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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. Inhibition of p38-MAPK signaling pathway attenuates breast cancer induced bone pain and disease progression in a murine model of cancer-induced bone pain

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    Vanderah Todd W

    2011-10-01

    Full Text Available Abstract Background Mechanisms driving cancer-induced bone pain are poorly understood. A central factor implicated to be a key player in the process of tumorigenesis, osteoclastogenesis and nociception is p38 MAPK. We determined the role of p38 MAPK in a mouse model of breast cancer induced bone pain in which mixed osteolytic and osteoblastic remodeling occurs. Results In cancer-treated mice, acute as well as chronic inhibition of p38 MAPK with SB203580 blocked flinching and guarding behaviors in a dose-dependent manner whereas no effect on thresholds to tactile stimuli was observed. Radiographic analyses of bones demonstrated that chronic inhibition of p38 MAPK reduced bone loss and incidence of spontaneous fracture in cancer-treated mice. Histological analysis of bones collected from mice treated with the p38 MAPK inhibitor showed complete absence of osteoblastic growth in the intramedullary space as well as significantly reduced tumor burden. Conclusions Blockade of non-evoked pain behaviors but not hypersensitivity suggests differences in the underlying mechanisms of specific components of the pain syndrome and a possibility to individualize aspects of pain management. While it is not known whether the role of p38 MAPK signaling can be expanded to other cancers, the data suggest a need for understanding molecular mechanisms and cellular events that initiate and maintain cancer-induced bone pain for effective management for both ongoing pain as well as breakthrough pain.

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

    DEFF Research Database (Denmark)

    Hald, Andreas; Hansen, Rikke Rie; Thomsen, Mette W

    2009-01-01

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

  4. Pain and nociception: mechanisms of cancer-induced bone pain.

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    Falk, Sarah; Dickenson, Anthony H

    2014-06-01

    Cancer pain, especially pain caused by metastasis to bone, is a severe type of pain, and unless the cause and consequences can be resolved, the pain will become chronic. As detection and survival among patients with cancer have improved, pain has become an increasing challenge, because traditional therapies are often only partially effective. Until recently, knowledge of cancer pain mechanisms was poor compared with understanding of neuropathic and inflammatory pain states. We now view cancer-induced bone pain as a complex pain state involving components of both inflammatory and neuropathic pain but also exhibiting elements that seem unique to cancer pain. In addition, the pain state is often unpredictable, and the intensity of the pain is highly variable, making it difficult to manage. The establishment of translational animal models has started to reveal some of the molecular components involved in cancer pain. We present the essential pharmacologic and neurobiologic mechanisms involved in the generation and continuance of cancer-induced bone pain and discuss these in the context of understanding and treating patients. We discuss changes in peripheral signaling in the area of tumor growth, examine spinal cord mechanisms of sensitization, and finally address central processing. Our aim is to provide a mechanistic background for the sensory characteristics of cancer-induced bone pain as a basis for better understanding and treating this condition.

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

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    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...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Pain is a common and debilitating complication for cancer patients significantly compromising their quality of life. Cancer-induced bone pain involves a complex interplay of molecular events, including mechanisms observed in inflammatory and neuropathic pain states, but also changes unique...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    for cancer-induced bone pain. The P2X7 receptor (P2X7R) is involved in a variety of cellular functions and has been linked to both inflammatory and neuropathic pain. Here we study the analgesic potential of P2X7 receptor antagonism in a rat model of cancer-induced bone pain. In cancer-bearing animals, the P2......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....... 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...

  8. 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...

  9. Breast Cancer and Bone Loss

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

    OpenAIRE

    2015-01-01

    Cancer-induced bone pain (CIBP) is a severe type of chronic pain. It is imperative to explore safe and effective analgesic drugs for CIBP treatment. Baicalein (BE), isolated from the traditional Chinese herbal medicine Scutellaria baicalensis Georgi (or Huang Qin), has been demonstrated to have anti-inflammatory and neuroprotective effects. In this study, we examined the effect of BE on CIBP and the mechanism of this effect. Intrathecal and oral administration of BE at different doses could a...

  11. Monocyte chemoattractant protein-1 contributes to morphine tolerance in rats with cancer-induced bone pain.

    Science.gov (United States)

    Liu, Lei; Gao, Xiu-Juan; Ren, Chun-Guang; Hu, Ji-Hua; Liu, Xian-Wen; Zhang, Ping; Zhang, Zong-Wang; Fu, Zhi-Jian

    2017-02-01

    Cancer-induced bone pain can severely compromise the life quality of patients, while tolerance limits the use of opioids in the treatment of cancer pain. Monocyte chemoattractant protein-1 (MCP-1) is known to contribute to neuropathic pain. However, the role of spinal MCP-1 in the development of morphine tolerance in patients with cancer-induced bone pain remains unclear. The aim of the present study was to investigate the role of spinal MCP-1 in morphine tolerance in bone cancer pain rats (MTBP rats). Bone cancer pain was induced by intramedullary injection of Walker 256 cells into the tibia of the rats, while morphine tolerance was induced by continuous intrathecal injection of morphine over a period of 9 days. In addition, anti-MCP-1 antibodies were intrathecally injected to rats in various groups in order to investigate the association of MCP-1 with mechanical and heat hyperalgesia using the paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL) tests, respectively. Furthermore, MCP-1 and CCR2 expression levels were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, and CCR2 expression levels were measured using RT-qPCR. The results indicated that MCP-1 and CCR2 expression levels were significantly increased in the spinal cord of MTBP rats. Intrathecal administration of anti-MCP-1 neutralizing antibodies was observed to attenuate the mechanical and thermal allodynia in MTBP rats. Therefore, the upregulation of spinal MCP-1 and CCR2 expression levels may contribute to the development of mechanical allodynia in MTBP rats. In conclusion, MCP-1/CCR2 signaling may serve a crucial role in morphine tolerance development in rats suffering from cancer-induced bone pain.

  12. Inducible models of bone loss.

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    Doucette, Casey R; Rosen, Clifford J

    2014-12-11

    Bone is an essential organ that not only confers structural stability to the organism, but also serves as a reservoir for hematopoietic elements and is thought to affect systemic homeostasis through the release of endocrine factors as well as calcium. The loss of bone mass due to an uncoupling of bone formation and bone resorption leads to increased fragility that can result in devastating fractures. Further understanding of the effects of environmental stimuli on the development of bone disease in humans is needed, and they can be studied using animal models. Here, we present established and novel methods for the induction of bone loss in mice, including manipulation of diet and environment, administration of drugs, irradiation, and surgically induced hormone deficiency. All of these models are directly related to human cases, and thus, can be used to investigate the causes of bone loss resulting from these interventions.

  13. What causes bone loss?

    Science.gov (United States)

    ... bone biology. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, eds. Williams Textbook of Endocrinology . 13th ed. Philadelphia, PA: Elsevier; 2016:chap 29. Maes C, Kronenberg HM. Bone development and remodeling. In: Jameson JL, ...

  14. 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.

  15. Aromatase inhibitors and bone loss.

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    Perez, Edith A; Weilbaecher, Katherine

    2006-08-01

    The aromatase inhibitors (AIs) anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin) are significantly more effective than the selective estrogen-receptor modulator (SERM) tamoxifen in preventing recurrence in estrogen receptor-positive early breast cancer. Aromatase inhibitors are likely to replace SERMs as first-line adjuvant therapy for many patients. However, AIs are associated with significantly more osteoporotic fractures and greater bone mineral loss. As antiresorptive agents, oral and intravenous bisphosphonates such as alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva), pamidronate (Aredia), and zoledronic acid (Zometa) have efficacy in preventing postmenopausal osteoporosis, cancer treatment-related bone loss, or skeletal complications of metastatic disease. Clinical practice guidelines recommend baseline and annual follow-up bone density monitoring for all patients initiating AI therapy. Bisphosphonate therapy should be prescribed for patients with osteoporosis (T score vitamin D intake, weight-bearing exercise, and smoking cessation should be addressed. Adverse events associated with bisphosphonates include gastrointestinal toxicity, renal toxicity, and osteonecrosis of the jaw. These safety concerns should be balanced with the potential of bisphosphonates to minimize or prevent the debilitating effects of AI-associated bone loss in patients with early, hormone receptor-positive breast cancer.

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

    Directory of Open Access Journals (Sweden)

    Shan Hu

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  18. Extracellular signal-regulated kinase activation in spinal astrocytes and microglia contributes to cancer-induced bone pain in rats.

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    Wang, X-W; Li, T-T; Zhao, J; Mao-Ying, Q-L; Zhang, H; Hu, S; Li, Q; Mi, W-L; Wu, G-C; Zhang, Y-Q; Wang, Y-Q

    2012-08-16

    Cancer pain, especially cancer-induced bone pain, affects the quality of life of cancer patients, and current treatments for this pain are limited. The present study demonstrates that spinal extracellular signal-regulated kinase (ERK) activation in glial cells plays a crucial role in cancer-induced bone pain. From day 4 to day 21 after the intra-tibia inoculation with Walker 256 mammary gland carcinoma cells, significant mechanical allodynia was observed as indicated by the decrease of mechanical withdrawal thresholds in the von Frey hair test. Intra-tibia inoculation with carcinoma cells induced a vast and persistent (>21 D) activation of ERK in the bilateral L2-L3 and L4-L5 spinal dorsal horn. The increased pERK1/2-immunoreactivity was observed in both Iba-1-expressing microglia and GFAP-expressing astrocytes but not in NeuN-expressing neurons. A single intrathecal injection of the selective MEK (ERK kinase) inhibitors PD98059 (10 μg) on day 12 and U0126 (1.25 and 3 μg) on day 14, attenuated the bilateral mechanical allodynia in the von Frey hair test. Altogether, our results suggest that ERK activation in spinal microglia and astrocytes is correlated with the onset of allodynia and is important for allodynia maintenance in the cancer pain model. This study indicated that inhibition of the ERK pathway may provide a new therapy for cancer-induced bone pain.

  19. Regulation of bone mineral loss during lactation

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    Brommage, R.; Deluca, H. F.

    1985-01-01

    The effects of varyng dietary calcium and phosphorous levels, vitamin D deficiency, oophorectomy, adrenalectomy, and simultaneous pregnancy on bone mineral loss during lactation in rats are studied. The experimental procedures and evaluations are described. The femur ash weight of lactating and nonlactating rats are calculated. The data reveals that a decrease in dietary calcium of 0.02 percent results in an increased loss of bone mineral, an increase in calcium to 1.4 percent does not lessen bone mineral loss, and bone mineral loss in vitamin D deficient rats is independent of calcium levels. It is observed that changes in dietary phosphorous level, oophorectomy, adrenalectomy, and simultaneous pragnancy do not reduce bone mineral loss during lactation. The analysis of various hormones to determine the mechanism that triggers bone mineral loss during lactation is presented.

  20. Involvement of spinal monocyte chemoattractant protein-1 (MCP-1) in cancer-induced bone pain in rats.

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    Hu, Ji-Hua; Zheng, Xiao-Yan; Yang, Jian-Ping; Wang, Li-Na; Ji, Fu-Hai

    2012-05-23

    In this study, we examined the involvement of chemokine monocyte chemoattractant protein-1 (MCP-1) in the spinal cord of a rat model of cancer-induced bone pain (CIBP). In this model, CIBP was established by an intramedullary injection of Walker 256 cells into the tibia of rats. We observed a significant increase in expression levels of MCP-1 and its receptor CCR2 in the spinal cord of CIBP rats. Furthermore, the intrathecal administration of an anti-MCP-1 neutralizing antibody attenuated the mechanical allodynia established in CIBP rats. Likewise, an intrathecal injection of exogenous recombinant MCP-1 induced a striking mechanical allodynia in naïve rats. These results suggest that increases in spinal MCP-1 and CCR2 expression are involved in the development of mechanical allodynia associated with bone cancer rats.

  1. Horizontal alveolar bone loss: A periodontal orphan

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    Jayakumar A

    2010-01-01

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

  2. Prevent and cure disuse bone loss

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    Jee, Webster S. S.

    1994-01-01

    Anabolic agents like parathyroid hormone and postagladin E-like substances were studied in dogs and rats to determine their effectiveness in the prevention and cure of bone loss due to immobilization. It was determined that postagladin E2 administration prevented immobilization while at the same time it added extra bone in a dose responsive manner. Although bone mass returns, poor trabecular architecture remains after normal ambulation recovery from immobilization. Disuse related bone loss and poor trabecular architecture were cured by post-immobilization postagladin E2 treatment.

  3. Vitamin C prevents hypogonadal bone loss.

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    Ling-Ling Zhu

    Full Text Available Epidemiologic studies correlate low vitamin C intake with bone loss. The genetic deletion of enzymes involved in de novo vitamin C synthesis in mice, likewise, causes severe osteoporosis. However, very few studies have evaluated a protective role of this dietary supplement on the skeleton. Here, we show that the ingestion of vitamin C prevents the low-turnover bone loss following ovariectomy in mice. We show that this prevention in areal bone mineral density and micro-CT parameters results from the stimulation of bone formation, demonstrable in vivo by histomorphometry, bone marker measurements, and quantitative PCR. Notably, the reductions in the bone formation rate, plasma osteocalcin levels, and ex vivo osteoblast gene expression 8 weeks post-ovariectomy are all returned to levels of sham-operated controls. The study establishes vitamin C as a skeletal anabolic agent.

  4. 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

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    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.

  5. Functional upregulation of nav1.8 sodium channels on the membrane of dorsal root Ganglia neurons contributes to the development of cancer-induced bone pain.

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    Xiao-Dan Liu

    Full Text Available We have previously reported that enhanced excitability of dorsal root ganglia (DRG neurons contributes to the development of bone cancer pain, which severely decreases the quality of life of cancer patients. Nav1.8, a tetrodotoxin-resistant (TTX-R sodium channel, contributes most of the sodium current underlying the action potential upstroke and accounts for most of the current in later spikes in a train. We speculate that the Nav1.8 sodium channel is a potential candidate responsible for the enhanced excitability of DRG neurons in rats with bone cancer pain. Here, using electrophysiology, Western blot and behavior assays, we documented that the current density of TTX-R sodium channels, especially the Nav1.8 channel, increased significantly in DRG neurons of rats with cancer-induced bone pain. This increase may be due to an increased expression of Nav1.8 on the membrane of DRG neurons. Accordantly, blockade of Nav1.8 sodium channels by its selective blocker A-803467 significantly alleviated the cancer-induced mechanical allodynia and thermal hyperalgesia in rats. Taken together, these results suggest that functional upregulation of Nav1.8 channels on the membrane of DRG neurons contributes to the development of cancer-induced bone pain.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

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    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

  8. Bone Cell-autonomous Contribution of Type 2 Cannabinoid Receptor to Breast Cancer-induced Osteolysis.

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    Sophocleous, Antonia; Marino, Silvia; Logan, John G; Mollat, Patrick; Ralston, Stuart H; Idris, Aymen I

    2015-09-04

    The cannabinoid type 2 receptor (CB2) has previously been implicated as a regulator of tumor growth, bone remodeling, and bone pain. However, very little is known about the role of the skeletal CB2 receptor in the regulation of osteoblasts and osteoclasts changes associated with breast cancer. Here we found that the CB2-selective agonists HU308 and JWH133 reduced the viability of a variety of parental and bone-tropic human and mouse breast cancer cells at high micromolar concentrations. Under conditions in which these ligands are used at the nanomolar range, HU308 and JWH133 enhanced human and mouse breast cancer cell-induced osteoclastogenesis and exacerbated osteolysis, and these effects were attenuated in cultures obtained from CB2-deficient mice or in the presence of a CB2 receptor blocker. HU308 and JWH133 had no effects on osteoblast growth or differentiation in the presence of conditioned medium from breast cancer cells, but under these circumstances both agents enhanced parathyroid hormone-induced osteoblast differentiation and the ability to support osteoclast formation. Mechanistic studies in osteoclast precursors and osteoblasts showed that JWH133 and HU308 induced PI3K/AKT activity in a CB2-dependent manner, and these effects were enhanced in the presence of osteolytic and osteoblastic factors such as RANKL (receptor activator of NFκB ligand) and parathyroid hormone. When combined with published work, these findings suggest that breast cancer and bone cells exhibit differential responses to treatment with CB2 ligands depending upon cell type and concentration used. We, therefore, conclude that both CB2-selective activation and antagonism have potential efficacy in cancer-associated bone disease, but further studies are warranted and ongoing.

  9. Involvement of Spinal CCR5/PKCγ Signaling Pathway in the Maintenance of Cancer-Induced Bone Pain.

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    Hang, Li-Hua; Li, Shu-Na; Dan, Xiang; Shu, Wei-Wei; Luo, Hong; Shao, Dong-Hua

    2017-02-01

    Cancer-induced bone pain (CIBP) is a challenging medical problem that considerably influences cancer patients' quality of life. Currently, few treatments have been developed to conquer CIBP because of a poor understanding of the potential mechanisms. Our previous work has proved that spinal RANTES (a major ligand for CCR5) was involved in the maintenance of CIBP. In this study, we attempted to investigate whether spinal CCR5 and its downstream PKCγ pathway is involved in the maintenance of CIBP. Inoculation of Walker 256 cells into the tibia could induce a marked mechanical allodynia with concomitant upregulation of spinal CCR5 and p-PKCγ expression from day 6 to day 15 after inoculation. Spinal CCR5 was prominently expressed in microglia, and mechanical allodynia was attenuated by intrathecal injection of DAPTA (a specific antagonist of CCR5) with downregulation of spinal CCR5 and p-PKCγ expression levels at day 15 in inoculated rats. Pre-intrathecal injection of RANTES could reverse the anti-allodynia effects of DAPTA. Intrathecal administration of GF109203X (an inhibitor of PKC) could alleviate mechanical allodynia as well as decrease of spinal p-PKCγ expression level, but no influence on spinal CCR5 level. Our findings suggest that CCR5/PKCγ signaling pathway in microglia may contribute to the maintenance of CIBP in rats.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  11. 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.

  12. Intrathecal injection of lentivirus-mediated glial cell line-derived neurotrophic factor RNA interference relieves bone cancer-induced pain in rats.

    Science.gov (United States)

    Meng, Fu-Fen; Xu, Yang; Dan, Qi-Qin; Wei, La; Deng, Ying-Jie; Liu, Jia; He, Mu; Liu, Wei; Xia, Qing-Jie; Zhou, Fiona H; Wang, Ting-Hua; Wang, Xi-Yan

    2015-04-01

    Bone cancer pain is a common symptom in cancer patients with bone metastases and the underlying mechanisms are largely unknown. The aim of this study is to explore the endogenous analgesic mechanisms to develop new therapeutic strategies for bone-cancer induced pain (BCIP) as a result of metastases. MRMT-1 tumor cells were injected into bilateral tibia of rats and X-rays showed that the area suffered from bone destruction, accompanied by an increase in osteoclast numbers. In addition, rats with bone cancer showed apparent mechanical and thermal hyperalgesia at day 28 after intratibial MRMT-1 inoculation. However, intrathecal injection of morphine or lentivirus-mediated glial cell line-derived neurotrophic factor RNAi (Lvs-siGDNF) significantly attenuated mechanical and thermal hyperalgesia, as shown by increases in paw withdrawal thresholds and tail-flick latencies, respectively. Furthermore, Lvs-siGDNF interference not only substantially downregulated GDNF protein levels, but also reduced substance P immunoreactivity and downregulated the ratio of pERK/ERK, where its activation is crucial for pain signaling, in the spinal dorsal horn of this model of bone-cancer induced pain. In this study, Lvs-siGDNF gene therapy appeared to be a beneficial method for the treatment of bone cancer pain. As the effect of Lvs-siGDNF to relieve pain was similar to morphine, but it is not a narcotic, the use of GDNF RNA interference may be considered as a new therapeutic strategy for the treatment of bone cancer pain in the future.

  13. 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.

  14. Spinal IFN-γ-induced protein-10 (CXCL10) mediates metastatic breast cancer-induced bone pain by activation of microglia in rat models.

    Science.gov (United States)

    Bu, Huilian; Shu, Bin; Gao, Feng; Liu, Cheng; Guan, Xuehai; Ke, Changbin; Cao, Fei; Hinton, Antentor Othrell; Xiang, Hongbing; Yang, Hui; Tian, Xuebi; Tian, Yuke

    2014-01-01

    Cancer-induced bone pain (CIBP) is a common clinical problem in breast cancer patients with bone metastasis. Recent studies shows chemokines are novel targets for treatment of CIBP. In this study, we intra-tibial inoculated with Walker 256 rat mammary gland carcinoma cells into rat bone to established metastatic breast cancer. Then we measured the expression of CXCL10 in the spinal cord of metastatic bone cancer rats, investigated the role of CXCL10 in the development of CIBP, and the underlying mechanism. Results revealed that after intra-tibial inoculation with Walker 256 cells, rats showed up-regulation of CXCL10 and its receptor CXCR3 in the spinal cord. Interestingly, intrathecally injection of recombinant CXCL10 protein induced mechanical allodynia in naïve rats. Blocking the function of CXCL10/CXCR3 pathway via anti-CXCL10 antibody or CXCR3 antagonist prevented the development of CIBP and microglial activation. Moreover, CXCL10-induced mechanical allodynia was rescued by minocycline treatment during the late-stage of CIBP, days 10-14. The regulation of CXCL10 expression involved microglial activation in a manner of autocrine positive feedback. These results suggest that CXCL10 may be a necessary algogenic molecule, especially in the development of CIBP. Its function was partly mediated via spinal microglial activation. This study provides a novel insight into the biological function of chemokine CXCL10 in the molecular mechanism underlying cancer pain. It also provides new target for clinical treatment of metastatic breast cancer-induced bone pain in future.

  15. 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.

  16. Finite element analysis of bone loss around failing implants

    NARCIS (Netherlands)

    Wolff, J.; Narra, N.; Antalainen, A.K.; Valášek, J.; Kaiser, J.; Sandór, G.K.; Marcián, P.

    2014-01-01

    Dental implants induce diverse forces on their surrounding bone. However, when excessive unphysiological forces are applied, resorption of the neighbouring bone may occur. The aim of this study was to assess possible causes of bone loss around failing dental implants using finite element analysis. A

  17. 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

  18. 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.

  19. Norepinephrine Regulates Condylar Bone Loss via Comorbid Factors.

    Science.gov (United States)

    Jiao, K; Niu, L; Xu, X; Liu, Y; Li, X; Tay, F R; Wang, M

    2015-06-01

    Degenerative changes of condylar subchondral bone occur frequently in temporomandibular disorders. Although psychologic stresses and occlusal abnormalities have been implicated in temporomandibular disorder, it is not known if these risks represent synergistic comorbid factors that are involved in condylar subchondral bone degradation that is regulated by the sympathetic nervous system. In the present study, chronic immobilization stress (CIS), chemical sympathectomy, and unilateral anterior crossbite (UAC) were sequentially applied in a murine model. Norepinephrine contents in the subjects' serum and condylar subchondral bone were detected by ELISA; bone and cartilage remodeling parameters and related gene expression in the subchondral bone were examined. Subchondral bone loss and increased subchondral bone norepinephrine level were observed in the CIS and UAC groups. These groups exhibited decreased bone mineral density, volume fraction, and bone formation rate; decreased expressions of osterix, collagen I, and osteocalcin; but increased trabecular separation, osteoclast number and surface, and RANKL expression. Combined CIS + UAC produced more severe subchondral bone loss, higher bone norepinephrine level, and decreased chondrocyte density and cartilage thickness when compared to CIS or UAC alone. Sympathectomy simultaneously prevented subchondral bone loss and decreased bone norepinephrine level in all experimental subgroups when compared to the vehicle-treated counterparts. Norepinephrine also decreased mRNA expression of osterix, collagen I, and osteocalcin by mesenchymal stem cells at 7 and 14 d of stimulation and increased the expression of RANKL and RANKL/OPG ratio by mesenchymal stem cells at 2 h. In conclusion, CIS and UAC synergistically promote condylar subchondral bone loss and cartilage degradation; such processes are partially regulated by norepinephrine within subchondral bone.

  20. Biglycan deficiency interferes with ovariectomy-induced bone loss

    DEFF Research Database (Denmark)

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

    2003-01-01

    (OPG) and RANKL revealed increased levels of OPG and decreased levels of RANKL in the bgn KO mice compared with wt mice. In conclusion, the bgn deficiency protects against increased trabecular bone turnover and bone loss in response to estrogen depletion, supporting the concept that bgn has dual roles......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 biglycan deficiency. INTRODUCTION: Biglycan (bgn) is a small extracellular matrix proteoglycan enriched in skeletal tissues, and biglycan-deficient male mice have decreased trabecular bone mass and bone strength. The purpose of this study was to investigate the bone phenotype of the biglycan...

  1. Metastasis and bone loss: advancing treatment and prevention.

    Science.gov (United States)

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

    2010-12-01

    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 bone loss have recently reported exciting and intriguing results. A multidisciplinary consensus conference convened to review recent progress in basic and clinical research, assess gaps in current knowledge and prioritize recommendations to advance research over the next 5 years. The program addressed three topics: advancing understanding of metastasis prevention in the context of bone pathophysiology; developing therapeutic approaches to prevent metastasis and defining strategies to prevent cancer therapy-induced bone loss. Several priorities were identified: (1) further investigate the effects of bone-targeted therapies on tumor and immune cell interactions within the bone microenvironment; (2) utilize and further develop preclinical models to study combination therapies; (3) conduct clinical studies of bone-targeted therapies with radiation and chemotherapy across a range of solid tumors; (4) develop biomarkers to identify patients most likely to benefit from bone-targeted therapies; (5) educate physicians on bone loss and fracture risk; (6) define optimal endpoints and new measures of efficacy for future clinical trials; and (7) define the optimum type, dose and schedule of adjuvant bone-targeted therapy.

  2. Metastasis and bone loss: Advancing treatment and prevention

    Science.gov (United States)

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

    2011-01-01

    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 bone loss have recently reported exciting and intriguing results. A multidisciplinary consensus conference convened to review recent progress in basic and clinical research, assess gaps in current knowledge and prioritize recommendations to advance research over the next 5 years. The program addressed three topics: advancing understanding of metastasis prevention in the context of bone pathophysiology; developing therapeutic approaches to prevent metastasis and defining strategies to prevent cancer therapy-induced bone loss. Several priorities were identified: (1) further investigate the effects of bone-targeted therapies on tumor and immune cell interactions within the bone microenvironment; (2) utilize and further develop preclinical models to study combination therapies; (3) conduct clinical studies of bone-targeted therapies with radiation and chemotherapy across a range of solid tumors; (4) develop biomarkers to identify patients most likely to benefit from bone-targeted therapies; (5) educate physicians on bone loss and fracture risk; (6) define optimal endpoints and new measures of efficacy for future clinical trials; and (7) define the optimum type, dose and schedule of adjuvant bone-targeted therapy. PMID:20478658

  3. 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

  4. 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.

  5. 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.

  6. Differential Bone Loss in Mouse Models of Colon Cancer Cachexia

    Science.gov (United States)

    Bonetto, Andrea; Kays, Joshua K.; Parker, Valorie A.; Matthews, Ryan R.; Barreto, Rafael; Puppa, Melissa J.; Kang, Kyung S.; Carson, James A.; Guise, Theresa A.; Mohammad, Khalid S.; Robling, Alexander G.; Couch, Marion E.; Koniaris, Leonidas G.; Zimmers, Teresa A.

    2017-01-01

    Cachexia is a distinctive feature of colorectal cancer associated with body weight loss and progressive muscle wasting. Several mechanisms responsible for muscle and fat wasting have been identified, however it is not known whether the physiologic and molecular crosstalk between muscle and bone tissue may also contribute to the cachectic phenotype in cancer patients. The purpose of this study was to clarify whether tumor growth associates with bone loss using several experimental models of colorectal cancer cachexia, namely C26, HT-29, and ApcMin/+. The effects of cachexia on bone structure and strength were evaluated with dual energy X-ray absorptiometry (DXA), micro computed tomography (μCT), and three-point bending test. We found that all models showed tumor growth consistent with severe cachexia. While muscle wasting in C26 hosts was accompanied by moderate bone depletion, no loss of bone strength was observed. However, HT-29 tumor bearing mice showed bone abnormalities including significant reductions in whole-body bone mineral density (BMD), bone mineral content (BMC), femoral trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th), but no declines in strength. Similarly, cachexia in the ApcMin/+ mice was associated with significant decreases in BMD, BMC, BV/TV, Tb.N, and Tb.Th as well as decreased strength. Our data suggest that colorectal cancer is associated with muscle wasting and may be accompanied by bone loss dependent upon tumor type, burden, stage and duration of the disease. It is clear that preserving muscle mass promotes survival in cancer cachexia. Future studies will determine whether strategies aimed at preventing bone loss can also improve outcomes and survival in colorectal cancer cachexia. PMID:28123369

  7. Bilateral sudden sensorineural hearing loss following unilateral temporal bone fracture.

    Science.gov (United States)

    Hunchaisri, Niran

    2009-06-01

    Temporal bone fractures usually cause unilateral sensorineural hearing loss (SNHL) by fracture that violated otic capsule of that side. Bilateral SNHL from unilateral temporal bone fracture were rarely seen. Labyrinthine concussion was considered to be the pathogenesis in these cases. This article reports an additional case of bilateral SNHL from unilateral temporal bone fracture but in a different pattern of SNHL which may result from an occlusion of the internal auditory artery.

  8. P2Y12 receptor-mediated activation of spinal microglia and p38MAPK pathway contribute to cancer-induced bone pain

    Directory of Open Access Journals (Sweden)

    Liu MJ

    2017-02-01

    Full Text Available Mingjuan Liu,1 Ming Yao,1,2 Hanqi Wang,1 Longsheng Xu,1 Ying Zheng,1 Bing Huang,1 Huadong Ni,1 Shijie Xu,1 Xuyan Zhou,1 Qingquan Lian2 1Department of Anesthesiology and Pain Medicine, The First Hospital of Jiaxing, The First Affiliated Hospital of Jiaxing University, Jiaxing, 2Department of Anesthesiology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China Background: Cancer-induced bone pain (CIBP is one of the most challenging clinical problems due to a lack of understanding the mechanisms. Recent evidence has demonstrated that activation of microglial G-protein-coupled P2Y12 receptor (P2Y12R and proinflammatory cytokine production play an important role in neuropathic pain generation and maintenance. However, whether P2Y12R is involved in CIBP remains unknown.Methods: The purpose of this study was to investigate the role of P2Y12R in CIBP and its molecular mechanisms. Using the bone cancer model inoculated with Walker 256 tumor cells into the left tibia of Sprague Dawley rat, we blocked spinal P2Y12R through intrathecal administration of its selective antagonist MRS2395 (400 pmol/µL, 15 µL.Results: We found that not only the ionized calcium-binding adapter molecule 1 (Iba-1-positive microglia in the ipsilateral spinal cord but also mechanical allodynia was significantly inhibited. Furthermore, it decreased the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK and the production of proinflammatory cytokines interleukin-1β (IL-1β and interleukin-6 (IL-6, whereas it increased tumor necrosis factor-α (TNF-α.Conclusion: Taken together, our present results suggest that microglial P2Y12R in the spinal cord may contribute to CIBP by the activation of spinal microglia and p38MAPK pathway, thus identifying a potential therapeutic target for the treatment of CIBP. Keywords: P2Y12 receptor, cancer-induced bone pain, p38MAPK pathway, cytokines

  9. Inducible nitric oxide synthase mediates bone loss in ovariectomized mice.

    NARCIS (Netherlands)

    Cuzzocrea, S.; Mazzon, E.; Dugo, L.; Genovese, T.; Paola, R. Di; Ruggeri, Z.; Vegeto, E.; Caputi, A.P.; Loo, F.A.J. van de; Puzzolo, D.; Maggi, A.

    2003-01-01

    Several clinical studies have shown that bone loss may be attributed to osteoclast recruitment induced by mediators of inflammation. In different experimental paradigms we have recently demonstrated that estrogen exhibits antiinflammatory activity by preventing the induction of inducible nitric oxid

  10. Bed Rest and Immobilization: Risk Factors for Bone Loss

    Science.gov (United States)

    ... browser. Home Osteoporosis Osteoporosis and Other Conditions Bed Rest and Immobilization: Risk Factors for Bone Loss Publication ... Line For Your Information The Impact of Bed Rest and Inactivity Some people can’t perform weight- ...

  11. 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...

  12. 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.

  13. Inhibition on Breast Cancer Induced Bone Pain, Metastasis and Osteolysis in Nude Mice by LOVAZA and DHA Fattty Acids

    Science.gov (United States)

    2011-10-01

    Paw withdrawal latency to thermal stimuli of radiant heat was measured using a device (Plantar test, 7370; Ugo Basile, Comerio, Italy). Briefly...1115. II. Hargreaves K, Dubner R, Brown F, Flores C, Joris J (1988) A new and sensitive method for measuring thermal nociception in cutaneous... hyperalgesia . Pain 32:77–88. FIGURE 3 LC CO Fatty Acids on MDA-231bone Bone Tumors of Tibial

  14. Emerging therapeutic targets in cancer induced bone disease: A focus on the peripheral type 2 cannabinoid receptor.

    Science.gov (United States)

    Marino, Silvia; Idris, Aymen I

    2017-03-05

    Skeletal complications are a common cause of morbidity in patients with primary bone cancer and bone metastases. The type 2 cannabinoid (Cnr2) receptor is implicated in cancer, bone metabolism and pain perception. Emerging data have uncovered the role of Cnr2 in the regulation of tumour-bone cell interactions and suggest that agents that target Cnr2 in the skeleton have potential efficacy in the reduction of skeletal complications associated with cancer. This review aims to provide an overview of findings relating to the role of Cnr2 receptor in the regulation of skeletal tumour growth, osteolysis and bone pain, and highlights the many unanswered questions and unmet needs. This review argues that development and testing of peripherally-acting, tumour-, Cnr2-selective ligands in preclinical models of metastatic cancer will pave the way for future research that will advance our knowledge about the basic mechanism(s) by which the endocannabinoid system regulate cancer metastasis, stimulate the development of a safer cannabis-based therapy for the treatment of cancer and provide policy makers with powerful tools to assess the science and therapeutic potential of cannabinoid-based therapy. Thus, offering the prospect of identifying selective Cnr2 ligands, as novel, alternative to cannabis herbal extracts for the treatment of advanced cancer patients.

  15. 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.

  16. Isoflavones prevent bone loss following ovariectomy in young adult rats

    Directory of Open Access Journals (Sweden)

    Chen Li-Ting

    2008-03-01

    Full Text Available Abstract Soy protein, a rich source of phytoestrogens, exhibit estrogen-type bioactivity. The purpose of this study was to determine if ingestion of isoflavones before ovariectomy can prevent bone loss following ovariectomy. Twenty-four nulliparous Wistar rats were randomly divided into four groups. In the normal diet groups, a sham operation was performed on Group A, while ovariectomy was performed on Group B. For Groups C and D, all rats were fed with an isoflavone-rich (25 mg/day diet for one month, then bilateral ovariectomy were performed. In the rats in Group C, a normal diet was begun following the ovariectomy. The rats in Groups D continued to receive the isoflavone-rich diet for two additional months postoperatively. All rats were sacrificed 60 days after surgery. The weight of bone ash of the long bones and whole lumbar spine were determined. A histological study of cancellous bone was done and biochemical indices of skeletal metabolism were performed and analyzed. The markers of bone metabolism exhibited no significant changes. When compared with the sham-operated rats fed a normal diet, the bone mass of ovariectomized rats decreased significantly; pre-ovariectomy ingestion of an isoflavone-rich diet did not prevent bone loss. The bone mass of rats treated with an isoflavone-rich diet for three months was higher than controls two months after ovariectomy. Dietary isoflavones did not prevent the development of post-ovariectomy bone loss, but long-term ingestion of an isoflavone-rich diet increased the bone mineral contents after ovariectomy in young rats.

  17. 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.

  18. 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.

  19. Phytoestrogens in the prevention of postmenopausal bone loss.

    Science.gov (United States)

    Lagari, Violet S; Levis, Silvina

    2013-01-01

    Postmenopausal osteoporosis is a condition associated with low bone mass resulting from the increased bone resorption that occurs following a decline in estrogen levels. Phytoestrogens are plant-derived compounds that have affinity to the estrogen receptor and are able to act as either estrogen agonists or antagonists. Because of their structural similarity to 17-beta-estradiol, they have been studied extensively for their role in the prevention of postmenopausal bone loss. An extensive number of studies employing different types of isoflavone preparations (including soy foods, soy-enriched foods, and soy isoflavone tablets) have been conducted in a wide range of populations, including Western and Asian women. Although there is considerable variability in study design and duration, study population, type of soy isoflavone employed in the intervention, and study outcomes, the evidence points to a lack of a protective role of soy isoflavones in the prevention of postmenopausal bone loss.

  20. P2Y12 receptor-mediated activation of spinal microglia and p38MAPK pathway contribute to cancer-induced bone pain

    Science.gov (United States)

    Liu, Mingjuan; Yao, Ming; Wang, Hanqi; Xu, Longsheng; Zheng, Ying; Huang, Bing; Ni, Huadong; Xu, Shijie; Zhou, Xuyan; Lian, Qingquan

    2017-01-01

    Background Cancer-induced bone pain (CIBP) is one of the most challenging clinical problems due to a lack of understanding the mechanisms. Recent evidence has demonstrated that activation of microglial G-protein-coupled P2Y12 receptor (P2Y12R) and proinflammatory cytokine production play an important role in neuropathic pain generation and maintenance. However, whether P2Y12R is involved in CIBP remains unknown. Methods The purpose of this study was to investigate the role of P2Y12R in CIBP and its molecular mechanisms. Using the bone cancer model inoculated with Walker 256 tumor cells into the left tibia of Sprague Dawley rat, we blocked spinal P2Y12R through intrathecal administration of its selective antagonist MRS2395 (400 pmol/µL, 15 µL). Results We found that not only the ionized calcium-binding adapter molecule 1 (Iba-1)-positive microglia in the ipsilateral spinal cord but also mechanical allodynia was significantly inhibited. Furthermore, it decreased the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and the production of proinflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6), whereas it increased tumor necrosis factor-α (TNF-α). Conclusion Taken together, our present results suggest that microglial P2Y12R in the spinal cord may contribute to CIBP by the activation of spinal microglia and p38MAPK pathway, thus identifying a potential therapeutic target for the treatment of CIBP.

