding of muscle biochemical and functional properties that have recognized roles in systemic health. Skeletal muscle quality is a classification beyond mass, and is aligned with muscle's metabolic capacity and substrate utilization flexibility. This supplies an additional role for the mitochondria in cancer-induced muscle wasting. While the historical assessment of mitochondria content and function during cancer-induced muscle loss was closely aligned with energy flux and wasting susceptibility, this understanding has expanded to link mitochondria dysfunction to cellular processes regulating myofiber wasting. The primary objective of this article is to highlight muscle mitochondria and oxidative metabolism as a biological target of cancer cachexia and also as a cellular regulator of cancer-induced muscle wasting. Initially, we examine the role of muscle metabolic phenotype and mitochondria content in cancer-induced wasting susceptibility. We then assess the evidence for cancer-induced regulation of skeletal muscle mitochondrial biogenesis, dynamics, mitophagy, and oxidative stress. In addition, we discuss environments associated with cancer cachexia that can impact the regulation of skeletal muscle oxidative metabolism. The article also examines the role of cytokine-mediated regulation of mitochondria function, followed by the potential role of cancer-induced hypogonadism. Lastly, a role for decreased muscle use in cancer-induced mitochondrial dysfunction is reviewed. PMID:26593326

  17. Subcutaneous administration of insulin-like growth factor (IGF)-II/IGF binding protein-2 complex stimulates bone formation and prevents loss of bone mineral density in a rat model of disuse osteoporosis

    Science.gov (United States)

    Conover, Cheryl A.; Johnstone, Edward W.; Turner, Russell T.; Evans, Glenda L.; John Ballard, F. John; Doran, Patrick M.; Khosla, Sundeep

    2002-01-01

    Elevated serum levels of insulin-like growth factor binding protein-2 (IGFBP-2) and a precursor form of IGF-II are associated with marked increases in bone formation and skeletal mass in patients with hepatitis C-associated osteosclerosis. In vitro studies indicate that IGF-II in complex with IGFBP-2 has high affinity for bone matrix and is able to stimulate osteoblast proliferation. The purpose of this study was to determine the ability of the IGF-II/IGFBP-2 complex to increase bone mass in vivo. Osteopenia of the femur was induced by unilateral sciatic neurectomy in rats. At the time of surgery, 14-day osmotic minipumps containing vehicle or 2 microg IGF-II+9 microg IGFBP-2/100g body weight/day were implanted subcutaneously in the neck. Bone mineral density (BMD) measurements were taken the day of surgery and 14 days later using a PIXImus small animal densitometer. Neurectomy of the right hindlimb resulted in a 9% decrease in right femur BMD (PIGFBP-2. On the control limb, there was no loss of BMD over the 14 days and IGF-II/IGFBP-2 treatment resulted in a 9% increase in left femur BMD (PIGFBP-2 complex can prevent loss of BMD associated with disuse osteoporosis and stimulate bone formation in adult rats. Furthermore, they provide proof of concept for a novel anabolic approach to increasing bone mass in humans with osteoporosis.

  18. Treatment of an open distal tibia fracture with segmental bone loss in combination with a closed proximal tibia fracture: a case report.

    Science.gov (United States)

    Park, Jin; Yang, Kyu Hyun

    2012-08-01

    The treatment of open distal tibia fractures remains challenging, particularly when the fracture is infected and involves segmental bone loss. We report the case of a 38-year-old man who sustained an open distal tibiofibular fracture with segmental bone loss and a closed proximal tibial fracture. The fractures were initially fixed with a temporary external fixator. The open distal tibial fracture was infected, and the skin was covered after the wound became culture negative. The tibia was then internally transported with a ring external fixator; the closed fracture of the proximal tibia served as the corticotomy for internal transport without conventional corticotomy. After 5 cm internal transport, the docking site of the distal tibia was fixed with a locking plate and autogenous cancellous bone graft. Bone graft was also used to the distal tibiofibular space to achieve distal tibiofibular synostosis. We describe one treatment option for an infected open fracture of the distal tibia with segmental bone loss that is accompanied by a closed fracture of the proximal tibia. This method can treat two fractures simultaneously. PMID:22526200

  19. ASSOCIATION OF THE BONE LOSS WITH MAIN CLINICAL AND MICROBIOLOGICAL PARAMETERS IN CHRONIC PERIODONTITIS

    Directory of Open Access Journals (Sweden)

    Velitchka Dosseva-Panova

    2014-07-01

    Full Text Available Literature data have reported that certain Gram-negative anaerobe bacteria from the subgingival environment are important etiological agents of chronic periodontal disease. Based on published criteria identifying periodontal pathogens, major evidences has been shown for: Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Tannerella forsythia; moderate evidences for: Prevotella intermedia, Peptostreptococcus /Micromonas/ micros, Fusobacterium nucleatum, Eubacterium nodatum, Campylobacter rectus, and spirochetes (Treponema denticola. Microbiological data has been suggested by several studies as a useful indicator of disease progression, selection of an adjunctive antimicrobial administration, healing assessment and disease recurrence. The results of this study demonstrate statistically significant correlation between periodontal attachment loss and the prevalence of Porphyromonas gingivalis, Tannerella forsythia and Peptostreptococcus (Micromonas micros in deep periodontal pockets of severe chronic periodontitis patients.

  20. Microgravity induces pelvic bone loss through osteoclastic activity, osteocytic osteolysis, and osteoblastic cell cycle inhibition by CDKN1a/p21.

    Science.gov (United States)

    Blaber, Elizabeth A; Dvorochkin, Natalya; Lee, Chialing; Alwood, Joshua S; Yousuf, Rukhsana; Pianetta, Piero; Globus, Ruth K; Burns, Brendan P; Almeida, Eduardo A C

    2013-01-01

    Bone is a dynamically remodeled tissue that requires gravity-mediated mechanical stimulation for maintenance of mineral content and structure. Homeostasis in bone occurs through a balance in the activities and signaling of osteoclasts, osteoblasts, and osteocytes, as well as proliferation and differentiation of their stem cell progenitors. Microgravity and unloading are known to cause osteoclast-mediated bone resorption; however, we hypothesize that osteocytic osteolysis, and cell cycle arrest during osteogenesis may also contribute to bone loss in space. To test this possibility, we exposed 16-week-old female C57BL/6J mice (n = 8) to microgravity for 15-days on the STS-131 space shuttle mission. Analysis of the pelvis by µCT shows decreases in bone volume fraction (BV/TV) of 6.29%, and bone thickness of 11.91%. TRAP-positive osteoclast-covered trabecular bone surfaces also increased in microgravity by 170% (p = 0.004), indicating osteoclastic bone degeneration. High-resolution X-ray nanoCT studies revealed signs of lacunar osteolysis, including increases in cross-sectional area (+17%, p = 0.022), perimeter (+14%, p = 0.008), and canalicular diameter (+6%, p = 0.037). Expression of matrix metalloproteinases (MMP) 1, 3, and 10 in bone, as measured by RT-qPCR, was also up-regulated in microgravity (+12.94, +2.98 and +16.85 fold respectively, p<0.01), with MMP10 localized to osteocytes, and consistent with induction of osteocytic osteolysis. Furthermore, expression of CDKN1a/p21 in bone increased 3.31 fold (p<0.01), and was localized to osteoblasts, possibly inhibiting the cell cycle during tissue regeneration as well as conferring apoptosis resistance to these cells. Finally the apoptosis inducer Trp53 was down-regulated by -1.54 fold (p<0.01), possibly associated with the quiescent survival-promoting function of CDKN1a/p21. In conclusion, our findings identify the pelvic and femoral region of the mouse skeleton as an active site of rapid bone

  1. 牙周炎性牙槽骨吸收与T细胞间的关系%Periodontitis of alveolar bone loss and T cells

    Institute of Scientific and Technical Information of China (English)

    戴丽娜

    2012-01-01

    Periodontitis of alveolar bone loss is a common inflammatory destructive periodontal disease that leads to loss of the supporting structures of the teeth. T lymphocytes play an important role in the occurrence and development of periodontal disease. On one hand, T cells activated by antigens of periodontal pathogens are necessary for immune defense against periodontal pathogens. On the other hand, activated T cell is not only important regulator of activation or maturation of osteoclasts and bone resorption, but also the important damage cells in periodontal alveovar bone loss. This review elutidated the research progress on periodontitis of alveolar bone loss, T cells in the alveolar bone loss in periodontal diseases, T cells and interferon-γ on the role of osteoclasts.%牙周炎性牙槽骨吸收是常见的牙周组织炎症性破坏性疾病,是导致牙丧失的主要原因.T细胞在牙周炎的发生发展过程中发挥了重要的作用.一方面,牙周致病菌抗原活化T细胞是机体抗牙周致病菌感染所必需;另一方面,活化的T细胞是破骨细胞分化成熟和骨吸收活性的重要调节细胞,也是牙周炎性牙槽骨吸收的损伤细胞.本文就牙周炎性牙槽骨吸收,T细胞在牙周炎性牙槽骨吸收中的作用,T细胞和干扰素-γ对破骨细胞的作用等研究进展作一综述.

  2. Bone loss at implant with titanium abutments coated by soda lime glass containing silver nanoparticles: a histological study in the dog.

    Directory of Open Access Journals (Sweden)

    Arturo Martinez

    Full Text Available The aim of the present study was to evaluate bone loss at implants connected to abutments coated with a soda-lime glass containing silver nanoparticles, subjected to experimental peri-implantitis. Also the aging and erosion of the coating in mouth was studied. Five beagle dogs were used in the experiments. Three implants were placed in each mandible quadrant: in 2 of them, Glass/n-Ag coated abutments were connected to implant platform, 1 was covered with a Ti-mechanized abutment. Experimental peri-implantitis was induced in all implants after the submarginal placement of cotton ligatures, and three months after animals were euthanatized. Thickness and morphology of coating was studied in abutment cross-sections by SEM. Histology and histo-morphometric studies were carried on in undecalfied ground slides. After the induced peri-implantitis: 1.The abutment coating shown losing of thickness and cracking. 2. The histometry showed a significant less bone loss in the implants with glass/n-Ag coated abutments. A more symmetric cone of bone resorption was observed in the coated group. There were no significant differences in the peri-implantitis histological characteristics between both groups of implants. Within the limits of this in-vivo study, it could be affirmed that abutments coated with biocide soda-lime-glass-silver nanoparticles can reduce bone loss in experimental peri-implantitis. This achievement makes this coating a suggestive material to control peri-implantitis development and progression.

  3. Bone loss at implant with titanium abutments coated by soda lime glass containing silver nanoparticles: a histological study in the dog.

    Science.gov (United States)

    Martinez, Arturo; Guitián, Francisco; López-Píriz, Roberto; Bartolomé, José F; Cabal, Belén; Esteban-Tejeda, Leticia; Torrecillas, Ramón; Moya, José S

    2014-01-01

    The aim of the present study was to evaluate bone loss at implants connected to abutments coated with a soda-lime glass containing silver nanoparticles, subjected to experimental peri-implantitis. Also the aging and erosion of the coating in mouth was studied. Five beagle dogs were used in the experiments. Three implants were placed in each mandible quadrant: in 2 of them, Glass/n-Ag coated abutments were connected to implant platform, 1 was covered with a Ti-mechanized abutment. Experimental peri-implantitis was induced in all implants after the submarginal placement of cotton ligatures, and three months after animals were euthanatized. Thickness and morphology of coating was studied in abutment cross-sections by SEM. Histology and histo-morphometric studies were carried on in undecalfied ground slides. After the induced peri-implantitis: 1.The abutment coating shown losing of thickness and cracking. 2. The histometry showed a significant less bone loss in the implants with glass/n-Ag coated abutments. A more symmetric cone of bone resorption was observed in the coated group. There were no significant differences in the peri-implantitis histological characteristics between both groups of implants. Within the limits of this in-vivo study, it could be affirmed that abutments coated with biocide soda-lime-glass-silver nanoparticles can reduce bone loss in experimental peri-implantitis. This achievement makes this coating a suggestive material to control peri-implantitis development and progression. PMID:24466292

  4. Three-year experience with combined treatment with alendronate and alfacalcidol in Japanese patients with severe bone loss and osteoporotic fracture

    Directory of Open Access Journals (Sweden)

    Iwamoto J

    2011-06-01

    Full Text Available Jun Iwamoto1, Yoshihiro Sato2, Mitsuyoshi Uzawa3, Tsuyoshi Takeda1, Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Neurology, Mitate Hospital, Fukuoka, Japan; 3Department of Orthopaedic Surgery, Keiyu Orthopaedic Hospital, Gunma, JapanPurpose: Combined treatment with alendronate and alfacalcidol is more useful to increase bone mineral density (BMD than alendronate or alfacalcidol alone. A retrospective study was conducted to investigate the 3-year outcome of combined treatment with alendronate and alfacalcidol in patients with severe bone loss (BMD ≤ 50% of the young adult mean and osteoporotic fracture.Methods: Thirty-four patients (six men and 28 postmenopausal women with primary or secondary osteoporosis who had been treated with alendronate and alfacalcidol for more than 3 years were analyzed. The lumbar spine or total hip BMD and bone turnover markers were monitored, and the incidence of osteoporotic fractures was assessed.Results: The urinary level of cross-linked N-terminal telopeptides of type I collagen and serum level of alkaline phosphatase significantly decreased (-42.5% at 3 months and -18.9% at 3 years, and the lumbar spine BMD, but not the total hip BMD, significantly increased (14.8% at 3 years, compared with the baseline values. However, the incidence of vertebral and nonvertebral fractures was 26.5% and 2.9%, respectively, suggesting a high incidence of vertebral fractures.Conclusion: The results of the present study suggest that combined treatment with alendronate and alfacalcidol may be useful to reduce bone turnover and increase the lumbar spine BMD in patients with severe bone loss and osteoporotic fracture. However, its efficacy against vertebral fractures appears not to be sufficient. Thus, anabolic agents such as teriparatide should be taken into consideration as first-line drugs in patients with severe osteoporosis.Keywords: osteoporosis

  5. Intravenous administration of bone marrow mononuclear cells alleviates hearing loss after transient cochlear ischemia through paracrine effects.

    Science.gov (United States)

    Takagi, Taro; Yoshida, Tadashi; Okada, Masahiro; Hata, Ryuji; Hato, Naohito; Gyo, Kiyofumi; Hakuba, Nobuhiro

    2014-05-16

    Bone marrow mononuclear cells (BMMCs) are known to enhance recovery from ischemic insults by secreting angiogenic factors and inducing the expression of angiogenic factors from host tissues. Therefore, the transplantation of BMMCs is considered a potential approach to promoting the repair of ischemic damaged organs. Here, we investigated the influence of BMMCs on progressive hair cell degeneration after transient cochlear ischemia in gerbils. Transient cochlear ischemia was produced by extracranial occlusion of the bilateral vertebral arteries immediately before their entry into the transverse foramen of the cervical vertebra. An intravenous injection of BMMCs prevented ischemia-induced hair cell degeneration and ameliorated hearing impairment. A tracking study showed that BMMCs injected into the femoral vein were limited in the spiral artery of the cochlea, suggesting that, although transplanted BMMCs were retained within the spiral ganglion area of the cochlea, they were neither transdifferentiated into cochlear cells nor fused with the injured hair cells and supporting cells in the organ of Corti to restore their functions. We also showed that the protein level of neurotrophin-3 and glial cell line-derived neurotrophic factor in the organ of Corti was upregulated after treatment with BMMCs. These results suggested that BMMCs have therapeutic potential possibly through paracrine effects. Thus, we propose the use of BMMCs as a potential new therapeutic strategy for hearing loss. PMID:24840930

  6. Analysis of Bone Density in Patients with Urolithiasis; Role of Hypercalciuria in Bone Loss: Do These Patients Need a Low-Calcium Diet?

    OpenAIRE

    Ali-Asghar Yarmohammadi; Mahmood Molaei; Samira Yaghoobi; Fateme Ahmadi

    2008-01-01

    Introduction: Kidney stone is a common urologic complaint. In this study, bone density in stone formers was compared with that of a control group; bone density of stone formers was also analyzed based on age, sex and stone configuration. Methods: In a group of 85 patients with upper urinary calcium stones and 85 healthy people, variables such as age, height, weight, BMI, T-score and Z-score results of bone densitometry of lumbar vertebrae (L2-L4) and femoral neck were recorded. The serum leve...

  7. Conventional radiography requires a MRI-estimated bone volume loss of 20% to 30% to allow certain detection of bone erosions in rheumatoid arthritis metacarpophalangeal joints

    DEFF Research Database (Denmark)

    Ejbjerg, B.; Vestergaard, Aage Steen; Jacobsen, S.; Thomsen, H.S.; Østergaard, Mikkel

    2006-01-01

    The aim of this study was to demonstrate the ability of conventional radiography to detect bone erosions of different sizes in metacarpophalangeal (MCP) joints of rheumatoid arthritis (RA) patients using magnetic resonance imaging (MRI) as the standard reference. A 0.2 T Esaote dedicated extremity...... MRI unit was used to obtain axial and coronal T1-weighted gradient echo images of the dominant 2nd to 5th MCP joints of 69 RA patients. MR images were obtained and evaluated for bone erosions according to the OMERACT recommendations. Conventional radiographs of the 2nd to 5th MCP joints were obtained...... in posterior-anterior projection and evaluated for bone erosions. The MRI and radiography readers were blinded to each other's assessments. Grade 1 MRI erosions (1% to 10% of bone volume eroded) were detected by radiography in 20%, 4%, 7% and 13% in the 2nd, 3rd, 4th and 5th MCP joint, respectively...

  8. Interaction between muscle and bone, and improving the effects of electrical muscle stimulation on amyotrophy and bone loss in a denervation rat model via sciatic neurectomy

    OpenAIRE

    Feng, Bo; Wu, Wei; WANG Hua; Wang, Junchen; Huang, DongYa; Cheng, Ling

    2016-01-01

    The side-to-side difference in bone mineral content and soft tissue composition of extremities and their associations have been observed in patients with stroke and the results are inconsistent. The aim of the present study was to investigate the interaction between bone mineral content (BMC), lean mass (LM) and fat mass (FM) in the paretic extremities in patients following stroke and to determine the effectiveness of electrical muscle stimulation (EMS) following sciatic neurectomy (SN) in ra...

  9. Involvement of periostin-sclerostin-Wnt/β-catenin signaling pathway in the prevention of neurectomy-induced bone loss by naringin.

    Science.gov (United States)

    Lv, Jianwei; Sun, Xiaolei; Ma, Jianxiong; Ma, Xinlong; Xing, Guosheng; Wang, Ying; Sun, Lei; Wang, Jianbao; Li, Fengbo; Li, Yanjun

    2015-12-25

    Periostin has an essential role in mechanotransduction in bone. Naringin, a natural flavonoid, has been evidenced for its osteoprotective role in osteoporosis, while its mechanism is far from clear. Here we show that down-regulation of periostin, and up-regulation of its downstream sclerostin and inactivation of Wnt/β-catenin signaling were implicated in neurectomy-induced bone loss. Naringin could up-regulate periostin and prevent neurectomy-induced deterioration of BMD, trabecular microstructure and bone mechanical characteristics. In conclusion, naringin could prevent progress of disuse osteoporosis in rats, which may be mediated by increased periostin expression and subsequently inhibition of sclerostin and activation of Wnt/β-catenin signaling pathways. PMID:26541456

  10. Bone Marrow Adipose Tissue: A New Player in Cancer Metastasis to Bone

    Science.gov (United States)

    Morris, Emma V.; Edwards, Claire M.

    2016-01-01

    The bone marrow is a favored site for a number of cancers, including the hematological malignancy multiple myeloma, and metastasis of breast and prostate cancer. This specialized microenvironment is highly supportive, not only for tumor growth and survival but also for the development of an associated destructive cancer-induced bone disease. The interactions between tumor cells, osteoclasts and osteoblasts are well documented. By contrast, despite occupying a significant proportion of the bone marrow, the importance of bone marrow adipose tissue is only just emerging. The ability of bone marrow adipocytes to regulate skeletal biology and hematopoiesis, combined with their metabolic activity, endocrine functions, and proximity to tumor cells means that they are ideally placed to impact both tumor growth and bone disease. This review discusses the recent advances in our understanding of how marrow adipose tissue contributes to bone metastasis and cancer-induced bone disease.

  11. Establishment of a murine model for radiation-induced bone loss using micro-computed tomography in adult C3H/HeN mice

    International Nuclear Information System (INIS)

    Bone changes are common sequela of radiation therapy for cancer. The purpose of this study was to establish an experimental model of radiation-induced bone loss in adult mice using micro-computed tomography (µCT). The extent of changes following 2 Gy gamma irradiation (2 Gy/min) was studied at 4, 8, 12 or 16 weeks after exposure. Adult mice that received 1, 2, 4 or 6 Gy of gamma-rays were examined 12 weeks after irradiation. Tibiae were analyzed using µCT. Serum markers and biomechanical properties were measured and the osteoclast surface was examined. A significant loss of trabecular bone in tibiae was evident 12 weeks after exposure. Measurements performed after irradiation showed a dose-related decrease in trabecular bone volume fraction (BV/TV) and bone mineral density (BMD), respectively. The best-fitting dose-response curves were linear-quadratic. Taking the controls into accounts, the lines of best fit were as follows: BV/TV (%)= -0.071D(2)-1.799D+18.835 (r (2)=0.968, D=dose in Gy) and BMD (mg/cm(3)) = -3.547D(2)-14.8D+359.07 (r (2)=0.986, D=dose in Gy). Grip strength and body weight did not differ among the groups. No dose-dependent differences were apparent among the groups with regard to mechanical and anatomical properties of tibia, serum biochemical markers and osteoclast activity. The findings provide the basis required for better understanding of the results that will be obtained in any further studies of radiation-induced bone responses. (author)

  12. Mutan: A mixed linkage α-[(1,3)- and (1,6)]-d-glucan from Streptococcus mutans, that induces osteoclast differentiation and promotes alveolar bone loss.

    Science.gov (United States)

    Kwon, Hyun-Jung; Kim, Jung Min; Han, Kook-Il; Jung, Eui-Gil; Kim, Yong Hyun; Patnaik, Bharat Bhusan; Yoon, Mi Sook; Chung, Sung Kyun; Kim, Wan Jong; Han, Man-Deuk

    2016-02-10

    Mutan is an extracellular polysaccharide of Streptococcus mutans (S. mutans) that consists of α-(1,3)-linked glucose residues in main chains and α-(1,6) bonds in side chains. In the present study, mutan was isolated from S. mutans, and its structural characteristics were determined using Fourier-transform infrared spectroscopy (FT-IR) and (13)C nuclear magnetic resonance (NMR) spectroscopy. The effects of mutan on RANKL-induced osteoclast differentiation in RAW 264.7 cells were examined. Furthermore, microCT and morphometric analyses were used to determine the contribution of mutan to alveolar bone loss in the maxilla of a rat periodontitis model. Mutan increased (more than 2-fold) RANKL-induced osteoclast differentiation in a dose-dependent manner. Mutan also enhanced the alveolar bone loss in the rat maxilla 2.3-fold. In mutan-treated rats, the bone mineral density, bone volume, trabecular number, and trabecular thickness decreased, whereas trabecular separation significantly increased. In addition, mutan and lipopolysaccharide (LPS) induced similar microarray profiles in RAW 264.7 cells. A total of 43 genes related to osteoclastogenesis were differentially expressed after either mutan or LPS treatment. Five-fold increases in the expression of several genes, including IL-1β, IL-1α, IL-6, and chemokine ligands, were observed in mutan-treated RAW 264.7 cells. These results suggest a molecular mechanism for the inflammation induced by S. mutans during the establishment of periodontal disease. PMID:26686164

  13. Outcome of revision total knee arthroplasty with the use of trabecular metal cone for reconstruction of severe bone loss at the proximal tibia

    DEFF Research Database (Denmark)

    Jensen, Claus L; Olsen, Nikolaj Winther; Schrøder, Henrik M; Petersen, Michael M

    2014-01-01

    technology (TMT) cones for the reconstruction of tibial bone loss at the time of rTKA. METHODS: Thirty-six patients had rTKA with the use of a TMT Cone. Bone loss was classified according to the AORI classification and 25% of the patients suffered from T3 AORI defects and 75% of the patients from T2 AORI...... from 42 to 77 points (p<0.0005) and 19 to 63 points (p<0.0005) respectively. Twenty-seven patients (follow-up 44 months (range 12-72 months)) showed no signs of radiological loosening of rTKA components. CONCLUSION: Based on our study, it was concluded that the use of TMT Cones provided an effective...

