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Sample records for alcohol-induced bone loss

  1. Alcohol-induced bone loss is blocked in p47phox -/- mice lacking functional nadph oxidases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic ethanol (EtOH) consumption produces bone loss. Previous data suggest a role for NADPH oxidase enzymes (Nox) since the pan-Nox inhibitor diphenylene iodonium (DPI) blocks EtOH-induced bone loss in rats. The current study utilized mice in which Nox enzymes 1,2,3 and 5 are inactivated as a resu...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  4. Bone Loss in IBD

    MedlinePlus

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

  5. Alcohol-induced autophagy contributes to loss in skeletal muscle mass

    PubMed Central

    Thapaliya, Samjhana; Runkana, Ashok; McMullen, Megan R; Nagy, Laura E; McDonald, Christine; Prasad, Sathyamangla V Naga; Dasarathy, Srinivasan

    2014-01-01

    Patients with alcoholic cirrhosis and hepatitis have severe muscle loss. Since ethanol impairs skeletal muscle protein synthesis but does not increase ubiquitin proteasome-mediated proteolysis, we investigated whether alcohol-induced autophagy contributes to muscle loss. Autophagy induction was studied in: A) Human skeletal muscle biopsies from alcoholic cirrhotics and controls, B) Gastrocnemius muscle from ethanol and pair-fed mice, and C) Ethanol-exposed murine C2C12 myotubes, by examining the expression of autophagy markers assessed by immunoblotting and real-time PCR. Expression of autophagy genes and markers were increased in skeletal muscle from humans and ethanol-fed mice, and in myotubes following ethanol exposure. Importantly, pulse-chase experiments showed suppression of myotube proteolysis upon ethanol-treatment with the autophagy inhibitor, 3-methyladenine (3MA) and not by MG132, a proteasome inhibitor. Correspondingly, ethanol-treated C2C12 myotubes stably expressing GFP-LC3B showed increased autophagy flux as measured by accumulation of GFP-LC3B vesicles with confocal microscopy. The ethanol-induced increase in LC3B lipidation was reversed upon knockdown of Atg7, a critical autophagy gene and was associated with reversal of the ethanol-induced decrease in myotube diameter. Consistently, CT image analysis of muscle area in alcoholic cirrhotics was significantly reduced compared with control subjects. In order to determine whether ethanol per se or its metabolic product, acetaldehyde, stimulates autophagy, C2C12 myotubes were treated with ethanol in the presence of the alcohol dehydrogenase inhibitor (4-methylpyrazole) or the acetaldehyde dehydrogenase inhibitor (cyanamide). LC3B lipidation increased with acetaldehyde treatment and increased further with the addition of cyanamide. We conclude that muscle autophagy is increased by ethanol exposure and contributes to sarcopenia. PMID:24492484

  6. Breast Cancer and Bone Loss

    MedlinePlus

    ... 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 ...

  7. Suppression of NADPH oxidases prevents chronic ethanol-induced bone loss

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since the molecular mechanisms through which chronic excessive alcohol consumption induces osteopenia and osteoporosis are largely unknown, potential treatments for prevention of alcohol-induced bone loss remain unclear. We have previously demonstrated that, chronic ethanol (EtOH) treatment leads to...

  8. Menopause and Bone Loss

    MedlinePlus

    ... You reach your highest bone mass (size and density) at about age 30. Then, sometime between age ... your bones, your doctor may do a bone density test (DEXA scan). This test gives exact measurements ...

  9. Importance of genetics in fetal alcohol effects: null mutation of the nNOS gene worsens alcohol-induced cerebellar neuronal losses and behavioral deficits

    PubMed Central

    Bonthius, Daniel J.; Winters, Zachary; Karacay, Bahri; Bousquet, Samantha Larimer; Bonthius, Daniel J.

    2014-01-01

    The cerebellum is a major target of alcohol-induced damage in the developing brain. However, the cerebella of some children are much more seriously affected than others by prenatal alcohol exposure. As a consequence of in utero alcohol exposure, some children have substantial reductions in cerebellar volume and corresponding neurodevelopmental problems, including microencephaly, ataxia, and balance deficits, while other children who were exposed to similar alcohol quantities are spared. One factor that likely plays a key role in determining the impact of alcohol on the fetal cerebellum is genetics. However, no specific gene variant has yet been identified that worsens cerebellar function as a consequence of developmental alcohol exposure. Previous studies have revealed that mice carrying a homozygous mutation of the gene for neuronal nitric oxide synthase (nNOS−/− mice) have more severe acute alcohol-induced neuronal losses from the cerebellum than wild type mice. Therefore, the goals of this study were to determine whether alcohol induces more severe cerebellum-based behavioral deficits in nNOS−/− mice than in wild type mice and to determine whether these worsened behavior deficits are associated with worsened cerebellar neuronal losses. nNOS−/− mice and their wild type controls received alcohol (0.0, 2.2, or 4.4 mg/g) daily over postnatal days 4–9. In adulthood, the mice underwent behavioral testing, followed by neuronal quantification. Alcohol caused dose-related deficits in rotarod and balance beam performance in both nNOS−/− and wild type mice. However, the alcohol-induced behavioral deficits were substantially worse in the nNOS−/− mice than in wild type. Likewise, alcohol exposure led to losses of Purkinje cells and cerebellar granule cells in mice of both genotypes, but the cell losses were more severe in the nNOS−/− mice than in wild type. Behavioral performances were correlated with neuronal number in the nNOS−/− mice, but not

  10. Peptidergic Agonists of Activity-Dependent Neurotrophic Factor Protect Against Prenatal Alcohol-Induced Neural Tube Defects and Serotonin Neuron Loss

    PubMed Central

    Zhou, Feng C.; Fang, Yuan; Goodlett, Charles

    2009-01-01

    Introduction Prenatal alcohol exposure via maternal liquid diet consumption by C57BL/6 (B6) mice causes conspicuous midline neural tube deficit (dysraphia) and disruption of genesis and development of serotonin (5-HT) neurons in the raphe nuclei, together with brain growth retardation. The current study tested the hypothesis that concurrent treatment with either an activity-dependent neurotrophic factor (ADNF) agonist peptide [SALLRSIPA, (SAL)] or an activity-dependent neurotrophic protein (ADNP) agonist peptide [NAPVSIPQ, (NAP)] would protect against these alcohol-induced deficits in brain development. Methods Timed-pregnant B6 dams consumed alcohol from embryonic day 7 (E7, before the onset of neurulation) until E15. Fetuses were obtained on E15 and brain sections processed for 5-HT immunocytochemistry, for evaluation of morphologic development of the brainstem raphe and its 5-HT neurons. Additional groups were treated either with SAL or NAP daily from E7 to E15 to assess the potential protective effects of these peptides. Measures of incomplete occlusion of the ventral canal and the frequency and extent of the openings in the rhombencephalon were obtained to assess fetal dysraphia. Counts of 5-HT-immunostained neurons were also obtained in the rostral and caudal raphe. Results Prenatal alcohol exposure resulted in abnormal openings along the midline and delayed closure of ventral canal in the brainstem. This dysraphia was associated with reductions in the number of 5-HT neurons both in the rostral raphe nuclei (that gives rise to ascending 5-HT projections) and in the caudal raphe (that gives rise to the descending 5-HT projections). Concurrent treatment of the alcohol-consuming dams with SAL prevented dysraphia and protected against the alcohol-induced reductions in 5-HT neurons in both the rostral and caudal raphe. NAP was less effective in protecting against dysraphia and did not protect against 5-HT loss in the rostral raphe, but did protect against loss in

  11. Effect of dietary fat/carbohydrate ratio on progression of alcoholic liver injury and bone loss in rats fed via total enteral nutrition (TEN)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Few studies have examined the effects of diet on the dynamics of injury progression or on alcohol-induced bone loss. In the current study, 300 g male Sprague-Dawley rats (N = 10/group) were treated with alcohol containing liquid diets via a stomach tube. Dietary fat content was either 5% (high carbo...

  12. Regulation of bone mineral loss during lactation

    NASA Technical Reports Server (NTRS)

    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.

  13. The osteoimmunology of alveolar bone loss.

    PubMed

    Tompkins, Kevin A

    2016-03-01

    The mineralized structure of bone undergoes constant remodeling by the balanced actions of bone-producing osteoblasts and bone-resorbing osteoclasts (OCLs). Physiologic bone remodeling occurs in response to the body's need to respond to changes in electrolyte levels, or mechanical forces on bone. There are many pathological conditions, however, that cause an imbalance between bone production and resorption due to excessive OCL action that results in net bone loss. Situations involving chronic or acute inflammation are often associated with net bone loss, and research into understanding the mechanisms regulating this bone loss has led to the development of the field of osteoimmunology. It is now evident that the skeletal and immune systems are functionally linked and share common cells and signaling molecules. This review discusses the signaling system of immune cells and cytokines regulating aberrant OCL differentiation and activity. The role of these cells and cytokines in the bone loss occurring in periodontal disease (PD) (chronic inflammation) and orthodontic tooth movement (OTM) (acute inflammation) is then described. The review finishes with an exploration of the emerging role of Notch signaling in the development of the immune cells and OCLs that are involved in osteoimmunological bone loss and the research into Notch signaling in OTM and PD. PMID:26950207

  14. Associated among endocrine, inflammatory, and bone markers, body composition and weight loss induced bone loss

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Weight loss reduces co-¬morbidities of obesity but decreases bone mass. Our aims were to determine whether adequate dairy intake could prevent weight loss related bone loss and to evaluate the contribution of energy-related hormones and inflammatory markers to bone metabolism. Overweight and obese w...