  1. Bone Loss During Spaceflight: Available Models and Counter-Measures

    Science.gov (United States)

    Morris, Jonathan; Bach, David; Geller, David

    2015-01-01

    There is ongoing concern for human health during spaceflights. Of particular interest is the uncoupling of bone remodeling and its resultant effect on calcium metabolism and bone loss. The calculated average loss of bone mineral density (BMD) is approximately 1-1.5% per month of spaceflight. The effect of decreased BMD on associated fractures in astronauts is not known. Currently on the International Space Station (ISS), bone loss is managed through dietary supplements and modifications and resistance exercise regimen. As the duration of space flights increases, a review of the current methods available for the prevention of bone loss is warranted. The goal of this project is to review and summarize recent studies that have focused on maintaining BMD during exposure to microgravity. Interventions were divided into physical (Table 1), nutritional (Table 2), or pharmacologic (Table 3) categories. Physical modalities included resistance exercise, low level vibration, and low intensity pulsed ultrasound. Nutritional interventions included altering protein, salt, and fat intake; and vitamin D supplementation. Pharmacologic interventions included the use of bisphosphonates and beta blockers. Studies reported outcomes based on bone density determined by DXA bone scan, micro-architecture of histology and microCT, and serum and urine markers of bone turnover. The ground analog models utilized to approximate osseous physiology in microgravity included human patients previously paralyzed or subjects confined to bedrest. Ground analog animal models include paralysis, immobilization and ovariectomies. As a result of the extensive research performed there is a multi-modality approach available for the management of BMD during spaceflight that includes resistance training, nutrition and dietary supplements. However, there is a paucity of literature describing a formalized tiered protocol to guide investigators through the progression from animal models to human patient ground

  2. 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.

  3. 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.

  4. Numerical analysis of an osseointegrated prosthesis fixation with reduced bone failure risk and periprosthetic bone loss.

    Science.gov (United States)

    Tomaszewski, P K; van Diest, M; Bulstra, S K; Verdonschot, N; Verkerke, G J

    2012-07-26

    Currently available implants for direct attachment of prosthesis to the skeletal system after transfemoral amputation (OPRA system, Integrum AB, Sweden and ISP Endo/Exo prosthesis, ESKA Implants AG, Germany) show many advantages over the conventional socket fixation. However, restraining biomechanical issues such as considerable bone loss around the stem and peri-prosthetic bone fractures are present. To overcome these limiting issues a new concept of the direct intramedullary fixation was developed. We hypothesize that the new design will reduce the peri-prosthetic bone failure risk and adverse bone remodeling by restoring the natural load transfer in the femur. Generic CT-based finite element models of an intact femur and amputated bones implanted with 3 analyzed implants were created and loaded with a normal walking and a forward fall load. The strain adaptive bone remodeling theory was used to predict long-term bone changes around the implants and the periprosthetic bone failure risk was evaluated by the von Mises stress criterion. The results show that the new design provides close to physiological distribution of stresses in the bone and lower bone failure risk for the normal walking as compared to the OPRA and the ISP implants. The bone remodeling simulations did not reveal any overall bone loss around the new design, as opposed to the OPRA and the ISP implants, which induce considerable bone loss in the distal end of the femur. This positive outcome shows that the presented concept has a potential to considerably improve safety of the rehabilitation with the direct fixation implants.

  5. 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.

  6. Microthreaded Implants and Crestal Bone Loss: A Systematic Review.

    Science.gov (United States)

    Al-Thobity, Ahmad; Kutkut, Ahmad; Almas, Khalid

    2016-11-21

    This systematic literature review investigated the effect of microthreaded-neck dental implants on crestal bone loss. Using the participants, interventions, comparison groups, outcomes, and study design (PICOS) system, we addressed the following focused question: Do microthreaded-neck dental implants positively affect the crestal bone level around dental implants? We searched 3 electronic databases to find articles published between January 1995 and June 2016 that contained any combination of the following keywords: dental implant, microthread, microthreaded, crestal bone level, crestal bone loss, and alveolar bone level. We excluded case reports, review articles, letters to the editor, commentaries, and articles published in a language other than English. We found a total of 70 articles. After eliminating duplicates and applying PICOS eligibility criteria, we selected only articles that reported the results of randomized controlled trials, prospective or retrospective cohort studies, case-control studies, cross-sectional studies, or other types of clinical trials that compared the microthreaded implant design to other implant designs. We were left with 23 articles for review. The 23 articles reported crestal bone loss ranging from 0.05 mm to 0.9 mm, with a range of 12 to 96 months of follow-up. Less crestal bone was lost with dental implants that had a microthreaded neck design than with machined-surface or conventional rough-surface dental implants. Thus, microthreaded dental implants are a better choice than are implants with other designs. Future studies should use standardized imaging techniques to to evaluate the placement of these implants in bone-augmented sites.

  7. Blocking antibody to the beta-subunit of FSH prevents bone loss by inhibiting bone resorption and stimulating bone synthesis

    Science.gov (United States)

    Low estrogen levels undoubtedly underlie menopausal bone thinning. However, rapid and profuse bone loss begins three years prior to the last menstrual period, when serum estrogen is relatively normal. We have shown that the pituitary hormone FSH, the levels of which are high during the late peri-men...

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

    Science.gov (United States)

    Rendina, Elizabeth; Hembree, Kelsey D; Davis, McKale R; Marlow, Denver; Clarke, Stephen L; Halloran, Bernard P; Lucas, Edralin A; Smith, Brenda J

    2013-01-01

    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.

  9. 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

  10. 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.

  11. Green tea polyphenols mitigate bone loss of female rats in a chronic inflammation-induced bone loss model

    Science.gov (United States)

    The purpose of this study was to explore bioavailability, efficacy, and molecular mechanisms of green tea polyphenols (GTP) related to preventing bone loss in rats with chronic inflammation. A 2 (placebo vs. lipopolysaccharide, LPS) × 2 (no GTP vs. 0.5% GTP in drinking water) factorial design using ...

  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. Prolyl hydroxylase inhibitors protect from the bone loss in ovariectomy rats by increasing bone vascularity.

    Science.gov (United States)

    Liu, Xiaodong; Tu, Yihui; Zhang, Lianfang; Qi, Jin; Ma, Tong; Deng, Lianfu

    2014-05-01

    The hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway is involved in skeletal development, bone repair, and postmenopausal osteoporosis. Inhibitors of prolyl hydroxylases (PHD) enhance vascularity, increase callus formation in a stabilized fracture model, and activate the HIF-1α/VEGF pathway. This study examined the effects of estrogen on the HIF-1α/VEGF pathway in osteoblasts and whether PHD inhibitors can protect from bone loss in postmenopausal osteoporosis. Osteoblasts were treated with estrogen, and expressions of HIF-1α and VEGF were measured at mRNA (qPCR) and protein (Western blot) levels. Further, osteoblasts were treated with inhibitors of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway, and levels of VEGF mRNA and protein expression were detected. In addition, ovariectomized rats were treated with PHD inhibitors, and bone microarchitecture and bone mechanical strength were assessed using micro-CT and biomechanical analyses (lower ultimate stress, modulus, and stiffness). Blood vessel formation was measured with India Ink Perfusion and immunohistochemistry. Estrogen, in a dose- and time-dependent manner, induced VEGF expression at both mRNA and protein levels and enhanced HIF-1α protein stability. Further, the estrogen-induced VEGF expression in osteoblasts involved the PI3K/Akt pathway. PHD inhibitors increased bone mineral density, bone microarchitecture and bone mechanical strength, and promoted blood vessel formation in ovariectomized rats. In conclusion, estrogen and PHD inhibitors activate the HIF-1α/VEGF pathway in osteoblasts. PHD inhibitors can be utilized to protect bone loss in postmenopausal osteoporosis by improving bone vascularity and angiogenesis in bone marrow.

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

    Science.gov (United States)

    Pennline, James A.

    2009-01-01

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

  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.

  16. 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.

  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. Tanshinone prevents cancellous bone loss induced by ovariectomy in rats

    Institute of Scientific and Technical Information of China (English)

    Liao CUI; Tie WU; Yu-yu LIU; Yi-feng DENG; Chun-mei AI; Huai-qing CHEN

    2004-01-01

    AIM: To investigate the skeletal effects of total tanshinone in ovariectomized rats by analyzing cancellous bone histomorphometry of fourth lumbar vertebrae (LV4) and proximal tibial metaphyses (PTM). METHODS: Fourmonth-old Sprague-Dawley female rats were sham-operated and treated with vehicle or ovariectomized and treated with either vehicle, total tanshinone (200 mg.kg-1.d-1, equivalent to 35 μg.kg-1.d-1 of tanshinone II A and 16 mg.kg-1.d-1 of gery for 10 weeks. Double in vivo fiuorochrome labeling was administered to all rats. The undecalcified longitudinal LV4 and PTM sections were cut and stained with Goldner's Trichrome (4-μm thickness) or unstained (8-μm thickness) for the bone histomorphometric analysis. RESULTS: A significant decrease in trabecular bone volume (BV/TV) and trabecular number (Tb.N) and a significant increase in osteoclast surface (OCS/BS) and mineralizing surface (MS/BS) were found in both LV and PTM of vehicle-treated OVX rats compared with sham controls.Tanshinone completely prevented the decreases in BV/TV and Tb.N and the increase in OCS/BS in the LV4, and partially prevented the decreases in BV/TV and Tb.N in the PTM of OVX rats. In addition, tanshinone increased trabecular thickness (Tb.Th) whereas it did not alter MS/BS. Moreover, tanshinone had no effect on uterine weight and body weight of OVX rats. Estrogen treatment increased BV/TV and Tb.N and decreased OCS/BS, but, also markedly decreased MS/BS and increased uterine weight in OVX rats. CONCLUSION: The current study demonstrated that the adequate supply of tanshinone prevented OVX-induced cancellous bone loss in rats through inhibition of elevated bone resorption.

  1. 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.

  2. 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.

  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'.

  4. Treatment of excessive bone loss from both crus bones with internal bone transport using an intramedullary nail. Case report.

    Science.gov (United States)

    Bereza, Przemysław; Wojciechowski, Piotr; Kusz, Damian

    2013-01-01

    We present a case report of a 16-year-old patient who suffered multisite and multiorgan injuries following a road accident. The most prominent musculoskeletal problem was a bilateral crush injury of the crus in combination with open fractures. The aim of this study is to present the possibilities and available methods of treatment of patients with extensive posttraumatic and postinflammatory bone loss of the lower limbs that make it possible to avoid amputation. We used intramedullary nailing and internal bone transport to reconstruct continuity and leg length of both crus bones. The treatment was complicated by poor vascularity and emerging complications. After several months and multi-stage treatment the patient was able to walk with full weight-bearing without crutches. Importantly, the patient is satisfied with the outcome of the treatment and does not consider herself disabled. The study presents our approach to the dilemma of choosing between prolonged reconstruction surgery and amputation as a final method.

  5. Donepezil prevents RANK-induced bone loss via inhibition of osteoclast differentiation by downregulating acetylcholinesterase

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Sato

    2015-09-01

    Conclusions: AChE promotes osteoclast differentiation in vitro. Donepezil inhibits osteoclast function in vitro and prevents bone loss by suppressing bone resorption in vivo, suggesting the possibility that donepezil reduces fracture risk in patients with Alzheimer's disease.

  6. 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...

  7. 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

    in 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.......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...

  8. The Science and Practice of Bone Health in Oncology: Managing Bone Loss and Metastasis in Patients With Solid Tumors

    Science.gov (United States)

    Lipton, Allan; Uzzo, Robert; Amato, Robert J.; Ellis, Georgiana K.; Hakimian, Behrooz; Roodman, G. David; Smith, Matthew R.

    2011-01-01

    Cancer and its treatment can compromise bone health, leading to fracture, pain, loss of mobility, and hypercalcemia of malignancy. Bone metastasis occurs frequently in advanced prostate and breast cancers, and bony manifestations are commonplace in multiple myeloma. Osteoporosis and osteopenia may be consequences of androgen-deprivation therapy for prostate cancer, aromatase inhibition for breast cancer, or chemotherapy-induced ovarian failure. Osteoporotic bone loss and bone metastasis ultimately share a pathophysiologic pathway that stimulates bone resorption by increasing the formation and activity of osteoclasts. Important mediators of pathologic bone metabolism include substances produced by osteoblasts, such as RANKL, the receptor activator of nuclear factor kappa B ligand, which spurs osteoclast differentiation from myeloid cells. Available therapies are targeted to various steps in cascade of bone metastasis. PMID:19878635

  9. Vascularized fibular graft in infected tibial bone loss

    Directory of Open Access Journals (Sweden)

    C Cheriyan Kovoor

    2011-01-01

    Full Text Available Background : The treatment options of bone loss with infections include bone transport with external fixators, vascularized bone grafts, non-vascularized autogenous grafts and vascularized allografts. The research hypothesis was that the graft length and intact ipsilateral fibula influenced hypertrophy and stress fracture. We retrospectively studied the graft hypertrophy in 15 patients, in whom vascularized fibular graft was done for post-traumatic tibial defects with infection. Materials and Methods : 15 male patients with mean age 33.7 years (range 18 - 56 years of post traumatic tibial bone loss were analysed. The mean bony defect was 14.5 cm (range 6.5 - 20 cm. The mean length of the graft was 16.7 cm (range 11.5 - 21 cm. The osteoseptocutaneous flap (bone flap with attached overlying skin flap from the contralateral side was used in all patients except one. The graft was fixed to the recipient bone at both ends by one or two AO cortical screws, supplemented by a monolateral external fixator. A standard postoperative protocol was followed in all patients. The hypertrophy percentage of the vascularized fibular graft was calculated by a modification of the formula described by El-Gammal. The followup period averaged 46.5 months (range 24 - 164 months. The Pearson correlation coefficient (r was worked out, to find the relationship between graft length and hypertrophy. The t-test was performed to find out if there was any significant difference in the graft length of those who had a stress fracture and those who did not and to find out whether there was any significant difference in hypertrophy with and without ipsilateral fibula union. The Chi square test was performed to identify whether there was any association between the stress fracture and the fibula union. Given the small sample size we have not used any statistical analysis to determine the relation between the percentage of the graft hypertrophy and stress fracture. Results : Graft

  10. 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.

  11. 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.

  12. 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.

  13. Increased osteoblastogenesis and decreased bone resorption protect against ovariectomy-induced bone loss in thrombospondin-2-null mice.

    Science.gov (United States)

    Hankenson, K D; James, I E; Apone, S; Stroup, G B; Blake, S M; Liang, X; Lark, M W; Bornstein, P

    2005-08-01

    Although bone is composed primarily of extracellular matrix (ECM), the dynamic role that the ECM plays in regulating bone remodeling secondary to estrogen loss is relatively unexplored. Previous studies have shown that mice deficient in the matricellular protein thrombospondin-2 (TSP2-null) form excess endocortical bone; thus, we postulated that enhanced bone formation in TSP2-null mice could protect against ovariectomy (OVX)-induced bone loss. Wild-type (WT) OVX mice showed a significant loss of both midfemoral endocortical and proximal tibial trabecular bone, but OVX did not significantly alter TSP2-null bone. TSP2-null mice showed an increase in bone formation, as indicated by a 70% increase in serum osteocalcin two weeks post OVX and a two-fold increase in bone formation rate (BFR) five weeks post OVX as measured by dynamic histomorphometry. WT animals showed only a 20% increase in serum osteocalcin at two weeks and no change in BFR at five weeks. This increase in bone formation in TSP2-null OVX mice was accompanied by a three-fold increase in osteoprogenitor number. Although these results provide a partial explanation for the maintenance of bone geometry post-OVX, TSP2-null mice five weeks post-OVX also showed a significantly lower level of bone resorption than OVX WT mice, as determined by serum levels of the amino-terminal telopeptide of type I collagen (NTx). We conclude that the absence of TSP2 protects against OVX-induced bone loss by two complementary processes: increased formation and decreased resorption.

  14. 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.

  15. 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

    bone mass reductions. DESIGN: Randomized control study. SETTING: Out-patient research hospital clinic. PARTICIPANTS: Thirty-seven healthy obese women. BMI 34±0.5 kg/m(2), age 46±2 years. INTERVENTION: After a low-calorie diet-induced 12% weight loss, participants were randomized to treatment...... with or without administration of the GLP-1 RA liraglutide (1.2mg/day) for 52 weeks. In case of weight gain, up to two meals per day could be substituted with a low-calorie diet product in order to maintain the weight loss. MAIN OUTCOME MEASURES: Total, pelvic and arm-leg bone mineral content (BMC) and bone......% and prevented bone loss after weight loss obtained through a low calorie-diet, supporting its role as a safe weight-lowering agent....

  16. 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.

  17. The correlation between postmenopausal osteoporosis and inflammatory periodontitis regarding bone loss in experimental models.

    Science.gov (United States)

    Kobayashi, Megumi; Matsumoto, Chiho; Hirata, Michiko; Tominari, Tsukasa; Inada, Masaki; Miyaura, Chisato

    2012-01-01

    We have invented a mouse model of periodontitis associated with alveolar bone loss induced by lipopolysaccharide. Ovariectomized (OVX) animals are widely used as a model for osteoporosis due to estrogen deficiency. To define the relationship between periodontitis and osteoporosis, we examined the influence of estrogen deficiency on the mouse alveolar bone mass. In OVX mice, bone loss was detected not only in the femur, but also in the alveolar bone, indicating that estrogen deficiency could induce resorption in alveolar bone. In experiments using a combination of osteoporosis and periodontitis models, OVX significantly enhanced the alveolar bone loss in the model of periodontitis. Therefore, postmenopausal osteoporosis may enhance the risk of periodontitis associated with inflammatory alveolar bone resorption.

  18. Bone mineral density in rheumatoid arthritis patients 1 year after adalimumab therapy: arrest of bone loss

    Science.gov (United States)

    Wijbrandts, C A; Klaasen, R; Dijkgraaf, M G W; Gerlag, D M; van Eck-Smit, B L F; Tak, P P

    2009-01-01

    Objective: To explore the effects of anti-tumour necrosis factor (TNF)α antibody therapy on bone mineral density (BMD) of the lumbar spine and femur neck in patients with rheumatoid arthritis (RA). Methods: A total of 50 patients with active RA (DAS28⩾3.2) who started adalimumab (40 mg subcutaneously/2 weeks) were included in an open label prospective study. All patients used stable methotrexate and were allowed to use prednisone (⩽10 mg/day). The BMD of the lumbar spine and femur neck was measured before and 1 year after start of treatment. Results: Disease activity at baseline (28-joint Disease Activity Score (DAS28)) and disease duration were inversely correlated with femoral neck BMD and lumbar spine BMD (p<0.05). Mean BMD of lumbar spine and femur neck remained unchanged after 1 year of adalimumab therapy (+0.3% and +0.3%, respectively). Of interest, a beneficial effect of prednisone on change in femur neck BMD was observed with a relative increase with prednisone use (+2.5%) compared to no concomitant prednisone use (−0.7%), (p = 0.015). Conclusion: In contrast to the progressive bone loss observed after conventional disease-modifying antirheumatic drug therapy, TNF blockade may result in an arrest of general bone loss. Consistent with previous observations, the data also suggest that the net effect of low-dose corticosteroids on BMD in RA may be beneficial, possibly resulting from their anti-inflammatory effects. PMID:18408246

  19. AST-induced bone loss in men with prostate cancer: exercise as a potential countermeasure.

    Science.gov (United States)

    Bolam, K A; Galvão, D A; Spry, N; Newton, R U; Taaffe, D R

    2012-12-01

    Androgen suppression treatment (AST) for men with prostate cancer is associated with a number of treatment-related side effects including an accelerated rate of bone loss. This loss of bone is greatest within the first year of AST and increases the risk for fracture. Pharmaceutical treatment in the form of bisphosphonates is currently used to counter the effects of hormone suppression on bone but is costly and associated with potential adverse effects. Recently, exercise has been shown to be an important adjuvant therapy to manage a range of treatment-related toxicities and enhance aspects of quality of life for men receiving AST. We propose that physical exercise may also have an important role in not only attenuating the bone loss associated with AST but in improving bone health and reducing fracture risk. In this review, the rationale underlying exercise as a countermeasure to AST-induced bone loss is provided.

  20. 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...

  1. 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

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

    Science.gov (United States)

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

    1993-01-01

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

  3. 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.

  4. 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

  5. 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.

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

    Science.gov (United States)

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

    2016-07-05

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

  7. The relevance of mouse models for investigating age-related bone loss in humans.

    Science.gov (United States)

    Jilka, Robert L

    2013-10-01

    Mice are increasingly used for investigation of the pathophysiology of osteoporosis because their genome is easily manipulated, and their skeleton is similar to that of humans. Unlike the human skeleton, however, the murine skeleton continues to grow slowly after puberty and lacks osteonal remodeling of cortical bone. Yet, like humans, mice exhibit loss of cancellous bone, thinning of cortical bone, and increased cortical porosity with advancing age. Histologic evidence in mice and humans alike indicates that inadequate osteoblast-mediated refilling of resorption cavities created during bone remodeling is responsible. Mouse models of progeria also show bone loss and skeletal defects associated with senescence of early osteoblast progenitors. Additionally, mouse models of atherosclerosis, which often occurs in osteoporotic participants, also suffer bone loss, suggesting that common diseases of aging share pathophysiological pathways. Knowledge of the causes of skeletal fragility in mice should therefore be applicable to humans if inherent limitations are recognized.

  8. Accelerated features of age-related bone loss in zmpste24 metalloproteinase-deficient mice.

    Science.gov (United States)

    Rivas, Daniel; Li, Wei; Akter, Rahima; Henderson, Janet E; Duque, Gustavo

    2009-10-01

    Age-related bone loss is associated with changes in bone cellularity, which include marrow fat infiltration and decreasing levels of osteoblastogenesis. The mechanisms that explain these changes remain unclear. Although nuclear lamina alterations occur in premature aging syndromes that include changes in body fat and severe osteoporosis, the role of proteins of the nuclear lamina in age-related bone loss remains unknown. Using the Zmpste24-null progeroid mice (Zmpste24(-/-)), which exhibit nuclear lamina defects and accumulate unprocessed prelamin A, we identified several alterations in bone cellularity in vivo. We found that defective prelamin A processing induced accelerated features of age-related bone loss including lower osteoblast and osteocyte numbers and higher levels of marrow adipogenesis. In summary, processing of prelamin A could become a new approach to regulate osteoblastogenesis and bone turnover and thus for the prevention and treatment of senile osteoporosis.

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

    Science.gov (United States)

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

    1992-01-01

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

  10. The Use of Structural Allograft in Primary and Revision Knee Arthroplasty with Bone Loss

    Directory of Open Access Journals (Sweden)

    Raul A. Kuchinad

    2011-01-01

    Full Text Available Bone loss around the knee in the setting of total knee arthroplasty remains a difficult and challenging problem for orthopaedic surgeons. There are a number of options for dealing with smaller and contained bone loss; however, massive segmental bone loss has fewer options. Small, contained defects can be treated with cement, morselized autograft/allograft or metal augments. Segmental bone loss cannot be dealt with through simple addition of cement, morselized autograft/allograft, or metal augments. For younger or higher demand patients, the use of allograft is a good option as it provides a durable construct with high rates of union while restoring bone stock for future revisions. Older patients, or those who are low demand, may be better candidates for a tumour prosthesis, which provides immediate ability to weight bear and mobilize.

  11. TLR2 signaling and Th2 responses drive Tannerella forsythia-induced periodontal bone loss.

    Science.gov (United States)

    Myneni, Srinivas R; Settem, Rajendra P; Connell, Terry D; Keegan, Achsah D; Gaffen, Sarah L; Sharma, Ashu

    2011-07-01

    Periodontal disease (PD) is a chronic inflammation of the tooth-supporting soft tissue and alveolar bone due to infection by a select group of gram-negative microbes, which leads to tooth loss if untreated. Because mice deficient in CD4(+) cells are resistant to infection-induced alveolar bone loss, Th cells have been implicated in bone-destructive processes during PD. However, the extent to which different Th cell subtypes play roles in pathogenesis or host protection remains to be defined and is likely to vary depending on the dominant microorganism involved. By far, Porphyromonas gingivalis is the best-studied periodontal microbe in PD. Although the gram-negative anaerobe Tannerella forsythia is also a vital contributor to periodontal bone loss, almost nothing is known about immune responses to this organism. Previous studies from our laboratory revealed that T. forsythia induces periodontal bone loss in mice and that this bone loss depends on the bacterially expressed BspA protein. In this study, we showed that T. forsythia activates murine APCs primarily through TLR2-dependent signaling via BspA. Furthermore, T. forsythia infection causes a pronounced Th2 bias, evidenced by T cell expression of IL-5, but not IFN-γ or IL-17, in draining lymph nodes. Consistently, deficiencies in TLR2 or STAT6 result in resistance to T. forsythia-induced alveolar bone loss. Thus, TLR2 signaling and Th2 cells play pathogenic roles in T. forsythia-induced alveolar bone destruction.

  12. Contribution of mechanical unloading to trabecular bone loss following non-invasive knee injury in mice.

    Science.gov (United States)

    Anderson, Matthew J; Diko, Sindi; Baehr, Leslie M; Baar, Keith; Bodine, Sue C; Christiansen, Blaine A

    2016-10-01

    Development of osteoarthritis commonly involves degeneration of epiphyseal trabecular bone. In previous studies, we observed 30-44% loss of epiphyseal trabecular bone (BV/TV) from the distal femur within 1 week following non-invasive knee injury in mice. Mechanical unloading (disuse) may contribute to this bone loss; however, it is unclear to what extent the injured limb is unloaded following injury, and whether disuse can fully account for the observed magnitude of bone loss. In this study, we investigated the contribution of mechanical unloading to trabecular bone changes observed following non-invasive knee injury in mice (female C57BL/6N). We investigated changes in gait during treadmill walking, and changes in voluntary activity level using Open Field analysis at 4, 14, 28, and 42 days post-injury. We also quantified epiphyseal trabecular bone using μCT and weighed lower-limb muscles to quantify atrophy following knee injury in both ground control and hindlimb unloaded (HLU) mice. Gait analysis revealed a slightly altered stride pattern in the injured limb, with a decreased stance phase and increased swing phase. However, Open Field analysis revealed no differences in voluntary movement between injured and sham mice at any time point. Both knee injury and HLU resulted in comparable magnitudes of trabecular bone loss; however, HLU resulted in considerably more muscle loss than knee injury, suggesting another mechanism contributing to bone loss following injury. Altogether, these data suggest that mechanical unloading likely contributes to trabecular bone loss following non-invasive knee injury, but the magnitude of this bone loss cannot be fully explained by disuse. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1680-1687, 2016.

  13. Programmed administration of parathyroid hormone increases bone formation and reduces bone loss in hindlimb-unloaded ovariectomized rats

    Science.gov (United States)

    Turner, R. T.; Evans, G. L.; Cavolina, J. M.; Halloran, B.; Morey-Holton, E.

    1998-01-01

    Gonadal insufficiency and reduced mechanical usage are two important risk factors for osteoporosis. The beneficial effects of PTH therapy to reverse the estrogen deficiency-induced bone loss in the laboratory rat are well known, but the influence of mechanical usage in this response has not been established. In this study, the effects of programed administration of PTH on cancellous bone volume and turnover at the proximal tibial metaphysis were determined in hindlimb-unloaded, ovariectomized (OVX), 3-month-old Sprague-Dawley rats. PTH was administered to weight-bearing and hindlimb-unloaded OVX rats with osmotic pumps programed to deliver 20 microg human PTH (approximately 80 microg/kg x day) during a daily 1-h infusion for 7 days. Compared with sham-operated rats, OVX increased longitudinal and radial bone growth, increased indexes of cancellous bone turnover, and resulted in net resorption of cancellous bone. Hindlimb unloading of OVX rats decreased longitudinal and radial bone growth, decreased osteoblast number, increased osteoclast number, and resulted in a further decrease in cancellous bone volume compared with those in weight-bearing OVX rats. Programed administration of PTH had no effect on either radial or longitudinal bone growth in weight-bearing and hindlimb-unloaded OVX rats. PTH treatment had dramatic effects on selected cancellous bone measurements; PTH maintained cancellous bone volume in OVX weight-bearing rats and greatly reduced cancellous bone loss in OVX hindlimb-unloaded rats. In the latter animals, PTH treatment prevented the hindlimb unloading-induced reduction in trabecular thickness, but the hormone was ineffective in preventing either the increase in osteoclast number or the loss of trabecular plates. Importantly, PTH treatment increased the retention of a baseline flurochrome label, osteoblast number, and bone formation in the proximal tibial metaphysis regardless of the level of mechanical usage. These findings demonstrate that

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Salvianolic acid B prevents bone loss in prednisone-treated rats through stimulation of osteogenesis and bone marrow angiogenesis.

    Directory of Open Access Journals (Sweden)

    Liao Cui

    Full Text Available Glucocorticoid (GC induced osteoporosis (GIO is caused by the long-term use of GC for treatment of autoimmune and inflammatory diseases. The GC related disruption of bone marrow microcirculation and increased adipogenesis contribute to GIO development. However, neither currently available anti-osteoporosis agent is completely addressed to microcirculation and bone marrow adipogenesis. Salvianolic acid B (Sal B is a polyphenolic compound from a Chinese herbal medicine, Salvia miltiorrhiza Bunge. The aim of this study was to determine the effects of Sal B on osteoblast bone formation, angiogenesis and adipogenesis-associated GIO by performing marrow adipogenesis and microcirculation dilation and bone histomorphometry analyses. (1 In vivo study: Bone loss in GC treated rats was confirmed by significantly decreased BMD, bone strength, cancellous bone mass and architecture, osteoblast distribution, bone formation, marrow microvessel density and diameter along with down-regulation of marrow BMPs expression and increased adipogenesis. Daily treatment with Sal B (40 mg/kg/d for 12 weeks in GC male rats prevented GC-induced cancellous bone loss and increased adipogenesis while increasing cancellous bone formation rate with improved local microcirculation by capillary dilation. Treatment with Sal B at a higher dose (80 mg/kg/d not only prevented GC-induced osteopenia, but also increased cancellous bone mass and thickness, associated with increase of marrow BMPs expression, inhibited adipogenesis and further increased microvessel diameters. (2 In vitro study: In concentration from 10(-6 mol/L to 10(-7 mol/L, Sal B stimulated bone marrow stromal cell (MSC differentiation to osteoblast and increased osteoblast activities, decreased GC associated adipogenic differentiation by down-regulation of PPARγ mRNA expression, increased Runx2 mRNA expression without osteoblast inducement, and, furthermore, Sal B decreased Dickkopf-1 and increased β-catenin m

  19. Salvianolic Acid B Prevents Bone Loss in Prednisone-Treated Rats through Stimulation of Osteogenesis and Bone Marrow Angiogenesis

    Science.gov (United States)

    Cui, Liao; Li, Ting; Liu, Yuyu; Zhou, Le; Li, Pinghua; Xu, Bilian; Huang, Lianfang; Chen, Yan; Liu, Yanzhi; Tian, Xiaoyan; Jee, Webster S. S.; Wu, Tie

    2012-01-01

    Glucocorticoid (GC) induced osteoporosis (GIO) is caused by the long-term use of GC for treatment of autoimmune and inflammatory diseases. The GC related disruption of bone marrow microcirculation and increased adipogenesis contribute to GIO development. However, neither currently available anti-osteoporosis agent is completely addressed to microcirculation and bone marrow adipogenesis. Salvianolic acid B (Sal B) is a polyphenolic compound from a Chinese herbal medicine, Salvia miltiorrhiza Bunge. The aim of this study was to determine the effects of Sal B on osteoblast bone formation, angiogenesis and adipogenesis-associated GIO by performing marrow adipogenesis and microcirculation dilation and bone histomorphometry analyses. (1) In vivo study: Bone loss in GC treated rats was confirmed by significantly decreased BMD, bone strength, cancellous bone mass and architecture, osteoblast distribution, bone formation, marrow microvessel density and diameter along with down-regulation of marrow BMPs expression and increased adipogenesis. Daily treatment with Sal B (40 mg/kg/d) for 12 weeks in GC male rats prevented GC-induced cancellous bone loss and increased adipogenesis while increasing cancellous bone formation rate with improved local microcirculation by capillary dilation. Treatment with Sal B at a higher dose (80 mg/kg/d) not only prevented GC-induced osteopenia, but also increased cancellous bone mass and thickness, associated with increase of marrow BMPs expression, inhibited adipogenesis and further increased microvessel diameters. (2) In vitro study: In concentration from 10−6 mol/L to 10−7 mol/L, Sal B stimulated bone marrow stromal cell (MSC) differentiation to osteoblast and increased osteoblast activities, decreased GC associated adipogenic differentiation by down-regulation of PPARγ mRNA expression, increased Runx2 mRNA expression without osteoblast inducement, and, furthermore, Sal B decreased Dickkopf-1 and increased β-catenin mRNA expression with

  20. Clinical Impact and Cellular Mechanisms of Iron Overload-Associated Bone Loss

    Science.gov (United States)

    Jeney, Viktória

    2017-01-01

    Diseases/conditions with diverse etiology, such as hemoglobinopathies, hereditary hemochromatosis and menopause, could lead to chronic iron accumulation. This condition is frequently associated with a bone phenotype; characterized by low bone mass, osteoporosis/osteopenia, altered microarchitecture and biomechanics, and increased incidence of fractures. Osteoporotic bone phenotype constitutes a major complication in patients with iron overload. The purpose of this review is to summarize what we have learnt about iron overload-associated bone loss from clinical studies and animal models. Bone is a metabolically active tissue that undergoes continuous remodeling with the involvement of osteoclasts that resorb mineralized bone, and osteoblasts that form new bone. Growing evidence suggests that both increased bone resorption and decreased bone formation are involved in the pathological bone-loss in iron overload conditions. We will discuss the cellular and molecular mechanisms that are involved in this detrimental process. Fuller understanding of this complex mechanism may lead to the development of improved therapeutics meant to interrupt the pathologic effects of excess iron on bone. PMID:28270766

  1. 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.

  2. Associations of genetic lactase non-persistence and sex with bone loss in young adulthood.

    Science.gov (United States)

    Laaksonen, Marika M L; Impivaara, Olli; Sievänen, Harri; Viikari, Jorma S A; Lehtimäki, Terho J; Lamberg-Allardt, Christel J E; Kärkkäinen, Merja U M; Välimäki, Matti; Heikkinen, Jorma; Kröger, Liisa M; Kröger, Heikki P J; Jurvelin, Jukka S; Kähönen, Mika A P; Raitakari, Olli T

    2009-05-01

    Some studies have reported that after attainment of peak bone mass (PBM), slow bone loss may occur in both men and women; however, findings are inconsistent. Genetic factors play a significant role in bone loss, but the available evidence is conflicting. Genetic lactase non-persistence (lactase C/C(-13910) genotype) is suggested to increase risk for inadequate calcium intake predisposing to poorer bone health. We investigated whether this genotype is associated with PBM and bone loss in young Finnish adults. Subjects belong to the Cardiovascular Risk in Young Finns Study that is an ongoing multi-centre follow-up of atherosclerosis risk factors. From the original cohort, randomly selected subjects aged 20-29 participated in baseline bone mineral density (BMD) measurements (n=358), and in follow-up measurements 12 years later (n=157). Bone mineral content (BMC) and BMD at lumbar spine (LS) and femoral neck (FN) were measured at baseline and follow-up with dual energy X-ray absorptiometry (DXA). Lactase C/T(-13910) polymorphism was determined by PCR and allele-specific fluorogenic probes. Information on lifestyle was elicited with questionnaires. During the follow-up, bone loss at both bone sites was greater in males (LS BMD: -1.1%, FN BMD: -5.2%) than in females (LS BMD: +2.1%, FN BMD: -0.7%) (both bone sites p=0.001). Younger age predicted greater loss of FN BMC and BMD in females (p=0.013 and p=0.001, respectively). Increased calcium intake predicted FN BMD gain in both sexes (in females B=0.007 g/cm(2)/mg, p=0.002; in males B=0.006, p=0.045), and increased physical activity LS BMD gain in females (B=0.091 g/cm(2)/physical activity point, p=0.023). PBM did not differ between the lactase genotypes, but males with the CC(-13910) genotype seemed to be prone to greater bone loss during the follow-up (LS BMD: C/C vs. T/T p=0.081). In conclusion, bone loss in young adulthood was more common in males than in females and seemed to occur mainly at the femoral neck. Young

  3. Inflammation, bone loss and fracture risk in spondyloarthritis

    Science.gov (United States)

    Briot, Karine; Roux, Christian

    2015-01-01

    Osteoporosis (ie, low bone mineral density) is common in ankylosing spondylitis, related to both systemic inflammation and decreased mobility. Vertebral fracture risk is increased; acute back pain in these patients is not always a flare-up of the disease, as it can be related to bone complications. Intervertebral disc fractures in the ankylosed spine are associated with severe neurological complications. As expected from pathophysiology, treatments effective against inflammation have a positive effect on bone, and prospective open studies have shown that tumour-necrosis-factor blockers can improve bone mineral density at the spine and the hip. There is so far no evidence of a decreased risk of fractures with such treatment. PMID:26509065

  4. Prevention of alveolar bone loss in an osteoporotic animal model via interference of semaphorin 4d.

    Science.gov (United States)

    Zhang, Y; Wei, L; Miron, R J; Zhang, Q; Bian, Z

    2014-11-01

    Semaphorin 4d (Sema4d) has been proposed as a novel target gene for the treatment of osteoporosis. Recently, we fabricated a site-specific bone-targeting system from polymeric nanoparticles that demonstrates an ability to prevent bone loss in an osteoporotic model by interfering with Sema4d gene expression using small interference RNA (siRNA) molecules. The aim of the present investigation was to determine the effects of this targeting system on the periodontium, an area of high bone turnover. We demonstrated, by single photon emission computed tomography, that intravenous injection of this molecule in ovariectomized Balb/C mice is able to target alveolar bone peaking 4 hr post-injection. We then compared, by histological analysis, the bone volume/total volume (BV/TV), alveolar bone height loss, immunohistochemical expression of Sema4d, and total number of osteoclasts in mandibular alveolar bone. Four treatment modalities were compared as follows: (1) sham-operated, (2) OVX-operated, (3) OVX+estrogen replacement therapy, and (4) OVX+siRNA-Sema4d animals. The results from the present study demonstrate that an osteoporotic condition significantly increases alveolar bone height loss, and that the therapeutic effects via bone-targeting systems featuring interference of Sema4d are able to partly counteract alveolar bone loss caused by osteoporosis. While the future therapeutic demand for the large number of patients suffering from osteoporosis faces many challenges, we demonstrate within the present study an effective drug-delivery moiety with anabolic effects on the bone remodeling cycle able to locate and target alveolar bone regeneration.