  14. Are patterns of bone loss in anorexic and postmenopausal women similar? Preliminary results using high resolution peripheral computed tomography.

    Science.gov (United States)

    Milos, Gabriella; Häuselmann, Hans-Jörg; Krieg, Marc-Antoine; Rüegsegger, Peter; Gallo, Luigi M

    2014-01-01

    This study intended to compare bone density and architecture in three groups of women: young women with anorexia nervosa (AN), an age-matched control group of young women, and healthy late postmenopausal women. Three-dimensional peripheral quantitative high resolution computed-tomography (HR-pQCT) at the ultradistal radius, a technology providing measures of cortical and trabecular bone density and microarchitecture, was performed in the three cohorts. Thirty-six women with AN aged 18-30 years (mean duration of AN: 5.8 years), 83 healthy late postmenopausal women aged 70-81 as well as 30 age-matched healthy young women were assessed. The overall cortical and trabecular bone density (D100), the absolute thickness of the cortical bone (CTh), and the absolute number of trabecules per area (TbN) were significantly lower in AN patients compared with healthy young women. The absolute number of trabecules per area (TbN) in AN and postmenopausal women was similar, but significantly lower than in healthy young women. The comparison between AN patients and post-menopausal women is of interest because the latter reach bone peak mass around the middle of the fertile age span whereas the former usually lose bone before reaching optimal bone density and structure. This study shows that bone mineral density and bone compacta thickness in AN are lower than those in controls but still higher than those in postmenopause. Bone compacta density in AN is similar as in controls. However, bone inner structure in AN is degraded to a similar extent as in postmenopause. This last finding is particularly troubling. PMID:24084384

  15. The quantification of glenoid bone loss in anterior shoulder instability; MR-arthro compared to 3D-CT

    International Nuclear Information System (INIS)

    The purpose of this study is to investigate if magnetic resonance imaging with intra-articular contrast (MR-arthro) is as reliable as three-dimensionally reconstructed computed tomography imaging (3D-CT) in quantifying the glenoid bone loss in patients with anterior shoulder instability. Thirty-five patients were included. Sagittal MR-arthro and 3D-CT images of the glenoid surface were obtained pre-operatively. Two observers measured these images twice with OsiriX software in a randomized and blinded way. The intraclass correlations (ICC) of the intra- and inter-observer reliability within one method and an additional Bland-Altman plot for calculating agreement between the two methods were obtained. The joint estimates of the intra-observer reliability, taking into account the data from both observer A and B, for 3D-CT and MR-arthro were good to excellent. The intra-observer reliability was 0.938 (95 % CI: 0.879, 0.968) for 3D-CT and 0.799 (95 % CI: 0.639, 0.837) for MR-arthro. The inter-observer reliability between the two observers within one method (3D-CT or MR-arthro) was moderate to good. 3D-CT: 0.724 (95 % CI: 0.236, 0.886) and MR-arthro: 0.534 (95 % CI: 0.128, 0.762). Comparing both the 3D-CT and MR-arthro method, a Bland-Altman plot showed satisfying differences with the majority of outcomes (89 %) within 1 SD. Good to excellent intra- and moderate to good inter-observer correlations and a satisfying Bland-Altman plot when compared to 3D-CT show tendencies that MR-arthro is reliable and valid for measuring bony defects of the glenoid. (orig.)

  16. High-fat-diet-induced weight gain ameliorates bone loss without exacerbating AβPP processing and cognition in female APP/PS1 mice

    Directory of Open Access Journals (Sweden)

    Yunhua ePeng

    2014-08-01

    Full Text Available Osteoporosis is negatively correlated with body mass, whereas both osteoporosis and weight loss occur at higher incidence during the progression of Alzheimer’s disease (AD than the age-matched non-dementia individuals. Given that there is no evidence that overweight associated with AD-type cognitive dysfunction, we hypothesized that moderate weight gain might have a protective effect on the bone loss in AD without exacerbating cognitive dysfunction. In the present study, feeding a high-fat-diet (HFD, 45% calorie from fat to female APP/PS1 transgenic mice, an AD animal model, induced weight gain. The bone mineral density, microarchitecture, and biomechanical properties of the femurs were then evaluated. The results showed that the middle-aged female APP/PS1 transgenic mice were susceptible to osteoporosis of the femoral bones and that weight gain significantly enhanced bone mass and mechanical properties. Notably, HFD was not detrimental to brain insulin signaling and AβPP processing, as well as to exploration ability and working, learning and memory performance of the transgenic mice measured by T maze and water maze, compared with the mice fed a normal fat diet (10% calorie from fat. In addition, the circulating levels of leptin but not estradiol were remarkably elevated in HFD-treated mice. These results suggest that a body weight gain induced by the HFD feeding regimen significantly improved bone mass in female APP/PS1 mice with no detriments to exploration ability and spatial memory, most likely via the action of elevated circulating leptin.

  17. Murine Lung Cancer Induces Generalized T Cell Exhaustion

    Science.gov (United States)

    Mittal, Rohit; Chen, Ching-Wen; Lyons, John D; Margoles, Lindsay M; Liang, Zhe; Coopersmith, Craig M; Ford, Mandy L

    2015-01-01

    Background Cancer is known to modulate tumor-specific immune responses by establishing a micro-environment that leads to the upregulation of T cell inhibitory receptors, resulting in the progressive loss of function and eventual death of tumor-specific T cells. However, the ability of cancer to impact the functionality of the immune system on a systemic level is much less well characterized. Because cancer is known to predispose patients to infectious complications including sepsis, we hypothesized that the presence of cancer alters pathogen-directed immune responses on a systemic level. Materials and Methods We assessed systemic T cell coinhibitory receptor expression, cytokine production, and apoptosis in mice with established subcutaneous lung cancer tumors and in unmanipulated mice without cancer. Results Results indicated that the frequencies of PD-1+, BTLA+, and 2B4+ cells in both the CD4+ and CD8+ T cell compartments were increased in mice with localized cancer relative to non-cancer controls, and the frequencies of both CD4+ and CD8+ T cells expressing multiple different inhibitory receptors was increased in cancer animals relative to non-cancer controls. Additionally, 2B4+CD8+ T cells in cancer mice exhibited reduced IL-2 and IFN-γ, while BTLA+CD8+ T cells in cancer mice exhibited reduced IL-2 and TNF. Conversely, CD4+ T cells in cancer animals demonstrated an increase in the frequency of Annexin V+ apoptotic cells. Conclusion Taken together, these data suggest that the presence of cancer induces systemic T cell exhaustion and generalized immune suppression. PMID:25748104

  18. Strontium fructose 1,6-diphosphate prevents bone loss in a rat model of postmenopausal osteoporosis via the OPG/RANKL/RANK pathway

    Science.gov (United States)

    Ma, Bo; Zhang, Qi; Wu, Di; Wang, Yong-lu; Hu, Ying-ying; Cheng, Yan-ping; Yang, Zhen-dong; Zheng, Ya-ya; Ying, Han-Jie

    2012-01-01

    Aim: To evaluate the protective effects of strontium fructose 1,6-diphosphate (FDP-Sr), a novel strontium salt that combined fructose 1,6-diphosphate (FDP) with strontium, on bone in an ovariectomy-induced model of bone loss. Methods: Eighty female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated. Three months later, the rats were assigned to six groups (10 for each): sham-operated, OVX control, OVX+FDP-Sr (110, 220, or 440 mg/kg), or OVX+strontium ranelate (SR, 180 mg/kg). Drugs were administered orally for 3 months. When the treatment was terminated, the following parameters were assessed: bone mineral density (BMD), the biomechanical properties of the femur and lumbar vertebrae, trabecular histomorphology, serum phosphorus, calcium, bone-specific alkaline phosphatase (B-ALP), tartrate-resistant acid phosphatase 5b (TRACP5b), N-telopeptide of type I collagen (NTx) and a series of markers for oxidative stress. Receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) levels in serum were measured using ELISA and their gene expression levels in the bone were measured using R-T PCR. Results: Treatment with FDP-Sr (220 or 440 mg/kg) or SR (180 mg/kg) significantly increased the BMD and improved the bone microarchitecture and bone strength in OVX rats. The treatments also decreased in the levels of H2O2 and MDA, restored the CAT level in serum and bone marrow, increased the serum B-ALP and decreased NTx and TRACP 5b in OVX rats. Treatment with FDP-Sr decreased the RANKL level, and increased the OPG level in serum in a dose-dependent manner. It also significantly down-regulated the RANKL expression and up-regulated OPG expression in bone marrow. Conclusion: FDP-Sr may be an effectve treatment for postmenopausal osteoporosis that acts, in part, via a decrease in osteoclastogenesis through the OPG\\RANKL\\RANK pathway. PMID:22426695

  19. Critical appraisal of denosumab in the treatment and prevention of postmenopausal osteoporosis and bone loss in patients undergoing hormone ablation

    Directory of Open Access Journals (Sweden)

    David L Kendler

    2010-09-01

    Full Text Available David L Kendler1, Kenneth Shawn Davison21Prohealth Clinical Research, University of British Columbia, Vancouver, British Columbia, Canada; 2Department of Medicine, Division of Immunology and Rheumatology, Laval University, Quebec, CanadaAbstract: Antiresorptive therapies are the mainstay for treating patients with excessively high rates of bone resorption. The receptor activator of nuclear factor-κB (RANK ligand (RANKL, secreted by osteoblasts, binds to the RANK receptor on the surface of preosteoclasts and osteoclasts to elicit osteoclast formation, survival, and activity. Osteoprotegerin, also secreted by the osteoblast, acts as a decoy RANK receptor reducing RANKL binding to RANK and reducing bone resorption. Denosumab, a fully human monoclonal antibody, has a high affinity and specificity for RANKL. Denosumab rapidly decreases bone resorption and increases bone mineral density (BMD at the lumbar spine, total hip, femoral neck, and one-third radius sites. In head-to-head trials, denosumab increased BMD and decreased bone resorption to a significantly greater degree than alendronate. In postmenopausal osteoporotic women, denosumab decreased the risk of vertebral fracture (68%, nonvertebral fracture (20%, and hip fracture (40% over 36 months, compared to placebo. In patients with iatrogenic hypogonadism, denosumab rapidly decreased markers of bone resorption and increased BMD. In men treated with GnRH agonist for prostate cancer, treatment with denosumab led to a 62% decreased risk of new vertebral fracture over 3 years, as compared to placebo. In all trials completed to date, comparable adverse events have been observed in both denosumab and placebo or treatment groups.Keywords: medication adherence, fracture, bone mineral density, bone turnover markers

  20. Minimally invasive piezosurgery for a safe placement of blade dental implants in jaws with severe bone loss

    OpenAIRE

    Rossi, F; M.E. Pasqualini; L. Grivet Brancot; Colombo, D.; Corradini, M.; LORÈ, B.; L. Calabrese

    2014-01-01

    Aim :Severe atrophies of edentulous jaws require major reconstructive bone surgery in order to allow the placement of root-form implants with standard diameter. These bone augmentation techniques represent the best option reported in the literature, but they are often rejected by patients because of their high economic and biological costs in addition to the possibility of failure in the short and/or long term. In the maxilla regenerative methods (onlay, inlay, and distraction) have high succ...

  1. N-acetylcysteine increases the frequency of bone marrow pro-B/pre-B cells, but does not reverse cigarette smoking-induced loss of this subset.

    Directory of Open Access Journals (Sweden)

    Victoria L Palmer

    Full Text Available BACKGROUND: We previously showed that mice exposed to cigarette smoke for three weeks exhibit loss of bone marrow B cells at the Pro-B-to-pre-B cell transition, but the reason for this is unclear. The antioxidant N-acetylcysteine (NAC, a glutathione precursor, has been used as a chemopreventive agent to reduce adverse effects of cigarette smoke exposure on lung function. Here we determined whether smoke exposure impairs B cell development by inducing cell cycle arrest or apoptosis, and whether NAC treatment prevents smoking-induced loss of developing B cells. METHODOLOGY/PRINCIPAL FINDINGS: Groups of normal mice were either exposed to filtered room air or cigarette smoke with or without concomitant NAC treatment for 5 days/week for three weeks. Bone marrow B cell developmental subsets were enumerated, and sorted pro-B (B220(+CD43(+ and pre-B (B220(+CD43(- cell fractions were analyzed for cell cycle status and the percentage of apoptotic cells. We find that, compared to sham controls, smoke-exposed mice have ∼60% fewer pro-B/pre-B cells, regardless of NAC treatment. Interestingly, NAC-treated mice show a 21-38% increase in total bone marrow cellularity and lymphocyte frequency and about a 2-fold increase in the pro-B/pre-B cell subset, compared to sham-treated controls. No significant smoking- or NAC-dependent differences were detected in frequency of apoptotic cells or the percentage cells in the G1, S, or G2 phases of the cycle. CONCLUSIONS/SIGNIFICANCE: The failure of NAC treatment to prevent smoking-induced loss of bone marrow pre-B cells suggests that oxidative stress is not directly responsible for this loss. The unexpected expansion of the pro-B/pre-B cell subset in response to NAC treatment suggests oxidative stress normally contributes to cell loss at this developmental stage, and also reveals a potential side effect of therapeutic administration of NAC to prevent smoking-induced loss of lung function.

  2. Transplantation of human umbilical cord blood-derived mesenchymal stem cells or their conditioned medium prevents bone loss in ovariectomized nude mice.

    Science.gov (United States)

    An, Jee Hyun; Park, Hyojung; Song, Jung Ah; Ki, Kyung Ho; Yang, Jae-Yeon; Choi, Hyung Jin; Cho, Sun Wook; Kim, Sang Wan; Kim, Seong Yeon; Yoo, Jeong Joon; Baek, Wook-Young; Kim, Jung-Eun; Choi, Soo Jin; Oh, Wonil; Shin, Chan Soo

    2013-03-01

    Umbilical cord blood (UCB) has recently been recognized as a new source of mesenchymal stem cells (MSCs) for use in stem cell therapy. We studied the effects of systemic injection of human UCB-MSCs and their conditioned medium (CM) on ovariectomy (OVX)-induced bone loss in nude mice. Ten-week-old female nude mice were divided into six groups: Sham-operated mice treated with vehicle (Sham-Vehicle), OVX mice subjected to UCB-MSCs (OVX-MSC), or human dermal fibroblast (OVX-DFB) transplantation, OVX mice treated with UCB-MSC CM (OVX-CM), zoledronate (OVX-Zol), or vehicle (OVX-Vehicle). Although the OVX-Vehicle group exhibited significantly less bone mineral density (BMD) gain compared with the Sham-Vehicle group, transplantation of hUCB-MSCs (OVX-MSC group) has effectively prevented OVX-induced bone mass attenuation. Notably, the OVX-CM group also showed BMD preservation comparable to the OVX-MSC group. In addition, microcomputed tomography analysis demonstrated improved trabecular parameters in both the OVX-MSC and OVX-CM groups compared to the OVX-Vehicle or OVX-DFB group. Histomorphometric analysis showed increased bone formation parameters, accompanied by increased serum procollagen type-I N-telopeptide levels in OVX-MSC and OVX-CM mice. However, cell-trafficking analysis failed to demonstrate engraftment of MSCs in bone tissue 48 h after cell infusion. In vitro, hUCB-MSC CM increased alkaline phosphatase (ALP) activity in human bone marrow-derived MSCs and mRNA expression of collagen type 1, Runx2, osterix, and ALP in C3H10T1/2 cells. Furthermore, hUCB-MSC CM significantly increased survival of osteocyte-like MLO-Y4 cells, while it inhibited osteoclastic differentiation. To summarize, transplantation of hUCB-MSCs could effectively prevent OVX-mediated bone loss in nude mice, which appears to be mediated by a paracrine mechanism rather than direct engraftment of the MSCs. PMID:23215868

  3. Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women.

    Science.gov (United States)

    Koitaya, Noriko; Sekiguchi, Mariko; Tousen, Yuko; Nishide, Yoriko; Morita, Akemi; Yamauchi, Jun; Gando, Yuko; Miyachi, Motohiko; Aoki, Mami; Komatsu, Miho; Watanabe, Fumiko; Morishita, Koji; Ishimi, Yoshiko

    2014-03-01

    Menaquinone-4 (MK-4) administered at a pharmacological dosage of 45 mg/day has been used for the treatment of osteoporosis in Japan. However, it is not known whether a lower dose of MK-4 supplementation is beneficial for bone health in healthy postmenopausal women. The aim of this study was to examine the long-term effects of 1.5-mg daily supplementation of MK-4 on the various markers of bone turnover and bone mineral density (BMD). The study was performed as a randomized, double-blind, placebo-controlled trial. The participants (aged 50-65 years) were randomly assigned to one of two groups according to the MK-4 dose received: the placebo-control group (n = 24) and the 1.5-mg MK-4 group (n = 24). The baseline concentrations of undercarboxylated osteocalcin (ucOC) were high in both groups (>5.1 ng/ml). After 6 and 12 months, the serum ucOC concentrations were significantly lower in the MK-4 group than in the control group. In the control group, there was no significant change in serum pentosidine concentrations. However, in the MK-4 group, the concentration of pentosidine at 6 and 12 months was significantly lower than that at baseline. The forearm BMD was significantly lower after 12 months than at 6 months in the control group. However, there was no significant decrease in BMD in the MK-4 group during the study period. These results suggest that low-dose MK-4 supplementation for 6-12 months improved bone quality in the postmenopausal Japanese women by decreasing the serum ucOC and pentosidine concentrations, without any substantial adverse effects. PMID:23702931

  4. SH3BP2 gain-of-function mutation exacerbates inflammation and bone loss in a murine collagen-induced arthritis model.

    Directory of Open Access Journals (Sweden)

    Tomoyuki Mukai

    Full Text Available OBJECTIVE: SH3BP2 is a signaling adapter protein which regulates immune and skeletal systems. Gain-of-function mutations in SH3BP2 cause cherubism, characterized by jawbone destruction. This study was aimed to examine the role of SH3BP2 in inflammatory bone loss using a collagen-induced arthritis (CIA model. METHODS: CIA was induced in wild-type (Sh3bp2(+/+ and heterozygous P416R SH3BP2 cherubism mutant knock-in (Sh3bp2(KI/+ mice, an SH3BP2 gain-of-function model. Severity of the arthritis was determined by assessing the paw swelling and histological analyses of the joints. Micro-CT analysis was used to determine the levels of bone loss. Inflammation and osteoclastogenesis in the joints were evaluated by quantitating the gene expression of inflammatory cytokines and osteoclast markers. Furthermore, involvement of the T- and B-cell responses was determined by draining lymph node cell culture and measurement of the serum anti-mouse type II collagen antibody levels, respectively. Finally, roles of the SH3BP2 mutation in macrophage activation and osteoclastogenesis were determined by evaluating the TNF-α production levels and osteoclast formation in bone marrow-derived M-CSF-dependent macrophage (BMM cultures. RESULTS: Sh3bp2(KI/+ mice exhibited more severe inflammation and bone loss, accompanying an increased number of osteoclasts. The mRNA levels for TNF-α and osteoclast marker genes were higher in the joints of Sh3bp2(KI/+ mice. Lymph node cell culture showed that lymphocyte proliferation and IFN-γ and IL-17 production were comparable between Sh3bp2(+/+ and Sh3bp2(KI/+ cells. Serum anti-type II collagen antibody levels were comparable between Sh3bp2(+/+ and Sh3bp2(KI/+ mice. In vitro experiments showed that TNF-α production in Sh3bp2(KI/+ BMMs is elevated compared with Sh3bp2(+/+ BMMs and that RANKL-induced osteoclastogenesis is enhanced in Sh3bp2(KI/+ BMMs associated with increased NFATc1 nuclear localization. CONCLUSION: Gain-of-function of

  5. Cytokines and bone loss in a 5-year longitudinal study--hormone replacement therapy suppresses serum soluble interleukin-6 receptor and increases interleukin-1-receptor antagonist: the Danish Osteoporosis Prevention Study

    DEFF Research Database (Denmark)

    Abrahamsen, Bo; Bonnevie-Nielsen, V; Ebbesen, E N; Gram, J; Beck-Nielsen, H

    2000-01-01

    The proinflammatory cytokines interleukin-1 beta (IL-1 beta) and IL-6 may play a central role in the acceleration of postmenopausal bone loss, but observational studies have led to contradictory results. Estrogen-dependent changes in the production of IL-1 receptor antagonist (IL-1ra) and the.......16; p = 0.17). In conclusion, serum IL-1ra and sIL-6R are influenced by HRT and are associated with the rate of bone loss in perimenopausal women....

  6. The effect of smoking on survival and bone loss of implants with a fluoride-modified surface: a 2-year retrospective analysis of 1106 implants placed in daily practice

    OpenAIRE

    D'Haese, Jan; Bruyn, Hugo De

    2012-01-01

    Aim: To compare survival and peri-implant bone loss of implants with a fluoride-modified surface in smokers and nonsmokers. Materials and Methods: Patient files of all patients referred for implant treatment from November 2004 to 2007 were scrutinized. All implants were placed by the same experienced surgeon (BC). The only inclusion criterion was a follow-up time of at least 2 years. Implant survival and bone loss were assessed by an external calibrated examiner (SV) comparing digital pe...

  7. Transplantation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells or Their Conditioned Medium Prevents Bone Loss in Ovariectomized Nude Mice

    OpenAIRE

    An, Jee Hyun; Park, Hyojung; Song, Jung Ah; Ki, Kyung Ho; Yang, Jae-Yeon; Choi, Hyung Jin; Cho, Sun Wook; Kim, Sang Wan; Kim, Seong Yeon; Yoo, Jeong Joon; Baek, Wook-Young; Kim, Jung-Eun; Choi, Soo Jin; Oh, Wonil; Shin, Chan Soo

    2013-01-01

    Umbilical cord blood (UCB) has recently been recognized as a new source of mesenchymal stem cells (MSCs) for use in stem cell therapy. We studied the effects of systemic injection of human UCB-MSCs and their conditioned medium (CM) on ovariectomy (OVX)-induced bone loss in nude mice. Ten-week-old female nude mice were divided into six groups: Sham-operated mice treated with vehicle (Sham-Vehicle), OVX mice subjected to UCB-MSCs (OVX-MSC), or human dermal fibroblast (OVX-DFB) transplantation, ...

  8. Bone Loss at Implant with Titanium Abutments Coated by Soda Lime Glass Containing Silver Nanoparticles: A Histological Study in the Dog

    OpenAIRE

    Martinez, Arturo; Guitián, Francisco; López-Píriz, R.; Bartolomé, J. F.; Cabal, B.; Esteban-Tejeda, L.; Torrecillas, Ramón; J. S. Moya

    2014-01-01

    The aim of the present study was to evaluate bone loss at implants connected to abutments coated with a soda-lime glass containing silver nanoparticles, subjected to experimental peri-implantitis. Also the aging and erosion of the coating in mouth was studied. Five beagle dogs were used in the experiments. Three implants were placed in each mandible quadrant: in 2 of them, Glass/n-Ag coated abutments were connected to implant platform, 1 was covered with a Ti-mechanized abutment. Experimental...

