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Sample records for cancer-induced bone loss

  1. 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.

  2. 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 Rie; Thomsen, Mette W;

    2009-01-01

    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 osteolysis......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...

  3. 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...

  4. 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 ...

  5. 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- ...

  6. 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...

  7. 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...

  8. 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...

  9. 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 ...

  10. 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.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    to low intensity or electrical stimulation. In contrast, A839977 had no effect on the tested parameters in naïve or sham animals. In awake animals, 40mg/kg A839977 (i.p) significantly reduced both early and late stage pain behavior. In contrast, no effect was observed in sham or vehicle-treated animals....... 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 advantageous......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...

  12. 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

  13. 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

  14. 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

  15. 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

  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

    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.

  17. 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 ...

  18. 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...

  19. Pathobiology and management of prostate cancer-induced bone pain: recent insights and future treatments.

    Science.gov (United States)

    Muralidharan, Arjun; Smith, Maree T

    2013-10-01

    Prostate cancer (PCa) has a high propensity for metastasis to bone. Despite the availability of multiple treatment options for relief of PCa-induced bone pain (PCIBP), satisfactory relief of intractable pain in patients with advanced bony metastases is challenging for the clinicians because currently available analgesic drugs are often limited by poor efficacy and/or dose-limiting side effects. Rodent models developed in the past decade show that the pathobiology of PCIBP comprises elements of inflammatory, neuropathic and ischemic pain arising from ectopic sprouting and sensitization of sensory nerve fibres within PCa-invaded bones. In addition, at the cellular level, PCIBP is underpinned by dynamic cross talk between metastatic PCa cells, cellular components of the bone matrix, factors associated with the bone microenvironment as well as peripheral components of the somatosensory system. These insights are aligned with the clinical management of PCIBP involving use of a multimodal treatment approach comprising analgesic agents (opioids, NSAIDs), radiotherapy, radioisotopes, cancer chemotherapy agents and bisphosphonates. However, a major drawback of most rodent models of PCIBP is their short-term applicability due to ethical concerns. Thus, it has been difficult to gain insight into the mal(adaptive) neuroplastic changes occurring at multiple levels of the somatosensory system that likely contribute to intractable pain at the advanced stages of metastatic disease. Specifically, the functional responsiveness of noxious circuitry as well as the neurochemical signature of a broad array of pro-hyperalgesic mediators in the dorsal root ganglia and spinal cord of rodent models of PCIBP is relatively poorly characterized. Hence, recent work from our laboratory to develop a protocol for an optimized rat model of PCIBP will enable these knowledge gaps to be addressed as well as identification of novel targets for drug discovery programs aimed at producing new analgesics

  20. 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

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

    Science.gov (United States)

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

    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 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.

  2. Arthroscopic treatment of glenoid bone loss.

    Science.gov (United States)

    Taverna, Ettore; Garavaglia, Guido; Ufenast, Henri; D'Ambrosi, Riccardo

    2016-02-01

    Recurrent anterior instability of the glenohumeral joint has long been an arduous problem to solve surgically, owing to its difficulty to the need to restore both osseous and dynamic constraints in the unstable shoulder. Biomechanical studies have indicated that glenoid bone loss shortens the safe arc through which the glenoid can resist axial forces; in these cases, a soft tissue repair alone may be insufficient to maintain stability. Clinical studies have confirmed that major bone loss is associated with an unfavourable outcome. The benefits of using arthroscopic procedures for surgical stabilization of the shoulder include smaller incisions and less soft tissue dissection, better access for repair and, potentially, the maximum respect for the undamaged anatomical structures. The biggest disadvantage of arthroscopic procedures until recently was the inability to successfully treat a significant bone defect. Over the last 10 years, several new arthroscopic techniques have been developed, providing new surgical options for successfully treating soft tissues and bony lesions in anterior-inferior glenohumeral instability. Level of evidence V. PMID:26658567

  3. 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.

  4. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Wahner, H.W.

    1987-02-01

    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.

  6. 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...

  7. 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

  8. 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

  9. 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...... in bone, where it may modulate both formation and resorption ultimately influencing the bone turnover process....

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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...

  15. 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

  16. 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 ...

  17. Effect of sex in the MRMT-1 model of cancer-induced bone pain [version 3; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Sarah Falk

    2015-11-01

    Full Text Available 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 commonly used in both males and females. Here we demonstrate that compared to male rats, female rats have an increased capacity for recovery following inoculation of MRMT-1 mammary cells, thus potentially causing a sex-dependent bias in interpretation of the data.

  18. Massive acetabular bone loss: Limits of trabecular metal cages

    Directory of Open Access Journals (Sweden)

    Villanueva-Martínez Manuel

    2011-01-01

    Full Text Available Massive acetabular bone loss (more than 50% of the acetabular area can result in insufficient native bone for stable fixation and long-term bone ingrowth of conventional porous cups. The development of trabecular metal cages with osteoconductive properties may allow a more biological and versatile approach that will help restore bone loss, thus reducing the frequency of implant failure in the short-to-medium term. We report a case of massive bone loss affecting the dome of the acetabulum and the ilium, which was treated with a trabecular metal cage and particulate allograft. Although the trabecular metal components had no intrinsic stability, they did enhance osseointegration and incorporation of a non-impacted particulate graft, thus preventing failure of the reconstruction. The minimum 50% contact area between the native bone and the cup required for osseointegration with the use of porous cups may not hold for new trabecular metal cups, thus reducing the need for antiprotrusio cages. The osteoconductive properties of trabecular metal enhanced allograft incorportation and iliac bone rebuilding without the need to fill the defect with multiple wedges nor protect the reconstruction with an antiprotrusio cage.

  19. Serum markers of bone metabolism show bone loss in hibernating bears

    Science.gov (United States)

    Donahue, S.W.; Vaughan, M.R.; Demers, L.M.; Donahue, H.J.

    2003-01-01

    Disuse osteopenia was studied in hibernating black bears (Ursus americanus) using serum markers of bone metabolism. Blood samples were collected from male and female, wild black bears during winter denning and active summer periods. Radioimmunoassays were done to determine serum concentrations of cortisol, the carboxy-terminal cross-linked telopeptide, and the carboxy-terminal propeptide of Type I procollagen, which are markers of hone resorption and formation, respectively. The bone resorption marker was significantly higher during winter hibernation than it was in the active summer months, but the bone formation marker was unchanged, suggesting an imbalance in bone remodeling and a net bone loss during disuse. Serum cortisol was significantly correlated with the bone resorption marker, but not with the bone formation marker. The bone formation marker was four- to fivefold higher in an adolescent and a 17-year-old bear early in the remobilization period compared with the later summer months. These findings raise the possibility that hibernating black bears may minimize bone loss during disuse by maintaining osteoblastic function and have a more efficient compensatory mechanism for recovering immobilization-induced bone loss than that of humans or other animals.

  20. 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.

  1. 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.

  2. 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

  3. Fractal texture analysis of the healing process after bone loss.

    Science.gov (United States)

    Borowska, Marta; Szarmach, Janusz; Oczeretko, Edward

    2015-12-01

    Radiological assessment of treatment effectiveness of guided bone regeneration (GBR) method in postresectal and postcystal bone loss cases, observed for one year. Group of 25 patients (17 females and 8 males) who underwent root resection with cystectomy were evaluated. The following combination therapy of intraosseous deficits was used, consisting of bone augmentation with xenogenic material together with covering regenerative membranes and tight wound closure. The bone regeneration process was estimated, comparing the images taken on the day of the surgery and 12 months later, by means of Kodak RVG 6100 digital radiography set. The interpretation of the radiovisiographic image depends on the evaluation ability of the eye looking at it, which leaves a large margin of uncertainty. So, several texture analysis techniques were developed and used sequentially on the radiographic image. For each method, the results were the mean from the 25 images. These methods compute the fractal dimension (D), each one having its own theoretic basis. We used five techniques for calculating fractal dimension: power spectral density method, triangular prism surface area method, blanket method, intensity difference scaling method and variogram analysis. Our study showed a decrease of fractal dimension during the healing process after bone loss. We also found evidence that various methods of calculating fractal dimension give different results. During the healing process after bone loss, the surfaces of radiographic images became smooth. The result obtained show that our findings may be of great importance for diagnostic purpose.

  4. 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...

  5. 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.

  6. 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

  7. Effect of bone loss in anterior shoulder instability

    Science.gov (United States)

    Garcia, Grant H; Liu, Joseph N; Dines, David M; Dines, Joshua S

    2015-01-01

    Anterior shoulder instability with bone loss can be a difficult problem to treat. It usually involves a component of either glenoid deficiency or a Hill-Sachs lesion. Recent data shows that soft tissue procedures alone are typically not adequate to provide stability to the shoulder. As such, numerous surgical procedures have been described to directly address these bony deficits. For glenoid defects, coracoid transfer and iliac crest bone block procedures are popular and effective. For humeral head defects, both remplissage and osteochondral allografts have decreased the rates of recurrent instability. Our review provides an overview of current literature addressing these treatment options and others for addressing bone loss complicating anterior glenohumeral instability. PMID:26085984

  8. Cadmium accelerates bone loss in ovariectomized mice and fetal rat limb bones in culture

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharyya, M.H.; Whelton, B.D.; Stern, P.H.; Peterson, D.P. (Argonne National Lab., IL (USA))

    1988-11-01

    Loss of bone mineral after ovariectomy was studied in mice exposed to dietary cadmium at 0.25, 5, or 50 ppm. Results show that dietary cadmium at 50 ppm increased bone mineral loss to a significantly greater extent in ovariectomized mice than in sham-operated controls. These results were obtained from two studies, one in which skeletal calcium content was determined 6 months after ovariectomy and a second in which {sup 45}Ca release from {sup 45}Ca-prelabeled bones was measured immediately after the start of dietary cadmium exposure. Furthermore, experiments with {sup 45}Ca-prelabeled fetal rat limb bones in culture demonstrated that Cd at 10 nM in the medium, a concentration estimated to be in the plasma of mice exposed to 50 ppm dietary Cd, strikingly increased bone resorption. These in vitro results indicate that cadmium may enhance bone mineral loss by a direct action on bone. Results of the in vivo studies are consistent with a significant role of cadmium in the etiology of Itai-Itai disease among postmenopausal women in Japan and may in part explain the increased risk of postmenopausal osteoporosis among women who smoke.

  9. 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...

  10. 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.

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

    Science.gov (United States)

    Fan, Ruoxun; Gong, He; 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. PMID:27403206

  12. Cell Mechanisms of Bone Tissue Loss Under Space Flight Conditions

    Science.gov (United States)

    Rodionova, Natalia

    bone tissue. The macrophages are incorporated into resorption lacunaes and utilize the organic matrix and cellular detritus. The products are secreted to remodeling zones and act as haemoattractants for recruiting and subsequent differentiation here of the osteogenic precursor cells. However, as shown by our results with 3H-glycine, in absence of mechanical stimulus the activization of osteoblastogenesis either doesn't occur, or takes place on a smaller scale. According to our electron-microscopic data a load deficit leads to an adaptive differentiation of fibroblasts and adipocytes in this remodeling zones. This sequence of events is considered as a mechanism of bone tissue loss which underlies the development of osteopenia and osteoporosis under space flight condition.

  13. 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.

  14. Protection by salidroside against bone loss via inhibition of oxidative stress and bone-resorbing mediators.

    Directory of Open Access Journals (Sweden)

    Jin-Kang Zhang

    Full Text Available Oxidative stress is a pivotal pathogenic factor for bone loss in mouse model. Salidroside, a phenylpropanoid glycoside extracted from Rhodiola rosea L, exhibits potent antioxidative effects. In the present study, we used an in vitro oxidative stress model induced by hydrogen peroxide (H(2O(2 in MC3T3-E1 cells and a murine ovariectomized (OVX osteoporosis model to investigate the protective effects of salidroside on bone loss and the related mechanisms. We demonstrated that salidroside caused a significant (P<0.05 elevation of cell survival, alkaline phosphatase (ALP staining and activity, calcium deposition, and the transcriptional expression of Alp, Col1a1 and Osteocalcin (Ocn in the presence of H(2O(2. Moreover, salidroside decreased the production of intracellular reactive oxygen species (ROS, and osteoclast differentiation inducing factors such as receptor activator of nuclear factor-kB ligand (RANKL and IL-6 induced by H(2O(2. In vivo studies further demonstrated that salidroside supplementation for 3 months caused a decrease in malondialdehyde (MDA and an increase in reduced glutathione (GSH concentration in blood of ovariectomized mouse (P<0.05, it also improved trabecular bone microarchitecture and bone mineral density in the fourth lumbar vertebra and distal femur. Our study indicated that the protection provided by salidroside in alleviating bone loss was mediated, at least in part, via inhibition of the release of bone-resorbing mediators and oxidative damage to bone-forming cells, suggesting that salidroside can be used as an effective remedy in the treatment or prevention of osteoporosis.

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. Plasma cell gingivitis with severe alveolar bone loss.

    Science.gov (United States)

    Kumar, Vivek; Tripathi, Amitandra Kumar; Saimbi, Charanjit Singh; Sinha, Jolly

    2015-01-16

    Plasma cell gingivitis is a rare benign condition of the gingiva characterised by sharply demarcated erythaematous and oedematous gingiva often extending up to the muco gingival junction. It is considered a hypersensitive reaction. It presents clinically as a diffuse, erythaematous and papillary lesion of the gingiva, which frequently bleeds, with minimal trauma. This paper presents a case of a 42-year-old man who was diagnosed with plasma cell gingivitis, based on the presence of plasma cells in histological sections, and severe alveolar bone loss at the affected site, which was managed by surgical intervention.

  1. 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.

  2. 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...

  3. 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

  4. 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...

  5. 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....

  6. The osteogenic effects of swimming, jumping, and vibration on the protection of bone quality from disuse bone loss.

    Science.gov (United States)

    Falcai, M J; Zamarioli, A; Okubo, R; de Paula, F J A; Volpon, J B

    2015-06-01

    We assessed and compared the effects of swimming, jumping, and vibration therapies on the prevention of bone loss because of unloading. Eighty Wistar rats were randomly divided into eight groups: S, permanent hind limb-suspended rats; CON, control rats; S + Swim, unloading interrupted by swimming exercise; S + C(Swim), suspension interrupted by regular weight-bearing with the same duration as in the S + Swim protocol; S + Jump, unloading interrupted by jumping exercise; S + C(Jump), suspension interrupted for regular weight-bearing as in the S + Jump group; S + Vibr, unloading interrupted by vibration; and S + C(Vibr), suspension with interruptions for regular weight-bearing with the same protocol as that used for the S + Vibr rats. At the end of the experiment, the bone mineral density, bone strength, histomorphometric parameters, and serum levels of the bone markers were analyzed. The hind limb-suspended rats exhibited bone quality loss. In contrast, the trained rats showed a significant increase in bone mass, bone strength, bone formation, and serum levels of bone markers compared with the respective controls. Although we did not find a significant difference among the three physical exercises, the osteogenic effect of vibration was slightly lower than that of swimming and jumping. Thus, all physical exercises were efficient in preventing bone loss because of unloading and preserving bone quality. PMID:24779886

  7. 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...

  8. Intrusion of incisors in adult patients with marginal bone loss.

    Science.gov (United States)

    Melsen, B; Agerbaek, N; Markenstam, G

    1989-09-01

    Elongated and spaced incisors are common problems in patients suffering from severe periodontal disease. Thirty patients characterized by marginal bone loss and deep overbite were treated by intrusion of incisors. Three different methods for intrusion were applied: (1) J hooks and extraoral high-pull headgear, (2) utility arches, (3) intrusion bent into a loop in a 0.17 x 0.25-inch wire, and (4) base arch as described by Burstone. The intrusion was evaluated from the displacement of the apex, incision, and the center of resistance of the most prominent or elongated central incisor. Change in the marginal bone level and the amount of root resorption were evaluated on standardized intraoral radiographs. The pockets were assessed by standardized probing and the clinical crown length was measured on study casts. The results showed that the true intrusion of the center of resistance varied from 0 to 3.5 mm and was most pronounced when intrusion was performed with a base arch. The clinical crown length was generally reduced by 0.5 to 1.0 mm. The marginal bone level approached the cementoenamel junction in all but six cases. All cases demonstrated root resorption varying from 1 to 3 mm. The total amount of alveolar support--that is, the calculated area of the alveolar wall--was unaltered or increased in 19 of the 30 cases. The dependency of the results on the oral hygiene, the force distribution, and the perioral function was evaluated in relation to the individual cases. It was obvious that intrusion was best performed when (1) forces were low (5 to 15 gm per tooth) with the line of action of the force passing through or close to the center of resistance, (2) the gingiva status was healthy, and (3) no interference with perioral function was present.

  9. Epigallocatechin gallate (EGCG) suppresses lipopolysaccharide-induced inflammatory bone resorption, and protects against alveolar bone loss in mice.

    Science.gov (United States)

    Tominari, Tsukasa; Matsumoto, Chiho; Watanabe, Kenta; Hirata, Michiko; Grundler, Florian M W; Miyaura, Chisato; Inada, Masaki

    2015-01-01

    Epigallocatechin gallate (EGCG), a major polyphenol in green tea, possesses antioxidant properties and regulates various cell functions. Here, we examined the function of EGCG in inflammatory bone resorption. In calvarial organ cultures, lipopolysaccharide (LPS)-induced bone resorption was clearly suppressed by EGCG. In osteoblasts, EGCG suppressed the LPS-induced expression of COX-2 and mPGES-1 mRNAs, as well as prostaglandin E2 production, and also suppressed RANKL expression, which is essential for osteoclast differentiation. LPS-induced bone resorption of mandibular alveolar bones was attenuated by EGCG in vitro, and the loss of mouse alveolar bone mass was inhibited by the catechin in vivo.

  10. Effect of anti-osteoporotic agents on the prevention of bone loss in unloaded bone.

    Science.gov (United States)

    Siu, Wing Sum; Ko, Chun Hay; Hung, Leung Kim; Lau, Ching Po; Lau, Clara Bik San; Fung, Kwok Pui; Leung, Ping Chung

    2013-10-01

    Pharmaceutical countermeasures to treat disuse osteoporosis are rarely studied. Pharmaceutical studies for the treatment and prevention of osteoporosis depend on the ovariectomized rat model, which is a suitable model for the disease in women. Disuse osteoporosis affects men and women, but there is lack of awareness and relevant pharmaceutical studies for this condition. The objectives of this study were to verify the validity of an unusual tail-suspension rat model in the induction of disuse osteoporosis and subsequent pharmaceutical treatments. This model was created by unloading the hind limbs of the rats in order to create a state of weightlessness in their hindlimb bones. Validation of the model was performed with non-suspended rats. This study included five groups of suspended rats fed with different agents, such as distilled water (control), high-, medium- and low-dose raloxifene and a bisphosphonate (alendronate). The experiment lasted for 28 days. Comparisons were made between the suspended control and treatment groups. Ovariectomized and sham‑operated rats were also included as a reference for bone changes during osteoporosis. Changes in bone mineral density (BMD) at the distal femur and proximal tibia, microarchitecture at the distal femur and biomechanical strength at the diaphyseal femur were studied. Reduction of BMD and deterioration of trabeculae were similar between the suspended control and ovariectomized rats. Loss of BMD induced by tail suspension was reduced most effectively by medium-dose raloxifene. Deterioration of trabecular microarchitecture was also prevented by raloxifene. The tail-suspension rat model is suitable for the study of disuse osteoporosis under the effects of various therapeutic agents. The preventive effects of raloxifene against bone loss under disuse conditions have been demonstrated using this model.

  11. 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

  12. 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.

  13. 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...

  14. Vitamin K supplementation does not prevent bone loss in ovariectomized Norway rats

    Science.gov (United States)

    Despite plausible biological mechanisms, the differential abilities of phylloquinone (PK) and menaquinones (MKn) to prevent bone loss remain controversial. The objective of the current study was to compare the effects of PK, menaquinone-4 (MK-4) and menaquinone-7(MK-7) on the rate of bone loss in o...

  15. An "S-shaped" relationship between smoking duration and alveolar bone loss : generating a hypothesis

    NARCIS (Netherlands)

    Schuller, A A; Holst, D

    2001-01-01

    BACKGROUND: A number of epidemiological studies have shown that smoking is a risk factor for periodontal disease. Little is known about the relationship between smoking duration and alveolar bone loss. The purpose of this research was to describe the prevalence of alveolar bone loss according to smo

  16. 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...

  17. 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 ...

  18. 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

  19. Bone loss during simulated weightlessness - Is it glucocorticoid mediated?

    Science.gov (United States)

    Bikle, D. D.; Halloran, B. P.; Cone, C. M.; Morey-Holton, E.

    1985-01-01

    Elevating the hindquarters of a rat by the tail unweights the hind limbs but maintains normal weight-bearing by the forelimbs. This maneuver leads to a decrease in bone mass and calcium content in the unweighted bones (e.g., tibia and L1 vertebra), but not in the normally weighted bones (e.g., humerus and mandible). Potentially, the stress of the maneuver, mediated by increased glucocorticoid production and secretion, could explain the decreased bone formation, rather than the skeletal unweighting per se. To test this possibility, the effects of adrenalectomy on the response of bone to the unweighting of the hind limbs of normal rats were evaluated.

  20. 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.

  1. 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

  2. GLP-1 receptor agonist treatment increases bone formation and prevents bone loss in weight-reduced obese women

    DEFF Research Database (Denmark)

    Iepsen, Eva Pers Winning; Lundgren, Julie Rehné; Hartmann, Bolette;

    2015-01-01

    markers (CTX-1 and P1NP) were investigated before, after weight loss and after 52 weeks weight maintenance. Primary end points: Change in BMC and bone markers after 52 weeks weight maintenance with or without GLP-1 RA treatment. RESULTS: Total, pelvic and arm-leg BMC decreased during weight maintenance....... In the liraglutide group, the bone formation marker P1NP increased by 16% (7±3 μg/L) vs a 2% (-1±4 μg/L) decrease in the control group (pmaintenance phase. CONCLUSIONS: Treatment with a long-acting GLP-1 RA increased bone formation by 16......% and prevented bone loss after weight loss obtained through a low calorie-diet, supporting its role as a safe weight-lowering agent....

  3. Genetic polymorphisms of the interleukin-1 gene and early marginal bone loss around endosseous dental implants.

    Science.gov (United States)

    Shimpuku, Hitomi; Nosaka, Yasuhiro; Kawamura, Tatsuya; Tachi, Yoichi; Shinohara, Mitsuko; Ohura, Kiyoshi

    2003-08-01

    Dental implant surgery commonly proceeds in two stages. It is generally accepted that bone loss around implants does not occur at stage-II surgery because implants do not receive mechanical loading. However, early marginal bone loss around implants occasionally does occur during the healing period. Genetic polymorphisms in the interleukin-1 (IL-1) gene have been reported to be important for bone homeostasis and susceptibility to bone disease. We therefore investigated whether the idiopathic early marginal bone loss around implants is related to polymorphisms in the IL-1 gene. We performed a case-control study. Patients demonstrating marginal bone loss around implants at stage-II surgery were designated as the 'marginal bone loss (+)' group and those without bone loss as the 'marginal bone loss (-)' group. Polymorphisms of the IL-1alpha and IL-1beta genes (IL-1A-889, IL-1B-511 and IL-1B+3954) were detected by restriction fragment length polymorphism using NcoI, AvaI and TaqI after polymerase chain reactions. A total of 251 implants were placed in 39 patients. Marginal bone loss was observed in 36 implants. The patients with IL-1B-511 2/2 genotype exhibited a significantly higher occurrence of marginal bone loss than those with IL-1B-511 1/1 or 1/2 genotypes (OR=5.63; 95% CI=1.20-26.42; P=0.033). Multiple logistic regression analyses showed a markedly increased odds ratio (OR=10.86; 95% CI=1.64-71.90) in IL-1B-511 2/2 genotype carriers, while ORs of the other risk factors for bone loss, such as age, smoking status, post-menopausal women and bone quality, remained between 0.44 and 6.20. There was no significant difference in the distributions of the IL-1B+3954 and IL-1 A-889 genotypes between cases and controls. These data suggest that the IL-1B-511 2/2 genotype has a significant association with the incidence of early marginal bone loss around endosseous implants. PMID:12869004

  4. Bone marrow transplantation improves autoinflammation and inflammatory bone loss in SH3BP2 knock-in cherubism mice.

    Science.gov (United States)

    Yoshitaka, Teruhito; Kittaka, Mizuho; Ishida, Shu; Mizuno, Noriyoshi; Mukai, Tomoyuki; Ueki, Yasuyoshi

    2015-02-01

    Cherubism (OMIM#118400) is a genetic disorder in children characterized by excessive jawbone destruction with proliferation of fibro-osseous lesions containing a large number of osteoclasts. Mutations in the SH3-domain binding protein 2 (SH3BP2) are responsible for cherubism. Analysis of the knock-in (KI) mouse model of cherubism showed that homozygous cherubism mice (Sh3bp2(KI/KI)) spontaneously develop systemic autoinflammation and inflammatory bone loss and that cherubism is a TNF-α-dependent hematopoietic disorder. In this study, we investigated whether bone marrow transplantation (BMT) is effective for the treatment of inflammation and bone loss in Sh3bp2(KI/KI) mice. Bone marrow (BM) cells from wild-type (Sh3bp2(+/+)) mice were transplanted to 6-week-old Sh3bp2(KI/KI) mice with developing inflammation and to 10-week-old Sh3bp2(KI/KI) mice with established inflammation. Six-week-old Sh3bp2(KI/KI) mice transplanted with Sh3bp2(+/+) BM cells exhibited improved body weight loss, facial swelling, and survival rate. Inflammatory lesions in the liver and lung as well as bone loss in calvaria and mandibula were ameliorated at 10weeks after BMT compared to Sh3bp2(KI/KI) mice transplanted with Sh3bp2(KI/KI) BM cells. Elevation of serum TNF-α levels was not detected after BMT. BMT was effective for up to 20weeks in 6-week-old Sh3bp2(KI/KI) mice transplanted with Sh3bp2(+/+) BM cells. BMT also ameliorated the inflammation and bone loss in 10-week-old Sh3bp2(KI/KI) mice. Thus our study demonstrates that BMT improves the inflammation and bone loss in cherubism mice. BMT may be effective for the treatment of cherubism patients.

  5. 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.

  6. Anti-transforming growth factor ß antibody treatment rescues bone loss and prevents breast cancer metastasis to bone.

    Science.gov (United States)

    Biswas, Swati; Nyman, Jeffry S; Alvarez, JoAnn; Chakrabarti, Anwesa; Ayres, Austin; Sterling, Julie; Edwards, James; Rana, Tapasi; Johnson, Rachelle; Perrien, Daniel S; Lonning, Scott; Shyr, Yu; Matrisian, Lynn M; Mundy, Gregory R

    2011-01-01

    Breast cancer often metastasizes to bone causing osteolytic bone resorption which releases active TGFβ. Because TGFβ favors progression of breast cancer metastasis to bone, we hypothesized that treatment using anti-TGFβ antibody may reduce tumor burden and rescue tumor-associated bone loss in metastatic breast cancer. In this study we have tested the efficacy of an anti-TGFβ antibody 1D11 preventing breast cancer bone metastasis. We have used two preclinical breast cancer bone metastasis models, in which either human breast cancer cells or murine mammary tumor cells were injected in host mice via left cardiac ventricle. Using several in vivo, in vitro and ex vivo assays, we have demonstrated that anti-TGFβ antibody treatment have significantly reduced tumor burden in the bone along with a statistically significant threefold reduction in osteolytic lesion number and tenfold reduction in osteolytic lesion area. A decrease in osteoclast numbers (p = 0.027) in vivo and osteoclastogenesis ex vivo were also observed. Most importantly, in tumor-bearing mice, anti-TGFβ treatment resulted in a twofold increase in bone volume (ptreatment with anti-TGFβ antibody increased the mineral-to-collagen ratio in vivo, a reflection of improved tissue level properties. Moreover, anti-TGFβ antibody directly increased mineralized matrix formation in calverial osteoblast (p = 0.005), suggesting a direct beneficial role of anti-TGFβ antibody treatment on osteoblasts. Data presented here demonstrate that anti-TGFβ treatment may offer a novel therapeutic option for tumor-induced bone disease and has the dual potential for simultaneously decreasing tumor burden and rescue bone loss in breast cancer to bone metastases. This approach of intervention has the potential to reduce skeletal related events (SREs) in breast cancer survivors.

  7. 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.

  8. 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.

  9. 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.

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

    Science.gov (United States)

    Zhu, Xiaofu; Amir, Eitan; Singh, Gurmit; Clemons, Mark; Addison, Christina

    2014-03-01

    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.

  11. 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.

  12. 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.

  13. 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

  14. 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...

  15. 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.

  16. 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...

  17. The Ovariectomized Rat as a Model for Studying Alveolar Bone Loss in Postmenopausal Women

    Directory of Open Access Journals (Sweden)

    Bryan D. Johnston

    2015-01-01

    Full Text Available In postmenopausal women, reduced bone mineral density at the hip and spine is associated with an increased risk of tooth loss, possibly due to a loss of alveolar bone. In turn, having fewer natural teeth may lead to compromised food choices resulting in a poor diet that can contribute to chronic disease risk. The tight link between alveolar bone preservation, tooth retention, better nutritional status, and reduced risk of developing a chronic disease begins with the mitigation of postmenopausal bone loss. The ovariectomized rat, a widely used preclinical model for studying postmenopausal bone loss that mimics deterioration of bone tissue in the hip and spine, can also be used to study mineral and structural changes in alveolar bone to develop drug and/or dietary strategies aimed at tooth retention. This review discusses key findings from studies investigating mandible health and alveolar bone in the ovariectomized rat model. Considerations to maximize the benefits of this model are also included. These include the measurement techniques used, the age at ovariectomy, the duration that a rat is studied after ovariectomy and habitual diet consumed.

  18. 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.

  19. Network Analysis Implicates Alpha-Synuclein (Snca) in the Regulation of Ovariectomy-Induced Bone Loss

    Science.gov (United States)

    Calabrese, Gina; Mesner, Larry D.; Foley, Patricia L.; Rosen, Clifford J.; Farber, Charles R.

    2016-01-01

    The postmenopausal period in women is associated with decreased circulating estrogen levels, which accelerate bone loss and increase the risk of fracture. Here, we gained novel insight into the molecular mechanisms mediating bone loss in ovariectomized (OVX) mice, a model of human menopause, using co-expression network analysis. Specifically, we generated a co-expression network consisting of 53 gene modules using expression profiles from intact and OVX mice from a panel of inbred strains. The expression of four modules was altered by OVX, including module 23 whose expression was decreased by OVX across all strains. Module 23 was enriched for genes involved in the response to oxidative stress, a process known to be involved in OVX-induced bone loss. Additionally, module 23 homologs were co-expressed in human bone marrow. Alpha synuclein (Snca) was one of the most highly connected “hub” genes in module 23. We characterized mice deficient in Snca and observed a 40% reduction in OVX-induced bone loss. Furthermore, protection was associated with the altered expression of specific network modules, including module 23. In summary, the results of this study suggest that Snca regulates bone network homeostasis and ovariectomy-induced bone loss. PMID:27378017

  20. Loss of bone mass after Colles' fractrur:a follow-up study

    Institute of Scientific and Technical Information of China (English)

    戴力扬; 蒋雷生

    2004-01-01

    Background Colles' fracture usually associated with osteoporosis is regarded as the predictor of subsequent osteoporotic fracture. However, it is not clear how the local changes of bone mass take place during the course of treatment and whether the changes are related to clinical practice. The objective of the current study was to investigate the local changes of bone mass in patients with Colles' fracture and their possible clinical relevance in a follow-up study.Methods The radiograms of the second metacarpal in 64 patients with Colles' fracture were assessed for bone density immediately after fracture, 6 weeks, 6 months and 1 year after fracture, respectively. Functional results were evaluated at one year.Results Bone mass six weeks after Colles' fracture was significantly decreased without returning to normal at one year though increased bone mass had been identified 6 months after fracture (P< 0.05), (P< 0.01). At one year significant (P< 0.05) or highly significant (P< 0.01) correlations were observed between bone mass indices of metacarpal and functional results, indicating that poor function is associated with lower bone density. Significant differences (P< 0.05) between fracture patterns also suggested that patients with more severe fractures have a more pronounced bone loss.Conclusions Bone loss during the course of treatment will have a direct effect upon the prognosis, so different treatment should be proposed for different patterns of fractures. Active exercise should be made to improve the recovery of bone mass.