  15. Metaphyseal bone loss in revision knee arthroplasty.

    PubMed

    Ponzio, Danielle Y; Austin, Matthew S

    2015-12-01

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

  16. Prevent and cure disuse bone loss

    NASA Technical Reports Server (NTRS)

    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.

  17. Men Miss Out on Bone Loss Screening

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_158810.html Men Miss Out on Bone Loss Screening Yet, millions ... THURSDAY, May 12, 2016 (HealthDay News) -- Unlike women, men at risk for osteoporosis don't get routinely ...

  18. Men Miss Out on Bone Loss Screening

    MedlinePlus

    ... nlm.nih.gov/medlineplus/news/fullstory_158810.html Men Miss Out on Bone Loss Screening Yet, millions ... THURSDAY, May 12, 2016 (HealthDay News) -- Unlike women, men at risk for osteoporosis don't get routinely ...

  19. Countermeasures against space flight related bone loss

    NASA Technical Reports Server (NTRS)

    Leblanc, Adrian; Schneider, Victor

    1992-01-01

    A general review is presented of data on bone loss with references to countermeasures for use during spaceflight and bedrest. The two primary countermeasures against skeletal atrophy are skeletal loading such as centrifugation and exercise and/or the administration of drugs designed to alter the rate of bone remodeling. Bone loss is argued to be unavoidable in long-duration spaceflight in spite of countermeasures utilized, but a combination of exercise, biochemical treatments, and post-flight therapy is considered the optimal solution.

  20. Weightlessness and bone loss in man

    NASA Technical Reports Server (NTRS)

    Rambaut, P. C.

    1983-01-01

    A review is presented of data whicih has been accumulated on the calcium and skeletal changes occurring in humans subjected to various periods of weightlessness. These data reveal that spaceflight induces an overall loss of calcium which continues unabated for at least three months. Urinary calcium levels reach a constant level within approximately four weeks while fecal calcium losses continue to increase throughout the flight period. A decline in the mineral density of weight-bearing bones accompanies these changes. Available data support the contention that the demineralization affects primarily the weight bearing bones. The rates of loss and recovery of calcium and bone mineral density are approximately equal to those observed during and following bedrest of comparable duration. No measure to wholly prevent these losses has yet been devised.

  1. Alcohol induced liver disease.

    PubMed Central

    Fleming, K A; McGee, J O

    1984-01-01

    Alcohol induces a variety of changes in the liver: fatty change, hepatitis, fibrosis, and cirrhosis. The histopathological appearances of these conditions are discussed, with special attention to differential diagnosis. Many forms of alcoholic liver disease are associated with Mallory body formation and fibrosis. Mallory bodies are formed, at least in part, from intermediate filaments. Associated changes in intermediate filament organisation in alcoholic liver disease also occur. Their significance in the pathogenesis of hepatocyte death may be related to abnormalities in messenger RNA function. The mechanisms underlying hepatic fibrogenesis are also discussed. Images PMID:6086722

  2. Periprosthetic bone loss: diagnostic and therapeutic approaches

    PubMed Central

    Cavalli, Loredana; Brandi, Maria Luisa

    2014-01-01

    Total joint replacement surgery is being performed on an increasingly large part of the population. Clinical longevity of implants depends on their osseointegration, which is influenced by the load, the characteristics of the implant and the bone-implant interface, as well as by the quality and quantity of the surrounding bone. Aseptic loosening due to periprosthetic osteolysis is the most frequent known cause of implant failure. Wear of prosthetic materials results in the formation of numerous particles of debris that cause a complex biological response. Dual-energy X-ray Absorptiometry (DXA) is regarded as an accurate method to evaluate Bone Mineral Density (BMD) around hip or knee prostheses. Further data may be provided by a new device, the Bone Microarchitecture Analysis (BMA), which combines bone microarchitecture quantification and ultra high resolution osteo-articular imaging. Pharmacological strategies have been developed to prevent bone mass loss and to extend implant survival. Numerous trials with bisphosphonates show a protective effect on periprosthetic bone mass, up to 72 months after arthroplasty. Strontium ranelate has been demonstrated to increase the osseointegration of titanium implants in treated animals with improvement of bone microarchitecture and bone biomaterial properties. PMID:25642325

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

    PubMed

    Bolotin, H H

    2009-06-01

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

  4. Tobacco smoking and vertical periodontal bone loss.

    PubMed

    Baljoon, Mostafa

    2005-01-01

    Cigarette smoking is associated with increased prevalence and severity of destructive periodontal disease in terms of periodontal pocketing, periodontal bone loss, and tooth loss. The smoking destructive effect on periodontal bone may be of even "horizontal" and vertical "angular" pattern. The vertical bone loss or the "vertical defect" is a sign of progressive periodontal breakdown that involves the periodontal bone. Water pipe smoking has a sharp rise by the popularity in the recent years by men and women in Middle East countries. The general objective of this thesis was to investigate the relationship between tobacco smoking and vertical periodontal bone loss cross-sectionally and longitudinally. This thesis is based on two study populations, Swedish musicians and a Saudi Arabian population. All participants had a full set of intra-oral radiographs including 16 periapical and 4 bitewing projections that were assessed with regard to presence or absence of vertical defects. In Study I, the number of defects per person increased with age. Vertical defects were more common in the posterior as compared to the anterior region of the dentition and the distribution of defects within the maxilla as well as the mandible typically revealed a right-left hand side symmetry. Cigarette smoking was significantly associated with the prevalence and severity of vertical bone defects (Studies II and III). The relative risk associated with cigarette smoking was 2 to 3-fold increased. The impact of water pipe smoking was of the same magnitude as that of cigarette smoking and the relative risk associated with water pipe smoking was 6-fold increased compared to non-smoking. In addition, the risk of vertical defects increased with increased exposure in cigarette smokers as well as water pipe smokers (Study III). In Study IV, the proportion of vertical defects increased over a 10-year period and the increase over time was significantly associated with smoking. Moreover, the 10-year

  5. Characterization of Posterior Glenoid Bone Loss

    PubMed Central

    Yanke, Adam Blair; Frank, Rachel M.; Shin, Jason J.; Van Thiel, Geoffrey S.; Verma, Nikhil N.; Cole, Brian J.; Romeo, Anthony A.; Provencher, Matthew T.

    2016-01-01

    Objectives: The purpose of this study was to characterize the morphology and location of posterior glenoid bone loss in pat ients with posterior instability instability utilizing computed tomography (CT). Methods: Clinical data was selected for patients with posterior shoulder instability that had undergone posterior stabilization (open or arthroscopic) or posterior osseous augmentation (distal tibia or iliac crest). Three fellowship-trained surgeons from two institutions contributed patients. Pre-operative CT data was collected for all patients. The axial cuts were segmented and reformatted in three-dimensions for glenoid analysis using Osirix. From this three-dimensional model, the following was calculated: percent bone loss (Nobuhara), total arc of the defect (degrees), and a clock-face description (start point, stop point, and average or direction). Pearson correlation coefficients were performed using significance of p<0.05. Results: Fifty shoulders from 50 patients were reviewed. Fourteen patients (average age 30 years; 93% male) had evidence of posterior glenoid bone loss and were included for evaluation. Defects on average involved 13.7±8.6% of the glenoid (range, 2-35%). The average start time (assuming all right shoulders) on the clock face was 10 o’clock ± 40 minutes and stopped at 6:30 ± 25 minutes. The average direction of the defect pointed toward 8:15 ± 25 minutes. The percent bone loss correlated with the total arc of the defect (Pearson: 0.93, p<0.05, R2: 0.86) and the direction of the bone loss (Pearson: 0.64, p<0.05, R2: 0.40). The direction of bone loss significantly moved more posterosuperior the larger the defect became (Pearson: 0.63, p<0.05, R2: 0.40). Conclusion: Posterior bone loss associated with posterior glenohumeral instability is typically directed posteriorly at 8:15 on the clock. As defect get bigger, this direction moves more posterosuperior. This information will help guide clinicians in understanding the typical location of

  6. The pathogenesis of bone loss following total knee arthroplasty.

    PubMed

    Lewis, P L; Brewster, N T; Graves, S E

    1998-04-01

    Bone loss following total knee arthroplasty (TKA) may be focal or diffuse. It may be caused mechanically, either by unloading of the bone leading to disuse osteoporosis, or by overloading of the bone leading to trabecular fractures and bone destruction. Osteolysis, instigated by an inflammatory reaction to particulate wear debris, is an important and common cause of bone loss after TKA. Less common, though sometimes dramatic, causes of bone loss are infection and osteonecrosis. PMID:9553564

  7. Vitamin C reverses hypogonadal bone loss

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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, ...