  9. Trimegestone in a low-dose, continuous-combined hormone therapy regimen prevents bone loss in osteopenic postmenopausal women

    DEFF Research Database (Denmark)

    Warming, Lise; Ravn, Pernille; Spielman, Danièle;

    2004-01-01

    OBJECTIVE: To determine the efficacy of estrogen + progestogen therapy with 1 mg 17beta-estradiol and 0.125 mg trimegestone in the prevention of postmenopausal osteoporosis. DESIGN: For this study, 360 healthy, postmenopausal women with osteopenia [lumbar spine bone mineral density (BMD) between ...

  10. Computer-aided and manual quantifications of MRI synovitis, bone marrow edema-like lesions, erosion and cartilage loss in rheumatoid arthritis of the wrist

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Haitao [The First Affiliated Hospital of Chongqing Medical University, Department of Radiology, Chongqing (China); University of California, San Francisco (UCSF), Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Rivoire, Julien; Hoppe, Michael; Link, Thomas M.; Li, Xiaojuan [University of California, San Francisco (UCSF), Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Srikhum, Waraporn [University of California, San Francisco (UCSF), Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Thammasat University, Department of Radiology, Pathumthani (Thailand); Imboden, John [San Francisco General Hospital, University of California, Department of Medicine, San Francisco and Division of Rheumatology, San Francisco, CA (United States)

    2014-12-10

    To investigate the reliability and validity of computer-aided automated and manual quantification as well as semiquantitative analysis for MRI synovitis, bone marrow edema-like lesions, erosion and cartilage loss of the wrist in rheumatoid arthritis (RA) compared to the OMERACT-RAMRIS. Wrist MRI was performed at 3 T in 16 patients with RA. Synovial volume and perfusion, bone marrow edema-like lesion (BMEL) volume, signal intensity and perfusion, and erosion dimensions were measured manually and using an in-house-developed automated software algorithm; findings were correlated with the OMERAC-RAMRIS gradings. In addition, a semiquantitative MRI cartilage loss score system was developed. Intraclass correlation coefficients (ICCs) were used to test the reproducibility of these quantitative and semiquantitative techniques. Spearman correlation coefficients were calculated between lesion quantifications and RAMRIS and between the MRI cartilage score and radiographic Sharp van der Heijde joint space narrowing scores. The intra- and interobserver ICCs were excellent for synovial, BMEL and erosion quantifications and cartilage loss grading (all >0.89). The synovial volume, BMEL volume and signal intensity, and erosion dimensions were significantly correlated with the corresponding RAMRIS (r = 0.727 to 0.900, p < 0.05). Synovial perfusion parameter maximum enhancement (Emax) was significantly correlated with synovitis RAMRIS (r = 0.798). BMEL perfusion parameters were not correlated with the RAMRIS BME score. Cartilage loss gradings from MRI were significantly correlated with the Sharp joint space narrowing scores (r = 0.635, p = 0.008). The computer-aided, manual and semiquantitative methods presented in this study can be used to evaluate MRI pathologies in RA with excellent reproducibility. Significant correlations with standard RAMRIS were found in the measurements using these methods. (orig.)

  11. Computer-aided and manual quantifications of MRI synovitis, bone marrow edema-like lesions, erosion and cartilage loss in rheumatoid arthritis of the wrist

    International Nuclear Information System (INIS)

    To investigate the reliability and validity of computer-aided automated and manual quantification as well as semiquantitative analysis for MRI synovitis, bone marrow edema-like lesions, erosion and cartilage loss of the wrist in rheumatoid arthritis (RA) compared to the OMERACT-RAMRIS. Wrist MRI was performed at 3 T in 16 patients with RA. Synovial volume and perfusion, bone marrow edema-like lesion (BMEL) volume, signal intensity and perfusion, and erosion dimensions were measured manually and using an in-house-developed automated software algorithm; findings were correlated with the OMERAC-RAMRIS gradings. In addition, a semiquantitative MRI cartilage loss score system was developed. Intraclass correlation coefficients (ICCs) were used to test the reproducibility of these quantitative and semiquantitative techniques. Spearman correlation coefficients were calculated between lesion quantifications and RAMRIS and between the MRI cartilage score and radiographic Sharp van der Heijde joint space narrowing scores. The intra- and interobserver ICCs were excellent for synovial, BMEL and erosion quantifications and cartilage loss grading (all >0.89). The synovial volume, BMEL volume and signal intensity, and erosion dimensions were significantly correlated with the corresponding RAMRIS (r = 0.727 to 0.900, p < 0.05). Synovial perfusion parameter maximum enhancement (Emax) was significantly correlated with synovitis RAMRIS (r = 0.798). BMEL perfusion parameters were not correlated with the RAMRIS BME score. Cartilage loss gradings from MRI were significantly correlated with the Sharp joint space narrowing scores (r = 0.635, p = 0.008). The computer-aided, manual and semiquantitative methods presented in this study can be used to evaluate MRI pathologies in RA with excellent reproducibility. Significant correlations with standard RAMRIS were found in the measurements using these methods. (orig.)

  12. Polymorphisms in the P2X7 receptor gene are associated with low lumbar spine bone mineral density and accelerated bone loss in post-menopausal women

    DEFF Research Database (Denmark)

    Gartland, Alison; Skarratt, Kristen K; Hocking, Lynne J;

    2012-01-01

    The P2X7 receptor gene (P2RX7) is highly polymorphic with five previously described loss-of-function (LOF) single-nucleotide polymorphisms (SNP; c.151+1G>T, c.946G>A, c.1096C>G, c.1513A>C and c.1729T>A) and one gain-of-function SNP (c.489C>T). The purpose of this study was to determine whether th...

  13. A novel small-molecule PPI inhibitor targeting integrin αvβ3-osteopontin interface blocks bone resorption in vitro and prevents bone loss in mice.

    Science.gov (United States)

    Park, Doori; Park, Chan-Won; Choi, YoungJin; Lin, Jingjing; Seo, Dong-Hyun; Kim, Han-Sung; Lee, Soo Young; Kang, In-Cheol

    2016-08-01

    Small molecule-inhibition targeting protein-protein interaction (PPI) is now recognized as an emerging and challenging area in drug design. We developed a novel interactive drug discovery methodology known as Protein Chip technology (ProteoChip) as a cutting-edge PPI assay system applicable for unique PPI-targeting therapeutics integrated with computer-aided drug design (CADD). Here, we describe a novel small molecular PPI inhibitor, IPS-02001, which the blocks integrin αvβ3-osteopontin interface a novel PPI inhibitor identified by the interactive methodology of both ProteoChip- and CADD-based PPI assay. IPS-02001 (6,7-Dichloro-2,3,5,8-tetrahydroxy-1,4-naphthoquinone) was screened from different compound libraries (InterBioScreen, Commercial libraries) using an in silico structure-based molecular docking simulation method and a protein chip-based protein-protein interaction assay system. Additionally, integrin αvβ3, an adhesion receptor expressed in osteoclasts (OCs), was implicated in the regulation of OC function via regulation of the cytoskeletal organization of OCs. IPS-02001 blocked OC maturation from murine bone marrow-derived macrophages, as well as the resorptive function of OCs. Moreover, treatment with IPS-02001 impaired downstream signaling of integrin αvβ3 linked to Pyk2, c-Src, PLCγ2, and Vav3 and disrupted the actin cytoskeleton in mature OCs. Furthermore, IPS-02001 blocked RANKL-induced bone destruction by reducing the number of OCs and protected against ovariectomy-induced bone loss in mice. Thus, IPS-02001 may represent a promising new class of anti-resorptive drugs for treatment of bone diseases associated with increased OC function. PMID:27187277

  14. Receptor activator of nuclear factor-κB ligand and osteoprotegerin: maintaining the balance to prevent bone loss

    OpenAIRE

    Anne-Priscille Trouvin; Vincent Goëb

    2010-01-01

    Anne-Priscille Trouvin, Vincent GoëbDepartment of Rheumatology, Rouen University Hospital, Rouen, FranceAbstract: Bone remodeling requires a precise balance between resorption and formation. It is a complex process that involves numerous factors: hormones, growth factors, vitamins, and cytokines, and notably osteoprotegerin (OPG) and receptor activator for nuclear factor-κB (RANK) ligand. The signaling pathway OPG/RANK/RANKL is key to regulation for maintaining the balance ...

  15. Equol, via Dietary Sources or Intestinal Production, May Ameliorate Estrogen Deficiency-Induced Bone Loss1–3

    OpenAIRE

    Weaver, Connie M.; Legette, LeeCole L.

    2010-01-01

    Equol, a product of intestinal metabolism of daidzein, is chemically similar to estrogen (without the lipophilic moiety) and has higher estrogen receptor-β binding affinity than its parent precursor. In 2004, a long-term, randomized controlled trial that characterized postmenopausal women by their equol-producing status showed stronger advantages to lumbar spine bone mineral density (BMD) in equol- compared with nonequol-producers. Subsequent studies have related equol status of participants ...

  16. Minimally invasive piezosurgery for a safe placement of blade dental implants in jaws with severe bone loss

    Directory of Open Access Journals (Sweden)

    F. Rossi

    2014-10-01

    Full Text Available Aim :Severe atrophies of edentulous jaws require major reconstructive bone surgery in order to allow the placement of root-form implants with standard diameter. These bone augmentation techniques represent the best option reported in the literature, but they are often rejected by patients because of their high economic and biological costs in addition to the possibility of failure in the short and/or long term. In the maxilla regenerative methods (onlay, inlay, and distraction have high success rates, whereas in the mandible, especially in the distal atrophic area, they are not so predictable. In such situations an alternative technique for fixed prosthethic rebilitation is the insertion of platform blade implants, which have their elective indication for atrophic bone ridges with reduced width, owing to their reduced thickness. The aim of this study is to assess the effectiveness of the use of piezoelectric ultrasonic handpieces, in order to simplify the placement of blade implants, making it safer and less traumatic than with conventional surgical procedures. Materials and methods: Platform blade implants are extension implant functionally and aesthetically reliable, even if they require a more difficult surgical technique compared with the one currently in use for screw implants. A minimally invasive procedure by means of piezosurgery that was performed on 142 subjects is presented and a case is reported which highlights the successful results. Results: and conclusion The use of piezoelectric ultrasonic handpieces simplifies the surgical procedure for the placement of blade implant, making it safer and less traumatic.

  17. 1,25-Dihydroxyvitamin D3 prevents bone loss of the secondary spongiosa in arthritic rats by an increase of bone formation and mineralization and inhibition of bone resorption

    OpenAIRE

    Oelzner, Peter; Petrow, Peter K; Wolf, Gunter; Bräuer, Rolf

    2014-01-01

    Background Active vitamin D metabolites have been shown to have protective effects in experimental arthritis especially when used as preventive treatment. However, because the direct effects of 1,25-dihydroxyvitamin D3 (1,25(OH) 2D3) on bone formation and resorption are very complex, the net effect of 1,25(OH)2D3 on histomorphometric parameters of bone turnover and mineralisation should be investigated. Therefore, we examined the influence of 1,25(OH)2D3 therapy on arthritis-induced alteratio...

  18. On Academician Behounek's paper ''Lung cancer induced by ionizing radiation''

    International Nuclear Information System (INIS)

    The significance and scientific contribution are discussed of the paper ''Lung Cancer Induced by Ionizing Radiation'' submitted by Academician Frantisek Behounek to the nation-wide workshop of the Czechoslovak Society of Pneumology and Oncology in Prague, October 3 and 4, 1952 and published in the Proceedings in 1953. The paper discussed the problem which still remains topical, ie., lung exposure to radon daughters, which Academician Behounek considered to be the true cause of lung cancer in Jachymov miners. (B.S.)

  19. Association of Bone Loss with the Upregulation of Survival-Related Genes and Concomitant Downregulation of Mammalian Target of Rapamycin and Osteoblast Differentiation-Related Genes in the Peripheral Blood of Late Postmenopausal Osteoporotic Women

    OpenAIRE

    Tchetina, Elena V.; Karina A. Maslova; Mikhail Y. Krylov; Myakotkin, Valery A.

    2015-01-01

    We aimed to identify bone related markers in the peripheral blood of osteoporotic (OP) patients that pointed toward molecular mechanisms underlying late postmenopausal bone loss. Whole blood from 22 late postmenopausal OP patients and 26 healthy subjects was examined. Bone mineral density (BMD) was measured by DXA. Protein levels of p70-S6K, p21, MMP-9, TGFβ1, and caspase-3 were quantified by ELISA. Gene expression was measured using real-time RT-PCR. OP registered by low BMD indices in late ...

  20. TAHU MENGHAMBAT KEHILANGAN TULANG LUMBAR TIKUS BETINA OVARIEKTOMI [Tofu Attenuates Lumbar Bone Loss of Ovariectomized Female Rats

    Directory of Open Access Journals (Sweden)

    Suyanto Pawiroharsono 4

    2002-12-01

    Full Text Available The objectives of this research were to examine the efeects of feed containing soybean tofu and tempeh on lumbar bone density and mass of ovariectomized female rats. Twenty four 17 weeks-old Sprague-Dawley rats were randomly assigned to four group, i.e.: (1 non-ovariectomized rats fed casein based diet (NonOvx, (2 ovariectomized rats fed casein based diet (OvxC, (3 ovariectomized rats fed diet containing soybean tofu (OvxH, and (4 ovariectomized rats fed diet containing soybean tempeh (OvxT; in three block based on their body weight. The result show that body weight gram of ovariectomized rats was greater than nonovariectomized. Ovariectomy caused atrophy of the uterus, and resulted in higher serum calcium level. The lower lumbar vertebrae density of ovariectomized rats was observed and the decrease was prevented by tofu.

  1. Evaluation of diagnostic accuracy of conventional and digital periapical radiography, panoramic radiography, and cone-beam computed tomography in the assessment of alveolar bone loss

    Science.gov (United States)

    Takeshita, Wilton Mitsunari; Vessoni Iwaki, Lilian Cristina; Da Silva, Mariliani Chicarelli; Tonin, Renata Hernandes

    2014-01-01

    Background: To evaluate the diagnostic accuracy of different radiographic methods in the assessment of proximal alveolar bone loss (ABL). Materials and Methods: ABL, the distance between cement-enamel junction and alveolar bone crest, was measured in 70 mandibular human teeth – directly on the mandibles (control), using conventional periapical radiography with film holders (Rinn XCP and Han-Shin), digital periapical radiography with complementary metal-oxide semiconductor sensor, conventional panoramic, and cone-beam computed tomography (CBCT). Three programs were used to measure ABL on the images: Image tool 3.0 (University of Texas Health Sciences Center, San Antonio, Texas, USA), Kodak Imaging 6.1 (Kodak Dental Imaging 6.1, Carestream Health®, Rochester, NY, USA), and i-CAT vision 1.6.20. Statistical analysis used ANOVA and Tukey's test at 5% significance level. Results: The tomographic images showed the highest means, whereas the lowest were found for periapical with Han-Shin. Controls differed from periapical with Han-Shin (P digital periapical (P = 0.0027). Conventional periapicals with film holders differed from each other (P = 0.0007). Digital periapical differed from conventional periapical with Han-Shin (P = 0.0004). Conclusions: Conventional periapical with Han-Shin film holder was the only method that differed from the controls. CBCT had the closest means to the controls. PMID:25191066

  2. Sensorineural hearing loss: there is no correlation with isolated dysplasia of the lateral semi-circular canal on temporal bone CT

    International Nuclear Information System (INIS)

    Background: Inner ear malformations may cause sensorineural hearing loss (SNHL). However, the correlation between the small lateral semi-circular canal (LSCC) and SNHL is controversial. Purpose: To determine whether there is a correlation between the two using CT-based measurement. Material and Methods: We retrospectively reviewed the high-resolution CT images of the temporal bone obtained from consecutive patients. A total 136 ears of 68 patients (25 men and 43 women; age range 20-85 years, mean 49.8 years) were included in this study. Patients who were clinically suspected to have otosclerosis were also excluded. Two radiologists independently measured the width and cross-sectional area of the bony island of LSCC. We evaluated the correlation between LSCC bone island width or cross-sectional area and hearing level in all cases using Pearson correlation co-efficients. In addition, we compared hearing levels among the patient group with normal-sized LSCC (≥mean-SD), small LSCC (0.05). No significant difference in hearing levels were found among groups of the normal-sized, small and very small LSCC (P>0.05). Conclusion: We conclude that there is no correlation between isolated small LSCC and SNHL

  3. Extraoral Cementation Technique to Minimize Cement-Associated Peri-implant Marginal Bone Loss: Can a Thin Layer of Zinc Oxide Cement Provide Sufficient Retention?

    Science.gov (United States)

    Frisch, Eberhard; Ratka-Krüger, Petra; Weigl, Paul; Woelber, Johan

    2016-01-01

    This report describes the use of laboratory-fabricated crown intaglio replicas for extraorally prepared cementation of fixed restorations to implants. This technique minimizes excess cement and may therefore reduce the risk of cement-related marginal peri-implant bone loss. It is unclear whether the remaining thin layer of luting agent provides sufficient retention if low-adhesive zinc oxide (ZnO) cement is used. In 85 consecutive patients, 113 single crowns were cemented to implants using extraoral cementation technique (ECT) and ZnO cement. All patients were followed for 6 months and investigated for decementation. Seven events of decementation (incidence: 6.19%) were found in 7 patients (8.24%). ECT may represent a viable cementation technique for implant-supported single crowns, even using low-adhesion cements. PMID:27479343

  4. Effects of Tai Chi and Walking Exercises on Weight Loss, Metabolic Syndrome Parameters, and Bone Mineral Density: A Cluster Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Stanley Sai-Chuen Hui

    2015-01-01

    Full Text Available Tai Chi and walking are both moderate-intensity physical activity (PA that can be easily practiced in daily life. The objective of the study was to determine the effects of these two PAs on weight loss, metabolic syndrome parameters, and bone mineral density (BMD in Chinese adults. We randomized 374 middle-aged subjects (45.8 ± 5.3 years into 12-week training (45 minutes per day, 5 days per week of Tai Chi (n=124 or self-paced walking (n=121 or control group (n=129. On average, Tai Chi and walking groups lost 0.50 and 0.76 kg of body weight and 0.47 and 0.59 kg of fat mass after intervention, respectively. The between-group difference of waist circumference (WC and fasting blood glucose (FBG was −3.7 cm and −0.18 mmol/L for Tai Chi versus control and −4.1 cm and −0.22 mmol/L for walking versus control. No significant differences were observed regarding lean mass, blood pressure, triglycerides, total cholesterol, high-density and low-density lipoprotein cholesterol, and BMD compared to control. Change in lean mass, not fat mass or total weight loss, was significantly correlated to the change in BMD. Our results suggest that both of these two PAs can produce moderate weight loss and significantly improve the WC and FBG in Hong Kong Chinese adults, with no additional effects on BMD.

  5. The Effects of Topical Application of Polycal (a 2:98 (g/g Mixture of Polycan and Calcium Gluconate on Experimental Periodontitis and Alveolar Bone Loss in Rats

    Directory of Open Access Journals (Sweden)

    Sang-In Park

    2016-04-01

    Full Text Available The aim of this study was to observe whether Polycal has inhibitory activity on ligation-induced experimental periodontitis and related alveolar bone loss in rats following topical application to the gingival regions. One day after the ligation placements, Polycal (50, 25, and 12.5 mg/mL solutions at 200 μL/rat was topically applied to the ligated gingival regions daily for 10 days. Changes in bodyweight, alveolar bone loss index, and total number of buccal gingival aerobic bacterial cells were monitored, and the anti-inflammatory effects were investigated via myeloperoxidase activity and levels of the pro-inflammatory cytokines IL-1β and TNF-α. The activities of inducible nitric oxide synthase (iNOS and lipid peroxidation (MDA were also evaluated. Bacterial proliferation, periodontitis, and alveolar bone loss induced by ligature placements were significantly inhibited after 10 days of continuous topical application of Polycal. These results indicate that topical application of Polycal has a significant inhibitory effect on periodontitis and related alveolar bone loss in rats mediated by antibacterial, anti-inflammatory, and anti-oxidative activities.

  6. Bone grafting: An overview

    Directory of Open Access Journals (Sweden)

    D. O. Joshi

    2010-08-01

    Full Text Available Bone grafting is the process by which bone is transferred from a source (donor to site (recipient. Due to trauma from accidents by speedy vehicles, falling down from height or gunshot injury particularly in human being, acquired or developmental diseases like rickets, congenital defects like abnormal bone development, wearing out because of age and overuse; lead to bone loss and to replace the loss we need the bone grafting. Osteogenesis, osteoinduction, osteoconduction, mechanical supports are the four basic mechanisms of bone graft. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. An ideal bone graft material is biologically inert, source of osteogenic, act as a mechanical support, readily available, easily adaptable in terms of size, shape, length and replaced by the host bone. Except blood, bone is grafted with greater frequency. Bone graft indicated for variety of orthopedic abnormalities, comminuted fractures, delayed unions, non-unions, arthrodesis and osteomyelitis. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. By adopting different procedure of graft preservation its antigenicity can be minimized. The concept of bone banking for obtaining bone grafts and implants is very useful for clinical application. Absolute stability require for successful incorporation. Ideal bone graft must possess osteogenic, osteoinductive and osteocon-ductive properties. Cancellous bone graft is superior to cortical bone graft. Usually autologous cancellous bone graft are used as fresh grafts where as allografts are employed as an alloimplant. None of the available type of bone grafts possesses all these properties therefore, a single type of graft cannot be recomm-ended for all types of orthopedic abnormalities. Bone grafts and implants can be selected as per clinical problems, the equipments available and preference of

  7. Frequent mechanical stress suppresses proliferation of mesenchymal stem cells from human bone marrow without loss of multipotency.

    Science.gov (United States)

    Frank, Viktoria; Kaufmann, Stefan; Wright, Rebecca; Horn, Patrick; Yoshikawa, Hiroshi Y; Wuchter, Patrick; Madsen, Jeppe; Lewis, Andrew L; Armes, Steven P; Ho, Anthony D; Tanaka, Motomu

    2016-01-01

    Mounting evidence indicated that human mesenchymal stem cells (hMSCs) are responsive not only to biochemical but also to physical cues, such as substrate topography and stiffness. To simulate the dynamic structures of extracellular environments of the marrow in vivo, we designed a novel surrogate substrate for marrow derived hMSCs based on physically cross-linked hydrogels whose elasticity can be adopted dynamically by chemical stimuli. Under frequent mechanical stress, hMSCs grown on our hydrogel substrates maintain the expression of STRO-1 over 20 d, irrespective of the substrate elasticity. On exposure to the corresponding induction media, these cultured hMSCs can undergo adipogenesis and osteogenesis without requiring cell transfer onto other substrates. Moreover, we demonstrated that our surrogate substrate suppresses the proliferation of hMSCs by up to 90% without any loss of multiple lineage potential by changing the substrate elasticity every 2nd days. Such "dynamic in vitro niche" can be used not only for a better understanding of the role of dynamic mechanical stresses on the fate of hMSCs but also for the synchronized differentiation of adult stem cells to a specific lineage. PMID:27080570

  8. Frequent mechanical stress suppresses proliferation of mesenchymal stem cells from human bone marrow without loss of multipotency

    Science.gov (United States)

    Frank, Viktoria; Kaufmann, Stefan; Wright, Rebecca; Horn, Patrick; Yoshikawa, Hiroshi Y.; Wuchter, Patrick; Madsen, Jeppe; Lewis, Andrew L.; Armes, Steven P.; Ho, Anthony D.; Tanaka, Motomu

    2016-04-01

    Mounting evidence indicated that human mesenchymal stem cells (hMSCs) are responsive not only to biochemical but also to physical cues, such as substrate topography and stiffness. To simulate the dynamic structures of extracellular environments of the marrow in vivo, we designed a novel surrogate substrate for marrow derived hMSCs based on physically cross-linked hydrogels whose elasticity can be adopted dynamically by chemical stimuli. Under frequent mechanical stress, hMSCs grown on our hydrogel substrates maintain the expression of STRO-1 over 20 d, irrespective of the substrate elasticity. On exposure to the corresponding induction media, these cultured hMSCs can undergo adipogenesis and osteogenesis without requiring cell transfer onto other substrates. Moreover, we demonstrated that our surrogate substrate suppresses the proliferation of hMSCs by up to 90% without any loss of multiple lineage potential by changing the substrate elasticity every 2nd days. Such “dynamic in vitro niche” can be used not only for a better understanding of the role of dynamic mechanical stresses on the fate of hMSCs but also for the synchronized differentiation of adult stem cells to a specific lineage.