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

    Directory of Open Access Journals (Sweden)

    Bauer M

    2012-06-01

    Full Text Available M Bauer,1 J Bryce,2 P Hadji11University of Marburg, Marburg, Germany; 2National Cancer Institute, Naples, ItalyAbstract: Postmenopausal women have an increased risk of osteopenia and osteoporosis due to loss of the bone-protective effects of estrogen. Disease-related processes may also contribute to the risk of bone loss in postmenopausal women with breast cancer. One of the most common and severe safety issues associated with cancer therapy for patients with breast cancer is bone loss and the associated increase in risk of fractures. This paper reviews the recent literature pertaining to aromatase inhibitor (AI-associated bone loss, and discusses suggested management and preventative approaches that may help patients remain on therapy to derive maximum clinical benefit. A case study is presented to illustrate the discussion. We observed that AIs are in widespread use for women with hormone receptor-positive breast cancer and are now recommended as adjuvant therapy, either as primary therapy or sequential to tamoxifen, for postmenopausal women. AIs target the estrogen biosynthetic pathway and deprive tumor cells of the growth-promoting effects of estrogen, and AI therapies provide benefits to patients in terms of improved disease-free survival. However, there is a concern regarding the increased risk of bone loss with prolonged AI therapy, which can be managed in many cases with the use of bisphosphonates and other interventions (eg, calcium, vitamin D supplementation, exercise.Keywords: aromatase inhibitors, bisphosphonates, bone loss, breast cancer, estrogen

  2. Bone loss in women with type 1 diabetes

    DEFF Research Database (Denmark)

    tanderup joergensen, maj-britt; christensen, jesper olund; Svendsen, Ole Lander

    2015-01-01

    Background: Although osteoporosis has been investigated and debated in the diabetic population over the past decades, very little is known about the spontaneous changes in bone mineral density (BMD) and biochemical markers of bone turnover in pre- and postmenopausal type 1 diabetic (T1DM) women...... over time. Aim: To measure spontaneous changes in BMD and biochemical markers of bone turnover in pre- and postmenopausal T1DM women. Subjects: 53 T1DM women (31 premenopausal and 22 postmenopausal) from the outpatient clinic were enrolled in the study in 1993 and 35 (22 premenopausal, 13...... postmenopausal) were reexamined in 1997. Method: BMD was measured at femoral neck (f.n.), spine (L2 - L4), total body and forearm with DXA or SXA in 53 T1DM women. 4 years later a re-scan was carried out on 35 T1DM. Results: In premenopausal subjects a yearly decrease less than 1% at f.n., spine, forearm...

  3. 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...

  4. Dihydroartemisinin attenuates lipopolysaccharide-induced osteoclastogenesis and bone loss via the mitochondria-dependent apoptosis pathway.

    Science.gov (United States)

    Dou, C; Ding, N; Xing, J; Zhao, C; Kang, F; Hou, T; Quan, H; Chen, Y; Dai, Q; Luo, F; Xu, J; Dong, S

    2016-01-01

    Dihydroartemisinin (DHA) is a widely used antimalarial drug isolated from the plant Artemisia annua. Recent studies suggested that DHA has antitumor effects utilizing its reactive oxygen species (ROS) yielding mechanism. Here, we reported that DHA is inhibitory on lipopolysaccharide (LPS)-induced osteoclast (OC) differentiation, fusion and bone-resorption activity in vitro. Intracellular ROS detection revealed that DHA could remarkably increase ROS accumulation during LPS-induced osteoclastogenesis. Moreover, cell apoptosis was also increased by DHA treatment. We found that DHA-activated caspase-3 increased Bax/Bcl-2 ratio during LPS-induced osteoclastogenesis. Meanwhile, the translocation of apoptotic inducing factor (AIF) and the release of cytochrome c from the mitochondria into the cytosol were observed, indicating that ROS-mediated mitochondrial dysfunction is crucial in DHA-induced apoptosis during LPS-induced osteoclastogenesis. In vivo study showed that DHA treatment decreased OC number, prevents bone loss, rescues bone microarchitecture and restores bone strength in LPS-induced bone-loss mouse model. Together, our findings indicate that DHA is protective against LPS-induced bone loss through apoptosis induction of osteoclasts via ROS accumulation and the mitochondria-dependent apoptosis pathway. Therefore, DHA may be considered as a new therapeutic candidate for treating inflammatory bone loss. PMID:27031959

  5. 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

  6. Alveolar bone loss associated to periodontal disease in lead intoxicated rats under environmental hypoxia.

    Science.gov (United States)

    Terrizzi, Antonela R; Fernandez-Solari, Javier; Lee, Ching M; Bozzini, Clarisa; Mandalunis, Patricia M; Elverdin, Juan C; Conti, María Ines; Martínez, María Pilar

    2013-10-01

    Previously reported studies from this laboratory revealed that rats chronically intoxicated with lead (Pb) under hypoxic conditions (HX) impaired growth parameters and induced damages on femoral and mandibular bones predisposing to fractures. We also described periodontal inflammatory processes under such experimental conditions. Periodontitis is characterised by inflammation of supporting tissues of the teeth that result in alveolar bone loss. The existence of populations living at high altitudes and exposed to lead contamination aimed us to establish the macroscopic, biochemical and histological parameters consistent with a periodontal disease in the same rat model with or without experimental periodontitis (EP). Sixty female rats were divided into: Control; Pb (1000ppm of lead acetate in drinking water); HX (506mbar) and PbHX (both treatments simultaneously). EP was induced by placing ligatures around the molars of half of the rats during the 14 days previous to the autopsy. Hemi-mandibles were extracted to evaluate bone loss by histomorphometrical techniques. TNFα plasmatic concentration was greater (palveolar bone loss, while Pb showed spontaneous bone loss also. In conclusion, these results show that lead intoxication under hypoxic environment enhanced not only alveolar bone loss but also systemic and oral tissues inflammatory parameters, which could aggravate the physiopathological alterations produced by periodontal disease.

  7. 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

  8. 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

  9. Grizzly bears (Ursus arctos horribilis) and black bears (Ursus americanus) prevent trabecular bone loss during disuse (hibernation).

    Science.gov (United States)

    McGee-Lawrence, Meghan E; Wojda, Samantha J; Barlow, Lindsay N; Drummer, Thomas D; Castillo, Alesha B; Kennedy, Oran; Condon, Keith W; Auger, Janene; Black, Hal L; Nelson, O Lynne; Robbins, Charles T; Donahue, Seth W

    2009-12-01

    Disuse typically causes an imbalance in bone formation and bone resorption, leading to losses of cortical and trabecular bone. In contrast, bears maintain balanced intracortical remodeling and prevent cortical bone loss during disuse (hibernation). Trabecular bone, however, is more detrimentally affected than cortical bone in other animal models of disuse. Here we investigated the effects of hibernation on bone remodeling, architectural properties, and mineral density of grizzly bear (Ursus arctos horribilis) and black bear (Ursus americanus) trabecular bone in several skeletal locations. There were no differences in bone volume fraction or tissue mineral density between hibernating and active bears or between pre- and post-hibernation bears in the ilium, distal femur, or calcaneus. Though indices of cellular activity level (mineral apposition rate, osteoid thickness) decreased, trabecular bone resorption and formation indices remained balanced in hibernating grizzly bears. These data suggest that bears prevent bone loss during disuse by maintaining a balance between bone formation and bone resorption, which consequently preserves bone structure and strength. Further investigation of bone metabolism in hibernating bears may lead to the translation of mechanisms preventing disuse-induced bone loss in bears into novel treatments for osteoporosis.

  10. 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

  11. 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)

  12. Androgen receptors and experimental bone loss - an in vivo and in vitro study.

    Science.gov (United States)

    Steffens, Joao Paulo; Coimbra, Leila Santana; Rossa, Carlos; Kantarci, Alpdogan; Van Dyke, Thomas E; Spolidorio, Luis Carlos

    2015-12-01

    Testosterone is a sex hormone that exhibits many functions beyond reproduction; one such function is the regulation of bone metabolism. The role played by androgen receptors during testosterone-mediated biological processes associated with bone metabolism is largely unknown. This study aims to use a periodontal disease model in vivo in order to assess the involvement of androgen receptors on microbial-induced inflammation and alveolar bone resorption in experimental bone loss. The impact of hormone deprivation was tested through both orchiectomy and chemical blockage of androgen receptor using flutamide (FLU). Additionally, the direct effect of exogenous testosterone, and the role of the androgen receptor, on osteoclastogenesis were investigated. Thirty male adult rats (n=10/group) were subjected to: 1-orchiectomy (OCX); 2-OCX sham surgery; or 3-OCX sham surgery plus FLU, four weeks before the induction of experimental bone loss. Ten OCX sham-operated rats were not subjected to experimental bone loss and served as healthy controls. The rats were euthanized two weeks later, so as to assess bone resorption and the production of inflammatory cytokines in the gingival tissue and serum. In order to study the in vitro impact of testosterone, osteoclasts were differentiated from RAW264.7 cells and testosterone was added at increasing concentrations. Both OCX and FLU increased bone resorption, but OCX alone was observed to increase osteoclast count. IL-1β production was increased only in the gingival tissue of OCX animals, whereas FLU-treated animals presented a decreased expression of IL-6. Testosterone reduced the osteoclast formation in a dose-dependent manner, and significantly impacted the production of TNF-α; FLU partially reversed these actions. When taken together, our results indicate that testosterone modulates experimental bone loss, and that this action is mediated, at least in part, via the androgen receptor.

  13. Combined oral administration of bovine collagen peptides with calcium citrate inhibits bone loss in ovariectomized rats.

    Directory of Open Access Journals (Sweden)

    JunLi Liu

    Full Text Available Collagen peptides (CPs and calcium citrate are commonly used as bone health supplements for treating osteoporosis. However, it remains unknown whether the combination of oral bovine CPs with calcium citrate is more effective than administration of either agent alone.Forty 12-week-old Sprague-Dawley rats were randomly divided into five groups (n = 8 for once-daily intragastric administration of different treatments for 3 months at 3 months after ovariectomy (OVX as follows: sham + vehicle; OVX + vehicle; OVX + 750 mg/kg CP; OVX + CP-calcium citrate (75 mg/kg; OVX + calcium citrate (75 mg/kg. After euthanasia, the femurs were removed and analyzed by dual energy X-ray absorptiometry and micro-computed tomography, and serum samples were analyzed for bone metabolic markers.OVX rats supplemented with CPs or CP-calcium citrate showed osteoprotective effects, with reductions in the OVX-induced decreases in their femoral bone mineral density. Moreover, CP-calcium citrate prevented trabecular bone loss, improved the microarchitecture of the distal femur, and significantly inhibited bone loss with increased bone volume, connectivity density, and trabecular number compared with OVX control rats. CP or CP-calcium citrate administration significantly increased serum procollagen type I N-terminal propeptide levels and reduced serum bone-specific alkaline phosphatase, osteocalcin, and C-telopeptide of type I collagen levels.Our data indicate that combined oral administration of bovine CPs with calcium citrate inhibits bone loss in OVX rats. The present findings suggest that combined oral administration of bovine CPs with calcium citrate is a promising alternative for reducing bone loss in osteopenic postmenopausal women.

  14. Platform switching minimises crestal bone loss around dental implants: truth or myth?

    Science.gov (United States)

    Romanos, G E; Javed, F

    2014-09-01

    The aim was to assess the role of platform switching (PS) in minimising crestal bone loss around dental implants through a systematic review of the currently available clinical evidence. To address the focused question 'Does PS minimise crestal bone loss compared with non-platform-switched (NPS) implants?', PubMed/Medline and Google Scholar databases were explored from 1986 up to and including December 2013 using the following key words in different combinations: 'bone loss', 'dental implant', 'diameter', 'mandible', 'maxilla' and 'platform switching'. Letters to the Editor, unpublished data, historical reviews, case reports and articles published in languages other than English were excluded. Fifteen clinical studies were included. In seven studies, PS and NPS implants were placed in both the maxilla and mandible. In 13 studies, implants were placed at crestal bone levels whereas in one study, implants were placed supracrestally. Three studies reported the bucco-lingual (or transversal) width of the alveolar ridge which ranged between 7-8 mm. Seven studies reported that implants placed according to the PS concept did not minimise crestal bone loss as compared with NPS implants. 3D-Implant positioning, width of alveolar ridge and control of micromotion at the implant-abutment interface are the more critical factors that influence crestal bone levels than PS.

  15. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Nogueira, Liebert P.; Braz, Delson; Lopes, Ricardo T. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia (COPPE). Lab. de Instrumentacao Nuclear]. E-mails: lnogueira@con.ufrj.br; Barroso, Regina C.; Oliveira, Luis F. [Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ (Brazil). Inst. de Fisica]. E-mail: cely@uerj.br

    2007-07-01

    Bone is a connective tissue largely composed of an organic protein, collagen and the inorganic mineral hydroxyapatite [Ca{sub 10}(PO{sub 4}){sub 6}OH{sub 2}], 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 {mu}m ({+-}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{sup -3} and 1.92 g.cm{sup -3} respectively. The correlation of the measured absorption coefficient with the mineral content

  17. 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 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

  18. FSH aggravates bone loss in ovariectomised rats with experimental periapical periodontitis

    Science.gov (United States)

    Qian, Hua; Guan, Xiaoyue; Bian, Zhuan

    2016-01-01

    Periapical bone loss is one of the prominent pathological and clinical features of periapical periodontitis. Previous studies have demonstrated that follicle-stimulating hormone (FSH) could directly affect skeletal remodelling by stimulating the formation and the function of osteoclasts in vitro and in vivo. However, the effect of FSH on periapical bone loss remained to be fully elucidated. In the current study, a rat model was established in order to verify the effect of FSH in experimental periapical lesions. It was identified that FSH aggravated the bone loss of periapical lesions. In addition, RANKL-, TRAP-, TNF-α- and IL-1β-positive cells were increased significantly in FSH-treated groups, which indicated that the function of FSH in bone loss may be mediated through the increasing activity of osteoclasts and the increased secretion of inflammatory cytokines. The results of the current study suggested that FSH, independent of oestrogen, may aggravate periapical bone loss by FSH receptors, which may serve an important role in the immune and inflammatory response of the host to root canal and periradicular infection during menopause. PMID:27510616

  19. 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.)

  20. 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.)

  1. 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

  2. CD44 deficiency inhibits unloading-induced cortical bone loss through downregulation of osteoclast activity

    Science.gov (United States)

    Li, Yuheng; Zhong, Guohui; Sun, Weijia; Zhao, Chengyang; Zhang, Pengfei; Song, Jinping; Zhao, Dingsheng; Jin, Xiaoyan; Li, Qi; Ling, Shukuan; Li, Yingxian

    2015-01-01

    The CD44 is cellular surface adhesion molecule that is involved in physiological processes such as hematopoiesis, lymphocyte homing and limb development. It plays an important role in a variety of cellular functions including adhesion, migration, invasion and survival. In bone tissue, CD44 is widely expressed in osteoblasts, osteoclasts and osteocytes. However, the mechanisms underlying its role in bone metabolism remain unclear. We found that CD44 expression was upregulated during osteoclastogenesis. CD44 deficiency in vitro significantly inhibited osteoclast activity and function by regulating the NF-κB/NFATc1-mediated pathway. In vivo, CD44 mRNA levels were significantly upregulated in osteoclasts isolated from the hindlimb of tail-suspended mice. CD44 deficiency can reduce osteoclast activity and counteract cortical bone loss in the hindlimb of unloaded mice. These results suggest that therapeutic inhibition of CD44 may protect from unloading induced bone loss by inhibiting osteoclast activity. PMID:26530337

  3. CD44 deficiency inhibits unloading-induced cortical bone loss through downregulation of osteoclast activity.

    Science.gov (United States)

    Li, Yuheng; Zhong, Guohui; Sun, Weijia; Zhao, Chengyang; Zhang, Pengfei; Song, Jinping; Zhao, Dingsheng; Jin, Xiaoyan; Li, Qi; Ling, Shukuan; Li, Yingxian

    2015-01-01

    The CD44 is cellular surface adhesion molecule that is involved in physiological processes such as hematopoiesis, lymphocyte homing and limb development. It plays an important role in a variety of cellular functions including adhesion, migration, invasion and survival. In bone tissue, CD44 is widely expressed in osteoblasts, osteoclasts and osteocytes. However, the mechanisms underlying its role in bone metabolism remain unclear. We found that CD44 expression was upregulated during osteoclastogenesis. CD44 deficiency in vitro significantly inhibited osteoclast activity and function by regulating the NF-κB/NFATc1-mediated pathway. In vivo, CD44 mRNA levels were significantly upregulated in osteoclasts isolated from the hindlimb of tail-suspended mice. CD44 deficiency can reduce osteoclast activity and counteract cortical bone loss in the hindlimb of unloaded mice. These results suggest that therapeutic inhibition of CD44 may protect from unloading induced bone loss by inhibiting osteoclast activity.

  4. Simulation analysis for effects of bone loss on acceleration tolerance of human lumbar vertebra

    Science.gov (United States)

    Ma, Honglei; Zhang, Feng; Zhu, Yu; Xiao, Yanhua; Wazir, Abrar

    2014-02-01

    The purpose of the present study was to analyze and predict the changes in acceleration tolerance of human vertebra as a result of bone loss caused by long-term space flight. A human L3-L4 vertebra FEM model was constructed, in which the cancellous bone was separated, and surrounding ligaments were also taken into account. The simulation results demonstrated that bone loss has more of an effect on the acceleration tolerance in x-direction. The results serve to aid in the creation of new acceleration tolerance standards, ensuring astronauts return home safely after long-term space flight. This study shows that more attention should be focused on the bone degradation of crew members and to create new protective designs for space capsules in the future.

  5. 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

  6. 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

    Large animals as sheep are often used as models for human osteoporosis. Our aim was therefore to determine how glucocorticoid treatment of ovariectomised sheep affects the cancellous bone, determining the cellular events within the bone remodelling process that contributes to their bone loss. Twe...

  7. 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...

  8. 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

  9. Bone mineral content and bone metabolism in young adults with severe periodontitis

    DEFF Research Database (Denmark)

    Wowern von, N.; Westergaard, J.; Kollerup, G.

    2001-01-01

    Bone loss, bone markers, bone metabolism, bone mineral content, osteoporosis, severe periodontitis......Bone loss, bone markers, bone metabolism, bone mineral content, osteoporosis, severe periodontitis...

  10. 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

    indicated that risk of low bone mass and increased bone loss caused by thinness could be compensated by alendronate treatment. In conclusion, thinness is an important risk factor for low bone mass and increased bone loss in postmenopausal women. Because the response to alendronate treatment is independent......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...... (r = -0.12 to -0.15, p risk factors, the group treated with 5 mg of alendronate was included (n = 403). There were no associations between fat mass parameters and response to alendronate treatment, which...

  11. Management of Humeral and Glenoid Bone Loss in Recurrent Glenohumeral Instability

    Directory of Open Access Journals (Sweden)

    Randy Mascarenhas

    2014-01-01

    Full Text Available Recurrent shoulder instability and resultant glenoid and humeral head bone loss are not infrequently encountered in the population today, specifically in young, athletic patients. This review on the management of bone loss in recurrent glenohumeral instability discusses the relevant shoulder anatomy that provides stability to the shoulder joint, relevant history and physical examination findings pertinent to recurrent shoulder instability, and the proper radiological imaging choices in its workup. Operative treatments that can be used to treat both glenoid and humeral head bone loss are outlined. These include coracoid transfer procedures and allograft/autograft reconstruction at the glenoid, as well as humeral head disimpaction/humeroplasty, remplissage, humeral osseous allograft reconstruction, rotational osteotomy, partial humeral head arthroplasty, and hemiarthroplasty on the humeral side. Clinical outcomes studies reporting general results of these techniques are highlighted.

  12. 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.

  13. 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

  14. [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

  15. [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

  16. Effect of obesity on alveolar bone loss in experimental periodontitis in Wistar rats

    Directory of Open Access Journals (Sweden)

    Giliano Nicolini Verzeletti

    2012-04-01

    Full Text Available Obesity has been linked to higher inflammatory status and periodontal breakdown. OBJECTIVE: The purpose of this study was to investigate the effect of obesity on alveolar bone loss in experimental periodontitis in rats. MATERIAL AND METHODS: Twenty-four female Wistar rats were randomly divided into two groups: obese (n=13, which were fed with "cafeteria diet" (CAF diet - high amounts of sucrose and fat for 90 days in order to gain weight, and non-obese (n=11 regularly fed rats. Ligature-induced experimental periodontitis was created in all animals. Body weight differed statistically between obese and non-obese groups (277.59 and 223.35 g, respectively at the moment of the ligature placement. Morphometric registration of alveolar bone loss was carried out after 30 days of ligature placement to determine the effect of obesity on the progression of experimental periodontitis. RESULTS: Intra-group comparisons showed significantly higher alveolar bone loss mean values in maxillary teeth with ligature (P<0.05. Alveolar bone loss [mean (SD, mm] was not statistically different between obese and non-obese groups [0.71 (0.09 and 0.65 (0.07 mm, respectively]. However, when palatal sides are analyzed separately, obese group presented significantly higher alveolar bone loss (P<0.05 as compared to non-obese [0.68 (0.12 and 0.53 (0.13 mm, respectively]. CONCLUSIONS: In spite of the weak differences, it is possible to conclude that the progression of alveolar bone loss in ligature-induced periodontitis can be potentially influenced by body weight in rats.

  17. Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis).

    Science.gov (United States)

    McGee, Meghan E; Maki, Aaron J; Johnson, Steven E; Nelson, O Lynne; Robbins, Charles T; Donahue, Seth W

    2008-02-01

    Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. Here we show decreased cortical bone turnover during hibernation with balanced formation and resorption in grizzly bear femurs. Hibernating grizzly bear femurs were less porous and more mineralized, and did not demonstrate any changes in cortical bone geometry or whole bone mechanical properties compared to active grizzly bear femurs. The activation frequency of intracortical remodeling was 75% lower during hibernation than during periods of physical activity, but the normalized mineral apposition rate was unchanged. These data indicate that bone turnover decreases during hibernation, but osteons continue to refill at normal rates. There were no changes in regional variation of porosity, geometry, or remodeling indices in femurs from hibernating bears, indicating that hibernation did not preferentially affect one region of the cortex. Thus, grizzly bears prevent bone loss during disuse by decreasing bone turnover and maintaining balanced formation and resorption, which preserves bone structure and strength. These results support the idea that bears possess a biological mechanism to prevent disuse osteoporosis.

  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. 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.

  20. Loss of Insulin Receptor in Osteoprogenitor Cells Impairs Structural Strength of Bone

    Directory of Open Access Journals (Sweden)

    Kathryn Thrailkill

    2014-01-01

    Full Text Available Type 1 diabetes mellitus (T1D is associated with decreased bone mineral density, a deficit in bone structure, and subsequently an increased risk of fragility fracture. These clinical observations, paralleled by animal models of T1D, suggest that the insulinopenia of T1D has a deleterious effect on bone. To further examine the action of insulin signaling on bone development, we generated mice with an osteoprogenitor-selective (osterix-Cre ablation of the insulin receptor (IR, designated OIRKO. OIRKO mice exhibited an 80% decrease in IR in osteoblasts. Prenatal elimination of IR did not affect fetal survival or gross morphology. However, loss of IR in mouse osteoblasts resulted in a postnatal growth-constricted phenotype. By 10–12 weeks of age, femurs of OIRKO mice were more slender, with a thinner diaphyseal cortex and, consequently, a decrease in whole bone strength when subjected to bending. In male mice alone, decreased metaphyseal trabecular bone, with thinner and more rodlike trabeculae, was also observed. OIRKO mice did not, however, exhibit abnormal glucose tolerance. The skeletal phenotype of the OIRKO mouse appeared more severe than that of previously reported bone-specific IR knockdown models, and confirms that insulin receptor expression in osteoblasts is critically important for proper bone development and maintenance of structural integrity.

  1. 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;

    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...

  2. 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

  3. 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.

  4. Effects of glucocorticoid treatment on focal and systemic bone loss in rheumatoid arthritis.

    Science.gov (United States)

    Di Munno, O; Delle Sedie, A

    2008-07-01

    Rheumatoid arthritis (RA) is characterized by an extensive dysregulation in skeletal homeostasis recognized as 1) focal articular bone erosions, 2) iuxta-articular osteopenia, 3) systemic osteoporosis (OP) and fractures, as is well documented in both cross-sectional and prospective studies. The disease activity, as a consequence of new insights into the complex interaction between bone cells and a variety of cells of the immune system, has emerged as the main responsible for both focal and systemic bone loss. Given this background, the therapeutic approach to RA has become more aggressive, and a more widespread use of low-dose glucocorticoids (GC), recently categorized as disease modifying antirheumatic drugs (DMARD) because of their additional joint sparing effect on the long-term, has also been recommended from the early stages. Addressing the effects of GC on systemic bone loss in RA, GC are considered, in addition to inflammation and inactivity, the major risk factors for OP and fractures. As a consequence, among the most recent recommendations (i.e. dosing, timing, and tapering strategies) for patients receiving GC for more than 3 months, prevention and treatment of GC-induced OP (i.e. calcium, vitamin D, and bisphosphonates) are included. However, innovative GC, characterized by a more favorable risk/benefit profile such as selective GC receptor agonists (SEGRA), are currently in the pipeline. This article reviews the major points of evidence so far available, regarding the effects of GC on focal and systemic bone loss.

  5. The loss of activating transcription factor 4 (ATF4) reduces bone toughness and fracture toughness.

    Science.gov (United States)

    Makowski, Alexander J; Uppuganti, Sasidhar; Wadeer, Sandra A; Whitehead, Jack M; Rowland, Barbara J; Granke, Mathilde; Mahadevan-Jansen, Anita; Yang, Xiangli; Nyman, Jeffry S

    2014-05-01

    Even though age-related changes to bone tissue affecting fracture risk are well characterized, only a few matrix-related factors have been identified as important to maintaining fracture resistance. As a gene critical to osteoblast differentiation, activating transcription factor 4 (ATF4) is possibly one of these important factors. To test the hypothesis that the loss of ATF4 affects the fracture resistance of bone beyond bone mass and structure, we harvested bones from Atf4+/+ and Atf4-/- littermates at 8 and 20 weeks of age (n≥9 per group) for bone assessment across several length scales. From whole bone mechanical tests in bending, femurs from Atf4-/- mice were found to be brittle with reduced toughness and fracture toughness compared to femurs from Atf4+/+ mice. However, there were no differences in material strength and in tissue hardness, as determined by nanoindentation, between the genotypes, irrespective of age. Tissue mineral density of the cortex at the point of loading as determined by micro-computed tomography was also not significantly different. However, by analyzing local composition by Raman Spectroscopy (RS), bone tissue of Atf4-/- mice was found to have higher mineral to collagen ratio compared to wild-type tissue, primarily at 20 weeks of age. From RS analysis of intact femurs at 2 orthogonal orientations relative to the polarization axis of the laser, we also found that the organizational-sensitive peak ratio, ν1Phosphate per Amide I, changed to a greater extent upon bone rotation for Atf4-deficient tissue, implying bone matrix organization may contribute to the brittleness phenotype. Target genes of ATF4 activity are not only important to osteoblast differentiation but also in maintaining bone toughness and fracture toughness.

  6. Effect of galactooligosaccharides on calcium absorption and preventing bone loss in ovariectomized rats.

    Science.gov (United States)

    Chonan, O; Matsumoto, K; Watanuki, M

    1995-02-01

    The effects of galactooligosaccharides (GOS), a mixture of galactosyl oligosaccharides formed from lactose by the transgalactosyl reaction of beta-D-galactosidase derived from Bacillus circulans, on calcium absorption and prevention of bone loss were examined in ovariectomized (OVX) Wistar rats. Rats fed on a diet containing GOS absorbed calcium more efficiently than those on the control diet after 8-10 days and 18-20 days, and the bone (femur and tibia) ash weight and tibia calcium content of OVX rats fed on the GOS diet were significantly higher than those of the control animals. Although the serum total cholesterol of the ovariectomized rats was significantly elevated, GOS produced a significant hypocholesterolemic effect in the OVX rats. GOS, which is fermented by bacteria in the lower part of the intestine, enhanced volatile fatty acid production, and thus prevented bone loss and lower serum total cholesterol concentration in the ovariectomized rats.

  7. 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

  8. The influence of smoking on bone loss and response to nasal estradiol

    DEFF Research Database (Denmark)

    Bjarnason, N.H.; Nielsen, T.F.; Jørgensen, Henrik Løvendahl;

    2009-01-01

    Objective To investigate the influence of smoking on bone during therapy with nasally administrated estradiol in sequential combination with oral progesterone in early postmenopausal women. In addition, to observe the consequences of smoking on bone in untreated women. Methods Post-hoc exploratory......-smokers (1.4% vs. 1.4%, p=0.89), whereas the change in the hip on the placebo was similar to that seen in the spine (-3.7% vs. -2.6%, p=0.08). Supportive changes were seen in urinary CTX and in serum osteocalcin. Conclusions These results indicate that cigarette smoking may reduce the efficacy of nasal...... estradiol to increase bone mass in early postmenopausal women. In addition, smoking may increase spontaneous bone loss in untreated women Udgivelsesdato: 2009...

  9. 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...

  10. Validation of a dental image analyzer tool to measure alveolar bone loss in periodontitis patients

    NARCIS (Netherlands)

    W.J. Teeuw; L. Coelho; A. de Silva; C.J.N.M. van der Palen; F.G.J.M. Lessmann; U. van der Velden; B.G. Loos

    2009-01-01

    Background and Objective:  Radiographs are an essential adjunct to the clinical examination for periodontal diagnoses. Over the past few years, digital radiographs have become available for use in clinical practice. Therefore, the present study investigated whether measuring alveolar bone loss, usin

  11. Evaluation of Implant Collar Surfaces for Marginal Bone Loss: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Roodabeh Koodaryan

    2016-01-01

    Full Text Available Background. It is important to understand the influence of different collar designs on peri-implant marginal bone loss, especially in the critical area. Objectives. The purpose of the present systematic review and meta-analysis was to compare dental implants with different collar surfaces, evaluating marginal bone loss and survival rates of implants. Methods. Eligibility criteria included clinical human studies, randomized controlled trials, and prospective and retrospective studies, which evaluated dental implants with different collar surface in the same study. Results. Twelve articles were included, with a total of 492 machined, 319 rough-surfaced, and 352 rough-surfaced microthreaded neck implants. There was less marginal bone loss at implants with rough-surfaced and rough-surfaced microthreaded neck than at machined-neck implants (difference in means: 0.321, 95% CI: 0.149 to 0.493; p<0.01. Conclusion. Rough and rough-surfaced microthreaded implants are considered a predictable treatment for preserving early marginal bone loss.

  12. Evaluation of Implant Collar Surfaces for Marginal Bone Loss: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    2016-01-01

    Background. It is important to understand the influence of different collar designs on peri-implant marginal bone loss, especially in the critical area. Objectives. The purpose of the present systematic review and meta-analysis was to compare dental implants with different collar surfaces, evaluating marginal bone loss and survival rates of implants. Methods. Eligibility criteria included clinical human studies, randomized controlled trials, and prospective and retrospective studies, which evaluated dental implants with different collar surface in the same study. Results. Twelve articles were included, with a total of 492 machined, 319 rough-surfaced, and 352 rough-surfaced microthreaded neck implants. There was less marginal bone loss at implants with rough-surfaced and rough-surfaced microthreaded neck than at machined-neck implants (difference in means: 0.321, 95% CI: 0.149 to 0.493; p < 0.01). Conclusion. Rough and rough-surfaced microthreaded implants are considered a predictable treatment for preserving early marginal bone loss. PMID:27493957

  13. 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

  14. 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.