  8. Bone loss in chronic kidney disease: Quantity or quality?

    PubMed

    Zheng, Cai-Mei; Zheng, Jin-Quan; Wu, Chia-Chao; Lu, Chien-Lin; Shyu, Jia-Fwu; Yung-Ho, Hsu; Wu, Mei-Yi; Chiu, I-Jen; Wang, Yuan-Hung; Lin, Yuh-Feng; Lu, Kuo-Cheng

    2016-06-01

    Chronic kidney disease (CKD) patients experience bone loss and fracture because of a specific CKD-related systemic disorder known as CKD-mineral bone disorder (CKD-MBD). The bone turnover, mineralization, and volume (TMV) system describes the morphological bone lesions in renal osteodystrophy related to CKD-MBD. Bone turnover and bone volume are defined as high, normal, or low, and bone mineralization is classified as normal or abnormal. All types of bone histology related to TMV are responsible for both bone quantity and bone quality losses in CKD patients. This review focuses on current bone quantity and bone quality losses in CKD patients and finally discusses potential therapeutic measures. PMID:27049042

  9. Postmenopausal bone loss and the risk of osteoporosis.

    PubMed

    Christiansen, C

    1994-01-01

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

  10. Photobiomodulation on alcohol induced dysfunction

    NASA Astrophysics Data System (ADS)

    Yang, Zheng-Ping; Liu, Timon C.; Zhang, Yan; Wang, Yan-Fang

    2007-05-01

    Alcohol, which is ubiquitous today, is a major health concern. Its use was already relatively high among the youngest respondents, peaked among young adults, and declined in older age groups. Alcohol is causally related to more than 60 different medical conditions. Overall, 4% of the global burden of disease is attributable to alcohol, which accounts for about as much death and disability globally as tobacco and hypertension. Alcohol also promotes the generation of reactive oxygen species (ROS) and/or interferes with the body's normal defense mechanisms against these compounds through numerous processes, particularly in the liver. Photobiomodulation (PBM) is a cell-specific effect of low intensity monochromatic light or low intensity laser irradiation (LIL) on biological systems. The cellular effects of both alcohol and LIL are ligand-independent so that PBM might rehabilitate alcohol induced dysfunction. The PBM on alcohol induced human neutrophil dysfunction and rat chronic atrophic gastritis, the laser acupuncture on alcohol addiction, and intravascular PBM on alcoholic coma of patients and rats have been observed. The endonasal PBM (EPBM) mediated by Yangming channel, autonomic nervous systems and blood cells is suggested to treat alcohol induced dysfunction in terms of EPBM phenomena, the mechanism of alcohol induced dysfunction and our biological information model of PBM. In our opinion, the therapeutic effects of PBM might also be achieved on alcoholic myopathy.

  11. Prostaglandin E2 Prevents Disuse-Induced Cortical Bone Loss

    NASA Technical Reports Server (NTRS)

    Jee, Webster S. S.; Akamine, T.; Ke, Hua Zhu; Li, Xiao Jian; Tang, L. Y.; Zeng, Q. Q.

    1992-01-01

    The object of this study was to determine whether prostaglandin E2 (PGE2) can prevent disuse (underloaded)-induced cortical bone loss as well as add extra bone to underloaded bones. Thirteen-month-old retired female Sprague-Dawley breeders served as controls or were subjected to simultaneous right hindlimb immobilization by bandaging and daily subcutaneous doses of 0, 1, 3, or 6 mg PGE2/kg/d for two and six weeks. Histomorphometric analyses were performed on double-fluorescent labeled undecalcified tibial shaft sections (proximal to the tibiofibular junction). Disuse-induced cortical bone loss occurred by enlarging the marrow cavity and increasing intracortical porosity. PGE2 treatment of disuse shafts further increased intracortical porosity above that in disuse alone controls. This bone loss was counteracted by enhancement of periosteal and corticoendosteal bone formation. Stimulation of periosteal and corticoendosteal bone formation slightly enlarged the total tissue (cross-sectional) area and inhibited marrow cavity enlargement. These PGE2-induced activities netted the same percentage of cortical bone with a different distribution than the beginning and age related controls. These findings indicate the PGE2-induced increase in bone formation compensated for the disuse and PGE2-induced bone loss, and thus prevented immobilization induced bone loss.

  12. Subtle shake-up in bone-loss research.

    PubMed

    Flinn, Edward D

    2002-03-01

    Recent research in the prevention of bone loss during weightlessness is described. Scientists are studying the effects of vibration on bone loss in laboratory animals and humans. Research is focused on determining how bone formation is triggered, the effects of stimulation of the stress response in bones, and the mechanisms behind the effects. Clinton Rubin at the State University of New York at Stony Brook is experimenting with 90 Hz vibration frequencies in rats. Other researchers are studying the effects of vibration plates in the treatment of osteoporosis in postmenopausal women and in children with low bone density. Tests among astronauts have been proposed, but none are scheduled. PMID:11898823

  13. Pathogenesis of Age-Related Bone Loss in Humans

    PubMed Central

    2013-01-01

    Background. Although data from rodent systems are extremely useful in providing insights into possible mechanisms of age-related bone loss, concepts evolving from animal models need to ultimately be tested in humans. Methods. This review provides an update on mechanisms of age-related bone loss in humans based on the author’s knowledge of the field and focused literature reviews. Results. Novel imaging, experimental models, biomarkers, and analytic techniques applied directly to human studies are providing new insights into the patterns of bone mass acquisition and loss as well as the role of sex steroids, in particular estrogen, on bone metabolism and bone loss with aging in women and men. These studies have identified the onset of trabecular bone loss at multiple sites that begins in young adulthood and remains unexplained, at least based on current paradigms of the mechanisms of bone loss. In addition, estrogen appears to be a major regulator of bone metabolism not only in women but also in men. Studies assessing mechanisms of estrogen action on bone in humans have identified effects of estrogen on RANKL expression by several different cell types in the bone microenvironment, a role for TNF-α and IL-1β in mediating effects of estrogen deficiency on bone, and possible regulation of the Wnt inhibitor, sclerostin, by estrogen. Conclusions. There have been considerable advances in our understanding of age-related bone loss in humans. However, there are also significant gaps in knowledge, particularly in defining cell autonomous changes in bone in human studies to test or validate concepts emerging from studies in rodents. Decision Editor: Luigi Ferrucci, MD, PhD PMID:22923429

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

    PubMed

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

    2014-05-01

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

  15. Alcohol-induced Purkinje cell loss with a single binge exposure in neonatal rats: a stereological study of temporal windows of vulnerability.

    PubMed

    Goodlett, C R; Eilers, A T

    1997-06-01

    Previous research has shown that the early neonatal period of rats is one of enhanced vulnerability to cerebellar Purkinje cell loss associated with binge-like alcohol exposure, with a prominent sensitive period during the first neonatal week. In this study, an unbiased count of the total number of Purkinje cells was obtained using the stereological optical fractionator, in groups of rats given a single binge-like alcohol exposure either during the most vulnerable neonatal period [postnatal day (PD) 4] or during a later, less vulnerable period (PD 9). Using artificial rearing methods, rats were given 6.6 g/kg of alcohol either on PD 4 or on PD 9, delivered as a 15% (v/v) solution in milk formula on two consecutive feedings of the designated day. Control groups included an artificially reared gastrostomy control and a normally reared suckle control. The mean peak blood alcohol concentrations were not different between the PD 4 and PD 9 alcohol groups, averaging 374 and 347 mg/dl, respectively. The rats were perfused on PD 27. A uniform random sample of sections was obtained from serial frozen sections through the cerebellum, stained with thionin, and Purkinje cells were counted from a uniform random sample of locations on each section with the three-dimensional optical fractionator. The number of Purkinje cells in the suckle control and gastrostomy control groups did not differ from each other, averaging 3.94 (+/- 0.19) and 3.58 (+/- 0.22) x 10(5) cells, respectively. Binge exposure on PD 4 induced significant cell loss (mean of 2.05 +/- 0.20 x (10(5) Purkinje cells), whereas binge exposure on PD 9 did not induce significant Purkinje cell loss (3.70 +/- 0.39 x 10(5) Purkinje cells). These findings confirm that a single neonatal binge alcohol exposure produces pathological Purkinje cell loss, provided that it occurs during the period of enhanced vulnerability coinciding with the early stages of dendritic outgrowth. PMID:9194933

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

    NASA Technical Reports Server (NTRS)

    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.

  17. ZIP4 silencing improves bone loss in pancreatic cancer

    PubMed Central

    Yang, Jingxuan; Ding, Hao; LeBrun, Drake; Ding, Kai; Houchen, Courtney W.; Postier, Russell G.; Ambrose, Catherine G.; Li, Zhaoshen; Bi, Xiaohong; Li, Min

    2015-01-01

    Metabolic bone disorders are associated with several types of human cancers. Pancreatic cancer patients usually suffer from severe nutrition deficiency, muscle wasting, and loss of bone mass. We have previously found that silencing of a zinc transporter ZIP4 prolongs the survival and reduces the severity of the cachexia in vivo. However, the role of ZIP4 in the pancreatic cancer related bone loss remains unknown. In this study we investigated the effect of ZIP4 knockdown on the bone structure, composition and mechanical properties of femurs in an orthotopic xenograft mouse model. Our data showed that silencing of ZIP4 resulted in increased bone tissue mineral density, decreased bone crystallinity and restoration of bone strength through the RANK/RANKL pathway. The results further support the impact of ZIP4 on the progression of pancreatic cancer, and suggest its potential significance as a therapeutic target for treating patients with such devastating disease and cancer related disorders. PMID:26305676

  18. Modeling Calcium Loss from Bones During Space Flight

    NASA Technical Reports Server (NTRS)

    Wastney, Meryl E.; Morukov, Boris V.; Larina, Irina M.; Abrams, Steven A.; Nillen, Jeannie L.; Davis-Street, Janis E.; Lane, Helen W.; Smith, Scott M.; Paloski, W. H. (Technical Monitor)

    1999-01-01

    Calcium loss from bones during space flight creates a risk for astronauts who travel into space, and may prohibit space flights to other planets. The problem of calcium loss during space flight has been studied using animal models, bed rest (as a ground-based model), and humans in-flight. In-flight studies have typically documented bone loss by comparing bone mass before and after flight. To identify changes in metabolism leading to bone loss, we have performed kinetic studies using stable isotopes of calcium. Oral (Ca-43) and intravenous (Ca-46) tracers were administered to subjects (n=3), three-times before flight, once in-flight (after 110 days), and three times post-flight (on landing day, and 9 days and 3 months after flight). Samples of blood, saliva, urine, and feces were collected for up to 5 days after isotope administration, and were analyzed for tracer enrichment. Tracer data in tissues were analyzed using a compartmental model for calcium metabolism and the WinSAAM software. The model was used to: account for carryover of tracer between studies, fit data for all studies using the minimal number of changes between studies, and calculate calcium absorption, excretion, bone calcium deposition and bone calcium resorption. Results showed that fractional absorption decreased by 50% during flight and that bone resorption and urinary excretion increased by 50%. Results were supported by changes in biochemical markers of bone metabolism. Inflight bone loss of approximately 250 mg Ca/d resulted from decreased calcium absorption combined with increased bone resorption and excretion. Further studies will assess the time course of these changes during flight, and the effectiveness of countermeasures to mitigate flight-induced bone loss. The overall goal is to enable human travel beyond low-Earth orbit, and to allow for better understanding and treatment of bone diseases on Earth.