  9. Role of Osteoprotegerin and Receptor Activator of Nuclear Factor-κB Ligand in Bone Loss Related to Advanced Chronic Obstructive Pulmonary Disease

    Science.gov (United States)

    Ugay, Ludmila; Kochetkova, Evgenia; Nevzorova, Vera; Maistrovskaia, Yuliya

    2016-01-01

    Background: Osteoporosis is a common complication of chronic obstructive pulmonary disease (COPD). Recent clinical and biological researches have increasingly delineated the biomolecular pathways of bone metabolism regulation in COPD. We extended this work by examining the specific association and potential contribution of the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) axis to the pathogenesis of osteoporosis in advanced COPD. The aim of this study was to assess the relationships of serum OPG, RANKL, and tumor necrosis factor-alpha (TNF-α) with bone turnover in men with very severe COPD. Methods: Pulmonary function, T-score at the lumbar spine (LS) and femoral neck (FN), serum OPG, RANKL, soluble receptor of tumor necrosis factor-alpha-I and II (sTNFR-I, sTNFR-II), osteocalcin (OC), and β-CrossLaps (βCL) levels were measured in 45 men with very severe stage COPD and 36 male non-COPD volunteers. COPD patients and healthy controls were compared using an independent t-test and Mann–Whitney U-test. The Pearson coefficient was used to assess the relationships between variables. Results: OPG and OC were lower in male COPD patients than in control subjects whereas RANKL, serum βCL, TNF-α, and its receptors were higher. OPG directly correlated with forced expiratory volume in 1 s (FEV1) % predicted (r = 0.46, P < 0.005), OC (r = 0.34, P < 0.05), LS (r = 0.56, P < 0.001), and FN T-score (r = 0.47, P < 0.01). In contrast, serum RANKL inversely associated with LS and FN T-score (r = −0.62, P < 0.001 and r = −0.48, P < 0.001) but directly correlated with βCL (r = 0.48, P < 0.001). In addition, OPG was inversely correlated with RANKL (r = −0.39, P < 0.01), TNF-α (r = −0.56, P < 0.001), and sTNFR-I (r = −0.40, P < 0.01). Conclusion: Our results suggest that serum OPG and RANKL levels are inversely associated with bone loss in men with advanced stage COPD. PMID:27411457

  10. The research for trend of bone loss in highly educated middle-aged and elderly population in Beijing%北京中老年高知人群骨质流失趋势研究

    Institute of Scientific and Technical Information of China (English)

    黄南杰; 谢红志

    2012-01-01

    目的 在分析北京中老年高知人群骨质流失的年龄差异、性别特征及骨质流失率现状基础上,探讨北京中老年高知人群骨质流失的现状与骨质流失的趋势.方法 采用BCA-2A型身体成份仪与双能X射线骨密度吸收仪测量北京市某高校1280名中老年教师骨质重指标,通过独立样本T检验比较不同性别之间的骨质流失,采用单因素方差分析比较不同组别间的骨质流失,采用回归分析(Regression)建立骨质重流失曲线.结果 ①北京中老年高知男性与高知女性骨质重随年龄增加逐渐降低,处于骨质丢失期.②北京中老年高知男性骨质重高于高知女性骨质重,差异显著(P<0.01),高知男性骨量峰值高于高知女性骨量峰值.③北京中老年高知男性和高知女性的骨质重各组间差异显著(P<0.01),骨质流失率逐渐增加.④北京中老年高知男性和高知女性骨质流失曲线在46 ~ 55岁斜率最高,且高知女性的骨质流失曲线斜率高于高知男性,高知女性较高知男性骨质流失迅速.%Objective To explore the recent status and future trend of bone loss in highly educated middle -aged and elderly population based on the difference of age, characterization of gender, and bone loss rate. Method The bone mass indexes of 1280 middle-aged and elderly teachers of a university in Beijing using the BCA-2A modeled machine and DEXA. The bone loss between different genders was compared using the independent-samples T testing. The bone loss between different groups was analyzed using the single element variance analysis. The bone loss curve was established using the regression analysis. Measuring bony index for 1,280 teachers they are middle-aged and old with the BCA-2A modeled machine and dual-energy X-ray bone densometer, contrasting the bone losing rate between different sexes through the independent-samples T testing. In addition, putting the one-factor analysis of variance into use to

  11. Biophotonics and Bone Biology

    Science.gov (United States)

    Zimmerli, Gregory; Fischer, David; Asipauskas, Marius; Chauhan, Chirag; Compitello, Nicole; Burke, Jamie; Tate, Melissa Knothe

    2004-01-01

    One of the more-serious side effects of extended space flight is an accelerated bone loss [Bioastronautics Critical Path Roadmap, http://research.hq.nasa.gov/code_u/bcpr/index.cfm]. Rates of bone loss are highest in the weight-bearing bones of the hip and spine regions, and the average rate of bone loss as measured by bone mineral density measurements is around 1.2% per month for persons in a microgravity environment. It shows that an extrapolation of the microgravity induced bone loss rates to longer time scales, such as a 2.5 year round-trip to Mars (6 months out at 0 g, 1.5 year stay on Mars at 0.38 g, 6 months back at 0 g), could severely compromise the skeletal system of such a person.

  12. 前列腺癌雄激素剥夺治疗与骨质丢失%Androgen deprivation therapy for prostate cancer and bone loss

    Institute of Scientific and Technical Information of China (English)

    吴燕华; 刘伟

    2013-01-01

    Prostate cancer is one of the common malignant tumors of the urinary system in the male. The incidence of prostate cancer in China is rising rapidly. At present, the vast majority of patients are receiving androgen deprivation therapy (ADT). Compared with chemotherapy, ADT has less toxic side effect, and it is more likely to be accepted by patients. However, ADT causes a range of adverse reactions. This paper reviews the risk of bone loss after ADT and the prevention and treatment strategies in patients with prostate cancer.%目的 前列腺癌是男性泌尿系统常见的恶性肿瘤之一.我国前列腺癌的发病率在迅速上升.目前绝大多数患者采取雄激素剥夺治疗,与化疗相比,雄激素剥夺治疗的毒副作用较轻,更容易被患者接受,但仍会引起一系列的不良反应,本文将对前列腺癌雄激素剥夺治疗后骨质丢失的情况及防治策略进行综述.

  13. Bone Regeneration in Odontostomatology

    OpenAIRE

    Tonelli, P; Duvina, M.; Brancato, L.; Delle Rose, G.; Biondi, E.; Civitelli, V.

    2010-01-01

    Maxillary edentulism, together with periodontal disease, is the condition that most frequently induces disruption of alveolar bone tissue. Indeed, the stimulus of the periodontal ligament is lost and the local bone tissue becomes subject to resorption processes that, in the six months following the loss of the tooth, result in alveolar defects or more extensive maxillary atrophy. In both cases, loss of vestibular cortical bone is followed by reduction in the vertical dimension of the alveolar...

  14. Bone regeneration in dentistry

    OpenAIRE

    Tonelli, Paolo; Duvina, Marco; Barbato, Luigi; Biondi, Eleonora; Nuti, Niccolò; Brancato, Leila; Rose, Giovanna Delle

    2011-01-01

    The edentulism of the jaws and the periodontal disease represent conditions that frequently leads to disruption of the alveolar bone. The loss of the tooth and of its bone of support lead to the creation of crestal defects or situation of maxillary atrophy. The restoration of a functional condition involves the use of endosseous implants who require adequate bone volume, to deal with the masticatory load. In such situations the bone need to be regenerated, taking advantage of the biological p...

  15. Anti-catabolic effect of caffeic acid phenethyl ester, an active component of honeybee propolis on bone loss in ovariectomized mice: a micro-computed tomography study and histological analysis

    Institute of Scientific and Technical Information of China (English)

    Duan Wangping; Wang Qing; Li Fang; Xiang Chuan; Zhou Lin; Xu Jiake; Feng Haotian

    2014-01-01

    Background Osteoporosis (OP) is a common bone disease,which adversely affects life quality.Effective treatments are necessary to combat both the loss and fracture of bone.Recent studies indicated that caffeic acid phenethyl ester (CAPE) is a natural chemical compound from honeybee propolis which is capable of attenuating osteoclastogenesis and bone resorption.Therefore,this study aimed to investigate the effect of CAPE on bone loss in OP mice using micro-computed tomography (CT) and histology.Methods Eighteen mice were prepared and evenly divided into three groups.The six mice in the sham+PBS group did not undergo ovariectomy and were intraperitoneally injected with PBS during the curing period.Twelve mice were ovariectomized (OVX) to induce OP.Six of them in the OVX+CAPE group were intraperitoneally injected with 0.5 mg/kg CAPE twice per week for 4 weeks after ovariectomy.The other six OVX mice in OVX+PBS group were treated with PBS.All the mice were sacrificed 4 weeks after ovariectomy.The tibias were bilaterally excised for micro-CT scan and histological analysis.The Mann-Whitney U test was used to test the statistical differences among groups.Results Bone loss occurred in OVX mice.Compared with the sham+PBS group,mice in the OVX+PBS group exhibited a significant decrease in bone mineral density (BMD,P <0.05),bone volume fraction (BV/TV,P <0.01),trabecular thickness (Tb.Th,P <0.05),and trabecular number (Tb.N,P <0.01),as well as a non-insignificant increase in the number of osteoclasts (N.Oc/B.Pm).With CAPE treatment,the microarchitecture of the tibial metaphyses was significantly improved with a reduction of osteoclast formation.Compared with the OVX+PBS group,BV/TV in the OVX+CAPE group was significantly increased by 33.9% (P <0.05).Conclusion CAPE therapy results in the protection of bone loss induced by OVX.

  16. Bone health in eating disorders.

    Science.gov (United States)

    Zuckerman-Levin, N; Hochberg, Z; Latzer, Y

    2014-03-01

    Eating disorders (EDs) put adolescents and young adults at risk for impaired bone health. Low bone mineral density (BMD) with ED is caused by failure to accrue peak bone mass in adolescence and bone loss in young adulthood. Although ED patients diagnosed with bone loss may be asymptomatic, some suffer bone pains and have increased incidence of fractures. Adolescents with ED are prone to increased prevalence of stress fractures, kyphoscoliosis and height loss. The clinical picture of the various EDs involves endocrinopathies that contribute to impaired bone health. Anorexia nervosa (AN) is characterized by low bone turnover, with relatively higher osteoclastic (bone resorptive) than osteoblastic (bone formation) activity. Bone loss in AN occurs in both the trabecular and cortical bones, although the former is more vulnerable. Bone loss in AN has been shown to be influenced by malnutrition and low weight, reduced fat mass, oestrogen and androgen deficiency, glucocorticoid excess, impaired growth hormone-insulin-like growth factor 1 axis, and more. Bone loss in AN may not be completely reversible despite recovery from the illness. Treatment modalities involving hormonal therapies have limited effectiveness, whereas increased caloric intake, weight gain and resumption of menses are essential to improved BMD. PMID:24165231

  17. Long-Duration Spaceflight During the Bion-M1 Spaceflight Experiment Resulted in Significant Bone Loss in the Femoral Head and Alterations in Stem Cell Differentiation Potential in Male Mice

    Science.gov (United States)

    Blaber, Elizabeth; Almeida, Eduardo; Grigoryan, Eleonora; Globus, Ruth

    Scientific understanding of the effects of microgravity on mammalian physiology has been limited to short duration spaceflight experiments (10-15 days). As long duration and inter-planetary missions are being initiated, there is a great need to understand the long-term effects of spaceflight on various physiological processes, including stem cell-based tissue regeneration. Bion-M1, for the first time, enabled the possibility of studying the effects of 30-days of microgravity exposure on a mouse model with sufficient sample size to enable statistical analysis. In this experiment, we hypothesized that microgravity negatively impacts stem cell based tissue regeneration, such as bone remodeling and regeneration from hematopoietic and mesenchymal precursors, thereby resulting in tissue degeneration in mice exposed to spaceflight. To test this hypothesis we collected the pelvis and proximal femur from space-flown mice and asynchronous ground controls and analyzed bone and bone marrow using techniques including Microcomputed Tomography (MicroCT), and in-vitro differentiation and differentiating cell motility assays. To determine the effects of 30-days spaceflight on bone tissue mass, we used MicroCT to analyze the trabecular bone of the femoral head and the cortical bone of the femoral neck and mid-shaft. We found that spaceflight caused a 45% decrease in bone volume ratio, a 17% decrease in trabecular thickness, a 25% decrease in trabecular number, and a 17% increase in trabecular spacing of trabecular bone. Furthermore, structural model index and trabecular pattern factor were increased by 32% and 82% respectively indicating that 30-days spaceflight resulted not only in a large loss of trabecular bone but also in a decrease of bone strength indicators. Analysis of the femoral neck cortical bone showed an increase in marrow area and cortical porosity indicating an overall widening of the femoral neck. Interestingly, no significant alterations were found in the cortical

  18. Microgravity Induces Pelvic Bone Loss through Osteoclastic Activity, Osteocytic Osteolysis, and Osteoblastic Cell Cycle Inhibition by CDKN1a/p21

    OpenAIRE

    Blaber, Elizabeth A.; Dvorochkin, Natalya; Lee, Chialing; Alwood, Joshua S.; Yousuf, Rukhsana; Pianetta, Piero; Globus, Ruth K.; Burns, Brendan P.; Almeida, Eduardo A.C.

    2013-01-01

    Bone is a dynamically remodeled tissue that requires gravity-mediated mechanical stimulation for maintenance of mineral content and structure. Homeostasis in bone occurs through a balance in the activities and signaling of osteoclasts, osteoblasts, and osteocytes, as well as proliferation and differentiation of their stem cell progenitors. Microgravity and unloading are known to cause osteoclast-mediated bone resorption; however, we hypothesize that osteocytic osteolysis, and cell cycle arres...

  19. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  20. Detection of Pancreatic Cancer-Induced Cachexia Using a Fluorescent Myoblast Reporter System and Analysis of Metabolite Abundance.

    Science.gov (United States)

    Winnard, Paul T; Bharti, Santosh K; Penet, Marie-France; Marik, Radharani; Mironchik, Yelena; Wildes, Flonne; Maitra, Anirban; Bhujwalla, Zaver M

    2016-03-15

    The dire effects of cancer-induced cachexia undermine treatment and contribute to decreased survival rates. Therapeutic options for this syndrome are limited, and therefore efforts to identify signs of precachexia in cancer patients are necessary for early intervention. The applications of molecular and functional imaging that would enable a whole-body "holistic" approach to this problem may lead to new insights and advances for diagnosis and treatment of this syndrome. Here we have developed a myoblast optical reporter system with the purpose of identifying early cachectic events. We generated a myoblast cell line expressing a dual tdTomato:GFP construct that was grafted onto the muscle of mice-bearing human pancreatic cancer xenografts to provide noninvasive live imaging of events associated with cancer-induced cachexia (i.e., weight loss). Real-time optical imaging detected a strong tdTomato fluorescent signal from skeletal muscle grafts in mice with weight losses of only 1.2% to 2.7% and tumor burdens of only approximately 79 to 170 mm(3). Weight loss in cachectic animals was also associated with a depletion of lipid, cholesterol, valine, and alanine levels, which may provide informative biomarkers of cachexia. Taken together, our findings demonstrate the utility of a reporter system that is capable of tracking tumor-induced weight loss, an early marker of cachexia. Future studies incorporating resected tissue from human pancreatic ductal adenocarcinoma into a reporter-carrying mouse may be able to provide a risk assessment of cachexia, with possible implications for therapeutic development. Cancer Res; 76(6); 1441-50. ©2015 AACR. PMID:26719527

  1. Bone markers and osteoporosis therapy

    Directory of Open Access Journals (Sweden)

    Francisco Bandeira

    2014-07-01

    Full Text Available Several factors are involved in determining bone quality including bone density, bone turnover, the extent of trabecular bone connectivity, cortical porosity and geometry. Metabolically active and in a continuous process of remodeling, approximately 20% of bone tissue is renewed annually. Bone turn over markers (BTM are frequently used in clinical trials and to provide valid information about the effectiveness of osteoporosis treatment, reflecting the state of bone metabolism and its response to treatment, although they are not useful alone to estimate bone loss. In this review the behavior of BTM from different clinical trials or different osteoporotic drugs will be addressed.

  2. A Retrospective Cohort Study on the Influence of Comorbidity on Soft Tissue Reactions, Revision Surgery, and Implant Loss in Bone-anchored Hearing Implants

    NARCIS (Netherlands)

    Besten, C.A. den; Nelissen, R.C.; Peer, P.G.M.; Faber, H.T.; Dun, C.A.; Wolf, M.J.; Kunst, H.P.M.; Cremers, C.W.R.J.; Mylanus, E.A.M.; Hol, M.K.

    2015-01-01

    OBJECTIVE: To identify risk factors for complications after bone-anchored hearing implant (BAHI) surgery. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: All adult patients who received titanium bone-anchored hearing implants at our clinic between September 1,

  3. Role of denosumab in the management of skeletal complications in patients with bone metastases from solid tumors

    Directory of Open Access Journals (Sweden)

    Stopeck AT

    2012-04-01

    Full Text Available Ursa Brown-Glaberman, Alison T StopeckUniversity of Arizona Cancer Center, Tucson, AZ, USAAbstract: Skeletal-related events (SREs including pain, fractures, and hypercalcemia are a major source of morbidity for cancer patients with bone metastases. The receptor activator of NF-κB ligand (RANKL is a key mediator of osteoclast formation and activity in normal bone physiology as well as cancer-induced bone resorption. The first commercially available drug that specifically targets and inhibits the RANKL pathway is denosumab, a fully human monoclonal antibody that binds and neutralizes RANKL, thereby inhibiting osteoclast function. In this review, we summarize the major studies leading to the US Food and Drug Administration-approval of denosumab for the prevention of SREs in patients with bone metastases from solid tumors. Further, we discuss the role of denosumab in the prevention and treatment of SREs and bone loss in cancer patients. As a monoclonal antibody, denosumab has several advantages over bisphosphonates, including improved efficacy, better tolerability, and the convenience of administration by subcutaneous injection. In addition, as denosumab has no known renal toxicity, it may be the preferred choice over bisphosphonates in patients with baseline renal insufficiency or receiving nephrotoxic therapies. However, other toxicities, including osteonecrosis of the jaw and hypocalcemia, appear to be class effects of agents that potently inhibit osteoclast activity and are associated with both denosumab and bisphosphonate use. The data presented highlight the differences associated with intravenous bisphosphonate and denosumab use as well as confirm the essential role bone-modifying agents play in maintaining the quality of life for patients with bone metastases.Keywords: denosumab, bone metastases, solid tumor, breast cancer, prostate cancer, skeletal related events, skeletal complications 

  4. Preventing and Treating Brittle Bones and Osteoporosis | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... Javascript on. Feature: Osteoporosis Preventing and Treating Brittle Bones and Osteoporosis Past Issues / Winter 2011 Table of ... at high risk due to low bone mass. Bone and Bone Loss Bone is living, growing tissue. ...

  5. Bone Biopsy

    Science.gov (United States)

    ... Physician Resources Professions Site Index A-Z Bone Biopsy Bone biopsy uses a needle and imaging guidance ... limitations of Bone Biopsy? What is a Bone Biopsy? A bone biopsy is an image-guided procedure ...

  6. Loss of Gsα in the Postnatal Skeleton Leads to Low Bone Mass and a Blunted Response to Anabolic Parathyroid Hormone Therapy.

    Science.gov (United States)

    Sinha, Partha; Aarnisalo, Piia; Chubb, Rhiannon; Poulton, Ingrid J; Guo, Jun; Nachtrab, Gregory; Kimura, Takaharu; Swami, Srilatha; Saeed, Hamid; Chen, Min; Weinstein, Lee S; Schipani, Ernestina; Sims, Natalie A; Kronenberg, Henry M; Wu, Joy Y

    2016-01-22

    Parathyroid hormone (PTH) is an important regulator of osteoblast function and is the only anabolic therapy currently approved for treatment of osteoporosis. The PTH receptor (PTH1R) is a G protein-coupled receptor that signals via multiple G proteins including Gsα. Mice expressing a constitutively active mutant PTH1R exhibited a dramatic increase in trabecular bone that was dependent upon expression of Gsα in the osteoblast lineage. Postnatal removal of Gsα in the osteoblast lineage (P-Gsα(OsxKO) mice) yielded markedly reduced trabecular and cortical bone mass. Treatment with anabolic PTH(1-34) (80 μg/kg/day) for 4 weeks failed to increase trabecular bone volume or cortical thickness in male and female P-Gsα(OsxKO) mice. Surprisingly, in both male and female mice, PTH administration significantly increased osteoblast numbers and bone formation rate in both control and P-Gsα(OsxKO) mice. In mice that express a mutated PTH1R that activates adenylyl cyclase and protein kinase A (PKA) via Gsα but not phospholipase C via Gq/11 (D/D mice), PTH significantly enhanced bone formation, indicating that phospholipase C activation is not required for increased bone turnover in response to PTH. Therefore, although the anabolic effect of intermittent PTH treatment on trabecular bone volume is blunted by deletion of Gsα in osteoblasts, PTH can stimulate osteoblast differentiation and bone formation. Together these findings suggest that alternative signaling pathways beyond Gsα and Gq/11 act downstream of PTH on osteoblast differentiation. PMID:26598522

  7. Anorexia nervosa and bone metabolism.

    Science.gov (United States)

    Fazeli, Pouneh K; Klibanski, Anne

    2014-09-01

    Anorexia nervosa (AN) is a psychiatric disorder characterized by self-induced starvation with a lifetime prevalence of 2.2% in women. The most common medical co-morbidity in women with AN is bone loss, with over 85% of women having bone mineral density values more than one standard deviation below an age comparable mean. The low bone mass in AN is due to multiple hormonal adaptations to under nutrition, including hypothalamic amenorrhea and growth hormone resistance. Importantly, this low bone mass is also associated with a seven-fold increased risk of fracture. Therefore, strategies to effectively prevent bone loss and increase bone mass are critical. We will review hormonal adaptations that contribute to bone loss in this population as well as promising new therapies that may increase bone mass and reduce fracture risk in AN. PMID:24882734

  8. Anorexia nervosa and bone metabolism

    Science.gov (United States)

    Fazeli, Pouneh K.; Klibanski, Anne

    2014-01-01

    Anorexia nervosa (AN) is a psychiatric disorder characterized by self-induced starvation with a lifetime prevalence of 2.2% in women. The most common medical co-morbidity in women with AN is bone loss, with over 85% of women having bone mineral density values more than one standard deviation below an age comparable mean. The low bone mass in AN is due to multiple hormonal adaptations to under nutrition, including hypothalamic amenorrhea and growth hormone resistance. Importantly, this low bone mass is also associated with a seven-fold increased risk of fracture. Therefore, strategies to effectively prevent bone loss and increase low bone mass are critical. We will review hormonal adaptations that contribute to bone loss in this population as well as promising new therapies that may increase bone mass and reduce fracture risk in AN. PMID:24882734

  9. Vestibular Evoked Myogenic Potential Produced by Bone-Conducted Stimuli: A Study on its Basics and Clinical Applications in Patients With Conductive and Sensorineural Hearing Loss and a Group With Vestibular Schawannoma

    Directory of Open Access Journals (Sweden)

    Parvane Mahdi

    2013-06-01

    Full Text Available Introduction: Vestibular evoked myogenic potential (VEMP has recently been broadly studied in vestibular disorders. As it is evoked by loud sound stimulation, even mild conductive hearing loss may affect VEMP results. Bone-conducted (BC stimulus is an alternative stimulation for evoking this response. This study aims to assess the characteristics of BC-VEMP in different groups of patients.   Materials and Methods: We performed a cross sectional analysis on 20 healthy volunteers with normal pure-tone audiometry as a control group; and on a group of patients consisted of 20 participants with conductive hearing loss, five with bilateral sensorineural hearing loss and four with vestibular schawannoma. AC and BC-VEMP were performed in all participants.   Results: In control group the VEMP responses to both kinds of stimuli had an acceptable morphology and consisted of p13 and n23 waves. Latency value of these main components in each type of stimulus was not significantly different (P>0.05. However, the mean amplitude was larger in BC modality than AC stimulation (P=0.025. In the group with conductive hearing loss, the VEMP response was absent in fifteen (46.87% of the 32 ears using the AC method, whereas all (100% displayed positive elicitability of VEMP by BC method. Normal VEMP responses in both stimuli were evoked in all patients with sensorineural hearing loss. In patients with unilateral vestibular schwannomas (VS, 2 (50.00% had neither AC-VEMP nor BC-VEMP. Conclusion:  Auditory stimuli delivered by bone conduction can evoke VEMP response. These responses are of vestibular origin and can be used in vestibular evaluation of patients with conductive hearing loss.