  15. 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

  16. High-impact exercise in rats prior to and during suspension can prevent bone loss.

    Science.gov (United States)

    Yanagihara, G R; Paiva, A G; Gasparini, G A; Macedo, A P; Frighetto, P D; Volpon, J B; Shimano, A C

    2016-03-01

    High-impact exercise has been considered an important method for treating bone loss in osteopenic experimental models. In this study, we investigated the effects of osteopenia caused by inactivity in femora and tibiae of rats subjected to jump training using the rat tail suspension model. Eight-week-old female Wistar rats were divided into five groups (n=10 each group): jump training for 2 weeks before suspension and training during 3 weeks of suspension; jump training for 2 weeks before suspension; jump training only during suspension; suspension without any training; and a control group. The exercise protocol consisted of 20 jumps/day, 5 days/week, with a jump height of 40 cm. The bone mineral density of the femora and tibiae was measured by double energy X-ray absorptiometry and the same bones were evaluated by mechanical tests. Bone microarchitecture was evaluated by scanning electron microscopy. One-way ANOVA was used to compare groups. Significance was determined as Pbone mineral density, mechanical properties and bone microarchitecture, the beneficial effects were greater in the bones of animals subjected to pre-suspension training and subsequently to training during suspension, compared with the bones of animals subjected to pre-suspension training or to training during suspension. Our results indicate that a period of high impact exercise prior to tail suspension in rats can prevent the installation of osteopenia if there is also training during the tail suspension.

  17. 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.

  18. 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.

  19. 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.

  20. Arctic Ground Squirrels Limit Bone Loss during the Prolonged Physical Inactivity Associated with Hibernation.

    Science.gov (United States)

    Wojda, Samantha J; Gridley, Richard A; McGee-Lawrence, Meghan E; Drummer, Thomas D; Hess, Ann; Kohl, Franziska; Barnes, Brian M; Donahue, Seth W

    2016-01-01

    Prolonged disuse (e.g., physical inactivity) typically results in increased bone porosity, decreased mineral density, and decreased bone strength, leading to increased fracture risk in many mammals. However, bears, marmots, and two species of ground squirrels have been shown to preserve macrostructural bone properties and bone strength during long seasons of hibernation while they remain mostly inactive. Some small hibernators (e.g., 13-lined ground squirrels) show microstructural bone loss (i.e., osteocytic osteolysis) during hibernation, which is not seen in larger hibernators (e.g., bears and marmots). Arctic ground squirrels (Urocitellus parryii) are intermediate in size between 13-lined ground squirrels and marmots and are perhaps the most extreme rodent hibernator, hibernating for up to 8 mo annually with body temperatures below freezing. The goal of this study was to quantify the effects of hibernation and inactivity on cortical and trabecular bone properties in arctic ground squirrels. Cortical bone geometrical properties (i.e., thickness, cross-sectional area, and moment of inertia) at the midshaft of the femur were not different in animals sampled over the hibernation and active seasons. Femoral ultimate stress tended to be lower in hibernators than in summer animals, but toughness was not affected by hibernation. The area of osteocyte lacunae was not different between active and hibernating animals. There was an increase in osteocytic lacunar porosity in the hibernation group due to increased lacunar density. Trabecular bone volume fraction in the proximal tibia was unexpectedly greater in the hibernation group than in the active group. This study shows that, similar to other hibernators, arctic ground squirrels are able to preserve many bone properties during hibernation despite being physically inactive for up to 8 mo. PMID:27082526

  1. 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

  2. Preventive Effects of Collagen Peptide from Deer Sinew on Bone Loss in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    He Zhang

    2014-01-01

    Full Text Available Deer sinew (DS has been used traditionally for various illnesses, and the major active constituent is collagen. In this study, we assessed the effects of collagen peptide from DS on bone loss in the ovariectomized rats. Wister female rats were randomly divided into six groups as follows: sham-operated (SHAM, ovariectomized control (OVX, OVX given 1.0 mg/kg/week nylestriol (OVX + N, OVX given 0.4 g/kg/day collagen peptide (OVX + H, OVX given 0.2 g/kg/day collagen peptide (OXV + M, and OVX given 0.1 g/kg/day collagen peptide (OXV + L, respectively. After 13 weeks of treatment, the rats were euthanized, and the effects of collagen peptide on body weight, uterine weight, bone mineral density (BMD, serum biochemical indicators, bone histomorphometry, and bone mechanics were observed. The data showed that BMD and concentration of serum hydroxyproline were significantly increased and the levels of serum calcium, phosphorus, and alkaline phosphatase were decreased. Besides, histomorphometric parameters and mechanical indicators were improved. However, collagen peptide of DS has no effect on estradiol level, body weight, and uterine weight. Therefore, these results suggest that the collagen peptide supplementation may also prevent and treat bone loss.

  3. 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

  4. 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

  5. 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...

  6. 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

  7. Spaceflight-induced bone loss alters failure mode and reduces bending strength in murine spinal segments.

    Science.gov (United States)

    Berg-Johansen, Britta; Liebenberg, Ellen C; Li, Alfred; Macias, Brandon R; Hargens, Alan R; Lotz, Jeffrey C

    2016-01-01

    Intervertebral disc herniation rates are quadrupled in astronauts following spaceflight. While bending motions are main contributors to herniation, the effects of microgravity on the bending properties of spinal discs are unknown. Consequently, the goal of this study was to quantify the bending properties of tail discs from mice with or without microgravity exposure. Caudal motion segments from six mice returned from a 30-day Bion M1 mission and eight vivarium controls were loaded to failure in four-point bending. After testing, specimens were processed using histology to determine the location of failure, and adjacent motion segments were scanned with micro-computed tomography (μCT) to quantify bone properties. We observed that spaceflight significantly shortened the nonlinear toe region of the force-displacement curve by 32% and reduced the bending strength by 17%. Flight mouse spinal segments tended to fail within the growth plate and epiphyseal bone, while controls tended to fail at the disc-vertebra junction. Spaceflight significantly reduced vertebral bone volume fraction, bone mineral density, and trabecular thickness, which may explain the tendency of flight specimens to fail within the epiphyseal bone. Together, these results indicate that vertebral bone loss during spaceflight may degrade spine bending properties and contribute to increased disc herniation risk in astronauts.

  8. Hospitalization for fractures and bone loss in adults. Why do we regard these phenomena as dull?

    Science.gov (United States)

    Wylie, C M

    1977-01-01

    The epidemiology of serious fractures in adults relates less to the frequency of forceful accidents and more directly to the loss of bone in middle-aged and older people. To support this statement, hospital discharge rates for fractures in recent years are examined from different geographic areas. Rates for the United States rise with age, so that serious fractures form 10 percent of all hospital discharges at 85 years and older. Saskatchewan data suggest that rates for men remain low until 60 years; for women the figures began to rise at 45 years, before many had reached the menopause. Rates are lower among women than men in Saskatchewan until around 50 years, surpassing those of men at age 55 and older. Among Medicare enrollees in 1967 in the United States, women had higher discharge rates for fractures than men of the same age and race. Whites also had higher rates than blacks, so much so that white males had higher rates than black women of the same age. Such data confirm the past impression that blacks who survive into the older ages are a biological elite, more able to maintain bone strength than whites of either sex, although by no means being exempt from bone loss with age. A fractured femur was the most frequent diagnosis, forming a higher percentage of all fractures in women than men, and rising steeply with age in both sexes. The pattern of fractures by sex differs from the epidemiology of forceful accidents, which more often involve men than women. Bone loss with age, or osteoporosis, is perhaps the most powerful host factor to dominate the picture of fractures in the elderly. The existing possibilities for preventing or slowing this change are thus assessed; women may no longer accept as natural the widespread bone loss and accompanying fractures that lower the quality of life in later years. PMID:319479

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss.

    Science.gov (United States)

    Turner, Russell T; Dube, Michael; Branscum, Adam J; Wong, Carmen P; Olson, Dawn A; Zhong, Xiaoying; Kweh, Mercedes F; Larkin, Iske V; Wronski, Thomas J; Rosen, Clifford J; Kalra, Satya P; Iwaniec, Urszula T

    2015-12-01

    Excessive weight gain in adults is associated with a variety of negative health outcomes. Unfortunately, dieting, exercise, and pharmacological interventions have had limited long-term success in weight control and can result in detrimental side effects, including accelerating age-related cancellous bone loss. We investigated the efficacy of using hypothalamic leptin gene therapy as an alternative method for reducing weight in skeletally-mature (9 months old) female rats and determined the impact of leptin-induced weight loss on bone mass, density, and microarchitecture, and serum biomarkers of bone turnover (CTx and osteocalcin). Rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either recombinant adeno-associated virus encoding the gene for rat leptin (rAAV-Leptin, n=7) or a control vector encoding green fluorescent protein (rAAV-GFP, n=10) and sacrificed 18 weeks later. A baseline control group (n=7) was sacrificed at vector administration. rAAV-Leptin-treated rats lost weight (-4±2%) while rAAV-GFP-treated rats gained weight (14±2%) during the study. At study termination, rAAV-Leptin-treated rats weighed 17% less than rAAV-GFP-treated rats and had lower abdominal white adipose tissue weight (-80%), serum leptin (-77%), and serum IGF1 (-34%). Cancellous bone volume fraction in distal femur metaphysis and epiphysis, and in lumbar vertebra tended to be lower (Pweight compared to baseline and rAAV-GFP-treated rats with minimal effects on bone mass, density, microarchitecture, or biochemical markers of bone turnover.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. Bone Loss During Space Flights: Implication of the Vestibular System, Sex-Dependence and Countermeasure

    Science.gov (United States)

    Vignaux, G.; Besnard, S.; Philoxene, B.; Sabatier, J. P.; Allouche, S.; Denise, P.

    2008-06-01

    The decrease of mechanical load due to microgravity induces bone loss (BL) during long-term space flights. We previously postulated that vestibular system could also be involved in bone modeling. Herein, we evaluated by tomography, long-term (2 months) effects of bilateral vestibular lesion (Bilab) on BL compared to a model of diffuse osteoporosis induced by gonadectomy in male and female rats. BL (about 12%) was observed on femoral metaphysis and femoral metaphysis/diaphysis respectively in male and female Bilab groups compared to shams. Whole body and spine mineralization remained unchanged in Bilab groups while it appeared decreased in gonadectomy groups as expected. BL in Bilab groups was reported at 1 month and recovered at 2 months while it remained decreased at 2 months in our model of diffuse osteoporosis. Risedronate over counterbalanced BL in both models of BL (Bilab and gonadectomy) at 1 and 2 months. Bilateral vestibular lesions on Earth induced regional bone loss focused on bearing bones in male and female at 1 month with unknown compensatory mechanisms 2 months later.

  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. 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...

  2. 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 ...

  3. 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 ...

  4. Massive Bone Loss from Fungal Infection after Anterior Cruciate Ligament Arthroscopic Reconstruction

    OpenAIRE

    Muscolo, D. Luis; Carbo, Lisandro; Aponte-Tinao, Luis A.; Ayerza, Miguel A.; Makino, Arturo

    2009-01-01

    Although there are numerous reports of septic pyogenic arthritis after arthroscopic anterior cruciate ligament (ACL) reconstruction, there is limited information regarding the outcomes of fungal infection. We determined the outcomes of six patients with mycotic infection after regular ACL reconstruction. There were four males and two females with a mean age of 33 years. We determined the number of procedures performed, bone loss originating to control infection, and final reconstruction in th...

  5. Eriodicyol inhibits osteoclast differentiation and ovariectomy-induced bone loss in vivo.

    Science.gov (United States)

    Lee, Juhyun; Noh, A Long Sae Mi; Zheng, Ting; Kang, Ju-hee; Yim, Mijung

    2015-12-10

    Osteoclasts are responsible for bone erosion in diseases such as osteoporosis and rheumatoid arthritis. In the present study, we investigate the effects of eriodictyol, a flavonoid found naturally in citrus fruits, on the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation using mouse bone marrow macrophages (BMMs). Eriodictyol inhibited RANKL-induced osteoclast formation in a dose-dependent manner without cytotoxicity. In addition, eriodictyol suppressed bone resorption activity of differentiated osteoclasts. The inhibitory effect of eriodictyol was associated with impaired activation of multiple signaling events downstream of RANK, including extracellular signal-regulated kinase, p38, and c-Jun terminal kinase phosphorylation, followed by decreased nuclear factor of activated T cells (NFAT)c1 expression. Ectopic overexpression of a constitutively active form of NFATc1 completely rescued the anti-osteoclastogenic effect of eriodictyol, suggesting that the anti-osteoclastogenic effect was mainly attributed to the reduction in NFATc1 expression. Consistent with the in vitro anti-osteoclastogenic effect, eriodictyol suppressed lipopolysaccharide-induced osteoclast formation in the calvarial model and ovariectomy-induced bone loss in vivo. Taken together, our data demonstrate that eriodictyol is a new therapeutic agent with the potential to prevent bone destructive diseases by reducing both osteoclast differentiation and function.

  6. 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

  7. Exercise and pharmacological countermeasures for bone loss during long-duration space flight

    Science.gov (United States)

    Cavanagh, Peter R.; Licata, Angelo A.; Rice, Andrea J.

    2005-01-01

    Bone loss in the lower extremities and lumbar spine is an established consequence of long-duration human space flight. Astronauts typically lose as much bone mass in the proximal femur in 1 month as postmenopausal women on Earth lose in 1 year. Pharmacological interventions have not been routinely used in space, and countermeasure programs have depended solely upon exercise. However, it is clear that the osteogenic stimulus from exercise has been inadequate to maintain bone mass, due to insufficient load or duration. Attention has therefore been focused on several pharmacological interventions that have been successful in preventing or attenuating osteoporosis on Earth. Anti-resorptives are the class of drugs most commonly used to treat osteoporosis in postmenopausal women, notably alendronate sodium, risedronate sodium, zoledronic acid, and selective estrogen receptor modulators, such as raloxifene. There has also been considerable recent interest in anabolic agents such as parathyroid hormone (PTH) and teriparatide (rhPTH [1-34]). Vitamin D and calcium supplementation have also been used. Recent studies of kindreds with abnormally high bone mineral density have provided insight into the genetic regulation of bone mass. This has led to potential therapeutic interventions based on the LRP5, Wnt and BMP2 pathways. Another target is the RANK-L/osteoprotegerin signaling pathway, which influences bone turnover by regulating osteoclast formation and maturation. Trials using such therapies in space are being planned. Among the factors to be considered are dose-response relationships, bone quality, post-use recovery, and combination therapies--all of which may have unique characteristics when the drugs are used in space.

  8. 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.

  9. Myricetin Prevents Alveolar Bone Loss in an Experimental Ovariectomized Mouse Model of Periodontitis.

    Science.gov (United States)

    Huang, Jialiang; Wu, Chuanlong; Tian, Bo; Zhou, Xiao; Ma, Nian; Qian, Yufen

    2016-03-22

    Periodontitis is a common chronic inflammatory disease, which leads to alveolar bone resorption. Healthy and functional alveolar bone, which can support the teeth and enable their movement, is very important for orthodontic treatment. Myricetin inhibited osteoclastogenesis by suppressing the expression of some genes, signaling pathways, and cytokines. This study aimed to investigate the effects of myricetin on alveolar bone loss in an ovariectomized (OVX) mouse model of periodontitis as well as in vitro osteoclast formation and bone resorption. Twenty-four healthy eight-week-old C57BL/J6 female mice were assigned randomly to four groups: phosphate-buffered saline (PBS) control (sham) OVX + ligature + PBS (vehicle), and OVX + ligature + low or high (2 or 5 mg∙kg(-1)∙day(-1), respectively) doses of myricetin. Myricetin or PBS was injected intraperitoneally (i.p.) every other day for 30 days. The maxillae were collected and subjected to further examination, including micro-computed tomography (micro-CT), hematoxylin and eosin (H&E) staining, and tartrate-resistant acid phosphatase (TRAP) staining; a resorption pit assay was also performed in vitro to evaluate the effects of myricetin on receptor activator of nuclear factor κ-B ligand (RANKL)-induced osteoclastogenesis. Myricetin, at both high and low doses, prevented alveolar bone resorption and increased alveolar crest height in the mouse model and inhibited osteoclast formation and bone resorption in vitro. However, myricetin was more effective at high dose than at low dose. Our study demonstrated that myricetin had a positive effect on alveolar bone resorption in an OVX mouse model of periodontitis and, therefore, may be a potential agent for the treatment of periodontitis and osteoporosis.

  10. 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.

  11. 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.

  12. 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

  13. 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....

  14. Quantitative Computerized Assessment of the Degree of Acetabular Bone Deficiency: Total radial Acetabular Bone Loss (TrABL

    Directory of Open Access Journals (Sweden)

    Frederik Gelaude

    2011-01-01

    Full Text Available A novel quantitative, computerized, and, therefore, highly objective method is presented to assess the degree of total radical acetabular bone loss. The method, which is abbreviated to “TrABL”, makes use of advanced 3D CT-based image processing and effective 3D anatomical reconstruction methodology. The output data consist of a ratio and a graph, which can both be used for direct comparison between specimens. A first dataset of twelve highly deficient hemipelves, mainly Paprosky types IIIB, is used as illustration. Although generalization of the findings will require further investigation on a larger population, it can be assumed that the presented method has the potential to facilitate the preoperative use of existing classifications and related decision schemes for treatment selection in complex revision cases.

  15. Treatment And Results Of Combined Mild Bone Loss Instability With The Modified Laterjet

    Science.gov (United States)

    Yang, Justin Shu; Mazzocca, Augustus D.; Arciero, Robert A.

    2015-01-01

    Objectives: Recurrent anterior glenohumeral dislocation in the setting of an engaging Hill-Sachs lesion is high. The Latarjet procedure has been well-described for restoring glenohumeral stability in patients with over 25% glenoid bone loss. However, the treatment for patients with combined humeral head and mild (<25%) glenoid bone loss remains unclear. We report on the outcomes of the modified Latarjet for this population. Methods: Modified Latarjet was performed in twenty three patients with recurrent anterior shoulder instability, engaging Hill-Sachs by exam confirmed with arthroscopy, and less than 25% anterior glenoid bone loss. The mean follow-up was 3.5 years. All patients were assessed for their risk of recurrence using the Instability Severity Index Score (ISIS), had pre-operative 3D imaging to assess humeral and glenoid bone loss. Single Assessment Numeric Evaluation (SANE), Western Ontario Shoulder Instability Index (WOSI), recurrence rate, radiographs, range of motion and dynamometer strength were used to assess outcomes. Results: Average pre-operative instability severity index score was 6.2 (range 4-9). Pre-operative glenoid bone loss averaged 15.1% (range 5-25%). The humeral defect averaged 40.4% in width and 13.7% in depth on axial computed tomography scan, with an average Hill-Sachs angle of 28°. The mean WOSI index was 457 of 2100 (range 0-1398). The mean SANE score was 81.2 (range 60-100). Five out of ten competitive athletes returned to play for at least one season. There were no recurrent dislocation and three patients had a single episode of recurrent subluxation. Loss of external rotation at the side averaged 8°, and there was no significant loss of abduction. Subscapularis, abduction and external rotation strength averaged greater than 85% of the contralateral shoulder. Fourteen patients on average had 1.4 (range 1-4) previous open or arthroscopic stabilization procedures prior to the Latarjet, nine others had Latarjet done primarily. WOSI

  16. 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...

  17. 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.

  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. 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

  20. 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.

  1. Estrogen Deficiency Leads to Further Bone Loss in the Mandible of CKD Mice.

    Directory of Open Access Journals (Sweden)

    Yuchen Guo

    Full Text Available Chronic kidney disease (CKD has been regarded as a grave public health problem. Estrogen is a critical factor for both renal protection and bone remodeling. Our previous study demonstrated that CKD impairs the healing of titanium implants. The aim of this study was to investigate the effects of estrogen deficiency on the mandibular bone in CKD mice.Forty eleven-week-old female C57BL mice were used in this study. Uremia and estrogen deficiency were induced by 5/6 nephrectomy and ovariectomy (OVX, respectively. After 8 weeks, the mice were sacrificed, and their mandibles were collected for micro-CT analysis and histological examination.All the mice survived the experimental period. Serum measurements confirmed a significant increase in BUN in the CKD group that was further increased by OVX. OVX led to significant decreases in both the BV/TV and cortical thickness of the mandibular bone in CKD mice.In summary, our findings indicate that estrogen deficiency leads to further mandibular bone loss in CKD mice.

  2. High dietary calcium intake does not counteract disuse-induced bone loss

    Science.gov (United States)

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

    Reduction of mechanical stress on bone inhibits osteoblast-mediated bone formation, increases osteoclast-mediated bone resorption, and leads to what has been called disuse osteoporosis. Prolonged therapeutic bed rest, immobilization and space flight are common causes of disuse osteoporosis. There are sufficient data supporting the use of calcium in combination with vitamin D in the prevention and treatment of postmenopausal osteoporosis. In our study we examined the potential of high dietary calcium intake as a nutrition therapy for disuse-induced bone loss during head-down bed rest in healthy young men. In 2 identical metabolic ward, head-down bed rest (HDBR) experiments (crossover design), we studied the effect of high dietary calcium intake (2000 mg/d) in comparison to the recommended calcium intake of 1000 mg/d on markers of bone turnover. Experiment A (EA) was a 6-day randomized, controlled HDBR study. Experiment B (EB) was a 14-day randomized, controlled HDBR study. In both experiments, the test subjects stayed under well-controlled environmental conditions in our metabolic ward. Subjects' diets in the relevant study phases (HDBR versus Ambulatory Control) of EA and EB were identical except for the calcium intake. The subjects obtained 2000 mg/d Calcium in EA and 2000 mg/d in EB. Blood was drawn at baseline, before entering the relevant intervention period, on day 5 in study EA, and on days 6, 11 and 14 in study EB. Serum calcium, bone formation markers - Procollagen-I-C-Propeptide (PICP) and bone alkaline phosphatase (bAP) were analyzed in serum. 24h-urine was collected throughout the studies for determination of the excretion of calcium (UCaV) and a bone resorption marker, C-terminal telopeptide of collagen type I (UCTX). In both studies, serum calcium levels were unchanged. PICP tended to decrease in EA (p=0.08). In EB PICP decreased significantly over time (p=0.003) in both the control and HDBR periods, and tended to further decrease in the HDBR period (p

  3. 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...

  4. 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.

  5. Quantitative evaluation of bone-mineral density loss using X-ray coherent scattering

    Science.gov (United States)

    Barroso, Regina Cély; Oliveira, Luis Fernando; Castro, Carlos Roberto Ferreira; Lima, João Carlos; Braz, Delson; Lopes, Ricardo Tadeu; Droppa, Roosevel; Tromba, Giuliana; Mancini, Lucia; Zanini, Franco; Rigon, Luigi; Dreossi, Diego

    2007-08-01

    In this work, we intend to relate the mineral to non-mineral bone scattering intensity ratio with the bone-mineral density (BMD) reduction. In this way, EDXRD can be a novel technique to measure BMD loss in function of the mineral and non-mineral scattering intensity. The scattering profiles were obtained at Laboratório Nacional de Luz Síncrotron (LNLS) at the X-ray diffraction beamline XD2. A double-crystal Si(1 1 1) pre-monochromator, upstream of the beamline, was used to select a small energy bandwidth (Δ λ/ λ≈10 -4) at 11 keV. The sample holder has a circle depression in the center to contain a range of bone and fat mixture ratios. The mixture consists of powdered cortical bone and fat, which together simulate in vivo bone. The diffraction patterns were carried out with 0.5 mm slits after and behind of the sample holder. The data were collected in 0.05° increments every 0.5 s. EDXRD results show an indication of different bone densities may be distinguished which suggested that X-ray coherent scattering technique may have a role in monitoring changes in BMD via changes in the related scattering intensity of mineral and non-mineral bone. The main aim of the Synchrotron Radiation for MEdical Physics (SYRMEP) project at the ELETTRA is the investigation and the development of innovative techniques for medical imaging. The beamline provides, at a distance of about 23 m from the source, a monochromatic, laminar section X-ray beam with a maximum area of about 160×5 mm 2 at 20 keV. The monochromator, that covers the entire angular acceptance of the beamline, is based on a double-Si (1 1 1) crystal system working in Bragg configuration. A micrometric vertical and horizontal translation stage allows the positioning and scanning of the sample with respect to the stationary beam. In this case, the detector is kept stationary in front of the beam, while the object is rotated in discrete steps in front of it. At each rotation, a projection is acquired. A goniometric

  6. Effects of Smoking on Alveolar Bone Loss of Dental Undergraduate Students in University of Malaya

    Directory of Open Access Journals (Sweden)

    Fouad Hussain Al-Bayaty

    2015-10-01

    Full Text Available Purpose of the study: This study is undertaken to investigate the prevalence of smoking among dental undergraduate students in the University of Malaya, and to study the effects of smoking on the interproximal bone height. Materials and method: A smoking habits questionnaire was distributed to the 299 dental undergraduate students of Year 2 to Year 5. Students were divided into groups of smokers (history of smoking for at least 1 year, former smokers (history of smoking and stopped more than 1 year and non-smokers (no smoking history. Two bitewing radiographs (left and right were taken from 14 smokers and 5 former smokers. In addition, 14 students were randomly picked as control group, and their previously taken bitewing radiographs were collected. Interproximal bone loss defined as the distance (mm from CEJ to the alveolar crest (AC was measured using caliper, magnifier and metal ruler. Results: The prevalence of smokers and former smokers among dental students was 5.57% and 1.99% respectively. Mean  SEM of the CEJ-AC distance for smokers and non-smokers was 1.063  0.066 mm and 0.849  0.050 mm, respectively. The difference was statistically significant between the smokers and non-smokers (p<0.05. Mean SEM of bone loss among the smoker was 0.204  0.066 mm. There was no statistically significant difference between former smokers and non-smokers (p>0.05. Premolar is the most affected tooth in smokers, with a mean SEM of the CEJ-AC distance of 1.350  0.102 mm. Conclusions: Smoking prevalence among dental undergraduate students was very low. Smokers have more bone destruction than the non-smokers.

  7. 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

  8. Atorvastatin decreases bone loss, inflammation and oxidative stress in experimental periodontitis.

    Directory of Open Access Journals (Sweden)

    Raimundo Fernandes de Araújo Júnior

    Full Text Available The aim of this study is to determine the effects of Atorvastatin treatment, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA reductase, in periodontal disease. Male Wistar albino rats were randomly divided into five groups of ten rats each: (1 non-ligated treatment (NL, (2 ligature only (L, (3 ligature plus 1 mg/kg Atorvastatin daily for 10 days, (4 ligature plus 5 mg/kg Atorvastatin daily for 10 days, and (5 ligature plus 10 mg/kg Atorvastatin daily for 10 days. Following the treatment course, the periodontal tissue of the animals was analyzed by Measurement of alveolar bone loss, Histopathology and immunohistochemistry to determine of the expression of COX-2, MMP-2, MMP9, and RANKL/RANK/OPG. ELISA assay was used to quantitate the levels of IL-1β, IL-10, TNF-α, myeloperoxidase, malondialdehyde, and glutathione. The periodontal group treated with 10 mg/kg of Atorvastatin (3.9±0.9 mm; p<0.05 showed reverse the alveolar bone loss caused Experimental Periodontal Disease compared to (L (7.02±0.17 mm. The periodontal group treated with 10 mg/kg of Atorvastatin showed a significant reduction in MPO and MDA (p<0.05 compared to ligature only group (L. Similarly in this group, the levels of the proinflammatory cytokines IL-1β and TNF-α were significantly decreased (p<0.05. Furthermore, MMP-2, MMP-9, RANKL/RANK, and COX-2 were all downregulated by Atorvastatin treatment, while OPG expression was increased. The findings support a role of Atorvastatin for reducing the bone loss, inflammatory response, oxidative stress, and expression of extracellular matrix proteins, while reducing RANK/RANKL and increase OPG in periodontal disease.

  9. Feeding blueberry diets in early life prevent senescence of osteoblasts and bone loss in ovariectomized adult female rats.

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    Jian Zhang

    Full Text Available BACKGROUND: Appropriate nutrition during early development is essential for maximal bone mass accretion; however, linkage between early nutrition, childhood bone mass, peak bone mass in adulthood, and prevention of bone loss later in life has not been studied. METHODOLOGY AND PRINCIPAL FINDINGS: In this report, we show that feeding a high quality diet supplemented with blueberries (BB to pre-pubertal rats throughout development or only between postnatal day 20 (PND20 and PND34 prevented ovariectomy (OVX-induced bone loss in adult life. This protective effect of BB is due to suppression of osteoblastic cell senescence associated with acute loss of myosin expression after OVX. Early exposure of pre-osteoblasts to serum from BB-fed rats was found to consistently increase myosin expression. This led to maintenance osteoblastic cell development and differentiation and delay of cellular entrance into senescence through regulation of the Runx2 gene. High bone turnover after OVX results in insufficient collagenous matrix support for new osteoblasts and their precursors to express myosin and other cytoskeletal elements required for osteoblast activity and differentiation. CONCLUSIONS/SIGNIFICANCE: These results indicate: 1 a significant prevention of OVX-induced bone loss from adult rats can occur with only 14 days consumption of a BB-containing diet immediately prior to puberty; and 2 the molecular mechanisms underlying these effects involves increased myosin production which stimulates osteoblast differentiation and reduces mesenchymal stromal cell senescence.

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

    DEFF Research Database (Denmark)

    Grubbe, M-C; Thomsen, Jesper Skovhus; Nyengaard, J R;

    2014-01-01

    limb. Sixty female Wistar rats, 14 weeks old, were divided into the following groups: baseline, controls, BTX, BTX+GH, and GH. GH was given at a dosage of 5 mg/kg/d for 4 weeks. Compared with controls, BTX resulted in lower periosteal bone formation rate (BFR/BS,-79%, P...BMD, -13%, Pstrength (-12%, P... of periosteal BFR/BS (2-fold increase vs. BTX, Pstrength was found. In addition, GH partly prevented loss of muscle mass (+29% vs. BTX, P

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

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    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.

  12. Diagnosis of osteoarthritis and prognosis of tibial cartilage loss by quantification of tibia trabecular bone from MRI

    DEFF Research Database (Denmark)

    Marques, Joselene; Genant, Harry K; Lillholm, Martin;

    2013-01-01

    A longitudinal study was used to investigate the quantification of osteoarthritis and prediction of tibial cartilage loss by analysis of the tibia trabecular bone from magnetic resonance images of knees. The Kellgren Lawrence (KL) grades were determined by radiologists and the levels of cartilage...... loss were assessed by a segmentation process. Aiming to quantify and potentially capture the structure of the trabecular bone anatomy, a machine learning approach used a set of texture features for training a classifier to recognize the trabecular bone of a knee with radiographic osteoarthritis. Using...... cross-validation, the bone structure marker was used to estimate for each knee both the probability of having radiographic osteoarthritis (KL >1) and the probability of rapid cartilage volume loss. The diagnostic ability reached a median area under the receiver-operator-characteristics curve of 0.92 (P...

  13. 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;

    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......: DXR-BMD was measured from hand x-rays in a reference cohort (1485 men/2541 women) without arthritis randomly selected from an urban Danish population. Sex- and age-related HBL/year was estimated. DXR-BMD was measured in rheumatoid arthritis patients (n = 350: at start of TNFI, and ~2 years after TNFI...... increased HBL during TNFI treatment. In the 350 patients, increased HBL during TNFI was associated with time-averaged 28-joint disease activity score (odds ratio 1.69 (95 % Confidence Interval 1.34-2.15)/unit increase, p 

  14. 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.