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

    NASA Technical Reports Server (NTRS)

    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

  20. Probiotics Protect Mice from Ovariectomy-Induced Cortical Bone Loss

    PubMed Central

    Ohlsson, Claes; Engdahl, Cecilia; Fåk, Frida; Andersson, Annica; Windahl, Sara H.; Farman, Helen H.; Movérare-Skrtic, Sofia; Islander, Ulrika; Sjögren, Klara

    2014-01-01

    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. PMID:24637895

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

    SciTech Connect

    Nurmio, Mirja; Joki, Henna; Kallio, Jenny; Maeaettae, Jorma A.; Vaeaenaenen, H. Kalervo; Toppari, Jorma; Jahnukainen, Kirsi; Laitala-Leinonen, Tiina

    2011-08-01

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

  2. Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss

    NASA Technical Reports Server (NTRS)

    LeBlanc, Adrian; Matsumoto, Toshio; Jones, Jeffrey A.; Shapiro, Jay; Lang, Thomas F.; Smith, Scott M.; Shackelford, Linda C.; Sibonga, Jean; Evans, Harlan; Spector, Elisabeth; Koslovskaya, Inessa

    2009-01-01

    Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss (Bisphosphonates) will determine whether antiresorptive agents, in conjunction with the routine inflight exercise program, will protect ISS crewmembers from the regional decreases in bone mineral density documented on previous ISS missions.

  3. Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss

    NASA Technical Reports Server (NTRS)

    LeBlanc, Adrian; Matsumoto, Toshio; Jones, Jeff; Shapiro, Jay; Lang, Tom; Smith, Scott M.; Shackelford, Linda C.; Sibonga, Jean; Evans, Harlan; Spector, Elisabeth; Ploutz-Snyder, Robert; Nakamura, Toshitaka; Kohri,Kenjiro; Ohshima, Hiroshi

    2011-01-01

    Experiment Hypothesis -- The combined effect of anti-resorptive drugs plus in-flight exercise regimen will have a measurable effect in preventing space flight induced bone mass and strength loss and reducing renal stone risk.

  4. Pathophysiology of bone loss in the female athlete.

    PubMed

    Lambrinoudaki, Irene; Papadimitriou, Dimitra

    2010-09-01

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

  5. Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss

    NASA Technical Reports Server (NTRS)

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

    2011-01-01

    This poster reviews the possibility of using Bisphosphonates to counter the bone loss that is experienced during space flight. The Hypothesis that is tested in this experiment is that the combined effect of anti-resorptive drugs plus in-flight exercise regimen will attenuate space flight induced loss in bone mass and strength and reduce renal stone risk. The experiment design, the status and the results are described.

  6. Bone loss: Quantitative imaging techniques for assessing bone mass in rheumatoid arthritis

    PubMed Central

    Njeh, Christopher F; Genant, Harry K

    2000-01-01

    Osteoporosis is associated with low bone mass and microarchitectural deterioration of bone tissue with clinical manifestation of low trauma fractures. Rheumatoid arthritis (RA) is a risk factor due to generalized and articular bone loss. This minireview presents past and current bone mass measurement techniques in RA. These techniques include: plain radiographs, absorptiometry, quantitative computed tomography (QCT) and ultrasound. The most widely used technique is dual x-ray absorptiometry (DXA). RA patients have lower bone mass as compared with normals and substantial bone loss may occur early after the onset of disease. Measurement of bone mineral density (BMD) at the hand using either DXA or ultrasound maybe a useful tool in the management of RA patients. PMID:11094457

  7. Sclerostin is essential for alveolar bone loss in occlusal hypofunction

    PubMed Central

    XU, YANG; WANG, LUFEI; SUN, YAO; HAN, XIANGLONG; GAO, TIAN; XU, XIN; CHEN, TIAN; ZHAO, XUEFENG; ZENG, HUAN; WANG, YANMIN; BAI, DING

    2016-01-01

    Bone loss is caused by occlusal hypofunction and is a serious health concern. This is particularly true of tooth loss, which is common in the elderly. However, the cellular and molecular mechanisms underlying bone loss have yet to be fully elucidated. Sclerostin and Wnt/β-catenin signaling have previously been reported to serve important roles in regulating bone remodeling. Therefore, the present study aimed to investigate the involvement of sclerostin and Wnt/β-catenin signaling in occlusal hypofunction-induced alveolar bone remodeling. The unilateral maxillary molars of 14 male Sprague-Dawley rats were extracted in order to establish a model of occlusal hypofunction. For each rat, the non-extraction side was treated as the control group for comparisons with the extraction side. At 8 weeks after tooth extraction, the rats were sacrificed and alveolar bone specimens were harvested for X-ray radiography, micro-computed tomography (CT) and histological and immunohistochemical examinations. Bone loss and architecture deterioration were observed at the occlusal hypofunction side. The bone mineral density was markedly decreased and the ratio of bone volume to total volume was significantly decreased at the hypofunction side, as compared with the control side (P<0.001). In addition, the number of osteoclasts at the hypofunction side were significantly increased compared with that in the control side (P<0.001), as demonstrated using tartrate-resistant acid phosphatase staining. Furthermore, the protein expression levels of sclerostin and receptor activator of nuclear factor-κB ligand were increased, whereas those of β-catenin were decreased, at the hypofunction side when compared with the control side. In conclusion, the results of the present study suggested that occlusal hypofunction-induced bone loss may be associated with upregulated expression of sclerostin, which, in turn, may inhibit the activity of the Wnt/β-catenin signaling pathway. PMID:27168809

  8. Oncogenic and Therapeutic Targeting of PTEN Loss in Bone Malignancies.

    PubMed

    Xi, Yongming; Chen, Yan

    2015-09-01

    Being a tumor suppressor, PTEN functions as a dual-specificity protein and phospholipid phosphatase and regulates a variety of cellular processes and signal transduction pathways. Loss of PTEN function has been detected frequently in different forms of cancers, such as breast, prostate and lung cancer, gastric and colon cancer, skin cancer, as well as endometrial carcinoma. In this review, we provide a summary of PTEN and its role in bone malignancies including bone metastases, multiple myeloma, and osteosarcoma, etc. We highlight the importance of PTEN loss leading to activation of the oncogenic PI3K/Akt/mTOR pathway in tumorigenesis and progression, which can be attributed to both genetic and non-genetic alterations involving gene mutation, loss of heterozygosity, promoter hypermethylation, and microRNA mediated negative regulation. We also discuss the emerging therapeutic applications targeting PTEN loss for the treatment of these bone malignant diseases. PMID:25773992

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

    PubMed Central

    Villanueva-Martínez, Manuel; Ríos-Luna, Antonio; Diaz-Mauriño, Juán

    2011-01-01

    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. PMID:21221229

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

    USGS Publications Warehouse

    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.

  11. Phytoestrogens in the prevention of postmenopausal bone loss.

    PubMed

    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. PMID:24090647

  12. Role of Corticosteroids in Bone Loss During Space Flight

    NASA Technical Reports Server (NTRS)

    Wronski, Thomas J.; Halloran, Bernard P.; Miller, Scott C.

    1998-01-01

    The primary objective of this research project is to test the hypothesis that corticosteroids contribute to the adverse skeletal effects of space flight. To achieve this objective, serum corticosteroids, which are known to increase during space flight, must be maintained at normal physiologic levels in flight rats by a combination of adrenalectomy and corticosteroid supplementation via implanted hormone pellets. Bone analyses in these animals will then be compared to those of intact flight rats that, based on past experience, will undergo corticosteroid excess and bone loss during space flight. The results will reveal whether maintaining serum corticosteroids at physiologic levels in flight rats affects the skeletal abnormalities that normally develop during space flight. A positive response to this question would indicate that the bone loss and decreased bone formation associated with space flight are mediated, at least in part, by corticosteroid excess.