  5. 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.

  6. 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.

  7. 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.

  8. Disruption of PTH Receptor 1 in T Cells Protects against PTH-Induced Bone Loss

    Science.gov (United States)

    Tawfeek, Hesham; Bedi, Brahmchetna; Li, Jau-Yi; Adams, Jonathan; Kobayashi, Tatsuya; Weitzmann, M. Neale; Kronenberg, Henry M.; Pacifici, Roberto

    2010-01-01

    Background Hyperparathyroidism in humans and continuous parathyroid hormone (cPTH) treatment in mice cause bone loss by regulating the production of RANKL and OPG by stromal cells (SCs) and osteoblasts (OBs). Recently, it has been reported that T cells are required for cPTH to induce bone loss as the binding of the T cell costimulatory molecule CD40L to SC receptor CD40 augments SC sensitivity to cPTH. However it is unknown whether direct PTH stimulation of T cells is required for cPTH to induce bone loss, and whether T cells contribute to the bone catabolic activity of PTH with mechanisms other than induction of CD40 signaling in SCs. Methodology/Principal Findings Here we show that silencing of PTH receptor 1 (PPR) in T cells blocks the bone loss and the osteoclastic expansion induced by cPTH, thus demonstrating that PPR signaling in T cells is central for PTH-induced reduction of bone mass. Mechanistic studies revealed that PTH activation of the T cell PPR stimulates T cell production of the osteoclastogenic cytokine tumor necrosis factor α (TNF). Attesting to the relevance of this effect, disruption of T cell TNF production prevents PTH-induced bone loss. We also show that a novel mechanism by which TNF mediates PTH induced osteoclast formation is upregulation of CD40 expression in SCs, which increases their RANKL/OPG production ratio. Conclusions/Significance These findings demonstrate that PPR signaling in T cells plays an essential role in PTH induced bone loss by promoting T cell production of TNF. A previously unknown effect of TNF is to increase SC expression of CD40, which in turn increases SC osteoclastogenic activity by upregulating their RANKL/OPG production ratio. PPR-dependent stimulation of TNF production by T cells and the resulting TNF regulation of CD40 signaling in SCs are potential new therapeutic targets for the bone loss of hyperparathyroidism. PMID:20808842

  9. Disruption of PTH receptor 1 in T cells protects against PTH-induced bone loss.

    Directory of Open Access Journals (Sweden)

    Hesham Tawfeek

    Full Text Available BACKGROUND: Hyperparathyroidism in humans and continuous parathyroid hormone (cPTH treatment in mice cause bone loss by regulating the production of RANKL and OPG by stromal cells (SCs and osteoblasts (OBs. Recently, it has been reported that T cells are required for cPTH to induce bone loss as the binding of the T cell costimulatory molecule CD40L to SC receptor CD40 augments SC sensitivity to cPTH. However it is unknown whether direct PTH stimulation of T cells is required for cPTH to induce bone loss, and whether T cells contribute to the bone catabolic activity of PTH with mechanisms other than induction of CD40 signaling in SCs. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that silencing of PTH receptor 1 (PPR in T cells blocks the bone loss and the osteoclastic expansion induced by cPTH, thus demonstrating that PPR signaling in T cells is central for PTH-induced reduction of bone mass. Mechanistic studies revealed that PTH activation of the T cell PPR stimulates T cell production of the osteoclastogenic cytokine tumor necrosis factor alpha (TNF. Attesting to the relevance of this effect, disruption of T cell TNF production prevents PTH-induced bone loss. We also show that a novel mechanism by which TNF mediates PTH induced osteoclast formation is upregulation of CD40 expression in SCs, which increases their RANKL/OPG production ratio. CONCLUSIONS/SIGNIFICANCE: These findings demonstrate that PPR signaling in T cells plays an essential role in PTH induced bone loss by promoting T cell production of TNF. A previously unknown effect of TNF is to increase SC expression of CD40, which in turn increases SC osteoclastogenic activity by upregulating their RANKL/OPG production ratio. PPR-dependent stimulation of TNF production by T cells and the resulting TNF regulation of CD40 signaling in SCs are potential new therapeutic targets for the bone loss of hyperparathyroidism.

  10. 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.

  11. 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

  12. Antiresorptive therapy in the management of cancer treatment-induced bone loss.

    Science.gov (United States)

    Garg, Ashwani; Leitzel, Kim; Ali, Suhail; Lipton, Allan

    2015-04-01

    Cancer treatment-induced bone loss treatment has an important role to prevent bone loss-related events like fracture, significant morbidity, mortality, disfigurement and loss of self-esteem, and health-care expenditure. Numerous factors, including treatment regimens and bone metastasis, increase the risk of osteoporosis or local bone destruction in most breast and prostate cancer patients. Cytotoxic chemotherapies, radiation, and hormonal therapies can lead to premature menopause and decrease bone mineral density. Over 60 % of breast cancer patients within 1 year of beginning postoperative adjuvant chemotherapy experience ovarian failure. Also, ovarian ablation and aromatase inhibitors used to treat breast cancer and orchiectomy and androgen deprivation therapy (ADT; to treat prostate cancer) cause substantial bone loss. In this article, we will focus mainly on antiresorptive therapy in the management of cancer treatment-induced bone loss (CTIBL). An understanding of CTIBL is critical for determining how to assess the risk and identify which patients may benefit from preventive therapy.

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

    OpenAIRE

    Ramesh, Aruna; Soroushian, Sheila; Ganguly, Rumpa

    2013-01-01

    Purpose 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. Materials and Methods 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 as...

  14. Risk factors for longitudinal bone loss in elderly men and women: the Framingham Osteoporosis Study.

    Science.gov (United States)

    Hannan, M T; Felson, D T; Dawson-Hughes, B; Tucker, K L; Cupples, L A; Wilson, P W; Kiel, D P

    2000-04-01

    Few studies have evaluated risk factors for bone loss in elderly women and men. Thus, we examined risk factors for 4-year longitudinal change in bone mineral density (BMD) at the hip, radius, and spine in elders. Eight hundred elderly women and men from the population-based Framingham Osteoporosis Study had BMD assessed in 1988-1989 and again in 1992-1993. BMD was measured at femoral neck, trochanter, Ward's area, radial shaft, ultradistal radius, and lumbar spine using Lunar densitometers. We examined the relation of the following factors at baseline to percent BMD loss: age, weight, change in weight, height, smoking, caffeine, alcohol use, physical activity, serum 25-OH vitamin D, calcium intake, and current estrogen replacement in women. Multivariate regression analyses were conducted with simultaneous adjustment for all variables. Mean age at baseline was 74 years +/-4.5 years (range, 67-90 years). Average 4-year BMD loss for women (range, 3.4-4.8%) was greater than the loss for men (range, 0.2-3.6%) at all sites; however, BMD fell with age in both elderly women and elderly men. For women, lower baseline weight, weight loss in interim, and greater alcohol use were associated with BMD loss. Women who gained weight during the interim gained BMD or had little change in BMD. For women, current estrogen users had less bone loss than nonusers; at the femoral neck, nonusers lost up to 2.7% more BMD. For men, lower baseline weight and weight loss also were associated with BMD loss. Men who smoked cigarettes at baseline lost more BMD at the trochanter site. Surprisingly, bone loss was not affected by caffeine, physical activity, serum 25-OH vitamin D, or calcium intake. Risk factors consistently associated with bone loss in elders include female sex, thinness, and weight loss, while weight gain appears to protect against bone loss for both men and women. This population-based study suggests that current estrogen use may help to maintain bone in women, whereas current

  15. 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.

  16. Inhibition of Bone Loss by Cissus quadrangularis in Mice: A Preliminary Report

    Directory of Open Access Journals (Sweden)

    Jameela Banu

    2012-01-01

    Full Text Available Women drastically loose bone during and after menopause leading to osteoporosis, a disease characterized by low bone mass increasing the risk of fractures with minor trauma. Existing therapies mainly reduce bone resorption, however, all existing drugs have severe side effects. Recently, the focus is to identify alternative medicines that can prevent and treat osteoporosis with minimal or no side effects. We used Cissus quadrangularis (CQ, a medicinal herb, to determine its effects on bone loss after ovariectomy in C57BL/6 mice. Two-month old mice were either sham operated or ovariectomized and fed CQ diet. After eleven weeks, mice were sacrificed and the long bones scanned using pQCT and μCT. In the distal femoral metaphysis, femoral diaphysis, and proximal tibia, control mice had decreased cancellous and cortical bone, while CQ-fed mice showed no significant differences in the trabecular number, thickness, and connectivity density, between Sham and OVX mice, except for cortical bone mineral content in the proximal tibia. There were no changes in the bone at the tibio-fibular junction between groups. We conclude that CQ effectively inhibited bone loss in the cancellous and cortical bones of femur and proximal tibia in these mice.

  17. 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

  18. 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

    A remarkable property of bone remodeling is that osteoblasts form bone matrix exactly where and when osteoclasts have removed it. The bone remodeling compartment (BRC) canopies that cover bone surfaces undergoing remodeling, were proposed to be critical players in this mechanism. Here, we provide...... 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...

  19. 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...

  20. Diet-Induced Obesity and Its Differential Impact on Periodontal Bone Loss.

    Science.gov (United States)

    Muluke, M; Gold, T; Kiefhaber, K; Al-Sahli, A; Celenti, R; Jiang, H; Cremers, S; Van Dyke, T; Schulze-Späte, U

    2016-02-01

    Obesity is associated with abnormal lipid metabolism and impaired bone homeostasis. The aim of our study was to investigate the impact of specific elevated fatty acid (FA) levels on alveolar bone loss in a Porphyromonas gingivalis-induced model of periodontal disease and to analyze underlying cellular mechanisms in bone-resorbing osteoclasts and bone-forming osteoblasts in mice. Four-week-old male C57BL/6 mice were randomly divided in groups and subjected to a palmitic acid (PA)- or oleic acid (OA)-enriched high-fat diet (HFD) (20% of calories from FA) or a normal caloric diet (C group) (10% of calories from FA) for 16 wk. Starting at week 10, mice were infected orally with P. gingivalis (W50) or placebo to induce alveolar bone loss. Animals were sacrificed, and percentage fat, serum inflammation (tumor necrosis factor [TNF]-α), and bone metabolism (osteocalcin [OC], carboxy-terminal collagen crosslinks [CTX], and N-terminal propeptides of type I procollagen [P1NP]) markers were measured. Osteoblasts and osteoclasts were cultured in the presence of elevated PA or OA levels and exposed to P. gingivalis. Animals on FA-enriched diets weighed significantly more compared with animals on a normal caloric diet (P diet rather than weight gain and obesity alone modulates bone metabolism and can therefore influence alveolar bone loss.

  1. Spaceflight-induced Bone Loss: Is there a Risk for Accelerated Osteoporosis after Return?

    Science.gov (United States)

    Sibonga, Jean

    2008-01-01

    The evidence-to to-date suggests that the rapid rate of site-specific bone loss in space, due to the unbalanced stimulation of bone resorption, may predispose crew members to irreversible changes in bone structure and microarchitecture. No analyses conducted in the postflight period to assess microarchitectural changes. There is no complete analysis of skeletal recovery in the postflight period to evaluate the structural changes that accompany increases in DXA aBMD. Postflight analyses based upon QCT scans performed on limited crew members indicate reductions in hip bone strength and incomplete recovery at 1 year. No recovery of trabecular vBMD after 1 year return (HRP IWG). Time course of bone loss in space unknown.

  2. Primary Hyperparathyroidism: The Influence of Bone Marrow Adipose Tissue on Bone Loss and of Osteocalcin on Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Maira L. Mendonça

    Full Text Available OBJECTIVES: Bone marrow adipose tissue has been associated with low bone mineral density. However, no data exist regarding marrow adipose tissue in primary hyperparathyroidism, a disorder associated with bone loss in conditions of high bone turnover. The objective of the present study was to investigate the relationship between marrow adipose tissue, bone mass and parathyroid hormone. The influence of osteocalcin on the homeostasis model assessment of insulin resistance was also evaluated. METHODS: This was a cross-sectional study conducted at a university hospital, involving 18 patients with primary hyperparathyroidism (PHPT and 21 controls (CG. Bone mass was assessed by dual-energy x-ray absorptiometry and marrow adipose tissue was assessed by 1H magnetic resonance spectroscopy. The biochemical evaluation included the determination of parathyroid hormone, osteocalcin, glucose and insulin levels. RESULTS: A negative association was found between the bone mass at the 1/3 radius and parathyroid hormone levels (r = -0.69; p<0.01. Marrow adipose tissue was not significantly increased in patients (CG = 32.8±11.2% vs PHPT = 38.6±12%. The serum levels of osteocalcin were higher in patients (CG = 8.6±3.6 ng/mL vs PHPT = 36.5±38.4 ng/mL; p<0.005, but no associations were observed between osteocalcin and insulin or between insulin and both marrow adipose tissue and bone mass. CONCLUSION: These results suggest that the increment of adipogenesis in the bone marrow microenvironment under conditions of high bone turnover due to primary hyperparathyroidism is limited. Despite the increased serum levels of osteocalcin due to primary hyperparathyroidism, these patients tend to have impaired insulin sensitivity.

  3. Biochemical markers of bone turnover, hip bone loss, and fracture in older men: the MrOS study.

    Science.gov (United States)

    Bauer, Douglas C; Garnero, Patrick; Harrison, Stephanie L; Cauley, Jane A; Eastell, Richard; Ensrud, Kris E; Orwoll, Eric

    2009-12-01

    We used data from the Osteoporotic Fractures in Men (MrOS) study to test the hypothesis that men with higher levels of bone turnover would have accelerated bone loss and an elevated risk of fracture. MrOS enrolled 5995 subjects >65 yr; hip BMD was measured at baseline and after a mean follow-up of 4.6 yr. Nonspine fractures were documented during a mean follow-up of 5.0 yr. Using fasting serum collected at baseline and stored at -190 degrees C, bone turnover measurements (type I collagen N-propeptide [PINP]; beta C-terminal cross-linked telopeptide of type I collagen [betaCTX]; and TRACP5b) were obtained on 384 men with nonspine fracture (including 72 hip fractures) and 947 men selected at random. Among randomly selected men, total hip bone loss was 0.5%/yr among those in the highest quartile of PINP (>44.3 ng/ml) and 0.3%/yr among those in the lower three quartiles (p = 0.01). Fracture risk was elevated among men in the highest quartile of PINP (hip fracture relative hazard = 2.13; 95% CI: 1.23, 3.68; nonspine relative hazard = 1.57, 95% CI: 1.21, 2.05) or betaCTX (hip fracture relative hazard = 1.76, 95 CI: 1.04, 2.98; nonspine relative hazard = 1.29, 95% CI: 0.99, 1.69) but not TRACP5b. Further adjustment for baseline hip BMD eliminated all associations between bone turnover and fracture. We conclude that higher levels of bone turnover are associated with greater hip bone loss in older men, but increased turnover is not independently associated with the risk of hip or nonspine fracture.

  4. 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.

  5. 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.

  6. A Losing Battle: Weight Regain Does Not Restore Weight Loss-Induced Bone Loss in Postmenopausal Women

    Science.gov (United States)

    Villalon, Karen L.; Gozansky, Wendolyn S.; Van Pelt, Rachael E.; Wolfe, Pam; Jankowski, Catherine M.; Schwartz, Robert S.; Kohrt, Wendy M.

    2013-01-01

    Previously, we reported significant bone mineral density (BMD) loss in postmenopausal women after modest weight loss. It remains unclear whether the magnitude of BMD change in response to weight loss is appropriate (i.e., proportional to weight loss) and whether BMD is recovered with weight regain. We now report changes in BMD after a 1-year follow-up. Subjects (n = 23) in this secondary analysis were postmenopausal women randomized to placebo as part of a larger trial. They completed a 6-month exercise-based weight loss program and returned for follow-up at 18 months. Dual-energy X-ray absorptiometry (DXA) was performed at baseline, 6, and 18 months. At baseline, subjects were aged 56.8 ± 5.4 years (mean ± s.d.), 10.0 ± 9.2 years postmenopausal, and BMI was 29.6 ± 4.0 kg/m2. They lost 3.9 ± 3.5 kg during the weight loss intervention. During follow-up, they regained 2.9 ± 3.9 kg. Six months of weight loss resulted in a significant decrease in lumbar spine (LS) (−1.7 ± 3.5%; P = 0.002) and hip (−0.04 ± 3.5%; P = 0.03) BMD that was accompanied by an increase in a biomarker of bone resorption (serum C-terminal telopeptide of type I collagen, CTX: 34 ± 54%; P = 0.08). However, weight regain was not associated with LS (0.05 ± 3.8%; P = 0.15) or hip (−0.6 ± 3.0%; P = 0.81) bone regain or decreased bone resorption (CTX: −3 ± 37%; P = 0.73). The findings suggest that BMD lost during weight reduction may not be fully recovered with weight regain in hormone-deficient, postmenopausal women. Future studies are needed to identify effective strategies to prevent bone loss during periods of weight loss. PMID:21852813

  7. 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.

  8. Two Different Isomers of Vitamin E Prevent Bone Loss in Postmenopausal Osteoporosis Rat Model

    Directory of Open Access Journals (Sweden)

    Norliza Muhammad

    2012-01-01

    Full Text Available Postmenopausal osteoporotic bone loss occurs mainly due to cessation of ovarian function, a condition associated with increased free radicals. Vitamin E, a lipid-soluble vitamin, is a potent antioxidant which can scavenge free radicals in the body. In this study, we investigated the effects of alpha-tocopherol and pure tocotrienol on bone microarchitecture and cellular parameters in ovariectomized rats. Three-month-old female Wistar rats were randomly divided into ovariectomized control, sham-operated, and ovariectomized rats treated with either alpha-tocopherol or tocotrienol. Their femurs were taken at the end of the four-week study period for bone histomorphometric analysis. Ovariectomy causes bone loss in the control group as shown by reduction in both trabecular volume (BV/TV and trabecular number (Tb.N and an increase in trabecular separation (Tb.S. The increase in osteoclast surface (Oc.S and osteoblast surface (Ob.S in ovariectomy indicates an increase in bone turnover rate. Treatment with either alpha-tocopherol or tocotrienol prevents the reduction in BV/TV and Tb.N as well as the increase in Tb.S, while reducing the Oc.S and increasing the Ob.S. In conclusion, the two forms of vitamin E were able to prevent bone loss due to ovariectomy. Both tocotrienol and alpha-tocopherol exert similar effects in preserving bone microarchitecture in estrogen-deficient rat model.

  9. 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.

  10. 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.

  11. 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.

  12. Preventing bone loss and weight gain with combinations of vitamin D and phytochemicals.

    Science.gov (United States)

    Lai, Ching-Yi; Yang, Jeong-Yeh; Rayalam, Srujana; Della-Fera, Mary Anne; Ambati, Suresh; Lewis, Richard D; Hamrick, Mark W; Hartzell, Diane L; Baile, Clifton A

    2011-11-01

    Vitamin D and certain natural compounds have been shown to regulate both lipid metabolism and bone formation. Treatments that prevent or reverse age-related increase in bone marrow adiposity could both increase new bone formation and inhibit bone destruction. We tested the hypothesis that dietary supplementation with combinations of vitamin D and phytochemicals inhibits bone loss and decreases adiposity to a greater extent than control or vitamin D-alone diets. Aged ovariectomized female rats (12 months old, n=50, initial body weight=240 g) were given control (AIN-93M diet), vitamin D (2,400 IU/kg), or vitamin D plus resveratrol (16, 80, or 400 mg/kg of diet [low, medium, and high dose, respectively]), quercetin (80, 400, or 2,000 mg/kg of diet), and genistein (64, 256, or 1,040 mg/kg of diet) for 8 weeks. The high-dose treatment (vitamin D+400 mg/kg resveratrol+2,000 mg/kg quercetin+1,040 mg/kg genistein) reduced body weight gain (P<.05) and the fat pad weights (P<.05). This treatment also increased the serum concentration of insulin-like growth factor-1 (P<.05) and the bone mineral content of the femur. Micro-computed tomography and histomorphometric analyses indicated that the high-dose treatment prevented loss of trabecular bone (P<.05) and reduced marrow adipocytes (P<.001) and osteoclasts (P<.05) compared with the control and vitamin D alone (P<.05). We conclude that aged ovariectomized female rats supplemented with vitamin D combined with genistein, quercetin, and resveratrol had improved bone mineral density and reduced body weight gain and a significant decrease in bone marrow adipocytes. The synergistic effects of a combination of phytochemicals with vitamin D may be effective in reducing bone loss and weight gain after menopause.

  13. Protective Effects of Vildagliptin against Pioglitazone-Induced Bone Loss in Type 2 Diabetic Rats

    Science.gov (United States)

    Kwak, Kyung Min; Kim, Ju-Young; Yu, Seung Hee; Lee, Sihoon; Kim, Yeun Sun; Park, Ie Byung; Kim, Kwang-Won; Lee, Kiyoung

    2016-01-01

    Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model. We randomly divided 12-week-old male Zucker Diabetic Fatty (ZDF) rats into four groups; control, vildagliptin, pioglitazone, and vildagliptin and pioglitazone combination. Animals in each group received the respective treatments for 5 weeks. We performed an intraperitoneal glucose tolerance test (IPGTT) before and after treatment. BMD and the trabecular micro-architecture were measured by DEXA and micro CT, respectively, at the end of the treatment. The circulating levels of active GLP-1, bone turnover markers, and sclerostin were assayed. Vildagliptin treatment significantly increased BMD and trabecular bone volume. The combination therapy restored BMD, trabecular bone volume, and trabecular bone thickness that were decreased by pioglitazone. The levels of the bone formation marker, osteocalcin, decreased and that of the bone resorption marker, tartrate-resistant acid phosphatase (TRAP) 5b increased in the pioglitazone group. These biomarkers were ameliorated and the pioglitazone-induced increase in sclerostin level was lowered to control values by the addition of vildagliptin. In conclusion, our results indicate that orally administered vildagliptin demonstrated a protective effect on pioglitazone-induced bone loss in a type 2 diabetic rat model. PMID:27997588

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

    Science.gov (United States)

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

    2014-01-01

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

  15. Age-related bone loss in the LOU/c rat model of healthy ageing.

    Science.gov (United States)

    Duque, Gustavo; Rivas, Daniel; Li, Wei; Li, Ailian; Henderson, Janet E; Ferland, Guylaine; Gaudreau, Pierrette

    2009-03-01

    Inbred albino Louvain (LOU) rats are considered a model of healthy aging due to their increased longevity in the absence of obesity and with a low incidence of common age-related diseases. In this study, we characterized the bone phenotype of male and female LOU rats at 4, 20 and 27 months of age using quantitative micro computed tomographic (mCT) imaging, histology and biochemical analysis of circulating bone biomarkers. Bone quality and morphometry of the distal femora, assessed by mCT, was similar in male and female rats at 4 months of age and deteriorated over time. Histochemical staining of undecalcified bone showed a significant reduction in cortical and trabecular bone by 20 months of age. The reduction in mineralized tissue was accompanied by reduced numbers of osteoblasts and osteoclasts and a significant increase in marrow adiposity. Biochemical markers of bone turnover, C-telopeptide and osteocalcin, correlated with the age-related bone loss whereas the calciotropic hormones PTH and vitamin D remained unchanged over time. In summary, aged LOU rats exhibit low-turnover bone loss and marrow fat infiltration, which are the hallmarks of senile osteoporosis, and thus represent a novel model in which to study the molecular mechanisms leading to this disorder.

  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. P2Y1 purinoceptor inhibition reduces extracellular signal-regulated protein kinase 1/2 phosphorylation in spinal cord and dorsal root ganglia: implications for cancer-induced bone pain

    Institute of Scientific and Technical Information of China (English)

    Jun Chen; Lina Wang; Yanbing Zhang; Jianping Yang

    2012-01-01

    It remains unclear as to whether P2Y1 purinergic receptor (P2Y1R) and the molecules that act downstream,such as extracellular signal-regulated protein kinase 1/2 (ERK1/2),are involved in the development of cancer-induced bone pain (CIBP) in vivo.Here,we investigated the role of the P2Y1R in the modulation of CIBP-associated nociception in spinal cord and dorsal root ganglia (DRG).A CIBP model was established by inoculating Walker 256 gland carcinoma cells into the tibia of female rats.Tactile ailodynia and spontaneous pain were assessed using von Frey filaments and ambulatory scores.The results showed that both the paw withdrawal latency to tactile allodynia and the ambulatory score to spontaneous pain were significantly different between the CIBP group and the sham group on days 7-9 post-inoculation (P < 0.01).Furthermore,rats in the CIBP group also showed a progressive increase in ambulatory score,which is different from the sham group (P<0.01).Furthermore,P2Y1R mRNA and phosphory lated ERK1/2 (p-ERK1/2) protein expression levels were increased in the spinal dorsal horn and DRG of the CIBP group relative to the sham group.However,intrathecal injection of the P2Y1R antagonist MRS2179 decreased P2Y1R mRNA and p-ERK1/2 protein expression in the spinal dorsal horn and DRG (P<0.01).These results provide evidence that the inhibition of P2Y1R-mediated ERK1/2 phosphorylation in the spinal dorsal horn and DRG can attenuate nociception transmission.

  18. 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.)

  19. Fusobacterium nucleatum and Tannerella forsythia induce synergistic alveolar bone loss in a mouse periodontitis model.

    Science.gov (United States)

    Settem, Rajendra P; El-Hassan, Ahmed Taher; Honma, Kiyonobu; Stafford, Graham P; Sharma, Ashu

    2012-07-01

    Tannerella forsythia is strongly associated with chronic periodontitis, an inflammatory disease of the tooth-supporting tissues, leading to tooth loss. Fusobacterium nucleatum, an opportunistic pathogen, is thought to promote dental plaque formation by serving as a bridge bacterium between early- and late-colonizing species of the oral cavity. Previous studies have shown that F. nucleatum species synergize with T. forsythia during biofilm formation and pathogenesis. In the present study, we showed that coinfection of F. nucleatum and T. forsythia is more potent than infection with either species alone in inducing NF-κB activity and proinflammatory cytokine secretion in monocytic cells and primary murine macrophages. Moreover, in a murine model of periodontitis, mixed infection with the two species induces synergistic alveolar bone loss, characterized by bone loss which is greater than the additive alveolar bone losses induced by each species alone. Further, in comparison to the single-species infection, mixed infection caused significantly increased inflammatory cell infiltration in the gingivae and osteoclastic activity in the jaw bones. These data show that F. nucleatum subspecies and T. forsythia synergistically stimulate the host immune response and induce alveolar bone loss in a murine experimental periodontitis model.

  20. Association of testosterone and bone mineral density with tooth loss in men with chronic periodontitis.

    Science.gov (United States)

    Singh, Balendra P; Makker, Annu; Tripathi, Arvind; Singh, Man M; Gupta, Vivek

    2011-09-01

    A study was conducted to compare the mean testosterone and bone mineral density (BMD) levels in men with and without tooth loss. Two hundred three male subjects aged 30-65 years satisfying the study criteria were selected and then examined for bone mineral density, testosterone level, clinical attachment loss, probing pocket depth, tooth mobility and tooth loss due to periodontal disease. Statistical analysis was performed using the Statistical Package for Social Sciences (version 15.0) (SPSS Inc., Chicago, Ill, USA), and differences were considered to be significant at P < 0.05. Independent sample "t" test was used to compare the results, and receiver-operator curve (ROC) analysis was performed to obtain the cut-off. The mean testosterone level in subjects without tooth loss was 4.41 ± 2.57, whereas that in subjects with tooth loss was 2.79 ± 1.15 (P = 0.001). The mean BMD in subjects without tooth loss was 0.99 ± 0.13, whereas that in subjects with tooth loss was 0.96 ± 0.12 (P = 0.046). The testosterone level and BMD in subjects with tooth loss were significantly lower than those in subjects without tooth loss. Testosterone is a good predictor of tooth loss, but its efficiency decreases with increasing tooth loss. BMD is not a good predictor of tooth loss.

  1. Subchondral bone loss following orthodontically induced cartilage degradation in the mandibular condyles of rats.

    Science.gov (United States)

    Jiao, Kai; Niu, Li-Na; Wang, Mei-Qing; Dai, Juan; Yu, Shi-Bin; Liu, Xiao-Dong; Wang, Jun

    2011-02-01

    Osteoarthritis (OA) is a degenerative joint disease generally characterized by progressive cartilage degradation and subchondral bone changes. Subchondral bone changes have been proposed to initiate or accompany with cartilage degradation in OA. The purpose of this study was to characterize cartilage damage, subchondral bone remodeling, and the possible mechanism involved in these morphological changes in our reported rat model with OA-like lesions in the mandibular condyle. In experimental groups, the dental occlusion was orthodontically disturbed. By histological analysis, transmission electron microscopy (TEM), micro-CT scanning and serum tests, changes in condylar cartilage and subchondral bone were analyzed at 8 and 12 weeks after treatment. The mRNA and protein levels of bone pro-resorptive and pro-formative factors by chondrocytes were investigated. Increased degraded cartilage areas and obvious cartilage calcification were observed in 8- and 12-week treated (EXP) groups compared to the age-matched controls. Subchondral bone loss, characterized as decreased bone mineral density (BMD), bone volume fraction (BV/TV) and trabecular thickness (Tb.Th), but increased trabecular separation (Tb.Sp), was observed in the 12-week but not the 8-week EXP group, respectively, versus their age-matched controls. The subchondral bone loss in the 12-week EXP group was accompanied with decreased new bone formation rate, but increased serum carboxy terminal telopeptides (CTXs), and increased osteoclast numbers and proportion of surface area in the subchondral bone regions. Increased mRNA and protein levels of M-CSF, VEGF, RUNX and RANKL/OPG ratio, but decreased OPG, were found in condylar cartilage in the 12-week EXP group versus its age-matched controls, and those of RANKL/OPG ratios were significantly higher in the 12-week EXP group than the 8-week EXP. In addition, increased mRNA levels of VEGF, RUNX and RANKL/OPG ratio, but decreased OPG, were also found in condylar

  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.

  3. Computational Analysis of Artificial Gravity as a Possible Countermeasure to Spaceflight Induced Bone Loss

    Science.gov (United States)

    Mulugeta, L.; Werner, C. R.; Pennline, J. A.

    2015-01-01

    During exploration class missions, such as to asteroids and Mars, astronauts will be exposed to reduced gravity for extended periods. Data has shown that astronauts lose bone mass at a rate of 1% to 2% a month in microgravity, particularly in lower extremities such as the proximal femur. Exercise countermeasures have not completely eliminated bone loss from long duration spaceflight missions, which leaves astronauts susceptible to early onset osteoporosis and greater risk of fracture. Introduction of the Advanced Resistive Exercise Device and other large exercise devices on the International Space Station (ISS), coupled with improved nutrition, has further minimized bone loss. However, unlike the ISS, exploration vehicles will have very limited volume and power available to accommodate such capabilities. Therefore, novel concepts like artificial gravity systems are being explored as a means to provide sufficient load stimulus to the musculoskeletal system to mitigate bone changes that may lead to early onset osteoporosis and increased risk of fracture. Currently, there is minimal data available to drive further research and development efforts to appropriately explore such options. Computational modeling can be leveraged to gain insight on the level of osteoprotection that may be achieved using artificial gravity produced by a spinning spacecraft or centrifuge. With this in mind, NASA's Digital Astronaut Project (DAP) has developed a bone remodeling model that has been validated for predicting volumetric bone mineral density (vBMD) changes of trabecular and cortical bone both for gravitational unloading condition and the equivalent of 1g daily load stimulus. Using this model, it is possible to simulate vBMD changes in trabecular and cortical bone under different gravity conditions. In this presentation, we will discuss our preliminary findings regarding if and how artificial gravity may be used to mitigate spaceflight induced bone loss.

  4. Virgin Coconut Oil Supplementation Prevents Bone Loss in Osteoporosis Rat Model

    Directory of Open Access Journals (Sweden)

    Zil Hayatullina

    2012-01-01

    Full Text Available Oxidative stress and free radicals have been implicated in the pathogenesis of osteoporosis. Therefore, antioxidant compounds have the potential to be used in the prevention and treatment of the disease. In this study, we investigated the effects of virgin coconut oil (VCO on bone microarchitecture in a postmenopausal osteoporosis rat model. VCO is a different form of coconut oil as it is rich with antioxidants. Three-month-old female rats were randomly grouped into baseline, sham-operated, ovariectomized control (Ovx, and ovariectomized rats fed with 8% VCO in their diet for six weeks (Ovx+VCO. Bone histomorphometry of the right femora was carried out at the end of the study. Rats supplemented with VCO had a significantly greater bone volume and trabecular number while trabecular separation was lower than the Ovx group. In conclusion, VCO was effective in maintaining bone structure and preventing bone loss in estrogen-deficient rat model.

  5. Virgin coconut oil supplementation prevents bone loss in osteoporosis rat model.

    Science.gov (United States)

    Hayatullina, Zil; Muhammad, Norliza; Mohamed, Norazlina; Soelaiman, Ima-Nirwana

    2012-01-01

    Oxidative stress and free radicals have been implicated in the pathogenesis of osteoporosis. Therefore, antioxidant compounds have the potential to be used in the prevention and treatment of the disease. In this study, we investigated the effects of virgin coconut oil (VCO) on bone microarchitecture in a postmenopausal osteoporosis rat model. VCO is a different form of coconut oil as it is rich with antioxidants. Three-month-old female rats were randomly grouped into baseline, sham-operated, ovariectomized control (Ovx), and ovariectomized rats fed with 8% VCO in their diet for six weeks (Ovx+VCO). Bone histomorphometry of the right femora was carried out at the end of the study. Rats supplemented with VCO had a significantly greater bone volume and trabecular number while trabecular separation was lower than the Ovx group. In conclusion, VCO was effective in maintaining bone structure and preventing bone loss in estrogen-deficient rat model.

  6. Management of humeral and glenoid bone loss in recurrent glenohumeral instability.

    Science.gov (United States)

    Mascarenhas, Randy; Rusen, Jamie; Saltzman, Bryan M; Leiter, Jeff; Chahal, Jaskarndip; Romeo, Anthony A; MacDonald, Peter

    2014-01-01

    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.

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    Atul F. Kamath

    2011-01-01

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

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

    Science.gov (United States)

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

    2009-01-01

    The purpose of this research is to determine whether anti-resorptive pharmaceuticals such as bisphosphonates, in conjunction with the routine in-flight exercise program, will protect ISS crewmembers from the regional decreases in bone mineral density and bone strength and the increased renal stone risk documented on previous long-duration space flights [1-3]. Losses averaged 1 to 2 percent per month in such regions as the lumbar spine and hip. Although losses showed significant heterogeneity among individuals and between bones within a given subject, space flight-induced bone loss was a consistent finding. More than 90 percent of astronauts and cosmonauts on long-duration flights (average 171 days) aboard Mir and the ISS, had a minimum 5 percent loss in at least one skeletal site, 40 percent of them had a 10 percent or greater loss in at least one skeletal site, and 22 percent of the Mir cosmonauts experienced a 15 to 20 percent loss in at least one site. These losses occurred even though the crewmembers performed time-consuming in-flight exercise regimens. Moreover, a recent study of 16 ISS astronauts using quantitative computed tomography (QCT) demonstrated trabecular bone losses from the hip averaging 2.3 percent per month [4]. These losses were accompanied by significant losses in hip bone strength that may not be recovered quickly [5]. This rapid loss of bone mass results from a combination of increased and uncoupled remodeling, as demonstrated by increased resorption with little or no change in bone formation markers [6-7]. This elevated remodeling rate likely affects the cortical and trabecular architecture and may lead to irreversible changes. In addition to bone loss, the resulting hypercalciuria increases renal stone risk. Therefore, it is logical to attempt to attenuate this increased remodeling with anti-resorption drugs such as bisphosphonates. Success with alendronate was demonstrated in a bed rest study [8]. This work has been extended to space

  10. Trabecular metal cup without augments for acetabular revision in case of extensive bone loss and low bone-prosthesis contact.