  15. 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

  16. 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

  17. 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

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

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    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

  19. 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

  20. Massive bone loss from fungal infection after anterior cruciate ligament arthroscopic reconstruction.

    Science.gov (United States)

    Muscolo, D Luis; Carbo, Lisandro; Aponte-Tinao, Luis A; Ayerza, Miguel A; Makino, Arturo

    2009-09-01

    Although there are numerous reports of septic pyogenic arthritis after arthroscopic anterior cruciate ligament (ACL) reconstruction, there is limited information regarding the outcomes of fungal infection. We determined the outcomes of six patients with mycotic infection after regular ACL reconstruction. There were four males and two females with a mean age of 33 years. We determined the number of procedures performed, bone loss originating to control infection, and final reconstruction in these patients. An average of five arthroscopic lavage procedures had been performed at the referring centers. Fungal infection was diagnosed based on pathologic samples; five infections were the result of mucormycosis and one was Candida. After final débridement, the mean segmental bone loss was 12.8 cm. All patients were treated with intravenous antifungal coverage and cement spacers before final reconstruction. At final followup, all patients were free of clinical infection. Three had reconstruction with an allograft-prosthesis composite, two with hemicylindrical allografts, and one with an intercalary allograft arthrodesis. Despite the extremely unusual presentation of this complication, surgeons should be aware of potential and catastrophic consequences of this severe complication after ACL reconstruction.

  1. Massive bone loss from fungal infection after anterior cruciate ligament arthroscopic reconstruction.

    Science.gov (United States)

    Muscolo, D Luis; Carbo, Lisandro; Aponte-Tinao, Luis A; Ayerza, Miguel A; Makino, Arturo

    2009-09-01

    Although there are numerous reports of septic pyogenic arthritis after arthroscopic anterior cruciate ligament (ACL) reconstruction, there is limited information regarding the outcomes of fungal infection. We determined the outcomes of six patients with mycotic infection after regular ACL reconstruction. There were four males and two females with a mean age of 33 years. We determined the number of procedures performed, bone loss originating to control infection, and final reconstruction in these patients. An average of five arthroscopic lavage procedures had been performed at the referring centers. Fungal infection was diagnosed based on pathologic samples; five infections were the result of mucormycosis and one was Candida. After final débridement, the mean segmental bone loss was 12.8 cm. All patients were treated with intravenous antifungal coverage and cement spacers before final reconstruction. At final followup, all patients were free of clinical infection. Three had reconstruction with an allograft-prosthesis composite, two with hemicylindrical allografts, and one with an intercalary allograft arthrodesis. Despite the extremely unusual presentation of this complication, surgeons should be aware of potential and catastrophic consequences of this severe complication after ACL reconstruction. PMID:19190972

  2. 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

  3. Dried Plum Protects From Radiation-Induced Bone Loss by Attenuating Pro-Osteoclastic and Oxidative Stress Responses

    Science.gov (United States)

    Globus, Ruth

    2015-01-01

    Future space explorations beyond the earths magnetosphere will increase human exposure to space radiation and associated risks to skeletal health. We hypothesize that oxidative stress resulting from radiation exposure plays a major role in progressive bone loss and dysfunction in associated tissue. In animal studies, increased free radical formation is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility. Our long-term goals are to define the mechanisms and risk of bone loss in the spaceflight environment and to facilitate the development of effective countermeasures. We had previously reported that exposure to low or high-LET radiation correlates with an acute increase in the expression of pro-osteoclastic and oxidative stress genes in bone during the early response to radiation followed by pathological changes in skeletal structure. We then conducted systematic screening for potential countermeasures against bone loss where we tested the ability of various antioxidants to mitigate the radiation-induced increase in expression of these markers. For the screen, 16-week old C57Bl6J mice were treated with a dietary antioxidant cocktail, injectable DHLA or a dried plum-enriched diet (DP). Mice were then exposed to 2Gy 137Cs radiation and one day later, marrow cells were collected and the relevant genes analyzed for expression levels. Among the candidate countermeasures tested, DP was most effective in reducing the expression of genes associated with bone loss. Furthermore, analysis of skeletal structure by microcomputed tomography (microCT) revealed that DP also prevents the radiation-induced deterioration in skeletal microarchitecture as indicated by parameters such as percent bone volume (BVTV), trabecular spacing and trabecular number. We also found that DP has similar protective effects on skeletal structure in a follow-up study using 1 Gy of

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

    Energy Technology Data Exchange (ETDEWEB)

    Griffith, James F.; Yeung, David K.W. [Chinese University of Hong Kong, Department of Imaging and Interventional Radiology, Prince of Wales Hospital, Shatin, New Territories (China); Leung, Jason Chi Shun; Leung, Ping C. [Chinese University of Hong Kong, Jockey Club Centre for Osteoporosis Care and Control, Prince of Wales Hospital, Shatin (China); Kwok, Timothy C.Y. [Chinese University of Hong Kong, Department of Medicine and Therapeutics, Prince of Wales Hospital, Shatin (China)

    2011-06-15

    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 (E{sup slope}) (-5.6 {+-} 1.2 Vs -1.1 {+-} 1.2 (mean {+-} standard error) p = 0.014) or muscle maximum enhancement (E{sup max}) (-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 E{sup slope} r = 0.517, p = 0.0003; muscle E{sup max} r = 0.306, p = 0.043) as well as traditionally applied clinical risk factors. Acetabulum E{sup slope}, femoral neck E{sup max} 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.)

  5. Cadium-induced bone loss: Effects in ovariectomized mice and osteoclast-like cells in culture

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharyya, M.H.; Seed, T.M.; Peterson, D.P.; Moretti, E.S.; Kuhn, C.; Brice, L.F.; Choi, T.T.

    1988-01-01

    The research reported here was conducted to investigate the possibility that cadmium might be a factor that increases bone loss after the menopause. In our first study, we exposed female CF1 mice to a purified diet containing CdCl2 at either 0.25, 5.0, or 50 ppM Cd starting at 70 days of age. After 12 months of exposure, mice were ovariectomized (OV) or sham-operated (SO). After surgery, they remained on their respective diets for an additional six months before sacrifice. Results showed that neither ovariectomy alone nor dietary Cd exposure alone significantly decrease bone calcium content. However, dietary Cd at 50 ppM in combination with ovariectomy caused a striking decrease in the calcium content of mouse bones. The mice in the above study were quite old (435 days old at ovariectomy; 617 days old at sacrifice) and had been exposed to dietary cadmium for one year prior to removal of the ovaries. Consequently, the follow-up study reported here was conducted in mice whose skeletons were pre-labelled with UVCa. This study was designed to determine whether cadmium exposure would cause as increased release of UVCa from the skeletons of OV mice immediately after the start of cadmium exposure and in the absence of the one-year pre-exposure period present in our first study. Such results would indicate that cadmium might act directly on bone rather than indirectly by way of damage to another organ such as the kidney. 14 refs., 1 fig.

  6. 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

  7. 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.

  8. 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

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

    Science.gov (United States)

    Andreasen, Christina M; Ding, Ming; Overgaard, Søren; Bollen, Peter; Andersen, Thomas L

    2015-06-01

    Large animals as sheep are often used as models for human osteoporosis. Our aim was therefore to determine how glucocorticoid treatment of ovariectomised sheep affects the cancellous bone, determining the cellular events within the bone remodelling process that contributes to their bone loss. Twenty female sheep were assigned for two groups; an untreated control group and an ovariectomised group treated with glucocorticoids (0.6 mg/kg/day, 5 times weekly) for 7 months. At 7 months the glucocorticoid-treated ovariectomised sheep showed a significant change in the bone microstructure revealed by a decreased trabecular bone volume and thickness compared to the control sheep. The treatment led to a temporary elevation of the bone resorption marker CTX (c-terminal collagen telopeptide), while the bone formation marker osteocalcin remained suppressed all 7 months. Histomorphometrically, the treated sheep had a complete absence of osteoid surfaces, and a 5-fold increase in the extent of eroded/reversal surfaces after 7 months. 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 recently demonstrated in postmenopausal women with glucocorticoid-induced osteoporosis. This supports the relevance of the sheep model to the pathophysiology of glucocorticoid

  10. 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

  11. 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

  12. 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

  13. 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

    the implants and 3) whether the presence of mandibular osteoporosis affects the loss of bone height around the implants. The material consisted of 22 long-term edentulous healthy persons, 18 women and 4 men from 54 to 78 years of age with 1 Astra Tech Dental Implant in both canine regions, connected by a bar......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...... of bone height around implants was measured on periodically identical intraoral radiographs. The fixed parts of the implant-system were stable during the trial in all patients. In conclusion: 1) the increased function after this treatment seems to cause a load-related bone formation which minimizes...

  14. 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...

  15. Prolactin Expression in the Cochlea of Aged BALB/c Mice Is Gender Biased and Correlates to Loss of Bone Mineral Density and Hearing Loss

    Science.gov (United States)

    Marano, Robert J.; Tickner, Jennifer; Redmond, Sharon L.

    2013-01-01

    Prolactin is a versatile hormone with over 300 known functions and predominantly expressed in the pituitary. However, its expression has additionally been found in a number of extrapituitary organs. Recently, we described the expression of prolactin in the inner ear of mice, where it was correlated to age. Previous research has shown prolactin to be linked to abnormal bone metabolism and hearing loss due to changes in morphology of the bony otic capsule. Here we further investigated the relationship between prolactin, hearing loss and cochlea bone metabolism. BALB/c mice were tested for hearing using ABR at 6 and 12 months of age. Bone mineral density of the cochlea was evaluated using microCT scanning. Prolactin expression was calculated using quantitative real time PCR. Expression of the key regulators of bone metabolism, osteoprotegerin and receptor activator of nuclear factor-kappaB ligand were also determined. We found that prolactin expression was exclusive to the female mice. This also correlated to a greater threshold shift in hearing for the females between 6 and 12 months of age. Analyses of the cochlea also show that the bone mineral density was lower in females compared to males. However, no gender differences in expression of osteoprotegerin or receptor activator of nuclear factor-kappaB ligand could be found. Further analysis of cochlea histological sections revealed larger ostocyte lacunae in the females. These results provide a possible mechanism for an age related hearing loss sub-type that is associated with gender and provides clues as to how this gender bias in hearing loss develops. In addition, it has the potential to lead to treatment for this specific type of hearing loss. PMID:23667691

  16. Prolactin expression in the cochlea of aged BALB/c mice is gender biased and correlates to loss of bone mineral density and hearing loss.

    Directory of Open Access Journals (Sweden)

    Robert J Marano

    Full Text Available Prolactin is a versatile hormone with over 300 known functions and predominantly expressed in the pituitary. However, its expression has additionally been found in a number of extrapituitary organs. Recently, we described the expression of prolactin in the inner ear of mice, where it was correlated to age. Previous research has shown prolactin to be linked to abnormal bone metabolism and hearing loss due to changes in morphology of the bony otic capsule. Here we further investigated the relationship between prolactin, hearing loss and cochlea bone metabolism. BALB/c mice were tested for hearing using ABR at 6 and 12 months of age. Bone mineral density of the cochlea was evaluated using microCT scanning. Prolactin expression was calculated using quantitative real time PCR. Expression of the key regulators of bone metabolism, osteoprotegerin and receptor activator of nuclear factor-kappaB ligand were also determined. We found that prolactin expression was exclusive to the female mice. This also correlated to a greater threshold shift in hearing for the females between 6 and 12 months of age. Analyses of the cochlea also show that the bone mineral density was lower in females compared to males. However, no gender differences in expression of osteoprotegerin or receptor activator of nuclear factor-kappaB ligand could be found. Further analysis of cochlea histological sections revealed larger ostocyte lacunae in the females. These results provide a possible mechanism for an age related hearing loss sub-type that is associated with gender and provides clues as to how this gender bias in hearing loss develops. In addition, it has the potential to lead to treatment for this specific type of hearing loss.

  17. 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...

  18. Lycopene treatment against loss of bone mass, microarchitecture and strength in relation to regulatory mechanisms in a postmenopausal osteoporosis model.

    Science.gov (United States)

    Ardawi, Mohammed-Salleh M; Badawoud, Mohammed H; Hassan, Sherif M; Rouzi, Abdulrahim A; Ardawi, Jumanah M S; AlNosani, Nouf M; Qari, Mohammed H; Mousa, Shaker A

    2016-02-01

    Lycopene supplementation decreases oxidative stress and exhibits beneficial effects on bone health, but the mechanisms through which it alters bone metabolism in vivo remain unclear. The present study aims to evaluate the effects of lycopene treatment on postmenopausal osteoporosis. Six-month-old female Wistar rats (n=264) were sham-operated (SHAM) or ovariectomized (OVX). The SHAM group received oral vehicle only and the OVX rats were randomized into five groups receiving oral daily lycopene treatment (mg/kg body weight per day): 0 OVX (control), 15 OVX, 30 OVX, and 45 OVX, and one group receiving alendronate (ALN) (2μg/kg body weight per day), for 12weeks. Bone densitometry measurements, bone turnover markers, biomechanical testing, and histomorphometric analysis were conducted. Micro computed tomography was also used to evaluate changes in microarchitecture. Lycopene treatment suppressed the OVX-induced increase in bone turnover, as indicated by changes in biomarkers of bone metabolism: serum osteocalcin (s-OC), serum N-terminal propeptide of type 1 collagen (s-PINP), serum crosslinked carboxyterminal telopeptides (s-CTX-1), and urinary deoxypyridinoline (u-DPD). Significant improvement in OVX-induced loss of bone mass, bone strength, and microarchitectural deterioration was observed in lycopene-treated OVX animals. These effects were observed mainly at sites rich in trabecular bone, with less effect in cortical bone. Lycopene treatment down-regulated osteoclast differentiation concurrent with up-regulating osteoblast together with glutathione peroxidase (GPx) catalase (CAT) and superoxide dismutase (SOD) activities. These findings demonstrate that lycopene treatment in OVX rats primarily suppressed bone turnover to restore bone strength and microarchitecture.

  19. 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 ...

  20. Short communication: Proteins in heat-processed skim milk powder have no positive effects on bone loss of ovariectomized rats.

    Science.gov (United States)

    Du, M; Kong, Y; Wang, C; Gao, H; Han, X; Yi, H; Zhang, L

    2011-06-01

    Milk has positive effects on bone growth. However, the effect of skim milk powder (SMP) on bone properties has not been reported. This study investigated the effect of SMP on bone loss in ovariectomized (OVX) rats. Forty female Sprague-Dawley rats were ovariectomized and another 10 rats received a sham operation. The OVX rats were randomly separated into 4 groups: OVX control, OVX SMP1 (SMP at 0.04 g/d), OVX SMP2 (SMP at 0.20 g/d), and OVX SMP3 (SMP at 0.40 g/d). Skim milk powder was supplied in the rat diet for 12 wk, and the rats were gavaged once per day. The effects of SMP on calcium content and bone mineral density of femur were determined by atomic absorption spectrophotometry and dual-energy x-ray absorptiometry, respectively. Compared with the control, SMP at all dose levels tested had no particular effect on weight:length, calcium content, or bone mineral density of femurs. It was demonstrated that SMP (0.04 to 0.40 g/d) had no positive effect on bone loss in OVX rats, probably because the heat treatment used during SMP processing caused a loss of biological activity in the protein.

  1. WIse-2005: Combined Aerobic and Resistive Exercise May Help Mitigate Bone Loss During 60-D Simulated Microgravity in Women

    Science.gov (United States)

    Smith, Scott M.; Zwart, S. R.; Heer, M. A.; Lee, S. M. C.; Macias, B. R.; Schneider, S. M.; Trappe, S. M.; Hargens, A. R.

    2006-01-01

    Exercise can attenuate bone loss associated with disuse during bed rest (BR), an analog of space flight. Previous studies have examined the efficacy of aerobic or resistive exercise countermeasures, but not in combination. We sought to determine the effect of a combined resistive and aerobic exercise regimen on bone metabolism during BR. After a 20-d ambulatory adaptation to confinement and diet, 16 women participated in a 60-d head-down-tilt BR. Control subjects (CN, n=8) performed no countermeasures. Exercise subjects, (EX, n=8) participated in exercise alternating daily between supine treadmill exercise within lower body negative pressure and resistive fly-wheel exercise (6-d wk(sup -1)). In the last week of BR, bone resorption was greater (p less than 79 plus or minus 44%, mean plus or minus SD) and EX groups (64 50%). N-telopeptide also increased (CN: 51 plus or minus 34%; EX: 43 plus or minus 56%). However, bone-specific alkaline phosphatase, a bone formation marker, tended to be higher in EX (26 plus or minus 18%) than in CN (8 plus or minus 33%) groups. The combination of resistive and aerobic exercise does not prevent bone resorption, but may promote formation, potentially mitigating the net bone loss associated with simulated microgravity. This study was supported by CNES, CSA, ESA, NASA, and NASA grant NNJ04HF71G to ARH. MEDES (French Institute for Space Medicine and Physiology) organized the study.

  2. Effects of local vibration on bone loss in -tail-suspended rats.

    Science.gov (United States)

    Sun, L W; Luan, H Q; Huang, Y F; Wang, Y; Fan, Y B

    2014-06-01

    We investigated the effects of vibration (35 Hz, 45 Hz and 55 Hz) as countermeasure locally applied to unloading hind limbs on bone, muscle and Achilles tendon. 40 female Sprague Dawley rats were divided into 5 groups (n=8, each): tail-suspension (TS), TS plus 35 Hz/0.3 g vibration (TSV35), TS plus 45 Hz/0.3 g vibration (TSV45), TS plus 55 Hz/0.3 g vibration (TSV55) and control (CON). After 21 days, bone mineral density (BMD) and the microstructure of the femur and tibia were evaluated by μCT in vivo. The biomechanical properties of the femur and Achilles tendon were determined by a materials testing system. Ash weight of bone, isotonic contraction and wet weight of soleus were also investigated. 35 Hz and 45 Hz localized vibration were able to significantly ameliorate the decrease in trabecular BMD (expressed as the percentage change from TS, TSV35: 48.11%, TSV45: 31.09%), microstructure and ash weight of the femur and tibia induced by TS. Meanwhile, 35 Hz vibration significantly improved the biomechanical properties of the femur (57.24% bending rigidity and 41.66% Young's modulus vs. TS) and Achilles tendon (45.46% maximum load and 66.67% Young's modulus vs. TS). Additionally, Young's modulus of the femur was highly correlated with microstructural parameters. Localized vibration was useful for counteracting microgravity-induced musculoskeletal loss. In general, the efficacy of 35 Hz was better than 45 Hz or 55 Hz in tail-suspended rats.

  3. 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.

  4. 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

  5. Alveolar bone loss and gingival recession due to lip and tongue piercing.

    Science.gov (United States)

    Levin, Liran

    2007-01-01

    Oral piercing is a practice that has gained acceptance as a sign of individuality, marginality, decoration or group membership. In spite of its banal appearance, as seen in various scientific studies, piercing is not without risks. Complications include infection, bleeding and local trauma, which are frequent enough to raise questions about the safety and dangers of piercing. The case presented here revealed marked gingival recession accompanied by substantial bone loss caused by piercing the lower lip and tongue. Dental practitioners should be aware of the increasing number of patients with pierced intraoral and perioral sites and be prepared to provide appropriate guidance to patients who contemplate body piercing that involves oral sites. PMID:17891882

  6. 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

  7. Resveratrol attenuates ovariectomy-induced hypertension and bone loss in stroke-prone spontaneously hypertensive rats.

    Science.gov (United States)

    Mizutani, K; Ikeda, K; Kawai, Y; Yamori, Y

    2000-04-01

    We examined the effect of resveratrol (3,4',5-trihydroxy stilbene), a phenolic compound found in the skins of most grapes, on blood pressure and bone loss in ovariectomized (OVX), stroke-prone spontaneously hypertensive rats (SHRSP). Nineteen-week-old female SHRSP were divided into a sham-ovariectomized (sham) group fed a control diet and two OVX groups fed either a control diet (OVX-Cont) or a diet supplemented with resveratrol (5 mg/kg per d; OVX-Resv). Ovariectomy induced significant increases in systolic blood pressure (SBP). Resveratrol lowered the SBP by 15%) by the third week of administration, and this effect was maintained throughout the study. Resveratrol treatment also significantly enhanced endothelium-dependent vascular relaxation in response to acetylcholine (ACh) in OVX rats. Finally, femur breaking energies measured for the resveratrol-treated (OVX-Resv) group were significantly higher than those of the resveratrol-untreated (OVX-Cont) group. While no significant differences in calcium, magnesium and phosphorus content were found between the femurs of OVX-Cont and OVX-Resv rats, the femur hydroxyproline content in the OVX-Resv group was significantly higher than of the OVX-Cont group. We conclude that, in OVX-SHRSP, resveratrol acts by a similar mechanism to mammalian estrogens, lowering blood pressure by increasing dilatory responses to ACh. The present study also demonstrated that resveratrol was able to prevent ovariectomy-induced decreases in femoral bone strength.

  8. 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.

  9. Histopathological Verification of Osteoimmunological Mediators in Peri-Implantitis and Correlation to Bone Loss and Implant Functional Period.

    Science.gov (United States)

    Konermann, Anna; Götz, Werner; Le, Michael; Dirk, Cornelius; Lossdörfer, Stefan; Heinemann, Friedhelm

    2016-02-01

    Peri-implantitis (PI) is characterized by inflammation and bone resorption eventually leading to implant failure, but the characteristic pathologic determinants are undefined to date. This study aims to elucidate the parameters involved in PI pathogenesis, including intraoral implant retention time, extent of bone loss, smoking history, and identification of osteoimmunological markers for inflammation and bone loss. Peri-implant tissues (n = 21) displaying clinically diagnosed PI from patients with vertical bone loss ranging from 0-12 mm and implant function period between 1 and 60 months were evaluated by histochemistry and immunohistochemistry for TRAP, CD3, RANK, RANKL, OPG, and TNF-α. Statistical analyses were performed with the Welch test and correlation coefficients were calculated. Most bone resorption occurred during the first 12 months of implant function and correlated with the extent of inflammation, although histological signs of inflammation strongly varied between samples from minimal appearance of inflammatory cells to extended infiltrates. Implant function period and smoking history did not significantly affect the degree of inflammation. Higher RANK levels emerged in the first 12 months of implant function compared to longer retention times and were negatively correlated to the occurrence of RANKL. Additionally, histological signs of inflammation were about two-fold higher in specimens with bone resorption up from 5 mm compared to under 5 mm. CD3(+) cells were more prevalent in extensive inflammatory infiltrates and samples derived from smokers. Our analyses proved that PI-induced bone loss is differentially influenced by the parameters evaluated in this study, but a distinct interconnection between disease severity and implant retention time can be established.

  10. 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.

  11. 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.

  12. High-volume FES-cycling partially reverses bone loss in people with chronic spinal cord injury.

    Science.gov (United States)

    Frotzler, Angela; Coupaud, Sylvie; Perret, Claudio; Kakebeeke, Tanja H; Hunt, Kenneth J; Donaldson, Nick de N; Eser, Prisca

    2008-07-01

    Spinal cord injury (SCI) leads to severe bone loss in the paralysed limbs and to a resulting increased fracture risk thereof. Since long bone fractures can lead to comorbidities and a reduction in quality of life, it is important to improve bone strength in people with chronic SCI. In this prospective longitudinal cohort study, we investigated whether functional electrical stimulation (FES) induced high-volume cycle training can partially reverse the loss of bone substance in the legs after chronic complete SCI. Eleven participants with motor-sensory complete SCI (mean age 41.9+/-7.5 years; 11.0+/-7.1 years post injury) were recruited. After an initial phase of 14+/-7 weeks of FES muscle conditioning, participants performed on average 3.7+/-0.6 FES-cycling sessions per week, of 58+/-5 min each, over 12 months at each individual's highest power output. Bone and muscle parameters were investigated in the legs by means of peripheral quantitative computed tomography before the muscle conditioning (t1), and after six (t2) and 12 months (t3) of high-volume FES-cycle training. After 12 months of FES-cycling, trabecular and total bone mineral density (BMD) as well as total cross-sectional area in the distal femoral epiphysis increased significantly by 14.4+/-21.1%, 7.0+/-10.8% and 1.2+/-1.5%, respectively. Bone parameters in the femoral shaft showed small but significant decreases, with a reduction of 0.4+/-0.4% in cortical BMD, 1.8+/-3.0% in bone mineral content, and 1.5+/-2.1% in cortical thickness. These decreases mainly occurred between t1 and t2. No significant changes were found in any of the measured bone parameters in the tibia. Muscle CSA at the thigh increased significantly by 35.5+/-18.3%, while fat CSA at the shank decreased by 16.7+/-12.3%. Our results indicate that high-volume FES-cycle training leads to site-specific skeletal changes in the paralysed limbs, with an increase in bone parameters at the actively loaded distal femur but not the passively loaded

  13. 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

  14. 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

  15. Skeletal Health Part 1: Overview Of Bone Health and Management In the Cancer Setting.

    Science.gov (United States)

    Turner, Bruce; Ali, Sacha; Drudge-Coates, Lawrence; Pati, Jhumur; Nargund, Vinod; Wells, Paula

    2016-01-01

    Cancer-induced bone disease and cancer therapy-induced bone loss are significant skeletal problems related to the treatment for urological and other cancers. Our team of specialists and nurse practitioners developed a nurse practitioner-led Bone Support Clinic for urologic cancer patients at a university hospital in London, England, United Kingdom, to address this issue. The clinic has been well-accepted, has made a positive impact on the patient journey, helps to ensure continuity of care, and highlights patients who require assessment or treatment for impending skeletal-related events in a timely fashion. This article has been divided into two parts for improved readability.

  16. 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.

  17. 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...

  18. 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.

  19. Arthroscopic Treatment for Shoulder Instability with Glenoid Bone Loss Using Distal Tibia Allograft Augmentation - Short Term Results

    Science.gov (United States)

    Wong, Ivan; Amar, Eyal; Coady, Catherine M.; Dilman, Daryl B.; Smith, Ben

    2016-01-01

    Objectives: Background: The results of arthroscopic anterior labral (Bankart) repair have been shown to have high failure rate in patients with significant glenoid bone loss. Several reconstruction procedures using bone graft have been described to overcome the bone loss, including autogenous coracoid transfer to the anterior glenoid (Latarjet procedure) as well as iliac crest autograft and tibial allografts. In recent years, trends toward minimally invasive shoulder surgery along with improvements in technology and technique have led surgeons to expand the application of arthroscopic treatment. Purpose: This study aims to perform a retrospective analysis of prospectively collected data to evaluate the clinical and radiological follow up of patient who underwent anatomic glenoid reconstruction using distal tibia allograft for the treatment of shoulder instability with glenoid bone loss at 1-year post operation time point. Methods: Between December 2011 and January 2015, 55 patients underwent arthroscopic stabilization of the shoulder by means of capsule-labral reattachment to glenoid ream and bony augmentation of glenoid bone loss with distal tibial allograft for recurrent instability of the shoulder. Preoperative and postoperative evaluation included general assessment by the western Ontario shoulder instability index (WOSI) questionnaire, preoperative and postoperative radiographs and CT scans. Results: Fifty-five patients have been evaluated with mean age of 29.73 years at time of the index operation. There were 40 males (mean age of 29.66) and 15 female (mean age of 29.93). Minimum follow up time was 12 months. The following adverse effects were recorded: none suffered from recurrent dislocation, 2 patients suffered from bone resorption but without overt instability, 1 patient had malunion due to screw fracture, none of the patients had nonunion. The mean pre-operative WOSI score was 36.54 and the mean postoperative WOSI score was 61.0. Conclusion: Arthroscopic

  20. 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

  1. 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

  2. Disrupted bone remodeling leads to cochlear overgrowth and hearing loss in a mouse model of fibrous dysplasia.

    Directory of Open Access Journals (Sweden)

    Omar Akil

    Full Text Available Normal hearing requires exquisite cooperation between bony and sensorineural structures within the cochlea. For example, the inner ear secretes proteins such as osteoprotegrin (OPG that can prevent cochlear bone remodeling. Accordingly, diseases that affect bone regulation can also result in hearing loss. Patients with fibrous dysplasia develop trabecular bone overgrowth resulting in hearing loss if the lesions affect the temporal bones. Unfortunately, the mechanisms responsible for this hearing loss, which could be sensorineural and/or conductive, remain unclear. In this study, we used a unique transgenic mouse model of increased Gs G-protein coupled receptor (GPCR signaling induced by expression of an engineered receptor, Rs1, in osteoblastic cells. These ColI(2.3+/Rs1+ mice showed dramatic bone lesions that histologically and radiologically resembled fibrous dysplasia. We found that ColI(2.3+/Rs1+ mice showed progressive and severe conductive hearing loss. Ossicular chain impingement increased with the size and number of dysplastic lesions. While sensorineural structures were unaffected, ColI(2.3+/Rs1+ cochleae had abnormally high osteoclast activity, together with elevated tartrate resistant acid phosphatase (TRAP activity and receptor activator of nuclear factor kappa-B ligand (Rankl mRNA expression. ColI(2.3+/Rs1+ cochleae also showed decreased expression of Sclerostin (Sost, an antagonist of the Wnt signaling pathway that normally increases bone formation. The osteocyte canalicular networks of ColI(2.3+/Rs1+ cochleae were disrupted and showed abnormal osteocyte morphology. The osteocytes in the ColI(2.3+/Rs1+ cochleae showed increased expression of matrix metalloproteinase 13 (MMP-13 and TRAP, both of which can support osteocyte-mediated peri-lacunar remodeling. Thus, while the ossicular chain impingement is sufficient to account for the progressive hearing loss in fibrous dysplasia, the deregulation of bone remodeling extends to the

  3. 15-deoxy-δ12,14-prostaglandin j2 inhibits osteolytic breast cancer bone metastasis and estrogen deficiency-induced bone loss.

    Directory of Open Access Journals (Sweden)

    Ki Rim Kim

    Full Text Available Breast cancer is the major cause of cancer death in women worldwide. The most common site of metastasis is bone. Bone metastases obstruct the normal bone remodeling process and aberrantly enhance osteoclast-mediated bone resorption, which results in osteolytic lesions. 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2 is an endogenous ligand of peroxisome proliferator-activated receptor gamma (PPARγ that has anti-inflammatory and antitumor activity at micromolar concentrations through PPARγ-dependent and/or PPARγ-independent pathways. We investigated the inhibitory activity of 15d-PGJ2 on the bone loss that is associated with breast cancer bone metastasis and estrogen deficiency caused by cancer treatment. 15d-PGJ2 dose-dependently inhibited viability, migration, invasion, and parathyroid hormone-related protein (PTHrP production in MDA-MB-231 breast cancer cells. 15d-PGJ2 suppressed receptor activator of nuclear factor kappa-B ligand (RANKL mRNA levels and normalized osteoprotegerin (OPG mRNA levels in hFOB1.19 osteoblastic cells treated with culture medium from MDA-MB-231 cells or PTHrP, which decreased the RANKL/OPG ratio. 15d-PGJ2 blocked RANKL-induced osteoclastogenesis and inhibited the formation of resorption pits by decreasing the activities of cathepsin K and matrix metalloproteinases, which are secreted by mature osteoclasts. 15d-PGJ2 exerted its effects on breast cancer and bone cells via PPARγ-independent pathways. In Balb/c nu/nu mice that received an intracardiac injection of MDA-MB-231 cells, subcutaneously injected 15d-PGJ2 substantially decreased metastatic progression, cancer cell-mediated bone destruction in femora, tibiae, and mandibles, and serum PTHrP levels. 15d-PGJ2 prevented the destruction of femoral trabecular structures in estrogen-deprived ICR mice as measured by bone morphometric parameters and serum biochemical data. Therefore, 15d-PGJ2 may be beneficial for the prevention and treatment of breast cancer

  4. 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...