  13. Telomerized presenescent osteoblasts prevent bone mass loss in vivo.

    PubMed

    Yudoh, K; Nishioka, K

    2004-06-01

    Previously, we showed that human osteoblasts expressing the human telomerase reverse transcriptase (hTERT) gene exhibited specific survival advantages--the result of breaching the replicative senescence barrier and maintaining the phenotypic and functional properties of primary osteoblasts in vitro over the total replicative capacity of primary osteoblasts. We postulated that rejuvenated osteoblasts may have a potential to correct bone loss or osteopenia in age-related osteoporotic diseases. In the present study, we studied whether telomerized presenescent osteoblasts prevent bone mass loss in vivo. After obtaining the informed consent from a patient with osteoarthritis who underwent the arthroplastic knee surgery, osteoblastic cells were isolated from donor bone sample. We transfected the gene encoding hTERT into human osteoblastic cells. Human bone fragments from a donor were incubated with human hTERT-transfected presenescent (in vitro aged) osteoblasts or mock-transfected presenescent osteoblasts in culture medium containing Matrigel. We subcutaneously implanted human bone fragments with telomerized presenescent osteoblasts or primary presenescent osteoblasts as three-dimensional Matrigel xenografts in severe combined immunodeficiency (SCID) mice (each group: six mice) and analyzed the grafts at 6 weeks after implantation. We also determined whether telomerized osteoblasts affect the bone-forming capacity in vivo, using a well-established mouse transplantation model in which ceramic hydroxyapatite/tricalcium phosphate particles are used as carrier vehicle. Telomerized presenescent osteoblasts were rejuvenated, and maintained the functional properties of young osteoblasts in vitro. Bone mineral content (BMC) and bone mineral density (BMD) were measured by ash weight and dual-energy X-ray absorptiometry, respectively. Whereas BMC and BMD of human bone fragments, which were inoculated with aged osteoblasts in SCID mice, decreased with time, telomerized

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

    NASA Technical Reports Server (NTRS)

    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

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

    PubMed

    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. PMID:22677337

  16. Anabolic Vitamin D Analogs as Countermeasures to Bone Loss

    NASA Technical Reports Server (NTRS)

    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.

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

    PubMed

    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. PMID:26362075

  18. A mechanism of bone tissue loss in monkeys (BION - 11).

    NASA Astrophysics Data System (ADS)

    Rodionova, N. V.; Oganov, V. S.

    The elucidation of mechanisms of bone tissue loss under the spaceflight conditions remains an actual problem until now It was established that primary reactions to a mechanical stress evolve at the cellular level therefore the main attention of the researchers was aimed at studying bone tissue cells and their interactions With the use of electron microscopy we studied osteoblasts osteocytes osteoclasts and stromal cells in bioptats of the iliac bone crest from monkeys flown on board the satellite guillemotleft BION - 11 guillemotright during 2 weeks The flight samples were compared with the vivarium and simulation controls The functional state of cells was evaluated by the degree of development of organelles for specific biosyntheses rough endoplasmic reticulum Golgy complex nucleus state interrelation with a mineralized matrix The analysis of the obtained results and data of other authors Klein -- Nulend et al 2003 etc permits to suppose that the following sequence of cell interactions underlies the bone tissue loss during mechanical stress microgravity reaction of mechano-sensitive osteocytes to a mechanical stimulus consisting in enhancement of osteolytic processes in cells which results in a partial bone tissue loss along the local unloading Simultaneously the modulating signals are transmitted through a system of canals and processes towards active osteoblasts surface osteocytes and bone marrow stromal cells as well As a reply to a mechanical stimulus there occurs a reduction slowing down of proliferation

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

    PubMed

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

    2010-03-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  1. SOCS-3 Regulates Alveolar Bone Loss in Experimental Periodontitis.

    PubMed

    Papathanasiou, E; Kantarci, A; Konstantinidis, A; Gao, H; Van Dyke, T E

    2016-08-01

    The host immune response plays a key role in bacteria-induced alveolar bone resorption. Endogenous control of the magnitude and duration of inflammatory signaling is considered an important determinant of the extent of periodontal pathology. Suppressor of cytokine signaling (SOCS) proteins are inhibitors of cytokine signaling pathways and may play a role in restraining periodontal inflammation. We hypothesized that SOCS-3 regulates alveolar bone loss in experimental periodontitis. Periodontal bone loss was induced in 16-wk-old myeloid-specific SOCS-3-knockout and wild-type (WT) C57Bl6-B.129 mice by oral inoculation 9 times with 10(9) colony-forming units of Porphyromonas gingivalis A7436 through an oral gavage model for periodontitis. Sham controls for both types of mice received vehicle without bacteria. The mice were euthanized 6 wk after the last oral inoculation. Increased bone loss was demonstrated in P. gingivalis-infected SOCS-3-knockout mice as compared with P. gingivalis-infected WT mice by direct morphologic measurements, micro-computed tomography analyses, and quantitative histology. Loss of SOCS-3 function resulted in an increased number of alveolar bone osteoclasts and increased RANKL expression after P. gingivalis infection. SOCS-3 deficiency in myeloid cells also promotes a higher P. gingivalis lipopolysaccharide-induced inflammatory response with higher secretion of IL-1β, IL-6, and KC (IL-8) by peritoneal macrophages as compared with WT controls. Our data implicate SOCS-3 as a critical negative regulator of alveolar bone loss in periodontitis. PMID:27126447

  2. Bone density in limb-immobilized beagles: An animal model for bone loss in weightlessness

    NASA Technical Reports Server (NTRS)

    Wolinsky, Ira

    1987-01-01

    Prolonged weightlessness is man in space flight results in a slow progressive demineralization of bone accompanied by an increased calcium output in the urine resulting in negative calcium balances. This possibly irreversible bone loss may constitute a serious limiting factor to long duration manned space flight. In order to seek and test preventative measures an appropriate ground based animal model simulating weightlessness is necessary. Use of the mature Beagle in limb immobilization has been documented as an excellent model for orthopedic research since this animal most closely simulates the phenomenom of bone loss with regards to growth, remodeling, structure, chemistry and mineralization. The purpose of this project is to develop a research protocol for the study of bone loss in Beagles during and after cast immobilization of a hindleg; research will then be initiated.

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

    PubMed

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

    2016-01-01

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

  4. CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss.

    PubMed

    Rodríguez-Sanz, M; García-Giralt, N; Prieto-Alhambra, D; Servitja, S; Balcells, S; Pecorelli, R; Díez-Pérez, A; Grinberg, D; Tusquets, I; Nogués, X

    2015-08-01

    Aromatase inhibitors (AIs) used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer cause diverse musculoskeletal side effects that include bone loss and its associated fracture. About half of the 391 patients treated with AIs in the Barcelona-Aromatase induced bone loss in early breast cancer cohort suffered a significant bone loss at lumbar spine (LS) and/or femoral neck (FN) after 2 years on AI-treatment. In contrast, up to one-third (19.6% LS, 38.6% FN) showed no decline or even increased bone density. The present study aimed to determine the genetic basis for this variability. SNPs in candidate genes involved in vitamin D and estrogen hormone-response pathways (CYP11A1, CYP17A1, HSD3B2, HSD17B3, CYP19A1, CYP2C19, CYP2C9, ESR1, DHCR7, GC, CYP2R1, CYP27B1, VDR and CYP24A1) were genotyped for association analysis with AI-related bone loss (AIBL). After multiple testing correction, 3 tag-SNPs (rs4077581, s11632698 and rs900798) located in the CYP11A1 gene were significantly associated (P<0.005) with FN AIBL at 2 years of treatment. Next, CYP11A1 expression in human fresh bone tissue and primary osteoblasts was demonstrated by RT-PCR. Both common isoforms of human cholesterol side-chain cleavage enzyme (encoded by CYP11A1 gene) were detected in osteoblasts by western blot. In conclusion, the genetic association of CYP11A1 gene with AIBL and its expression in bone tissue reveals a potential local function of this enzyme in bone metabolism regulation, offering a new vision of the steroidogenic ability of this tissue and new understanding of AI-induced bone loss. PMID:26108486

  5. Alendronate as an Effective Countermeasure to Disuse Induced Bone loss

    NASA Technical Reports Server (NTRS)

    LeBlanc, Adrian D.; Driscol, Theda B.; Shackelford, Linda C.; Evans, Harlan J.; Rianon, Nahid J.; Smith, Scott M.; Lai, Dejian

    2002-01-01

    Microgravity, similar to diuse immobilization on earth, causes rapid bone loss. This loss is believed to be an adaptive response to the reduced musculoskelatal forces in space and occurs gradually enough that changes occurring during short duration space flight are not a concern. Bone loss, however, will be a major impediment for long duration missions if effective countermeasures are not developed and implemented. Bed rest is used to simulate the reduced mechanical forces in humans and was used to test the hypothesis that oral alendronate would reduce the effects of long duration (17 weeks) inactivity on bone. Eight male subjects were given daily oral doses of alendronate during 17 weeks of horizontal bed rest and compared with 13 male control subjects not given the drug. Efficacy was evaluated based on measurements of bone markers, calcium balance and bone density performed before, during and after the bed rest. The results show that oral alendronate attenuates most of the characteristic changes associated with long duration bed rest and presumably space flight.