    Science.gov (United States)

    Pierannunzii, L; Mambretti, A; D'Imporzano, M

    2011-01-01

    Current evidences in revision hip arthroplasty suggest to treat severe acetabular bone loss with dedicated implants, such as anti-protrusio cages, stemmed cups, modular systems supplied with iliac flanges and obturatory hook. However recent literature is reporting satisfactory outcomes with simple elliptical Trabecular Metal cups. Purpose of the study was to evaluate mid-term results of such a surgical procedure. All hip revisions performed from 2008 to 2009 with implantation of a TMT multi-hole acetabular cup without augmentations were retrospectively reviewed. The cases with low-degree acetabular bone loss (stage I and II according to GIR classification), with surgical report poorly describing the bone defect, with inadequate pre- and post-operative x-rays were ruled out. Twenty-five cases were identified, but four were lost to follow-up. The twenty-one patients were 71 year-old on average (from 60 to 82), with stage IV bone loss in 6 cases and stage III bone loss in 15 cases. Mean interval from surgery to evaluation was 20.9 months (from 13 to 30). The evaluation included bone-prosthesis contact estimation, component position, survivorship, complications, final Harris Hip Score, presence of periprosthetic radiolucencies. Host bone-prosthesis contact was estimated to be about 35%. Only three implant were subsequently reoperated (for infection, early migration, recurrent dislocation). The HHS among non-reoperated 18 patients was 81.96 on average (from 63.44 to 95.82). Six cases showed thin radiolucencies in one of the three Charnley zones, while three cases showed radiolucencies in two. None of these images was evolutive, thus they were not considered signs of loosening. The mid-term results of this series confirm the hypothesis that a porous tantalum acetabular cup is an effective option to deal with difficult acetabular revisions. Although no extra-acetabular fixation device is available, the very high surface friction guaranteed by the material and the

  11. 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.

  12. 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...

  13. 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.

  14. Limb salvage after infected knee arthroplasty with bone loss and extensor mechanism deficiency using a modular segmental replacement system.

    Science.gov (United States)

    Namdari, Surena; Milby, Andrew H; Garino, Jonathan P

    2011-09-01

    Multiple total knee arthroplasty revisions pose significant surgical challenges, such as bone loss and soft tissue compromise. For patients with bone loss and extensor mechanism insufficiency after total knee arthroplasty, arthrodesis is a treatment option for the avoidance of amputation. However, arthrodesis is both difficult to achieve in situations with massive bone loss and potentially undesirable due to the dramatic shortening that follows. Although intramedullary nailing for knee arthrodesis has been widely reported, this technique has traditionally relied on the achievement of bony union. We report a case of a patient with massive segmental bone loss in which a modular intercalary prosthesis was used for arthrodesis to preserve limb length without bony union.

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

    Energy Technology Data Exchange (ETDEWEB)

    Yanagihara, G.R.; Paiva, A.G.; Gasparini, G.A.; Macedo, A.P. [Laboratório de Bioengenharia, Departamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Frighetto, P.D. [Instituto Federal de Educação, Ciência e Tecnologia de São Paulo, São Paulo, SP (Brazil); Volpon, J.B.; Shimano, A.C. [Laboratório de Bioengenharia, Departamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2016-02-02

    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 P<0.05. Regarding bone 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.

  16. 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.

  17. Lymphatic Endothelial Cells Produce M-CSF, Causing Massive Bone Loss in Mice.

    Science.gov (United States)

    Wang, Wensheng; Wang, Hua; Zhou, Xichao; Li, Xing; Sun, Wen; Dellinger, Michael; Boyce, Brendan F; Xing, Lianping

    2017-01-04

    Gorham-Stout disease (GSD) is a rare bone disorder characterized by aggressive osteolysis associated with lymphatic vessel invasion within bone marrow cavities. The etiology of GSD is not known, and there is no effective therapy or animal model for the disease. Here, we investigated if lymphatic endothelial cells (LECs) affect osteoclasts (OCs) to cause a GSD osteolytic phenotype in mice. We examined the effect of a mouse LEC line on osteoclastogenesis in co-cultures. LECs significantly increased receptor activator of NF-κB ligand (RANKL)-mediated OC formation and bone resorption. LECs expressed high levels of macrophage colony-stimulating factor (M-CSF), but not RANKL, interleukin-6 (IL-6), and tumor necrosis factor (TNF). LEC-mediated OC formation and bone resorption were blocked by an M-CSF neutralizing antibody or Ki20227, an inhibitor of the M-CSF receptor, c-Fms. We injected LECs into the tibias of wild-type (WT) mice and observed massive osteolysis on X-ray and micro-CT scans. Histology showed that LEC-injected tibias had significant trabecular and cortical bone loss and increased OC numbers. M-CSF protein levels were significantly higher in serum and bone marrow plasma of mice given intra-tibial LEC injections. Immunofluorescence staining showed extensive replacement of bone and marrow by podoplanin+ LECs. Treatment of LEC-injected mice with Ki20227 significantly decreased tibial bone destruction. In addition, lymphatic vessels in a GSD bone sample were stained positively for M-CSF. Thus, LECs cause bone destruction in vivo in mice by secreting M-CSF, which promotes OC formation and activation. Blocking M-CSF signaling may represent a new therapeutic approach for treatment of patients with GSD. Furthermore, tibial injection of LECs is a useful mouse model to study GSD. © 2017 American Society for Bone and Mineral Research.

  18. Tamoxifen in the rat prevents estrogen-deficiency bone loss elicited with the LHRH agonist buserelin.

    Science.gov (United States)

    Goulding, A; Gold, E; Feng, W

    1992-08-01

    In young women chronic use of luteinizing hormone releasing hormone (LHRH) agonists such as buserelin to treat endometriosis leads to estrogen-deficiency bone loss. Tamoxifen citrate is an estrogen agonist/antagonist which protects the skeleton from osteopenia when ovarian hormones are depleted. The present study was undertaken to determine whether tamoxifen citrate (20 mg/kg body wt/week s.c.) could prevent the osteopenic effect of buserelin (25 micrograms/kg body wt/day s.c.). Four groups of rats with 45Ca-labelled bones were studied for 4 weeks: group A--placebo controls; group B--buserelin; Group C--tamoxifen; group D--buserelin+tamoxifen. Bone resorption was monitored by measuring the urinary excretion of 45Ca and hydroxyproline. Interestingly buserelin lowered both blood 17 beta-estradiol values and uterine weights in the presence and absence of tamoxifen. However, tamoxifen slowed bone breakdown and inhibited the bone-thinning effects of buserelin. Total body calcium values (mg; means +/- S.D.) were: 2227 +/- 137; 1926 +/- 124; 2233 +/- 94 and 2268 +/- 163, in groups A to D respectively. Osteopenia was thus present only in group B (P less than 0.001). Because tamoxifen inhibits estrogen-deficiency bone loss in buserelin-treated rats without depressing the hypoestrogenic actions of this LHRH-agonist, we suggest that use of tamoxifen to protect the skeleton during LHRH-agonist therapy in young women should be explored. Tamoxifen citrate might also help to prevent postmenopausal osteoporosis.

  19. Role of Sclerostin in the Bone Loss of Postmenopausal Chinese Women with Type 2 Diabetes

    Institute of Scientific and Technical Information of China (English)

    Yi-jun Zhou; Ai Li; Yu-ling Song; Hui Zhou; Yan Li; Yin-si Tang

    2013-01-01

    Objective To evaluate the role of sclerostin in bone loss of postmenopausal Chinese women with type 2 diabetes mellitus. Methods The postmenopausal patients suffering from type 2 diabetes mellitus and age, body mass index, and duration of menopause matched healthy controls were enrolled into this cross-sectional study according to criteria of inclusion and exclusion. The serum sclerostin level and bone mineral density of the anterior-posterior lumbar spine (L1-L4), femoral neck, and total hip were determined by using a quantitative sandwich ELISA kit and dual X-ray absorptiometry, respectively. Meanwhile, the clinical and laboratory indexes of bone mineral metabolism were analyzed. Associations between serum sclerostin level and bone mineral density as well as bone turnover markers were evaluated by linear regression analysis. Results Finally, 265 postmenopausal women with type 2 diabetes and 225 non-diabetic women were recruited in the diabetic group and control group, respectively. Serum sclerostin level of the diabetic group was significantly higher than that of the control group (48.2±19.4 vs. 37.2±18.6 pmol/L, P Conclusions Sclerostin might participate in the pathogenesis of bone loss of type 2 diabetes. The high sclerostin level might serve as a marker of increased osteocyte activity in postmenopausal patients with type 2 diabetes mellitus.

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  1. Evaluation of the efficacy of zoledronic acid and amifostine on radiation induced bone loss in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Wook; Lee, Sueum; Kang, Sohi; Moon, Cahng Jong; Kim, Jong Choon; Kim, Sung Ho [College of Veterinary Medicine, Chonnam National University, Gwangju (Korea, Republic of); Jung, Uhee; Jo, Sung Kee [Advanced Radiation Technology Institute, Jeungeup (Korea, Republic of); Jang, Jong Sik [College of Ecology and Environmental Science, Kyungpook National University, Sangju (Korea, Republic of)

    2016-09-15

    This study investigated the effects of zoledronic acid (ZA) on radiation-induced bone loss in C3H/HeN mice. C3H/HeN mice were divided into sham control and three irradiated groups (3 Gy, gamma ray). The irradiated mice were treated for 12 weeks with vehicle, amifostine (intraperitoneal injection), or ZA (subcutaneous injection). Grip strength, uterus weight, and serum alkaline phosphatase (ALP), and tartrate-resistant acid phosphatase (TRAP) levels were measured. Tibiae were analyzed using micro-computed tomography. Treatment of ZA (100 μg·kg{sup -1}·week{sup -1}) significantly preserved trabecular bone volume, trabecular thickness, trabecular number, trabecular separation, bone mineral density of proximal tibia metaphysic, and cortical bone volume, but did not alter the uterus weight of the mice. The administration of ZA for 12 weeks lowered serum ALP and TRAP levels in irradiated mice, suggesting that ZA can reduce the bone turnover rate in mice. No differences were apparent between the amifostine-treated group and the irradiation control group. The results indicate that ZA can prevent radiation-induced bone loss in mice.

  2. 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.

  3. A hypomagnetic field aggravates bone loss induced by hindlimb unloading in rat femurs.

    Directory of Open Access Journals (Sweden)

    Bin Jia

    Full Text Available A hypomagnetic field is an extremely weak magnetic field--it is considerably weaker than the geomagnetic field. In deep-space exploration missions, such as those involving extended stays on the moon and interplanetary travel, astronauts will experience abnormal space environments involving hypomagnetic fields and microgravity. It is known that microgravity in space causes bone loss, which results in decreased bone mineral density. However, it is unclear whether hypomagnetic fields affect the skeletal system. In the present study, we aimed to investigate the complex effects of a hypomagnetic field and microgravity on bone loss. To study the effects of hypomagnetic fields on the femoral characteristics of rats in simulated weightlessness, we established a rat model of hindlimb unloading that was exposed to a hypomagnetic field. We used a geomagnetic field-shielding chamber to generate a hypomagnetic field of <300 nT. The results show that hypomagnetic fields can exacerbate bone mineral density loss and alter femoral biomechanical characteristics in hindlimb-unloaded rats. The underlying mechanism might involve changes in biological rhythms and the concentrations of trace elements due to the hypomagnetic field, which would result in the generation of oxidative stress responses in the rat. Excessive levels of reactive oxygen species would stimulate osteoblasts to secrete receptor activator of nuclear factor-κB ligand and promote the maturation and activation of osteoclasts and thus eventually cause bone resorption.

  4. A hypomagnetic field aggravates bone loss induced by hindlimb unloading in rat femurs.

    Science.gov (United States)

    Jia, Bin; Xie, Li; Zheng, Qi; Yang, Peng-fei; Zhang, Wei-ju; Ding, Chong; Qian, Ai-rong; Shang, Peng

    2014-01-01

    A hypomagnetic field is an extremely weak magnetic field--it is considerably weaker than the geomagnetic field. In deep-space exploration missions, such as those involving extended stays on the moon and interplanetary travel, astronauts will experience abnormal space environments involving hypomagnetic fields and microgravity. It is known that microgravity in space causes bone loss, which results in decreased bone mineral density. However, it is unclear whether hypomagnetic fields affect the skeletal system. In the present study, we aimed to investigate the complex effects of a hypomagnetic field and microgravity on bone loss. To study the effects of hypomagnetic fields on the femoral characteristics of rats in simulated weightlessness, we established a rat model of hindlimb unloading that was exposed to a hypomagnetic field. We used a geomagnetic field-shielding chamber to generate a hypomagnetic field of <300 nT. The results show that hypomagnetic fields can exacerbate bone mineral density loss and alter femoral biomechanical characteristics in hindlimb-unloaded rats. The underlying mechanism might involve changes in biological rhythms and the concentrations of trace elements due to the hypomagnetic field, which would result in the generation of oxidative stress responses in the rat. Excessive levels of reactive oxygen species would stimulate osteoblasts to secrete receptor activator of nuclear factor-κB ligand and promote the maturation and activation of osteoclasts and thus eventually cause bone resorption.

  5. Bone loss over one year of training and competition in female cyclists

    Science.gov (United States)

    Sherk, Vanessa D; Barry, Daniel W; Villalon, Karen L; Hansen, Kent C; Wolfe, Pamela; Kohrt, Wendy M

    2014-01-01

    Objective To observe changes in hip, spine, and tibia bone characteristics in female cyclists over the course of 1 year of training. Design Prospective observational study Setting Laboratory Participants Female cyclists (n=14) aged 26-41 years with at least 1 year of competition history and intent to compete in 10 or more races in the coming year. Assessment of Risk Factors Women who train and compete in road cycling as their primary sport. Main Outcome Measures Total body fat-free and fat mass, and lumbar spine and proximal femur areal bone mineral density (aBMD) and bone mineral content (BMC) assessments by DXA. Volumetric BMD (vBMD) and BMC of the tibia were measured by pQCT at sites corresponding to 4%, 38%, 66%, and 96% of tibia length. Time points were baseline and after 12 months of training and competition. Results Weight and body composition did not change significantly over 12 months. Total hip aBMD and BMC decreased by −1.4±1.9% and −2.1±2.3% (p0.11). Conclusions Bone loss in female cyclists was site-specific and similar in magnitude to losses previously reported in male cyclists. Research is needed to understand the mechanisms for bone loss in cyclists. PMID:24326929

  6. 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.

  7. Epiphyseal abnormalities, trabecular bone loss and articular chondrocyte hypertrophy develop in the long bones of postnatal Ext1-deficient mice.

    Science.gov (United States)

    Sgariglia, Federica; Candela, Maria Elena; Huegel, Julianne; Jacenko, Olena; Koyama, Eiki; Yamaguchi, Yu; Pacifici, Maurizio; Enomoto-Iwamoto, Motomi

    2013-11-01

    Long bones are integral components of the limb skeleton. Recent studies have indicated that embryonic long bone development is altered by mutations in Ext genes and consequent heparan sulfate (HS) deficiency, possibly due to changes in activity and distribution of HS-binding/growth plate-associated signaling proteins. Here we asked whether Ext function is continuously required after birth to sustain growth plate function and long bone growth and organization. Compound transgenic Ext1(f/f);Col2CreERT mice were injected with tamoxifen at postnatal day 5 (P5) to ablate Ext1 in cartilage and monitored over time. The Ext1-deficient mice exhibited growth retardation already by 2weeks post-injection, as did their long bones. Mutant growth plates displayed a severe disorganization of chondrocyte columnar organization, a shortened hypertrophic zone with low expression of collagen X and MMP-13, and reduced primary spongiosa accompanied, however, by increased numbers of TRAP-positive osteoclasts at the chondro-osseous border. The mutant epiphyses were abnormal as well. Formation of a secondary ossification center was significantly delayed but interestingly, hypertrophic-like chondrocytes emerged within articular cartilage, similar to those often seen in osteoarthritic joints. Indeed, the cells displayed a large size and round shape, expressed collagen X and MMP-13 and were surrounded by an abundant Perlecan-rich pericellular matrix not seen in control articular chondrocytes. In addition, ectopic cartilaginous outgrowths developed on the lateral side of mutant growth plates over time that resembled exostotic characteristic of children with Hereditary Multiple Exostoses, a syndrome caused by Ext mutations and HS deficiency. In sum, the data do show that Ext1 is continuously required for postnatal growth and organization of long bones as well as their adjacent joints. Ext1 deficiency elicits defects that can occur in human skeletal conditions including trabecular bone loss

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

    DEFF Research Database (Denmark)

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

    1999-01-01

    States and Europe. PARTICIPANTS: 1609 postmenopausal women 45 to 59 years of age. INTERVENTION: Participants were randomly assigned to receive oral alendronate, 5 mg/d or 2.5 mg/d; placebo; or open-label estrogen-progestin. Women in the alendronate groups received alendronate for the first 2 years...... alendronate to placebo than in those who continuously received placebo. In years 3 and 4, bone loss in participants who switched from alendronate to placebo was similar to that seen during years 1 and 2 in those who continuously received placebo. Compared with 5 mg of alendronate per day, estrogen......-medroxyprogesterone acetate produced similar increases in bone mineral density and estradiol-norethisterone acetate produced increases that were substantially greater. CONCLUSIONS: Four years of treatment with alendronate or estrogen-progestin prevented postmenopausal bone loss. A residual effect was seen 2 years after...

  9. 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.

  10. Loss of rotator cuff tendon-to-bone interface pressure after reattachment using a suture anchor.

    Science.gov (United States)

    Brassart, Nicolas; Sanghavi, Sanjay; Hansen, Ulrich N; Emery, Roger J; Amis, Andrew A

    2008-01-01

    The purpose of this study was to examine the tendon-to-bone interface pressure, contact area, and force after reattaching a tendon to bone by use of a suture and suture anchor. Repairs were made in 8 ovine shoulders in vitro, by use of 3 suture types in each: Ethibond, polydioxanone, or Orthocord. A Tekscan pressure sensor was placed between the tendon and bone and monitored for 1 hour after the repair. The principal finding was a significant loss of approximately 60% of the contact parameters immediately after the suture was tied, followed by further significant loss over the next hour to a mean of only 14% of the initial readings. We concluded that pressure measurement systems that only record the initial maximum pressure would yield overly optimistic results for the actual repair pressure after the repair is completed. The Tekscan system, however, allowed us to monitor pressure reductions that occurred both during and after the repair.

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

    OpenAIRE

    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 (

  12. 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.

  13. 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

  14. 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

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

    NARCIS (Netherlands)

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

    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

  16. 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.

  17. 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...

  18. 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.

  19. 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.

  20. 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.

  1. Severity and pattern of bone mineral loss in endocrine causes of osteoporosis as compared to age-related bone mineral loss

    Directory of Open Access Journals (Sweden)

    D Dutta

    2016-01-01

    Full Text Available Background: Data are scant on bone health in endocrinopathies from India. This study evaluated bone mineral density (BMD loss in endocrinopathies [Graves′ disease (GD, type 1 diabetes mellitus (T1DM, hypogonadotrophic hypogonadism (HypoH, hypergonadotropic hypogonadism (HyperH, hypopituitarism, primary hyperparathyroidism (PHPT] as compared to age-related BMD loss [postmenopausal osteoporosis (PMO, andropause]. Materials and Methods: Retrospective audit of records of patients >30 years age attending a bone clinic from August 2014 to January 2016 was done. Results: Five-hundred and seven records were screened, out of which 420 (females:male = 294:126 were analyzed. A significantly higher occurrence of vitamin D deficiency and insufficiency was noted in T1DM (89.09%, HyperH (85%, and HypoH (79.59% compared to age-related BMD loss (60.02%; P < 0.001. The occurrence of osteoporosis among females and males was 55.41% and 53.97%, respectively, and of osteopenia among females and males was 28.91% and 32.54%, respectively. In females, osteoporosis was significantly higher in T1DM (92%, HyperH (85%, and HypoH (59.26% compared to PMO (49.34%; P < 0.001. Z score at LS, TF, NOF, and greater trochanter (GT was consistently lowest in T1DM women. Among men, osteoporosis was significantly higher in T1DM (76.67% and HypoH (54.55% compared to andropause (45.45%; P = 0.001. Z score at LS, TF, NOF, GT, and TR was consistently lowest in T1DM men. In GD, the burden of osteoporosis was similar to PMO and andropause. BMD difference among the study groups was not significantly different after adjusting for body mass index (BMI and vitamin D. Conclusion: Low bone mass is extremely common in endocrinopathies, warranting routine screening and intervention. Concomitant vitamin D deficiency compounds the problem. Calcium and vitamin D supplementations may improve bone health in this setting.

  2. 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.

  3. Calcium supplementation prevents seasonal bone loss and changes in biochemical markers of bone turnover in elderly New England women: a randomized placebo-controlled trial.

    Science.gov (United States)

    Storm, D; Eslin, R; Porter, E S; Musgrave, K; Vereault, D; Patton, C; Kessenich, C; Mohan, S; Chen, T; Holick, M F; Rosen, C J

    1998-11-01

    Elderly women are at increased risk for bone loss and fractures. In previous cross-sectional and longitudinal studies of women residing in northern latitudes, bone loss was most pronounced during winter months and in those consuming less than 1 g calcium per day. In this study we sought to test the hypothesis that calcium supplementation by either calcium carbonate or dietary means would prevent seasonal bone loss and preserve bone mass. Sixty older postmenopausal women without osteoporosis were randomized to one of three treatment arms: Dietary milk supplementation (D-4 glasses of milk/day), Calcium carbonate (CaCO3-1000 mg/day in two divided doses), or placebo (P). After 2 yr, placebo-treated women consumed a mean of 683 mg/day of calcium and lost 3.0% of their greater trochanteric (GT) bone mineral density (BMD) (P intake of 1028 mg/day and sustained minimal loss from the GT (-1.5%; P = 0.30), whereas CaCO3-treated women (total Ca intake, 1633 mg/day) suffered no bone loss from the GT and showed a significant increase in spinal and femoral neck BMD (P vitamin D declined by more than 20% (P intake was the strongest predictor of bone loss from the hip. Urinary N-telopeptide also closely correlated with GT BMD but only during winter (P = 0.003). We conclude that calcium supplementation prevents bone loss in elderly women by suppressing bone turnover during the winter when serum 25-OH vitamin D declines and serum PTH increases. The precise amount of calcium necessary to preserve BMD in elderly women requires further studies, although in this study, at least 1000 mg/day of supplemental calcium was adequate prophylaxis against femoral bone loss.

  4. Validity of arthroscopic measurement of glenoid bone loss using the bare spot

    Directory of Open Access Journals (Sweden)

    Miyatake K

    2014-03-01

    Full Text Available Katsutoshi Miyatake, Yoshitsugu Takeda, Koji Fujii, Tomoya Takasago, Toshiyuki Iwame Department of Orthopaedic Surgery, Tokushima Red Cross Hospital, Komatsushima, Tokushima, Japan Purpose: Our aim was to test the validity of using the bare spot method to quantify glenoid bone loss arthroscopically in patients with shoulder instability. Methods: Twenty-seven patients with no evidence of instability (18 males, nine females; mean age 59.1 years were evaluated arthroscopically to assess whether the bare spot is consistently located at the center of the inferior glenoid. Another 40 patients with glenohumeral anterior instability who underwent shoulder arthroscopy (30 males, ten females; mean age 25.9 years were evaluated for glenoid bone loss with preoperative three-dimensional computed tomography (3D-CT and arthroscopic examination. In patients without instability, the distances from the bare spot of the inferior glenoid to the anterior (Da and posterior (Dp glenoid rim were measured arthroscopically. In patients with instability, we compared the percentage glenoid bone loss calculated using CT versus arthroscopic measurements. Results: Among patients without instability, the bare spot could not be identified in three of 27 patients. Da (9.5±1.2 mm was smaller than Dp (10.1±1.5 mm, but it was not significantly different. However, only 55% of glenoids showed less than 1 mm of difference between Da and Dp, and 18% showed more than 2 mm difference in length. The bare spot could not be identified in five of 40 patients with instability. Pearson's correlation coefficient showed significant (P<0.001 and strong (R2=0.63 correlation in percentage glenoid bone loss between the 3D-CT and arthroscopy method measurements. However, in ten shoulders (29%, the difference in percentage glenoid bone loss between 3D-CT and arthroscopic measurements was greater than 5%. Conclusion: The bare spot was not consistently located at the center of the inferior glenoid

  5. 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.

  6. 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

  7. Glucosamines Attenuate Bone Loss Due to Menopause by Regulating Osteoclast Function in Ovariectomized Mice.

    Science.gov (United States)

    Asai, Hironobu; Nakatani, Sachie; Kato, Takuya; Shimizu, Tatsuo; Mano, Hiroshi; Kobata, Kenji; Wada, Masahiro

    2016-01-01

    The effect of glucosamine (GlcN) and N-acetylglucosamine (GlcNAc) on bone metabolism in ovariectomized (OVX) mice was studied. After 12 weeks of feeding with 0.2% GlcN and 0.2% GlcNAc, the femoral bone mineral density in OVX mice was significantly increased compared with that in OVX mice fed the control diet. Histomorphometric analysis of the tibia indicated that the rates of osteogenesis and bone resorption were reduced due to the GlcN diet. The erosion depth of osteoclasts on the tibia in GlcN- and GlcNAc-fed OVX mice was significantly lower than that in the control OVX mice. The number of tartrate-resistant acid phosphatase-positive osteoclasts induced from bone marrow stem cells isolated from GlcN-fed OVX mice was significantly lower than that from control OVX mice. A loss of uterine weight and higher serum calcium concentration in the GlcN- and GlcNAc-fed OVX mice were observed. The results suggest that the intake of GlcN suppresses bone loss by inhibiting osteoclast differentiation and activity in a nonestrogenic manner.

  8. Rac-null leukocytes are associated with increased inflammation-mediated alveolar bone loss.

    Science.gov (United States)

    Sima, Corneliu; Gastfreund, Shoshi; Sun, Chunxiang; Glogauer, Michael

    2014-02-01

    Periodontitis is characterized by altered host-biofilm interactions that result in irreversible inflammation-mediated alveolar bone loss. Genetic and epigenetic factors that predispose to ineffective control of biofilm composition and maintenance of tissue homeostasis are not fully understood. We elucidated how leukocytes affect the course of periodontitis in Rac-null mice. Mouse models of acute gingivitis and periodontitis were used to assess the early inflammatory response and patterns of chronicity leading to loss of alveolar bone due to inflammation in Rac-null mice. Leukocyte margination was differentially impaired in these mice during attachment in conditional Rac1-null (granulocyte/monocyte lineage) mice and during rolling and attachment in Rac2-null (all blood cells) mice. Inflammatory responses to subgingival ligatures, assessed by changes in peripheral blood differential leukocyte numbers, were altered in Rac-null compared with wild-type mice. In response to persistent subgingival ligature-mediated challenge, Rac-null mice had increased loss of alveolar bone with patterns of resorption characteristic of aggressive forms of periodontitis. These findings were partially explained by higher osteoclastic coverage of the bone-periodontal ligament interface in Rac-null compared with wild-type mice. In conclusion, this study demonstrates that leukocyte defects, such as decreased endothelial margination and tissue recruitment, are rate-limiting steps in the periodontal inflammatory process that lead to more aggressive forms of periodontitis.

  9. Aromatase inhibitor-associated bone loss in breast cancer patients is distinct from postmenopausal osteoporosis.

    Science.gov (United States)

    Hadji, Peyman

    2009-01-01

    Women with breast cancer are increasingly being diagnosed and treated earlier in the disease process, resulting in significantly improved clinical outcomes. Aromatase inhibitor (AI) therapy has shown superior efficacy compared with tamoxifen in postmenopausal women and is quickly becoming the therapy of choice in this setting. However, adjuvant AI therapy depletes residual estrogen and is associated with rapid bone loss and increased fracture risk distinctly different from those observed in postmenopausal osteoporosis. Aromatase inhibitor-associated bone loss (AIBL) occurs at a rate at least 2-fold higher than bone loss seen in healthy, age-matched postmenopausal women, resulting in a significantly higher fracture incidence regardless of the AI administered. Thus, antiresorptive treatments designed to address postmenopausal osteoporosis may not be sufficient in this unique population. Furthermore, current guidelines for the management of bone health in women with breast cancer may not correctly identify patients who may benefit from therapy. Consequently, breast cancer patients receiving adjuvant AI therapy will require specialized management strategies to identify and treat patients at high risk for fracture. Recently, nitrogen-containing bisphosphonates have emerged as the treatment of choice for the prevention of AIBL and the reduction of fracture risk in this setting.

  10. Preventive effect of zinc acexamate administration in streptozotocin-diabetic rats: Restoration of bone loss.

    Science.gov (United States)

    Yamaguchi, Masayoshi; Uchiyama, Satoshi

    2003-11-01

    The preventive effect of zinc compounds on bone loss in streptozotocin (STZ)-diabetic rats was investigated. Rats received a single subcutaneous administration of STZ (6.0 mg/100 g body weight), and 7, 14 or 21 days later the animals were sacrificed by bleeding. STZ administration caused a significant decrease in body weight and a significant increase in serum glucose and triglyceride levels, indicating diabetic condition. Femoral-diaphyseal and -metaphyseal alkaline phosphatase activity, calcium and deoxyribonucleic acid (DNA) contents were significantly decreased by STZ administration, showing that diabetic condition causes bone loss. Zinc sulfate (2.5 mg Zn/100 g) or zinc acexamate (2.5 mg Zn/100 g) was orally administered once daily for 14 days to rats received a single subcutaneous administration of STZ (6.0 mg/100 g). STZ administration-induced increase in serum glucose and triglyceride levels and decrease in body weight, femoral-diaphyseal and -metaphyseal alkaline phosphatase activity, DNA and calcium contents were significantly prevented by the administration of zinc acexamate. The preventive effect of zinc sulfate on bone components was not seen. The present results demonstrate that the administration of zinc acexamate has a preventive effect on bone loss in STZ-diabetic rats in vivo.

  11. Simplified Tai Chi Resistance Training versus Traditional Tai Chi in Slowing Bone Loss in Postmenopausal Women.

    Science.gov (United States)

    Wang, Huiru; Yu, Bo; Chen, Wenhua; Lu, Yingzhi; Yu, Dinghai

    2015-01-01

    Background. This study examined whether simplified Tai Chi resistance training is superior to traditional Tai Chi in slowing bone loss in postmenopausal women. Methods. This prospective trial included 119 postmenopausal women (age: 52-65 years). Subjects were randomly assigned to participate in a traditional Tai Chi program (TTC, n = 40), a simplified Tai Chi resistance training program (TCRT, n = 40), or a blank control group (routine activity, n = 39). The TTC involved traditional Yang Style Tai Chi. The primary outcome was the change of lumbar bone mass density (L2-L4) at 12 months over the baseline. Femoral neck and Ward's triangle were also measured using dual-energy X-ray absorptiometry. Results. The L2-L4 density was significantly lower at 12 months in comparison to the baseline in the blank control group. In both the TCRT and TTC groups, the L2-L4 density was comparable to the baseline. There was a trend for less bone loss in the TCRT than in the TTC group. Similar findings were observed with femoral neck and Ward's triangle. Conclusion. Simplified Tai Chi resistance training could slow bone loss in menopausal women. The results also suggested, but did not confirm, superiority to traditional Tai Chi.

  12. Potent inhibitory effect of Foeniculum vulgare Miller extract on osteoclast differentiation and ovariectomy-induced bone loss.

    Science.gov (United States)

    Kim, Tae-Ho; Kim, Hyun-Ju; Lee, Sang-Han; Kim, Shin-Yoon

    2012-06-01

    Inhibition of osteoclast differentiation and bone resorption is considered an effective therapeutic approach to the treatment of postmenopausal bone loss. To find natural compounds that may inhibit osteoclastogenesis, we screened herbal extracts on bone marrow cultures. In this study, we found that an aqueous extract of Foeniculum vulgare Miller seed (FvMs) at low concentration, which has traditionally been used as a treatment for a variety of ailments, inhibits the osteoclast differentiation and bone resorptive activity of mature osteoclasts. We further investigated the effects of FvMs on ovariectomy (OVX)-induced bone loss using microcomputed tomography, biomechanical tests and serum marker assays for bone remodeling. Oral administration of FvMs (30 mg or 100 mg/kg/day) for 6 weeks had an intermediary effect on the prevention of femoral bone mineral density (BMD), bone mineral content (BMC), and other parameters compared to OVX controls. In addition, FvMs slightly decreased bone turnover markers that were accelerated by OVX. The bone-protective effects of FvMs may be due to suppression of an OVX-induced increase in bone turnover. Collectively, our findings indicate that FvMs have potential in preventing bone loss in postmenopausal osteoporosis by reducing both osteoclast differentiation and function.

  13. Bone loss in adult offspring induced by low-dose exposure to teratogens.

    Science.gov (United States)

    Torchinsky, Arkady; Mizrahi, Limor; Savion, Shoshana; Shahar, Ron; Toder, Vladimir; Kobyliansky, Eugene

    2012-05-01

    Maternal malnutrition during pregnancy was shown by numerous studies to result in the birth of offspring exhibiting altered bone characteristics, which are indicative of bone loss. We hypothesized that not only maternal malnutrition but also some developmental toxicants (teratogens) given at a dose inducing neither structural anomalies nor growth retardation can detrimentally affect skeletal health in adult offspring. To check this hypothesis, pregnant mice were exposed to a single injection of 5-aza-2-deoxycytidine (5-AZA) (a teratogen capable of inducing phocomelia of the hind limbs) at a sub-threshold teratogenic dose. Micro-computed tomography scanning revealed that femora of 5-month-old male offspring exposed in uterus to 5-AZA had trabecular microarchitecture indicative of bone loss. Furthermore, exposure to 5-AZA increased the susceptibility of offspring to postnatal chronic mild stress, which has been shown to induce bone loss in mice. While exploring possible mechanisms underlying this phenomenon, we observed that the expression of some microRNAs, which have been demonstrated as regulators of key osteoblastogenic genes, was altered in hind limb buds of embryos exposed to 5-AZA. Furthermore, the expression of receptor activator of nuclear factor kappa B ligand (RANKL) in femoral stromal/osteoblastic cells of 5-month-old offspring of 5-AZA-treated females was found to be increased. Collectively, this study implies for the first time that single low-dose exposure to a teratogen can induce bone loss in adult offspring, possibly via alteration of embryonic microRNAs and RANKL expression.

  14. Can we stop bone loss and prevent hip fractures in the elderly?

    Science.gov (United States)

    Meunier, P J; Chapuy, M C; Arlot, M E; Delmas, P D; Duboeuf, F

    1994-01-01

    The two main determinants of hip fractures are falls and bone loss leading to an intrinsic femoral fragility. Substantial femoral bone loss continues throughout old age, with a continuous and exponential increase in the risk of hip fracture; thus any reduction or arrest of this loss will induce an important reduction in the incidence of hip fracture. Preventive measures may be achieved during childhood by increasing peak bone mass with calcium and exercise, by using long-term estrogen replacement therapy after menopause, but also by using vitamin D and calcium supplements for late prevention in the elderly. Vitamin D insufficiency and a deficit in calcium intake are very common in the elderly living either in institutions or at home and the cumulative response to these deficits is a negative calcium balance which stimulates parathyroid hormone secretion. This senile secondary hyperparathyroidism is one of the determinants of femoral bone loss and can be reversed by calcium and vitamin D supplements. We have shown in a 3-year controlled prospective study that the daily use of supplements (1.2 g calcium and 800 IU vitamin D3) given in a large population of 3270 elderly ambulatory women living in nursing homes reduced the number of hip fractures by 23% (intention-to-treat analysis). In parallel, serum parathyroid hormone concentrations were reduced by 28% and low baseline serum 25-hydroxyvitamin D concentration returned to normal values. After 18 months of treatment the bone density of the total proximal femoral region had increased by 2.7% in the vitamin D3-calcium group and decreased by 4.6% in the placebo group (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

  15. 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

  16. 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.

  17. Amphibian skull evolution: the developmental and functional context of simplification, bone loss and heterotopy.

    Science.gov (United States)

    Schoch, Rainer R

    2014-12-01

    Despite their divergent morphology, extant and extinct amphibians share numerous features in the timing and spatial patterning of dermal skull elements. Here, I show how the study of these features leads to a deeper understanding of morphological evolution. Batrachians (salamanders and frogs) have simplified skulls, with dermal bones appearing rudimentary compared with fossil tetrapods, and open cheeks resulting from the absence of other bones. The batrachian skull bones may be derived from those of temnospondyls by truncation of the developmental trajectory. The squamosal, quadratojugal, parietal, prefrontal, parasphenoid, palatine, and pterygoid form rudimentary versions of their homologs in temnospondyls. In addition, failure to ossify and early fusion of bone primordia both result in the absence of further bones that were consistently present in Paleozoic tetrapods. Here, I propose a new hypothesis explaining the observed patterns of bone loss and emargination in a functional context. The starting observation is that jaw-closing muscles are arranged in a different way than in ancestors from the earliest ontogenetic stage onwards, with muscles attaching to the dorsal side of the frontal, parietal, and squamosal. The postparietal and supratemporal start to ossify in a similar way as in branchiosaurids, but are fused to neighboring elements to form continuous attachment areas for the internal adductor. The postfrontal, postorbital, and jugal fail to ossify, as their position is inconsistent with the novel arrangement of adductor muscles. Thus, rearrangement of adductors forms the common theme behind cranial simplification, driven by an evolutionary flattening of the skull in the batrachian stem.

  18. Methanolic extract of Cuminum cyminum inhibits ovariectomy-induced bone loss in rats.

    Science.gov (United States)

    Shirke, Sarika S; Jadhav, Sanket R; Jagtap, Aarti G

    2008-11-01

    Several animal and clinical studies have shown that phytoestrogens, plant-derived estrogenic compounds, can be useful in treating postmenopausal osteoporosis. Phytoestrogens and phytoestrogen-containing plants are currently under active investigation for their role in estrogen-related disorders. The present study deals with anti-osteoporotic evaluation of phytoestrogen-rich plant Cuminum cyminum, commonly known as cumin. Adult Sprague-Dawley rats were bilaterally ovariectomized (OVX) and randomly assigned to 3 groups (10 rats/group). Additional 10 animals were sham operated. OVX and sham control groups were orally administered with vehicle while the other two OVX groups were administered 0.15 mg/kg estradiol and 1 g/kg of methanolic extract of Cuminum cyminum fruits (MCC) in two divided doses for 10 weeks. At the end of the study blood, bones and uteri of the animals were collected. Serum was evaluated for calcium, phosphorus, alkaline phosphatase and tartarate resistant acid phosphatase. Bone density, ash density, mineral content and mechanical strength of bones were evaluated. Scanning electron microscopic (SEM) analysis of bones (tibia) was performed. Results were analyzed using ANOVA and Tukeys multiple comparison test. MCC (1 g/kg, p.o.) significantly reduced urinary calcium excretion and significantly increased calcium content and mechanical strength of bones in comparison to OVX control. It showed greater bone and ash densities and improved microarchitecture of bones in SEM analysis. Unlike estradiol it did not affect body weight gain and weight of atrophic uterus in OVX animals. MCC prevented ovariectomy-induced bone loss in rats with no anabolic effect on atrophic uterus. The osteoprotective effect was comparable with estradiol.