  5. PTH (1–34), but not strontium ranelate counteract loss of trabecular thickness and bone strength in disuse osteopenic rats

    DEFF Research Database (Denmark)

    Brüel, Annemarie; Vegger, Jens Bay; Raffalt, Anders Christer;

    2013-01-01

    -covered surfaces (+53%) compared with controls. This was accompanied by significantly lower trabecular bone volume fraction (−24%), trabecular thickness (−16%), and bone strength (−14% to −32% depending on site). PTH alone counteracted immobilization-induced losses in trabecular (4-fold increase vs. BTX......R in combination could counteract immobilization-induced bone loss in a rat model.Immobilization was induced by injecting 4IU Botox (BTX) into the muscles of the right hind limb. Seventy-two female Wistar rats, 3-months-old, were divided into the following groups: Baseline, Controls, BTX, BTX+PTH, BTX+SrR, and BTX......+PTH+SrR (n=12 in each group). PTH was given as injections (SC) at a dosage of 60 μg/kg/d, and SrR as 900 mg/kg/d in the diet. The experiment lasted for 4weeks.BTX resulted in lower trabecular bone formation rate (−68%) and periosteal bone formation rate (−91%), and a higher fraction of osteoclast...

  6. 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.

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

    Science.gov (United States)

    Spilmont, Mélanie; Léotoing, Laurent; Davicco, Marie-Jeanne; Lebecque, Patrice; Miot-Noirault, Elisabeth; Pilet, Paul; Rios, Laurent; Wittrant, Yohann; Coxam, Véronique

    2015-11-01

    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 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. PMID:26569295

  8. Protective effect of salidroside against bone loss via hypoxia-inducible factor-1α pathway-induced angiogenesis.

    Science.gov (United States)

    Li, Ling; Qu, Ye; Jin, Xin; Guo, Xiao Qin; Wang, Yue; Qi, Lin; Yang, Jing; Zhang, Peng; Li, Ling Zhi

    2016-01-01

    Hypoxia-inducible factor (HIF)-1α plays a critical role in coupling angiogenesis with osteogenesis during bone development and regeneration. Salidroside (SAL) has shown anti-hypoxic effects in vitro and in vivo. However, the possible roles of SAL in the prevention of hypoxia-induced osteoporosis have remained unknown. Two osteoblast cell lines, MG-63 and ROB, were employed to evaluate the effects of SAL on cell viability, apoptosis, differentiation and mineralization in vitro. Rats subjected to ovariectomy-induced bone loss were treated with SAL in vivo. Our results showed that pre-treatment with SAL markedly attenuated the hypoxia-induced reductions in cell viability, apoptosis, differentiation and mineralization. SAL down-regulated HIF-1α expression and inhibited its translocation; however, SAL increased its transcriptional activity and, consequently, up-regulated vascular endothelial growth factor (VEGF). In vivo studies further demonstrated that SAL caused decreases in the mineral, alkaline phosphatase (ALP), and BGP concentrations in the blood of ovariectomized (OVX) rats. Moreover, SAL improved the trabecular bone microarchitecture and increased bone mineral density in the distal femur. Additionally, SAL administration partially ameliorated this hypoxia via the HIF-1α-VEGF signalling pathway. Our results indicate that SAL prevents bone loss by enhancing angiogenesis and osteogenesis and that these effects are associated with the activation of HIF-1α signalling. PMID:27558909

  9. Osteoprotegerin-deficient male mice as a model for severe alveolar bone loss: comparison with RANKL-overexpressing transgenic male mice.

    Science.gov (United States)

    Koide, Masanori; Kobayashi, Yasuhiro; Ninomiya, Tadashi; Nakamura, Midori; Yasuda, Hisataka; Arai, Yoshinori; Okahashi, Nobuo; Yoshinari, Nobuo; Takahashi, Naoyuki; Udagawa, Nobuyuki

    2013-02-01

    Periodontitis, an inflammatory disease of periodontal tissues, is characterized by excessive alveolar bone resorption. An increase in the receptor activator of nuclear factor-κB ligand (RANKL) to osteoprotegerin (OPG) ratio is thought to reflect the severity of periodontitis. Here, we examined alveolar bone loss in OPG-deficient (OPG(-/-)) mice and RANKL-overexpressing transgenic (RANKL-Tg) mice. Alveolar bone loss in OPG(-/-) mice at 12 weeks was significantly higher than that in RANKL-Tg mice. OPG(-/-) but not RANKL-Tg mice exhibited severe bone resorption especially in cortical areas of the alveolar bone. An increased number of osteoclasts was observed in the cortical areas in OPG(-/-) but not in RANKL-Tg mice. Immunohistochemical analyses showed many OPG-positive signals in osteocytes but not osteoblasts. OPG-positive osteocytes in the cortical area of alveolar bones and long bones were abundant in both wild-type and RANKL-Tg mice. This suggests the resorption in cortical bone areas to be prevented by OPG produced locally. To test the usefulness of OPG(-/-) mice as an animal model for screening drugs to prevent alveolar bone loss, we administered an antimouse RANKL antibody or risedronate, a bisphosphonate, to OPG(-/-) mice. They suppressed alveolar bone resorption effectively. OPG(-/-) mice are useful for screening therapeutic agents against alveolar bone loss.

  10. 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

  11. 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

  12. A calcium-collagen chelate dietary supplement attenuates bone loss in postmenopausal women with osteopenia: a randomized controlled trial.

    Science.gov (United States)

    Elam, Marcus L; Johnson, Sarah A; Hooshmand, Shirin; Feresin, Rafaela G; Payton, Mark E; Gu, Jennifer; Arjmandi, Bahram H

    2015-03-01

    Menopause leads to an increased risk for osteoporosis in women. Although drug therapies exist, increasing numbers of people prefer alternative therapies such as dietary supplements, for example, calcium, vitamin D, and collagen hydrolysates for the prevention and treatment of osteoporosis. We have previously shown that a 3-month intervention using a calcium-collagen chelate (CC) dietary supplement was efficacious in improving bone mineral density (BMD) and blood biomarkers of bone turnover in osteopenic postmenopausal women. This study reports the long-term efficacy of CC in reducing bone loss in postmenopausal women with osteopenia. Thirty-nine women were randomly assigned to one of two groups: 5 g of CC containing 500 mg of elemental calcium and 200 IU vitamin D (1,25-dihydroxyvitamin D3) or control (500 mg of calcium and 200 IU vitamin D) daily for 12 months. Total body, lumbar, and hip BMD were evaluated at baseline, 6 and 12 months using dual-energy X-ray absorptiometry. Blood was collected at baseline, 6 and 12 months to assess levels of blood biomarkers of bone turnover. Intent-to-treat (ITT) analysis was performed using repeated measures analysis of variance pairwise comparisons and multivariate analysis to assess time and group interactions. The loss of whole body BMD in women taking CC was substantially lower than that of the control group at 12 months in those who completed the study and the ITT analysis, respectively (CC: -1.33% and -0.33% vs. control: -3.75% and -2.17%; P=.026, P=.035). The CC group had significantly reduced levels of sclerostin and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) (P<.05), and higher bone-specific alkaline phosphatase/TRAP5b ratio (P<.05) than control at 6 months. These results support the use of CC in reducing bone loss in osteopenic postmenopausal women.

  13. 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.

  14. Disuse bone loss in hindquarter suspended rats: partial weightbearing, exercise and ibandronate treatment as countermeasures.

    Science.gov (United States)

    Schultheis, L; Ruff, C B; Rastogi, S; Bloomfield, S; Hogan, H A; Fedarko, N; Thierry-Palmer, M; Ruiz, J; Bauss, F; Shapiro, J R

    2000-07-01

    The purpose of this study was to evaluate potential countermeasures for bone loss during long-term space missions in the hindquarter suspended rat, including partial weight bearing (surrogate for artificial gravity) episodic full weight bearing (2 hour/day full weight bearing) and treatment with the third generation bisphosphonate ibandronate (Roche). Graded mechanical loading was studied by housing the animals on a novel servo controlled force plate system which permitted the titration of mechanical force at varying frequency and amplitude and different levels of weight bearing. The force plate, which forms the cage floor, is a glass platform supported by an 18" diameter speaker cone filled with expanding polyurethane foam. An infrared optical sensor attached to the speaker cone yields a voltage linearly related to vertical displacement of the glass platform. The dynamic force on the paw was computed as a product of the apparent mass of the animal on the platform at rest and the acceleration of the platform determined from the second derivative of the optical sensor output. The mass of the animal on the platform was varied by adjusting tension on the tether suspending the animal. Mechanical impact loading was titrated with the force plate resonating at different frequencies, including 3 Hz and 16 Hz.

  15. 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

  16. Elcatonin prevents bone loss caused by skeletal unloading by inhibiting preosteoclast fusion through the unloading-induced high expression of calcitonin receptors in bone marrow cells.

    Science.gov (United States)

    Tsukamoto, Manabu; Menuki, Kunitaka; Murai, Teppei; Hatakeyama, Akihisa; Takada, Shinichiro; Furukawa, Kayoko; Sakai, Akinori

    2016-04-01

    This study aimed to clarify whether elcatonin (EL) has a preventive action on bone dynamics in skeletal unloading. Seven-week-old male C57BL/6J mice with either ground control (GC) or tail suspension (TS) were administered EL 20U/kg or a vehicle (veh) three times per week and assigned to one of the following four groups: GCEL, GCveh, TSEL, and TSveh. Blood samples and bilateral femurs and tibias of the mice were obtained for analysis. After 7days of unloading, the trabecular bone mineral density in the distal femur obtained via peripheral quantitative computed tomography and the trabecular bone volume were significantly higher in the TSEL group than in the TSveh group. The bone resorption histomorphometric parameters, such as the osteoclast surface and osteoclast number, were significantly suppressed in the TSEL mice, whereas the number of preosteoclasts was significantly increased. The plasma level of tartrate-resistant acid phosphatase-5b (TRACP-5b) was significantly lower in the TSEL group than in all other groups. In the bone marrow cell culture, the number of TRACP-positive (TRACP(+)) multinucleated cells was significantly lower in the TSEL mice than in the TSveh mice, whereas the number of TRACP(+) mononucleated cells was higher in the TSEL mice. On day 4, the expression of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), cathepsin K and d2 isoform of vacuolar ATPase V0 domain (ATP6V0D2) mRNA in the bone marrow cells in the TSEL mice was suppressed, and the expression of calcitonin receptor (Calcr) mRNA on day 1 and Calcr antigen on day 4 were significantly higher in the TSveh mice than in the GCveh mice. EL prevented the unloading-induced bone loss associated with the high expression of Calcr in the bone marrow cells of mouse hindlimbs after tail suspension, and it suppressed osteoclast development from preosteoclasts to mature osteoclasts through bone-resorbing activity. This study of EL-treated unloaded mice provides the

  17. Bone

    Science.gov (United States)

    Helmberger, Thomas K.; Hoffmann, Ralf-Thorsten

    The typical clinical signs in bone tumours are pain, destruction and destabilization, immobilization, neurologic deficits, and finally functional impairment. Primary malignant bone tumours are a rare entity, accounting for about 0.2% of all malignancies. Also benign primary bone tumours are in total rare and mostly asymptomatic. The most common symptomatic benign bone tumour is osteoid osteoma with an incidence of 1:2000.

  18. Inadequate Loading Stimulus on ISS Results in Bone and Muscle Loss

    Science.gov (United States)

    Rice, A. J.; Genc, K. O.; Maender, C. C.; Gopalakrishnan, R.; Kuklis, M. M.; Cavanagh, P. R.

    2011-01-01

    INTRODUCTION Exercise has been the primary countermeasure to combat musculoskeletal changes during International Space Station (ISS) missions. However, these countermeasures have not been successful in preventing loss of bone mineral density (BMD) or muscle volume in crew members. METHODS We examined lower extremity loading during typical days on-orbit and on Earth for four ISS crew members. In-shoe forces were monitored using force-measuring insoles placed inside the shoes. BMD (by DXA), muscle volumes (by MRI), and strength were measured before and after long-duration spaceflight (181 +/- 15 days). RESULTS The peak forces measured during ISS activity were significantly less than those measured in 1g for the same activities. Typical single-leg loads on-orbit during walking and running were 0.89 +/- 0.17 body weights (BW) and 1.28 +/- 0.18 BW compared to 1.18 +/- 0.11 BW and 2.36 +/- .22 BW in 1g, respectively [2]. Crew members were only loaded for an average of 43.17 +/- 14.96 min a day while performing exercise on-orbit even though 146.8 min were assigned for exercise each day. Areal BMD decreased in the femoral neck and total hip by 0.71 +/- 0.34% and 0.81 +/- 0.21% per month, respectively. Changes in muscle volume were observed in the lower extremity (-10 to -16% calf; -4 to -7% thigh) but there were no changes in the upper extremity (+0.4 to -0.8%). Decrements in isometric and isokinetic strength at the knee (range: -10.4 to -24.1%), ankle (range: -4 to -22.3%), and elbow (range: -7.5 to - 16.7%) were also observed. Knee extension endurance tests showed an overall decline in total work (-14%) but an increased resistance to fatigue post-flight. DISCUSSION AND CONCLUSIONS Our findings support the conclusion that the measured exercise durations and/or loading stimuli were insufficient to protect bone and muscle health.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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

  1. Crohn's Disease and Primary Alveolar Bone Loss A literature Review and Case Report

    Institute of Scientific and Technical Information of China (English)

    HUANG Xing-xing; ZHANG Wen-feng; CHEN Xin-min; ZHAO Yi-fa

    2006-01-01

    Crohn's disease is a granulomatous inflammatory bowel disease of unknown cause. Intraoral tissues can be affected occasionally. Oral lesions most frequently appear in lips, gingival tissue, and buccal mucosa. We reported here a case of a 24-year-old man with a 6-month history of mouth ulceration and 2-month history of occasional obdominal pain. Histopathological diagnosis was Crohn's disease. Clinical examinations revealed established intestinal lesions, mouth ulcerations, thickening of the antral mucosa and an unusual pattern presentation rarely previously reported in the literature: generalized alveolar bone loss without obvious periodontitis and history of steroids use.%克罗恩病是一种病因尚不明确的慢性肠道炎性肉芽肿性疾病.偶有口腔组织受累,损害主要见于唇、颊黏膜及牙龈.本文报道一例有口腔病变的克罗恩病,24岁,男性,口腔溃疡不愈半年,伴有2月腹痛史.口腔溃疡活检病理诊断为克罗恩病.临床检查发现除了消化道病损、口腔溃疡、上颌窦黏膜增厚外,出现了罕见的广泛牙槽骨吸收,而患者无牙周病及激素用药史,这一特点在以前的文献中未见报道.

  2. 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...

  3. 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.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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;

    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...

  7. 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...

  8. 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...

  9. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Bone loss in tail-suspended rats in restricted to the unweighted limbs

    Science.gov (United States)

    Bikle, D. D.; Globus, R.; Morey-Holton, E. R.

    1984-01-01

    Space flight which results in certain characteristic changes in the skeleton and it was hypothesized that these abnormalities are a direct result of the weightless state. To determine the role of PTH and 1,25(OH)2D in the bone changes associated with weightlessness, we studied bone metabolism under various dietary conditions using an Earth based rat model system which simulates weightlessness. In this model, rats are suspended by their tails such that their rear limbs are completely unloaded while their fore limbs are normally loaded. It is suggested that skeletal unloading induces a localized defect in the unloaded bone which results in abnormal growth and mineralization. It is concluded that skeletal unloading may make the unloaded bone more or less sensitive to a systemic factor which in turn could account for a change in bone metabolism.

  12. 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)

  13. 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

  14. 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

  15. 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

  16. No major effect of estrogen receptor gene polymorphisms on bone mineral density or bone loss in postmenopausal Danish women

    DEFF Research Database (Denmark)

    Bagger, Y Z; Jørgensen, H L; Heegaard, Anne-Marie;

    2000-01-01

    years). Genotyping was performed through the restriction cleavage of polymerase chain reaction-amplified genomic DNA with the two restriction enzymes, PvuII and XbaI. Restriction fragment-length polymorphisms were represented as P or p (PvuII) and X or x (XbaI), with the lower case letters signifying......The polymorphisms of the estrogen receptor (ER) gene defined by the restriction enodonucleases PvuII and XbaI have recently been reported to be associated with bone mineral density (BMD) in postmenopausal women. To investigate the possible relation of the PvuII and XbaI restriction fragment...... the presence of the restriction site. The frequencies of the ER genotypes were similar to previously published genotype frequencies in Caucasian and Asian populations. No significant effect of the ER genotypes or alleles on BMD was found at any site, nor was there a relation between ER genotypes and the rate...

  17. 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...

  18. 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...

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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.

  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...

  8. 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...

  9. 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...

  10. Effect of 15% Alcohol Dependence on Alveolar Bone Loss and TNF-α Secretion in Wistar Rats.

    Science.gov (United States)

    Wagner, Marcius Comparsi; Rocha, José Mariano da; Gaio, Eduardo José; Cavagni, Juliano; Carrard, Vinícius Coelho; Rösing, Cassiano Kuchenbecker

    2016-01-01

    The aim of the present study was to evaluate the effect of 15% alcohol dependence on ligature-induced alveolar bone loss and TNF-α secretion in Wistar rats. Thirty-three male Wistar rats aged 45-60 days (mean weight=253 g) were randomly allocated test or control groups. Test group (n=18) received 15% alcohol as liquid intake and control group (n=15) received water during the experimental period. TNF-α was analyzed by ELISA assay in 11 animals per group. After 14 days of alcohol/water intake, alcohol dependency was assessed and silk ligatures were placed around the left second upper molars. Ligature presence and body weight were checked weekly. After 40 days, animals were sacrificed and the maxillae were defleshed for morphometric analysis using standardized images. All animals in the test group displayed signs of alcohol dependency at day 14. No statistically significant differences in final body weight (334.83±21.38 vs. 322.48±30.65 g, p=0.20) were observed between groups. In relation to alveolar bone loss, no statistically significant difference was observed among test and control groups both for ligated teeth (0.76±0.06 vs. 0.74±0.10 mm, p=0.60) and unligated teeth (0.41±0.16 vs. 0.35±0.05 mm, p=0.22). The TNF-α secretion also did not display statistically significant differences between test and control groups (10.78±1.84 vs. 12.13±2.11 pg/mL, p=0.12). It may be concluded that 15% alcohol dependency was not capable to alter alveolar bone loss and TNF-α secretion in Wistar rats.

  11. 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.

  12. 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...

  13. 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

  14. 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.

  15. B Cell IgD Deletion Prevents Alveolar Bone Loss Following Murine Oral Infection

    Directory of Open Access Journals (Sweden)

    Pamela J. Baker

    2009-01-01

    and CD4+ T cells in immune normal mice compared to IgD deficient mice. These data suggest that IgD is an important mediator of alveolar bone resorption, possibly through antigen-specific coactivation of B cells and CD4+ T cells.

  16. 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

    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...

  17. Is self-reported alcohol consumption associated with osteoporotic mandibular bone loss in women?

    NARCIS (Netherlands)

    O. Nackaerts; K. Horner; R. Jacobs; K. Karayianni; A. Mitsea; L. Berkas; M. Mastoris; C. Lindh; P.F. van der Stelt; E. Marjanovic; J.E. Adams; S. Pavitt; H. Devlin

    2009-01-01

    The aim of this study was to determine whether alcohol consumption would predict mandibular bone quality and quantity in a large European female population. In total, 672 middle-aged and elderly women (45-70 yr of age; standard deviation = 6) were recruited in the study. Alcohol consumption was reco

  18. 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.

  19. 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.)

  20. Anti-inflammatory and Anti-resorptive Effects of Atorvastatin on Alveolar Bone Loss in Wistar Rats.

    Science.gov (United States)

    Goes, Paula; Lima, Neiberg Alcântara; Rodrigues, José Ariévilo Gurgel; Benevides, Norma Maria Barros; Brito, Gerly Anne Castro; Lima, Vilma

    2016-01-01

    The aim of this study was to evaluate the anti-inflammatory and anti-resorptive effect of atorvastatin (ATV) in an experimental alveolar bone loss (ABL) model. Wistar rats were subjected to ligature placement around the maxillary second molar for 11 days. The animals received 0.9% saline (2 mL/kg) or ATV (0.3, 3 or 27 mg/kg) daily by gavage. ABL was evaluated by resorption area and histopathological analysis. Serum bone-specific alkaline phosphatase (BALP) activity was also evaluated. Leukogram was performed at 0 h, 6th h, 2nd, 7th and 11th days. Kidney and liver conditions and the body mass variation were analyzed. ATV (3 and 27 mg/kg) inhibited ABL by 39% and 56%, respectively. Histopathological analysis showed that ATV 27 mg/kg prevented ABL and cemental resorption, and inflammatory cell infiltration induced by ligature. ATV (27 mg/kg) prevented serum BALP levels reduction. ATV (27 mg/kg) prevented leukocytosis and did not affect either kidney or liver function nor body mass weight. ATV showed a protecting effect in the ligature-induced periodontitis, without affecting system parameters, by inhibition of inflammatory process and by its anabolic activity on the alveolar bone. PMID:27224558

  1. Inhibitory effects of the leaves of loquat (Eriobotrya japonica) on bone mineral density loss in ovariectomized mice and osteoclast differentiation.

    Science.gov (United States)

    Tan, Hui; Furuta, Syoko; Nagata, Toshiro; Ohnuki, Koichiro; Akasaka, Taiki; Shirouchi, Bungo; Sato, Masao; Kondo, Ryuichiro; Shimizu, Kuniyoshi

    2014-01-29

    The loquat, Eriobotrya japonica Lindl. (Rosaceae), is a small tree native to Japan and China that is widely cultivated for its succulent fruit. Its leaves are used as an ingredient of a tasty tea called "Biwa cha" in Japanese. The anti-osteoporosis effects of the leaves of loquat in vitro and in vivo have been investigated. After 15 days of feeding normal diet or diet supplemented with 5% loquat leaves, the body weight, viscera weights, and bone mineral density (BMD) of both groups of eight ovariectomized (OVX) mice were compared. The result showed that the loss of BMD in loquat-fed mice was significantly prevented in three parts of the body, especially in the trabecular bone of the head (P < 0.05), abdomen (P < 0.01), and lumbar (P < 0.05) compared to the control group. No hypertrophy in the uterus by the loquat leaves diet was observed. The effect of the extract (447.25 g) prepared from the dried leaves of loquat (2.36 kg) was further studied on RANKL-induced osteoclast differentiation and cell viability. The extract suppressed the differentiation of osteoclasts under 50, 125, 250, and 500 μg/mL. Through bioactivity-guided fractionation, ursolic acid (1) was isolated and inhibited osteoclast differentiation under 4 and 10 μg/mL. It was concluded that loquat leaves possess the potential to suppress ovariectomy-induced bone mineral density deterioration.

  2. 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...

  3. 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

  4. 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...

  5. 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...

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

    DEFF Research Database (Denmark)

    Jensen, T W; Hansen, M S; Hørslev-Petersen, Kim;

    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...... in hand, lumbar spine and femoral neck was negatively associated with the dose of intra-articular betamethasone (p...

  7. 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...

  8. 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

  9. 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...

  10. Evaluation of bone loss in antibacterial coated dental implants: An experimental study in dogs.

    Science.gov (United States)

    Godoy-Gallardo, Maria; Manzanares-Céspedes, Maria Cristina; Sevilla, Pablo; Nart, José; Manzanares, Norberto; Manero, José M; Gil, Francisco Javier; Boyd, Steven K; Rodríguez, Daniel

    2016-12-01

    The aim of this study was to evaluate the in vivo effect of antibacterial modified dental implants in the first stages of peri-implantitis. Thirty dental implants were inserted in the mandibular premolar sites of 5 beagle dogs. Sites were randomly assigned to Ti (untreated implants, 10units), Ti_Ag (silver electrodeposition treatment, 10units), and Ti_TSP (silanization treatment, 10units). Coated implants were characterized by scanning electron microscopy, interferometry and X-ray photoelectron spectroscopy. Two months after implant insertion, experimental peri-implantitis was initiated by ligature placement. Ligatures were removed 2months later, and plaque formation was allowed for 2 additional months. Clinical and radiographic analyses were performed during the study. Implant-tissue samples were prepared for micro computed tomography, backscattered scanning electron microscopy, histomorphometric and histological analyses and ion release measurements. X-ray, SEM and histology images showed that vertical bone resorption in treated implants was lower than in the control group (P<0.05). This effect is likely due to the capacity of the treatments to reduce bacteria colonization on the implant surface. Histological analysis suggested an increase of peri-implant bone formation on silanized implants. However, the short post-ligature period was not enough to detect differences in clinical parameters among implant groups. Within the limits of this study, antibacterial surface treatments have a positive effect against bone resorption induced by peri-implantitis. PMID:27612745

  11. Bone loss during partial weight bearing (1/6th gravity) is mitigated by resistance and aerobic exercise in mice

    Science.gov (United States)

    Boudreaux, R. D.; Metzger, C. E.; Macias, B. R.; Shirazi-Fard, Y.; Hogan, H. A.; Bloomfield, S. A.

    2014-06-01

    Astronauts on long duration missions continue to experience bone loss, as much as 1-2% each month, for up to 4.5 years after a mission. Mechanical loading of bone with exercise has been shown to increase bone formation, mass, and geometry. The aim of this study was to compare the efficacy of two exercise protocols during a period of reduced gravitational loading (1/6th body weight) in mice. Since muscle contractions via resistance exercise impart the largest physiological loads on the skeleton, we hypothesized that resistance training (via vertical tower climbing) would better protect against the deleterious musculoskeletal effects of reduced gravitational weight bearing when compared to endurance exercise (treadmill running). Young adult female BALB/cBYJ mice were randomly assigned to three groups: 1/6 g (G/6; n=6), 1/6 g with treadmill running (G/6+RUN; n=8), or 1/6 g with vertical tower climbing (G/6+CLB; n=9). Exercise was performed five times per week. Reduced weight bearing for 21 days was achieved through a novel harness suspension system. Treadmill velocity (12-20 m/min) and daily run time duration (32-51 min) increased incrementally throughout the study. Bone geometry and volumetric bone mineral density (vBMD) at proximal metaphysis and mid-diaphysis tibia were assessed by in vivo peripheral quantitative computed tomography (pQCT) on days 0 and 21 and standard dynamic histomorphometry was performed on undemineralized sections of the mid-diaphysis after tissue harvest. G/6 caused a significant decrease (P<0.001) in proximal tibia metaphysis total vBMD (-9.6%). These reductions of tibia metaphyseal vBMD in G/6 mice were mitigated in both G/6+RUN and G/6+CLB groups (P<0.05). After 21 days of G/6, we saw an absolute increase in tibia mid-diaphysis vBMD and in distal metaphysis femur vBMD in both G/6+RUN and G/6+CLB mice (P<0.05). Substantial increases in endocortical and periosteal mineralizing surface (MS/BS) at mid-diaphysis tibia in G/6+CLB demonstrate that

  12. Computer Aided Modeling to Determine the Effectiveness of Resistive Exercises as Countermeasures for Bone Mineral Density Loss

    Science.gov (United States)

    Murphy, Benjamin M.

    1999-01-01

    Due to the loss of gravitational loading, astronauts have a tendency to lose bone mineral density in their lumbar spine and lower extremities on orbit. NASA requires astronauts to perform exercises during space flight to help reduce the amount of demineralization. To test these exercises on earth, 17 week bed rest studies are conducted that consist of specific diet and exercise regimes. Developing a finite element model of these exercises will help to quantify the stress distribution imposed by of each of these exercises. To help develop this model, MRI images are acquired from individuals participating in the bed rest studies. The MRIs can be used to create a subject specific model of each individual for testing. The MRIs are processed in the Magnetic Resonance Imaging Data Transfer System program to develop a three-dimensional finite element model of the femur for evaluation. Modifications were made to the MRIDTS that simplified the model creation process. These modifications made it possible to construct two separate models of different portions of a bone simultaneously and then later connect them manually. This helped alleviate the warping problem associated with the drastic changes in geometry found in some body parts, such as the joints. The code was also modified to incorporate material properties of various bone components into the model. Interior meshing was also incorporated into the program to allow for both the cortical shell and the entire bone to be modeled. A prototype model of the right femur of an adult female is being constructed and tested to determine the feasibility of finite element analysis as a tool for evaluating exercise effectiveness. The model is being run through the ANSYS finite element program on the Alabama Super Computer Network. After the model is validated, models of bedrest subjects can be generated to investigate exercise countermeasures.

  13. 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

  14. 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...

  15. 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

  16. 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.

  17. Prolonged performance of a high repetition low force task induces bone adaptation in young adult rats, but loss in mature rats.

    Science.gov (United States)

    Massicotte, Vicky S; Frara, Nagat; Harris, Michele Y; Amin, Mamta; Wade, Christine K; Popoff, Steven N; Barbe, Mary F

    2015-12-01

    We have shown that prolonged repetitive reaching and grasping tasks lead to exposure-dependent changes in bone microarchitecture and inflammatory cytokines in young adult rats. Since aging mammals show increased tissue inflammatory cytokines, we sought here to determine if aging, combined with prolonged performance of a repetitive upper extremity task, enhances bone loss. We examined the radius, forearm flexor muscles, and serum from 16 mature (14-18 months of age) and 14 young adult (2.5-6.5 months of age) female rats after performance of a high repetition low force (HRLF) reaching and grasping task for 12 weeks. Young adult HRLF rats showed enhanced radial bone growth (e.g., increased trabecular bone volume, osteoblast numbers, bone formation rate, and mid-diaphyseal periosteal perimeter), compared to age-matched controls. Mature HRLF rats showed several indices of radial bone loss (e.g., decreased trabecular bone volume, and increased cortical bone thinning, porosity, resorptive spaces and woven bone formation), increased osteoclast numbers and inflammatory cytokines, compared to age-matched controls and young adult HRLF rats. Mature rats weighed more yet had lower maximum reflexive grip strength, than young adult rats, although each age group was able to pull at the required reach rate (4 reaches/min) and required submaximal pulling force (30 force-grams) for a food reward. Serum estrogen levels and flexor digitorum muscle size were similar in each age group. Thus, mature rats had increased bone degradative changes than in young adult rats performing the same repetitive task for 12 weeks, with increased inflammatory cytokine responses and osteoclast activity as possible causes.

  18. Harpagoside Inhibits RANKL-Induced Osteoclastogenesis via Syk-Btk-PLCγ2-Ca(2+) Signaling Pathway and Prevents Inflammation-Mediated Bone Loss.

    Science.gov (United States)

    Kim, Ju-Young; Park, Sun-Hyang; Baek, Jong Min; Erkhembaatar, Munkhsoyol; Kim, Min Seuk; Yoon, Kwon-Ha; Oh, Jaemin; Lee, Myeung Su

    2015-09-25

    Harpagoside (HAR) is a natural compound isolated from Harpagophytum procumbens (devil's claw) that is reported to have anti-inflammatory effects; however, these effects have not been investigated in the context of bone development. The current study describes for the first time that HAR inhibits receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis in vitro and suppresses inflammation-induced bone loss in a mouse model. HAR also inhibited the formation of osteoclasts from mouse bone marrow macrophages (BMMs) in a dose-dependent manner as well as the activity of mature osteoclasts, including filamentous actin (F-actin) ring formation and bone matrix breakdown. This involved a HAR-induced decrease in extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase (JNK) phosphorylation, leading to the inhibition of Syk-Btk-PLCγ2-Ca(2+) in RANKL-dependent early signaling, as well as the activation of c-Fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1), which resulted in the down-regulation of various target genes. Consistent with these in vitro results, HAR blocked lipopolysaccharide (LPS)-induced bone loss in an inflammatory osteoporosis model. However, HAR did not prevent ovariectomy-mediated bone erosion in a postmenopausal osteoporosis model. These results suggest that HAR is a valuable agent against inflammation-related bone disorders but not osteoporosis induced by hormonal abnormalities. PMID:26308264

  19. 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.

  20. 75 FR 76460 - Lymphohematopoietic Cancers Induced by Chemicals and Other Agents: Overview and Implications for...

    Science.gov (United States)

    2010-12-08

    ... AGENCY Lymphohematopoietic Cancers Induced by Chemicals and Other Agents: Overview and Implications for..., ``Lymphohematopoietic Cancers Induced by Chemicals and Other Agents: Overview and Implications for Risk Assessment.... ADDRESSES: The draft ``Lymphohematopoietic Cancers Induced by Chemicals and Other Agents: Overview...