  10. Biophotonics and Bone Biology

    Science.gov (United States)

    Zimmerli, Gregory; Fischer, David; Asipauskas, Marius; Chauhan, Chirag; Compitello, Nicole; Burke, Jamie; Tate, Melissa Knothe

    2004-01-01

    One of the more serious side effects of extended space flight is an accelerated bone loss. Rates of bone loss are highest in the weight-bearing bones of the hip and spine regions, and the average rate of bone loss as measured by bone mineral density measurements is around 1.2% per month for persons in a microgravity environment. It is well known that bone remodeling responds to mechanical forces. We are developing two-photon microscopy techniques to study bone tissue and bone cell cultures to better understand the fundamental response mechanism in bone remodeling. Osteoblast and osteoclast cell cultures are being studied, and the goal is to use molecular biology techniques in conjunction with Fluorescence Lifetime Imaging Microscopy (FLIM) to study the physiology of in-vitro cell cultures in response to various stimuli, such as fluid flow induced shear stress and mechanical stress. We have constructed a two-photon fluorescence microscope for these studies, and are currently incorporating FLIM detection. Current progress will be reviewed. This work is supported by the NASA John Glenn Biomedical Engineering Consortium.

  11. Mineral and Skeletal Homeostasis Influence the Manner of Bone Loss in Metabolic Osteoporosis due to Calcium-Deprived Diet in Different Sites of Rat Vertebra and Femur

    Directory of Open Access Journals (Sweden)

    Marzia Ferretti

    2015-01-01

    Full Text Available Rats fed calcium-deprived diet develop osteoporosis due to enhanced bone resorption, secondary to parathyroid overactivity resulting from nutritional hypocalcemia. Therefore, rats provide a good experimental animal model for studying bone modelling alterations during biochemical osteoporosis. Three-month-old Sprague-Dawley male rats were divided into 4 groups: (1 baseline, (2 normal diet for 4 weeks, (3 calcium-deprived diet for 4 weeks, and (4 calcium-deprived diet for 4 weeks and concomitant administration of PTH (1-34 40 µg/Kg/day. Histomorphometrical analyses were made on cortical and trabecular bone of lumbar vertebral body as well as of mid-diaphysis and distal metaphysis of femur. In all rats fed calcium-deprived diet, despite the reduction of trabecular number (due to the maintenance of mineral homeostasis, an intense activity of bone deposition occurs on the surface of the few remaining trabeculae (in answering to mechanical stresses and, consequently, to maintain the skeletal homeostasis. Different responses were detected in different sites of cortical bone, depending on their main function in answering mineral or skeletal homeostasis. This study represents the starting point for work-in-progress researches, with the aim of defining in detail timing and manners of evolution and recovery of biochemical osteoporosis.

  12. Randomized, Double-Blinded, Placebo-Controlled, Trial of Risedronate for the Prevention of Bone Mineral Density Loss in Nonmetastatic Prostate Cancer Patients Receiving Radiation Therapy Plus Androgen Deprivation Therapy

    International Nuclear Information System (INIS)

    Purpose: Androgen deprivation therapy (ADT) has been used as an adjuvant treatment to radiation therapy (RT) for the management of locally advanced prostate carcinoma. Long-term ADT decreases bone mineral density (BMD) and increases the risk of osteoporosis. The objective of this clinical trial was to evaluate the efficacy of risedronate for the prevention of BMD loss in nonmetastatic prostate cancer patients undergoing RT plus 2 to 3 years of ADT. Methods and Materials: A double-blinded, placebo-controlled, randomized trial was conducted for nonmetastatic prostate cancer patients receiving RT plus 2 to 3 years of ADT. All had T scores > −2.5 on dual energy x-ray absorptiometry at baseline. Patients were randomized 1:1 between risedronate and placebo for 2 years. The primary endpoints were the percent changes in the BMD of the lumbar spine at 1 and 2 years from baseline, measured by dual energy x-ray absorptiometry. Analyses of the changes in BMD and bone turnover biomarkers were carried out by comparing mean values of the intrapatient changes between the 2 arms, using standard t tests. Results: One hundred four patients were accrued between 2004 and 2007, with 52 in each arm. Mean age was 66.8 and 67.5 years for the placebo and risedronate, respectively. At 1 and 2 years, mean (±SE) BMD of the lumbar spine decreased by 5.77% ± 4.66% and 13.55% ± 6.33%, respectively, in the placebo, compared with 0.12% ± 1.29% at 1 year (P=.2485) and 0.85% ± 1.56% (P=.0583) at 2 years in the risedronate. The placebo had a significant increase in serum bone turnover biomarkers compared with the risedronate. Conclusions: Weekly oral risedronate prevented BMD loss at 2 years and resulted in significant suppression of bone turnover biomarkers for 24 months for patients receiving RT plus 2 to 3 years of ADT

  13. Randomized, Double-Blinded, Placebo-Controlled, Trial of Risedronate for the Prevention of Bone Mineral Density Loss in Nonmetastatic Prostate Cancer Patients Receiving Radiation Therapy Plus Androgen Deprivation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Choo, Richard [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Lukka, Himu [Department of Radiation Oncology, Juravinski Cancer Center, McMaster University, Hamilton (Canada); Cheung, Patrick [Department of Radiation Oncology, Odette Cancer Centre, University of Toronto, Toronto (Canada); Corbett, Tom [Department of Radiation Oncology, Juravinski Cancer Center, McMaster University, Hamilton (Canada); Briones-Urbina, Rosario [Department of Medicine, Women' s College Hospital, University of Toronto, Toronto (Canada); Vieth, Reinhold [Departments of Nutritional Sciences and Laboratory Medicine and Pathology, Mount Sinai Hospital, University of Toronto, Toronto (Canada); Ehrlich, Lisa [Department of Radiology, Sunnybrook Health Sciences Center, University of Toronto (Canada); Kiss, Alex [Department of Health Policy, Management, and Evaluation, Sunnybrook Health Sciences Center, University of Toronto, Toronto (Canada); Danjoux, Cyril, E-mail: Cyril.danjoux@sunnybrook.ca [Department of Radiation Oncology, Odette Cancer Centre, University of Toronto, Toronto (Canada)

    2013-04-01

    Purpose: Androgen deprivation therapy (ADT) has been used as an adjuvant treatment to radiation therapy (RT) for the management of locally advanced prostate carcinoma. Long-term ADT decreases bone mineral density (BMD) and increases the risk of osteoporosis. The objective of this clinical trial was to evaluate the efficacy of risedronate for the prevention of BMD loss in nonmetastatic prostate cancer patients undergoing RT plus 2 to 3 years of ADT. Methods and Materials: A double-blinded, placebo-controlled, randomized trial was conducted for nonmetastatic prostate cancer patients receiving RT plus 2 to 3 years of ADT. All had T scores > −2.5 on dual energy x-ray absorptiometry at baseline. Patients were randomized 1:1 between risedronate and placebo for 2 years. The primary endpoints were the percent changes in the BMD of the lumbar spine at 1 and 2 years from baseline, measured by dual energy x-ray absorptiometry. Analyses of the changes in BMD and bone turnover biomarkers were carried out by comparing mean values of the intrapatient changes between the 2 arms, using standard t tests. Results: One hundred four patients were accrued between 2004 and 2007, with 52 in each arm. Mean age was 66.8 and 67.5 years for the placebo and risedronate, respectively. At 1 and 2 years, mean (±SE) BMD of the lumbar spine decreased by 5.77% ± 4.66% and 13.55% ± 6.33%, respectively, in the placebo, compared with 0.12% ± 1.29% at 1 year (P=.2485) and 0.85% ± 1.56% (P=.0583) at 2 years in the risedronate. The placebo had a significant increase in serum bone turnover biomarkers compared with the risedronate. Conclusions: Weekly oral risedronate prevented BMD loss at 2 years and resulted in significant suppression of bone turnover biomarkers for 24 months for patients receiving RT plus 2 to 3 years of ADT.

  14. Healthy Bones at Every Age

    Science.gov (United States)

    ... include walking and running, as well as team sports like soccer and basketball. AAOS does not endorse ... to cause hormonal changes that stop menstrual periods (amenorrhea). This loss of estrogen can cause bone loss ...

  15. 雷洛昔芬对放疗去势大鼠骨丢失的保护作用%Protective effect of raloxifene in preventing bone loss in rats following radiotherapy induced gonadectomy

    Institute of Scientific and Technical Information of China (English)

    陈静; 朱芳; 李贵玲

    2011-01-01

    目的:观察雷洛昔芬(选择性雌激素受体调节剂)对放疗去势大鼠的骨代谢生化指标、骨密度及骨形态学的影响,探讨其对放疗所致卵巢早衰引起骨丢失的保护作用.方法:选用3月龄雌性Wistar大鼠40只,随机分为4组:假放疗组、放疗组、放疗+雷洛昔芬组、放疗+己烯雌酚组,每组10只,16周后,腹主动脉取血,检测血清雌二醇、卵泡刺激素、骨钙素及碱性磷酸酶的水平;处死大鼠,取大鼠右侧股骨,测定各组骨密度;同时取左侧股骨制作骨切片行HE染色,观察骨形态学变化.结果:放疗组及放疗+雷洛昔芬组的雌二醇水平明显低于假放疗组及放疗+己烯雌酚组(P<0.05);而两组的卵泡刺激素水平明显高于假放疗组及放疗+己烯雌酚组(P<0.05);放疗组骨钙素和碱性磷酸酶明显高于其他3组,而另3组无明显差异(P>0.05);放疗组大鼠骨密度显著低于其他3组,其骨小梁稀疏,部分断裂,而另3组骨小梁致密,无明显断裂.结论:大鼠卵巢放疗可致去势,放疗去势后大鼠有骨质丢失发生,而选择性雌激素受体调节剂雷洛昔芬对放疗去势后大鼠的骨丢失有保护作用.%OBJECTIVE To investigate the protective effect of the selective estrogen receptor modulators (SERMs) raloxifene in preventing hone loss secondary to radiotherapy induced premature ovarian failure(POF). This was studied by observing the effects of Raloxifene on biochemical markers of bone metabolism, bone morphology and bone mineral density of rats following radiotherapy induced gonadectomy. METHODS 40 female Wistar rats aged 3 months were randomly divided into 4 groups (10 rats in each group): Group A(sham radiotherapy), Group B(radiotherapy),Group C (radiotherapy and raloxifene) ,Group D(radiotherapy and diethylstilbestrol). All rats were killed 16 weeks later. Then serum estradiol (E2)、 follicle stimulating hormone(FSH),bone gla protein(BGP) and alkaline phosphatase

  16. Extrinsic Mechanisms Involved in Age-Related Defective Bone Formation

    DEFF Research Database (Denmark)

    Trinquier, Anne Marie-Pierre Emilie; Kassem, Moustapha

    2011-01-01

    Context: Age-related bone loss is associated with progressive changes in bone remodeling characterized by decreased bone formation relative to bone resorption. Both trabecular and periosteal bone formation decline with age in both sexes, which contributes to bone fragility and increased risk of...

  17. Cytokines and T-lymphocyte subsets in healthy post-menopausal women: estrogen retards bone loss without affecting the release of IL-1 or IL-1ra

    DEFF Research Database (Denmark)

    Abrahamsen, Bo; Bendtzen, Klaus; Beck-Nielsen, H

    1997-01-01

    flow cytometry. One group received cyclic estrogen-gestagen replacement therapy (ERT) while the other group was untreated. In spite of a significant bone maintaining effect of ERT, the basal and LPS-stimulated secretion of IL-1 alpha, IL-1 beta, and IL-1ra was identical in the two groups. There was no...

  18. Biochemical Assessment of Bone Health in Working Obese Egyptian Females with Metabolic Syndrome; the Effect of Weight Loss by Natural Dietary Therapies

    Directory of Open Access Journals (Sweden)

    Maha I.A. Moaty

    2015-12-01

    CONCLUSION: These results confirm the benefit of doum in improving bone health parameter [25 (OH D/PTH axis] in the MetS patients, beside the MetS criteria. So, we can conclude that natural effective supplements lead towards the optimization of biochemical parameters in favor of a healthy outcome.

  19. Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain

    Science.gov (United States)

    Westerlind, K. C.; Wronski, T. J.; Ritman, E. L.; Luo, Z. P.; An, K. N.; Bell, N. H.; Turner, R. T.

    1997-01-01

    Estrogen deficiency induced bone loss is associated with increased bone turnover in rats and humans. The respective roles of increased bone turnover and altered balance between bone formation and bone resorption in mediating estrogen deficiency-induced cancellous bone loss was investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in the distal femur. However, cancellous bone was preferentially lost in the metaphysis, a site that normally experiences low strain energy. No bone loss was observed in the epiphysis, a site experiencing higher strain energy. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased and decreased in long bones of ovariectomized rats by treadmill exercise and functional unloading, respectively. Functional unloading was achieved during orbital spaceflight and following unilateral sciatic neurotomy. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing loading accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in the unloaded and prevented loss in the loaded limb following unilateral sciatic neurotomy in part by reducing indices of bone turnover. These results suggest that estrogen regulates the rate of bone turnover, but the overall balance between bone formation and bone resorption is influenced by prevailing levels of mechanical strain.

  20. Pharmacological strategies in lung cancer-induced cachexia: effects on muscle proteolysis, autophagy, structure, and weakness.

    Science.gov (United States)

    Chacon-Cabrera, Alba; Fermoselle, Clara; Urtreger, Alejandro J; Mateu-Jimenez, Mercè; Diament, Miriam J; de Kier Joffé, Elisa D Bal; Sandri, Marco; Barreiro, Esther

    2014-11-01

    Cachexia is a relevant comorbid condition of chronic diseases including cancer. Inflammation, oxidative stress, autophagy, ubiquitin-proteasome system, nuclear factor (NF)-κB, and mitogen-activated protein kinases (MAPK) are involved in the pathophysiology of cancer cachexia. Currently available treatment is limited and data demonstrating effectiveness in in vivo models are lacking. Our objectives were to explore in respiratory and limb muscles of lung cancer (LC) cachectic mice whether proteasome, NF-κB, and MAPK inhibitors improve muscle mass and function loss through several molecular mechanisms. Body and muscle weights, limb muscle force, protein degradation and the ubiquitin-proteasome system, signaling pathways, oxidative stress and inflammation, autophagy, contractile and functional proteins, myostatin and myogenin, and muscle structure were evaluated in the diaphragm and gastrocnemius of LC (LP07 adenocarcinoma) bearing cachectic mice (BALB/c), with and without concomitant treatment with NF-κB (sulfasalazine), MAPK (U0126), and proteasome (bortezomib) inhibitors. Compared to control animals, in both respiratory and limb muscles of LC cachectic mice: muscle proteolysis, ubiquitinated proteins, autophagy, myostatin, protein oxidation, FoxO-1, NF-κB and MAPK signaling pathways, and muscle abnormalities were increased, while myosin, creatine kinase, myogenin, and slow- and fast-twitch muscle fiber size were decreased. Pharmacological inhibition of NF-κB and MAPK, but not the proteasome system, induced in cancer cachectic animals, a substantial restoration of muscle mass and force through a decrease in muscle protein oxidation and catabolism, myostatin, and autophagy, together with a greater content of myogenin, and contractile and functional proteins. Attenuation of MAPK and NF-κB signaling pathway effects on muscles is beneficial in cancer-induced cachexia. PMID:24615622

  1. Green Tea and Bone metabolism

    OpenAIRE

    Shen, Chwan-Li; Yeh, James K.; Cao, Jay; Wang, Jia-Sheng

    2009-01-01

    Osteoporosis is a major health problem in both elderly women and men. Epidemiological evidence has shown an association between tea consumption and the prevention of age-related bone loss in elderly women and men. Ingestion of green tea and green tea bioactive compounds may be beneficial in mitigating bone loss of this population and decreasing their risk of osteoporotic fractures. This review describes the effect of green tea or its bioactive components on bone health, with an emphasis on: (...

  2. Osteolytica: An automated image analysis software package that rapidly measures cancer-induced osteolytic lesions in in vivo models with greater reproducibility compared to other commonly used methods.

    Science.gov (United States)

    Evans, H R; Karmakharm, T; Lawson, M A; Walker, R E; Harris, W; Fellows, C; Huggins, I D; Richmond, P; Chantry, A D

    2016-02-01

    Methods currently used to analyse osteolytic lesions caused by malignancies such as multiple myeloma and metastatic breast cancer vary from basic 2-D X-ray analysis to 2-D images of micro-CT datasets analysed with non-specialised image software such as ImageJ. However, these methods have significant limitations. They do not capture 3-D data, they are time-consuming and they often suffer from inter-user variability. We therefore sought to develop a rapid and reproducible method to analyse 3-D osteolytic lesions in mice with cancer-induced bone disease. To this end, we have developed Osteolytica, an image analysis software method featuring an easy to use, step-by-step interface to measure lytic bone lesions. Osteolytica utilises novel graphics card acceleration (parallel computing) and 3-D rendering to provide rapid reconstruction and analysis of osteolytic lesions. To evaluate the use of Osteolytica we analysed tibial micro-CT datasets from murine models of cancer-induced bone disease and compared the results to those obtained using a standard ImageJ analysis method. Firstly, to assess inter-user variability we deployed four independent researchers to analyse tibial datasets from the U266-NSG murine model of myeloma. Using ImageJ, inter-user variability between the bones was substantial (±19.6%), in contrast to using Osteolytica, which demonstrated minimal variability (±0.5%). Secondly, tibial datasets from U266-bearing NSG mice or BALB/c mice injected with the metastatic breast cancer cell line 4T1 were compared to tibial datasets from aged and sex-matched non-tumour control mice. Analyses by both Osteolytica and ImageJ showed significant increases in bone lesion area in tumour-bearing mice compared to control mice. These results confirm that Osteolytica performs as well as the current 2-D ImageJ osteolytic lesion analysis method. However, Osteolytica is advantageous in that it analyses over the entirety of the bone volume (as opposed to selected 2-D images), it

  3. Osteolytica: An automated image analysis software package that rapidly measures cancer-induced osteolytic lesions in in vivo models with greater reproducibility compared to other commonly used methods☆

    Science.gov (United States)

    Evans, H.R.; Karmakharm, T.; Lawson, M.A.; Walker, R.E.; Harris, W.; Fellows, C.; Huggins, I.D.; Richmond, P.; Chantry, A.D.

    2016-01-01

    Methods currently used to analyse osteolytic lesions caused by malignancies such as multiple myeloma and metastatic breast cancer vary from basic 2-D X-ray analysis to 2-D images of micro-CT datasets analysed with non-specialised image software such as ImageJ. However, these methods have significant limitations. They do not capture 3-D data, they are time-consuming and they often suffer from inter-user variability. We therefore sought to develop a rapid and reproducible method to analyse 3-D osteolytic lesions in mice with cancer-induced bone disease. To this end, we have developed Osteolytica, an image analysis software method featuring an easy to use, step-by-step interface to measure lytic bone lesions. Osteolytica utilises novel graphics card acceleration (parallel computing) and 3-D rendering to provide rapid reconstruction and analysis of osteolytic lesions. To evaluate the use of Osteolytica we analysed tibial micro-CT datasets from murine models of cancer-induced bone disease and compared the results to those obtained using a standard ImageJ analysis method. Firstly, to assess inter-user variability we deployed four independent researchers to analyse tibial datasets from the U266-NSG murine model of myeloma. Using ImageJ, inter-user variability between the bones was substantial (± 19.6%), in contrast to using Osteolytica, which demonstrated minimal variability (± 0.5%). Secondly, tibial datasets from U266-bearing NSG mice or BALB/c mice injected with the metastatic breast cancer cell line 4T1 were compared to tibial datasets from aged and sex-matched non-tumour control mice. Analyses by both Osteolytica and ImageJ showed significant increases in bone lesion area in tumour-bearing mice compared to control mice. These results confirm that Osteolytica performs as well as the current 2-D ImageJ osteolytic lesion analysis method. However, Osteolytica is advantageous in that it analyses over the entirety of the bone volume (as opposed to selected 2-D images

  4. Potential sources of quantification error when retrospectively assessing metacarpal bone loss from historical radiographs by using digital X-ray radiogrammetry : an experimental study

    OpenAIRE

    Kälvesten, Johan; Brismar, Torkel B.; Persson, Anders

    2014-01-01

    During the past 15 yr, digital X-ray radiogrammetry (DXR) has been used to measure metacarpal bone mineral density (BMD). BMD is often measured in existing cohorts where X-ray images were not acquired in accordance with the DXR imaging protocol (DIP). The purpose of the present study was to analyze how deviations from DIP in historical radiographs may affect the reproducibility of DXR-BMD measurements. Cadaver hand phantoms were used to conduct repeat measurements of deviations from DIP with ...

  5. Specifically decreased collagen biosynthesis in scurvy dissociated from an effect on proline hydroxylation and correlated with body weight loss. In vitro studies in guinea pig calvarial bones.

    OpenAIRE

    Chojkier, M.; Spanheimer, R.; Peterkofsky, B

    1983-01-01

    The question whether ascorbate regulates collagen production solely through its direct role in proline hydroxylation was investigated. Proteins in calvarial bones from control and scorbutic weanling guinea pigs were labeled in short-term cultures with radioactive proline. Proteins were digested with purified bacterial collagenase to distinguish between effects on collagen polypeptide production and hydroxyproline formation. There was a preferential decrease in the absolute rate of collagen bi...

  6. Are you lactose intolerant and from an ethnic minority? A study on the effect of lactose intolerance on loss of bone mineral density, Case Study Lewisham Greenwich Hospital

    OpenAIRE

    Tammer, Q.; M. Youseffi; A Rashid; Javid, Farideh A.

    2015-01-01

    Lactose intolerance (LI) is a natural process where production of lactase, an intestinal disaccharide, decreases during the aging process due to lack of consumption. There are several sub-types of lactose tolerance: lactose tolerant (LT), intolerant (LI) and mal-absorber (LM). Osteoporosis (OP) is a degenerative endocrinal bone disorder affecting over 200 million people worldwide whereas LI affects up to 70% of the world’s population and approximately 15% of the UK population. OP develops pre...

  7. Sialoglycoproteins prepared from the eggs of Carassius auratus prevent bone loss by inhibiting the NF-κB pathway in ovariectomized rats.