  19. 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 (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 scores correlated directly with number of previous surgery (r=0.81, p=0

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

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    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.

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

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    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.

  2. 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 (PLeptin and rAAV-GFP rats. In summary, rAAV-Leptin-treated rats maintained a lower body weight compared to baseline and rAAV-GFP-treated rats with minimal effects on bone mass, density, microarchitecture, or biochemical markers of bone turnover.

  3. Prevention of Bone Loss with Risedronate in Breast Cancer Survivors: A Randomized, Controlled Clinical Trial

    Science.gov (United States)

    Greenspan, Susan L.; Vujevich, Karen T.; Brufsky, Adam; Lembersky, Barry C.; van Londen, G.J.; Jankowitz, Rachel C.; Puhalla, Shannon L.; Rastogi, Priya; Perera, Subashan

    2016-01-01

    Purpose Aromatase inhibitors (AIs), adjuvant endocrine therapy for postmenopausal women with hormone receptor positive breast cancer, are associated with bone loss and fractures. Our objectives were to determine if 1) oral bisphosphonate therapy can prevent bone loss in women on an AI and, 2) early changes in bone turnover markers (BTM) can predict later changes in bone mineral density (BMD). Methods We conducted a 2 year double-blind, placebo-controlled, randomized trial in 109 postmenopausal women with low bone mass on an aromatase inhibitor (AI-anastrozole, letrozole, or exemestane) for hormone receptor positive breast cancer. Participants were randomized to once weekly risedronate 35 mg or placebo and all received calcium plus vitamin D. The main outcome measures included BMD, BTM [carboxy-terminal collagen crosslinks (CTX) and N-terminal propeptide of type 1 procollagen (P1NP)] and safety. Results Eighty-seven percent completed 24 months. BMD increased more in the active treatment group compared to placebo with an adjusted difference at 24 months of 3.9 ± 0.7 percentage points at the spine and 3.2 ± 0.5 percentage points at the hip (both p<0.05). The adjusted difference between the active treatment and placebo groups were 0.09 ± 0.04 nmol/LBCE for CTX and 23.3 ± 4.8 µg/mL for P1NP (both p<0.05). Women with greater 12-month decreases in CTX and P1NP in the active treatment group had a greater 24-month increase in spinal BMD (p<0.05). The oral therapy was safe and well tolerated. Conclusion In postmenopausal women with low bone mass and breast cancer on an AI, the oral bisphosphonate risedronate maintained skeletal health. PMID:25792492

  4. 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.

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

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    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.

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

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    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.

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

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    Jialiang Huang

    2016-03-01

    Full Text Available 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.

  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. 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

    NARCIS (Netherlands)

    C.H. Alves (Celso Henrique); E. Farrell (Eric); M. Vis (M.); E.M. Colin (Edgar); E.W. Lubberts (Erik)

    2016-01-01

    textabstractThroughout 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 differentiati

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

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    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. Metaphyseal and diaphyseal bone loss in the tibia following transient muscle paralysis are spatiotemporally distinct resorption events.

    Science.gov (United States)

    Ausk, Brandon J; Huber, Philippe; Srinivasan, Sundar; Bain, Steven D; Kwon, Ronald Y; McNamara, Erin A; Poliachik, Sandra L; Sybrowsky, Christian L; Gross, Ted S

    2013-12-01

    When the skeleton is catabolically challenged, there is great variability in the timing and extent of bone resorption observed at cancellous and cortical bone sites. It remains unclear whether this resorptive heterogeneity, which is often evident within a single bone, arises from increased permissiveness of specific sites to bone resorption or localized resorptive events of varied robustness. To explore this question, we used the mouse model of calf paralysis induced bone loss, which results in metaphyseal and diaphyseal bone resorption of different timing and magnitude. Given this phenotypic pattern of resorption, we hypothesized that bone loss in the proximal tibia metaphysis and diaphysis occurs through resorption events that are spatially and temporally distinct. To test this hypothesis, we undertook three complimentary in vivo/μCT imaging studies. Specifically, we defined spatiotemporal variations in endocortical bone resorption during the 3weeks following calf paralysis, applied a novel image registration approach to determine the location where bone resorption initiates within the proximal tibia metaphysis, and explored the role of varied basal osteoclast activity on the magnitude of bone loss initiation in the metaphysis using μCT based bone resorption parameters. A differential response of metaphyseal and diaphyseal bone resorption was observed throughout each study. Acute endocortical bone loss following muscle paralysis occurred almost exclusively within the metaphyseal compartment (96.5% of total endocortical bone loss within 6days). Using our trabecular image registration approach, we further resolved the initiation of metaphyseal bone loss to a focused region of significant basal osteoclast function (0.03mm(3)) adjacent to the growth plate. This correlative observation of paralysis induced bone loss mediated by basal growth plate cell dynamics was supported by the acute metaphyseal osteoclastic response of 5-week vs. 13-month-old mice. Specifically

  13. Amphibian skull evolution: The developmental and functional context of simplification, bone loss and heterotopy.

    Science.gov (United States)

    Schoch, Rainer R

    2014-11-10

    Despite their divergent morphology, extant and extinct amphibians share numerous features in the timing and spatial patterning of dermal skull elements. Here, I show how the study of these features leads to a deeper understanding of morphological evolution. Batrachians (salamanders and frogs) have simplified skulls, with dermal bones appearing rudimentary compared with fossil tetrapods, and open cheeks resulting from the absence of other bones. The batrachian skull bones may be derived from those of temnospondyls by truncation of the developmental trajectory. The squamosal, quadratojugal, parietal, prefrontal, parasphenoid, palatine, and pterygoid form rudimentary versions of their homologs in temnospondyls. In addition, failure to ossify and early fusion of bone primordia both result in the absence of further bones that were consistently present in Paleozoic tetrapods. Here, I propose a new hypothesis explaining the observed patterns of bone loss and emargination in a functional context. The starting observation is that jaw-closing muscles are arranged in a different way than in ancestors from the earliest ontogenetic stage onwards, with muscles attaching to the dorsal side of the frontal, parietal, and squamosal. The postparietal and supratemporal start to ossify in a similar way as in branchiosaurids, but are fused to neighboring elements to form continuous attachment areas for the internal adductor. The postfrontal, postorbital, and jugal fail to ossify, as their position is inconsistent with the novel arrangement of adductor muscles. Thus, rearrangement of adductors forms the common theme behind cranial simplification, driven by an evolutionary flattening of the skull in the batrachian stem. J. Exp. Zool. (Mol. Dev. Evol.) 9999B: XX-XX, 2014. © 2014 Wiley Periodicals, Inc.

  14. Effects of electromagnetic fields on bone loss in hyperthyroidism rat model.

    Science.gov (United States)

    Liu, Chaoxu; Zhang, Yingchi; Fu, Tao; Liu, Yang; Wei, Sheng; Yang, Yong; Zhao, Dongming; Zhao, Wenchun; Song, Mingyu; Tang, Xiangyu; Wu, Hua

    2017-02-01

    Optimal therapeutics for hyperthyroidism-induced osteoporosis are still lacking. As a noninvasive treatment, electromagnetic fields (EMF) have been proven to be effective for treating osteoporosis in non-hyperthyroidism conditions. We herein systematically evaluated the reduced effects of EMF on osteoporosis in a hyperthyroidism rat model. With the use of Helmholtz coils and an EMF stimulator, 15 Hz/1 mT EMF was generated. Forty-eight 5-month-old male Sprague-Dawley rats were randomly divided into four different groups: control, levothyroxine treated (L-T4), EMF exposure + levothyroxine (EMF + L-T4), and EMF exposure without levothyroxine administration (EMF). All rats were treated with L-T4 (100 mg/day) except those in control and EMF groups. After 12 weeks, the results obtained from bone mineral density analyses and bone mechanical measurements showed significant differences between L-T4 and EMF + L-T4 groups. Micro CT and bone histomorphometric analyses indicated that trabecular bone mass and architecture in distal femur and proximal tibia were augmented and restored partially in EMF + L-T4 group. In addition, bone thyroid hormone receptors (THR) expression of hyperthyroidism rats was attenuated in EMF + L-T4 group, compared to control group, which was not observed in L-T4 group. According to these results, we concluded that 15 Hz/1 mT EMF significantly inhibited bone loss and micro architecture deterioration in hyperthyroidism rats, which might occur due to reduced THR expression caused by EMF exposure. Bioelectromagnetics. 38:137-150, 2017. © 2016 Wiley Periodicals, Inc.

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

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    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.

  16. Loss of functional NADPH oxidase-2 protects against alcohol-induced bone resorption in female p47phox-/- mice

    Science.gov (United States)

    In bone, oxidant signaling through NADPH oxidase (NOX)-derived reactive oxygen species (ROS) is an important stimulus for osteoclast differentiation and activity. We have previously demonstrated that chronic alcohol abuse produces bone loss through NOX-dependent mechanisms. In the current study, s...

  17. A Radiographic Comparison of Progressive and Conventional Loading on Crestal Bone Loss and Density in Single Implants

    Directory of Open Access Journals (Sweden)

    Majid Sorouri

    2013-01-01

    Full Text Available Objectives: Crestal bone loss is a biologic complication in implant dentistry. The aim of this study was to compare the effect of progressive and conventional loading on crestal bone height and bone density around single osseointegrated implants in posterior maxilla by a longitudinal radiographic assessment technique.Materials and methods: Twenty micro thread implants were placed in 10 patients (two implants per patient. One of the two implants of each patient was assigned to progressive and the other to conventional loading groups. Eight weeks after surgery, conventional implants were restored with a metal ceramic crown and progressive group underwent a progressive loading protocol. The progressive loading group takes different temporary acrylic crowns at 2, 4 and 6 months. After eight months, acrylic crowns were replaced with metal ceramic crown. Computer radiography of both progressive and conventional implants was taken at 2, 4, 6, and 12 months. Image analysis was performed to measure height of crestal bone loss and bone density.Results: The mean values of crestal bone loss at month 12 were 0.11 (0.19 mm for progressively and 0.36 (0.36 mm for conventionally loaded implants, with a statistically significant difference (P 0.05.Conclusion: Progressive group showed less crestal bone loss in single osseointegrated implant than conventional group. Bone density around progressively loaded implants showed increase in crestal, middle and apica

  18. Synergistic effects of green tea polyphenols and alphacalcidol on chronic inflammation-induced bone loss in female rats

    Science.gov (United States)

    Summary: Studies suggest that green tea polyphenols (GTP) or alphacalcidol is promising agent for preventing bone loss. Findings that GTP supplementation in the drinking water plus alphacalcidol administration resulted in increased bone mass via a decrease of oxidative stress and inflammation sugges...

  19. Synergistic Effect of Green Tea Polyphenols and Vitamin D on Chronic Inflammation-Induced Bone Loss in Female Rats

    Science.gov (United States)

    Our recent study demonstrated a bone-protective role of green tea polyphenols (GTPs), extracted from green tea, in chronic inflammation-induced bone loss of female rats through reduction of inflammation and oxidative stress. This study further examines effects of GTPs in conjunction with vitamin D (...

  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. Role of odanacatib in reducing bone loss due to endodontic disease: An overview

    Science.gov (United States)

    Bahuguna, Rachana; Jain, Atul; Khan, Suleman Abbas; Arvind, M. S.

    2016-01-01

    Aims and Objectives: Through a comprehensive literature review, this article provides an overview of the potential role of odanacatib (ODN) in reducing bone loss due to endodontic disease. Materials and Methods: A literature review was performed in PubMed Central, MEDLINE, Cochrane Library, and EBSCO databases. The articles identified included those published between 2002 and 2016. Based on the predetermined inclusion and exclusion criteria, out of 237 articles found, 50 were selected for this review. Results: Cathepsin K (CstK), which is indispensible to the immune system, also plays an important role in osteoclastic bone resorption. ODN, which is an orally active, selective, and effective inhibitor of CstK, decreases bone resorption by selectively inhibiting proteolysis of matrix proteins by CstK, without affecting other osteoclastic activity or osteoblast viability. Conclusion: The goal of endodontic treatment is to achieve a clinically asymptomatic state along with formation of reparative bone. This process could take 6 months or longer, hence, an earlier reversal of the resorption process could lead to faster healing and resolution of the periapical lesion. Use of ODN can be of help in achieving this goal. PMID:28217533

  2. 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.

  3. 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

  4. 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...

  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. 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.

  7. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-02-01

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

  9. 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.

  10. High-Dose Vitamin D and Calcium Attenuates Bone Loss with Antiretroviral Therapy Initiation

    Science.gov (United States)

    Overton, Edgar Turner; Chan, Ellen S.; Brown, Todd T.; Tebas, Pablo; McComsey, Grace A.; Melbourne, Kathleen M.; Napoli, Andrew; Hardin, William Royce; Ribaudo, Heather J.; Yin, Michael T.

    2015-01-01

    Background Antiretroviral therapy (ART) initiation for HIV-1 infection is associated with 2-6% loss in bone mineral density (BMD). Objective To evaluate vitamin D3 (4000 IU daily) plus calcium (1000 mg calcium carbonate daily) supplementation on bone loss associated with ART initiation. Design 48-week prospective, randomized, double-blind, placebo-controlled study. Setting Thirty nine AIDS Clinical Trials Network research units. Participants ART-naïve HIV-infected adults. Measurements BMD by dual-energy X-ray absorptiometry (DXA); 25-hydroxy vitamin D (25(OH)D) levels, parathyroid hormone (PTH), phosphate metabolism, markers of bone turnover and systemic inflammation. Results 165 eligible subjects were randomized (79 Vitamin D/calcium (VitD/Cal); 86 placebo); 142 subjects with evaluable DXA data were included in the primary analysis. The study arms were well-balanced at baseline: median age 33 years; 90% male; 33% non-Hispanic black; median CD4 count 341 cells/mm3; and median 25(OH)D 23 ng/mL (57 nmol/L). At 48 weeks, subjects receiving placebo had greater decline in total hip BMD than VitD/Cal: −3.19% median change (1st-3rd quartile (Q1, Q3) −5.12%, −1.02%) vs. (−1.46% −3.16%,−0.40%). respectively (p=0.001). Lumbar spine BMD loss for the two groups was similar: −2.91% (−4.84%, −1.06%) vs. −1.41% (−3.78%, 0.00%), (p=0.085). At week 48, 90% of participants achieved HIV-1 RNA <50 copies/mL. Levels of 25(OH)D3 increased in the VitD/Cal but not the placebo group: median change of 24.5 (14.6, 37.8) vs. 0.7 (−5.3, 4.3) ng/mL, respectively (p<0.001). Additionally, increases in markers of bone turnover were blunted in the VitD/Cal group. Limitations No international sites were included; only 48 weeks of follow up Conclusion Vitamin D/calcium supplementation mitigates the loss of BMD seen with initiation of efavirenz/emtricitabine/tenofovir, particularly at the total hip, which is the site of greatest concern for fragility fracture. Primary Funding

  11. Prevention and treatment of bone loss in patients with nonmetastatic breast or prostate cancer who receive hormonal ablation therapy.

    Science.gov (United States)

    Limburg, Connie; Maxwell, Cathy; Mautner, Beatrice

    2014-04-01

    Hormone ablation therapy is a mainstay in the treatment of breast and prostate cancers. However, aromatase inhibitors (AIs) used in postmenopausal women with breast cancer and androgen-deprivation therapy (ADT) used in men with prostate cancer contribute to substantial bone loss, thereby increasing the risk of osteoporotic fractures. Evidence-based guidelines, therefore, urge oncology practices to screen these patients for bone loss and, if needed, provide treatment to maintain bone health. In addition to lifestyle modification and calcium or vitamin D supplementation, bone protection strategies include treatment with bisphosphonates and denosumab, a monoclonal antibody against RANK ligand. Identification of patients at greater risk for bone loss and fracture and proper interventions can reduce fracture rates. Oncology nurses can play an important role in screening these patients. The purpose of this article is to inform oncology nurses about the effects of cancer treatment on bone health, review current prevention and treatment options for cancer treatment-induced bone loss, and discuss recommendations for identifying high-risk individuals.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Use of an optical comparator for radiographic measurement of bone loss around endosseous implants: a pilot study.

    Science.gov (United States)

    Siddiqui, A A; Caudill, R; Beatty, K

    1995-01-01

    A technique for the measurement of bone loss around endosseous implants using an optical comparator was investigated. Five operators were asked to measure the mesial and distal alveolar bone levels around a screw type dental implant on a periapical radiograph mounted on an optical comparator. The known size of a threaded implant was used as a reference. The bone loss around the implant was calculated by taking the average of the mesial and distal measurements. Statistical analysis at the 95 percent confidence level demonstrated that there was no significant difference among the measurements. Although the initial results are encouraging, additional research is necessary with a larger sample size to validate the accuracy of optical comparator readings and compare the efficacy of this technique with other currently used methods for determining bone loss around root form implants.

  14. Protective effect of steroidal saponins from rhizome of Anemarrhena asphodeloides on ovariectomy-induced bone loss in rats

    Institute of Scientific and Technical Information of China (English)

    Hua MAN; Lu-ping QIN; Wan-sheng CHEN; Qiao-yan ZHANG; Han-chen ZHENG; Yin WANG

    2006-01-01

    Aim: To investigate the protective effect of steroidal saponins from Anemarrhena asphodeloides (ATS) on ovariectomy (OVX)-induced bone loss. Methods: Sprague-Dawley rats were divided into sham and OVX groups. The OVX rats were treated with vehicle, nylestriol or steroidal saponins extract for 12 weeks. Serum calcium, phosphorus, estradiol (E2), osteocalcin concentration and serum alkaline phosphatase activity were measured. Bone density was assayed by dual-energy X-ray absorptiometry. The undecalcified longitudinal proximal tibial metaphysical (PTM) sections were cut and stained for histomorphometric analysis of the bone. Results: In OVX rats, alkaline phosphatase activities in serum were markedly increased and concentrations of osteocalcin were decreased by ATS treatment, which had no influence on the body weight. Meanwhile, atrophy of the uterus and descent of bone mineral density (BMD) was suppressed by treatment with ATS. In addition, ATS completely corrected the decreased the concentration of calcium and E2 in serum observed in OVX rats. Histological results showed ATS prevented decreases in trabecular thickness and increases in trabecular separation of proximal tibia metaphysis (PTM) in OVX rats. However, it did not alter osteoclast number in OVX rats. Moreover, ATS (300 mg/kg) had a remarkable effect on promoting bone formation action in OVX rats. Nylestriol treatment decreased the bone formation rate and mineral apposition rate. Conclusion: An adequate supply of steroidal saponins of Anemarrhena asphodeloides prevented OVX-induced bone loss in rats through the promotion of bone formation but not the inhibition of bone resorption.

  15. 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

    start), of which 135 patients had three x-rays (~2 years prior to TNFI, at start of TNFI, and ~2 years after TNFI start). Individual HBL/year prior to and during TNFI was calculated and compared to reference values. RESULTS: Estimated HBL/year varied strongly with age and sex. Compared to the reference...... remission (0.0032 vs. 0.0058 g/cm(2)/year; p sex-specific reference values for DXR-BMD in a large cohort without arthritis. HBL was increased in the majority of rheumatoid arthritis patients initiating TNFI in clinical practice, and only......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...

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

    DEFF Research Database (Denmark)

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

    1999-01-01

    Thinness (low percentage of body fat, low body mass index [BMI], or low body weight) was evaluated as a risk factor for low bone mineral density (BMD) or increased bone loss in a randomized trial of alendronate for prevention of osteoporosis in recently postmenopausal women with normal bone mass (n...... of fat mass parameters, prevention of postmenopausal osteoporosis can be equally achieved in thinner and heavier women....... (r = -0.12 to -0.15, p treatment effect of alendronate was dependent on these 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...

  17. Selective deletion of the membrane-bound colony stimulating factor 1 isoform leads to high bone mass but does not protect against estrogen-deficiency bone loss.

    Science.gov (United States)

    Yao, Gang-Qing; Wu, Jian-Jun; Troiano, Nancy; Zhu, Mei-Ling; Xiao, Xiao-Yan; Insogna, Karl

    2012-07-01

    To better define the biologic function of membrane-bound CSF1 (mCSF1) in vivo, we have generated mCSF1 knockout (k/o) mice. Spinal bone density (BMD) was 15.9% higher in k/o mice compared to wild-type (wt) controls (P bone marrow isolated from mCSF1 k/o mice was reduced compared to wt marrow. There were no defects in osteoblast number or function suggesting that the basis for the high bone mass phenotype was reduced resorption. In addition to a skeletal phenotype, k/o mice had significantly elevated serum triglyceride levels (123 ± 7 vs. 88 ± 3.2 mg/dl; k/o vs. wt, P bone loss following ovariectomy (OVX). OVX induced a significant fourfold increase in the expression of the soluble CSF1 isoform (sCSF1) in the bones of wt mice while expression of mCSF1 was unchanged. These findings indicate that mCSF1 is essential for normal bone remodeling since, in its absence, BMD is increased. Membrane-bound CSF1 does not appear to be required for estrogen-deficiency bone loss while in contrast; our data suggest that sCSF1 could play a key role in this pathologic process. The reasons why mCSF1 k/o mice have hypertriglyceridemia are currently under study.

  18. 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

    +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......) and periosteal (5-fold increase vs. BTX) bone formation rate, trabecular thickness (+25% vs. BTX) and femoral neck strength (+24% vs. BTX). In contrast, SrR did not influence BTX-induced loss of bone formation rate, trabecular bone volume fraction, trabecular thickness, or bone strength. Finally, no additive...

  19. 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-lym......-lymphocyte deficiency did not interfere with the development of periodontal disease in this model, whereas a temporary and moderate reduction in B-lymphocyte numbers seemed to predispose for aggravation of periodontal bone loss.......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...

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

    Directory of Open Access Journals (Sweden)

    Sun-Ouck Kim

    2009-04-01

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

  1. Screening, prevention and management of osteoporosis and bone loss in adult and pediatric hematopoietic cell transplant recipients.

    Science.gov (United States)

    McClune, B L; Polgreen, L E; Burmeister, L A; Blaes, A H; Mulrooney, D A; Burns, L J; Majhail, N S

    2011-01-01

    Long-term survivors of hematopoietic cell transplantation (HCT) are at risk for loss of bone mineral density (BMD) and subsequent osteoporosis. There is a lack of clear guidelines for the screening, prevention and treatment of bone loss after HCT. We reviewed the prevailing literature and provide guidelines developed by our center for the screening and management of this complication. Bone loss occurs predominantly within the first 6-12 months after autologous and allogeneic HCT. Recovery first occurs in the lumbar spine and is followed by a slower recovery of BMD in the femoral neck. BMD may not return to baseline levels in patients with continuing exposure to corticosteroids and calcineurin inhibitors. All HCT recipients should be advised general interventions to reduce fracture risk including adequate intake of calcium and vitamin D. We recommend screening all adult allogeneic and autologous HCT recipients with dual-energy X-ray absorptiometry 1 year after transplantation. Patients at high risk for bone loss (for example, patients receiving ≥ 5 mg of prednisone equivalent daily for > 3 months) can be screened earlier (for example, 3-6 months after HCT). Where indicated, bisphosphonates or other anti-resorptive agents (for example, calcitonin) can be used for prevention or treatment of osteoporosis in adult HCT recipients. Pediatric HCT recipients should be referred to a pediatric endocrinologist for evaluation and treatment of bone loss. There remain several areas of uncertainty that need further research in adult and pediatric HCT recipients, such as the optimal timing and frequency of screening for loss of bone mineral density, relationship of bone loss with risk of fractures, selection of appropriate patients for pharmacologic therapy, and optimal dosing schedule and duration of therapy with anti-resorptive agents.

  2. PTH1-34 Alleviates Radiotherapy-induced Local Bone Loss by Improving Osteoblast and Osteocyte Survival

    Science.gov (United States)

    Chandra, Abhishek; Lin, Tiao; Tribble, Mary Beth; Zhu, Ji; Altman, Allison R.; Tseng, Weiju; Zhang, Yejia; Akintoye, Sunday O.; Cengel, Keith; Liu, X. Sherry; Qin, Ling

    2014-01-01

    Cancer radiotherapy is often complicated by a spectrum of changes in the neighboring bone from mild osteopenia to osteoradionecrosis. We previously reported that parathyroid hormone (PTH, 1–34), an anabolic agent for osteoporosis, reversed bone structural deterioration caused by multiple microcomputed tomography (microCT) scans in adolescent rats. To simulate clinical radiotherapy for cancer patients and to search for remedies, we focally irradiated the tibial metaphyseal region of adult rats with a newly available small animal radiation research platform (SARRP) and treated these rats with intermittent injections of PTH1–34. Using a unique 3D image registration method that we recently developed, we traced the local changes of the same trabecular bone before and after treatments, and observed that, while radiation caused a loss of small trabecular elements leading to significant decreases in bone mass and strength, PTH1–34 preserved all trabecular elements in irradiated bone with remarkable increases in bone mass and strength. Histomorphometry demonstrated that SARRP radiation severely reduced osteoblast number and activity, which were impressively reversed by PTH treatment. In contrast, suppressing bone resorption by alendronate failed to rescue radiation-induced bone loss and to block the rescue effect of PTH1–34. Furthermore, histological analyses revealed that PTH1–34 protected osteoblasts and osteocytes from radiation-induced apoptosis and attenuated radiation-induced bone marrow adiposity. Taken together, our data strongly support a robust radioprotective effect of PTH on trabecular bone integrity through preserving bone formation and shed light on further investigations of an anabolic therapy for radiation-induced bone damage. PMID:24998454

  3. Deoxypyridinoline level in gingival crevicular fluid as alveolar bone loss biomarker in periodontal disease

    Directory of Open Access Journals (Sweden)

    Agustin Wulan Suci Dharmayanti

    2012-06-01

    Full Text Available Background: Periodontal diseases have high prevalence in Indonesia. They are caused by bacteria plaque that induced host response to release pro inflammatory mediator. Pro inflammatory mediators and bacteria product cause degradation of collagen fibers in periodontal tissue. Deoxypyridinoline is one of pyridinoline cross-link of collagen type I that can be used as biomarker in bone metabolic diseases, however, their contribution to detect alveolar bone loss in periodontal diseases remains unclear. Purpose: This study was to evaluate deoxypyridinoline level in gingival crevicular fluid as alveolar bone loss biomarker on periodontal disease. Methods: This study used 24 subjects with periodontal diseases and 6 healthy subjects. Dividing of periodontal disease was based on index periodontal. Gingival crevicular fluid was taken at mesial site of maxillary posterior tooth by paper point and deoxypyridinoline be measured by ELISA technique. Results: We found increasing of deoxypyridinoline level following of the severity of periodontal diseases. There was also significant difference between healthy subjects and periodontal diseases subjects (p<0.05. Conclusion: Deoxypyridinoline level in gingiva crevicular fluid can be used as alveolar bone loss biomarker in periodontal disease subjects.Latar belakang: Prevalensi penyakit periodontal di Indonesia cukup tinggi. Ini disebabkan oleh bakteri plak yang merangsang respon tubuh untuk mengeluarkan mediator keradangan. Mediator keradangan dan produk bakteri menyebabkan degradasi serat kolagen jaringan periodontal. Deoksipiridinolin merupakan salah satu ikatan piridinium dari kolagen tipe I yang dapat digunakan sebagai biomarker penyakit metabolisme tubuh. Akan tetapi, penggunaan deoksipiridinolin untuk mendeteksi kehilangan tulang alveolar pada penyakit periodontal masih belum jelas. Tujuan: Tujuan penelitian ini untuk mengetahui bahwa kadar deoksipiridinolin pada cairan krevikular gingival dapat digunakan

  4. One-stage emergency treatment of open grade IIIB tibial shaft fractures with bone loss.

    Science.gov (United States)

    Tropet, Y; Garbuio, P; Obert, L; Jeunet, L; Elias, B

    2001-02-01

    The purpose of this study was to report the authors' experience with emergency reconstruction of severe tibial shaft fractures. Five male patients were admitted to the emergency room with a grade IIIB open tibial shaft fracture with bone loss (average age, 33 years; age range, 18-65 years). Injuries were the result of motorcycle accidents (N = 2), pedestrian accidents (N = 1), gunshot wound (N = 1), and paragliding fall (N = 1). Primary emergent one-stage management for all patients consisted of administration of antibiotics, debridement, stabilization by locked intramedullary nailing, bone grafting from the iliac crest, and coverage using free muscle flaps (four latissimus dorsi and one gracilis). The average follow-up was 21 months (range, 8 months-3.5 years). Partial weight bearing with no immobilization was started at 3 months, and full weight bearing began 5 months after trauma. No angular complications and no nonunions were observed. There was one case of superficial infection without osteitis. All fractures healed within 6 months in 4 patients and within 10 months in 1 patient. At the last follow-up examination, ankle and knee motion was normal and no pain was noted, except for 1 patient who had associated lesions (ankle motion reduced by 50%). Aggressive emergency management of severe open tibial fractures provides good results. It improves end results markedly, not only by reducing tissue loss from infection, but also reducing healing and rehabilitation times.

  5. 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.

  6. 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.)

  7. 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

  8. 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.

  9. 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.

  10. High serum total bilirubin as a protective factor against hip bone loss in healthy middle-aged men.

    Science.gov (United States)

    Kim, Beom-Jun; Koh, Jung-Min; Ahn, Seong Hee; Lee, Seung Hun; Kim, Eun Hee; Bae, Sung Jin; Kim, Hong-Kyu; Choe, Jae Won; Kim, Ghi Su

    2013-06-01

    Bilirubin is known to have a physiologic role as an antioxidant that efficiently scavenges peroxyl radicals and suppresses oxidation, and oxidative stress has detrimental effects on bone metabolism. In the present study, we performed a 3-year longitudinal study of healthy middle-aged men, investigating the association between serum total bilirubin concentrations and annualized changes in bone mineral density (BMD). The study enrolled a total of 917 Korean men aged 40 years or older who had undergone comprehensive routine health examinations with an average follow-up interval of 3 years. BMD at proximal femur sites was measured with dual-energy X-ray absorptiometry using the same equipment at baseline and follow-up. The overall mean annualized rates of bone loss at the total femur, femoral neck, and trochanter were -0.25 %/year, -0.34 %/year, and -0.44 %/year, respectively. After adjustment for potential confounders, the rates of bone loss at all proximal femur sites were significantly attenuated in a dose-response fashion across increasing bilirubin concentrations (P = 0.006-0.046). Moreover, compared to subjects in the lowest bilirubin quartile category, those in the highest bilirubin quartile category showed significantly less bone loss at all proximal femur sites after adjustment for confounding factors (P = 0.010-0.048). This study provides the first clinical evidence that serum total bilirubin could be a protective marker against future bone loss, especially in subjects without liver diseases.

  11. 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...

  12. Interleukin-33 and RANK-L Interplay in the Alveolar Bone Loss Associated to Periodontitis

    Science.gov (United States)

    Lapérine, Olivier; Cloitre, Alexandra; Caillon, Jocelyne; Huck, Olivier; Bugueno, Isaac Maximiliano; Pilet, Paul; Sourice, Sophie; Le Tilly, Elodie; Palmer, Gaby; Davideau, Jean-Luc; Geoffroy, Valérie; Guicheux, Jérôme; Beck-Cormier, Sarah; Lesclous, Philippe

    2016-01-01

    Introduction Chronic Periodontitis (CP) is an inflammatory disease of bacterial origin that results in alveolar bone destruction. Porphyromonas gingivalis (Pg), one of the main periopathogens, initiates an inflammatory cascade by host immune cells thereby increasing recruitment and activity of osteoclasts, the bone resorbing cells, through enhanced production of the crucial osteoclastogenic factor, RANK-L. Antibodies directed against some cytokines (IL-1β, IL-6 and TNF-α) failed to exhibit convincing therapeutic effect in CP. It has been suggested that IL-33, could be of interest in CP. Objective the present study aims to analyze whether and how IL-33 and RANK-L and/or their interplay are involved in the bone destruction associated to CP. Material and Methods mRNAs and protein expressions of IL-33 and RANK-L were analyzed in healthy and CP human gingival samples by immunohistochemistry (IHC) and RT-qPCR. Murine experimental periodontitis (EP) was induced using Pg infected ligature and Pg free ligature around the first maxillary molar. Alveolar bone loss was recorded by μCT. Mouse gingival explants were stimulated for 24 hours with IL-33 and RANK-L mRNA expression investigated by RT-qPCR. Human oral epithelial cells were infected by Pg for 6, 12; 24 hours and IL-33 and RANK-L mRNA expressions were analyzed by RT-qPCR. Results IL-33 is overexpressed in gingival epithelial cells in human affected by CP as in the murine EP. In human as in murine gingival cells, RANK-L was independently induced by Pg and IL-33. We also showed that the Pg-dependent RANK-L expression in gingival epithelial cells occured earlier than that of IL-33. Conclusion Our results evidence that IL-33 overexpression in gingival epithelial cells is associated with CP and may trigger RANK-L expression in addition to a direct effect of Pg. Finally, IL-33 may act as an extracellular alarmin (danger signal) showing proinflammatory properties in CP perpetuating bone resorption induced by Pg infection

  13. 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.

  14. 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.

  15. Bone loss in rheumatoid arthritis. Influence of disease activity, duration of the disease, functional capacity, and corticosteroid treatment

    DEFF Research Database (Denmark)

    Hansen, M; Florescu, A; Stoltenberg, M;

    1996-01-01

    Axial and appendicular bone mass were studied in 95 patients with rheumatoid arthritis. The aims were to quantify bone mineral density (BMD) and to evaluate the importance of disease activity, duration of disease, functional capacity, and corticosteroid treatment for bone loss in patients...... BMDARM. The decreased BMD in patients with rheumatoid arthritis seems primarily to be caused by an impaired physical activity which may be related to disease activity. Corticosteroids did not decrease BMD in neither the axial nor the appendicular skeleton. The antiinflammatory effect of steroids lead...

  16. 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.

  17. 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.

  18. Adalimumab reduces hand bone loss in rheumatoid arthritis independent of clinical response: Subanalysis of the PREMIER study

    Directory of Open Access Journals (Sweden)

    Elden Aake

    2011-02-01

    Full Text Available Abstract Background Anti-TNF therapy has been shown to reduce radiographic joint damage in rheumatoid arthritis (RA independent of clinical response. This has previously not been examined for periarticular bone loss, the other characteristic feature of bone involvement in RA. The objective of this study was to examine if treatment with the TNF-α inhibitor adalimumab also could reduce periarticular bone loss in RA patients independent of disease activity. Methods RA patients were recruited from the PREMIER study and included 214 patients treated with methotrexate (MTX plus adalimumab and 188 patients treated with MTX monotherapy. Periarticular bone loss was assessed by digital X-ray radiogrammetry metacarpal cortical index (DXR-MCI. Change in DXR-MCI was evaluated in patients with different levels of clinical response, as assessed by changes in DAS28 score at 52 weeks and in mean C-reactive protein (CRP levels during follow-up. Results In the MTX group, there was a greater median DXR-MCI loss among patients with moderate and high disease activity compared to those in remission or with low disease activity (-3.3% vs. -2.2%, p = 0.01. In contrast, periarticular bone loss was independent of disease activity (-1.9% vs. -2.4%, p = 0.99 in the combination group. In the MTX group patients with a mean CRP of ≥ 10 mg/l lost significantly more DXR-MCI than patients with low CRP (-3.1% vs. -1.9%, p Conclusion Adalimumab in combination with MTX reduces periarticular bone loss independently of clinical response. These results support the hypothesis that TNF-α stimulates the osteoclast not only by the inflammatory pathway but do also have a direct effect on the osteoclast. Trial Registration ClinicalTrials (NCT: NCT001195663

  19. 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

  20. 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.

  1. Dairy Intake Is Protective against Bone Loss in Older Vitamin D Supplement Users: The Framingham Study.

    Science.gov (United States)

    Sahni, Shivani; Mangano, Kelsey M; Kiel, Douglas P; Tucker, Katherine L; Hannan, Marian T

    2017-04-01

    Background: Previous studies showed beneficial effects of specific dairy foods on bone health in middle-aged adults.Objective: We examined the association of milk, yogurt, cheese, cream, fluid dairy (milk + yogurt), and milk + yogurt + cheese intakes with bone mineral density (BMD) and 4-y percentage of change in BMD [▵%BMD; femoral neck, trochanter, and lumbar spine (LS)]. We further assessed whether these associations were modified by vitamin D supplement use in this cohort of older adults.Methods: Food-frequency questionnaire responses, baseline BMD (hip and spine, n = 862 in 1988-1989), and follow-up BMD (n = 628 in 1992-1993) were measured in the Framingham study, a prospective cohort study of older Caucasian men and women aged 67-93 y. Outcomes included baseline BMD and ▵%BMD. Dairy-food intakes (servings per week) were converted to energy-adjusted residuals, and linear regression was used, adjusting for covariates. These associations were further examined by vitamin D supplement use.Results: The mean age of the participants was 75 y. In the full sample, dairy-food items were not associated with BMD (P = 0.11-0.99) or with ▵%BMD (P = 0.29-0.96). Among vitamin D supplement users, but not among nonusers, higher milk, fluid dairy, and milk + yogurt + cheese intakes were associated with higher LS BMD (P = 0.011-0.009). Among vitamin D supplement users, but not among nonusers, higher milk + yogurt + cheese intakes were protective against trochanter BMD loss (P = 0.009).Conclusions: In this population of older adults, higher intakes of milk, fluid dairy, and milk + yogurt + cheese were associated with higher LS BMD, and a higher intake of milk + yogurt + cheese was protective against trochanter BMD loss among vitamin D supplement users but not among nonusers. These findings underscore that the benefits of dairy intake on the skeleton may be dependent on vitamin D intake.