  1. The transition state analog inhibitor of Purine Nucleoside Phosphorylase (PNP) Immucillin-H arrests bone loss in rat periodontal disease models.

    Science.gov (United States)

    Deves, Candida; de Assunção, Thiago Milech; Ducati, Rodrigo Gay; Campos, Maria Martha; Basso, Luiz Augusto; Santos, Diogenes Santiago; Batista, Eraldo L

    2013-01-01

    Purine nucleoside phosphorylase (PNP) is a purine-metabolizing enzyme that catalyzes the reversible phosphorolysis of 6-oxypurine (deoxy)nucleosides to their respective bases and (deoxy)ribose-1-phosphate. It is a key enzyme in the purine salvage pathway of mammalian cells. The present investigation sought to determine whether the PNP transition state analog inhibitor (Immucillin-H) arrests bone loss in two models of induced periodontal disease in rats. Periodontal disease was induced in rats using ligature or LPS injection followed by administration of Immucillin-H for direct analysis of bone loss, histology and TRAP staining. In vitro osteoclast differentiation and activation of T CD4+ cells in the presence of Immucillin-H were carried out for assessment of RANKL expression, PNP and Cathepsin K activity. Immucillin-H inhibited bone loss induced by ligatures and LPS, leading to a reduced number of infiltrating osteoclasts and inflammatory cells. In vitro assays revealed that Immucillin-H could not directly abrogate differentiation of osteoclast precursor cells, but affected lymphocyte-mediated osteoclastogenesis. On the other hand, incubation of pre-activated T CD4+ with Immucillin-H decreased RANKL secretion with no compromise of cell viability. The PNP transition state analog Immucillin-H arrests bone loss mediated by T CD4+ cells with no direct effect on osteoclasts. PNP inhibitor may have an impact in the treatment of diseases characterized by the presence of pathogens and imbalances of bone metabolism.

  2. A combination of Latarjet and Remplissage for treatment of severe glenohumeral instability and bone loss. A case report.

    Science.gov (United States)

    Ranne, Juha O; Sarimo, Janne J; Heinonen, Olli J; Orava, Sakari Y

    2013-01-01

    Recurrent glenohumeral instability is challenging to treat when large bony defects are present in the anterior glenoid and there is a large Hill-Sachs lesion. We present a case with extensive glenoid and humeral bone loss treated with open Latarjet procedure combined with posterior arthroscopic Remplissage. 3.5 years after surgery, there have been no dislocations or any subjective signs of instability. After half a year, the patient was able to return to work as an airline pilot. Constant score has improved from 33 to 74 and the Oxford instability score from 8 to 46. We find that in young patients with difficult instability combining the Latarjet and Remplissage is a good and replicable method.

  3. 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

  4. 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.

  5. 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.;

    2006-01-01

    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....... Corresponding results for grade 2 erosions (11% to 20% of bone volume eroded) were 42%, 10%, 60% and 24%, and for grade 3 erosions (21% to 30% of bone volume eroded) 75%, 67%, 75% and 100%. All grade 4 (and above) erosions were detected on radiographs. Conventional radiography required a MRI-estimated bone...

  6. 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.

  7. Effect of electroacupuncture treatment on pain behavior and calcitonin-gene related peptide expression in cancer induced bone pain-morphine tolerance rat model%电针对骨癌痛-吗啡耐受大鼠痛行为和降钙素基因相关肽的影响

    Institute of Scientific and Technical Information of China (English)

    司马蕾; 刘波涛; 厉建春; 刘乃刚; 张韫

    2013-01-01

    目的 探讨电针治疗对骨癌痛吗啡耐受模型大鼠痛行为的影响以及背根神经节降钙素基因相关肽(CGRP)表达的变化.方法 40只SD大鼠随机分为4组,每组10只:假手术组(Sham)、骨癌痛+吗啡耐受组(BM)、骨癌痛+电针组(BE)和骨癌痛+吗啡耐受+电针组(BME).BM、BE和BME组制备胫骨癌痛模型,接种后第7天3组分别实施吗啡、电针、吗啡+电针治疗,连续9d.电针选择足三里(ST36)和三阴交(SP6)穴位.痛行为采用机械刺激缩足阈值测定,以50%缩足阈表示.免疫组织化学测定背根神经节CGRP表达水平.结果 电针治疗第5天,BME组50%缩足阈值(10.9±0.8)g,与BM组[(8.7±0.6)g]和BE组[(6.2±0.9)g]相比,差异有统计学意义(P<0.01),并持续至第9天.BME组背根神经节CGRP免疫阳性表达的IOD值(9026.5±1827.4),与BM组(14803.1±2086.7)和BE组(15730.6±2712.5)比较,差异有统计学意义(P<0.01).结论 电针能够改善骨癌痛-吗啡耐受大鼠机械痛阈,机制可能与减少背根神经节CGRP过度释放有关.%Objective To explore the efficacy of electroacupuncture treatment in cancer induced bone pain (CIBP)-morphine tolerance rat model and the expression of calcitonin-gene related peptide(CGRP) immunohistochemisty in dorsal root ganglion (DRG).Methods Forty SD rats were divided into four groups:sham group,CIBP + morphine tolerance group (BM),CIBP + electroacupuncture group (BE),and CIBP + morphine tolerance + electroacupuncture group (BME).BM,BE and BME groups were prepared CIBP model by carcinoma cell tibia implanted.After six days,the three CIBP groups accepted treatment of morphine,electroacupuncture,and morphine combined electroacupuncture,separately,nine days continuously.Acupoints were selected Zusanli (ST36) and Sanyinjiao (SP6).50% mechanical withdraw threshold was evaluated by mechanical stimulation.CGRP expression in dorsal root ganglion was detected by immunohistochemisty.Results After five days of

  8. 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.

  9. Protection against T1DM-Induced Bone Loss by Zinc Supplementation: Biomechanical, Histomorphometric, and Molecular Analyses in STZ-Induced Diabetic Rats.

    Directory of Open Access Journals (Sweden)

    Raul Hernandes Bortolin

    Full Text Available Several studies have established an association between diabetes and alterations in bone metabolism; however, the underlying mechanism is not well established. Although zinc is recognized as a potential preventive agent against diabetes-induced bone loss, there is no evidence demonstrating its effect in chronic diabetic conditions. This study evaluated the effects of zinc supplementation in a chronic (90 days type 1 diabetes-induced bone-loss model. Male Wistar rats were distributed in three groups: control, type 1 diabetes mellitus (T1DM, and T1DM plus zinc supplementation (T1DMS. Serum biochemical analysis; tibia histomorphometric, biomechanical, and collagen-content analyses; and femur mRNA expression were evaluated. Relative to T1DM, the zinc-supplemented group showed increased histomorphometric parameters such as TbWi and BAr and decreased TbSp, increased biomechanical parameters (maximum load, stiffness, ultimate strain, and Young's modulus, and increased type I collagen content. Interestingly, similar values for these parameters were observed between the T1DMS and control groups. These results demonstrate the protective effect of zinc on the maintenance of bone strength and flexibility. In addition, downregulation of OPG, COL1A, and MMP-9 genes was observed in T1DMS, and the anabolic effects of zinc were evidenced by increased OC expression and serum ALP activity, both related to osteoblastogenesis, demonstrating a positive effect on bone formation. In contrast, T1DM showed excessive bone loss, observed through reduced histomorphometric and biomechanical parameters, characterizing diabetes-associated bone loss. The bone loss was also observed through upregulation of OPG, COL1A, and MMP-9 genes. In conclusion, zinc showed a positive effect on the maintenance of bone architecture and biomechanical parameters. Indeed, OC upregulation and control of expression of OPG, COL1A, and MMP-9 mRNAs, even in chronic hyperglycemia, support an anabolic

  10. Protection against T1DM-Induced Bone Loss by Zinc Supplementation: Biomechanical, Histomorphometric, and Molecular Analyses in STZ-Induced Diabetic Rats

    Science.gov (United States)

    Bortolin, Raul Hernandes; da Graça Azevedo Abreu, Bento João; Abbott Galvão Ururahy, Marcela; Costa de Souza, Karla Simone; Bezerra, João Felipe; Bezerra Loureiro, Melina; da Silva, Flávio Santos; Marques, Dáfiny Emanuele da Silva; Batista, Angélica Amanda de Sousa; Oliveira, Gisele; Luchessi, André Ducati; Lima, Valéria Morgiana Gualberto Duarte Moreira; Miranda, Carlos Eduardo Saraiva; Lia Fook, Marcus Vinicius; Almeida, Maria das Graças; de Rezende, Luciana Augusto; de Rezende, Adriana Augusto

    2015-01-01

    Several studies have established an association between diabetes and alterations in bone metabolism; however, the underlying mechanism is not well established. Although zinc is recognized as a potential preventive agent against diabetes-induced bone loss, there is no evidence demonstrating its effect in chronic diabetic conditions. This study evaluated the effects of zinc supplementation in a chronic (90 days) type 1 diabetes-induced bone-loss model. Male Wistar rats were distributed in three groups: control, type 1 diabetes mellitus (T1DM), and T1DM plus zinc supplementation (T1DMS). Serum biochemical analysis; tibia histomorphometric, biomechanical, and collagen-content analyses; and femur mRNA expression were evaluated. Relative to T1DM, the zinc-supplemented group showed increased histomorphometric parameters such as TbWi and BAr and decreased TbSp, increased biomechanical parameters (maximum load, stiffness, ultimate strain, and Young’s modulus), and increased type I collagen content. Interestingly, similar values for these parameters were observed between the T1DMS and control groups. These results demonstrate the protective effect of zinc on the maintenance of bone strength and flexibility. In addition, downregulation of OPG, COL1A, and MMP-9 genes was observed in T1DMS, and the anabolic effects of zinc were evidenced by increased OC expression and serum ALP activity, both related to osteoblastogenesis, demonstrating a positive effect on bone formation. In contrast, T1DM showed excessive bone loss, observed through reduced histomorphometric and biomechanical parameters, characterizing diabetes-associated bone loss. The bone loss was also observed through upregulation of OPG, COL1A, and MMP-9 genes. In conclusion, zinc showed a positive effect on the maintenance of bone architecture and biomechanical parameters. Indeed, OC upregulation and control of expression of OPG, COL1A, and MMP-9 mRNAs, even in chronic hyperglycemia, support an anabolic and protective

  11. 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.

  12. Microgravity induces pelvic bone loss through osteoclastic activity, osteocytic osteolysis, and osteoblastic cell cycle inhibition by CDKN1a/p21.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Blaber

    Full Text Available 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

  13. Simulating the Lunar Environment: Partial Weightbearing and High-LET Radiation-Induce Bone Loss and Increase Sclerostin-Positive Osteocytes.

    Science.gov (United States)

    Macias, B R; Lima, F; Swift, J M; Shirazi-Fard, Y; Greene, E S; Allen, M R; Fluckey, J; Hogan, H A; Braby, L; Wang, Suojin; Bloomfield, S A

    2016-09-01

    Exploration missions to the Moon or Mars will expose astronauts to galactic cosmic radiation and low gravitational fields. Exposure to reduced weightbearing and radiation independently result in bone loss. However, no data exist regarding the skeletal consequences of combining low-dose, high-linear energy transfer (LET) radiation and partial weightbearing. We hypothesized that simulated galactic cosmic radiation would exacerbate bone loss in animals held at one-sixth body weight (G/6) without radiation exposure. Female BALB/cByJ four-month-old mice were randomly assigned to one of the following treatment groups: 1 gravity (1G) control; 1G with radiation; G/6 control; and G/6 with radiation. Mice were exposed to either silicon-28 or X-ray radiation. (28)Si radiation (300 MeV/nucleon) was administered at acute doses of 0 (sham), 0.17 and 0.5 Gy, or in three fractionated doses of 0.17 Gy each over seven days. X radiation (250 kV) was administered at acute doses of 0 (sham), 0.17, 0.5 and 1 Gy, or in three fractionated doses of 0.33 Gy each over 14 days. Bones were harvested 21 days after the first exposure. Acute 1 Gy X-ray irradiation during G/6, and acute or fractionated 0.5 Gy (28)Si irradiation during 1G resulted in significantly lower cancellous mass [percentage bone volume/total volume (%BV/TV), by microcomputed tomography]. In addition, G/6 significantly reduced %BV/TV compared to 1G controls. When acute X-ray irradiation was combined with G/6, distal femur %BV/TV was significantly lower compared to G/6 control. Fractionated X-ray irradiation during G/6 protected against radiation-induced losses in %BV/TV and trabecular number, while fractionated (28)Si irradiation during 1G exacerbated the effects compared to single-dose exposure. Impaired bone formation capacity, measured by percentage mineralizing surface, can partially explain the lower cortical bone thickness. Moreover, both partial weightbearing and (28)Si-ion exposure contribute to a higher proportion of

  14. 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;

    2014-01-01

    BACKGROUND: The relative effectiveness of different methods for reconstructing large bone loss at the proximal tibia in revision total knee arthroplasty (rTKA) has not been established. The aim of this study was to evaluate the clinical and radiological outcome after the use of trabecular metal...

  15. High-frequency, low-magnitude vibration does not prevent bone loss resulting from muscle disuse in mice following botulinum toxin injection.

    Science.gov (United States)

    Manske, Sarah L; Good, Craig A; Zernicke, Ronald F; Boyd, Steven K

    2012-01-01

    High-frequency, low-magnitude vibration enhances bone formation ostensibly by mimicking normal postural muscle activity. We tested this hypothesis by examining whether daily exposure to low-magnitude vibration (VIB) would maintain bone in a muscle disuse model with botulinum toxin type A (BTX). Female 16-18 wk old BALB/c mice (N = 36) were assigned to BTX-VIB, BTX-SHAM, VIB, or SHAM. BTX mice were injected with BTX (20 µL; 1 U/100 g body mass) into the left hindlimb posterior musculature. All mice were anaesthetized for 20 min/d, 5 d/wk, for 3 wk, and the left leg mounted to a holder. Through the holder, VIB mice received 45 Hz, ± 0.6 g sinusoidal acceleration without weight bearing. SHAM mice received no vibration. At baseline and 3 wk, muscle cross-sectional area (MCSA) and tibial bone properties (epiphysis, metaphysis and diaphysis) were assessed by in vivo micro-CT. Bone volume fraction in the metaphysis decreased 12 ± 9% and 7 ± 6% in BTX-VIB and BTX-SHAM, but increased in the VIB and SHAM. There were no differences in dynamic histomorphometry outcomes between BTX-VIB and BTX nor between VIB and SHAM. Thus, vibration did not prevent bone loss induced by a rapid decline in muscle activity nor produce an anabolic effect in normal mice. The daily loading duration was shorter than would be expected from postural muscle activity, and may have been insufficient to prevent bone loss. Based on the approach used in this study, vibration does not prevent bone loss in the absence of muscle activity induced by BTX. PMID:22590551

  16. High-frequency, low-magnitude vibration does not prevent bone loss resulting from muscle disuse in mice following botulinum toxin injection.

    Directory of Open Access Journals (Sweden)

    Sarah L Manske

    Full Text Available High-frequency, low-magnitude vibration enhances bone formation ostensibly by mimicking normal postural muscle activity. We tested this hypothesis by examining whether daily exposure to low-magnitude vibration (VIB would maintain bone in a muscle disuse model with botulinum toxin type A (BTX. Female 16-18 wk old BALB/c mice (N = 36 were assigned to BTX-VIB, BTX-SHAM, VIB, or SHAM. BTX mice were injected with BTX (20 µL; 1 U/100 g body mass into the left hindlimb posterior musculature. All mice were anaesthetized for 20 min/d, 5 d/wk, for 3 wk, and the left leg mounted to a holder. Through the holder, VIB mice received 45 Hz, ± 0.6 g sinusoidal acceleration without weight bearing. SHAM mice received no vibration. At baseline and 3 wk, muscle cross-sectional area (MCSA and tibial bone properties (epiphysis, metaphysis and diaphysis were assessed by in vivo micro-CT. Bone volume fraction in the metaphysis decreased 12 ± 9% and 7 ± 6% in BTX-VIB and BTX-SHAM, but increased in the VIB and SHAM. There were no differences in dynamic histomorphometry outcomes between BTX-VIB and BTX nor between VIB and SHAM. Thus, vibration did not prevent bone loss induced by a rapid decline in muscle activity nor produce an anabolic effect in normal mice. The daily loading duration was shorter than would be expected from postural muscle activity, and may have been insufficient to prevent bone loss. Based on the approach used in this study, vibration does not prevent bone loss in the absence of muscle activity induced by BTX.

  17. 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.

  18. IL-1 gene polymorphism and smoking as risk factors for peri-implant bone loss in a well-maintained population.

    Science.gov (United States)

    Feloutzis, Andreas; Lang, Niklaus P; Tonetti, Maurizio S; Bürgin, Walter; Brägger, Urs; Buser, Daniel; Duff, Gordon W; Kornman, Kenneth S

    2003-02-01

    The aim of the present study was (i) to investigate the relation between specific interleukin-1 (IL-1) gene polymorphisms and peri-implant bone loss at osseointegrated ITI(R) dental implants and (ii) to explore the association between these allelic variants of the IL-1 gene complex and peri-implant mucosal inflammation, in both smoking and non-smoking individuals. A sample of 90 consecutive Caucasian patients (aged 33-88 years), treated with at least one ITI-implant participated in this retrospective investigation. Standardized periapical radiographs were taken after prosthetic rehabilitation (133.6 days, SD 136.9 days) and at the time of the re-examination, on average 5.6 years (SD 2.5 years) thereafter. The radiographs were analyzed by a calibrated examiner for changes in peri-implant bone levels. The examiner was blind with respect to clinical parameters and IL-1 status. The distance between the implant shoulder and the first visible bone-implant contact (DIB) at the respective time points were measured using a computerized method. The absolute bone level difference during the years of service (ABL) and the annual bone loss (DeltaBL/year) were calculated for all the implants. Percentages of full mouth bleeding on probing (BOP), as well as of BOP calculated separately for teeth and implants, were determined for all visits and averaged for the entire observation period. Out of the total patient sample, there were 14 heavy smokers (= 20 cigarettes/day), 14 moderate smokers (5-19 cigarettes/day), 23 previous smokers (smoking cessation > 5 years) and 39 non-smokers. Twenty-eight (31.11%) patients were IL-1 genotype positive. Upon stratification for smoking status, significant differences were found for the variables ABL (P polymorphism is associated with an increased risk for peri-implant bone loss following prosthetic reconstruction and during the supportive periodontal care phase of the treatment. PMID:12562360

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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...

  4. Impact of intra- and extra-osseous soft tissue composition on changes in bone mineral density with weight loss and regain.

    Science.gov (United States)

    Bosy-Westphal, Anja; Later, Wiebke; Schautz, Britta; Lagerpusch, Merit; Goele, Kristin; Heller, Martin; Glüer, Claus-C; Müller, Manfred J

    2011-07-01

    Recent studies report a significant gain in bone mineral density (BMD) after diet-induced weight loss. This might be explained by a measurement artefact. We therefore investigated the impact of intra- and extra-osseous soft tissue composition on bone measurements by dual X-ray absorptiometry (DXA) in a longitudinal study of diet-induced weight loss and regain in 55 women and 17 men (19-46 years, BMI 28.2-46.8 kg/m(2)). Total and regional BMD were measured before and after 12.7 ± 2.2 week diet-induced weight loss and 6 months after significant weight regain (≥30%). Hydration of fat free mass (FFM) was assessed by a 3-compartment model. Skeletal muscle (SM) mass, extra-osseous adipose tissue, and bone marrow were measured by whole body magnetic resonance imaging (MRI). Mean weight loss was -9.2 ± 4.4 kg (P BMAT) were not related to changes in BMD.

  5. 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...

  6. Primate Genome Gain and Loss: A Bone Dysplasia, Muscular Dystrophy, and Bone Cancer Syndrome Resulting from Mutated Retroviral-Derived MTAP Transcripts

    OpenAIRE

    Camacho-Vanegas, Olga; Camacho, Sandra Catalina; Till, Jacob; Miranda-Lorenzo, Irene; Terzo, Esteban; Ramirez, Maria Celeste; Schramm, Vern; Cordovano, Grace; Watts, Giles; Mehta, Sarju; Kimonis, Virginia; Hoch, Benjamin; Philibert, Keith D.; Raabe, Carsten A.; Bishop, David F.

    2012-01-01

    Diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMS-MFH) is an autosomal-dominant syndrome characterized by bone dysplasia, myopathy, and bone cancer. We previously mapped the DMS-MFH tumor-suppressing-gene locus to chromosomal region 9p21–22 but failed to identify mutations in known genes in this region. We now demonstrate that DMS-MFH results from mutations in the most proximal of three previously uncharacterized terminal exons of the gene encoding methylthioadenosine pho...

  7. Endogenous n 3 polyunsaturated fatty acids PUFAs mitigate ovariectomy-induced bone loss by attenuating bone marrow adipogenesis in FAT1 transgenic mice

    Directory of Open Access Journals (Sweden)

    Chen TY

    2013-06-01

    Full Text Available Tian-yu Chen,1,2,* Zhong-min Zhang,1,2,* Xiao-chen Zheng,1,2 Liang Wang,1,2 Min-jun Huang,1,2 Si Qin,3 Jian Chen,1,2 Ping-lin Lai,4 Cheng-liang Yang,1,2 Jia Liu,1,2 Yi-fan Dai,5 Da-di Jin,1,2 Xiao-chun Bai1,2,4 1Department of Orthopaedic, the Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, People's Republic of China; 2Academy of Orthopaedics, Guangdong Province, Guangzhou, Guangdong, People's Republic of China; 3Department of Dermatology and STD, Guangdong No.2 Provincial People's Hospital, Guangzhou, Guangdong, People's Republic of China; 4Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong, People's Republic of China; 5Center of Metabolic Disease Research, Nanjing Medical University, Jiangsu, People's Republic of China *These authors contributed equally to this work Aim: To investigate the effect of endogenous n-3 polyunsaturated fatty acids (PUFAs on bone marrow adipogenesis under osteoporosis conditions. Methods: A mouse osteoporosis model overexpressing the FAT1 gene from Caenorhabditis elegans and converting n-6 PUFAs to n-3 PUFAs endogenously was used. Results: The mice presented significantly lower bone marrow adiposity (adipocyte volume/tissue volume, mean adipocyte number but increased the bone parameters (bone mineral density, bone mineral content, bone volume/total volume in the distal femoral metaphysis. Conclusion: Endogenous n-3 PUFAs protect bone marrow adipogenesis, which provides a novel drug target. Keywords: antiosteoporosis, n-3 PUFAs, bone marrow, adipogenesis

  8. 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, Bo Jannik; Vestergaard, Aage; Jacobsen, Søren;

    2006-01-01

    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....... Corresponding results for grade 2 erosions (11% to 20% of bone volume eroded) were 42%, 10%, 60% and 24%, and for grade 3 erosions (21% to 30% of bone volume eroded) 75%, 67%, 75% and 100%. All grade 4 (and above) erosions were detected on radiographs. Conventional radiography required a MRI-estimated bone...

  9. p38α MAPK Regulates Lineage Commitment and OPG Synthesis of Bone Marrow Stromal Cells to Prevent Bone Loss under Physiological and Pathological Conditions

    Directory of Open Access Journals (Sweden)

    Qian Cong

    2016-04-01

    Full Text Available Bone marrow-derived mesenchymal stromal cells (BM-MSCs are capable of differentiating into osteoblasts, chondrocytes, and adipocytes. Skewed differentiation of BM-MSCs contributes to the pathogenesis of osteoporosis. Yet how BM-MSC lineage commitment is regulated remains unclear. We show that ablation of p38α in Prx1+ BM-MSCs produced osteoporotic phenotypes, growth plate defects, and increased bone marrow fat, secondary to biased BM-MSC differentiation from osteoblast/chondrocyte to adipocyte and increased osteoclastogenesis and bone resorption. p38α regulates BM-MSC osteogenic commitment through TAK1-NF-κB signaling and osteoclastogenesis through osteoprotegerin (OPG production by BM-MSCs. Estrogen activates p38α to maintain OPG expression in BM-MSCs to preserve the bone. Ablation of p38α in BM-MSCs positive for Dermo1, a later BM-MSC marker, only affected osteogenic differentiation. Thus, p38α mitogen-activated protein kinase (MAPK in Prx1+ BM-MSCs acts to preserve the bone by promoting osteogenic lineage commitment and sustaining OPG production. This study thus unravels previously unidentified roles for p38α MAPK in skeletal development and bone remodeling.

  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. 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

  12. 糖尿病牙周炎模型大鼠的牙槽骨丧失%Alveolar bone loss in rat models of diabetic periodontitis

    Institute of Scientific and Technical Information of China (English)

    王立刚; 徐彬; 迪丽努尔•阿吉; 古丽努尔•阿吾提

    2015-01-01

      结果与结论:钢丝结扎后1,2,3,4周大鼠牙槽骨丧失程度:糖尿病牙周炎组>慢性牙周炎组>正常对照组(P OBJECTIVE:To establish rat models of diabetic periodontitis and chronic periodontitis, and to further clarify diabetes-increased degree of alveolar bone resorption in periodontitis rats METHODS:Fifty-two eight-week-old specific-pathogen-free male Sprague-Dawley rats were randomly divided into diabetic periodontitis group, chronic periodontitis group and normal control group. In the diabetic periodontitis group, rat models of diabetic periodontitis were established by injection of streptozotocin+periodontal ligation. In the chronic periodontitis group, rat models of chronic periodontitis were established by periodontal ligation and constant pressure. In the normal control group, rats were fed normal y. At 1, 2, 3 and 4 weeks after ligation, changes in periodontium of rats of each group were observed. The maxil a alveolar bone specimens were taken. The degree of alveolar bone loss value in rats of each group was observed under a stereomicroscope. RESULTS AND CONCLUSION:At 1, 2, 3 and 4 weeks after ligation with steel wire, the degree of rat alveolar bone loss was as fol ows:diabetic periodontitis group>chronic periodontitis group>normal control group (P<0.05). Results verified that animal models of diabetic periodontitis and chronic periodontitis were successful y established. Diabetes can increase the destruction to periodontal tissue with periodontitis, and increase alveolar bone loss.

  13. What causes bone loss?

    Science.gov (United States)

    ... Sometimes, medicines that treat certain medical conditions can cause osteoporosis. Some of these are: Hormone-blocking treatments for prostate cancer or breast cancer Some medicines that are used ...

  14. 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

  15. A prospective 15-year follow-up study of mandibular fixed prostheses supported by osseointegrated implants. Clinical results and marginal bone loss.

    Science.gov (United States)

    Lindquist, L W; Carlsson, G E; Jemt, T

    1996-12-01

    In this prospective study 47 edentulous patients were treated with mandibular fixed prostheses supported by osseointegrated Brånemark implants and followed for 12 to 15 years. Three (1%) of the 273 inserted implants were lost, two before and one six years after placement of the fixed prosthesis. The cumulative success rate (CSR) of the implants was 98.9% both after 10 and 15 years. None of the fixed prostheses was lost and at the last follow-up, all patients had stable fixed prostheses in function (CSR 100%). The marginal bone loss around the implants was small, on average 0.5 mm during the first post surgical year and thereafter about 0.05 mm annually. More bone was lost around the anterior implants than around the most posterior ones. Smoking and poor oral hygiene had significant influence on bone loss, while occlusal loading factors such as maximal bite force, tooth clenching and length of cantilevers were of minor importance. It is concluded that the long-term results of the mandibular implant treatment were extremely successful, regarding both the fixed prostheses and implant stability. Bone resorption around the implants, albeit limited, was influenced by several factors, smoking and oral hygiene appeared to be most important. PMID:9151599

  16. Tenofovir accelerates bone mass loss of the lumbar spine in the first years of menopause in HIV-infected women

    Directory of Open Access Journals (Sweden)

    E Garlassi

    2012-11-01

    Full Text Available Background: HIV-infected postmenopausal women have higher rates of bone loss than HIV negative women. We aimed to identify predictors of body mass density (BMD in HIV infected women entering menopause and to evaluate the pre- and post-menopausal BMD change, with regard to tenofovir (TDF use. Methods: Women with at least one DEXA measurement were enrolled. The observation period was divided into: “Reproductive period”, “Menopause transition period”, “Early menopause period”, “Late menopause period”. BMD of the lumbar spine (L1-4 and femur neck were measured by DEXA. Lowess smoothing curves were drawn to analyze impact of menopause and TDF on BMD. Three different longitudinal linear regression models with random effects were built. Longitudinal regression analysis fits cross sectional time series regression models and allows to analyze repeated measures for each patient. Results: Fifty-five women were included. Median age at enrollment was 46 years (IQ range 44–49. Median observation period was 16 months (IQ range 8; 23 and 33 months (IQ range 23; 72 for pre- and post-menopausal respectively. At enrollment mean CD4 cell count was 553 cell/mL (±269.62 and HIV-VL was undetectable in 77.5% of patients: 6 women were not undergoing ART. Most common backbone TDF/FTC (46.9% and ABC/3TC (20.4%. At the time of inclusion in the cohort osteopenia and ostoeporosis were present in 60% and 3.64%, respectively. At the time of last DEXA evaluation osteopenia and osteoporosis were present in 78.18% and 36.36%, respectively. The impact of menopause on lumbar BMD was depicted (fig. 1 using a lowess smoothing analysis according to current TDF exposure (as treated model. Lumbar BMD change predictors were years from menopause and TDF current exposure in the “Early menopause period” and years from menopause, Baseline lumbar BMD, BMI and vitD supplementation in the “Late menopause period”. Discussion: This is the first study analyzing BMD

  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. PROTECTIVE EFFECT OF VITAMIN D3 IN METHYLPREDNISOLONE ACETATE (MPA INDUCED LOSS OF BONE METABOLISM MARKERS AND BONE MINERAL DENSITY IN THE LUMBAR SPINE OF RAT

    Directory of Open Access Journals (Sweden)

    I. Ragerdi-Kashani

    2007-05-01

    Full Text Available Although some vitamins have been shown to prevent glucocorticoids induced osteoporosis in short time, the magnitude of this effect remains to be clarified. The aim of this study was to evaluate protective effect of vitamin D3 on methylprednisolone acetate (MPA induced osteoporosis in rats. Twenty-four male Sprague Dawley rats were randomly divided into four groups: Group A (n = 6, was a base line control or normal animals. Group B (n = 6, was treated only normal saline, group C (n = 6, was treated MPA (0.2 mg/kg subcutaneously for 4 weeks (3 times per a week and finally group D (n = 6 were administered MPA resemble to group C and treated by Vitamin D3 (0.1 µg/kg dissolved in ethanol daily. Level of calcium, osteocalcin and acid phosphatase in serum were measured before and after treatment. Also, bone mineral density (BMD of lumber vertebrae was measured by dual energy X-ray absorptiometry. The results showed that the serum calcium level unaffected by MPA in all groups before and after treatment, but the serum osteocalcin level and bone mineral density of lumbar vertebrae were significantly (P < 0.05 decreased in group C compared with groups A and B. In group D serum osteocalcin level increased again significantly (P < 0.05 but increasing of BMD and bone mineral content were not significant. The findings indicate that by using of vitamin D3 in MPA treated rats could increase bone formation and decrease bone resorption.

  19. 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.

  20. Strontium fructose 1,6-diphosphate prevents bone loss in a rat model of postmenopausal osteoporosis via the OPG/RANKL/RANK pathway

    Institute of Scientific and Technical Information of China (English)

    Bo MA; Qi ZHANG; Di WU; Yong-lu WANG; Ying-ying HU; Yan-ping CHENG; Zhen-dong YANG; Ya-ya ZHENG; Han-jie YING

    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-kB 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 H202 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 ul-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.

  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. 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

  3. 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...

  4. 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

  5. Primate genome gain and loss: a bone dysplasia, muscular dystrophy, and bone cancer syndrome resulting from mutated retroviral-derived MTAP transcripts.