  6. Glycosylation of immunoglobulin G determines osteoclast differentiation and bone loss

    PubMed Central

    Harre, Ulrike; Lang, Stefanie C.; Pfeifle, René; Rombouts, Yoann; Frühbeißer, Sabine; Amara, Khaled; Bang, Holger; Lux, Anja; Koeleman, Carolien A.; Baum, Wolfgang; Dietel, Katharina; Gröhn, Franziska; Malmström, Vivianne; Klareskog, Lars; Krönke, Gerhard; Kocijan, Roland; Nimmerjahn, Falk; Toes, René E. M.; Herrmann, Martin; Scherer, Hans Ulrich; Schett, Georg

    2015-01-01

    Immunglobulin G (IgG) sialylation represents a key checkpoint that determines the engagement of pro- or anti-inflammatory Fcγ receptors (FcγR) and the direction of the immune response. Whether IgG sialylation influences osteoclast differentiation and subsequently bone architecture has not been determined yet, but may represent an important link between immune activation and bone loss. Here we demonstrate that desialylated, but not sialylated, immune complexes enhance osteoclastogenesis in vitro and in vivo. Furthermore, we find that the Fc sialylation state of random IgG and specific IgG autoantibodies determines bone architecture in patients with rheumatoid arthritis. In accordance with these findings, mice treated with the sialic acid precursor N-acetylmannosamine (ManNAc), which results in increased IgG sialylation, are less susceptible to inflammatory bone loss. Taken together, our findings provide a novel mechanism by which immune responses influence the human skeleton and an innovative treatment approach to inhibit immune-mediated bone loss. PMID:25825024

  7. Amlexanox Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss

    PubMed Central

    Zhang, Yong; Guan, Hanfeng; Li, Jing; Fang, Zhong; Chen, Wenjian; Li, Feng

    2015-01-01

    The activity of protein kinases IKK-ε and TANK-binding kinase 1 (TBK1) has been shown to be associated with inflammatory diseases. As an inhibitor of IKK-ε and TBK1, amlexanox is an anti-inflammatory, anti-allergic, immunomodulator and used for treatment of ulcer, allergic rhinitis and asthma in clinic. We hypothesized that amlexanox may be used for treatment of osteoclast-related diseases which frequently associated with a low grade of systemic inflammation. In this study, we investigated the effects of amlexanox on RANKL-induced osteoclastogenesis in vitro and ovariectomy-mediated bone loss in vivo. In primary bone marrow derived macrophages (BMMs), amlexanox inhibited osteoclast formation and bone resorption. At the molecular level, amlexanox suppressed RANKL-induced activation of nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPKs), c-Fos and NFATc1. Amlexanox decreased the expression of osteoclast-specific genes, including TRAP, MMP9, Cathepsin K and NFATc1. Moreover, amlexanox enhanced osteoblast differentiation of BMSCs. In ovariectomized (OVX) mouse model, amlexanox prevented OVX-induced bone loss by suppressing osteoclast activity. Taken together, our results demonstrate that amlexanox suppresses osteoclastogenesis and prevents OVX-induced bone loss. Therefore, amlexanox may be considered as a new therapeutic candidate for osteoclast-related diseases, such as osteoporosis and rheumatoid arthritis. PMID:26338477

  8. Cathepsin K Deficiency Suppresses Disuse-Induced Bone Loss.

    PubMed

    Moriya, Shuichi; Izu, Yayoi; Arayal, Smriti; Kawasaki, Makiri; Hata, Koki; Pawaputanon Na Mahasarakhahm, Chantida; Izumi, Yuichi; Saftig, Paul; Kaneko, Kazuo; Noda, Masaki; Ezura, Yoichi

    2016-05-01

    Unloading induces bone loss and causes disuse osteoporosis. However, the mechanism underlying disuse osteoporosis is still incompletely understood. Here, we examined the effects of cathepsin K (CatK) deficiency on disuse osteoporosis induced by using sciatic neurectomy (Nx) model. After 4 weeks of surgery, CatK KO and WT mice were sacrificed and subjected to analyses. For cancellous bone rich region, Nx reduced the bone mineral density (BMD) compared to the BMD in the sham operated side in wild type mice. In contrast, CatK deficiency suppressed such Nx-induced reduction of BMD in cancellous bone. Nx also reduced BMD in the mid shaft cortical bone compared to the BMD in the corresponding region on the sham operated side in wild type mice. In contrast, CatK deficiency suppressed such Nx-induced reduction of BMD in the mid shaft cortical bone. Bone volume (BV/TV) was reduced by Nx in WT mice. In contrast, Cat-K deficiency suppressed such reduction in bone volume. Interestingly, CatK deficiency suppressed osteoclast number and osteoclast surface in the Nx side compared to sham side. When bone marrow cells obtained from Nx side femur of CatK-KO mice were cultured, the levels of the calcified area in culture were increased. Further examination of gene expression indicated that Nx suppressed the expression of genes encoding osteoblast-phenotype-related molecules such as Runx2 and alkaline phosphatase in WT mice. In contrast, CatK deficiency suppressed such reduction. These data indicate that CatK is involved in the disuse-induced bone mass reduction. PMID:26460818

  9. Effect of bone loss in anterior shoulder instability

    PubMed Central

    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. Rate of bone loss in postmenopausal and osteoporotic women

    SciTech Connect

    Aloia, J.F.; Ross, P.; Vaswani, A.; Zanzi, I.; Cohn, S.H.

    1982-02-01

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

  11. Osteoprotegerin ameliorates sciatic nerve crush induced bone loss.

    PubMed

    Bateman, T A; Dunstan, C R; Lacey, D L; Ferguson, V L; Ayers, R A; Simske, S J

    2001-07-01

    This study examines the ability of osteoprotegerin (OPG) to prevent the local bone resorption caused by sciatic nerve damage. Sixty-five 18-week-old male mice were assigned to one of six groups (n = 10-11/group). A baseline control group was sacrificed on day zero of the 10-day study. The remaining groups were placebo sham operated, placebo nerve crush (Plac NC) operated, 0.1 mg/kg/day OPG + nerve crush (LOW), 0.3 mg/kg/day OPG + nerve crush (MED), and 1.0 mg/kg/day OPG + nerve crush (HI). Nerve crush or sham operations were performed on the right leg. The left leg served as a contralateral control to the nerve crushed (ipsilateral) leg. The difference in mass between the right and left femur and tibia was examined. Additionally, quantitative histomorphometry was performed on the right and left femur and tibia diaphyses. Nerve crush resulted in a significant loss of bone mass in the ipsilateral side compared to the contralateral side. Bone mass for the ipsilateral bones of the Plac NC group were significantly reduced by 3.8% in the femur and 3.5% in the tibia compared to the contralateral limb. The percent diminution was reduced for OPG treated mice compared to the Plac NC group for both the femur and tibia. In the femur, the percent reduction of ipsilateral bone mass was reduced to 1.0% (LOW), 1.3% (MED) and 1.6% (HI) compared to the contralateral limb. In the tibia, loss of bone mass in the ipsilateral limb was reduced to 1.4% (LOW), 1.4% (MED), and 2.4% (HI) compared to the contralateral. OPG also decreased the amount of tibial endocortical resorption compared to the Plac NC group. In summary, OPG mitigated bone loss caused by damage to the sciatic nerve. PMID:11518255

  12. Bone growth stimulators. New tools for treating bone loss and mending fractures.

    PubMed

    Whitfield, James F; Morley, Paul; Willick, Gordon E

    2002-01-01

    In the new millennium, humans will be traveling to Mars and eventually beyond with skeletons that respond to microgravity by self-destructing. Meanwhile in Earth's aging populations growing numbers of men and many more women are suffering from crippling bone loss. During the first decade after menopause all women suffer an accelerating loss of bone, which in some of them is severe enough to result in "spontaneous" crushing of vertebrae and fracturing of hips by ordinary body movements. This is osteoporosis, which all too often requires prolonged and expensive care, the physical and mental stress of which may even kill the patient. Osteoporosis in postmenopausal women is caused by the loss of estrogen. The slower development of osteoporosis in aging men is also due at least in part to a loss of the estrogen made in ever smaller amounts in bone cells from the declining level of circulating testosterone and is needed for bone maintenance as it is in women. The loss of estrogen increases the generation, longevity, and activity of bone-resorbing osteoclasts. The destructive osteoclast surge can be blocked by estrogens and selective estrogen receptor modulators (SERMs) as well as antiosteoclast agents such as bisphosphonates and calcitonin. But these agents stimulate only a limited amount of bone growth as the unaffected osteoblasts fill in the holes that were dug by the now suppressed osteoclasts. They do not stimulate osteoblasts to make bone--they are antiresorptives not bone anabolic agents. (However, certain estrogen analogs and bisphosphates may stimulate bone growth to some extent by lengthening osteoblast working lives.) To grow new bone and restore bone strength lost in space and on Earth we must know what controls bone growth and destruction. Here we discuss the newest bone controllers and how they might operate. These include leptin from adipocytes and osteoblasts and the statins that are widely used to reduce blood cholesterol and cardiovascular damage. But

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

    SciTech Connect

    Bhattacharyya, M.H.; Whelton, B.D.; Stern, P.H.; Peterson, D.P. )

    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.

  14. Weight, muscle and bone loss during space flight: another perspective.

    PubMed

    Stein, T P

    2013-09-01

    Space flight is a new experience for humans. Humans adapt if not perfectly, rather well to life without gravity. There is a reductive remodeling of the musculo-skeletal system. Protein is lost from muscles and calcium from bones with anti-gravity functions. The observed biochemical and physiological changes reflect this accommodative process. The two major direct effects of the muscle loss are weakness post-flight and the increased incidence of low back ache pre- and post-flight. The muscle protein losses are compromised by the inability to maintain energy balance inflight. Voluntary dietary intake is reduced during space flight by ~20 %. These adaptations to weightlessness leave astronauts ill-equipped for life with gravity. Exercise, the obvious counter-measure has been repeatedly tried and since the muscle and bone losses persist it is not unreasonable to assume that success has been limited at best. Nevertheless, more than 500 people have now flown in space for up to 1 year and have done remarkably well. This review addresses the question of whether enough is now known about these three problems (negative energy balance, muscle loss and bone loss) for to the risks to be considered either acceptable or correctible enough to meet the requirements for a Mars mission. PMID:23192310

  15. Inhibited osteoblastogenesis, enhanced bone resorption and disrupted vitamin d3 homeostasis in female c57bl/6 mice fed alcohol

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Alcohol abuse is a well-known factor for increased risk of osteoporosis. Previous studies have shown that molecular mechanisms underlying alcohol-induced bone loss are complex, involving direct effects on both bone formation and resorption and additional indirect actions via endocrine disruption. Wh...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  17. Aminohydroxybutane bisphosphonate inhibits bone loss due to immobilization in rats.