    Science.gov (United States)

    Xia, Guanghua; Wang, Jingfeng; Sun, Shuhong; Zhao, Yanlei; Wang, Yiming; Yu, Zhe; Wang, Shanshan; Xue, Changhu

    2016-02-17

    In this study, we investigated the improvement of osteoporosis by sialoglycoproteins isolated from the eggs of Carassius auratus (Ca-SGP) in ovariectomized rats. Ca-SGP was supplemented to ovariectomized Sprague-Dawley rats for 90 days. The results showed that Ca-SGP treatment remarkably prevented the reduction of bone mass, improved cancellous bone structure and biochemical properties. Ca-SGP also significantly decreased the serum contents of TRAP, Cath-K, MMP-9, DPD, CTX-1, Ca, and P. Mechanism investigation revealed that Ca-SGP significantly increased the OPG/RANKL ratio in mRNA expression, protein expression and serum content. Further research suggested that NF-κB signaling pathways were inhibited by suppressing the mRNA and protein expressions of NFATc1 and TRAF6, diminishing the mRNA expression and phosphorylation of NF-κB p65, three key transcription factors in NF-κB pathways. These results suggest that Ca-SGP can improve osteoporosis by inhibiting bone resorption via suppressing the activation of osteoclastogenesis related NF-κB pathways. PMID:26765587

  8. Metastatic Bone Disease

    Science.gov (United States)

    ... concern for patients with MBD is the general loss in quality of life. How much of an effect MBD has on ... to be most effective in maintaining quality of life. A technetium bone scan ... blood count, because loss of red blood cells (anemia) is a frequent ...

  9. [Effect of P2X7 receptor knock-out on bone cancer pain in mice].

    Science.gov (United States)

    Zhao, Xin; Liu, Hui-Zhu; Zhang, Yu-Qiu

    2016-06-25

    Cancer pain is one of the most common symptoms in patients with late stage cancer. Lung, breast and prostate carcinoma are the most common causes of pain from osseous metastasis. P2X7 receptor (P2X7R) is one of the subtypes of ATP-gated purinergic ion channel family, predominately distributed in microglia in the spinal cord. Activation of P2X7Rs in the spinal dorsal horn has been associated with release of proinflammatory cytokines from glial cells, causing increased neuronal excitability and exaggerated nociception. Mounting evidence implies a critical role of P2X7R in inflammatory and neuropathic pain. However, whether P2X7R is involved in cancer pain remains controversial. Here we established a bone cancer pain model by injecting the Lewis lung carcinoma cells into the femur bone marrow cavity of C57BL/6J wild-type mice (C57 WT mice) and P2X7R knockout mice (P2rx7(-/-) mice) to explore the role of P2X7R in bone cancer pain. Following intrafemur carcinoma inoculation, robust mechanical allodynia and thermal hyperalgesia in C57 WT mice were developed on day 7 and 14, respectively, and persisted for at least 28 days in the ipsilateral hindpaw of the affected limb. CatWalk gait analysis showed significant decreases in the print area and stand phase, and a significant increase in swing phase in the ipsilateral hindpaw on day 21 and 28 after carcinoma cells inoculation. Histopathological sections (hematoxylin and eosin stain) showed that the bone marrow of the affected femur was largely replaced by invading tumor cells, and the femur displayed medullary bone loss and bone destruction on day 28 after inoculation. Unexpectedly, no significant changes in bone cancer-induced hypersensitivity of pain behaviors were found in P2rx7(-/-) mice, and the changes of pain-related values in CatWalk gait analysis even occurred earlier in P2rx7(-/-) mice, as compared with C57 WT mice. Together with our previous study in rats that blockade of P2X7R significantly alleviated bone cancer

  10. Bone microenvironment-mediated resistance of cancer cells to bisphosphonates and impact on bone osteocytes/stem cells.

    Science.gov (United States)

    Alasmari, Abeer; Lin, Shih-Chun; Dibart, Serge; Salih, Erdjan

    2016-08-01

    Anti-resorptive bisphosphonates (BPs) have been clinically used to prevent cancer-bone metastasis and cancer-induced bone pathologies despite the fact that the phenotypic response of the cancer-bone interactions to BP exposure is "uncharted territory". This study offers unique insights into the interplay between cancer stem cells and osteocytes/osteoblasts and mesenchymal stem cells using a three-dimensional (3D) live cancer-bone interactive model. We provide extraordinary cryptic details of the biological events that occur as a result of alendronate (ALN) treatment using 3D live cancer-bone model systems under specific bone remodeling stages. While cancer cells are susceptible to BP treatment in the absence of bone, they are totally unaffected in the presence of bone. Cancer cells colonize live bone irrespective of whether the bone is committed to bone resorption or formation and hence, cancer-bone metastasis/interactions are though to be "independent of bone remodeling stages". In our 3D live bone model systems, ALN inhibited bone resorption at the osteoclast differentiation level through effects of mineral-bound ALN on osteocytes and osteoblasts. The mineral-bound ALN rendered bone incapable of osteoblast differentiation, while cancer cells colonize the bone with striking morphological adaptations which led to a conclusion that a direct anti-cancer effect of BPs in a "live or in vivo" bone microenvironment is implausible. The above studies were complemented with mass spectrometric analysis of the media from cancer-bone organ cultures in the absence and presence of ALN. The mineral-bound ALN impacts the bone organs by limiting transformation of mesenchymal stem cells to osteoblasts and leads to diminished endosteal cell population and degenerated osteocytes within the mineralized bone matrix. PMID:27155840

  11. Correção da falha óssea femoral e tibial pelo método do transporte ósseo de Ilizarov Femoral and tibial bone loss correction using Ilizarov's bone transport

    Directory of Open Access Journals (Sweden)

    Celso Herminio Ferraz Picado

    2000-12-01

    pacientes ficaram satisfeitos com o resultado do tratamento. Concluímos que a resposta biológica ao transporte ósseo é formidável, com a formação do regenerado reparando grandes falhas ósseas. Entretanto, consideramos que o aparelho circular externo preconizado por Ilizarov traz consigo diversas complicações principalmente relacionadas a presença dos fios transfixantes, causando sofrimento para os pacientes, principalmente quando instalados no fêmur.Eleven patients carrying diaphyseal bone fissure secondary to ressection of infected bone segments, 5 in the femur and 6 in the tibia, submitted to the Ilizarov bone transport technique were retrospectively analyzed. In the group of patients with femoral lesion the bone fissure varied from 7 cm to 12 cm, and in two there was a 2 cm shortening of the limb. In the group with tibial lesion the bone fissure varied from 2.5 cm to 10 cm, with limb shortening in two patients, respectively 1.5 cm and 2 cm. The mean follow-up period since the end of the treatment until evaluation was 49 months for the femoral lesion patients and 28.3 months for the tibial lesion patients. The femoral transports were bifocal and the tibial transports were bifocal in 4 patients and trifocal in 2. In all, patients formation of regenerate occurred. Consolidation of the target focus was naturally obtained in 7 patients; one patient needed bone grafting to obtain the focus consolidation. In three patients the nonunion of the target focus demanded modification of the treatment method with the external circular fixator withdrawal. In all the patients infection adjacent to the wires was observed. There was rupture of the wires in all assemblies made in the thigh. All the wires lost the tension initially imposed to them. Two patients submitted to femoral transport evolved with septic arthritis of the knee. Mobility of the knee was severely impaired in the patients submitted to femoral transport, and the same was observed in relation to the ankle of

  12. Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women

    OpenAIRE

    Knapen, M. H. J.; Schurgers, L.J.; Vermeer, C

    2007-01-01

    Summary Vitamin K mediates the synthesis of proteins regulating bone metabolism. We have tested whether high vitamin K2 intake promotes bone mineral density and bone strength. Results showed that K2 improved BMC and femoral neck width, but not DXA-BMD. Hence high vitamin K2 intake may contribute to preventing postmenopausal bone loss. Introduction Vitamin K is involved in the synthesis of several proteins in bone. The importance of K vitamins for optimal bone health has been suggested by popu...

  13. Targeting BCL2 Family in Human Myeloid Dendritic Cells: A Challenge to Cure Diseases with Chronic Inflammations Associated with Bone Loss

    Directory of Open Access Journals (Sweden)

    Selma Olsson Åkefeldt

    2013-01-01

    Full Text Available Rheumatoid arthritis (RA and Langerhans cell histiocytosis (LCH are common and rare diseases, respectively. They associate myeloid cell recruitment and survival in inflammatory conditions with tissue destruction and bone resorption. Manipulating dendritic cell (DC, and, especially, regulating their half-life and fusion, is a challenge. Indeed, these myeloid cells display pathogenic roles in both diseases and may be an important source of precursors for differentiation of osteoclasts, the bone-resorbing multinucleated giant cells. We have recently documented that the proinflammatory cytokine IL-17A regulates long-term survival of DC by inducing BCL2A1 expression, in addition to the constitutive MCL1 expression. We summarize bibliography of the BCL2 family members and their therapeutic targeting, with a special emphasis on MCL1 and BCL2A1, discussing their potential impact on RA and LCH. Our recent knowledge in the survival pathway, which is activated to perform DC fusion in the presence of IL-17A, suggests that targeting MCL1 and BCL2A1 in infiltrating DC may affect the clinical outcomes in RA and LCH. The development of new therapies, interfering with MCL1 and BCL2A1 expression, to target long-term surviving inflammatory DC should be translated into preclinical studies with the aim to increase the well-being of patients with RA and LCH.

  14. Pharmacologic management of bone-related complications and bone metastases in postmenopausal women with hormone receptor-positive breast cancer

    OpenAIRE

    Yardley DA

    2016-01-01

    Denise A Yardley1,2 1Sarah Cannon Research Institute, Nashville, TN, USA; 2Tennessee Oncology, Nashville, TN, USA Abstract: There is a high risk for bone loss and skeletal-related events, including bone metastases, in postmenopausal women with hormone receptor-positive breast cancer. Both the disease itself and its therapeutic treatments can negatively impact bone, resulting in decreases in bone mineral density and increases in bone loss. These negative effects on the bone can significantly ...

  15. Bone marrow fat.

    Science.gov (United States)

    Hardouin, Pierre; Pansini, Vittorio; Cortet, Bernard

    2014-07-01

    Bone marrow fat (BMF) results from an accumulation of fat cells within the bone marrow. Fat is not a simple filling tissue but is now considered as an actor within bone microenvironment. BMF is not comparable to other fat depots, as in subcutaneous or visceral tissues. Recent studies on bone marrow adipocytes have shown that they do not appear only as storage cells, but also as cells secreting adipokines, like leptin and adiponectin. Moreover bone marrow adipocytes share the same precursor with osteoblasts, the mesenchymal stem cell. It is now well established that high BMF is associated with weak bone mass in osteoporosis, especially during aging and anorexia nervosa. But numerous questions remain discussed: what is the precise phenotype of bone marrow adipocytes? What is the real function of BMF, and how does bone marrow adipocyte act on its environment? Is the increase of BMF during osteoporosis responsible for bone loss? Is BMF involved in other diseases? How to measure BMF in humans? A better understanding of BMF could allow to obtain new diagnostic tools for osteoporosis management, and could open major therapeutic perspectives. PMID:24703396

  16. Bone Cancer

    Science.gov (United States)

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

  17. Bone Cancer

    Science.gov (United States)

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another part of the body is more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 ...

  18. Bone Diseases

    Science.gov (United States)

    Your bones help you move, give you shape and support your body. They are living tissues that rebuild constantly ... childhood and your teens, your body adds new bone faster than it removes old bone. After about ...

  19. Physical activity increases bone mass during growth

    OpenAIRE

    Karlsson, Magnus K; Nordvist, Anders; Karlsson, Caroline

    2008-01-01

    Background: The incidence of fragility fractures has increased during the last half of the 1900?s. One important determinant of fractures is the bone mineral content (BMC) or bone mineral density (BMD), the amount of mineralised bone. If we could increase peak bone mass (the highest value of BMC reached during life) and/or decrease the age-related bone loss, we could possibly improve the skeletal resistance to fracture. Objective: This review evaluates the importance of exercise as a strategy...

  20. The Microenvironment Matters: Estrogen Deficiency Fuels Cancer Bone Metastases

    OpenAIRE

    Wright, Laura E; Guise, Theresa A.

    2014-01-01

    Factors released during osteoclastic bone resorption enhance disseminated breast cancer cell progression by stimulating invasiveness, growth and a bone-resorptive phenotype in cancer cells. Post-menopausal bone loss may accelerate progression of breast cancer growth in bone, explaining the anti-cancer benefit of the bone-specific anti-resorptive agent zoledronic acid in the post-menopausal setting.

  1. Are open-fit hearing aids a possible alternative to bone-anchored hearing devices in patients with mild to severe hearing loss? A preliminary trial

    Directory of Open Access Journals (Sweden)

    Amberley V. Ostevik

    2013-08-01

    Full Text Available Open-fit hearing aids (OFHAs may be of benefit for some individuals with chronic outer and middle ear conditions for which boneanchored hearing devices (BAHDs are normally recommended. The purpose of this study was to compare performance between OFHAs and BAHDs. A Starkey Destiny 800 OFHA was fit on eight adult BAHD users and speech perception measures in quiet and in background noise were compared under two different test conditions: i BAHD only and ii OFHA only. Equivalent outcome measure performance between these two conditions suggests that the OFHA was able to provide sufficient amplification for mild to moderate degrees of hearing loss (pure-tone averages (PTAs less than 47 dB HL. The improved speech perception performances and increased loudness ratings observed for several of the participants with moderately-severe to severe degrees of hearing loss (PTAs of 47 dB HL or greater in the BAHD only condition suggest that the OFHA did not provide sufficient amplification for these individuals. Therefore, OFHAs may be a successful alternative to the BAHD for individuals with no more than a moderate conductive hearing loss who are unable or unwilling to undergo implant surgery or unable to wear conventional hearing aids due to allergies, irritation, or chronic infection associated with the ear being blocked with a shell or earmold.

  2. Deregulation of Bone Forming Cells in Bone Diseases and Anabolic Effects of Strontium-Containing Agents and Biomaterials

    OpenAIRE

    Shuang Tan; Binbin Zhang; Xiaomei Zhu; Ping Ao; Huajie Guo; Weihong Yi; Guang-Qian Zhou

    2014-01-01

    Age-related bone loss and osteoporosis are associated with bone remodeling changes that are featured with decreased trabecular and periosteal bone formation relative to bone resorption. Current anticatabolic therapies focusing on the inhibition of bone resorption may not be sufficient in the prevention or reversal of age-related bone deterioration and there is a big need in promoting osteoblastogenesis and bone formation. Enhanced understanding of the network formed by key signaling pathways ...

  3. 唑来膦酸对髋关节置换后假体柄周围骨丢失的预防效果%Preventive effect of zoledronic acid on bone loss around the prosthesis stem after hip replacement

    Institute of Scientific and Technical Information of China (English)

    刘国青; 苑振峰; 刘鹏; 庞同涛; 张先巍

    2015-01-01

    背景:无论是股骨侧还是髋臼侧在髋关节置换后1年内均会出现不同程度的骨丢失,对假体的长期稳定性和骨强度造成严重影响。因而减少全髋关节置换后假体柄周围骨丢失量对延长假体使用时间、预防假体周围骨折具有重要意义。  目的:观察分析唑来膦酸对髋关节置换后假体柄周围骨丢失的预防效果。  方法:选取2011年2月至2014年9月莘县人民医院收治进行全髋关节置换的80例患者,采用随机数表法分为两组,每组40例。置换后第4天给予观察组患者唑来膦酸治疗,对照组患者不给予,两组其余用药相同。对两组置换前和置换后1年的髋部骨密度变化进行测量;观察两组置换前、用药后3d和用药后1年的血清钙、磷水平及碱性磷酸酶活性变化;对观察组患者用药期间出现的不良反应进行记录。  结果与结论:置换后1年两组患者股骨假体周围的平均骨密度均显著下降,与置换前比较差异有显著性意义(P0.05)。用药后1年,观察组患者的碱性磷酸酶活性较低,与置换前、对照组比较差异均有显著性意义(P0.05)。用药两三天内观察组有9例患者出现不同程度的肌肉酸痛和发热,给予乙酰氨基酚后症状得到缓解。提示全髋关节置换后给予唑来膦酸注射液能够有效预防患者置换后早期假体柄周围骨丢失,但是置换后1周内可能会出现发热的症状,因此建议在置换完成1周后给予患者唑来膦酸注射液,若出现发热等症状,可给予乙酰氨基酚进行缓解。%BACKGROUND:Bone loss to different degrees may appear within 1 year after hip replacement in the femoral or acetabular sides, and severely affect long-term stability of the prosthesis and bone strength. Thus, to reduce bone loss around the prosthesis stem after total hip replacement is significant to prolong the use time of the prosthesis and

  4. Bone Biochemistry on the International Space Station

    Science.gov (United States)

    Smith, Scott M.; Heer, Martina; Zwart, Sara R.

    2016-01-01

    Bone biochemical measures provide valuable insight into the nature and time course of microgravity effects on bone during space flight, where imaging technology cannot be employed. Increased bone resorption is a hallmark of space flight, while markers of bone formation are typically unchanged or decreased. Recent studies (after the deployment to ISS of the advanced resistive exercise device, ARED), have documented that astronauts with good nutritional intake (e.g., maintenance of body mass), good vitamin D status, and exercise maintained bone mineral density. These data are encouraging, but crewmembers exercising on the ARED do have alterations in bone biochemistry, specifically, bone resorption is still increased above preflight levels, but bone formation is also significantly increased. While this bone remodeling raises questions about the strength of the resulting bone, however documents beneficial effects of nutrition and exercise in counteracting bone loss of space flight.

  5. Diabetes mellitus related bone metabolism and periodontal disease

    Institute of Scientific and Technical Information of China (English)

    Ying-Ying Wu; E Xiao; Dana T Graves

    2015-01-01

    Diabetes mellitus and periodontal disease are chronic diseases affecting a large number of populations worldwide. Changed bone metabolism is one of the important long-term complications associated with diabetes mellitus. Alveolar bone loss is one of the main outcomes of periodontitis, and diabetes is among the primary risk factors for periodontal disease. In this review, we summarise the adverse effects of diabetes on the periodontium in periodontitis subjects, focusing on alveolar bone loss. Bone remodelling begins with osteoclasts resorbing bone, followed by new bone formation by osteoblasts in the resorption lacunae. Therefore, we discuss the potential mechanism of diabetes-enhanced bone loss in relation to osteoblasts and osteoclasts.

  6. [Abnormality in bone metabolism after burn].

    Science.gov (United States)

    Gong, X; Xie, W G

    2016-08-20

    Burn causes bone metabolic abnormality in most cases, including the changes in osteoblasts and osteoclasts, bone mass loss, and bone absorption, which results in decreased bone mineral density. These changes are sustainable for many years after burn and even cause growth retardation in burned children. The mechanisms of bone metabolic abnormality after burn include the increasing glucocorticoids due to stress response, a variety of cytokines and inflammatory medium due to inflammatory response, vitamin D deficiency, hypoparathyroidism, and bone loss due to long-term lying in bed. This article reviews the pathogenesis and regularity of bone metabolic abnormality after burn, the relationship between bone metabolic abnormality and burn area/depth, and the treatment of bone metabolic abnormality, etc. and discusses the research directions in the future. PMID:27562160

  7. Anorexia nervosa and bone metabolism

    OpenAIRE

    Fazeli, Pouneh K.; Klibanski, Anne

    2014-01-01

    Anorexia nervosa (AN) is a psychiatric disorder characterized by self-induced starvation with a lifetime prevalence of 2.2% in women. The most common medical co-morbidity in women with AN is bone loss, with over 85% of women having bone mineral density values more than one standard deviation below an age comparable mean. The low bone mass in AN is due to multiple hormonal adaptations to under nutrition, including hypothalamic amenorrhea and growth hormone resistance. Importa...

  8. Injection of testosterone may be safer and more effective than transdermal administration for combating loss of muscle and bone in older men.

    Science.gov (United States)

    Borst, Stephen E; Yarrow, Joshua F

    2015-06-15

    The value of testosterone replacement therapy (TRT) for older men is currently a topic of intense debate. While US testosterone prescriptions have tripled in the past decade (9), debate continues over the risks and benefits of TRT. TRT is currently prescribed for older men with either low serum testosterone (T) or low T plus accompanying symptoms of hypogonadism. The normal range for serum testosterone is 300 to 1,000 ng/dl. Serum T ≤ 300 ng/dl is considered to be low, and T ≤ 250 is considered to be frank hypogonadism. Most experts support TRT for older men with frank hypogonadism and symptoms. Treatment for men who simply have low T remains somewhat controversial. TRT is most frequently administered by intramuscular (im) injection of long-acting T esters or transdermally via patch or gel preparations and infrequently via oral administration. TRT produces a number of established benefits in hypogonadal men, including increased muscle mass and strength, decreased fat mass, increased bone mineral density, and improved sexual function, and in some cases those benefits are dose dependent. For example, doses of TRT administered by im injection are typically higher than those administered transdermally, which results in greater musculoskeletal benefits. TRT also produces known risks including development of polycythemia (Hct > 50) in 6% of those treated, decrease in HDL, breast tenderness and enlargement, prostate enlargement, increases in serum PSA, and prostate-related events and may cause suppression of the hypothalamic-pituitary-gonadal axis. Importantly, TRT does not increase the risk of prostate cancer. Putative risks include edema and worsening of sleep apnea. Several recent reports have also indicated that TRT may produce cardiovascular (CV) risks, while others report no risk or even benefit. To address the potential CV risks of TRT, we have recently reported via meta-analysis that oral TRT increases CV risk and suggested that the CV risk profile for im TRT

  9. Early Metacarpal Bone Mineral Density Loss Using Digital X-Ray Radiogrammetry and 3-Tesla Wrist MRI in Established Rheumatoid Arthritis: A Longitudinal One-Year Observational Study

    Directory of Open Access Journals (Sweden)

    Anshul Rastogi

    2015-01-01

    Full Text Available Objectives. Early change in rheumatoid arthritis (RA is characterised by periarticular osteopenia. We investigated the relationship of early metacarpal digital X-ray radiogrammetry bone mineral density (DXR-BMD change rate (RC-BMD, mg/cm2/month to longitudinal changes in hand and feet radiographic and wrist MRI scores over 1 year. Materials and Methods. 10 RA patients completed the study and had wrist 3T-MRI and hand and feet X-rays at various time points over 1 year. MRI was scored by RAMRIS, X-ray was done by van der Heijde modified Sharp scoring, and RC-BMD was analysed using dxr-online. Results. There was good correlation amongst the two scorers for MRI measures and ICC for erosions: 0.984, BME: 0.943, and synovitis: 0.657. Strong relationships were observed between RC-BMD at 12-week and 1-year change in wrist marrow oedema (BME (r=0.78, P=0.035 but not with erosion, synovitis, or radiographic scores. Conclusion. Early RC-BMD correlates with 1-year wrist BME change, which is a known predictor of future erosion and joint damage. However, in our pilot study, early RC-BMD did not show relationships to MRI erosion or radiographic changes over 1 year. This may reflect a slower kinetic in the appearance of MRI/radiographic erosions, generating the hypothesis that RC-BMD may be a more sensitive and early structural prognostic marker in RA follow-up.

  10. Loss of bone marrow adrenergic beta 1 and 2 receptors modifies transcriptional networks, reduces circulating inflammatory factors, and regulates blood pressure.