    Science.gov (United States)

    Camacho-Vanegas, Olga; Camacho, Sandra Catalina; Till, Jacob; Miranda-Lorenzo, Irene; Terzo, Esteban; Ramirez, Maria Celeste; Schramm, Vern; Cordovano, Grace; Watts, Giles; Mehta, Sarju; Kimonis, Virginia; Hoch, Benjamin; Philibert, Keith D; Raabe, Carsten A; Bishop, David F; Glucksman, Marc J; Martignetti, John A

    2012-04-01

    Diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMS-MFH) is an autosomal-dominant syndrome characterized by bone dysplasia, myopathy, and bone cancer. We previously mapped the DMS-MFH tumor-suppressing-gene locus to chromosomal region 9p21-22 but failed to identify mutations in known genes in this region. We now demonstrate that DMS-MFH results from mutations in the most proximal of three previously uncharacterized terminal exons of the gene encoding methylthioadenosine phosphorylase, MTAP. Intriguingly, two of these MTAP exons arose from early and independent retroviral-integration events in primate genomes at least 40 million years ago, and since then, their genomic integration has gained a functional role. MTAP is a ubiquitously expressed homotrimeric-subunit enzyme critical to polyamine metabolism and adenine and methionine salvage pathways and was believed to be encoded as a single transcript from the eight previously described exons. Six distinct retroviral-sequence-containing MTAP isoforms, each of which can physically interact with archetype MTAP, have been identified. The disease-causing mutations occur within one of these retroviral-derived exons and result in exon skipping and dysregulated alternative splicing of all MTAP isoforms. Our results identify a gene involved in the development of bone sarcoma, provide evidence of the primate-specific evolution of certain parts of an existing gene, and demonstrate that mutations in parts of this gene can result in human disease despite its relatively recent origin.

  6. 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...

  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. 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 ...

  9. WISE-2005: supine treadmill exercise within lower body negative pressure and flywheel resistive exercise as a countermeasure to bed rest-induced bone loss in women during 60-day simulated microgravity.

    Science.gov (United States)

    Smith, Scott M; Zwart, Sara R; Heer, Martina; Lee, Stuart M C; Baecker, Natalie; Meuche, Sabine; Macias, Brandon R; Shackelford, Linda C; Schneider, Suzanne; Hargens, Alan R

    2008-03-01

    Bone loss associated with disuse during bed rest (BR), an analog of space flight, can be attenuated by exercise. In previous studies, the efficacy of either aerobic or resistive exercise countermeasures has been examined separately. We hypothesized that a regimen of combined resistive and aerobic exercise during BR would prevent bone resorption and promote bone formation. After a 20-day ambulatory adaptation to controlled confinement and diet, 16 women participated in a 60-day, 6 degrees head-down-tilt BR and were assigned randomly to one of the two groups. Control subjects (CON, n=8) performed no countermeasure. Exercise subjects (EX, n=8) participated in an exercise program during BR, alternating between supine treadmill exercise within lower body negative pressure (3-4 d wk(-1)) and flywheel resistive exercise (2-3 d wk(-1)). By the last week of BR, excretion of helical peptide (CON, 79%+/-44 increase; EX, 64%+/-50, mean+/-SD) and N-terminal cross-linking telopeptide (CON, 51%+/-34; EX, 43%+/-56), markers of bone resorption, were greater than they were before BR in both groups (P<0.05). However, serum concentrations of the bone formation marker procollagen type I N propeptide were greater in EX than CON throughout and after bed rest (P<0.05), while concentrations of the bone formation marker bone alkaline phosphatase tended to be greater in EX than CON. Dual-energy X-ray absorptiometry results indicated that the exercise treatment significantly (P<0.05) attenuated loss of hip and leg bone mineral density in EX compared to CON. The combination of resistive and aerobic exercise did not prevent bone resorption but did promote bone formation, and helped mitigate the net bone loss associated with simulated microgravity. PMID:18249055

  10. Providing Flaxseed Oil but Not Menhaden Oil Protects against OVX Induced Bone Loss in the Mandible of Sprague-Dawley Rats.

    Science.gov (United States)

    Longo, Amanda B; Ward, Wendy E

    2016-01-01

    Higher intakes of polyunsaturated fatty acids (PUFA) are associated with benefits at several skeletal sites in postmenopausal women and in rodent models, but the effect of PUFA-containing oils on tooth-supporting alveolar bone of the mandible has not been studied. Moreover, direct comparison of the effect of flaxseed oil (a source of alpha-linolenic acid (ALA)) and menhaden oil (a source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) is unknown. One-month old female Sprague-Dawley rats (n = 48) were randomized to and fed a diet containing flaxseed oil or menhaden oil from one to six months of age. At three months of age, rats were randomized to receive SHAM or ovariectomy (OVX) surgery (n = 12/diet). The inter-radicular septum below the first molar of the mandible was imaged at 6 months of age (study endpoint) using micro-computed tomography (μCT) at a resolution of 9 μm. As expected, OVX significantly reduced percent bone volume (BV/TV), connectivity density (Conn. D.), trabecular number (Tb. N.), and increased trabecular separation (Tb. Sp.) compared to SHAM rats (p oil but not those fed flaxseed oil. These results suggest that providing flaxseed oil, possibly through its high ALA content, provides protection against the OVX-induced alveolar bone loss in rats.

  11. Providing Flaxseed Oil but Not Menhaden Oil Protects against OVX Induced Bone Loss in the Mandible of Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Amanda B. Longo

    2016-09-01

    Full Text Available Higher intakes of polyunsaturated fatty acids (PUFA are associated with benefits at several skeletal sites in postmenopausal women and in rodent models, but the effect of PUFA-containing oils on tooth-supporting alveolar bone of the mandible has not been studied. Moreover, direct comparison of the effect of flaxseed oil (a source of alpha-linolenic acid (ALA and menhaden oil (a source of eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA is unknown. One-month old female Sprague-Dawley rats (n = 48 were randomized to and fed a diet containing flaxseed oil or menhaden oil from one to six months of age. At three months of age, rats were randomized to receive SHAM or ovariectomy (OVX surgery (n = 12/diet. The inter-radicular septum below the first molar of the mandible was imaged at 6 months of age (study endpoint using micro-computed tomography (μCT at a resolution of 9 μm. As expected, OVX significantly reduced percent bone volume (BV/TV, connectivity density (Conn. D., trabecular number (Tb. N., and increased trabecular separation (Tb. Sp. compared to SHAM rats (p < 0.001. However, post hoc analysis revealed these differences were present in rats fed menhaden oil but not those fed flaxseed oil. These results suggest that providing flaxseed oil, possibly through its high ALA content, provides protection against the OVX-induced alveolar bone loss in rats.

  12. Accounting for beta-particle energy loss to cortical bone via paired-image radiation transport (PIRT).

    Science.gov (United States)

    Shah, Amish P; Rajon, Didier A; Patton, Phillip W; Jokisch, Derek W; Bolch, Wesley E

    2005-05-01

    Current methods of skeletal dose assessment in both medical physics (radionuclide therapy) and health physics (dose reconstruction and risk assessment) rely heavily on a single set of bone and marrow cavity chord-length distributions in which particle energy deposition is tracked within an infinite extent of trabecular spongiosa, with no allowance for particle escape to cortical bone. In the present study, we introduce a paired-image radiation transport (PIRT) model which provides a more realistic three-dimensional (3D) geometry for particle transport in the skeletal site at both microscopic and macroscopic levels of its histology. Ex vivo CT scans were acquired of the pelvis, cranial cap, and individual ribs excised from a 66-year male cadaver (BMI of 22.7 kg m(-2)). For the three skeletal sites, regions of trabecular spongiosa and cortical bone were identified and segmented. Physical sections of interior spongiosa were taken and subjected to microCT imaging. Voxels within the resulting microCT images were then segmented and labeled as regions of bone trabeculae, endosteum, active marrow, and inactive marrow through application of image processing algorithms. The PIRT methodology was then implemented within the EGSNRC radiation transport code whereby electrons of various initial energies are simultaneously tracked within both the ex vivo CT macroimage and the CT microimage of the skeletal site. At initial electron energies greater than 50-200 keV, a divergence in absorbed fractions to active marrow are noted between PIRT model simulations and those estimated under existing techniques of infinite spongiosa transport. Calculations of radionuclide S values under both methodologies imply that current chord-based models may overestimate the absorbed dose to active bone marrow in these skeletal sites by 0% to 27% for low-energy beta emitters (33P, 169Er, and 177Lu), by approximately 4% to 49% for intermediate-energy beta emitters (153Sm, 186Re, and 89Sr), and by

  13. 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.)

  14. 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.)

  15. 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...

  16. 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 ...

  17. Bone Health and Osteoporosis.

    Science.gov (United States)

    Lupsa, Beatrice C; Insogna, Karl

    2015-09-01

    Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone tissue leading to decreased bone strength and an increased risk of low-energy fractures. Central dual-energy X-ray absorptiometry measurements are the gold standard for determining bone mineral density. Bone loss is an inevitable consequence of the decrease in estrogen levels during and following menopause, but additional risk factors for bone loss can also contribute to osteoporosis in older women. A well-balanced diet, exercise, and smoking cessation are key to maintaining bone health as women age. Pharmacologic agents should be recommended in patients at high risk for fracture.

  18. 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.

  19. 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.)

  20. 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...

  1. 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 ...

  2. 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.

  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. Three-year experience with the Sophono in children with congenital conductive unilateral hearing loss: tolerability, audiometry, and sound localization compared to a bone-anchored hearing aid.

    Science.gov (United States)

    Nelissen, Rik C; Agterberg, Martijn J H; Hol, Myrthe K S; Snik, Ad F M

    2016-10-01

    Bone conduction devices (BCDs) are advocated as an amplification option for patients with congenital conductive unilateral hearing loss (UHL), while other treatment options could also be considered. The current study compared a transcutaneous BCD (Sophono) with a percutaneous BCD (bone-anchored hearing aid, BAHA) in 12 children with congenital conductive UHL. Tolerability, audiometry, and sound localization abilities with both types of BCD were studied retrospectively. The mean follow-up was 3.6 years for the Sophono users (n = 6) and 4.7 years for the BAHA users (n = 6). In each group, two patients had stopped using their BCD. Tolerability was favorable for the Sophono. Aided thresholds with the Sophono were unsatisfactory, as they did not reach under a mean pure tone average of 30 dB HL. Sound localization generally improved with both the Sophono and the BAHA, although localization abilities did not reach the level of normal hearing children. These findings, together with previously reported outcomes, are important to take into account when counseling patients and their caretakers. The selection of a suitable amplification option should always be made deliberately and on individual basis for each patient in this diverse group of children with congenital conductive UHL.

  5. 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

  6. Cobalt Alloy Implant Debris Induces Inflammation and Bone Loss Primarily through Danger Signaling, Not TLR4 Activation: Implications for DAMP-ening Implant Related Inflammation.

    Science.gov (United States)

    Samelko, Lauryn; Landgraeber, Stefan; McAllister, Kyron; Jacobs, Joshua; Hallab, Nadim James

    2016-01-01

    Cobalt alloy debris has been implicated as causative in the early failure of some designs of current total joint implants. The ability of implant debris to cause excessive inflammation via danger signaling (NLRP3 inflammasome) vs. pathogen associated pattern recognition receptors (e.g. Toll-like receptors; TLRs) remains controversial. Recently, specific non-conserved histidines on human TLR4 have been shown activated by cobalt and nickel ions in solution. However, whether this TLR activation is directly or indirectly an effect of metals or secondary endogenous alarmins (danger-associated molecular patterns, DAMPs) elicited by danger signaling, remains unknown and contentious. Our study indicates that in both a human macrophage cell line (THP-1) and primary human macrophages, as well as an in vivo murine model of inflammatory osteolysis, that Cobalt-alloy particle induced NLRP3 inflammasome danger signaling inflammatory responses were highly dominant relative to TLR4 activation, as measured respectively by IL-1β or TNF-α, IL-6, IL-10, tissue histology and quantitative bone loss measurement. Despite the lack of metal binding histidines H456 and H458 in murine TLR4, murine calvaria challenge with Cobalt alloy particles induced significant macrophage driven in vivo inflammation and bone loss inflammatory osteolysis, whereas LPS calvaria challenge alone did not. Additionally, no significant increase (p500pg/mL). Therefore, not only do the results of this investigation support Cobalt alloy danger signaling induced inflammation, but under normal homeostasis low levels of hematogenous PAMPs (danger signaling responses elicited by Cobalt alloy metal implant debris. This suggests the unique nature of Cobalt alloy particle bioreactivity is strong enough to illicit danger signaling that secondarily activate concomitant TLR activation, and may in part explain Cobalt particulate associated inflammatory and toxicity-like reactions of specific orthopedic implants.

  7. Loss of mesenchymal bone morphogenetic protein signaling leads to development of reactive stroma and initiation of the gastric neoplastic cascade

    Science.gov (United States)

    Roy, Sébastien A. B.; Allaire, Joannie M.; Ouellet, Camille; Maloum-Rami, Faiza; Pomerleau, Véronique; Lemieux, Étienne; Babeu, Jean-Philippe; Rousseau, Jasmin; Paquet, Marilène; Garde-Granger, Perrine; Boudreau, François; Perreault, Nathalie

    2016-09-01

    Bmps are morphogens involved in various gastric cellular functions. Studies in genetically-modified mice have shown that Bmp disruption in gastric epithelial and stromal cell compartments leads to the development of tumorigenesis. Our studies have demonstrated that abrogation of gastric epithelial Bmp signaling alone was not sufficient to recapitulate the neoplastic features associated with total gastric loss of Bmp signaling. Thus, epithelial Bmp signaling does not appear to be a key player in gastric tumorigenesis initiation. These observations suggest a greater role for stromal Bmp signaling in gastric polyposis initiation. In order to identify the specific roles played by mesenchymal Bmp signaling in gastric homeostasis, we generated a mouse model with abrogation of Bmp signaling exclusively in the gastro-intestinal mesenchyme (Bmpr1aΔMES). We were able to expose an unsuspected role for Bmp loss of signaling in leading normal gastric mesenchyme to adapt into reactive mesenchyme. An increase in the population of activated-fibroblasts, suggesting mesenchymal transdifferentiation, was observed in mutant stomach. Bmpr1aΔMES stomachs exhibited spontaneous benign polyps with presence of both intestinal metaplasia and spasmolytic-polypeptide-expressing metaplasia as early as 90 days postnatal. These results support the novel concept that loss of mesenchymal Bmp signaling cascade acts as a trigger in gastric polyposis initiation.

  8. Relationship between RANKL/RANK signaling pathway and bone loss in rheumatoid arthritis%RANKL/RANK信号途径与类风湿关节炎骨丢失的相关性

    Institute of Scientific and Technical Information of China (English)

    刘超; 肖涟波

    2013-01-01

    Rheumatoid arthritis ( RA) is a chronic systemic autoimmune disease. The key point of clinical treatment is to inhibit bone loss around the joint and bone loss of the whole body in patients with RA. Researches indicate that inflammatory cytokines, TNF-alpha, IL-1, IL-7, IL-17, etc., are important mediators leading to bone loss in patients with RA. Osteoclasts are the main cells involved in bone absorption. RANKL/RANK signaling pathway is the main pathway of RA inflammation leading to bone loss. RANKL/RANK signaling pathway builds a bridge between autoimmune diseases, represented by RA, and bone metabolism diseases. Its key role in the immune system and osteoclast development has formed the osteoimmunology theory, in order to more accurately reveal the complex interactions between the immune system and bone metabolism in the process of bone loss secondary to RA. This article reviews the correlation between bone loss secondary to RA and the RANKL/RANK signaling pathway.%类风湿关节炎(rheumatoid arthritis,RA)是一种慢性全身性自身免疫性疾病,临床上抑制RA患者关节周围及全身的骨丢失是治疗的关键.研究表明炎症细胞因子(TNF-α,IL-1,IL-7,IL-17等)是刺激导致RA患者骨丢失的重要介质,破骨细胞是参与骨吸收的主要细胞,RANKL/RANK信号途径是RA炎症导致骨丢失的主要通路.RANKL/RANK信号途径为以RA为代表的自身免疫性疾病与骨代谢疾病之间建起了一座桥梁,其在免疫系统和破骨细胞发育中的关键作用已经形成了"骨免疫"理论,以更准确的揭示在RA继发骨丢失的过程中免疫系统与骨代谢系统间复杂的交互作用.本文综述了RA继发骨丢失与RANKL/RANK信号途径间的相关性.

  9. 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.

  10. 抗性激素依赖性肿瘤药物引起的骨丢失%Anti-sex hormone-dependent neoplasm agents-induced bone loss

    Institute of Scientific and Technical Information of China (English)

    廖二元

    2008-01-01

    Chemotherapy can induce bone loss. It is especially severe and the incidence of estimated bone loss may be as high as almost 100% for cancer patients treated with anti-sex hormone agents because of inhibition and deficiency of estrogens and/or androgens with the inappropriate ratio of two hormones during and "after therapy. Anti-sex hormone-dependent neoplasm agents-induced bone loss, characterized by an increase of bone turnover rate, should be treated in the early stage in order to prevent it from deterioration and bone fractures. The etiology, mechanism and clinical management of anti-sex hormone-dependent neoplasm agents-induced bone loss are briefly discussed in this review.%一般的抗肿瘤化疗药物可引起骨丢失,而抗性激素依赖性肿瘤药物因其抑制雌激素/孕激素或雄激素的合成与分泌,导致雌激素和(或)雄激素缺乏和两者比例失调,骨丢失的发生率几乎为100%.以骨转换升高为特征的抗性激素依赖性肿瘤药物治疗往往导致多发性脆性骨折,故必须注重其预防和治疗.本文重点评论该类物所致骨丢失的病因、发生机制和防治.

  11. Evaluation of diagnostic accuracy of conventional and digital periapical radiography, panoramic radiography, and cone-beam computed tomography in the assessment of alveolar bone loss

    Directory of Open Access Journals (Sweden)

    Wilton Mitsunari Takeshita

    2014-01-01

    Full Text Available 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 < 0.0001. CBCT differed from panoramic (P = 0.0130, periapical with Rinn XCP (P = 0.0066, periapical with Han-Shin (P < 0.0001, and 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.

  12. 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

  13. 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.

  14. 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

  15. Management of peri-prosthetic fracture of the humerus with severe bone loss and loosening of the humeral component after total shoulder replacement.

    Science.gov (United States)

    Sewell, M D; Kang, S N; Al-Hadithy, N; Higgs, D S; Bayley, I; Falworth, M; Lambert, S M

    2012-10-01

    There is little information about the management of peri-prosthetic fracture of the humerus after total shoulder replacement (TSR). This is a retrospective review of 22 patients who underwent a revision of their original shoulder replacement for peri-prosthetic fracture of the humerus with bone loss and/or loose components. There were 20 women and two men with a mean age of 75 years (61 to 90) and a mean follow-up 42 months (12 to 91): 16 of these had undergone a previous revision TSR. Of the 22 patients, 12 were treated with a long-stemmed humeral component that bypassed the fracture. All their fractures united after a mean of 27 weeks (13 to 94). Eight patients underwent resection of the proximal humerus with endoprosthetic replacement to the level of the fracture. Two patients were managed with a clam-shell prosthesis that retained the original components. The mean Oxford shoulder score (OSS) of the original TSRs before peri-prosthetic fracture was 33 (14 to 48). The mean OSS after revision for fracture was 25 (9 to 31). Kaplan-Meier survival using re-intervention for any reason as the endpoint was 91% (95% confidence interval (CI) 68 to 98) and 60% (95% CI 30 to 80) at one and five years, respectively. There were two revisions for dislocation of the humeral head, one open reduction for modular humeral component dissociation, one internal fixation for nonunion, one trimming of a prominent screw and one re-cementation for aseptic loosening complicated by infection, ultimately requiring excision arthroplasty. Two patients sustained nerve palsies. Revision TSR after a peri-prosthetic humeral fracture associated with bone loss and/or loose components is a salvage procedure that can provide a stable platform for elbow and hand function. Good rates of union can be achieved using a stem that bypasses the fracture. There is a high rate of complications and function is not as good as with the original replacement.

  16. Correlation between the RANKL/RANK signaling pathway and bone loss in rheumatoid arthritis%RANKL/RANK 信号途径与类风湿关节炎骨量丢失的相关性

    Institute of Scientific and Technical Information of China (English)

    刘超; 肖涟波

    2013-01-01

    Rheumatoid arthritis ( RA) is a chronic systemic autoimmune disease .The key treatment of RA in clinical work is to inhibit the bone mass loss around the joints and in the whole body in patients with RA .Researches reveal that inflammatory cytokines ( TNF-α, IL-1, IL-7, and IL-17) are important mediators leading to bone loss in patients with RA .Osteoclasts are the main cells involved in bone absorption .RANKL/RANK signal pathway is the main pathway leading to bone loss in RA .RANKL/RANK signal pathway is a bridge between autoimmune diseases , which are represented by RA , and bone metabolism diseases . More importantly , osteoimmunology theory has been formed according to its key role in the immune system and osteoclast development , which can reveal the complex interactions between the immune system and bone metabolism in the process of bone loss secondary to RA more accurately . This article reviews the correlation between the bone loss secondary to RA and the RANKL /RANK signal pathway .%类风湿关节炎( rheumatoid arthritis ,RA)是一种慢性全身性自身免疫性疾病,临床上抑制RA患者关节周围及全身的骨量丢失是治疗的关键。研究表明炎症细胞因子( TNF-α、IL-1、IL-7、IL-17等)是刺激导致RA患者骨量丢失的重要介质,破骨细胞是参与骨吸收的主要细胞,RANKL/RANK信号途径是RA炎症导致骨量丢失的主要通路。 RANKL/RANK信号途径为以RA为代表的自身免疫性疾病与骨代谢疾病之间建起了一座桥梁,其在免疫系统和破骨细胞发育中的关键作用已经形成了“骨免疫”理论,以更准确的揭示在RA继发骨量丢失的过程中免疫系统与骨代谢系统间复杂的交互作用。本文综述了RA继发骨量丢失与RANKL/RANK信号途径间的相关性。

  17. 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

  18. 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.

  19. The Efficacy of Bisphosphonates in Preventing Aromatase Inhibitor Induced Bone Loss for Postmenopausal Women with Early Breast Cancer: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Pooleriveetil Padikkal Anagha

    2014-01-01

    Full Text Available Objectives. We aim to determine the efficacy of bisphosphonates in preventing aromatase inhibitor induced bone loss (AIBL in postmenopausal women with early breast cancer. The secondary objective was to determine the safety of bisphosphonates. Materials and Methods. We searched electronic databases in a time period of 1995 January to 2013 June. Random effects meta-analytical models were used; between study heterogeneity and publication bias was assessed. Results. A total of six eligible studies reported the BMD T score of LS at 12 months and from that 3 trials of Zoledronic acid compared the change in BMD in immediate ZOL versus delayed ZOL done with subgroups like patients with normal BMD at baseline (OR = 5.402, 95% CI = 1.329–21.959, P value = 0.018 and osteopenic BMD at baseline (OR = 4.008, 95% CI = 2.249–7.143, P value = 0.0002. Both had a significant decrease in BMD that favoured the delayed ZOL; 3 trials of risedronate and ibandronate also had a significant decrease in BMD in AIs alone group. Immediate ZOL versus delayed ZOL also showed increased risk of getting an ADR in immediate group. Conclusion. Third generation bisphosphonates has an effect on BMD of patients who are on treatment of AIs in breast cancer. Furthermore, the patients treated with immediate ZOL had a significantly high risk of musculoskeletal ADR’s than patients with delayed ZOL.

  20. 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.

  1. 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...

  2. 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.

  3. A new method for cone beam CT measurements of cyst of jaw bone loss%锥体束CT测量颌骨囊肿骨量缺失的新方法

    Institute of Scientific and Technical Information of China (English)

    张冬梅; 李锐; 李晓燕; 常平

    2015-01-01

    目的:探讨利用锥体束CT预测颌骨囊肿骨量缺失的新方法。方法:随机选取我院接诊的颌骨囊肿患者作为研究对象,拍摄锥体束CT,利用eXamVision软件进行测量,采用公式V=X*Y*Z对颌骨骨量缺失进行预测。结果:该方法所得数据能近似得出颌骨囊肿骨量缺失体积。结论:对颌骨囊肿缺失骨量的术前预测有助于术中植骨及手术方案的选择,锥体束CT能较准确的预测骨量的缺失体积,具有较好的临床指导意义。%Objective To study a new method for prediction of cyst of jaw bone loss by cone beam CT. Methods Random selection of jaw cyst patients as the research object, shooting cone beam CT,were measured using the eXamVision software, using the formula V=X*Y*Z to predict bone loss. Results The data from this method can approximate the missing volume of jaw cyst. Conclusion Contribute to bone grafting and operation scheme for the prediction of cyst of jaw bone loss of the preoperative selection. Cone beam CT can predict accurately the loss of bone volume, has better clinical directive significance.

  4. 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...

  5. 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 ...

  6. Macrophage inflammatory protein-1α shows predictive value as a risk marker for subjects and sites vulnerable to bone loss in a longitudinal model of aggressive periodontitis.

    Directory of Open Access Journals (Sweden)

    Daniel H Fine

    Full Text Available Improved diagnostics remains a fundamental goal of biomedical research. This study was designed to assess cytokine biomarkers that could predict bone loss (BL in localized aggressive periodontitis. 2,058 adolescents were screened. Two groups of 50 periodontally healthy adolescents were enrolled in the longitudinal study. One group had Aggregatibacter actinomycetemcomitans (Aa, the putative pathogen, while the matched cohort did not. Cytokine levels were assessed in saliva and gingival crevicular fluid (GCF. Participants were sampled, examined, and radiographed every 6 months for 2-3 years. Disease was defined as radiographic evidence of BL. Saliva and GCF was collected at each visit, frozen, and then tested retrospectively after detection of BL. Sixteen subjects with Aa developed BL. Saliva from Aa-positive and Aa-negative healthy subjects was compared to subjects who developed BL. GCF was collected from 16 subjects with BL and from another 38 subjects who remained healthy. GCF from BL sites in the 16 subjects was compared to healthy sites in these same subjects and to healthy sites in subjects who remained healthy. Results showed that cytokines in saliva associated with acute inflammation were elevated in subjects who developed BL (i.e., MIP-1α MIP-1β IL-α, IL-1β and IL-8; p<0.01. MIP-1α was elevated 13-fold, 6 months prior to BL. When MIP-1α levels were set at 40 pg/ml, 98% of healthy sites were below that level (Specificity; whereas, 93% of sites with BL were higher (Sensitivity, with comparable Predictive Values of 98%; p<0.0001; 95% C.I. = 42.5-52.7. MIP-1α consistently showed elevated levels as a biomarker for BL in both saliva and GCF, 6 months prior to BL. MIP-1α continues to demonstrate its strong candidacy as a diagnostic biomarker for both subject and site vulnerability to BL.

  7. The B Cell-Stimulatory Cytokines BLyS and APRIL Are Elevated in Human Periodontitis and Are Required for B Cell-Dependent Bone Loss in Experimental Murine Periodontitis.

    Science.gov (United States)

    Abe, Toshiharu; AlSarhan, Mohammed; Benakanakere, Manjunatha R; Maekawa, Tomoki; Kinane, Denis F; Cancro, Michael P; Korostoff, Jonathan M; Hajishengallis, George

    2015-08-15

    B-lineage cells (B lymphocytes and plasma cells) predominate in the inflammatory infiltrate of human chronic periodontitis. However, their role in disease pathogenesis and the factors responsible for their persistence in chronic lesions are poorly understood. In this regard, two cytokines of the TNF ligand superfamily, a proliferation-inducing ligand (APRIL) and B-lymphocyte stimulator (BLyS), are important for the survival, proliferation, and maturation of B cells. Thus, we hypothesized that APRIL and/or BLyS are upregulated in periodontitis and contribute to induction of periodontal bone loss. This hypothesis was addressed in both human and mouse experimental systems. We show that, relative to healthy controls, the expression of APRIL and BLyS mRNA and protein was upregulated in natural and experimental periodontitis in humans and mice, respectively. The elevated expression of these cytokines correlated with increased numbers of B cells/plasma cells in both species. Moreover, APRIL and BLyS partially colocalized with κ L chain-expressing B-lineage cells at the epithelial-connective tissue interface. Ligature-induced periodontitis resulted in significantly less bone loss in B cell-deficient mice compared with wild-type controls. Ab-mediated neutralization of APRIL or BLyS diminished the number of B cells in the gingival tissue and inhibited bone loss in wild-type, but not in B cell-deficient, mice. In conclusion, B cells and specific cytokines involved in their growth and differentiation contribute to periodontal bone loss. Moreover, APRIL and BLyS have been identified as potential therapeutic targets in periodontitis.

  8. 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,

  9. 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 

  10. Dextran sodium sulfate-induced colitis leads to bone loss in mice%葡聚糖硫酸钠诱导的小鼠肠炎中骨质丢失的分析

    Institute of Scientific and Technical Information of China (English)

    魏凡华; 胡志华

    2014-01-01

    建立小鼠葡聚糖硫酸钠肠炎(DSS)模型,并分析肠炎小鼠中骨质丢失的发生情况.C57BL/6小鼠口服DSS溶液2周以建立肠炎模型,第1周饮用2% DSS溶液,第2周饮用1% DSS溶液.饮用蒸馏水的C57BL/6小鼠作为对照.记录每组小鼠体质量变化,观察粪便和血便状况,μCT分析股骨骨质丢失的情况.结果表明DSS处理组小鼠和对照组相比,出现了明显的骨质丢失,骨量减少,骨小梁数目下降.说明DSS诱导的小鼠肠炎模型可以作为研究肠炎引发骨质丢失的良好模型.%To establish a colitis model induced by dextran sodium sulfate (DSS) and analyzed bone loss in colitic mice. Colitis was induced by administration of DSS solution for 2 weeks, 2%DSS and 1%DSS solution was administrated on the first week and second week, respectively. Body weight, stool and blood score of each group mice was recorded, and femoral bone loss were examined by micro computed tomography (μCT). The results demonstrate that DSS-treated mice exhibited a lower bone mass and decreased trabecular numbers as compared with the controls. Collectively, DSS-induced colitis model can be used to study pharmacological interventions for bone loss in mice.

  11. 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

    Interleukin (IL)-1 is a potent inducer of bone resorption, and an increased secretion of the IL-1 agonists IL-1 alpha and IL-1 beta relative to the IL-1 receptor antagonist (IL-1ra) has been proposed as a mechanism leading to post-menopausal osteoporosis. T-lymphocytes are capable of secreting bone...... resorptive cytokines and have also been linked with bone metabolism and the development of osteoporosis. Cytokine secretion from whole blood cell cultures was compared between two randomized groups of healthy early post-menopausal women (mean age 52.5 yrs, N = 91) and lymphocyte subsets were quantitated......, and there was no effect of ERT on lymphocyte subsets. The number of CD3+ CD56+ T-cells showed a highly significant negative correlation with femoral and lumbar bone density in untreated women (r = -0.42, p

  12. Using cone beam computed tomography to detect the relationship between the periodontal bone loss and mucosal thickening of the maxillary sinus

    Directory of Open Access Journals (Sweden)

    Mahnaz Sheikhi

    2014-01-01

    Full Text Available Background: Maxillary sinuses are covered by a 1 mm thick mucous membrane that when this membrane becomes inflamed, the thickness may increase 10-15 times. The common causes of odontogenic sinusitis are dental abscesses and periodontal disease. Computed tomography (CT is considered the gold standard for sinus diagnosis. Recently, cone beam computed tomography (CBCT has been introduced for dental and maxillofacial imaging, which has several advantages over traditional CT, including lower radiation dose and chairside process. This study aims to find the association between mucosal thickening (MT of the sinus and periodontal bone loss (PBL and pulpoperiapical condition. Materials and Methods: A total of 180 CBCT images were reviewed. PBL was assessed in six points under each sinus at the mesial and distal sides of the upper second premolar and first and second molars by measuring the distance from the alveolar crest to the point 2 mm under the cemento-enamel junction (CEJ. The MT was assessed at six points in the floor of the sinus precisely over the mentioned points. To assess the possible role of pulpoperiapical condition on the sinus MT, the existing teeth were classified into five groups due to the probable effect of each condition on the pulp and peri-apex. The statistical association between MT of sinus and PBL and pulpoperiapical condition was assessed using SPSS software (SPSS Inc., version 16.0, Chicago, IL, USA and bivariate correlation and binary linear regression statistical tests (P < 0.05. Results: MT was observed in 39.4% of patients (mean = 4.68 ± 5.25 mm. PBL was seen in 33% of the patients (mean = 1.87 ± 1.63 mm. Linear regression test showed that there is an association between both PBL and pulpoperiapical condition and MT, but the effect of PBL was about 4 times stronger. Conclusion: This study showed that MT of the maxillary sinus was common among patients with PBL and MT of the maxillary sinus was significantly associated

  13. 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.