  2. Increased EPO Levels Are Associated With Bone Loss in Mice Lacking PHD2 in EPO-Producing Cells.

    Science.gov (United States)

    Rauner, Martina; Franke, Kristin; Murray, Marta; Singh, Rashim Pal; Hiram-Bab, Sahar; Platzbecker, Uwe; Gassmann, Max; Socolovsky, Merav; Neumann, Drorit; Gabet, Yankel; Chavakis, Triantafyllos; Hofbauer, Lorenz C; Wielockx, Ben

    2016-10-01

    The main oxygen sensor hypoxia inducible factor (HIF) prolyl hydroxylase 2 (PHD2) is a critical regulator of tissue homeostasis during erythropoiesis, hematopoietic stem cell maintenance, and wound healing. Recent studies point toward a role for the PHD2-erythropoietin (EPO) axis in the modulation of bone remodeling, even though the studies produced conflicting results. Here, we used a number of mouse strains deficient of PHD2 in different cell types to address the role of PHD2 and its downstream targets HIF-1α and HIF-2α in bone remodeling. Mice deficient for PHD2 in several cell lineages, including EPO-producing cells, osteoblasts, and hematopoietic cells (CD68:cre-PHD2(f/f) ) displayed a severe reduction of bone density at the distal femur as well as the vertebral body due to impaired bone formation but not bone resorption. Importantly, using osteoblast-specific (Osx:cre-PHD2(f/f) ) and osteoclast-specific PHD2 knock-out mice (Vav:cre- PHD2(f/f) ), we show that this effect is independent of the loss of PHD2 in osteoblast and osteoclasts. Using different in vivo and in vitro approaches, we show here that this bone phenotype, including the suppression of bone formation, is directly linked to the stabilization of the α-subunit of HIF-2, and possibly to the subsequent moderate induction of serum EPO, which directly influenced the differentiation and mineralization of osteoblast progenitors resulting in lower bone density. Taken together, our data identify the PHD2:HIF-2α:EPO axis as a so far unknown regulator of osteohematology by controlling bone homeostasis. Further, these data suggest that patients treated with PHD inhibitors or EPO should be monitored with respect to their bone status. © 2016 American Society for Bone and Mineral Research.

  3. 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.

  4. 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.

  5. 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

    2015-11-11

    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.

  6. 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.

  7. 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

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

    Science.gov (United States)

    López-Píriz, Roberto; Solá-Linares, Eva; Granizo, Juan J; Díaz-Güemes, Idohia; Enciso, Silvia; Bartolomé, José F; Cabal, Belén; Esteban-Tejeda, Leticia; Torrecillas, Ramón; Moya, José S

    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 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.

  9. 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...

  10. Arthroscopic Remplissage and Open Latarjet Procedure for the Treatment of Anterior Glenohumeral Instability With Severe Bipolar Bone Loss.

    Science.gov (United States)

    Katthagen, J Christoph; Anavian, Jack; Tahal, Dimitri S; Millett, Peter J

    2016-10-01

    Bipolar bone loss in patients with anterior glenohumeral instability is challenging to treat. The goal of the treatment is to restore stability by ensuring that the humeral head remains within the glenoid vault. This can be achieved either with the combination of an arthroscopic Bankart procedure and remplissage (glenoid bone loss Latarjet procedure (glenoid bone loss >25%). In cases with more severe bipolar bone loss of both the glenoid and the humeral head, the conventional approach has been to lengthen the articular arc of the glenoid and to ignore the Hill-Sachs lesion. However, it has recently been shown that this can still lead to an "off-track" situation with persistent shoulder instability from engagement of the Hill-Sachs on the anterior glenoid. In these cases, the combination of a Hill-Sachs remplissage and the Latarjet procedure can be effective in preventing persistent instability. In this technical note, the surgical technique of an arthroscopic Hill-Sachs remplissage in combination with an open Latarjet procedure is presented.

  11. 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.

  12. 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

  13. Iron overload accelerates bone loss in healthy postmenopausal women and middle-aged men: a 3-year retrospective longitudinal study.

    Science.gov (United States)

    Kim, Beom-Jun; Ahn, Seong Hee; Bae, Sung Jin; Kim, Eun Hee; Lee, Seung-Hun; Kim, Hong-Kyu; Choe, Jae Won; Koh, Jung-Min; Kim, Ghi Su

    2012-11-01

    Despite extensive experimental and animal evidence about the detrimental effects of iron and its overload on bone metabolism, there have been no clinical studies relating iron stores to bone loss, especially in nonpathologic conditions. In the present study, we performed a large longitudinal study to evaluate serum ferritin concentrations in relation to annualized changes in bone mineral density (BMD) in healthy Koreans. A total of 1729 subjects (940 postmenopausal women and 789 middle-aged men) aged 40 years or older who had undergone comprehensive routine health examinations with an average 3 years of follow-up were enrolled. BMD in proximal femur sites (ie, the total femur, femur neck, and trochanter) was measured with dual-energy X-ray absorptiometry using the same equipment at baseline and follow-up. The mean age of women and men in this study was 55.8 ± 6.0 years and 55.5 ± 7.8 years, respectively, and serum ferritin levels were significantly higher in men than in women (p men. After adjustment for potential confounders, the rates of bone loss in all proximal femur sites in both genders were significantly accelerated in a dose-response fashion across increasing ferritin quartile categories (p for trend = 0.043 to <0.001). Consistently, compared with subjects in the lowest ferritin quartile category, those in the third and/or highest ferritin quartile category showed significantly faster bone loss in the total femur and femur neck in both genders (p = 0.023 to <0.001). In conclusion, these data provide the first clinical evidence that increased total body iron stores could be an independent risk factor for accelerated bone loss, even in healthy populations.

  14. Macrophage-specific TLR2 signaling mediates pathogen-induced TNF-dependent inflammatory oral bone loss.

    Science.gov (United States)

    Papadopoulos, George; Weinberg, Ellen O; Massari, Paola; Gibson, Frank C; Wetzler, Lee M; Morgan, Elise F; Genco, Caroline A

    2013-02-01

    Porphyromonas gingivalis is a primary etiological agent of chronic periodontal disease, an infection-driven chronic inflammatory disease that leads to the resorption of tooth-supporting alveolar bone. We previously reported that TLR2 is required for P. gingivalis-induced alveolar bone loss in vivo, and our in vitro work implicated TNF as a key downstream mediator. In this study, we show that TNF-deficient (Tnf(-/-)) mice are resistant to alveolar bone loss following oral infection with P. gingivalis, and thus establish a central role for TNF in experimental periodontal disease. Using bone marrow-derived macrophages (BMDM) from wild-type and gene-specific knockout mice, we demonstrate that the initial inflammatory response to P. gingivalis in naive macrophages is MyD88 dependent and requires cooperative signaling of TLR2 and TLR4. The ability of P. gingivalis to activate cells via TLR2 or TLR4 was confirmed in TLR2- or TLR4-transformed human embryonic kidney cells. Additional studies using bacterial mutants demonstrated a role for fimbriae in the modulation of TLR-mediated activation of NF-κB. Whereas both TLR2 and TLR4 contributed to TNF production in naive macrophages, P. gingivalis preferentially exploited TLR2 in endotoxin-tolerant BMDM to trigger excessive TNF production. We found that TNF induced surface TLR2 expression and augmented TLR-induced cytokine production in P. gingivalis-stimulated BMDM, establishing a previously unidentified TNF-dependent feedback loop. Adoptive transfer of TLR2-expressing macrophages to TLR2-deficient mice restored the ability of P. gingivalis to induce alveolar bone loss in vivo. Collectively, our results identify a TLR2- and TNF-dependent macrophage-specific mechanism underlying pathogen-induced inflammatory bone loss in vivo.

  15. Clinical and hormonal variables related to bone mass loss in anorexia nervosa patients.

    Science.gov (United States)

    Fernández-Soto, María Luisa; González-Jiménez, Amalia; Chamorro-Fernández, Marta; Leyva-Martínez, Socorro

    2013-01-01

    A better understanding of the prognostic factors of low bone mass in anorexia nervosa (AN) and development of effective therapeutic strategies is critical. In order to determine which clinical, biochemical, and/or hormonal parameters could be related to bone mineral density (BMD), 47 female AN patients were classified according to the WHO osteoporosis criteria at lumbar spine (LS). This was a cross-sectional study of 16 AN women with osteoporosis criteria and 31without. Control group was 25 healthy, normal-weight, age-matched women. We assessed BMD using dual-energy X-ray absorptiometry at the LS and body composition. We measured serum fasting cortisol, estradiol, insulin-like growth factor-1 (IGF-1), leptin, sex hormone-binding globulin, albumin and retinol binding protein levels. The prevalence of osteoporosis was 34% and osteopenia 19% at the LS. The AN group with osteoporosis had lower IGF-1 and estradiol levels (both p<0.001), lower serum leptin (p<0.02), and higher cortisolemia (p<0.03) levels compared with AN group without osteoporosis. The BMD and T-score at LS was inversely related to the duration of amenorrhea (p<0.02) and directly related to body mass index (BMI, p<0.002), total fat mass (p<0.03), serum IGF-1 (p<0.01), and estradiol levels (p<0.001) in AN patients. We conclude that AN women with a significant BMD loss have a high risk of developing osteoporosis. A low BMD is a consequence of hormonal alterations which include hypoestrogenism, hypoleptinemia, hypercortisolism, and decreases in IGF-1 levels, as well as a low BMI and fat mass.

  16. 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

  17. 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.

  18. 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

    BACKGROUND: Preventing bone loss associated with menopause and aging and maintaining the normal micro-architecture of bone provide important opportunities for the prevention of osteoporosis and fractures. OBJECTIVE: To determine the safety and efficacy of alendronate, an aminobisphosphonate......, for preventing postmenopausal bone loss. DESIGN: 3-year double-blind, randomized, placebo-controlled trial. SETTING: 15 osteoporosis centers throughout the world. PARTICIPANTS: 447 women who had recently experienced menopause (6 to 36 months before study entry). INTERVENTION: Participants were randomly assigned...

  19. 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

  20. 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.

  1. 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.

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

    Science.gov (United States)

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

    2015-01-01

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

  3. 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.

  4. 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.

  5. Loss of the Homeodomain Transcription Factor Prep1 Perturbs Adult Hematopoiesis in the Bone Marrow.

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    Kentaro Yoshioka

    Full Text Available Prep1, a TALE-family homeodomain transcription factor, has been demonstrated to play a critical role in embryonic hematopoiesis, as its insufficiency caused late embryonic lethality associated with defective hematopoiesis and angiogenesis. In the present study, we generated hematopoietic- and endothelial cell-specific Prep1-deficient mice and demonstrated that expression of Prep1 in the hematopoietic cell compartment is not essential for either embryonic or adult hematopoiesis, although its absence causes significant hematopoietic abnormalities in the adult bone marrow. Loss of Prep1 promotes cell cycling of hematopoietic stem/progenitor cells (HSPC, leading to the expansion of the HSPC pool. Prep1 deficiency also results in the accumulation of lineage-committed progenitors, increased monocyte/macrophage differentiation and arrested erythroid maturation. Maturation of T cells and B cells is also perturbed in Prep-deficient mice. These findings provide novel insight into the pleiotropic roles of Prep1 in adult hematopoiesis that were unrecognized in previous studies using germline Prep1 hypomorphic mice.

  6. 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.

  7. Comparative effects of riboflavin, nicotinamide and folic acid on alveolar bone loss: A morphometric and histopathologic study in rats

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    Akpınar Aysun

    2016-01-01

    Full Text Available Introduction. Periodontitis is a chronic inflammatory and osteolytic disease. Vitamin B complex is a class of water-soluble vitamins that play important roles in cell metabolism. Objective. The aim of this study was to evaluate the effects of riboflavin (RBF, nicotinamide (NA, and folic acid (FA on alveolar bone loss in experimental periodontitis rat model. Methods. Sixty-four male Wistar rats were randomly divided into the following eight groups: Control, Ligated, RBF50 (RBF, 50 mg/kg daily, NA50 (NA, 50 mg/kg daily, FA50 (FA, 50 mg/kg daily, RBF100 (RBF, 100 mg/kg daily, NA100 (NA, 100 mg/kg daily, and FA100 (FA, 100 mg/kg daily. Periodontitis was induced using silk ligature around the right first mandibular molar. After 11 days the rats were sacrificed. Mandible and serum samples were collected. Changes in alveolar bone levels were measured clinically, and periodontal tissues were examined histopathologically. Serum IL-1β (pg/ml levels were analyzed by using ELISA. Results. Mean alveolar bone loss in the mandibular first molar tooth revealed to be significantly lower in RBF100 group than in the Control group. In the Ligated group, alveolar bone loss was significantly higher than in all other groups. The ratio of presence of inflammatory cell infiltration in the Ligated group was significantly higher than in the Control group. The differences in the serum IL-1β levels between the groups were not statistically significant. Osteoclasts that were observed in the Ligated group were significantly higher than those of the Control and FA100 groups. The osteoblastic activity in the Ligated group, RBF100, and NA100 groups were shown to be significantly higher than those in the Control group. Conclusion. This study has demonstrated that systemic administration of RBF, NA, and FA in different dosages (50-100 mg/kg reduced alveolar bone loss in periodontal disease in rats.

  8. Evaluation in a Dog Model of Three Antimicrobial Glassy Coatings: Prevention of Bone Loss around Implants and Microbial Assessments.

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    Roberto López-Píriz

    Full Text Available The aim of the present study is to evaluate, in a ligature-induced peri-implantitis model, the efficacy of three antimicrobial glassy coatings in the prevention of biofilm formation, intrasulcular bacterial growth and the resulting peri-implant bone loss.Mandibular premolars were bilaterally extracted from five beagle dogs. Four dental implants were inserted on each hemiarch. Eight weeks after, one control zirconia abutment and three with different bactericidal coatings (G1n-Ag, ZnO35, G3 were connected. After a plaque control period, bacterial accumulation was allowed and biofilm formation on abutments was observed by Scanning Electron Microscopy (SEM. Peri-implantitis was induced by cotton ligatures. Microbial samples and peri-implant crestal bone levels of all implant sites were obtained before, during and after the breakdown period.During experimental induce peri-implantitis: colony forming units counts from intrasulcular microbial samples at implants with G1n-Ag coated abutment remained close to the basal inoculum; G3 and ZnO35 coatings showed similar low counts; and anaerobic bacterias counts at control abutments exhibited a logarithmic increase by more than 2. Bone loss during passive breakdown period was no statistically significant. Additional bone loss occurred during ligature-induce breakdown: 0.71 (SD 0.48 at G3 coating, 0.57 (SD 0.36 at ZnO35 coating, 0.74 (SD 0.47 at G1n-Ag coating, and 1.29 (SD 0.45 at control abutments; and statistically significant differences (p<0.001 were found. The lowest bone loss at the end of the experiment was exhibited by implants dressing G3 coated abutments (mean 2.1; SD 0.42.Antimicrobial glassy coatings could be a useful tool to ward off, diminish or delay peri-implantitis progression.

  9. 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...... between 2004 and 2011, supplemented with national Danish patient diagnosis and prescription reimbursement databases, a retrospective cohort study was performed. All subjects with more than one DXA scan were included, then stratified into "normonatremia" ([Na(+)]=[137.00-147.00] mmol/L) and "mild...

  10. 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

    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...

  11. Regulators of G protein signaling 12 (Rgs12) promotes osteoclastogenesis in bone remodeling and pathologic bone loss

    Science.gov (United States)

    Calcium (Ca2+) signaling plays a pivotal role in controlling various cellular processes such as secretion, differentiation, proliferation, motility, and cell death through the release of Ca2+ from internal stores and entry from extracellular fluid. In bone, receptor activator of NF-kB ligand (RANKL)...

  12. 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

  13. 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.

  14. Inhibition of osteocyte apoptosis prevents the increase in osteocytic receptor activator of nuclear factor κB ligand (RANKL) but does not stop bone resorption or the loss of bone induced by unloading.

    Science.gov (United States)

    Plotkin, Lilian I; Gortazar, Arancha R; Davis, Hannah M; Condon, Keith W; Gabilondo, Hugo; Maycas, Marta; Allen, Matthew R; Bellido, Teresita

    2015-07-31

    Apoptosis of osteocytes and osteoblasts precedes bone resorption and bone loss with reduced mechanical stimulation, and receptor activator of NF-κB ligand (RANKL) expression is increased with unloading in mice. Because osteocytes are major RANKL producers, we hypothesized that apoptotic osteocytes signal to neighboring osteocytes to increase RANKL expression, which, in turn, increases osteoclastogenesis and bone resorption. The traditional bisphosphonate (BP) alendronate (Aln) or IG9402, a BP analog that does not inhibit resorption, prevented the increase in osteocyte apoptosis and osteocytic RANKL expression. The BPs also inhibited osteoblast apoptosis but did not prevent the increase in osteoblastic RANKL. Unloaded mice exhibited high serum levels of the bone resorption marker C-telopeptide fragments of type I collagen (CTX), elevated osteoclastogenesis, and increased osteoclasts in bone. Aln, but not IG9402, prevented all of these effects. In addition, Aln prevented the reduction in spinal and femoral bone mineral density, spinal bone volume/tissue volume, trabecular thickness, mechanical strength, and material strength induced by unloading. Although IG9402 did not prevent the loss of bone mass, it partially prevented the loss of strength, suggesting a contribution of osteocyte viability to strength independent of bone mass. These results demonstrate that osteocyte apoptosis leads to increased osteocytic RANKL. However, blockade of these events is not sufficient to restrain osteoclast formation, inhibit resorption, or stop bone loss induced by skeletal unloading.

  15. Exercise Countermeasures for Bone Loss During Space Flight: A Method for the Study of Ground Reaction Forces and their Implications for Bone Strain

    Science.gov (United States)

    Peterman, M.; McCrory, J. L.; Sharkey, N. A.; Piazza, S.; Cavanagh, P. R.

    1999-01-01

    Effective countermeasures to prevent loss of bone mineral during long duration space flight remain elusive. Despite an exercise program on MIR flights, the data from LeBlanc et al. (1996) indicated that there was still a mean rate of loss of bone mineral density in the proximal femur of 1.58% per month (n=18, flight duration 4 - 14.4 months). The specific mechanisms regulating bone mass are not known, but most investigators agree that bone maintenance is largely dependent upon mechanical demand and the resultant local bone strains. A plausible hypothesis is that bone loss during space flight, such as that reported by LeBlanc et al. (1996), may result from failure to effectively load the skeleton in order to generate localized bone strains of sufficient magnitude to prevent disuse osteoporosis. A variety of methods have been proposed to simulate locomotor exercise in reduced gravity. In such simulations, and in an actual microgravity environment, a gravity replacement load (GRL) must always be added to return the exercising subject to the support surface and the resulting skeletal load is critically dependent upon the magnitude of the GRL. To our knowledge, GRLs during orbital flight have only been measured once (on STS 81) and it is likely that most or all prior treadmill exercise in space has used GRLs that were less than one body weight. McCrory (1997) has shown that subjects walking and running in simulated zero-G can tolerate GRLs of 1 if an appropriate harness is used. Several investigators have attempted to measure in vivo strains and forces in the bones of humans, but have faced ethical and technical limitations. The anteromedial aspect of the tibial midshaft has been a common site for the placement of strain gauges; one reason to measure strains in the anterior tibia is that this region is surgically accessible. Aamodt et al. (1997) were able to measure strains on the lateral surface of the proximal femur only because their experimental subjects were

  16. Does vitamin D deficiency contribute to post-burn bone loss? [v1; ref status: indexed, http://f1000r.es/QLDkCs

    Directory of Open Access Journals (Sweden)

    Gordon L Klein

    2012-11-01

    Full Text Available Burn injury results in the acute loss of bone as well as the development of progressive vitamin D deficiency. Bone loss occurs acutely due to resorption, which is then followed by apoptosis of osteoblasts preventing repair of the bone loss. The acute resorption is due to a combination of the inflammatory response and the stress response to the burn injury. The resultant production of inflammatory cytokines and endogenous glucocorticoids initially stimulate the osteoblasts to produce RANK ligand, which stimulates marrow stem cell differentiation into osteoclasts. As the stress response persists for approximately one year post-burn the glucocorticoids produced by the body will cause osteoblast apoptosis and adynamic bone, impairing the ability of bone to recover its resorptive losses. The vitamin D deficiency is due to the failure to supplement the diet of burn patients with vitamin D on discharge from hospital and to failure of the skin to make normal quantities of vitamin D on sunlight exposure. Because the bone resorption can be prevented by the acute administration of bisphosphonates it is unlikely that vitamin D deficiency is responsible for the early-onset bone loss following burns. However, because a deficit in trabecular bone remains for at least two years post-burn, it is possible that vitamin D deficiency prevents the recovery of trabecular bone density over the long term.

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

    DEFF Research Database (Denmark)

    González-Bofill, N; Husted, L B; Harsløf, T;

    2011-01-01

    : lumbar spine BMD 1.030 +/- 0.137 g/cm(2), 1.016 +/- 0.147 g/cm(2) and 0.988 +/- 0.124 g/cm(2) in women with the GG, GT and TT genotypes, respectively (p ..., respectively (p = 0.01). The effect remained after 10 years although statistical significance was lost. Haplotype 3 (-1997T-1663ins+1245G) was associated with lower bone mass and higher levels of bone turnover. Compared with haplotype 1, haplotype 3 carriers had lower BMD at the lumbar spine, femoral neck...... and total hip by 0.016 +/- 0.007 g/cm(2), 0.015 +/- 0.006 g/cm(2) and 0.017 +/- 0.006 g/cm(2), respectively (p risk and no overall interaction with the effects of hormone therapy could be demonstrated for any...

  19. β-Glucans (Saccharomyces cereviseae) Reduce Glucose Levels and Attenuate Alveolar Bone Loss in Diabetic Rats with Periodontal Disease.

    Science.gov (United States)

    Silva, Viviam de Oliveira; Lobato, Raquel Vieira; Andrade, Eric Francelino; de Macedo, Cristina Gomes; Napimoga, Juliana Trindade Clemente; Napimoga, Marcelo Henrique; Messora, Michel Reis; Murata, Ramiro Mendonça; Pereira, Luciano José

    2015-01-01

    The objective of this study was to assess the effects of oral ingestion of β-glucans isolated from Saccharomyces cereviseae on the metabolic profile, expression of gingival inflammatory markers and amount of alveolar bone loss in diabetic rats with periodontal disease. Diabetes mellitus was induced in 48 Wistar rats by intraperitoneal injection of streptozotocin (80 mg/kg). After confirming the diabetes diagnosis, the animals were treated with β-glucans (by gavage) for 28 days. On the 14th day of this period, periodontal disease was induced using a ligature protocol. β-glucans reduced the amount of alveolar bone loss in animals with periodontal disease in both the diabetic and non-diabetic groups (p periodontal disease (p periodontal disease (p periodontal effects in diabetic rats with periodontal disease.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Anne-Priscille Trouvin

    2010-11-01

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

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

    DEFF Research Database (Denmark)

    Rye Jørgensen, Niklas; Husted, Lise Bjerre; Skarratt, Kristen K;

    2012-01-01

    to bone mass and fracture incidence in post-menopausal women. A total of 1694 women (aged 45-58) participating in the Danish Osteoporosis Prevention Study were genotyped for 12 functional P2X7 receptor variants. Bone mineral density was determined at baseline and after 10 years. In addition, vertebral...... had increased bone loss. In contrast, the Gln460Arg polymorphism was associated with protection against bone loss. The Ala348Thr polymorphism was associated with a lower vertebral fracture incidence 10 years after menopause. Finally, we developed a risk model, which integrated P2RX7 genotypes. Using...

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

    OpenAIRE

    Ranne, Juha O.; Sarimo, Janne J.; Olli J Heinonen; 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 sco...

  4. 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.

  5. 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.

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

    Science.gov (United States)

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

    2016-03-01

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

  7. 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.

  8. Osteocyte-viability-based simulations of trabecular bone loss and recovery in disuse and reloading

    NARCIS (Netherlands)

    Wang, H.; Ji, B.; Liu, X.S.; van Oers, R.F.M.; Guo, X.E.; Huang, Y.; Hwang, K.C.

    2014-01-01

    Osteocyte apoptosis is known to trigger targeted bone resorption. In the present study, we developed an osteocyte-viability-based trabecular bone remodeling (OVBR) model. This novel remodeling model, combined with recent advanced simulation methods and analysis techniques, such as the element-by-ele

  9. Wii Fit is effective in women with bone loss condition associated with balance disorders: a randomized controlled trial.

    Science.gov (United States)

    Morone, Giovanni; Paolucci, Teresa; Luziatelli, Sara; Iosa, Marco; Piermattei, Cristina; Zangrando, Federico; Paolucci, Stefano; Vulpiani, Maria Chiara; Saraceni, Vincenzo Maria; Baldari, Carlo; Guidetti, Laura

    2016-12-01

    The use of exergame for balance competencies was recently explored in women affected by balance ability reduction with non-conclusive results. The aim of the study was to evaluate the efficacy of a supervised exergame performed with the Wii Fit(®) compared to conventional exercises on balance function, quality of life, fear of fall and well-being in women with bone loss. Thirty-eight female participants aged over 65 years, with a bone loss condition, were enrolled and random allocated in the Wii group or control group. Subject enrolled in Wii group performed a balance training with a Wii Fit supervised by a physiotherapist (1 h, 2 days per week, during 8 weeks) while in control subjects performed the same amount of conventional balance exercises. Subject enrolled in experimental group showed significantly higher scores in terms of Berg Balance Scale (p = 0.027). In SF-36 scores, a significant difference was reported for physical activity score after treatment (p = 0.031). Fear of falling and the psychological scales were not significantly different between the two groups. In women with bone loss condition, a supervised Wii Fit training has shown better efficacy in improving balance performance with respect to conventional balance exercises.

  10. 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.

  11. 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.

  12. Longitudinal evaluation of mouse hind limb bone loss after spinal cord injury using novel, in vivo, methodology.

    Science.gov (United States)

    McManus, Madonna M; Grill, Raymond J

    2011-12-07

    Spinal cord injury (SCI) is often accompanied by osteoporosis in the sublesional regions of the pelvis and lower extremities, leading to a higher frequency of fractures. As these fractures often occur in regions that have lost normal sensory function, the patient is at a greater risk of fracture-dependent pathologies, including death. SCI-dependent loss in both bone mineral density (BMD, grams/cm2) and bone mineral content (BMC, grams) has been attributed to mechanical disuse, aberrant neuronal signaling and hormonal changes. The use of rodent models of SCI-induced osteoporosis can provide invaluable information regarding the mechanisms underlying the development of osteoporosis following SCI as well as a test environment for the generation of new therapies. Mouse models of SCI are of great interest as they permit a reductionist approach to mechanism-based assessment through the use of null and transgenic mice. While such models have provided important data, there is still a need for minimally-invasive, reliable, reproducible, and quantifiable methods in determining the extent of bone loss following SCI, particularly over time and within the same cohort of experimental animals, to improve diagnosis, treatment methods, and/or prevention of SCI-induced osteoporosis. An ideal method for measuring bone density in rodents would allow multiple, sequential (over time) exposures to low-levels of X-ray radiation. This study describes the use of a new whole-animal scanner, the IVIS Lumina XR (Caliper Instruments) that can be used to provide low-energy (1-3 milligray (mGy)) high-resolution, high-magnification X-ray images of mouse hind limb bones over time following SCI. Significant bone density loss was seen in the tibiae of mice by 10 days post-spinal transection when compared to uninjured, age-matched control (naïve) mice (13% decrease, p analysis on mouse femurs post-mortem 30 days post-SCI (9). Our results suggest that the IVIS Lumina XR provides a novel, high

  13. A prospective study of thyroid function, bone loss, and fractures in older men: The MrOS study.

    Science.gov (United States)

    Waring, Avantika C; Harrison, Stephanie; Fink, Howard A; Samuels, Mary H; Cawthon, Peggy M; Zmuda, Joseph M; Orwoll, Eric S; Bauer, Douglas C

    2013-03-01

    Excess thyroid hormone is associated with increased bone loss and fracture risk in older women, but few data exist for men. We sought to determine if thyroid function is independently associated with bone loss and fracture risk in older men. Data were analyzed from the Osteoporotic Fractures in Men (MrOS) study, a cohort of community-dwelling U.S. men aged 65 years and older. Using a case-cohort design, fasting baseline serum archived at -80°C was assayed for thyroid-stimulating hormone (thyrotropin) (TSH) and free thyroxine (FT4) in 397 men with confirmed nonspine fracture, including 157 hip fractures, and 1420 randomly selected men without fracture. TSH and FT4 were analyzed as continuous variables and as thyroid function categories (subclinical hyperthyroid, euthyroid, and subclinical hypothyroid). Hip dual-energy X-ray absorptiometry (DXA) (Hologic QDR4500) was measured at baseline and after a mean follow-up of 4.6 years. Incident nonspine fractures were centrally adjudicated. Bone loss was evaluated with multivariate regression methods and fractures risk was evaluated using hazard models that accounted for the case-cohort sampling, adjusted for age, clinic-site, body mass index (BMI), race, physical activity, corticosteroid use, smoking, alcohol intake, and thyroid medication use. In fully adjusted analyses, TSH was not associated with risk of nonspine fracture (relative hazard [RH] 0.92 per SD decrease in TSH; 95% confidence interval [CI], 0.74-1.14), but was significantly associated with risk of hip fracture (RH 1.31; 95% CI, 1.01-1.71), which persisted among normal range TSH values (RH 1.21; 95% CI, 1.00-1.47). There was no association between TSH or FT4 and bone loss, and fracture risk did not differ significantly by thyroid function category. We conclude that although neither TSH nor FT4 are associated with bone loss, lower serum TSH may be associated with an increased risk of hip fractures in older men.

  14. Ablation of the Sam68 RNA binding protein protects mice from age-related bone loss.

    Directory of Open Access Journals (Sweden)

    Stéphane Richard

    2005-12-01

    Full Text Available The Src substrate associated in mitosis of 68 kDa (Sam68 is a KH-type RNA binding protein that has been shown to regulate several aspects of RNA metabolism; however, its physiologic role has remained elusive. Herein we report the generation of Sam68-null mice by homologous recombination. Aged Sam68-/- mice preserved their bone mass, in sharp contrast with 12-month-old wild-type littermates in which bone mass was decreased up to approximately 75%. In fact, the bone volume of the 12-month-old Sam68-/- mice was virtually indistinguishable from that of 4-month-old wild-type or Sam68-/- mice. Sam68-/- bone marrow stromal cells had a differentiation advantage for the osteogenic pathway. Moreover, the knockdown of Sam68 using short hairpin RNA in the embryonic mesenchymal multipotential progenitor C3H10T1/2 cells resulted in more pronounced expression of the mature osteoblast marker osteocalcin when differentiation was induced with bone morphogenetic protein-2. Cultures of mouse embryo fibroblasts generated from Sam68+/+ and Sam68-/- littermates were induced to differentiate into adipocytes with culture medium containing pioglitazone and the Sam68-/- mouse embryo fibroblasts shown to have impaired adipocyte differentiation. Furthermore, in vivo it was shown that sections of bone from 12-month-old Sam68-/- mice had few marrow adipocytes compared with their age-matched wild-type littermate controls, which exhibited fatty bone marrow. Our findings identify endogenous Sam68 as a positive regulator of adipocyte differentiation and a negative regulator of osteoblast differentiation, which is consistent with Sam68 being a modulator of bone marrow mesenchymal cell differentiation, and hence bone metabolism, in aged mice.

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

    Directory of Open Access Journals (Sweden)

    Katalin Lorinczy

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

  16. Loss of VHL in mesenchymal progenitors of the limb bud alters multiple steps of endochondral bone development.

    Science.gov (United States)

    Mangiavini, Laura; Merceron, Christophe; Araldi, Elisa; Khatri, Richa; Gerard-O'Riley, Rita; Wilson, Tremika LeShan; Rankin, Erinn B; Giaccia, Amato J; Schipani, Ernestina

    2014-09-01

    Adaptation to low oxygen tension (hypoxia) is a critical event during development. The transcription factors Hypoxia Inducible Factor-1α (HIF-1α) and HIF-2α are essential mediators of the homeostatic responses that allow hypoxic cells to survive and differentiate. Von Hippel-Lindau protein (VHL) is the E3 ubiquitin ligase that targets HIFs to the proteasome for degradation in normoxia. We have previously demonstrated that the transcription factor HIF-1α is essential for survival and differentiation of growth plate chondrocytes, whereas HIF-2α is not necessary for fetal growth plate development. We have also shown that VHL is important for endochondral bone development, since loss of VHL in chondrocytes causes severe dwarfism. In this study, in order to expand our understanding of the role of VHL in chondrogenesis, we conditionally deleted VHL in mesenchymal progenitors of the limb bud, i.e. in cells not yet committed to the chondrocyte lineage. Deficiency of VHL in limb bud mesenchyme does not alter the timely differentiation of mesenchymal cells into chondrocytes. However, it causes structural collapse of the cartilaginous growth plate as a result of impaired proliferation, delayed terminal differentiation, and ectopic death of chondrocytes. This phenotype is associated to delayed replacement of cartilage by bone. Notably, loss of HIF-2α fully rescues the late formation of the bone marrow cavity in VHL mutant mice, though it does not affect any other detectable abnormality of the VHL mutant growth plates. Our findings demonstrate that VHL regulates bone morphogenesis as its loss considerably alters size, shape and overall development of the skeletal elements.

  17. Growth Hormone Protects Against Ovariectomy-Induced Bone Loss in States of Low Circulating Insulin-like Growth Factor (IGF-1)*

    OpenAIRE

    Fritton, J. Christopher; Emerton, Kelly B; SUN, HUI; Kawashima, Yuki; Mejia, Wilson; Wu, Yingjie; Rosen, Clifford J.; Panus, David; Bouxsein, Mary; Majeska, Robert J.; Schaffler, Mitchell B.; Yakar, Shoshana

    2009-01-01

    Early after estrogen loss in postmenopausal women and ovariectomy (OVX) of animals, accelerated endosteal bone resorption leads to marrow expansion of long bone shafts that reduce mechanical integrity. Both growth hormone (GH) and insulin-like growth factor (IGF-1) are potent regulators of bone remodeling processes. To investigate the role of the GH/IGF-1 axis with estrogen deficiency, we used the liver IGF-1-deficient (LID) mouse. Contrary to deficits in controls, OVX of LID mice resulted in...

  18. Dihydroartemisinin prevents breast cancer-induced osteolysis via inhibiting both breast caner cells and osteoclasts.

    Science.gov (United States)

    Feng, Ming-Xuan; Hong, Jian-Xin; Wang, Qiang; Fan, Yong-Yong; Yuan, Chi-Ting; Lei, Xin-Huan; Zhu, Min; Qin, An; Chen, Hai-Xiao; Hong, Dun

    2016-01-08

    Bone is the most common site of distant relapse in breast cancer, leading to severe complications which dramatically affect the patients' quality of life. It is believed that the crosstalk between metastatic breast cancer cells and osteoclasts is critical for breast cancer-induced osteolysis. In this study, the effects of dihydroartemisinin (DHA) on osteoclast formation, bone resorption, osteoblast differentiation and mineralization were initially assessed in vitro, followed by further investigation in a titanium-particle-induced osteolysis model in vivo. Based on the proved inhibitory effect of DHA on osteolysis, DHA was further applied to MDA-MB-231 breast cancer-induced mouse osteolysis model, with the underlying molecular mechanisms further investigated. Here, we verified for the first time that DHA suppressed osteoclast differentiation, F-actin ring formation and bone resorption through suppressing AKT/SRC pathways, leading to the preventive effect of DHA on titanium-particle-induced osteolysis without affecting osteoblast function. More importantly, we demonstrated that DHA inhibited breast tumor-induced osteolysis through inhibiting the proliferation, migration and invasion of MDA-MB-231 cells via modulating AKT signaling pathway. In conclusion, DHA effectively inhibited osteoclastogenesis and prevented breast cancer-induced osteolysis.

  19. Bone mass loss is associated with systolic blood pressure in postmenopausal women with type 2 diabetes in Tibet: a retrospective cross-sectional study.

    Science.gov (United States)

    Zhou, L; Song, J; Yang, S; Meng, S; Lv, X; Yue, J; Mina, A; Puchi, B; Geng, Y; Yang, L

    2017-02-02

    We conducted an observational cross-section study to investigate the status of bone mineral mass of Tibetan postmenopausal women with type 2 diabetes and the possible predictors for osteoporosis. We found that prevalence of osteoporosis was 27.0% and blood pressure was an independent risk factor for bone mass loss.

  20. Anti IL-17A therapy inhibits bone loss in TNF-alpha-mediated murine arthritis by modulation of the T-cell balance.

    NARCIS (Netherlands)

    Zwerina, K.; Koenders, M.I.; Hueber, A.; Marijnissen, R.J.; Baum, W.; Heiland, G.R.; Zaiss, M.; McLnnes, I.; Joosten, L.A.B.; Berg, W.B. van den; Zwerina, J.; Schett, G.

    2012-01-01

    Tumour necrosis factor alpha (TNF-alpha) is a major inducer for inflammation and bone loss. Here, we investigated whether interleukin (IL)-17 plays a role in TNF-alpha-mediated inflammation and bone resorption. Human TNF-alpha transgenic (hTNFtg) mice were treated with a neutralizing anti-IL-17A ant

  1. 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.