    PubMed

    Thompson, D D; Seedor, J G; Weinreb, M; Rosini, S; Rodan, G A

    1990-03-01

    The purpose of this study was to document the effects of aminobutane bisphosphonate (AHBuP) on bone remodeling during immobilization in rats. Male Sprague-Dawley rats underwent unilateral sciatic neurectomy after receiving two daily subcutaneous injections of 0, 0.01, 0.10, or 1.0 mg P per kg AHBuP. Rats were sacrificed at 24 h or 10 or 20 days postimmobilization. Femora were ashed and tibiae were prepared for histomorphometric analysis. AHBuP was effective in inhibiting bone loss due to immobilization in a dose-dependent manner. The percentage loss of femoral ash weight due to immobilization decreased in a dose-dependent manner. In vehicle-treated rats, there was a significant decrease in trabecular bone volume (TBV) in the immobilized tibiae compared to the normal tibiae; in AHBuP-treated rats there was a dose-dependent increase in TBV both in the immobilized and control tibiae. The osteoid surface extent was decreased in AHBuP-treated rats in a dose-dependent manner. The mineral apposition rate was altered only in the intact leg of rats treated with 0.1 and 1.0 mg P AHBuP per kg compared to vehicle treated. Osteoclast number per mm was reduced by AHBuP treatment. In conclusion, aminohydroxybutane bisphosphonate effectively prevented the bone loss due to immobilization in this system. PMID:2333787

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

    PubMed Central

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

    2016-01-01

    The elderly are more likely to suffer from fracture because of age-related trabecular bone loss. Different bone loss locations and patterns have different effects on bone mechanical properties. Extended finite element method (XFEM) can simulate fracture process and was suited to investigate the effects of bone loss on trabecular bone. Age-related bone loss is indicated by trabecular thinning and loss and may occur at low-strain locations or other random sites. Accordingly, several ideal normal and aged trabecular bone models were created based on different bone loss locations and patterns; then, fracture processes from crack initiation to complete failure of these models were observed by XFEM; finally, the effects of different locations and patterns on trabecular bone were compared. Results indicated that bone loss occurring at low-strain locations was more detrimental to trabecular bone than that occurring at other random sites; meanwhile, the decrease in bone strength caused by trabecular loss was higher than that caused by trabecular thinning, and the effects of vertical trabecular loss on mechanical properties were more severe than horizontal trabecular loss. This study provided a numerical method to simulate trabecular bone fracture and distinguished different effects of the possible occurrence of bone loss locations and patterns on trabecular bone. PMID:27403206

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

    PubMed

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

    2016-01-01

    The elderly are more likely to suffer from fracture because of age-related trabecular bone loss. Different bone loss locations and patterns have different effects on bone mechanical properties. Extended finite element method (XFEM) can simulate fracture process and was suited to investigate the effects of bone loss on trabecular bone. Age-related bone loss is indicated by trabecular thinning and loss and may occur at low-strain locations or other random sites. Accordingly, several ideal normal and aged trabecular bone models were created based on different bone loss locations and patterns; then, fracture processes from crack initiation to complete failure of these models were observed by XFEM; finally, the effects of different locations and patterns on trabecular bone were compared. Results indicated that bone loss occurring at low-strain locations was more detrimental to trabecular bone than that occurring at other random sites; meanwhile, the decrease in bone strength caused by trabecular loss was higher than that caused by trabecular thinning, and the effects of vertical trabecular loss on mechanical properties were more severe than horizontal trabecular loss. This study provided a numerical method to simulate trabecular bone fracture and distinguished different effects of the possible occurrence of bone loss locations and patterns on trabecular bone. PMID:27403206

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

    Zhu, Ling-Ling; Blair, Harry; Cao, Jay; Yuen, Tony; Latif, Rauf; Guo, Lida; Tourkova, Irina L.; Li, Jianhua; Davies, Terry F.; Sun, Li; Bian, Zhuan; Rosen, Clifford; Zallone, Alberta; New, Maria I.; Zaidi, Mone

    2012-01-01

    Low estrogen levels undoubtedly underlie menopausal bone thinning. However, rapid and profuse bone loss begins 3 y before 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 late perimenopause, directly stimulates bone resorption by osteoclasts. Here, we generated and characterized a polyclonal antibody to a 13-amino-acid-long peptide sequence within the receptor-binding domain of the FSH β-subunit. We show that the FSH antibody binds FSH specifically and blocks its action on osteoclast formation in vitro. When injected into ovariectomized mice, the FSH antibody attenuates bone loss significantly not only by inhibiting bone resorption, but also by stimulating bone formation, a yet uncharacterized action of FSH that we report herein. Mesenchymal cells isolated from mice treated with the FSH antibody show greater osteoblast precursor colony counts, similarly to mesenchymal cells isolated from FSH receptor (FSHR)−/− mice. This suggests that FSH negatively regulates osteoblast number. We confirm that this action is mediated by signaling-efficient FSHRs present on mesenchymal stem cells. Overall, the data prompt the future development of an FSH-blocking agent as a means of uncoupling bone formation and bone resorption to a therapeutic advantage in humans. PMID:22908268

  2. Regulators of G protein signaling 12 promotes osteoclastogenesis in bone remodeling and pathological bone loss.

    PubMed

    Yuan, X; Cao, J; Liu, T; Li, Y-P; Scannapieco, F; He, X; Oursler, M J; Zhang, X; Vacher, J; Li, C; Olson, D; Yang, S

    2015-12-01

    Regulators of G protein signaling (Rgs) have pivotal roles in controlling various cellular processes, such as cell differentiation. How Rgs proteins regulate osteoclast (OC) differentiation, function and bone homeostasis is poorly understood. It was previously demonstrated that Rgs12, the largest protein in the Rgs family, is predominantly expressed in OCs and regulates OC differentiation in vitro. To further understand the role and mechanism of Rgs12 in OC differentiation and bone diseases in vivo, we created OC-targeted Rgs12 knockout mice by using inducible Mx1-Cre and CD11b-Cre. Deletion of Rgs12 in hematopoietic cells or specifically in OC precursors resulted in increased bone mass with decreased OC numbers. Loss of Rgs12 impaired OC differentiation and function with impaired Ca(2+) oscillations and reduced nuclear factor of activated T cells (NFAT) 2 expression. The introduction of wild-type osteoblasts did not rescue the defective osteoclastogenesis. Ectopic expression of NFAT2 rescued defective OC differentiation in CD11b;Rgs12(fl/fl) cells and promoted normal OC differentiation. Moreover, deletion of Rgs12 significantly inhibited pathological osteoclastogenesis and bone destruction in Rgs12-deficient mice that were subjected to ovariectomy and lipodysaccharide for bone loss. Thus our findings demonstrate that Rgs12 is an important regulator in OC differentiation and function and identify Rgs12 as a potential therapeutic target for osteoporosis and inflammation-induced bone loss. PMID:25909889

  3. L-arginine prevents bone loss and bone collagen breakdown in cyclosporin A-treated rats.

    PubMed

    Fiore, C E; Pennisi, P; Cutuli, V M; Prato, A; Messina, R; Clementi, G

    2000-11-24

    Cyclosporin A is implicated in the pathogenesis of post-transplantation bone disease. Because of recent evidence that cyclosporin A may cause renal and cardiovascular toxicity by inhibiting nitric oxide (NO) activity, and that NO slows bone remodeling and bone loss in animal and human studies, we investigated a possible link between NO production and beneficial effects on bone health in cyclosporin A-treated rats. Thirty-six 10-week-old male rats were assigned to six groups of six animals each, and treated for 4 weeks with: vehicle; cyclosporin A; L-arginine; N(G)-nitro-L-arginine methylester (L-NAME, a general inhibitor of NO synthase activity); a combination of cyclosporin A+L-arginine; and a combination of cyclosporin A+L-NAME. Whole body and regional (spine and pelvis) bone mineral content of rats were measured under basal conditions and at the end of the treatment period by dual-energy X-ray absorptiometry (DXA) scanning. Femur weights and serum concentrations of pyridinoline, a reliable marker of bone resorption, were measured at the end of the study period. Cyclosporin A-, L-NAME-, and cyclosporin A+L-NAME-treated rats had significantly lower bone mineral content and femur weights, and significantly higher pyridinoline levels than did control animals. The administration of L-arginine appeared to prevent bone loss caused by cyclosporin A, suggesting that this amino acid, which can be converted to produce NO, might prove useful in preventing disturbed bone modeling and inhibition of bone growth associated with cyclosporin A therapy. PMID:11090650

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

    NASA Technical Reports Server (NTRS)

    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.

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

    PubMed

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

    2016-06-01

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

  6. Massive Bone Loss Due to Orchidectomy and Localized Disuse: Preventive Effects of a Biosphonsphonate

    NASA Astrophysics Data System (ADS)

    Libouban, H.; Moreau, M. F.; Chappard, D.

    2008-06-01

    Orchidectomy (ORX) and hindlimb paralysis induced by botulinum neurotoxin (BTX) were combined to see if their effects were cumulative and if bone loss could be prevented by an antiresorptive agent (risedronate) or testosterone. Four groups of mature rats were studied for 1 month: SHAM operated; ORX and right hindlimb immobilization (BTX); ORX+BTX+risedronate or testosterone. Bone loss and microarchitecture deterioration were maximized on the immobilized bone. Risedronate but not testosterone prevented trabecular bone loss but was less effective on cortical bone loss. ORX and BTX had additive effects on bone loss which can be prevented by risedronate but not testosterone.