    Science.gov (United States)

    Ahmari, Niousha; Schmidt, Jordan T; Krane, Gregory A; Malphurs, Wendi; Cunningham, Bruce E; Owen, Jennifer L; Martyniuk, Christopher J; Zubcevic, Jasenka

    2016-07-01

    Hypertension (HTN) is a prevalent condition with complex etiology and pathophysiology. Evidence exists of significant communication between the nervous system and the immune system (IS), and there appears to be a direct role for inflammatory bone marrow (BM) cells in the pathophysiology of hypertension. However, the molecular and neural mechanisms underlying this interaction have not been characterized. Here, we transplanted whole BM cells from the beta 1 and 2 adrenergic receptor (AdrB1(tm1Bkk)AdrB2(tm1Bkk)/J) knockout (KO) mice into near lethally irradiated C57BL/6J mice to generate a BM AdrB1.B2 KO chimera. This allowed us to evaluate the role of the BM beta 1 and beta 2 adrenergic receptors in mediating BM IS homeostasis and regulating blood pressure (BP) in an otherwise intact physiological setting. Fluorescence-activated cell sorting demonstrated that a decrease in systolic and mean BP in the AdrB1.B2 KO chimera is associated with a decrease in circulating inflammatory T cells, macrophage/monocytes, and neutrophils. Transcriptomics in the BM identified 7,419 differentially expressed transcripts between the C57 and AdrB1.B2 KO chimera. Pathway analysis revealed differentially expressed transcripts related to several cell processes in the BM of C57 compared with AdrB1.B2 KO chimera, including processes related to immunity (e.g., T-cell activation, T-cell recruitment, cytokine production, leukocyte migration and function), the cardiovascular system (e.g., blood vessel development, peripheral nerve blood flow), and the brain (e.g., central nervous system development, neurite development) among others. This study generates new insight into the molecular events that underlie the interaction between the sympathetic drive and IS in modulation of BP. PMID:27235450

  11. Fusion of the ear bones

    Science.gov (United States)

    ... caused by: Birth (congenital) defect Infection Injury Symptoms Fusion of the bones leads to hearing loss, because the bones are not moving and vibrating in reaction to sound waves. Images Ear anatomy Medical findings based on ear anatomy References Torres AI, ...

  12. Green Tea and Bone Metabolism

    Science.gov (United States)

    Osteoporosis is a major health problem in elderly men and women. Epidemiological evidence has shown association between tea consumption and age-related bone loss in elderly men and women. The aim of this review is to provide a systemic review of green tea and bone health to cover the following topi...

  13. Oral Health and Bone Disease

    Science.gov (United States)

    ... for periodontitis and tooth loss. Role of the Dentist and Dental X Rays Research supported by the ... normal bone density. Because many people see their dentist more regularly than their doctor, dentists are in ...

  14. Bone metabolism in anorexia nervosa.

    Science.gov (United States)

    Fazeli, Pouneh K; Klibanski, Anne

    2014-03-01

    Anorexia nervosa (AN), a psychiatric disorder predominantly affecting young women, is characterized by self-imposed, chronic nutritional deprivation and distorted body image. AN is associated with a number of medical comorbidities including low bone mass. The low bone mass in AN is due to an uncoupling of bone formation and bone resorption, which is the result of hormonal adaptations aimed at decreasing energy expenditure during periods of low energy intake. Importantly, the low bone mass in AN is associated with a significant risk of fractures and therefore treatments to prevent bone loss are critical. In this review, we discuss the hormonal determinants of low bone mass in AN and treatments that have been investigated in this population. PMID:24419863

  15. Bone Metabolism in Anorexia Nervosa

    Science.gov (United States)

    Fazeli, Pouneh K.; Klibanski, Anne

    2014-01-01

    Anorexia nervosa (AN), a psychiatric disorder predominantly affecting young women, is characterized by self-imposed chronic nutritional deprivation and distorted body image. AN is associated with a number of medical co-morbidities including low bone mass. The low bone mass in AN is due to an uncoupling of bone formation and bone resorption, which is the result of hormonal adaptations aimed at decreasing energy expenditure during periods of low energy intake. Importantly, the low bone mass in AN is associated with a significant risk of fractures and therefore treatments to prevent bone loss are critical. In this review, we discuss the hormonal determinants of low bone mass in AN and treatments that have been investigated in this population. PMID:24419863

  16. Adynamic Bone Decreases Bone Toughness During Aging by Affecting Mineral and Matrix.

    Science.gov (United States)

    Ng, Adeline H; Omelon, Sidney; Variola, Fabio; Allo, Bedilu; Willett, Thomas L; Alman, Benjamin A; Grynpas, Marc D

    2016-02-01

    Adynamic bone is the most frequent type of bone lesion in patients with chronic kidney disease; long-term use of antiresorptive therapy may also lead to the adynamic bone condition. The hallmark of adynamic bone is a loss of bone turnover, and a major clinical concern of adynamic bone is diminished bone quality and an increase in fracture risk. Our current study aims to investigate how bone quality changes with age in our previously established mouse model of adynamic bone. Young and old mice (4 months old and 16 months old, respectively) were used in this study. Col2.3Δtk (DTK) mice were treated with ganciclovir and pamidronate to create the adynamic bone condition. Bone quality was evaluated using established techniques including bone histomorphometry, microcomputed tomography, quantitative backscattered electron imaging, and biomechanical testing. Changes in mineral and matrix properties were examined by powder X-ray diffraction and Raman spectroscopy. Aging controls had a natural decline in bone formation and resorption with a corresponding deterioration in trabecular bone structure. Bone turnover was severely blunted at all ages in adynamic animals, which preserved trabecular bone loss normally associated with aging. However, the preservation of trabecular bone mass and structure in old adynamic mice did not rescue deterioration of bone mechanical properties. There was also a decrease in cortical bone toughness in old adynamic mice that was accompanied by a more mature collagen matrix and longer bone crystals. Little is known about the effects of metabolic bone disease on bone fracture resistance. We observed an age-related decrease in bone toughness that was worsened by the adynamic condition, and this decrease may be due to material level changes at the tissue level. Our mouse model may be useful in the investigation of the mechanisms involved in fractures occurring in elderly patients on antiresorptive therapy who have very low bone turnover. PMID:26332924

  17. Bone Densitometry (Bone Density Scan)

    Science.gov (United States)

    ... of DXA Bone Densitometry? What is a Bone Density Scan (DXA)? Bone density scanning, also called dual-energy x-ray absorptiometry ( ... is today's established standard for measuring bone mineral density (BMD). An x-ray (radiograph) is a noninvasive ...

  18. Pleiotropic activity of lysophosphatidic acid in bone metastasis.

    Science.gov (United States)

    Peyruchaud, Olivier; Leblanc, Raphael; David, Marion

    2013-01-01

    Bone is a common metastatic site for solid cancers. Bone homeostasis is tightly regulated by intimate cross-talks between osteoblast (bone forming cells) and osteoclasts (bone resorbing cells). Once in the bone microenvironment, metastatic cells do not alter bone directly but instead perturb the physiological balance of the bone remodeling process controlled by bone cells. Tumor cells produce growth factors and cytokines stimulating either osteoclast activity leading to osteolytic lesions or osteoblast function resulting in osteoblastic metastases. Growth factors, released from the resorbed bone matrix or throughout osteoblastic bone formation, sustain tumor growth. Therefore, bone metastases are the sites of vicious cycles wherein tumor growth and bone metabolism sustain each other. Lysophosphatidic acid (LPA) promotes the growth of primary tumors and metastatic dissemination of cancer cells. We have shown that by acting on cancer cells via the contribution of blood platelets and the LPA-producing enzyme Autotaxin (ATX), LPA promotes the progression of osteolytic bone metastases in animal models. In the light of recent reports it would appear that the role of LPA in the context of bone metastases is complex involving multiple sources of lipid combined with direct and indirect effects on target cells. This review will present our current knowledge on the LPA/ATX axis involvement in osteolytic and osteoblastic skeletal metastases and will discuss the potential activity of LPA upstream and downstream metastasis seeding of cancer cells to bone as well as its implication in cancer induced bone pain. This article is part of a Special Issue entitled Advances in Lysophospholipid Research. PMID:22710393

  19. Bone metabolism during pregnancy.

    Science.gov (United States)

    Salles, Jean Pierre

    2016-06-01

    During pregnancy, mineral concentrations, of calcium and phosphorus in particular, are maintained at a high level in fetal blood so that the developing skeleton may accrete adequate mineral content. The placenta actively transports minerals for this purpose. Maternal intestinal absorption increases in order to meet the fetal demand for calcium, which is only partly dependent on calcitriol. Mineral regulation is essentially dependent on parathyroid hormone (PTH) and PTH-related protein (PTHrP). The calcium-sensing receptor (CaSR) regulates PTH and PTHrP production. If calcium intake is insufficient, the maternal skeleton will undergo resorption due to PTHrP. After birth, a switch from fetal to neonatal homeostasis occurs through increase in PTH and calcitriol, and developmental adaptation of the kidneys and intestines with bone turnover contributing additional mineral to the circulation. Calcium absorption becomes progressively active and dependent on calcitriol. The postnatal skeleton can transiently present with osteoposis but adequate mineral diet usually allows full restoration. Cases of primary osteoporosis must be identified. Loss of trabecular mineral content occurs during lactation in order to provide calcium to the newborn. This programmed bone loss is dependent on a "brain-breast-bone" circuit. The physiological bone resorption during reproduction does not normally cause fractures or persistent osteoporosis. Women who experience fracture are likely to have other causes of bone loss. PMID:27157104

  20. Bone morphogenetic proteins: Periodontal regeneration

    Directory of Open Access Journals (Sweden)

    Subramaniam M Rao

    2013-01-01

    Full Text Available Periodontitis is an infectious inflammatory disease that results in attachment loss and bone loss. Regeneration of the periodontal tissues entails de novo formation of cementum, periodontal ligament, and alveolar bone. Several different approaches are currently being explored to achieve complete, reliable, and reproducible regeneration of periodontal tissues. The therapeutic management of new bone formation is one of the key issues in successful periodontal regeneration. Bone morphogenetic proteins form a unique group of proteins within the transforming growth factor superfamily of genes and have a vital role in the regulation in the bone induction and maintenance. The activity of bone morphogenetic proteins was first identified in the 1960s, but the proteins responsible for bone induction were unknown until the purification and cloning of human bone morphogenetic proteins in the 1980s, because of their osteoinductive potential. Bone morphogenetic proteins have gained a lot of interest as therapeutic agents for treating periodontal defects. A systematic search for data related to the use of bone morphogenetic proteins for the regeneration of periodontal defects was performed to recognize studies on animals and human (PUBMED, MEDLINE, COCHRANE, and Google search. All the studies included showed noticeable regeneration of periodontal tissues with the use of BMP.

  1. Parathyroid Hormone Induces Bone Cell Motility and Loss of Mature Osteocyte Phenotype through L-Calcium Channel Dependent and Independent Mechanisms.

    Directory of Open Access Journals (Sweden)

    Matthew Prideaux

    results show that PTH induces loss of the mature osteocyte phenotype and promotes the motility of these cells. These two effects are mediated through different mechanisms. The loss of phenotype effect is independent and the cell motility effect is dependent on calcium signaling.

  2. Recursos fisioterapêuticos na prevenção da perda da densidade mineral óssea com lesão medular Physiotherapy resources on bone mineral density loss prevention in patients with spinal cord injuries

    Directory of Open Access Journals (Sweden)

    Daniele Rodrigues

    2004-09-01

    Full Text Available Este trabalho é uma revisão bibliográfica sobre os tratamentos fisioterápicos destinados a prevenção, estabilização ou lentificação da perda da densidade mineral óssea em pacientes portadores de lesão medular. Foram encontrados poucos trabalhos que se destinaram aos tratamentos fisioterápicos para desmineralização óssea. Em relação aos tipos de tratamentos encontrados foram: estimulação elétrica funcional, estimulação elétrica funcional com bicicleta ergométrica, ortostatismo e deambulação. Estes tratamentos são bastante questionáveis não tendo um consenso na metodologia, apresentando muitas controvérsias em relação à eficácia dos tratamentos, que serão discutidos no decorrer deste trabalho.This work is bibliographic review about the physiotherapy treatments for the attenuation, prevention and stabilization or slowing down of the bone mineral density loss in spinal cord injured patients. There are few studies focusing the efficiency the physiotherapy treatment for bone demineralization. The kinds of treatments found were: functional electrical stimulation, functional electrical stimulation with an bycicle ergometry, orthostatic and deambulation. These treatments are much questionable, and with no consensus on the methodology, with the lot of controversies in relation to the efficacy of the treatments, which are going to be discussed in the development of this study.

  3. Bone scanning in osteoporosis

    International Nuclear Information System (INIS)

    This paper reports on bone scanning in osteoporosis a diagnosis of osteoporosis most often follows fracture, and clearly this should be confirmed by x-ray. The bone scan therefore does not have an important role to play in the initial diagnosis of osteoporosis. While the exact mechanism by which the 99mTc-labeled diphosphonates localize in the skeleton is not fully understood, it is believed that they adsorb onto bone surfaces most probably via the calcium of hydroxyapatite crystals. Because the major factors that affect adsorption are osteoblastic activity and to a lesser extent skeletal vascularity, it is apparent that a bone scan image presents a functional display of skeletal metabolic activity. However, osteoporosis is a disorder in which gradual change in bone mass may occur over many years and, in keeping with this minor imbalance in skeletal metabolism, the bone scan appearances are usually normal. However, the scan images may appear of poor quality because of relatively low bone uptake of tracer with, on occasion, a washed-out pattern of activity in the axial and appendicular bone. It has been suggested that such a pattern occurs in severe or end-stage osteoporosis caused by markedly reduced osteoblastic activity. If kyphosis is observed on the bone scan or if there appears to be loss of spinal height with proximity of ribs to each other or increased closeness of rib cage to pelvis, then appearances suggest vertebral collapse and would be in keeping with a diagnosis of osteoporosis. Such evidence is, however, indirect and in practice a bone scan is an extremely unreliable means of diagnosing osteoporosis

  4. Immunosuppressant therapy and bone loss in ligature-induced periodontitis: a study in rats Terapia imunossupressora e perda óssea em periodontite induzida por ligaduras: um estudo em ratos

    Directory of Open Access Journals (Sweden)

    Patricia Furtado Gonçalves

    2003-03-01

    Full Text Available Immunosuppressive agents have been recognized as a factor affecting the soft tissues of the periodontium. However, little is known about their effect on periodontitis progression. The aim of the present study was to investigate the influence of cyclosporin A (CsA administration, associated or not with nifedipine, on the bone loss resulting from a ligature-induced periodontitis in rats. Twenty-four adult male Wistar rats were used. After anesthesia, the mandibular first molar was randomly assigned to receive the cotton ligature in the sulcular area while the contralateral tooth was left unligated. The animals were randomly assigned to one of the following treatments: Group A - saline solution; Group B - CsA (10 mg/kg; Group C - nifedipine (50 mg/kg; Group D - CsA (10 mg/kg plus nifedipine (50 mg/kg. Forty-five days later, the animals were sacrificed and the specimens routinely processed for serial decalcified sections. Intergroup analysis did not reveal significant differences regarding the bone loss volume in the ligated teeth between the experimental treatments (0.46 ± 0.11, 0.63 ± 0.32, 0.53 ± 0.14, 0.50 ± 0.18, for groups A, B, C and D, respectively - p > 0.05. However, intragroup analysis showed a greater bone loss volume in the ligated teeth than in the unligated ones (p O uso de agentes imunossupressores tem sido reconhecido como um fator que afeta os tecidos moles do periodonto. Entretanto, pouco se sabe sobre o seu efeito na progressão da periodontite. O objetivo do presente estudo foi investigar a influência da ciclosporina (CsA, associada ou não à nifedipina, na perda óssea resultante da periodontite induzida por ligaduras em ratos. Vinte e quatro ratos Wistar machos, adultos, foram incluídos no estudo. Após anestesia, foram colocadas ligaduras de fio de algodão ao redor do primeiro molar inferior direito ou esquerdo, aleatoriamente escolhido. O dente contralateral foi deixado sem ligadura. Os animais foram aleatoriamente

  5. Immunoregulation of bone remodelling

    Science.gov (United States)

    Singh, Ajai; Mehdi, Abbass A; Srivastava, Rajeshwer N; Verma, Nar Singh

    2012-01-01

    Remodeling, a continuous physiological process maintains the strength of the bones, which maintains a delicate balance between bone formation and resorption process. This review gives an insight to the complex interaction and correlation between the bone remodeling and the corresponding changes in host immunological environment and also summarises the most recent developments occuring in the understanding of this complex field. T cells, both directly and indirectly increase the expression of receptor activator of nuclear factor kB ligand (RANKL); a vital step in the activation of osteoclasts, thus positively regulates the osteoclastogenesis. Though various cytokines, chemikines, transcription factors and co-stimulatory molecules are shared by both skeletal and immune systems, but researches are being conducted to establish and analyse their role and / or control on this complex but vital process. The understanding of this part of research may open new horizons in the management of inflammatory and autoimmune diseases, resulting into bone loss and that of osteoporosis also. PMID:22837895

  6. Development of Bone Remodeling Model for Spaceflight Bone Physiology Analysis

    Science.gov (United States)

    Pennline, James A.; Werner, Christopher R.; Lewandowski, Beth; Thompson, Bill; Sibonga, Jean; Mulugeta, Lealem

    2015-01-01

    Current spaceflight exercise countermeasures do not eliminate bone loss. Astronauts lose bone mass at a rate of 1-2% a month (Lang et al. 2004, Buckey 2006, LeBlanc et al. 2007). This may lead to early onset osteoporosis and place the astronauts at greater risk of fracture later in their lives. NASA seeks to improve understanding of the mechanisms of bone remodeling and demineralization in 1g in order to appropriately quantify long term risks to astronauts and improve countermeasures. NASA's Digital Astronaut Project (DAP) is working with NASA's bone discipline to develop a validated computational model to augment research efforts aimed at achieving this goal.

  7. Low Bone Density

    Science.gov (United States)

    ... Density Exam/Testing › Low Bone Density Low Bone Density Low bone density is when your bone density ... people with normal bone density. Detecting Low Bone Density A bone density test will determine whether you ...

  8. Progesterone and Bone: Actions Promoting Bone Health in Women

    Directory of Open Access Journals (Sweden)

    Vanadin Seifert-Klauss

    2010-01-01

    Full Text Available Estradiol (E2 and progesterone (P4 collaborate within bone remodelling on resorption (E2 and formation (P4. We integrate evidence that P4 may prevent and, with antiresorptives, treat women's osteoporosis. P4 stimulates osteoblast differentiation in vitro. Menarche (E2 and onset of ovulation (P4 both contribute to peak BMD. Meta-analysis of 5 studies confirms that regularly cycling premenopausal women lose bone mineral density (BMD related to subclinical ovulatory disturbances (SODs. Cyclic progestin prevents bone loss in healthy premenopausal women with amenorrhea or SOD. BMD loss is more rapid in perimenopause than postmenopause—decreased bone formation due to P4 deficiency contributes. In 4 placebo-controlled RCTs, BMD loss is not prevented by P4 in postmenopausal women with increased bone turnover. However, 5 studies of E2-MPA co-therapy show greater BMD increases versus E2 alone. P4 fracture data are lacking. P4 prevents bone loss in pre- and possibly perimenopausal women; progesterone co-therapy with antiresorptives may increase bone formation and BMD.

  9. A tissue-engineered humanized xenograft model of human breast cancer metastasis to bone

    Directory of Open Access Journals (Sweden)

    Laure Thibaudeau

    2014-02-01

    Full Text Available The skeleton is a preferred homing site for breast cancer metastasis. To date, treatment options for patients with bone metastases are mostly palliative and the disease is still incurable. Indeed, key mechanisms involved in breast cancer osteotropism are still only partially understood due to the lack of suitable animal models to mimic metastasis of human tumor cells to a human bone microenvironment. In the presented study, we investigate the use of a human tissue-engineered bone construct to develop a humanized xenograft model of breast cancer-induced bone metastasis in a murine host. Primary human osteoblastic cell-seeded melt electrospun scaffolds in combination with recombinant human bone morphogenetic protein 7 were implanted subcutaneously in non-obese diabetic/severe combined immunodeficient mice. The tissue-engineered constructs led to the formation of a morphologically intact ‘organ’ bone incorporating a high amount of mineralized tissue, live osteocytes and bone marrow spaces. The newly formed bone was largely humanized, as indicated by the incorporation of human bone cells and human-derived matrix proteins. After intracardiac injection, the dissemination of luciferase-expressing human breast cancer cell lines to the humanized bone ossicles was detected by bioluminescent imaging. Histological analysis revealed the presence of metastases with clear osteolysis in the newly formed bone. Thus, human tissue-engineered bone constructs can be applied efficiently as a target tissue for human breast cancer cells injected into the blood circulation and replicate the osteolytic phenotype associated with breast cancer-induced bone lesions. In conclusion, we have developed an appropriate model for investigation of species-specific mechanisms of human breast cancer-related bone metastasis in vivo.

  10. Molecular Mechanisms of Bone Metastasis and Associated Muscle Weakness

    OpenAIRE

    Waning, David L.; Guise, Theresa A.

    2014-01-01

    Bone is a preferred site for breast cancer metastasis and leads to pathological bone loss due to increased osteoclast-induced bone resorption. The homing of tumor cells to the bone depends on the support of the bone microenvironment in which the tumor cells prime the pre-metastatic niche. The colonization and growth of tumor cells then depends on adaptations in the invading tumor cells to take advantage of normal physiological responses by mimicking bone marrow cells. This concerted effort by...

  11. High-dose therapy improved the bone remodelling compartment canopy and bone formation in multiple myeloma

    DEFF Research Database (Denmark)

    Hinge, Maja; Delaissé, Jean-Marie; Plesner, Torben; Clasen-Linde, Erik; Salomo, Morten; Levin Andersen, Thomas

    2015-01-01

    . Loss of this canopy has been associated with bone loss. This study addresses whether the bone remodelling in MM is improved by high-dose therapy. Bone marrow biopsies obtained from 20 MM patients, before and after first-line treatment with high-dose melphalan followed by autologous stem cell......Bone loss in multiple myeloma (MM) is caused by an uncoupling of bone formation to resorption trigged by malignant plasma cells. Increasing evidence indicates that the bone remodelling compartment (BRC) canopy, which normally covers the remodelling sites, is important for coupled bone remodelling...... transplantation, and from 20 control patients with monoclonal gammopathy of undetermined significance were histomorphometrically investigated. This investigation confirmed that MM patients exhibited uncoupled bone formation to resorption and reduced canopy coverage. More importantly, this study revealed that a...

  12. Bone tumor

    Science.gov (United States)

    ... physical exam. Tests that may be done include: Alkaline phosphatase blood level Bone biopsy Bone scan Chest x- ... also affect the results of the following tests: Alkaline phosphatase isoenzyme Blood calcium level Parathyroid hormone Blood phosphorus ...

  13. Odanacatib in postmenopausal women with low bone mineral density: a review of current clinical evidence

    OpenAIRE

    Zerbini, Cristiano A. F.; McClung, Michael R.

    2013-01-01

    Human bones are in a continuous process of remodeling that ensures renovation and maintenance of the skeletal mass. Bone remodeling has two phases that are normally coupled and balanced: bone resorption mediated by osteoclasts and bone formation mediated by osteoblasts. An increase in bone resorption over bone formation results in a progressive loss of bone mass and impairment of bone microarchitecture leading to osteoporosis and its associated fractures. Recent advances in the understanding ...