  2. Peri-Implant Bone Loss and Peri-Implantitis: A Report of Three Cases and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Vanchit John

    2016-01-01

    Full Text Available Dental implant supported restorations have been added substantially to the clinical treatment options presented to patients. However, complications with these treatment options also arise due to improper patient selection and inadequate treatment planning combined with poor follow-up care. The complications related to the presence of inflammation include perimucositis, peri-implant bone loss, and peri-implantitis. Prevalence rates of these complications have been reported to be as high as 56%. Treatment options that have been reported include nonsurgical therapy, the use of locally delivered and systemically delivered antibiotics, and surgical protocols aimed at regenerating the lost bone and soft tissue around the implants. The aim of this article is to report on three cases and review some of the treatment options used in their management.

  3. 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.

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

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    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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    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%, Pmineral density (a...

  10. 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...

  11. Retrograde nail for tibiotalocalcaneal arthrodesis as a limb salvage procedure for open distal tibia and talus fractures with severe bone loss.

    Science.gov (United States)

    Ochman, Sabine; Evers, Julia; Raschke, Michael J; Vordemvenne, Thomas

    2012-01-01

    The treatment of complex fractures of the distal tibia, ankle, and talus with soft tissue damage, bone loss, and nonreconstructable joints for which the optimal timing for reduction and fixation has been missed is challenging. In such cases primary arthrodesis might be a treatment option. We report a series of multi-injured patients with severe soft tissue damage and bone loss, who were treated with a retrograde tibiotalocalcaneal arthrodesis nail as a minimally invasive treatment option for limb salvage. After a median follow-up of 5.4 years, all patients returned to their former profession. The ankle and bone fusion was complete, with moderate functional results and quality of life. Calcaneotibial arthrodesis using a retrograde nail is a good treatment option for nonreconstructable fractures of the ankle joint with severe bone loss and poor soft tissue quality in selected patients with multiple injuries, in particular, those involving both lower extremities, as a salvage procedure.

  12. Immune deficiency augments the prevalence of p53 loss of heterozygosity in spontaneous tumors but not bi-directional loss of heterozygosity in bone marrow progenitors.

    Science.gov (United States)

    Shetzer, Yoav; Napchan, Yael; Kaufman, Tom; Molchadsky, Alina; Tal, Perry; Goldfinger, Naomi; Rotter, Varda

    2017-03-15

    p53 loss of heterozygosity (LOH) is a frequent event in tumors of somatic and Li-Fraumeni syndrome patients harboring p53 mutation. Here, we focused on resolving a possible crosstalk between the immune-system and p53 LOH. Previously, we reported that p53 heterozygous bone-marrow mesenchymal progenitor cells undergo p53 LOH in-vivo. Surprisingly, the loss of either the wild-type p53 allele or mutant p53 allele was detected with a three-to-one ratio in favor of losing the mutant allele. In this study, we examined whether the immune-system can affect the LOH directionality in bone marrow progenitors. We found that mesenchymal progenitor cells derived from immune-deficient mice exhibited the same preference of losing the mutant p53 allele as immune-competent matched cells, nevertheless, these animals showed a significantly shorter tumor-free survival, indicating the possible involvement of immune surveillance in this model. Surprisingly, spontaneous tumors of p53 heterozygous immune-deficient mice exhibited a significantly higher incidence of p53 LOH compared to that observed in tumors derived of p53 heterozygous immune-competent mice. These findings indicate that the immune-system may affect the p53 LOH prevalence in spontaneous tumors. Thus suggesting that the immune-system may recognize and clear cells that underwent p53 LOH, whereas in immune-compromised mice, those cells will form tumors with shorter latency. In individuals with a competent immune-system, p53 LOH independent pathways may induce malignant transformation which requires a longer tumor latency. Moreover, this data may imply that the current immunotherapy treatment aimed at abrogating the inhibition of cellular immune checkpoints may be beneficial for LFS patients.

  13. Guidance for the management of breast cancer treatment-induced bone loss: a consensus position statement from a UK Expert Group.

    Science.gov (United States)

    Reid, David M; Doughty, Julie; Eastell, Richard; Heys, Steven D; Howell, Anthony; McCloskey, Eugene V; Powles, Trevor; Selby, Peter; Coleman, Robert E

    2008-01-01

    In postmenopausal women, the use of aromatase inhibitors increases bone turnover and induces bone loss at sites rich in trabecular bone at an average rate of 1-3% per year leading to an increase in fracture incidence compared to that seen during tamoxifen use. The bone loss is much more marked in young women with treatment-induced ovarian suppression followed by aromatase inhibitor therapy (average 7-8% per annum). Pre-treatment with tamoxifen for 2-5 years may reduce the clinical significance of the adverse bone effects associated with aromatase inhibitors, particularly if this leads to a shortening in the duration of exposure to an aromatase inhibitor. However, skeletal status should still be assessed at the commencement of aromatase inhibitor therapy. The rate of bone loss in women who experience a premature menopause before the age of 45 or are receiving ovarian suppression therapy is accelerated by the concomitant use of aromatase inhibitors. These patients are considered to be at high risk of clinically important bone loss and should have a baseline dual energy X-ray absorptiometry (DXA) assessment of bone mineral density (BMD). Randomised clinical trials in postmenopausal women indicate that bisphosphonates prevent the bone loss and accelerated bone turnover associated with aromatase inhibitor therapy and are a promising strategy for the prevention and treatment of osteoporosis in this setting. Treatment initiation recommendations are based on a combination of risk factors for osteoporotic fracture and BMD levels. Bisphosphonates, along with a healthy lifestyle and adequate intake of calcium and vitamin D are the treatments of choice to prevent bone loss. Due to the rate of bone loss associated with breast cancer treatments, and uncertainties about the interaction between aromatase inhibitor use and BMD for fracture risk, the threshold for intervention has been set at a higher level than that generally recommended for postmenopausal osteoporosis. Management

  14. 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.

  15. 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.

  16. Reversal of bone loss in mice by nongenotropic signaling of sex steroids.

    Science.gov (United States)

    Kousteni, S; Chen, J R; Bellido, T; Han, L; Ali, A A; O'Brien, C A; Plotkin, L; Fu, Q; Mancino, A T; Wen, Y; Vertino, A M; Powers, C C; Stewart, S A; Ebert, R; Parfitt, A M; Weinstein, R S; Jilka, R L; Manolagas, S C

    2002-10-25

    We show that sex steroids protect the adult murine skeleton through a mechanism that is distinct from that used to preserve the mass and function of reproductive organs. The classical genotropic actions of sex steroid receptors are dispensable for their bone protective effects, but essential for their effects on reproductive tissues. A synthetic ligand (4-estren-3alpha,17beta-diol) that reproduces the nongenotropic effects of sex steroids, without affecting classical transcription, increases bone mass and strength in ovariectomized females above the level of the estrogen-replete state and is at least as effective as dihydrotestosterone in orchidectomized males, without affecting reproductive organs. Such ligands merit investigation as potential therapeutic alternatives to hormone replacement for osteoporosis in both women and men [corrected].

  17. Bone Loss after Allogeneic Haematopoietic Stem Cell Transplantation: A Pilot Study on the Use of Zoledronic Acid

    Directory of Open Access Journals (Sweden)

    Andreas Hausmann

    2012-01-01

    Full Text Available Purpose. Bone loss is a common phenomenon following allogeneic haematopoietic stem cell transplantation (allo-HSCT. The study aimed on tolerance and efficacy of zoledronic acid (ZA in patients after allo-HSCT. Methods. 40 patients’ with osteoporosis or osteopenia were recruited on this phase II study. ZA was given at a dose of 4 mg IV every 3 months for 2 years (yrs. BMD was determined by dual-energy X-ray absorptiometry (LS lumbar spine, FH femur hip. Patients were evaluated for deoxypyridinoline (Dpd and calcium excretion by longitudinal measurements. Results. 36 patients who had received at least 3 doses of ZA were evaluable. 26 patients had at least two BMD measurements since baseline (BMD group. Among these patients, BMD increased from 0.97±0.15 to 1.10±0.18 g/cm² (LS baseline—2 yrs, Δ+11.6±6.0%, P<0.001 and from 0.82±0.10 to 0.91±0.10 g/cm² (FH baseline—2 yrs, Δ+7.5±7.0%, P<0.001. Factors associated with an increase in BMD were younger age, female donor sex, and immunosuppression with CSA/MTX. Conclusion. ZA was generally well tolerated; it increases BMD and reduces Dpd excretion significantly in patients with bone loss after allo-HSCT.

  18. Effect of Angiotensin Converting Enzyme Inhibitor and Benzodiazepine Intake on Bone Loss in Older Japanese

    OpenAIRE

    2008-01-01

    We investigated the effects of several frequently described medication regimens on annual percentage change in bone mineral density (BMD). A longitudinal cohort study (a retrospective analysis) was conducted. Subjects in the Adult Health Study (a prospective cohort study begun in 1958) have been followed through biennial medical examinations in Hiroshima, Japan. Participants were 2,111 subjects (67% women; aged 47-95 years) who were undergoing biennial health examinations from 1994 to 2000. T...

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

    Directory of Open Access Journals (Sweden)

    Belsing Tina Z

    2010-09-01

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

  20. Combined photoacoustic and ultrasonic diagnosis of early bone loss and density variations

    Science.gov (United States)

    Lashkari, Bahman; Mandelis, Andreas

    2012-02-01

    Over the past two decades, osteoporosis has been recognized among the most serious public health problems. Fortunately with the growing awareness of osteoporosis, new treatments have been developed for the prevention of fracture. At the same time, there is a rapid improvement in diagnostic methods. In this study biomedical photoacoustics (PA) is applied to the analysis of bone mineral concentration. The PA signal depends on optical as well as mechanical properties of the object and therefore has the potential to provide higher sensitivity to density variations compared with standard diagnostic methods, like ultrasound. A laser source with 800 nm wavelength and different ultrasonic transducers with resonance frequencies in the range 1 to 5 MHz were employed. The CW or frequency-domain (FD) PA radar method was utilized with linear frequency modulation chirps to provide temporal gating control over the transmitted signal and higher sensitivity in the detected signal. The laser intensity was set below the safety standards for skin exposure. The preliminary studies showed adequate optical absorption by cortical bone to generate measurable PA signals and the transmission of laser light through this layer. Experiments are focused on detection and evaluation of PA signals from in-vitro animal cortical bones with and without a trabecular sublayer. The trabecular layer is then diluted by chemical etching and differences in the PA signals are discussed.

  1. 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

  2. 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.

  3. 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

  4. Evaluation of survival rate, bone loss and post operative complication in fixed retained prosthesis with All-on-4 technique: review article

    Directory of Open Access Journals (Sweden)

    Marzieh Alikhasi

    2013-05-01

    Full Text Available   Background and Aims The purpose of this study was to evaluate the survival rate, mean bone loss and post operative complication of implants inserted in All-on-4 technique .   Materials and Methods: The literature was searched using keywords angled implant, All-on-4, tilted implant and graftless technique in the last 10 years (2001 to 2011 and clinical trial article that evaluated survival rate and mean bone loss around axial and tilted implants in All-on-4 technique was selected and evaluated.   A total of 73 articles were found by searching. After evaluation of titles and abstracts, finally 10 clinical trial, that were fully consistent with including criteria such as mean of bone loss and survival rate was selected and evaluated.   Conclusion: Results showed that the survival rate (96-100% and mean bone loss (0.34-1.9 mm with All-on-4 technique in immediate loading is comparable with other implant support treatment plan. Comparison of implant survival and bone loss in axial and tilted implant in All-on-4 system is shown this treatment plan has consistent result with other conventional implant support prosthesis. Also, postoperative complication including fractures of the acrylic temporary prosthesis, detachment of the teeth, abutment or prosthesis screw loosening have been reported with All-on-4 technique.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    )). PATIENTS AND METHODS: A hundred and sixty patients with early, active rheumatoid arthritis (RA) received methotrexate, intra-articular betamethasone and ciclosporin /placebo-ciclosporin. Patients with Z-score ≤0 also started alendronate 10 mg/day. BMD of the hand (digital x-ray radiogrammetry (DXR......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 (CIMESTRA...

  6. Lack of Association of Bone Morphogenetic Protein 2 Gene Haplotypes with Bone Mineral Density, Bone Loss, or Risk of Fractures in Men

    Directory of Open Access Journals (Sweden)

    Satya S. Varanasi

    2011-01-01

    Full Text Available Introduction. The association of bone morphogenetic protein 2 (BMP2 with BMD and risk of fracture was suggested by a recent linkage study, but subsequent studies have been contradictory. We report the results of a study of the relationship between BMP2 genotypes and BMD, annual change in BMD, and risk of fracture in male subjects. Materials and Methods. We tested three single-nucleotide polymorphisms (SNPs across the BMP2 gene, including Ser37Ala SNP, in 342 Caucasian Englishmen, comprising 224 control and 118 osteoporotic subjects. Results. BMP2 SNP1 (Ser37Ala genotypes were found to have similar low frequency in control subjects and men with osteoporosis. The major informative polymorphism, BMP2 SNP3 (Arg190Ser, showed no statistically significant association with weight, height, BMD, change in BMD at hip or lumbar spine, and risk of fracture. Conclusion. There were no genotypic or haplotypic effects of the BMP2 candidate gene on BMD, change in BMD, or fracture risk identified in this cohort.

  7. Effect of angiotensin converting enzyme inhibitor and benzodiazepine intake on bone loss in older Japanese.

    Science.gov (United States)

    Masunari, Naomi; Fujiwara, Saeko; Nakata, Yoshihiro; Furukawa, Kyoji; Kasagi, Fumiyoshi

    2008-03-01

    We investigated the effects of several frequently described medication regimens on annual percentage change in bone mineral density (BMD). A longitudinal cohort study (a retrospective analysis) was conducted. Subjects in the Adult Health Study (a prospective cohort study begun in 1958) have been followed through biennial medical examinations in Hiroshima, Japan. Participants were 2,111 subjects (67% women; aged 47-95 years) who were undergoing biennial health examinations from 1994 to 2000. The subjects were examined for the effect of certain drugs on bone mineral change during baseline and one follow-up (4 year later) measurements. Mean annual percentage change in BMD at the femoral neck was -0.38% for men, and -1.14% for women. After adjustment for sex, age, change of weight, alcohol consumption, and smoking status, annual percentage change in BMD decreased by 0.61% among individuals taking angiotensin converting enzyme (ACE) inhibitors continuously in comparison with individuals who had not taken them (p = 0.002): also decreased 0.40% among individuals taking benzodiazepines (BZDs) continuously (p = 0.034). Our results suggest that careful consideration should be given to the use of ACE inhibitors and BZDs in a cohort of Japanese elderly.

  8. Anabolic Steroids as a Novel Therapeutic Strategy for the Prevention of Bone Loss after Spinal Cord Injury: Animal Model and Molecular Mechanism

    Science.gov (United States)

    2012-10-01

    osteoporosis . Curr Osteoporos Rep. 8(4): p. 212-8. 5. Kalincik, T., et al., Selected changes in spinal cord morphology after T4 transection and olfactory...mass and strength in animal models of bone loss due to estrogen deficiency and immobilization (4). Scl-Ab also increased bone mineral density (BMD) in... osteoporosis . Curr Osteoporos Rep. 2010, 8:212-218. 3. Jiang SD, Jiang LS, Dai L. Mechanisms of osteoporosis in spinal cord injury. Clin Endocrinol (Oxf

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

    Science.gov (United States)

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

    2015-04-01

    Microgravity induces less pressure on muscle/bone, which is a major reason for muscle atrophy as well as bone loss. Currently, physical exercise is the only countermeasure used consistently in the U.S. human space program to counteract the microgravity-induced skeletal muscle atrophy and bone loss. However, the routinely almost daily time commitment is significant and represents a potential risk to the accomplishment of other mission operational tasks. Therefore, development of more efficient exercise programs (with less time) to prevent astronauts from muscle atrophy and bone loss are needed. Consider the two types of muscle contraction: exercising forces muscle contraction and prevents microgravity-induced muscle atrophy/bone loss, which is a voluntary response through the motor nervous system; and cold temperature exposure-induced muscle contraction is an involuntary response through the vegetative nervous system, we formed a new hypothesis. The main purpose of this pilot study was to test our hypothesis that exercise at 4 °C is more efficient than at room temperature to prevent microgravity-induced muscle atrophy/bone loss and, consequently reduces physical exercise time. Twenty mice were divided into two groups with or without daily short-term (10 min × 2, at 12 h interval) cold temperature (4 °C) exposure for 30 days. The whole bodyweight, muscle strength and bone density were measured after terminating the experiments. The results from the one-month pilot study support our hypothesis and suggest that it would be reasonable to use more mice, in a microgravity environment and observe for a longer period to obtain a conclusion. We believe that the results from such a study will help to develop efficient exercise, which will finally benefit astronauts' heath and NASA's missions.

  10. 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.

  11. 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.

  12. 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.

  13. Relation of statin use and bone loss: a prospective population-based cohort study in early postmenopausal women.

    Science.gov (United States)

    Sirola, J; Sirola, J; Honkanen, R; Kröger, H; Jurvelin, J S; Mäenpää, P; Saarikoski, S

    2002-07-01

    Recent experimental and epidemiologic studies have suggested that the lipid-lowering drugs, statins, may have bone-protective effects. We studied the effects of statin use on the change in bone mineral density (BMD) in a prospective 4.5-year cohort study based on subjects from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) Study, Finland. Six hundred and twenty women aged 53-64 years were divided into four groups: 55 women reported continuous and 63 women occasional statin use during the follow-up; 142 non-users of statins reported hypercholesterolemia whereas 360 non-users did not. Spinal and femoral BMDs were measured by dual-energy X-ray densitometry in 1995-1996 and 1999-2000 and the BMD changes of the four groups were compared. Characteristics of the study population were obtained with postal inquiries. The mean annual spinal and femoral BMD changes of the study groups were 0.29% and -0.50% for the continuous statin users, 0.19% and -0.57% for the occasional statin users, 0.52% and -0.29% for the hypercholesterolemic non-users of statins, and 0.39% and -0.33% for the non-users of statins without hypercholesterolemia, ( p = 0.398 and p = 0.404) respectively. The corresponding BMD changes adjusted for age, years since menopause, body mass index, BMD at baseline, calcium intake, estrogen and cortisone therapy, duration of follow-up and statin use before the baseline were -0.20% and -0.47%, 0.19% and -0.54%, 0.54% and -0.32%, 0.47% and -0.33% ( p = 0.134 and p = 0.628), respectively. Our results suggest that statins do not protect from early postmenopausal bone loss. Randomized trials are needed to confirm these results.

  14. 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.

  15. Inhibitory Effects of KP-A159, a Thiazolopyridine Derivative, on Osteoclast Differentiation, Function, and Inflammatory Bone Loss via Suppression of RANKL-Induced MAP Kinase Signaling Pathway.

    Directory of Open Access Journals (Sweden)

    Hye Jung Ihn

    Full Text Available Abnormally elevated formation and activation of osteoclasts are primary causes for a majority of skeletal diseases. In this study, we found that KP-A159, a newly synthesized thiazolopyridine derivative, inhibited osteoclast differentiation and function in vitro, and inflammatory bone loss in vivo. KP-A159 did not cause a cytotoxic response in bone marrow macrophages (BMMs, but significantly inhibited the formation of multinucleated tartrate-resistant acid phosphatase (TRAP-positive osteoclasts induced by macrophage colony-stimulating factor (M-CSF and receptor activator of nuclear factor-κB ligand (RANKL. KP-A159 also dramatically inhibited the expression of marker genes related to osteoclast differentiation, including TRAP (Acp5, cathepsin K (Ctsk, dendritic cell-specific transmembrane protein (Dcstamp, matrix metallopeptidase 9 (Mmp9, and nuclear factor of activated T-cells, cytoplasmic 1 (Nfatc1. Moreover, actin ring and resorption pit formation were inhibited by KP-A159. Analysis of the signaling pathway involved showed that KP-A159 inhibited RANKL-induced activation of extracellular signal-regulated kinase (ERK, c-Jun N-terminal kinase (JNK, and mitogen-activated protein kinase kinase1/2 (MEK1/2. In a mouse inflammatory bone loss model, KP-A159 significantly rescued lipopolysaccharide (LPS-induced bone loss by suppressing osteoclast numbers. Therefore, KP-A159 targets osteoclasts, and may be a potential candidate compound for prevention and/or treatment of inflammatory bone loss.

  16. 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.

  17. 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 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.

  18. 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...

  19. Gastroresistant microparticles containing sodium alendronate prevent the bone loss in ovariectomized rats.

    Science.gov (United States)

    Cruz, Letícia; Assumpção, Evelise; Andrade, Sérgio F; Conrado, Daniela J; Kulkamp, Irene C; Guterres, Sílvia S; Pohlmann, Adriana R

    2010-08-11

    Sodium alendronate, an antiresorptive drug, primarily used in the treatment of osteoporosis was encapsulated in blended microparticles composed of Eudragit S100 and Methocel K15M. The micropowder obtained by spray-drying technique was characterized in terms of its morphology, particle size, encapsulation efficiency and in vitro drug release. In vivo studies were carried out in order to evaluate the pharmacodynamic effect and the ulcerogenic activity of sodium alendronate-loaded microparticles after oral administration in rats. Drug encapsulation efficiency was close to 80% and particle mean diameter of 13.8 microm. SEM analysis showed spherical collapsed shape particles with smooth surface. At pH 1.2, in vitro experiments showed that <10% of the drug was released from the microparticles. At pH 6.8, the microparticles were able to prolong the sodium alendronate release for 12h. In vivo experiments carried out in ovariectomized rats showed bone mineral density significantly higher for the sodium alendronate-loaded microparticles than for the negative control groups. Furthermore, the microencapsulation of the drug showed a significant reduction in the ulcerative lesion index. In conclusion, the blended microparticles are excellent oral carriers for sodium alendronate since they were able to maintain the drug antiresorptive effect and to reduce the gastrointestinal drug toxicity.

  20. Comparative study on reduction of bone loss and lipid metabolism abnormality in ovariectomized rats by soy isoflavones, daidzin, genistin, and glycitin.

    Science.gov (United States)

    Uesugi, T; Toda, T; Tsuji, K; Ishida, H

    2001-04-01

    The effects of the soy isoflavone glycoside, daidzin, genistin, and glycitin on bone loss and lipid metabolism in ovariectomized (ovx) rats were compared with those of estrone. Thirty-six 11-week-old female Sprague-Dawley rats were assigned to six groups, sham-operated, ovx, ovx+glycitin, ovx+daidzin, ovx+genistin, and ovx+estrone and fed matched amounts of a commercial calcium-deficient diet for 4 weeks. Throughout this period, daidzin, genistin or glycitin (25, 50 or 100 mg/kg/d) was given orally using a stomach tube, or estrone (7.5 microg/kg/d) was administered subcutaneously. Daidzin, genistin and glycitin significantly prevented bone loss in ovx rats at a dose of 50 mg/kg/d, like estrone. At this dose glycitin and daidzin also prevented ovx-induced uterine atrophy and increases in body weight gain, abdominal fat, serum total cholesterol and triglyceride, and urinary excretion of pyridinoline and deoxypyridinoline with statistical significance, like estrone. On the other hand, genistin prevented ovx-induced uterine atrophy only at a dose of 100 mg/kg, but did not block any other change of ovx rats at a dose of 50 or 100 mg/kg. These findings indicate that daidzin, glycitin, and genistin are effective in preventing bone loss and the former two compounds are effective in reversing the unfavorable changes of lipid metabolism in this model. It is suggested that the preventive effect of daidzin or glycitin on bone loss in ovx rats is due to suppression of bone turnover, as in the case of estrone, but genistin has a different mechanism of action from the other compounds. Soy isoflavone glycosides may represent a potential alternative therapy in the treatment of bone loss and lipid metabolism abnormality in ovarian hormone-deficient women.

  1. [Cytogenetic changes of the bone marrow in massive blood loss and their correction with mexidol].

    Science.gov (United States)

    Kozhura, V L; Tlatova, T A; Kondakova, N V; Sakharova, V V; Ripa, N V

    2003-01-01

    The citogenetic lesions were evaluated in the marrow erythroblasts of 45 anesthetized white nonlinear male rats, weight--200-300 g who were subjected to an acute blood loss with a 1-hour arterial hypotension (ABR = 40 mm Hg); the micronucleus tests was made use of. Two stages of the increase of polychromatophilic erythrocytes with micronuclei in the marrow of the animals, who underwent a massive blood loss, were registered: stage 1--an incomplete marrow ischemia with a subsequent arterial hypotension and with a reliably confirmed formation of cytogenetic lesions in the marrow polychromatophilic erythrocytes; stage 2--the reperfusion period contributed to a 1.7-fold increase of polychromatophilic erythrocytes with micronuclei versus the previous stage. Mexidole, when used at 50 mg/kg prior to blood reinfusion, decreased the quantity of polychromatophilic erythrocytes with micronuclei to the basic level, which is indicative of reversibility and instability of cytogenetics impairments in the marrow cells of animals observed in the early post-resuscitation period.

  2. A quantitative CT system applied to the femoral shaft and lateral condyle for evaluating bone loss in patients with secondary hyperparathyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Sakurai, Kiyoko [Kitasato Univ., Sagamihara, Kanagawa (Japan). School of Allied Health Sciences; Matsubayashi, Takashi; Tsukamoto, Yusuke

    1996-09-01

    An improved quantitative CT (QCT) system for evaluating bone loss was reported, which was based on the 3 parameters newly made obtainable on the CT scanner of BOCT (bone CT number, the mean CT number within bone region). PKCT (peak CT number, CT number at the peak of the frequency distribution of CT numbers in the histogram) and MXCT (maximum CT number within bone region). Subjects were 37 patients, who were treated with ordinary dose of 1,25(OH{sub 2})D{sub 3} or were of more progressed symptoms, and 87 normal healthy volunteers. A Quantex apparatus (YMS Co.) was used for CT scanning with the tube voltage of 120 kVp for the femoral shaft and 80 kVp for lateral condyle and vertebra and with slice thickness of 10 mm. A phantom consisting of an aluminum pipe inserted in an acrylic acid resin column was used to obtain the standard CT number, and the standard phantom of the BMD (bone mineral density) package (YMS Co.), in the QCT of the femoral lateral condyles. Results were analyzed by SAS statistical program. The 3 parameters together with BMD were found quite useful far evaluating bone loss in all patients. (K.H.)

  3. 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.

  4. 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

  5. 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; Loureiro, Melina Bezerra; 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

  6. 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

  7. Preventive effects of the plant isoflavones, daidzin and genistin, on bone loss in ovariectomized rats fed a calcium-deficient diet.

    Science.gov (United States)

    Ishida, H; Uesugi, T; Hirai, K; Toda, T; Nukaya, H; Yokotsuka, K; Tsuji, K

    1998-01-01

    The effects of the plant isoflavones, daidzin and genistin, on bone loss in ovariectomized (ovx) rats fed a calcium-deficient diet were investigated. Daidzin and genistin were orally administered to ovx rats for 4 weeks. The femurs of these rats showed significantly lower density, strength (breaking forces), ash weight and calcium and phosphorus content (pdaidzin or genistin for 4 weeks at a dose of 50 mg/kg/d and in animals receiving subcutaneous estrone (7.5 microg/kg/d) as a positive control. Ovariectomy caused atrophy of the uterus and increased the ratio of the urinary excretion of pyridinoline and deoxypyridinoline to endogenous creatinine excretion. This was prevented by administration of daidzin or estrone, but, interestingly, not genistin. The preventive effect of daidzin treatment on bone loss in ovariectomized rats appears to be due to suppression of bone turnover. Genistin has a different mechanism of action from daidzin.

  8. Treatment of bone loss in osteopenic patients with Crohn's disease : a double-blind, randomised trial of oral risedronate 35 mg once weekly or placebo, concomitant with calcium and vitamin D supplementation

    NARCIS (Netherlands)

    van Bodegraven, Ad A.; Bravenboer, Nathalie; Witte, Birgit I.; Dijkstra, Gerard; van der Woude, C. Janneke; Stokkers, Pieter C. M.; Russel, Maurice G.; Oldenburg, Bas; Pierik, Marieke; Roos, Jan C.; van Hogezand, Ruud A.; Dik, Vincent K.; Oostlander, Angela E.; Netelenbos, J. Coen; van de langerijt, Lex; Hommes, Daniel W.; Lips, Paul

    2014-01-01

    Objective Osteoporosis and fractures are frequently encountered in patients with Crohn's disease. In order to prevent fractures, treatment with bone protecting drugs appears warranted early in the course of bone disease when bone loss is not yet prominent. We therefore aimed to demonstrate a benefic

  9. Skipping breakfast and less exercise are risk factors for bone loss in young Japanese adults: a 3-year follow-up study.

    Science.gov (United States)

    Nagata, Keiji; Yoshida, Munehito; Ishimoto, Yuyu; Hashizume, Hiroshi; Yamada, Hiroshi; Yoshimura, Noriko

    2014-07-01

    Although bone loss contributes to osteoporosis (OP) in the elderly, little is known about changes in bone mineral density (BMD) in young adults that lead to bone loss. Here, we evaluated the rate of bone change and risk factors for bone loss in young men and women using data from a 3-year prospective study of Japanese medical students. The study included a self-administrated questionnaire survey, anthropometric measurements, and BMD measurements of the spine (L2-L4) and femoral neck (FN). After 3 years, the BMD of the participants was again measured at the same sites. In all, 458 students (95.4 %; 298 men and 160 women; age range, 18-29 years; mean age, 20.2 years) completed both the baseline and follow-up surveys. The mean L2-L4 BMD value at baseline increased significantly within 3 years. This tendency was also observed for the FN in men but not in women. The annual changes at L2-L4 were 1.78 % in men and 0.97 % in women per year; those for FN were 1.08 % in men and 0.08 % in women per year. However, 20.3 % and 38.5 % of the total freshmen lost BMD in the lumbar spine and FN, respectively. After adjustment for age and body mass index, logistic regression analysis revealed that bone loss in men at L2-L4 at the baseline was affected by skipping breakfast. In contrast, exercise (>2 h/week) increased lumbar spine BMD in both genders. These findings indicate that breakfast and exercise are important for maintaining BMD in young men and women.

  10. 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.

  11. Bariatric bypasses contribute to loss of bone mineral density but reduce axial back pain in morbidly obese patients considering spine surgery

    Science.gov (United States)

    Epstein, Nancy E.

    2017-01-01

    Background: Many spine surgeons recommend stringent weight loss, including bariatric bypass procedures, prior to “elective” spine surgery (should not be for axial back pain alone) in morbidly obese patients (defined by a body mass index (BMI) of >40 mg/kg2 or >35 mg/kg2 with two or more major comorbidities) to reduce their greater risk for major perioperative complications. Although bypasses typically lead to marked weight reduction and even reduced axial back pain, they also promote unrecognized and often insufficiently treated vitamin D deficiency and loss of bone mineral density. Methods: Morbidly obese patients who are under consideration for “elective” spine operations (other than for back pain alone) are often told to lose weight. Some choose to undergo bariatric bypass procedures, but are unaware of the potential risks/complications of these procedures. Results: Within the first 2 years following most bariatric bypass procedures, patients experience not only marked loss of weight and muscle mass, but also significant vitamin D deficiency and loss of bone mineral density, increasing their susceptibility to fractures. Nevertheless, some patients also experience a sufficient reduction of axial back pain to avoid spinal surgery. Conclusions: Morbidly obese patients under consideration for “elective” spine surgery may undergo bariatric bypass procedures that lead to a significant reduction of vitamin D levels and loss of bone mineral density. However, potential benefits may include a sufficient reduction of axial back pain to avoid surgery in a select subset of patients altogether. PMID:28217392

  12. Exercise to Counteract Loss of Bone and Muscle During Androgen Deprivation Therapy in Men with Prostate Cancer

    Science.gov (United States)

    2009-08-01

    to get a bone scintigraphy, 1) and 13 did not qualify (started medications that influence bone metabolism, 4; unrepaired hernias , 2; positive bone...before vs 0.785±0.098 g/cm2 after) subregions of the hip. However, BMD at the femoral neck, a common site of osteoporotic fracture, decreased over the

  13. 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.

  14. 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.

  15. Cross-sectional and longitudinal study protocols of the ‘ADIposity and BOne metabolism: effects of eXercise-induced weight loss in obese adolescents’ (ADIBOX) project

    Science.gov (United States)

    Chaplais, Elodie; Naughton, Geraldine; Greene, David; Pereira, Bruno; Thivel, David; Courteix, Daniel

    2016-01-01

    Introduction A need exists for sustainable and clinically effective weight management interventions, suitable for preventing well-linked chronic disease such as diabetes and cardiovascular disease and some less investigated secondary conditions such as bone alteration. The ADIposity and BOne metabolism: effects of eXercise-induced weight loss in obese adolescents (ADIBOX) protocol was designed to provide a better understanding of the interaction between adipokines and bone hormones in adolescents with obesity and how a 10-month physical activity programme may affect these interactions. Methods and analysis The ADIBOX protocol combines 2 studies. The first study involves a total of 68 adolescents aged 12–16 years. This cross-sectional study will include both males and females (1:1 ratio), either living with obesity/overweight (n=34; body mass index (BMI) ≤97th centile and ≥85th centile) or normal weight (n=34; BMI<85th centile). The second study is a longitudinal study that will include 50 obese adolescent girls and track them over a period of 42 weeks. Weight loss programme will consist of a combination of physical activity and a normocaloric diet. Bone and adiposity-related measurements will be performed every 14 weeks. Both studies will assess participants' anthropometric profile, nutrition and physical activity, body composition, bone densitometry and blood markers of bone, growth and adiposity. Ethics and dissemination The ADIBOX protocol complies with the ethics guidelines for clinical research and has been approved by their respective ethics committee (Australian Catholic University Committee Ethic, Australia and Hospital Sud Est 1 committee, France). Findings from this protocol are expected to clarify the possible interactions between adiposity and bone in childhood obesity and will be disseminated at several research conferences and published articles in peer-reviewed journals. Trial registration number NCT02626273; Pre-results. PMID:27797988

  16. 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.

  17. 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

  18. 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.

  19. Combined zoledronic acid and meloxicam reduced bone loss and tumour growth in an orthotopic mouse model of bone-invasive oral squamous cell carcinoma.

    Science.gov (United States)

    Martin, C K; Dirksen, W P; Carlton, M M; Lanigan, L G; Pillai, S P; Werbeck, J L; Simmons, J K; Hildreth, B E; London, C A; Toribio, R E; Rosol, T J

    2015-09-01

    Oral squamous cell carcinoma (OSCC) is common in cats and humans and invades oral bone. We hypothesized that the cyclooxygenase (COX)-2 inhibitor, meloxicam, with the bisphosphonate, zoledronic acid (ZOL), would inhibit tumour growth, osteolysis and invasion in feline OSCC xenografts in mice. Human and feline OSCC cell lines expressed COX-1 and COX-2 and the SCCF2 cells had increased COX-2 mRNA expression with bone conditioned medium. Luciferase-expressing feline SCCF2Luc cells were injected beneath the perimaxillary gingiva and mice were treated with 0.1 mg kg(-1) ZOL twice weekly, 0.3 mg kg(-1) meloxicam daily, combined ZOL and meloxicam, or vehicle. ZOL inhibited osteoclastic bone resorption at the tumour-bone interface. Meloxicam was more effective than ZOL at reducing xenograft growth but did not affect osteoclastic bone resorption. Although a synergistic effect of combined ZOL and meloxicam was not observed, combination therapy was well-tolerated and may be useful in the clinical management of bone-invasive feline OSCC.

  20. SH3BP2 cherubism mutation potentiates TNF-α-induced osteoclastogenesis via NFATc1 and TNF-α-mediated inflammatory bone loss.

    Science.gov (United States)

    Mukai, Tomoyuki; Ishida, Shu; Ishikawa, Remi; Yoshitaka, Teruhito; Kittaka, Mizuho; Gallant, Richard; Lin, Yi-Ling; Rottapel, Robert; Brotto, Marco; Reichenberger, Ernst J; Ueki, Yasuyoshi

    2014-12-01

    Cherubism (OMIM# 118400) is a genetic disorder with excessive jawbone resorption caused by mutations in SH3 domain binding protein 2 (SH3BP2), a signaling adaptor protein. Studies on the mouse model for cherubism carrying a P416R knock-in (KI) mutation have revealed that mutant SH3BP2 enhances tumor necrosis factor (TNF)-α production and receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation in myeloid cells. TNF-α is expressed in human cherubism lesions, which contain a large number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells, and TNF-α plays a critical role in inflammatory bone destruction in homozygous cherubism mice (Sh3bp2(KI/KI) ). The data suggest a pathophysiological relationship between mutant SH3BP2 and TNF-α-mediated bone loss by osteoclasts. Therefore, we investigated whether P416R mutant SH3BP2 is involved in TNF-α-mediated osteoclast formation and bone loss. Here, we show that bone marrow-derived M-CSF-dependent macrophages (BMMs) from the heterozygous cherubism mutant (Sh3bp2(KI/+) ) mice are highly responsive to TNF-α and can differentiate into osteoclasts independently of RANKL in vitro by a mechanism that involves spleen tyrosine kinase (SYK) and phospholipase Cγ2 (PLCγ2) phosphorylation, leading to increased nuclear translocation of NFATc1. The heterozygous cherubism mutation exacerbates bone loss with increased osteoclast formation in a mouse calvarial TNF-α injection model as well as in a human TNF-α transgenic mouse model (hTNFtg). SH3BP2 knockdown in RAW264.7 cells results in decreased TRAP-positive multinucleated cell formation. These findings suggest that the SH3BP2 cherubism mutation can cause jawbone destruction by promoting osteoclast formation in response to TNF-α expressed in cherubism lesions and that SH3BP2 is a key regulator for TNF-α-induced osteoclastogenesis. Inhibition of SH3BP2 expression in osteoclast progenitors could be a potential strategy for

  1. High serum carotenoids associated with lower risk for bone loss and osteoporosis in post-menopausal Japanese female subjects: prospective cohort study.