  14. 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 ...

  15. Bone Diseases

    Science.gov (United States)

    ... avoid smoking and drinking too much alcohol. Bone diseases can make bones easy to break. Different kinds ... break Osteogenesis imperfecta makes your bones brittle Paget's disease of bone makes them weak Bones can also ...

  16. Relationship between protein intake, weight loss, and bone mineral density in postmenopausal women%绝经期妇女蛋白摄入、体重减轻和骨矿物质密度的关系

    Institute of Scientific and Technical Information of China (English)

    薛芳

    2014-01-01

    目的:观察绝经期妇女蛋白摄入、体重减轻和骨矿物质密度的关系。方法30例女性,每天摄取3139.5 J(1 cal=4.186 J),分为正常蛋白质摄取(A组:n=15)和高蛋白摄取(B组:n=15),共12周。观察体重和骨质矿物质密度变化。结果A组体重减轻11.2%, B组体重减轻10.1%, A组骨质矿物质密度无显著变化[(-0.003±0.003) g/cm2,-0.3%], B组显著降低[(-0.0167±0.004) g/cm2,-1.4%, P<0.05]。结论较高的蛋白质摄取促进绝经期后妇女体重减轻和骨矿物质密度减低。%Objective To study the relationship between protein intake, weight loss, and bone mineral density in postmenopausal women. the protein intake in postmenopausal women, the relationship between weight loss and bone mineral density. Methods 30 females, daily intake of 3139.5 joules (1 calories=4.186 joules), divided into normal protein intake (group A:n=15) and high protein intake (group B:n=15) for a total of 12 weeks. The changes of body weight and bone mineral density was observed . Result Group A weight loss was 11.2%and group B was 10.1%, group A there was no significant change in bone mineral density[(-0.003±0.003) g/cm2,-0.3%]and significantly lower in Group B[(-0.0167±0.004) g/cm2,-1. 4%, P<0.05]. Conclusions The higher protein intake promote weight loss and bone mineral density of women after menopause reduced.

  17. Prevention of bone loss by aqueous extract of Epimedii sagittatum in an ovariectomized rat model of osteoporosis%箭叶淫羊藿对去卵巢大鼠骨量丢失的保护作用

    Institute of Scientific and Technical Information of China (English)

    年华; 徐玲玲; 马明华; 秦路平; 郑汉臣; 张巧艳

    2006-01-01

    Objective: To investigate the prevention effect of aqueous extract of Epimedii sagittatum (ESE) on ovariectomy-induced (OVX) bone loss in rats. Methods: Rats were divided into sham-operated and OVX groups. The OVX rats were divided into four groups treated with distilled water, 17β-estradiol (1 mg/kg, ig) and ESE (0.5 and 1 g /kg, ig) for 11 weeks. Serum calcium, phosphorus, estradiol, bone gla protein concentrations and serum alkaline phosphatase activity were measured. Bone density was assayed by dual-energy X-ray absorptiometry. The undecalcified longitudinal proximal tibial metaphysical sections were cut and stained for the bone histomorphometric analysis. Results: In OVX rats, alkaline phosphatase activity in serum was markedly increased by ESE treatment, which had no obvious influence on the body weight. Meanwhile, atrophy of uterus and descent of bone mineral density were suppressed by ESE treatment. In addition, ESE completely corrected the decreased concentrations of calcium and E2 in serum observed in OVX rats. Histological results also showed ESE prevented the increases in trabecular separation (Tb. Sp) in OVX rats whereas it did not alter trabecular thickness (Tb. Th) and trabecular number (Tb. N) in OVX rats. Moreover, ESE had remarkable effect on bone formation rate with bone volume as referent (BFR/BV) and bone formation rate with bone surface as referent (BFR/BS). Conclusion: The findings assessed on the basis of biochemical test, bone mineral density and histomorphornetric parameters show that aqueous extract of Epimedii sagittatum has a definite antiosteoporotic effect and can prevent the OVX-induced bone loss in rats.%目的:研究箭叶淫羊藿对去卵巢大鼠骨量丢失的保护作用.方法:大鼠分去卵巢组和假手术组.去卵巢组包括空白对照组、雌激素组、0.5 g/kg淫羊藿提取物组和1 g/kg淫羊藿提取物组.11周后,测定大鼠血清钙、磷的浓度和碱性磷酸酶的活性,竞争放射免疫法测定血

  18. 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.

  19. Estrogen Deficiency-Associated Bone Loss in the Maxilla: A Methodology to Quantify the Changes in the Maxillary Intra-radicular Alveolar Bone in an Ovariectomized Rat Osteoporosis Model.

    Science.gov (United States)

    Du, Zhibin; Steck, Roland; Doan, Nghiem; Woodruff, Maria Ann; Ivanovski, Saso; Xiao, Yin

    2015-05-01

    The effects of estrogen deficiency on bone characteristics are site-dependent, with the most commonly studied sites being appendicular long bones (proximal femur and tibia) and axial bones (vertebra). The effect on the maxillary and mandibular bones is still inconsistent and requires further investigation. This study was designed to evaluate bone quality in the posterior maxilla of ovariectomized rats to validate this site as an appropriate model to study the effect of osteoporotic changes. Forty-eight 3-month-old female Sprague-Dawley rats were randomly divided into two groups: an ovariectomized (OVX) group (n=24) and Sham-operated (SHAM) group (n=24). Six rats were randomly sacrificed from both groups at time points 8, 12, 16, and 20 weeks. The samples from tibia and maxilla were collected for micro computed tomography (μCT) and histological analysis. For the maxilla, the volume of interest area focused on the furcation areas of the first and second molar. Trabecular bone volume fraction (BV/TV, %), trabecular thickness (Tb.Th.), trabecular number (Tb.N.), trabecular separation (Tb.Sp.), and connectivity density (Conn.Dens) were analyzed after Micro CT scanning. At 8 weeks the indices BV/TV, Tb.Sp., Tb.N., and Conn.Dens showed significant differences (pbone density only occurring after 12 weeks. Compared with the SHAM group, both the first and second molars of the OVX group showed significantly decreased BV/TV values from 12 weeks, and these changes were sustained through 16 and 20 weeks. For Tb.Sp., there were significant increases in bone values for the OVX group compared with the SHAM group at 12, 16, and 20 weeks. Histological changes were highly consistent with Micro CT results. This study established a method to quantify the changes of intra-radicular alveolar bone in the posterior maxilla in an accepted rat osteoporosis model. The degree of the osteoporotic changes to trabecular bone architecture is site-dependent and at least 3 months are required for

  20. [Bone transplant].

    Science.gov (United States)

    San Julián, M; Valentí, A

    2006-01-01

    We describe the methodology of the Bone and Soft Tissue Bank, from extraction and storage until use. Since the year 1986, with the creation of the Bone Bank in the University Clinic of Navarra, more than 3,000 grafts have been used for very different types of surgery. Bone grafts can be classified into cortical and spongy; the former are principally used in surgery to save tumour patients, in large post-traumatic reconstructions and in replacement surgery where there are massive bone defects and a structural support is required. The spongy grafts are the most used due to their numerous indications; they are especially useful in filling cavities that require a significant quantity of graft when the autograft is insufficient, or as a complement. They are also of special help in treating fractures when there is bone loss and in the treatment of delays in consolidation and pseudoarthrosis in little vascularized and atrophic zones. They are also used in prosthetic surgery against the presence of cavity type defects. Allografts of soft tissues are specially recognised in multiple ligament injuries that require reconstructions. Nowadays, the most utilised are those employed in surgery of the anterior cruciate ligament although they can be used for filling any ligament or tendon defect. The principal difficulties of the cortical allografts are in the consolidation of the ends with the bone itself and in tumour surgery, given that these are patients immunodepressed by the treatment, the incidence of infection is increased with respect to spongy grafts and soft tissues, which is irrelevant. In short, the increasingly widespread use of allografts is an essential therapeutic weapon in orthopaedic surgery and traumatology. It must be used by expert hands.

  1. [Bone transplant].

    Science.gov (United States)

    San Julián, M; Valentí, A

    2006-01-01

    We describe the methodology of the Bone and Soft Tissue Bank, from extraction and storage until use. Since the year 1986, with the creation of the Bone Bank in the University Clinic of Navarra, more than 3,000 grafts have been used for very different types of surgery. Bone grafts can be classified into cortical and spongy; the former are principally used in surgery to save tumour patients, in large post-traumatic reconstructions and in replacement surgery where there are massive bone defects and a structural support is required. The spongy grafts are the most used due to their numerous indications; they are especially useful in filling cavities that require a significant quantity of graft when the autograft is insufficient, or as a complement. They are also of special help in treating fractures when there is bone loss and in the treatment of delays in consolidation and pseudoarthrosis in little vascularized and atrophic zones. They are also used in prosthetic surgery against the presence of cavity type defects. Allografts of soft tissues are specially recognised in multiple ligament injuries that require reconstructions. Nowadays, the most utilised are those employed in surgery of the anterior cruciate ligament although they can be used for filling any ligament or tendon defect. The principal difficulties of the cortical allografts are in the consolidation of the ends with the bone itself and in tumour surgery, given that these are patients immunodepressed by the treatment, the incidence of infection is increased with respect to spongy grafts and soft tissues, which is irrelevant. In short, the increasingly widespread use of allografts is an essential therapeutic weapon in orthopaedic surgery and traumatology. It must be used by expert hands. PMID:16998521

  2. 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.

  3. Hypercalciuric Bone Disease

    Science.gov (United States)

    Favus, Murray J.

    2008-09-01

    Hypercalciuria plays an important causal role in many patients with calcium oxalate (CaOx) stones. The source of the hypercalciuria includes increased intestinal Ca absorption and decreased renal tubule Ca reabsorption. In CaOx stone formers with idiopathic hypercalciuria (IH), Ca metabolic balance studies have revealed negative Ca balance and persistent hypercalciuria in the fasting state and during low dietary Ca intake. Bone resorption may also contribute to the high urine Ca excretion and increase the risk of bone loss. Indeed, low bone mass by DEXA scanning has been discovered in many IH patients. Thiazide diuretic agents reduce urine Ca excretion and may increase bone mineral density (BMD), thereby reducing fracture risk. Dietary Ca restriction that has been used unsuccessfully in the treatment of CaOx nephrolithiasis in the past may enhance negative Ca balance and accelerate bone loss. DEXA scans may demonstrate low BMD at the spine, hip, or forearm, with no predictable pattern. The unique pattern of bone histologic changes in IH differs from other causes of low DEXA bone density including postmenopausal osteoporosis, male hypogonadal osteoporosis, and glucocorticoid-induced osteoporosis. Hypercalciuria appears to play an important pathologic role in the development of low bone mass, and therefore correction of urine Ca losses should be a primary target for treatment of the bone disease accompanying IH.

  4. Loss of c-Kit and bone marrow failure upon conditional removal of the GATA-2 C-terminal zinc finger domain in adult mice.

    Science.gov (United States)

    Li, Haiyan S; Jin, Jin; Liang, Xiaoxuan; Matatall, Katie A; Ma, Ying; Zhang, Huiyuan; Ullrich, Stephen E; King, Katherine Y; Sun, Shao-Cong; Watowich, Stephanie S

    2016-09-01

    Heterozygous mutations in the transcriptional regulator GATA-2 associate with multilineage immunodeficiency, myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML). The majority of these mutations localize in the zinc finger (ZnF) domains, which mediate GATA-2 DNA binding. Deregulated hematopoiesis with GATA-2 mutation frequently develops in adulthood, yet GATA-2 function in the bone marrow remains unresolved. To investigate this, we conditionally deleted the GATA-2 C-terminal ZnF (C-ZnF) coding sequences in adult mice. Upon Gata2 C-ZnF deletion, we observed rapid peripheral cytopenia, bone marrow failure, and decreased c-Kit expression on hematopoietic progenitors. Transplant studies indicated GATA-2 has a cell-autonomous role in bone marrow hematopoiesis. Moreover, myeloid lineage populations were particularly sensitive to Gata2 hemizygosity, while molecular assays indicated GATA-2 regulates c-Kit expression in multilineage progenitor cells. Enforced c-Kit expression in Gata2 C-ZnF-deficient hematopoietic progenitors enhanced myeloid colony activity, suggesting GATA-2 sustains myelopoiesis via a cell intrinsic role involving maintenance of c-Kit expression. Our results provide insight into mechanisms regulating hematopoiesis in bone marrow and may contribute to a better understanding of immunodeficiency and bone marrow failure associated with GATA-2 mutation.

  5. 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.

  6. 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

    Science.gov (United States)

    Cavani, Francesco; Smargiassi, Alberto

    2015-01-01

    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. PMID:26064895

  7. 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.

  8. 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 ...

  9. KMUP-1 suppresses RANKL-induced osteoclastogenesis and prevents ovariectomy-induced bone loss: roles of MAPKs, Akt, NF-κB and calcium/calcineurin/NFATc1 pathways.

    Directory of Open Access Journals (Sweden)

    Shu-Fen Liou

    Full Text Available BACKGROUND: KMUP-1 is a xanthine derivative with inhibitory activities on the phosphodiesterase (PDE 3,4 and 5 isoenzymes to suppress the degradation of cyclic AMP and cyclic GMP. However, the effects of KMUP-1 on osteoclast differentiation are still unclear. In this study, we investigated whether KMUP-1 inhibits osteoclastogenesis induced by RANKL in RAW 264.7 cells and bone loss induced by ovariectomy in mice, and the underlying mechanisms. PRINCIPAL FINDINGS: In vitro, KMUP-1 inhibited RANKL-induced TRAP activity, the formation of multinucleated osteoclasts and resorption-pit formation. It also inhibited key mediators of osteoclastogenesis including IL-1β, IL-6, TNF-α and HMGB1. In addition, KMUP-1 inhibited RANKL-induced activation of signaling molecules (Akt, MAPKs, calcium and NF-κB, mRNA expression of osteoclastogensis-associated genes (TRAP, MMP-9, Fra-1, and cathepsin K and transcription factors (c-Fos and NFATc1. Furthermore, most inhibitory effects of KMUP-1 on RANKL-mediated signal activations were reversed by a protein kinase A inhibitor (H89 and a protein kinase G inhibitor (KT5823. In vivo, KMUP-1 prevented loss of bone mineral content, preserved serum alkaline phosphate and reduced serum osteocalcin in ovariectomized mice. CONCLUSIONS: KMUP-1 inhibits RANKL-induced osteoclastogenesis in vitro and protects against ovariectomy-induced bone loss in vivo. These effects are mediated, at least in part, by cAMP and cGMP pathways. Therefore, KMUP-1 may have a role in pharmacologic therapy of osteoporosis.

  10. 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

  11. An Evaluation of the Clinical and Anatomic Predictors of Outcomes at a Minimum of 2 yrs Following the Latarjet Procedure for Recurrent Anterior Shoulder Instability with Glenoid Bone Loss

    Science.gov (United States)

    Mook, William R.; Petri, Maximilian; Greenspoon, Joshua A.; Horan, Marilee P.; Millett, Peter J.

    2015-01-01

    Objectives: Although the Latarjet procedure for the treatment of recurrent shoulder instability is highly successful, reasons for failure are often unclear. The purpose of our study was to evaluate clinical and anatomic characteristics that were predictive of continued instability or poor outcomes following the Latarjet procedure. Methods: In this IRB approved study, patients who underwent open coracoid Latarjet procedures for anteroinferior instability with glenoid bone loss (>20%) prior to October of 2012 were included. Anatomic measurements of coracoid size (anteroposterior surface area, maximal coracoid width), conjoint and subscapularis tendon widths, estimated glenoid defect surface area, Hill-Sach's Interval, and projected postoperative glenoid track engagement were obtained from preoperative cross-sectional imaging. When the projected glenoid track was smaller than the Hill-Sach's interval, the lesion was determined to be outside-&-engaged compared to inside-&-non-engaged. Patient reported subjective data that was prospectively collected and retrospectively reviewed included patient satisfaction, instability events, SANE score, ASES score, DASH score, and SF-12 PCS. Patients that progressed to another shoulder surgery not related to instability were considered complications and patients that continued to experience dislocations or who underwent revision instability surgeries were considered failures. Results: Thirty-nine shoulders in 39 patients (34 men, 5 women) with a mean age of 26 (range 16-43) were included at a mean follow-up was 3.3 years (2- 7.9 years). There were 25 out of 39 that had prior stabilization surgery and 6 workman's compensation claims. One patient was revised due to broken hardware at 2 months and one because of coracoid nonunion at 18 months. One patient experienced postsurgical adhesive capsulitis treated surgically at a year. All subjective outcome scores significantly improved (pLatarjet procedure for recurrent shoulder instability

  12. 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.

  13. 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.

  14. Inhibition of Xianlinggubao on bone loss in tail-suspended rats%仙灵骨葆对尾悬吊拟失重大鼠骨量丢失的抑制

    Institute of Scientific and Technical Information of China (English)

    皮俊杰; 吕志伟; 闫志荣; 荣建民

    2012-01-01

    背景:以淫羊藿苷为主要成分的中药制剂仙灵骨葆具有促进骨形成的作用.目的:观察仙灵骨葆对尾悬吊拟失重大鼠骨量丢失的抑制作用及机制.方法:将SD大鼠随机分为正常对照组、拟失重组、仙灵骨葆组,后两组大鼠采用尾悬吊法模拟失重,仙灵骨葆组悬吊同时灌胃给予仙灵骨葆250 mg/(kg?d),拟失重组悬吊同时灌胃给予双蒸水,4周后取右侧股骨行骨密度、三点弯曲生物力学及骨组织形态计量学检测.结果与结论:正常对照组骨密度、胫骨近端骨小梁相对体积、骨小梁厚度、骨小梁数量、生物力学最大载荷显著高于拟失重组、仙灵骨葆组(P < 0.05).仙灵骨葆组胫骨远端1/4骨密度、胫骨近端骨小梁相对体积显著高于拟失重组(P < 0.05),生物力学最大载荷也高于拟失重组,但差异无显著性意义.说明仙灵骨葆灌胃干预可促进松质骨的骨形成,部分阻止拟失重大鼠骨量的丢失.%BACKGROUND: Chinese herbal preparation Xianlinggubao whose main ingredient is icariin can promote bone formation. OBJECTIVE: To investigate the effect and related mechanism of Xianlinggubao on bone loss in tail-suspended rats. METHODS: Sprague-Dawley rats were divided into 3 groups: control group (A), simulated weightlessness group (B) and Xianlinggubao group (C). Rats in the group B and group C underwent tail-suspension, and in the group C was administered Xianlinggubao by gavage with dosage of 250 mg/(kg?d) at the same time while in the group B was administered double distilled water as control. Bone mineral density (BMD), biomechanical three-point bending and bone morphology of the right femurs were detected after 4 weeks removing the right femurs.RESULTS AND CONCLUSION: BMD, trabecular bone volume, bone trabecular thickness, trabecular number and biomechanics maximum load in the group A were markedly higher than those in groups B and C (P < 0.05), BMD of tibia distal 1/4, trabecular

  15. 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

  16. 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

  17. 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: (...

  18. 二维根尖周片与锥形束CT成像在牙周病理诊断中的运用比较%Detection of periodontal bone loss using cone beam CT and intraoral radiography

    Institute of Scientific and Technical Information of China (English)

    任迅

    2014-01-01

    目的:比较根尖周片与锥形束CT(Cone beam CT,CBCT)成像在牙周骨丧失中的检测与定位作用。方法:图像选自需进行牙周评价的患者牙片,样本共计51个测量位点,包括水平和垂直骨丧失,分别由三名检测者进行评价,主要通过测量骨丧失的线性高度、深度和宽度以及对X射线断层片上的联合骨缺损进行识别鉴定。结果:两种成像方式在定性骨缺损上差异无统计学意义(P>0.05),但在测量釉牙骨质界(CEJ)和牙槽脊顶(AC)间距离时两种成像方式差异有统计学意义(P0.05)。在本研究的39颗牙中,30.8%有联合骨缺损。结论:两种测量方式在测量牙槽脊的高度时有差异,但在测量骨缺失的深度和宽度时结论相似。应用CBCT 成像方式能对颊侧和舌侧/腭侧进行全面分析,并对骨缺失的表面形态进行观察。%To compare periapical radiographs with cone beam CT(CBCT) imaging in detecting and localizing alveolar bone loss by comparing linear measurements of the height, depth and width of the defects and identifying combined bone defects in tomographic images. Methods: The images were selected from a secondary database containing images of patients referred for periodontal evaluation. The sample consisted of 51 sites showing both horizontal and vertical bone loss, assessed by 3 trained examiners. Results: The results showed that there were no statisticaly significant differences between the imaging methods in terms of identification of the patern of bone loss. However, there were differences between the two methods when the distance between the cemento-enamel junction (CEJ) and the alveolar crest (AC) was measured. When the distance between the CEJ and the deepest point and width of the defect were measured, the methods showed no statisticaly significant difference. In this study, 30.8% of the 39 teeth evaluated had combined bone defects. Conclusions: The two methods

  19. Bone within a bone

    Energy Technology Data Exchange (ETDEWEB)

    Williams, H.J.; Davies, A.M. E-mail: wendy.turner@roh.nhs.uk; Chapman, S

    2004-02-01

    The 'bone within a bone' appearance is a well-recognized radiological term with a variety of causes. It is important to recognize this appearance and also to be aware of the differential diagnosis. A number of common conditions infrequently cause this appearance. Other causes are rare and some remain primarily of historical interest, as they are no longer encountered in clinical practice. In this review we illustrate some of the conditions that can give the bone within a bone appearance and discuss the physiological and pathological aetiology of each where known.

  20. 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...

  1. 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 ...

  2. 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...

  3. [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

  4. 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

  5. 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 ...

  6. The Walker 256 Breast Cancer Cell- Induced Bone Pain Model in Rats

    Directory of Open Access Journals (Sweden)

    Priyank Ashok Shenoy

    2016-08-01

    Full Text Available The majority of patients with terminal breast cancer show signs of bone metastasis, the most common cause of pain in cancer. Clinically available drug treatment options for the relief of cancer-associated bone pain are limited due to either inadequate pain relief and/or dose-limiting side-effects. One of the major hurdles in understanding the mechanism by which breast cancer causes pain after metastasis to the bones is the lack of suitable preclinical models. Until the late twentieth century, all animal models of cancer induced bone pain involved systemic injection of cancer cells into animals, which caused severe deterioration of animal health due to widespread metastasis. In this mini-review we have discussed details of a recently developed and highly efficient preclinical model of breast cancer induced bone pain: Walker 256 cancer cell- induced bone pain in rats. The model involves direct localized injection of cancer cells into a single tibia in rats, which avoids widespread metastasis of cancer cells and hence animals maintain good health throughout the experimental period. This model closely mimics the human pathophysiology of breast cancer induced bone pain and has great potential to aid in the process of drug discovery for treating this intractable pain condition.

  7. Prevention of bone loss in ovariectomized rats by combined treatment with risedronate and 1α,25-dihydroxyvitamin D3

    DEFF Research Database (Denmark)

    Erben, R.G.; Mosekilde, Li.; Thomsen, J.S.;

    2002-01-01

    with rats receiving risedronate alone. Furthermore, calcitriol enhanced the suppressive effects of risedronate on osteoclast number and partially counteracted the suppressive effects of risedronate on bone formation and histomorphometric indices of osteoblast team performance. Risedronate did not reduce...... the anabolic effect of calcitriol, and at the high dose it normalized hypercalcemia in calcitriol-treated OVX rats. Therefore, this study in OVX rats suggests that combined therapy with bisphosphonates and vitamin D analogs may offer advantages over the treatment with bisphosphonates or vitamin D analogs alone....

  8. 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.

  9. 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 ...

  10. Inflammation- and tumor-induced anorexia and weight loss require MyD88 in hematopoietic/myeloid cells but not in brain endothelial or neural cells.

    Science.gov (United States)

    Ruud, Johan; Wilhelms, Daniel Björk; Nilsson, Anna; Eskilsson, Anna; Tang, Yan-Juan; Ströhle, Peter; Caesar, Robert; Schwaninger, Markus; Wunderlich, Thomas; Bäckhed, Fredrik; Engblom, David; Blomqvist, Anders

    2013-05-01

    Loss of appetite is a hallmark of inflammatory diseases. The underlying mechanisms remain undefined, but it is known that myeloid differentiation primary response gene 88 (MyD88), an adaptor protein critical for Toll-like and IL-1 receptor family signaling, is involved. Here we addressed the question of determining in which cells the MyD88 signaling that results in anorexia development occurs by using chimeric mice and animals with cell-specific deletions. We found that MyD88-knockout mice, which are resistant to bacterial lipopolysaccharide (LPS)-induced anorexia, displayed anorexia when transplanted with wild-type bone marrow cells. Furthermore, mice with a targeted deletion of MyD88 in hematopoietic or myeloid cells were largely protected against LPS-induced anorexia and displayed attenuated weight loss, whereas mice with MyD88 deletion in hepatocytes or in neural cells or the cerebrovascular endothelium developed anorexia and weight loss of similar magnitude as wild-type mice. Furthermore, in a model for cancer-induced anorexia-cachexia, deletion of MyD88 in hematopoietic cells attenuated the anorexia and protected against body weight loss. These findings demonstrate that MyD88-dependent signaling within the brain is not required for eliciting inflammation-induced anorexia. Instead, we identify MyD88 signaling in hematopoietic/myeloid cells as a critical component for acute inflammatory-driven anorexia, as well as for chronic anorexia and weight loss associated with malignant disease.

  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. 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

  13. Black Tea May Be a Prospective Adjunct for Calcium Supplementation to Prevent Early Menopausal Bone Loss in a Rat Model of Osteoporosis

    Directory of Open Access Journals (Sweden)

    Asankur Sekhar Das

    2013-01-01

    Full Text Available The present study was undertaken to find out the ability of black tea extract (BTE as a suitable alternative of adjunct for calcium supplementation in treating an ovariectomized rat model of early osteoporosis. Female Wistar rats weighing 140–150 g were divided into four groups consisting of six animals in each group: (A sham-operated control; (B bilaterally ovariectomized; (C bilaterally ovariectomized + BTE; (D bilaterally ovariectomized + 17β-estradiol. Results suggest that BTE could promote intestinal absorption of calcium significantly (P0.05. A comparative study with 17β-estradiol, a well-known adjunct for calcium supplementation, indicated that efficacy of BTE in maintaining skeletal health is close to that of 17β-estradiol. This study suggests that simultaneous use of BTE is promising as a prospective candidate for adjunctive therapies for calcium supplementation in the early stage of menopausal bone changes.

  14. Black tea may be a prospective adjunct for calcium supplementation to prevent early menopausal bone loss in a rat model of osteoporosis.

    Science.gov (United States)

    Das, Asankur Sekhar; Banerjee, Maitrayee; Das, Dolan; Mukherjee, Sandip; Mitra, Chandan

    2013-01-01

    The present study was undertaken to find out the ability of black tea extract (BTE) as a suitable alternative of adjunct for calcium supplementation in treating an ovariectomized rat model of early osteoporosis. Female Wistar rats weighing 140-150 g were divided into four groups consisting of six animals in each group: (A) sham-operated control; (B) bilaterally ovariectomized; (C) bilaterally ovariectomized + BTE; (D) bilaterally ovariectomized + 17 β -estradiol. Results suggest that BTE could promote intestinal absorption of calcium significantly (P 0.05). A comparative study with 17 β -estradiol, a well-known adjunct for calcium supplementation, indicated that efficacy of BTE in maintaining skeletal health is close to that of 17 β -estradiol. This study suggests that simultaneous use of BTE is promising as a prospective candidate for adjunctive therapies for calcium supplementation in the early stage of menopausal bone changes.

  15. 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...

  16. 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.

  17. 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 ...

  18. Effect of Sipjeondaebo-tang on cancer-induced anorexia and cachexia in CT-26 tumor-bearing mice.

    Science.gov (United States)

    Choi, Youn Kyung; Jung, Ki Yong; Woo, Sang-Mi; Yun, Yee Jin; Jun, Chan-Yong; Park, Jong Hyeong; Shin, Yong Cheol; Cho, Sung-Gook; Ko, Seong-Gyu

    2014-01-01

    Cancer-associated anorexia and cachexia are a multifactorial condition described by a loss of body weight and muscle with anorexia, asthenia, and anemia. Moreover, they correlate with a high mortality rate, poor response to chemotherapy, poor performance status, and poor quality of life. Cancer cachexia is regulated by proinflammatory cytokines such as interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor- α (TNF- α). In addition, glucagon like peptide-1 (GIP-1), peptide YY (PYY), ghrelin, and leptin plays a crucial role in food intake. In this study, we investigated the therapeutic effects of one of the traditional herbal medicines, Sipjeondaebo-tang (Juzen-taiho-to in Japanese; SJDBT), on cancer anorexia and cachexia in a fundamental mouse cancer anorexia/cachexia model, CT-26 tumor-bearing mice. SJDBT was more significantly effective in a treatment model where it was treated after anorexia and cachexia than in a prevention model where it was treated before anorexia and cachexia on the basis of parameters such as weights of muscles and whole body and food intakes. Moreover, SJDBT inhibited a production of IL-6, MCP-1, PYY, and GLP-1 and ameliorated cancer-induced anemia. Therefore, our in vivo studies provide evidence on the role of SJDBT in cancer-associated anorexia and cachexia, thereby suggesting that SJDBT may be useful for treating cancer-associated anorexia and cachexia.

  19. 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

  20. 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.

  1. 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.

  2. [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

  3. Is there a relation between local bone quality as assessed on panoramic radiographs and alveolar bone level?

    Science.gov (United States)

    Nackaerts, Olivia; Gijbels, Frieda; Sanna, Anna-Maria; Jacobs, Reinhilde

    2008-03-01

    The aim was to explore the relation between radiographic bone quality on panoramic radiographs and relative alveolar bone level. Digital panoramic radiographs of 94 female patients were analysed (mean age, 44.5; range, 35-74). Radiographic density of the alveolar bone in the premolar region was determined using Agfa Musica software. Alveolar bone level and bone quality index (BQI) were also assessed. Relationships between bone density and BQI on one hand and the relative loss of alveolar bone level on the other were assessed. Mandibular bone density and loss of alveolar bone level were weakly but significantly negatively correlated for the lower premolar area (r = -.27). The BQI did not show a statistically significant relation to alveolar bone level. Radiographic mandibular bone density on panoramic radiographs shows a weak but significant relation to alveolar bone level, with more periodontal breakdown for less dense alveolar bone. PMID:17690924

  4. Is there a relation between local bone quality as assessed on panoramic radiographs and alveolar bone level?

    Science.gov (United States)

    Nackaerts, Olivia; Gijbels, Frieda; Sanna, Anna-Maria; Jacobs, Reinhilde

    2008-03-01

    The aim was to explore the relation between radiographic bone quality on panoramic radiographs and relative alveolar bone level. Digital panoramic radiographs of 94 female patients were analysed (mean age, 44.5; range, 35-74). Radiographic density of the alveolar bone in the premolar region was determined using Agfa Musica software. Alveolar bone level and bone quality index (BQI) were also assessed. Relationships between bone density and BQI on one hand and the relative loss of alveolar bone level on the other were assessed. Mandibular bone density and loss of alveolar bone level were weakly but significantly negatively correlated for the lower premolar area (r = -.27). The BQI did not show a statistically significant relation to alveolar bone<