  14. Multi-slice CT evaluation of glenoid bone loss in patients with recurrent anterior shoulder dislocation%多层螺旋CT评价复发性肩关节前方脱位的前方关节盂骨质缺损的临床意义

    Institute of Scientific and Technical Information of China (English)

    崔志新; 张悦; 郑卓肇; 任阿红

    2012-01-01

    目的 在复发性肩关节前方脱位中,利用MSCT评估关节盂前方骨质缺损情况.方法 回顾分析108例复发性肩关节前脱位和12例单次肩关节脱位患者的MSCT检查,对比评价前方关节盂骨质缺损的发生率、程度及位置.利用Fisher精确概率法分析前方关节盂骨质缺损的发生率,利用Wilcoxon秩和检验比较前方关节盂骨质缺损的上下长径、深度及比例.结果 在复发性肩关节前脱位中,91.7%(99/108)存在前方关节盂的骨质缺损,缺损比例为(16.0±6.0)%,缺损中心位置介于时钟分区的2:20~ 4:25点(平均3:20点),62.0%(67/108)前方出现骨性Bankart病变,包括游离型39例(58.2%)及黏附型28例(41.8%).12例单次肩关节脱位中,9例出现前方关节盂骨质缺损,其缺损发生率(9/12;P=0.100)和缺损比例[(15.2±7.1)%;P=0.453]与复发性肩关节脱位比较差异均无统计学意义.结论 前方关节盂骨质缺损为复发性肩关节前方脱位的常见表现.%Objective To evaluate multi-slice CT (MSCT) in glenoid bone loss of patients with recurrent anterior shoulder dislocation.Methods MSCT findings of 108 patients with recurrent anterior shoulder dislocation and 12 with single anterior shoulder dislocation were retrospectively studied.The incidence,degrees and locations of glenoid bone losses were recorded.The incidence was analyzed with Fisher exact test.The maximum length,depth and proportion were compared with Wilcoxon rank sum test.Results Glenoid bone loss was detected in 91.7% (99/108)patients with recurrent anterior shoulder dislocation.The proportion of glenoid bone loss was ( 16.0 ± 6.0)%,and the central locations of glenoid bone loss were from 2: 20 to 4: 25 ( mean 3: 20).Sixty-two percent (67/108) patients had bony Bankart lesions in which 58.2% (39/67) bony fragments were free and 41.8% (28/67) were adherent to the anterior border of the glenoid cavity.Seventy-five percent (9/12) patients with single

  15. Tarsal bone disintegration in leprosy

    International Nuclear Information System (INIS)

    Tarsal bone disintegration is characterised by fragmentation and progressive collapse of one or more tarsal bones. It occurs in 10% of leprosy patients, and is responsible for many severe foot deformities associated with this disease. The main cause is micro-traumata, but sensory impairment, sepsis and osteoporosis are predisposing factors. In this series of 400 consecutive patients the talus and navicular were involved most frequently (72% of 119 tarsal lesions). Treatment, including prolonged immobilisation of the foot, results in dense sclerosis of the affected bone, and leaves a functional limb. Initial radiological features include bone fragmentation, calcified fragments in adjacent soft tissues, linear fractures, progressive compression and deformity of the affected bone, loss of density of the affected bone and flattening of the longitudinal plantar arch. Illustrative case histories are presented, and the differential diagnosis discussed. (author)

  16. Pharmacologic management of bone-related complications and bone metastases in postmenopausal women with hormone receptor-positive breast cancer

    Science.gov (United States)

    Yardley, Denise A

    2016-01-01

    There is a high risk for bone loss and skeletal-related events, including bone metastases, in postmenopausal women with hormone receptor-positive breast cancer. Both the disease itself and its therapeutic treatments can negatively impact bone, resulting in decreases in bone mineral density and increases in bone loss. These negative effects on the bone can significantly impact morbidity and mortality. Effective management and minimization of bone-related complications in postmenopausal women with hormone receptor-positive breast cancer remain essential. This review discusses the current understanding of molecular and biological mechanisms involved in bone turnover and metastases, increased risk for bone-related complications from breast cancer and breast cancer therapy, and current and emerging treatment strategies for managing bone metastases and bone turnover in postmenopausal women with hormone receptor-positive breast cancer.

  17. Bone effects of space flight analysis by quantum concept of bone remodelling

    Science.gov (United States)

    Parfitt, A. M.

    During the manned Skylab flights mineral losses from the calcaneum and changes in external calcium balance were in the ranges found for healthy subjects at bedrest. Calcium balance reached a nadir of -200 mg/day by two months with no change thereafter; the negative balance was due to increased urinary excretion with no change in net absorption. The total calcium loss averaged 18 g in the longest flight of 84 days; the densitiometric data suggested that about two-thirds of this came from trabecular bone and about one-third from cortical bone. These data could represent reversible bone loss due to increased birth rate of normal osteoclasts and osteoblasts and consequent increase in bone turnover and in reversible mineral deficit, or irreversible bone loss due to overactive osteoclasts and/or underactive osteoblasts. If the former explanation is correct, significant bone loss is unlikely whatever the duration of future flights, except in older persons already losing bone; if the latter explanation is correct, space flights longer than six months may lead to a significant increase in fracture risk in later life. Neither terrestrial immobilization nor unwilling animals in orbit are ideal models for the effects of space flight on human bone. To choose between reversible and irreversible mechanisms of bone loss, and to determine the effects of space flight on lifelong fracture risk, future astronauts and cosmonauts must undergo adequate histologic study of bone after in vivo tetracycline labeling.

  18. FSH and TSH in the Regulation of Bone Mass: The Pituitary/Immune/Bone Axis

    OpenAIRE

    Graziana Colaianni; Concetta Cuscito; Silvia Colucci

    2013-01-01

    Recent evidences have highlighted that the pituitary hormones have profound effects on bone, so that the pituitary-bone axis is now becoming an important issue in the skeletal biology. Here, we discuss the topical evidence about the dysfunction of the pituitary-bone axis that leads to osteoporotic bone loss. We will explore the context of FSH and TSH hormones arguing their direct or indirect role in bone loss. In addition, we will focus on the knowledge that both FSH and TSH have influence on...

  19. Men Miss Out on Bone Loss Screening

    Science.gov (United States)

    ... use, Gastrointestinal disease, Use of prostate cancer drugs, Alcohol abuse. Treatment options for men with osteoporosis are similar to those for women with the condition, the researchers said. Certain medications ...

  20. Targeting Bone Metabolism in Patients with Advanced Prostate Cancer: Current Options and Controversies

    OpenAIRE

    Tilman Todenhöfer; Arnulf Stenzl; Hofbauer, Lorenz C.; Rachner, Tilman D.

    2015-01-01

    Maintaining bone health remains a clinical challenge in patients with prostate cancer (PC) who are at risk of developing metastatic bone disease and increased bone loss due to hormone ablation therapy. In patients with cancer-treatment induced bone loss (CTIBL), antiresorptive agents have been shown to improve bone mineral density (BMD) and to reduce the risk of fractures. For patients with bone metastases, both zoledronic acid and denosumab delay skeletal related events (SREs) in the castrat...

  1. [Bone diseases].

    Science.gov (United States)

    Uebelhart, Brigitte; Rizzoli, René

    2016-01-13

    Calcium intake shows a small impact on bone mineral density and fracture risk. Denosumab is a more potent inhibitor of bone resorption than zoledronate. Abaloparatide, PTHrP analog, increases bone mineral density and decreases fracture incidence. Teriparatide could be delivered via a transdermic device. Romosozumab and odanacatib improve calculated bone strength. Sequential or combined treatments with denosumab and teriparatide could be of interest, but not denosumab followed by teriparatide. Fibrous dysplasia, Paget disease and hypophosphatasia are updated, as well as atypical femoral fracture and osteonecrosis of the jaw. PMID:26946704

  2. Bone Metabolism on ISS Missions

    Science.gov (United States)

    Smith, S. M.; Heer, M. A.; Shackelford, L. C.; Zwart, S. R.

    2014-01-01

    Spaceflight-induced bone loss is associated with increased bone resorption (1, 2), and either unchanged or decreased rates of bone formation. Resistive exercise had been proposed as a countermeasure, and data from bed rest supported this concept (3). An interim resistive exercise device (iRED) was flown for early ISS crews. Unfortunately, the iRED provided no greater bone protection than on missions where only aerobic and muscular endurance exercises were available (4, 5). In 2008, the Advanced Resistive Exercise Device (ARED), a more robust device with much greater resistance capability, (6, 7) was launched to the ISS. Astronauts who had access to ARED, coupled with adequate energy intake and vitamin D status, returned from ISS missions with bone mineral densities virtually unchanged from preflight (7). Bone biochemical markers showed that while the resistive exercise and adequate energy consumption did not mitigate the increased bone resorption, bone formation was increased (7, 8). The typical drop in circulating parathyroid hormone did not occur in ARED crewmembers. In 2014, an updated look at the densitometry data was published. This study confirmed the initial findings with a much larger set of data. In 42 astronauts (33 male, 9 female), the bone mineral density response to flight was the same for men and women (9), and those with access to the ARED did not have the typical decrease in bone mineral density that was observed in early ISS crewmembers with access to the iRED (Figure 1) (7). Biochemical markers of bone formation and resorption responded similarly in men and women. These data are encouraging, and represent the first in-flight evidence in the history of human space flight that diet and exercise can maintain bone mineral density on long-duration missions. However, the maintenance of bone mineral density through bone remodeling, that is, increases in both resorption and formation, may yield a bone with strength characteristics different from those

  3. From bone to breast and back - the bone cytokine RANKL and breast cancer

    OpenAIRE

    Hofbauer, Lorenz C; Rachner, Tilman D; Hamann, Christine

    2011-01-01

    Receptor activator of nuclear factor-κB ligand (RANKL) plays a pivotal role in regulating bone homeostasis. Osteoporosis and malignant bone disease secondary to breast cancer are characterized by enhanced RANKL production and increased bone turnover. Thus, denosumab, a monoclonal antibody to RANKL, has been developed and is now approved for various bone loss conditions. Recent results indicate that RANKL may also promote the development and osseous migration of breast cancer.

  4. Treatment of Infected Tibial Nonunion with Bone Defect Using Central Bone Grafting Technique

    OpenAIRE

    Gulan, Gordan; Jotanović, Zdravko; Jurdana, Hari; Šestan, Branko; Rapan, Saša; Rubinić, Dušan; Ravlić-Gulan, Jagoda

    2012-01-01

    Treatment of infected tibial nonunion with bone defect represents a challenge for every orthopaedic surgeon. Various methods of treatment have been described for nonunions with infection, bone loss or both. One of them is the central bone grafting technique, which is a safe and effective treatment for nonunions of the tibia. The technique involves placement of autogenous cancellous bone from the iliac crest on the anterior surface of the interosseous membrane with the aim of creating...

  5. Short Anabolic Peptides for Bone Growth.

    Science.gov (United States)

    Amso, Zaid; Cornish, Jillian; Brimble, Margaret A

    2016-07-01

    Loss of bone occurs in the age-related skeletal disorder, osteoporosis, leading to bone fragility and increased incidence of fractures, which are associated with enormous costs and substantial morbidity and mortality. Recent data indicate that osteoporotic fractures are more common than other diseases, which usually attract public attention (e.g., heart attack and breast cancer). The prevention and treatment of this skeletal disorder are therefore of paramount importance. Majority of osteoporosis medications restore skeletal balance by reducing osteoclastic activity, thereby reducing bone resorption. These agents, however, do not regenerate damaged bone tissue, leaving limited options for patients once bone loss has occurred. Recently, attention has turned to bone-anabolic agents. Such agents have the ability to increase bone mass and strength, potentially reversing structural damage. To date, only one bone-anabolic drug is available in the market. The discovery of more novel, cost-effective bone anabolic agents is therefore a priority to treat those suffering from this disabling condition. Short peptides offer an important alternative for the development of novel bone-anabolic agents given their high target binding specificity, which translates into potent activity with limited side effects. This review summarizes attempts in the identification of bone-anabolic peptides, and their development for promoting bone growth. PMID:27297498

  6. Bone tissue engineering

    OpenAIRE

    Black, Cameron R. M.; Goriainov, Vitali; Gibbs, David; Kanczler, Janos; Tare, Rahul S; Richard O. C. Oreffo

    2015-01-01

    Medical advances have led to a welcome increase in life expectancy. However, accompanying longevity introduces new challenges: increases in age-related diseases and associated reductions in quality of life. The loss of skeletal tissue that can accompany trauma, injury, disease or advancing years can result in significant morbidity and significant socio-economic cost and emphasise the need for new, more reliable skeletal regeneration strategies. To address the unmet need for bone augmentation,...

  7. Memory loss

    Science.gov (United States)

    ... as brain radiation , bone marrow transplant , or chemotherapy Concussion or head trauma Migraine headache Not enough oxygen ... tests) CT scan or MRI of the head EEG Lumbar puncture Treatment depends on the cause of ...

  8. Talking Bones.

    Science.gov (United States)

    Johnson, Jaclyn; Kassing, Sharon

    2002-01-01

    Describes cooperation with the Saint Louis Zoo to provide opportunities for elementary school students to learn about bones, how animals move, what they eat, and how much they grow. Uses biofacts which include bones, skulls, and other parts to make the laboratory a hands-on experience for students. (YDS)

  9. Bone Markers

    Science.gov (United States)

    ... bone turnover: C-telopeptide (C-terminal telopeptide of type 1 collagen (CTx)) – a marker for bone resorption. It is ... resorption include: N-telopeptide (N-terminal telopeptide of type 1 collagen (NTx)) – a peptide fragment from the amino terminal ...

  10. Bone-density changes after stroke.

    Science.gov (United States)

    Beaupre, Gary S; Lew, Henry L

    2006-05-01

    It has been many years since bone loss and fracture risk were first recognized as serious complications of stroke. Hip fracture is associated with a substantial increase in morbidity and mortality for stroke survivors, and therefore, assessing and maintaining skeletal health after stroke should be an important clinical goal. Recent long-term, prospective studies have illustrated a highly nonuniform pattern of bone changes after stroke. In general, there is significant bone loss on the paretic side, which is greatest in those patients with the most severe functional deficits. In some patients, bone loss in the paretic arm during the first year after stroke is the equivalent of >20 yrs of bone loss in healthy individuals of comparable age. Bone density in the nonparetic upper limb can actually increase after stroke, consistent with an increase in habitual use of the nonparetic hand. Bone density in the paretic lower limb can decrease by >10% in 12 mos poststroke are needed to determine how long excess bone loss continues after stroke. Studies with more subjects and with more varied disability levels are needed to better understand the relationships between functional deficits and bone loss. New metrics are needed to quantify the intensity and duration of physical activity in the upper and lower limbs that are consistent with previous research on the role of mechanical stimuli in bone adaptation. Finally, an assessment of skeletal health and the factors that affect bone quantity and quality should be a standard component in the clinical management of all survivors of stroke. PMID:16628156

  11. Bone densitometry

    DEFF Research Database (Denmark)

    Ravn, Pernille; Alexandersen, P; Møllgaard, A

    1999-01-01

    The bisphosphonates have been introduced as alternatives to hormone replacement therapy (HRT) for the treatment and prevention of postmenopausal osteoporosis. The expected increasing application in at clinical practice demands cost-effective and easily handled methods to monitor the effect on bone....... The weak response at the distal forearm during antiresorptive treatment has restricted the use of bone densitometry at this region. We describe a new model for bone densitometry at the distal forearm, by which the response obtained is comparable to the response in other regions where bone densitometry...... is much more expensive and technically complicated. By computerized iteration of single X-ray absorptiometry forearm scans we defined a region with 65% trabecular bone. The region was analyzed in randomized, double-masked, placebo- controlled trials: a 2-year trial with alendronate (n = 69), a 1-year...

  12. Abnormal bone remodelling in inflammatory arthritis

    Science.gov (United States)

    Bogoch, Earl R.; Moran, Erica

    1998-01-01

    Osteopenia is responsible for substantial comorbidity in patients suffering from rheumatoid arthritis and is an important factor in the surgical management of joint disease. In animal models of bone loss stimulated by inflammatory arthritis, increased bone remodelling and altered microstructure of bone have been documented. The subchondral bone plate near the joint surface is narrow and perforated by vascular inflammatory invasion, and in the shaft the thin cortices are weakened by giant resorption defects. Biomechanical tests and a mathematical model of bone strength suggest that cortical defects, much larger than those found in normal osteonal remodelling, are principally responsible for the experimentally observed loss of strength. Similarly, these defects may explain the increased femoral fracture risk in rheumatoid arthritis. The osteoclast, the cell resorbing bone, is demonstrated in increased number and activity in rheumatoid arthritis and in animal models. Bisphosphonates, drugs that inhibit osteoclast function, have been shown experimentally to reduce both focal and generalized osteopenia and to prevent loss of bone strength. Bisphosphonates also protect articular cartilage from damage characteristic of inflammatory arthritis. The mechanism of chondroprotection may be prevention of subchondral bone resorption by the osteoclast and also an altered distribution of bone marrow cells. Thus, bisphosphonates, currently in clinical use for other bone metabolic diseases, appear to have potential as prophylaxis and treatment for osteopenia and joint damage in inflammatory arthritis. PMID:9711159

  13. Effortless effort in bone regeneration: a review.

    Science.gov (United States)

    Nazirkar, Girish; Singh, Shailendra; Dole, Vinaykumar; Nikam, Akhilesh

    2014-06-01

    Since the beginning of the 20th century, the concept of osteoconduction in bony changes in the oral cavity showed a wide range of biomaterials and their osteoinductive potential that emerged gradually and has to a large extent improved the quality of the bone prior to the placement of an implant. Alveolar bone loss is a major concern after tooth extraction in patients and therefore atraumatic extraction procedures should be followed to avoid further bone loss. To overcome the alveolar bone loss and to augment support for placing dental implants, many bone regenerative substitutes are available such as allografts, autografts, xenografts, synthetic biomaterials and osteoactive agents. In light of the steady progress in bone grafting techniques and graft materials, it has become possible to improve the volume, width, and height of bone in deficient areas of the oral cavity. These advances in regenerative dentistry thus facilitate an easy and convenient placement of an implant in an ideal position and angulations resulting in superior esthetics and function. Bone grafting materials and their substitutes are the alternative filler materials, which facilitate to reduce additional surgical procedures, risks, chances of cross infection involved in placing autografts and allografts into the bony structures. This review literature highlights various biomaterials that are helpful in bone healing and thus create an anatomically favorable base for ideal implant placement. How to cite the article: Nazirkar G, Singh S, Dole V, Nikam A. Effortless effort in bone regeneration: A review. J Int Oral Health 2014;6(3):120-4. PMID:25083047

  14. Hearing Loss

    Science.gov (United States)

    ... labor & premature birth The newborn intensive care unit (NICU) Birth defects & other health conditions Loss & grief Tools & ... labor & premature birth The newborn intensive care unit (NICU) Birth defects & other health conditions Loss & grief Ask ...

  15. The response of bone to unloading

    Science.gov (United States)

    Bikle, D. D.; Halloran, B. P.

    1999-01-01

    Skeletal unloading leads to decreased bone formation and decreased bone mass. Bone resorption is uncoupled from bone formation, contributing to the bone loss. During spaceflight bone is lost principally from the bones most loaded in the 1-g environment, and some redistribution of bone from the lower extremities to the head appears to take place. Although changes in calcitropic hormones have been demonstrated during skeletal unloading (PTH and 1,25(OH)2D decrease), it remains unclear whether such changes account for or are in response to the changes in bone formation and resorption. Bed rest studies with human volunteers and hindlimb elevation studies with rats have provided useful data to help explain the changes in bone formation during spaceflight. These models of skeletal unloading reproduce a number of the conditions associated with microgravity, and the findings from such studies confirm many of the observations made during spaceflight. Determining the mechanism(s) by which loading of bone is sensed and translated into a signal(s) controlling bone formation remains the holy grail in this field. Such investigations couple biophysics to biochemistry to cell and molecular biology. Although studies with cell cultures have revealed biochemical responses to mechanical loads comparable to that seen in intact bone, it seems likely that matrix-cell interactions underlie much of the mechanocoupling. The role for systemic hormones such as PTH, GH, and 1,25(OH)2D compared to locally produced factors such as IGF-I, PTHrP, BMPs, and TGF-beta in modulating the cellular response to load remains unclear. As the mechanism(s) by which bone responds to mechanical load with increased bone formation are further elucidated, applications of this knowledge to other etiologies of osteoporosis are likely to develop. Skeletal unloading provides a perturbation in bone mineral homeostasis that can be used to understand the mechanisms by which bone mineral homeostasis is maintained, with

  16. Cancer treatment-related bone disease

    OpenAIRE

    Brown, Sue A.; Guise, Theresa A.

    2009-01-01

    Bone health may be impaired in many patients being treated for cancer. Primary tumors that reside in or form metastases to bone can result in compromised skeletal integrity. It has also been increasingly recognized that patients undergoing therapies for treatment of cancer are at higher risk of bone loss. These include androgen-deprivation therapy for prostate cancer and aromatase inhibitor therapy for breast cancer among others. Hypogonadism induced by many of these cancer treatments results...

  17. Bone Tumor

    Science.gov (United States)

    ... the knee in either the femur (thigh) or tibia (shinbone). Other common locations include the hip and ... bone that is weakened by a tumor to fracture, or break. This may be severely painful. Occasionally, ...

  18. Your Bones

    Science.gov (United States)

    ... a fall! If you play sports like football, soccer, lacrosse, or ice hockey, always wear all the ... to strengthen your bones is through exercise like running, jumping, dancing, and playing sports. Take these steps ...

  19. Streptozotocin, Type I Diabetes Severity and Bone

    Directory of Open Access Journals (Sweden)

    Motyl Katherine

    2009-03-01

    Full Text Available Abstract As many as 50% of adults with type I (T1 diabetes exhibit bone loss and are at increased risk for fractures. Therapeutic development to prevent bone loss and/or restore lost bone in T1 diabetic patients requires knowledge of the molecular mechanisms accounting for the bone pathology. Because cell culture models alone cannot fully address the systemic/metabolic complexity of T1 diabetes, animal models are critical. A variety of models exist including spontaneous and pharmacologically induced T1 diabetic rodents. In this paper, we discuss the streptozotocin (STZ-induced T1 diabetic mouse model and examine dose-dependent effects on disease severity and bone. Five daily injections of either 40 or 60 mg/kg STZ induce bone pathologies similar to spontaneously diabetic mouse and rat models and to human T1 diabetic bone pathology. Specifically, bone volume, mineral apposition rate, and osteocalcin serum and tibia messenger RNA levels are decreased. In contrast, bone marrow adiposity and aP2 expression are increased with either dose. However, high-dose STZ caused a more rapid elevation of blood glucose levels and a greater magnitude of change in body mass, fat pad mass, and bone gene expression (osteocalcin, aP2. An increase in cathepsin K and in the ratio of RANKL/OPG was noted in high-dose STZ mice, suggesting the possibility that severe diabetes could increase osteoclast activity, something not seen with lower doses. This may contribute to some of the disparity between existing studies regarding the role of osteoclasts in diabetic bone pathology. Examination of kidney and liver toxicity indicate that the high STZ dose causes some liver inflammation. In summary, the multiple low-dose STZ mouse model exhibits a similar bone phenotype to spontaneous models, has low toxicity, and serves as a useful tool for examining mechanisms of T1 diabetic bone loss.

  20. Streptozotocin, Type I Diabetes Severity and Bone

    Directory of Open Access Journals (Sweden)

    Motyl Katherine

    2009-01-01

    Full Text Available Abstract As many as 50% of adults with type I (T1 diabetes exhibit bone loss and are at increased risk for fractures. Therapeutic development to prevent bone loss and/or restore lost bone in T1 diabetic patients requires knowledge of the molecular mechanisms accounting for the bone pathology. Because cell culture models alone cannot fully address the systemic/metabolic complexity of T1 diabetes, animal models are critical. A variety of models exist including spontaneous and pharmacologically induced T1 diabetic rodents. In this paper, we discuss the streptozotocin (STZ-induced T1 diabetic mouse model and examine dose-dependent effects on disease severity and bone. Five daily injections of either 40 or 60 mg/kg STZ induce bone pathologies similar to spontaneously diabetic mouse and rat models and to human T1 diabetic bone pathology. Specifically, bone volume, mineral apposition rate, and osteocalcin serum and tibia messenger RNA levels are decreased. In contrast, bone marrow adiposity and aP2 expression are increased with either dose. However, high-dose STZ caused a more rapid elevation of blood glucose levels and a greater magnitude of change in body mass, fat pad mass, and bone gene expression (osteocalcin, aP2. An increase in cathepsin K and in the ratio of RANKL/OPG was noted in high-dose STZ mice, suggesting the possibility that severe diabetes could increase osteoclast activity, something not seen with lower doses. This may contribute to some of the disparity between existing studies regarding the role of osteoclasts in diabetic bone pathology. Examination of kidney and liver toxicity indicate that the high STZ dose causes some liver inflammation. In summary, the multiple low-dose STZ mouse model exhibits a similar bone phenotype to spontaneous models, has low toxicity, and serves as a useful tool for examining mechanisms of T1 diabetic bone loss.