    Directory of Open Access Journals (Sweden)

    Minoru Sugiura

    Full Text Available INTRODUCTION: Recent epidemiological studies show that high intakes of carotenoids might be useful to maintain bone health, but little is known about the association of serum carotenoids with change of bone mineral density (BMD. The objective of this study was to investigate longitudinally whether serum carotenoids are associated with bone loss. METHODS: We conducted a follow-up on 146 male and 99 pre- and 212 post-menopausal female subjects from the Mikkabi study. Those who participated in previous BMD surveys and completed four years of follow-up were examined longitudinally. RESULTS: During a 4-year follow-up, 15 of the post-menopausal female subjects developed new-onset osteoporosis. In contrast, none of the male and pre-menopausal female subjects did. In male and pre-menopausal female subjects, the six serum carotenoids at the baseline were not associated with bone loss. On the other hand, in post-menopausal female subjects, the 4-year bone loss of radius was inversely associated with the serum carotenoid concentrations, especially in β-carotene. After adjustments for confounders, the odds ratios (OR for osteoporosis in the highest tertiles of serum β-carotene and β-cryptoxanthin against the lowest tertiles were 0.24 (95% confidence interval 0.05-1.21 and 0.07 (CI: 0.01-0.88, respectively. Serum β-cryptoxanthin was also inversely associated with the risk for osteopenia and/or osteoporosis (P for trend, 0.037. In addition, our retrospective analysis revealed that subjects who developed osteoporosis and/or osteopenia during the survey period had significantly lower serum concentrations of β-cryptoxanthin and β-carotene at the baseline than those in the normal group. CONCLUSIONS: Antioxidant carotenoids, especially β-cryptoxanthin and β-carotene, are inversely associated with the change of radial BMD in post-menopausal female subjects.

  2. 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.

  3. Menopause and Bone Loss

    Science.gov (United States)

    ... only, or, if you have a uterus, combined estrogen plus progestin) in some women for short intervals ——Human parathyroid hormone (teriparatide) for severe osteoporosis ——Calcitonin All of these medicines are effective, but ...

  4. Bone Loss in IBD

    Science.gov (United States)

    ... a clinical trial of experimental treatments. Interactive Disease Tracker Use GI Buddy to keep a daily log ... increased risk of developing osteoporosis because their cytokine activity is greater. The cytokine connection also might explain ...

  5. 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.

  6. The quantification of glenoid bone loss in anterior shoulder instability; MR-arthro compared to 3D-CT

    Energy Technology Data Exchange (ETDEWEB)

    Markenstein, Jeroen E. [Onze Lieve Vrouwe Gasthuis, Department of Orthopedic Surgery, Postbox 95500, Amsterdam (Netherlands); Jaspars, Kjell C.C.J. [Van Weel-Bethesda Ziekenhuis, Department of Orthopedic Surgery, Dirksland (Netherlands); Hulst, Victor P.M. van der [Onze Lieve Vrouwe Gasthuis, Department of Radiology, Postbox 95500, Amsterdam (Netherlands); Willems, W.J. [Delairesse Kliniek, Department of Orthopedic Surgery, Amsterdam (Netherlands)

    2014-04-15

    The purpose of this study is to investigate if magnetic resonance imaging with intra-articular contrast (MR-arthro) is as reliable as three-dimensionally reconstructed computed tomography imaging (3D-CT) in quantifying the glenoid bone loss in patients with anterior shoulder instability. Thirty-five patients were included. Sagittal MR-arthro and 3D-CT images of the glenoid surface were obtained pre-operatively. Two observers measured these images twice with OsiriX software in a randomized and blinded way. The intraclass correlations (ICC) of the intra- and inter-observer reliability within one method and an additional Bland-Altman plot for calculating agreement between the two methods were obtained. The joint estimates of the intra-observer reliability, taking into account the data from both observer A and B, for 3D-CT and MR-arthro were good to excellent. The intra-observer reliability was 0.938 (95 % CI: 0.879, 0.968) for 3D-CT and 0.799 (95 % CI: 0.639, 0.837) for MR-arthro. The inter-observer reliability between the two observers within one method (3D-CT or MR-arthro) was moderate to good. 3D-CT: 0.724 (95 % CI: 0.236, 0.886) and MR-arthro: 0.534 (95 % CI: 0.128, 0.762). Comparing both the 3D-CT and MR-arthro method, a Bland-Altman plot showed satisfying differences with the majority of outcomes (89 %) within 1 SD. Good to excellent intra- and moderate to good inter-observer correlations and a satisfying Bland-Altman plot when compared to 3D-CT show tendencies that MR-arthro is reliable and valid for measuring bony defects of the glenoid. (orig.)

  7. 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

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

    Science.gov (United States)

    Wang, Hongkai; Zhuo, Yunyun; Hu, Xu; Shen, Weiwei; Zhang, Ying; Chu, Tongwei

    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.

  9. Selective deletion of the membrane-bound colony stimulating factor 1 isoform leads to high bone mass but does not protect against estrogen-deficiency bone loss

    OpenAIRE

    Yao, Gang-Qing; Wu, Jian-Jun; Troiano, Nancy; Zhu, Mei-Ling; Xiao, Xiao-Yan; Insogna, Karl

    2011-01-01

    To better define the biologic function of membrane-bound CSF1 (mCSF1) in vivo, we have generated mCSF1 knockout (k/o) mice. Spinal bone density (BMD) was 15.9% higher in k/o mice compared to wild-type (wt) controls (P < 0.01) and total BMD was increased by 6.8% (P < 0.05). A higher mean femur BMD was also observed but did not reach statistical significance (6.9% P = NS). The osteoclastogenic potential of bone marrow isolated from mCSF1 k/o mice was reduced compared to wt marrow. There were no...

  10. Comparison of the Influence of Crown to Implant Ratio on Marginal Bone Loss around Implants in Posterior Areas of the Maxilla and Mandible

    Directory of Open Access Journals (Sweden)

    M. Khoshhal

    2016-04-01

    Full Text Available Introduction & Objective: Due to the patients’ growing interest in the use of dental implants, medical staff should be completely aware of treatment success and prognostic factors to prevent failures. The purpose of this study was to evaluate the effect of different crown to implant ratio (C / I Ratio in the posterior areas of the maxilla and mandible as one of the most important principles of biomechanics on marginal bone loss around the implant neck (MBL. Material & Methods: This study was conducted as a prospective cohort study. In this study, patients treated at a private dental implants office during the years 2013-2014 were selected. Parallel digital radiographs 6 months and 12 months after loading the implants were measured to evaluate the effects of prosthetic implants on posterior areas of the maxillary and mandibular crowns by a digital caliper. All patients were evaluated radiographically and data were collected and analyzed by SPSS 16 with non parametrical tests. Results: A total of 48 fixtures of SIC Implant System in 18 patients, including 28 pcs in maxilla and 20 pcs in mandible were evaluated. Statistical analysis of marginal bone level around the implant neck in radiograpy taken showed no significant difference in the effect of different C/I Ratio of marginal bone loss around implants (P=0.094. Comparison of posterior areas of the maxilla and mandible also showed no difference between the effects of different amounts of C/I Ratio of the marginal bone. Conclusion: The present study showed that the marginal bone loss was not statistically significant after the placement of implants in the posterior region of the jaw with a different range of crown – to- implant ratio from 0.87 to 2.55. Thus, it seems that there is no relationship between marginal bone loss around the implant neck with different proportions of crown - implant and with the location of the treatment (P>0.05. (Sci J Hamadan Univ Med Sci 2016; 23 (1:5-16

  11. Electrical Stimulation of Denervated Rat Skeletal Muscle Ameliorates Bone Fragility and Muscle Loss in Early-Stage Disuse Musculoskeletal Atrophy.

    Science.gov (United States)

    Tamaki, Hiroyuki; Yotani, Kengo; Ogita, Futoshi; Hayao, Keishi; Nakagawa, Kouki; Sugawara, Kazuhiro; Kirimoto, Hikari; Onishi, Hideaki; Kasuga, Norikatsu; Yamamoto, Noriaki

    2017-04-01

    We tested whether daily muscle electrical stimulation (ES) can ameliorate the decrease in cortical bone strength as well as muscle and bone geometric and material properties in the early stages of disuse musculoskeletal atrophy. 7-week-old male F344 rats were randomly divided into three groups: age-matched control group (Cont); a sciatic denervation group (DN); and a DN + direct electrical stimulation group (DN + ES). Denervated tibialis anterior (TA) muscle in the DN + ES group received ES with 16 mA at 10 Hz for 30 min/day, 6 days/week. Micro CT, the three-point bending test, and immunohistochemistry were used to characterize cortical bone mechanical, structural, and material properties of tibiae. TA muscle in the DN + ES group showed significant improvement in muscle mass and myofiber cross-sectional area relative to the DN group. Maximal load and stiffness of tibiae, bone mineral density estimated by micro CT, and immunoreactivity of DMP1 in the cortical bone tissue were also significantly greater in the DN + ES group than in the DN group. These results suggest that daily ES-induced muscle contraction treatment reduced the decrease in muscle mass and cortical bone strength in early-stage disuse musculoskeletal atrophy and is associated with a beneficial effect on material properties such as mineralization of cortical bone tissue.

  12. Polymorphisms in the P2X7 receptor gene are associated with low lumbar spine bone mineral density and accelerated bone loss in post-menopausal women

    DEFF Research Database (Denmark)

    Gartland, Alison; Skarratt, Kristen K; Hocking, Lynne J;

    2012-01-01

    the functional P2RX7 SNPs are associated with lumbar spine (LS) bone mineral density (BMD), a key determinant of vertebral fracture risk, in post-menopausal women. We genotyped 506 post-menopausal women from the Aberdeen Prospective Osteoporosis Screening Study (APOSS) for the above SNPs. Lumbar spine BMD...

  13. 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.

  14. High-fat-diet-induced weight gain ameliorates bone loss without exacerbating AβPP processing and cognition in female APP/PS1 mice

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    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.

  15. 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.

  16. Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. Early Postmenopausal Intervention Cohort Study Group

    DEFF Research Database (Denmark)

    Hosking, D; Chilvers, C E; Christiansen, C

    1998-01-01

    BACKGROUND: Estrogen-replacement therapy prevents osteoporosis in postmenopausal women by inhibiting bone resorption, but the balance between its long-term risks and benefits remains unclear. Whether other antiresorptive therapies can prevent osteoporosis in these women is also not clear. METHODS......: We studied the effect of 2.5 mg or 5 mg of alendronate per day or placebo on bone mineral density in 1174 postmenopausal women under 60 years of age. An additional 435 women who were prepared to receive a combination of estrogen and progestin were randomly assigned to one of the above treatments...... or open-label estrogen-progestin. The main outcome measure was the change in bone mineral density of the lumbar spine, hip, distal forearm, and total body measured annually for two years by dual-energy x-ray absorptiometry. RESULTS: The women who received placebo lost bone mineral density at all measured...

  17. The “Love Hormone” Oxytocin Regulates the Loss and Gain of the Fat–Bone Relationship

    Science.gov (United States)

    Colaianni, Graziana; Sun, Li; Zaidi, Mone; Zallone, Alberta

    2015-01-01

    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 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. PMID:26042088

  18. N-acetylcysteine increases the frequency of bone marrow pro-B/pre-B cells, but does not reverse cigarette smoking-induced loss of this subset.

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    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.

  19. Critical appraisal of denosumab in the treatment and prevention of postmenopausal osteoporosis and bone loss in patients undergoing hormone ablation

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    David L Kendler

    2010-09-01

    Full Text Available David L Kendler1, Kenneth Shawn Davison21Prohealth Clinical Research, University of British Columbia, Vancouver, British Columbia, Canada; 2Department of Medicine, Division of Immunology and Rheumatology, Laval University, Quebec, CanadaAbstract: Antiresorptive therapies are the mainstay for treating patients with excessively high rates of bone resorption. The receptor activator of nuclear factor-κB (RANK ligand (RANKL, secreted by osteoblasts, binds to the RANK receptor on the surface of preosteoclasts and osteoclasts to elicit osteoclast formation, survival, and activity. Osteoprotegerin, also secreted by the osteoblast, acts as a decoy RANK receptor reducing RANKL binding to RANK and reducing bone resorption. Denosumab, a fully human monoclonal antibody, has a high affinity and specificity for RANKL. Denosumab rapidly decreases bone resorption and increases bone mineral density (BMD at the lumbar spine, total hip, femoral neck, and one-third radius sites. In head-to-head trials, denosumab increased BMD and decreased bone resorption to a significantly greater degree than alendronate. In postmenopausal osteoporotic women, denosumab decreased the risk of vertebral fracture (68%, nonvertebral fracture (20%, and hip fracture (40% over 36 months, compared to placebo. In patients with iatrogenic hypogonadism, denosumab rapidly decreased markers of bone resorption and increased BMD. In men treated with GnRH agonist for prostate cancer, treatment with denosumab led to a 62% decreased risk of new vertebral fracture over 3 years, as compared to placebo. In all trials completed to date, comparable adverse events have been observed in both denosumab and placebo or treatment groups.Keywords: medication adherence, fracture, bone mineral density, bone turnover markers

  20. SH3BP2 gain-of-function mutation exacerbates inflammation and bone loss in a murine collagen-induced arthritis model.

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    Tomoyuki Mukai

    Full Text Available OBJECTIVE: SH3BP2 is a signaling adapter protein which regulates immune and skeletal systems. Gain-of-function mutations in SH3BP2 cause cherubism, characterized by jawbone destruction. This study was aimed to examine the role of SH3BP2 in inflammatory bone loss using a collagen-induced arthritis (CIA model. METHODS: CIA was induced in wild-type (Sh3bp2(+/+ and heterozygous P416R SH3BP2 cherubism mutant knock-in (Sh3bp2(KI/+ mice, an SH3BP2 gain-of-function model. Severity of the arthritis was determined by assessing the paw swelling and histological analyses of the joints. Micro-CT analysis was used to determine the levels of bone loss. Inflammation and osteoclastogenesis in the joints were evaluated by quantitating the gene expression of inflammatory cytokines and osteoclast markers. Furthermore, involvement of the T- and B-cell responses was determined by draining lymph node cell culture and measurement of the serum anti-mouse type II collagen antibody levels, respectively. Finally, roles of the SH3BP2 mutation in macrophage activation and osteoclastogenesis were determined by evaluating the TNF-α production levels and osteoclast formation in bone marrow-derived M-CSF-dependent macrophage (BMM cultures. RESULTS: Sh3bp2(KI/+ mice exhibited more severe inflammation and bone loss, accompanying an increased number of osteoclasts. The mRNA levels for TNF-α and osteoclast marker genes were higher in the joints of Sh3bp2(KI/+ mice. Lymph node cell culture showed that lymphocyte proliferation and IFN-γ and IL-17 production were comparable between Sh3bp2(+/+ and Sh3bp2(KI/+ cells. Serum anti-type II collagen antibody levels were comparable between Sh3bp2(+/+ and Sh3bp2(KI/+ mice. In vitro experiments showed that TNF-α production in Sh3bp2(KI/+ BMMs is elevated compared with Sh3bp2(+/+ BMMs and that RANKL-induced osteoclastogenesis is enhanced in Sh3bp2(KI/+ BMMs associated with increased NFATc1 nuclear localization. CONCLUSION: Gain-of-function of

  1. DHEA prevents bone loss by suppressing the expansion of CD4(+) T cells and TNFa production in the OVX-mouse model for postmenopausal osteoporosis.

    Science.gov (United States)

    Zhang, Na; Gui, Yuyan; Qiu, Xuemin; Tang, Wei; Li, Lisha; Gober, Hans-Jürgen; Li, Dajin; Wang, Ling

    2016-09-05

    Recent studies have suggested that dehydroepiandrosterone (DHEA) might serve as a form of immunomodulatory therapy for postmenopausal osteoporosis (PMO). The current study investigated the effects of DHEA administration on ovariectomy (OVX)-induced bone loss and its corresponding immunological changes. Adult OVX mice were treated with DHEA or 17-β-estradiol (E2) for 12 weeks, with or without the aromatase inhibitor letrozole. DHEA improved bone mass after OVX and displayed action like that of E2 with regard to decreasing osteoclast-related parameters. DHEA also suppressed an OVX-induced increase in CD4(+) T cell subsets and TNF-α production. However, DHEA elevated serum E2 levels to a lesser extent than E2. Although letrozole decreased serum E2 levels in OVX mice treated with DHEA, it did not alter DHEA's effects on corresponding immunological changes due to OVX. In conclusion, DHEA may prevent bone loss by suppressing the OVX-induced expansion of CD4(+) T cells and TNF-α production in mice, independent of E2.

  2. Lupeol Isolated from Sorbus commixta Suppresses 1α,25-(OH)2D3-Mediated Osteoclast Differentiation and Bone Loss in Vitro and in Vivo.

    Science.gov (United States)

    Im, Nam Kyung; Lee, Dong-Sung; Lee, Seong-Ryong; Jeong, Gil Saeng

    2016-02-26

    Lupeol is a lupane-type triterpene isolated from Sorbus commixta, an oriental medicine used to treat arthritis and inflammatory diseases. However, the antiosteoporotic effects of S. commixta or any of its constituents have not been studied yet. In the present study, we have examined the effect of lupeol (a major active triterpenoid isolated from S. commixta) on osteoclastogenesis and sought to elucidate its underlying molecular mechanisms. We evaluated whether lupeol antagonized osteoclast differentiation and bone resorption. Lupeol markedly inhibited osteoclast differentiation and bone resorption activity through its effects on MAP kinases and transcription factors (NF-κB, NFATc1, and c-Fos) downstream of the osteoclast differentiation factor receptor RANK. Furthermore, in vivo efficacy of lupeol was confirmed by using an animal model of hypercalcemic mediated bone loss. Taken together, lupeol showed strong inhibitory effects on osteoclastogenesis. Supplementation with S. commixta and lupeol could be beneficial for bone health or osteoclast-related diseases such as osteoporosis, Paget's disease, osteolysis associated with periodontal disease, and multiple myeloma.

  3. 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 -1...... bone-specific alkaline phosphatase revealed a more retarded decrease of 40% and 33%, respectively. Of the women receiving hormone therapy, 75% had amenorrhea from the first cycle, and 5% withdrew prematurely due to metrorrhagia or mastalgia. CONCLUSION: This new estrogen + progestogen therapy...

  4. 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

    histomorphometry revealed decreased mineralized surface and bone-formation rate as well as increased osteoclast number and size in Terc(-/-) mice. Also, serum total deoxypyridinoline (tDPD) was increased in Terc(-/-) mice. MSCs and osteoprogenitors isolated from Terc(-l-) mice exhibited intrinsic defects...

  5. 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.)

  6. 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

  7. 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.

  8. Effects of Curculigoside on Memory Impairment and Bone Loss via Anti-Oxidative Character in APP/PS1 Mutated Transgenic Mice.

    Directory of Open Access Journals (Sweden)

    Lu Zhao

    Full Text Available Alzheimer's disease (AD and osteoporosis are two closely related multifactorial progressively degenerative diseases that predominantly affect aged people. These two diseases share many common risk factors, including old age, being female, smoking, excessive drinking, low estrogen, and vitamin D3 levels. Additionally, oxidative damage and the dysfunction of the antioxidant system play important roles in the pathogenesis of osteoporosis and AD. Aβ not only leads to impaired memory but also plays a crucial role in the demineralization process of bone tissues of older people and women with menopause. Curculigoside can promote calcium deposition and increase the levels of ALP and Runx2 in osteoblasts under oxidative stress via anti-oxidative character. Therefore, we investigated the effects of CUR on the spatial learning and memory by the Morris water maze and brain immunohistochemistry, and bone microstructure and material properties of femurs by micro-computed tomography and mechanical testing in APP/PS1 mutated transgenic mice. Oral administration of CUR can significantly enhance learning performance and ameliorate bone loss in APP/PS1 mutated transgenic mice, and the mechanism may be related to its antioxidant effect. Based on these results, CUR has real potential as a new natural resource for developing medicines or dietary supplements for the prevention and treatment of the two closely linked multifactorial progressive degenerative disorders, AD and osteoporosis.

  9. 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.

  10. Age-Related Loss in Bone Mineral Density of Rats Fed Lifelong on a Fish Oil-Based Diet Is Avoided by Coenzyme Q10 Addition

    Science.gov (United States)

    Varela-López, Alfonso; Ochoa, Julio J.; Llamas-Elvira, José M.; López-Frías, Magdalena; Planells, Elena; Ramirez-Tortosa, MCarmen; Ramirez-Tortosa, Cesar L.; Giampieri, Francesca; Battino, Maurizio; Quiles, José L.

    2017-01-01

    During aging, bone mass declines increasing osteoporosis and fracture risks. Oxidative stress has been related to this bone loss, making dietary compounds with antioxidant properties a promising weapon. Male Wistar rats were maintained for 6 or 24 months on diets with fish oil as unique fat source, supplemented or not with coenzyme Q10 (CoQ10), to evaluate the potential of adding this molecule to the n-3 polyunsaturated fatty acid (n-3 PUFA)-based diet for bone mineral density (BMD) preservation. BMD was evaluated in the femur. Serum osteocalcin, osteopontin, receptor activator of nuclear factor-κB ligand, ostroprotegerin, parathyroid hormone, urinary F2-isoprostanes, and lymphocytes DNA strand breaks were also measured. BMD was lower in aged rats fed a diet without CoQ10 respect than their younger counterparts, whereas older animals receiving CoQ10 showed the highest BMD. F2-isoprostanes and DNA strand breaks showed that oxidative stress was higher during aging. Supplementation with CoQ10 prevented oxidative damage to lipid and DNA, in young and old animals, respectively. Reduced oxidative stress associated to CoQ10 supplementation of this n-3 PUFA-rich diet might explain the higher BMD found in aged rats in this group of animals. PMID:28241421

  11. Age-Related Loss in Bone Mineral Density of Rats Fed Lifelong on a Fish Oil-Based Diet Is Avoided by Coenzyme Q10 Addition

    Directory of Open Access Journals (Sweden)

    Alfonso Varela-López

    2017-02-01

    Full Text Available During aging, bone mass declines increasing osteoporosis and fracture risks. Oxidative stress has been related to this bone loss, making dietary compounds with antioxidant properties a promising weapon. Male Wistar rats were maintained for 6 or 24 months on diets with fish oil as unique fat source, supplemented or not with coenzyme Q10 (CoQ10, to evaluate the potential of adding this molecule to the n-3 polyunsaturated fatty acid (n-3 PUFA-based diet for bone mineral density (BMD preservation. BMD was evaluated in the femur. Serum osteocalcin, osteopontin, receptor activator of nuclear factor-κB ligand, ostroprotegerin, parathyroid hormone, urinary F2-isoprostanes, and lymphocytes DNA strand breaks were also measured. BMD was lower in aged rats fed a diet without CoQ10 respect than their younger counterparts, whereas older animals receiving CoQ10 showed the highest BMD. F2-isoprostanes and DNA strand breaks showed that oxidative stress was higher during aging. Supplementation with CoQ10 prevented oxidative damage to lipid and DNA, in young and old animals, respectively. Reduced oxidative stress associated to CoQ10 supplementation of this n-3 PUFA-rich diet might explain the higher BMD found in aged rats in this group of animals.

  12. Sotatercept, a soluble activin receptor type 2A IgG-Fc fusion protein for the treatment of anemia and bone loss.

    Science.gov (United States)

    Raje, Noopur; Vallet, Sonia

    2010-10-01

    Sotatercept (ACE-011), under development by Acceleron Pharma Inc in collaboration with Celgene Corp, is a chimeric protein containing the extracellular domain of the activin receptor 2A (ACVR2A) fused to the Fc domain of human IgG1. Sotatercept contains the binding site of ACVR2A and interferes with downstream signaling cascades, in particular the SMAD pathway, by sequestering activin. The murine counterpart of sotatercept, referred to as RAP-011, has been extensively evaluated in preclinical studies, in particular in models of cancer- and osteoporosis-related bone loss, and the developing companies envisage that sotatercept may also have potential for the treatment of cancer and cancer-related bone loss. In a phase I clinical trial in postmenopausal females, sotatercept increased hematocrit levels, and, in a phase II trial in patients with multiple myeloma, a trend toward improvement in osteolytic lesions as well as antitumor activity was observed. At the time of publication, phase II trials in patients with anemia were ongoing. Future clinical development will rely on an evaluation of the benefits and complications of sotatercept administration, focusing in particular on suppression of ovarian function and increases in hematocrit levels without a consequent risk of hypertension and thrombosis.

  13. 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.

  14. 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.

  15. Dairy calcium intake and lifestyle risk factors for bone loss in hiv-infected and uninfected mediterranean subjects

    Directory of Open Access Journals (Sweden)

    Vecchi Valentina

    2012-08-01

    Full Text Available Abstract Background Despite the reported high prevalence of osteoporosis in the human immunodeficiency virus (HIV-population, there have been no previous studies examining dairy calcium intake and bone mineral density (BMD in HIV-subjects. We assessed the prevalence of low BMD in HIV-infected and uninfected subjects and analyzed the effects of calcium intake, lifestyle and HIV-related risk factors on BMD. Methods One hundred and twelve HIV-infected subjects were consecutively enrolled. Seventy- six HIV-uninfected subjects matched for age and sex were enrolled as the control group. The HIV-subjects were interviewed about lifestyle habits and completed a weekly food-frequency questionnaire to estimate calcium intake. HIV-RNA, CD4+ T-cell count and data on antiretroviral therapy were also recorded. Both biochemical bone turnover markers and BMD, assessed by dual-energy radiographic absorptiometry (DXA were recorded in the HIV-cases and controls. We also calculated the 10-year fracture risks using the WHO FRAX equation. Results Osteoporosis prevalence was significantly higher in the HIV-cases than controls (p p p BMI values were significantly correlated with dairy intake quartiles (p p p p p p p Conclusions Among the foods rich in calcium, yogurt was a protective predictor of BMD in HIV-subjects. HIV/HCV co-infection, nadir CD4 + T-cell count

  16. Bone loss in unclassified polyarthritis and early rheumatoid arthritis is better detected by digital x ray radiogrammetry than dual x ray absorptiometry: relationship with disease activity and radiographic outcome

    DEFF Research Database (Denmark)

    Jensen, T; Klarlund, Mette; Hansen, M

    2004-01-01

    every six months. RESULTS: DXR BMD decreased significantly only in patients with RA from month 6 and was associated with the mean disease activity. Patients with RA and erosive as well as non-erosive disease showed a significant decrease in the rate of bone loss, greatest in those with erosive disease...... is better than DXA for detecting and monitoring periarticular osteoporosis of the metacarpal bone. Udgivelsesdato: 2004-Jan...

  17. 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.

  18. High-Dose Diosgenin Reduces Bone Loss in Ovariectomized Rats via Attenuation of the RANKL/OPG Ratio

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    Zhiguo Zhang

    2014-09-01

    Full Text Available The aim of this study was to evaluate effect of diosgenin (DG on rats that had osteoporosis-like features induced by ovariectomy (OVX. Seventy-two six-month-old female Wistar rats were subjected to either ovariectomy (n = 60 or Sham operation (SHAM group, n = 12. Beginning at one week post-ovariectomy, the OVX rats were treated with vehicle (OVX group, n = 12, estradiol valerate (EV group, n = 12, or DG at three doses (DG-L, -M, -H group, n = 12, respectively. After a 12-week treatment, administration of EV or DG-H inhibited OVX-induced weight gain, and administration of EV or DG-H or DG-M had a significantly uterotrophic effect. Bone mineral density (BMD and indices of bone histomorphometry of tibia were measured. Levels of protein and mRNA expression of osteoprotegerin (OPG and receptor activator of nuclear factor kappa-B ligand (RANKL in tibia were evaluated by immunohistochemistry and in situ hybridization. Our results show that DG at a high dose (DG-H had a significant anti-osteoporotic effect compared to OVX control. DG-H treatment down-regulated expression of RANKL and up-regulated expression of OPG significantly in tibia from OVX rats compared to control, and thus lowered the RANKL/OPG ratio. This suggests that the anti-osteoporotic effect of DG might be associated with modulating the RANKL/OPG ratio and DG had potential to be developed as alternative therapeutic agents of osteoporosis induced by postmenopause.

  19. 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.

  20. Oral Health and Bone Disease

    Science.gov (United States)

    ... low bone mass. Research suggests a link between osteoporosis and bone loss in the jaw. The bone in the jaw supports and anchors the teeth. When the jawbone becomes less dense, tooth loss can occur, a common occurrence in older adults. Skeletal Bone Density and Dental Concerns Periodontal Disease ...

  1. 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.

  2. The association of concurrent vitamin D and sex hormone deficiency with bone loss and fracture risk in older men: the osteoporotic fractures in men (MrOS) study.

    Science.gov (United States)

    Barrett-Connor, Elizabeth; Laughlin, Gail A; Li, Hong; Nielson, Carrie M; Wang, P Ying; Dam, Tien T; Cauley, Jane A; Ensrud, Kristine E; Stefanick, Marcia L; Lau, Edith; Hoffman, Andrew R; Orwoll, Eric S

    2012-11-01

    Low 25-hydroxyvitamin D (VitD), low sex hormones (SH), and high sex hormone binding globulin (SHBG) levels are common in older men. We tested the hypothesis that combinations of low VitD, low SH, and high SHBG would have a synergistic effect on bone mineral density (BMD), bone loss, and fracture risk in older men. Participants were a random subsample of 1468 men (mean age 74 years) from the Osteoporotic Fractures in Men Study (MrOS) plus 278 MrOS men with incident nonspine fractures studied in a case-cohort design. "Abnormal" was defined as lowest quartile for VitD (59 nM). Overall, 10% had isolated VitD deficiency; 40% had only low SH or high SHBG; 15% had both SH/SHBG and VitD abnormality; and 35% had no abnormality. Compared to men with all normal levels, those with both SH/SHBG and VitD abnormality tended to be older, more obese, and to report less physical activity. Isolated VitD deficiency, and low BioT with or without low VitD, was not significantly related to skeletal measures. The combination of VitD deficiency with low BioE and/or high SHBG was associated with significantly lower baseline BMD and higher annualized rates of hip bone loss than SH abnormalities alone or no abnormality. Compared to men with all normal levels, the multivariate-adjusted hazard ratio (95% confidence interval [CI]) for incident nonspine fracture during 4.6-year median follow-up was 1.2 (0.8-1.8) for low VitD alone; 1.3 (0.9-1.9) for low BioE and/or high SHBG alone; and 1.6 (1.1-2.5) for low BioE/high SHBG plus low VitD. In summary, adverse skeletal effects of low sex steroid levels were more pronounced in older men with low VitD levels. The presence of low VitD in the presence of low BioE/high SHBG may contribute substantially to poor skeletal health.

  3. Multiscale Modeling of Bone

    Science.gov (United States)

    2014-12-01

    DISEASE Both age and disease can affect the structure of bone, the effects of which are often similar. The most common bone disease is osteoporosis ... Osteoporosis is a disease that results in reduced bone mass and density. This reduction of bone mass and density has a greater impact on trabecular...Bone loss in females is linked to a decrease in estrogen ; the decrease of estrogen associated with menopause increases osteoclast activity [89]. This

  4. 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.

  5. Effects of Administration of Amlodipine and Lacidipine on Inflammation-Induced Bone Loss in the Ovariectomized Rat.

    Science.gov (United States)

    Karakus, Emre; Halici, Zekai; Albayrak, Abdulmecit; Bayir, Yasin; Demirci, Elif; Aydin, Ali; Ozturk-Karagoz, Berna; Cadirci, Elif; Ayan, Arif Kursat; Sahin, Ali; Unal, Deniz

    2016-02-01

    This study was performed to evaluate the possible protective effect of two calcium channel blocker's "lacidipine (LAC) and amlodipine (AML)" on bone metabolism in an experimental ovariectomized and inflammation-induced osteoporosis rat model (OVXinf). For the purpose of this study, the rats were divided into eight groups, each containing eight rats: sham-operated control (group 1, SH), sham + inflammation (group 2, SHinf), ovariectomy (group 3, OVX), ovariectomy + inflammation (group 4, OVXinf), ovariectomy + LAC 4 mg/kg (group 5, OVX + LAC), ovariectomy + inflammation + LAC 4 mg/kg (group 6, OVXinf + LAC), ovariectomy + AML 5 mg/kg (group 7, OVX + AML), ovariectomy + inflammation + AML 5 mg/kg (group 8, OVXinf + AML). The levels of osteocalcin and osteopontin decreased in OVXinf + LAC and OVXinf + AML groups. The serum levels of TNF-α, IL-1β, and IL-6 were increased significantly in the OVXinf rats compared with the SH group. Gene expression levels of the osteogenic factor runt-related transcription factor 2 (Runx2) and type I collagen 1A1 (Col1A1) significantly decreased in the OVXinf group, when compared with the control group. AML or LAC administrations increased the levels of Runx2 and Col1A1. These results suggest that amlodipine and lacidipine may be a novel therapeutic target for radical osteoporosis treatment in hypertensive patients.

  6. Exogenous IL-4-Expressing Bone Marrow Mesenchymal Stem Cells for the Treatment of Autoimmune Sensorineural Hearing Loss in a Guinea Pig Model

    Directory of Open Access Journals (Sweden)

    Chang-qiang Tan

    2014-01-01

    Full Text Available Bone marrow mesenchymal stem cells (BMSCs expressing recombinant IL-4 have the potential to remediate inflammatory diseases. We thus investigated whether BMSCs expressing exogenous IL-4 could alleviate autoimmune sensorineural hearing loss. BMSCs isolated from guinea pigs were transfected with recombinant lentivirus expressing IL-4. A total of 33 animals were divided into three groups. Group A received scala tympani injection of IL-4-expressing BMSCs, and Group B received control vector-expressing BMSCs, and Group C received phosphate-buffered saline. The distribution of implanted BMSCs in the inner ears was assessed by immunohistochemistry and fluorescence microscopy. Auditory brain-stem response (ABR was monitored to evaluate the auditory changes. Following BMSCs transplantation, the threshold levels of ABR wave III decreased in Groups A and B and significant differences were observed between these two groups P<0.05. Transplanted BMSCs distributed in the scala tympani and scala vestibuli. In some ears with hearing loss, there was a decrease in the number of spiral ganglion cells and varying degrees of endolymphatic hydrops or floccule. Following transplantation, the lentivirus-infected BMSCs migrated to the inner ear and produced IL-4. Our results demonstrate that, upon transplantation, BMSCs and BMSCs expressing recombinant IL-4 have the ability to remediate the inflammatory injury in autoimmune inner ear diseases.

  7. Localized experimental bone metastasis drives osteolysis and sensory hypersensitivity at distant non-tumor-bearing sites.

    Science.gov (United States)

    Abdelaziz, Dareen M; Stone, Laura S; Komarova, Svetlana V

    2015-08-01

    Patients with breast cancer metastasis to bone suffer from inadequate pain relief. Animal models provide increased understanding of cancer-induced bone and sensory alterations. The objective of this study was to investigate the measures of pain at distant non-tumor-bearing sites in animals with localized bone metastasis. Immunocompetent BALB/c mice are injected intra-tibially with murine mammary carcinoma cells (4T1) or saline, and the sensitivity to mechanical and thermal stimuli in the contralateral paw was examined. In addition to previously demonstrated development of osteolysis and hypersensitivity to mechanical and thermal stimuli in the cancer-injected tibia, these animals exhibited an increase in sensory hypersensitivity in the contralateral limb. No bone lesions were evident on radiographs of the contralateral limbs. Histomorphometry detected decreased bone volume per tissue volume and increased osteoclast number in the contralateral tibia and vertebral bones of cancer-bearing animals. Neuroplasticity was examined by immunofluorescence for calcitonin gene-related peptide (CGRP) in sensory neurons and glial fibrillary acidic protein (GFAP) in lumbar spinal cords. CGRP-immunoreactivity and GFAP-immunoreactivity were significantly elevated both ipsilateral and contralateral in tumor-bearing animals. The anti-inflammatory and osteolysis-targeting drug rapamycin reduced hypersensitivity to mechanical and cold stimuli, attenuated GFAP over-expression, and lowered osteoclast number. The osteoclast-targeting drug pamidronate reduced sensitivity to cold and protected against bone loss. Localized bone cancer drives hypersensitivity, bone remodeling, and sensory neuron plasticity at sites distant from the primary tumor area. Drugs targeting these mechanisms may be useful in the treatment of pain distant from the primary tumor site.

  8. 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.

  9. The Effects of Topical Application of Polycal (a 2:98 (g/g Mixture of Polycan and Calcium Gluconate on Experimental Periodontitis and Alveolar Bone Loss in Rats

    Directory of Open Access Journals (Sweden)

    Sang-In Park

    2016-04-01

    Full Text Available The aim of this study was to observe whether Polycal has inhibitory activity on ligation-induced experimental periodontitis and related alveolar bone loss in rats following topical application to the gingival regions. One day after the ligation placements, Polycal (50, 25, and 12.5 mg/mL solutions at 200 μL/rat was topically applied to the ligated gingival regions daily for 10 days. Changes in bodyweight, alveolar bone loss index, and total number of buccal gingival aerobic bacterial cells were monitored, and the anti-inflammatory effects were investigated via myeloperoxidase activity and levels of the pro-inflammatory cytokines IL-1β and TNF-α. The activities of inducible nitric oxide synthase (iNOS and lipid peroxidation (MDA were also evaluated. Bacterial proliferation, periodontitis, and alveolar bone loss induced by ligature placements were significantly inhibited after 10 days of continuous topical application of Polycal. These results indicate that topical application of Polycal has a significant inhibitory effect on periodontitis and related alveolar bone loss in rats mediated by antibacterial, anti-inflammatory, and anti-oxidative activities.

  10. Cytokines and bone loss in a 5-year longitudinal study--hormone replacement therapy suppresses serum soluble interleukin-6 receptor and increases interleukin-1-receptor antagonist: the Danish Osteoporosis Prevention Study

    DEFF Research Database (Denmark)

    Abrahamsen, Bo; Bonnevie-Nielsen, V; Ebbesen, E N

    2000-01-01

    The proinflammatory cytokines interleukin-1 beta (IL-1 beta) and IL-6 may play a central role in the acceleration of p