  7. Bone loss and human adaptation to lunar gravity

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  8. Soy Isoflavones for Reducing Bone Loss (SIRBL) Study: Randomized Three Year Intervention in Postmenopausal Women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Research has indicated that soy protein with isoflavones may attenuate bone loss in postmenopausal women. We hypothesized that soy isoflavones would decrease bone loss in healthy postmenopausal women (45.8-65.0 years) by maintaining bone mineral density (BMD), and this bone-sparing effect would be g...

  9. NELL-1 in the treatment of osteoporotic bone loss.

    PubMed

    James, Aaron W; Shen, Jia; Zhang, Xinli; Asatrian, Greg; Goyal, Raghav; Kwak, Jin H; Jiang, Lin; Bengs, Benjamin; Culiat, Cymbeline T; Turner, A Simon; Seim Iii, Howard B; Wu, Benjamin M; Lyons, Karen; Adams, John S; Ting, Kang; Soo, Chia

    2015-01-01

    NELL-1 is a secreted, osteoinductive protein whose expression rheostatically controls skeletal ossification. Overexpression of NELL-1 results in craniosynostosis in humans and mice, whereas lack of Nell-1 expression is associated with skeletal undermineralization. Here we show that Nell-1-haploinsufficient mice have normal skeletal development but undergo age-related osteoporosis, characterized by a reduction in osteoblast:osteoclast (OB:OC) ratio and increased bone fragility. Recombinant NELL-1 binds to integrin β1 and consequently induces Wnt/β-catenin signalling, associated with increased OB differentiation and inhibition of OC-directed bone resorption. Systemic delivery of NELL-1 to mice with gonadectomy-induced osteoporosis results in improved bone mineral density. When extended to a large animal model, local delivery of NELL-1 to osteoporotic sheep spine leads to significant increase in bone formation. Altogether, these findings suggest that NELL-1 deficiency plays a role in osteoporosis and demonstrate the potential utility of NELL-1 as a combination anabolic/antiosteoclastic therapeutic for bone loss. PMID:26082355

  10. NELL-1 in the treatment of osteoporotic bone loss

    PubMed Central

    James, Aaron W.; Shen, Jia; Zhang, Xinli; Asatrian, Greg; Goyal, Raghav; Kwak, Jin H.; Jiang, Lin; Bengs, Benjamin; Culiat, Cymbeline T.; Turner, A. Simon; Seim III, Howard B.; Wu, Benjamin M.; Lyons, Karen; Adams, John S.; Ting, Kang; Soo, Chia

    2015-01-01

    NELL-1 is a secreted, osteoinductive protein whose expression rheostatically controls skeletal ossification. Overexpression of NELL-1 results in craniosynostosis in humans and mice, whereas lack of Nell-1 expression is associated with skeletal undermineralization. Here we show that Nell-1-haploinsufficient mice have normal skeletal development but undergo age-related osteoporosis, characterized by a reduction in osteoblast:osteoclast (OB:OC) ratio and increased bone fragility. Recombinant NELL-1 binds to integrin β1 and consequently induces Wnt/β-catenin signalling, associated with increased OB differentiation and inhibition of OC-directed bone resorption. Systemic delivery of NELL-1 to mice with gonadectomy-induced osteoporosis results in improved bone mineral density. When extended to a large animal model, local delivery of NELL-1 to osteoporotic sheep spine leads to significant increase in bone formation. Altogether, these findings suggest that NELL-1 deficiency plays a role in osteoporosis and demonstrate the potential utility of NELL-1 as a combination anabolic/antiosteoclastic therapeutic for bone loss. PMID:26082355

  11. Bioactive Silica Nanoparticles Reverse Age-Associated Bone Loss in Mice

    PubMed Central

    Vikulina, Tatyana; Roser-Page, Susanne; Lee, Jin-Kyu; Beck, George R.

    2015-01-01

    We recently reported that in vitro, engineered 50 nm spherical silica nanoparticles promote the differentiation and activity of bone building osteoblasts but suppress that of bone-resorbing osteoclasts. Furthermore, these nanoparticles promote bone accretion in young mice in vivo. In the present study the capacity of these nanoparticles to reverse bone loss in aged mice, a model of human senile osteoporosis, was investigated. Aged mice received nanoparticles weekly and bone mineral density (BMD), bone structure, and bone turnover was quantified. Our data revealed a significant increase in BMD, bone volume, and biochemical markers of bone formation. Biochemical and histological examinations failed to identify any abnormalities caused by nanoparticle administration. Our studies demonstrate that silica nanoparticles effectively blunt and reverse age-associated bone loss in mice by a mechanism involving promotion of bone formation. The data suggest that osteogenic silica nanoparticles may be a safe and effective therapeutic for counteracting age-associated bone loss. PMID:25680544

  12. Human Placenta-Derived Adherent Cells Prevent Bone loss, Stimulate Bone formation, and Suppress Growth of Multiple Myeloma in Bone

    PubMed Central

    Li, Xin; Ling, Wen; Pennisi, Angela; Wang, Yuping; Khan, Sharmin; Heidaran, Mohammad; Pal, Ajai; Zhang, Xiaokui; He, Shuyang; Zeitlin, Andy; Abbot, Stewart; Faleck, Herbert; Hariri, Robert; Shaughnessy, John D.; van Rhee, Frits; Nair, Bijay; Barlogie, Bart; Epstein, Joshua; Yaccoby, Shmuel

    2011-01-01

    Human placenta has emerged as a valuable source of transplantable cells of mesenchymal and hematopoietic origin for multiple cytotherapeutic purposes, including enhanced engraftment of hematopoietic stem cells, modulation of inflammation, bone repair, and cancer. Placenta-derived adherent cells (PDACs) are mesenchymal-like stem cells isolated from postpartum human placenta. Multiple myeloma is closely associated with induction of bone disease and large lytic lesions, which are often not repaired and are usually the sites of relapses. We evaluated the antimyeloma therapeutic potential, in vivo survival, and trafficking of PDACs in the severe combined immunodeficiency (SCID)–rab model of medullary myeloma-associated bone loss. Intrabone injection of PDACs into non-myelomatous and myelomatous implanted bone in SCID-rab mice promoted bone formation by stimulating endogenous osteoblastogenesis, and most PDACs disappeared from bone within 4 weeks. PDACs inhibitory effects on myeloma bone disease and tumor growth were dose-dependent and comparable with those of fetal human mesenchymal stem cells (MSCs). Intrabone, but not subcutaneous, engraftment of PDACs inhibited bone disease and tumor growth in SCID-rab mice. Intratumor injection of PDACs had no effect on subcutaneous growth of myeloma cells. A small number of intravenously injected PDACs trafficked into myelomatous bone. Myeloma cell growth rate in vitro was lower in coculture with PDACs than with MSCs from human fetal bone or myeloma patients. PDACs also promoted apoptosis in osteoclast precursors and inhibited their differentiation. This study suggests that altering the bone marrow microenvironment with PDAC cytotherapy attenuates growth of myeloma and that PDAC cytotherapy is a promising therapeutic approach for myeloma osteolysis. PMID:21732484

  13. Measurement of spinal or peripheral bone mass to estimate early postmenopausal bone loss

    SciTech Connect

    Riis, B.J.; Christiansen, C.

    1988-04-01

    This report presents data from 153 healthy, early postmenopausal women who were randomly allocated to two years of treatment with estrogen or placebo. Bone mineral content in the forearms was measured by single-photon absorptiometry, and bone mineral density of the lumbar spine and total-body bone mineral by dual-photon absorptiometry, before and after one and two years of treatment. At the end of the two years, there were highly significant differences of 6 to 7 percent between the estrogen and the placebo groups at all sites measured. The range of the changes of the spine measurement was twice that of the forearm and total-body measurements. It is concluded that measurement of the forearm by single-photon absorptiometry is superior to measurement of the spine by dual-photon absorptiometry both in clinical studies and in the individual patient for detecting estrogen-dependent bone loss and its treatment by estrogen replacement.

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2015-01-01

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

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

    NASA Technical Reports Server (NTRS)

    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.

  17. Autophagy in alcohol-induced liver diseases.

    PubMed

    Dolganiuc, Angela; Thomes, Paul G; Ding, Wen-Xing; Lemasters, John J; Donohue, Terrence M

    2012-08-01

    Alcohol is the most abused substance worldwide and a significant source of liver injury; the mechanisms of alcohol-induced liver disease are not fully understood. Significant cellular toxicity and impairment of protein synthesis and degradation occur in alcohol-exposed liver cells, along with changes in energy balance and modified responses to pathogens. Autophagy is the process of cellular catabolism through the lysosomal-dependent machinery, which maintains a balance among protein synthesis, degradation, and recycling of self. Autophagy is part of normal homeostasis and it can be triggered by multiple factors that threaten cell integrity, including starvation, toxins, or pathogens. Multiple factors regulate autophagy; survival and preservation of cellular integrity at the expense of inadequately folded proteins and damaged high-energy generating intracellular organelles are prominent targets of autophagy in pathological conditions. Coincidentally, inadequately folded proteins accumulate and high-energy generating intracellular organelles, such as mitochondria, are damaged by alcohol abuse; these alcohol-induced pathological findings prompted investigation of the role of autophagy in the pathogenesis of alcohol-induced liver damage. Our review summarizes the current knowledge about the role and implications of autophagy in alcohol-induced liver disease. PMID:22551004

  18. Alcohol-Induced Disruption of Endocrine Signaling

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This article contains the proceedings of a symposium at the 2006 ISBRA Meeting in Sydney Australia, organized and co-chaired by Martin J. Ronis and Thomas M. Badger. The presentations were (1) Effects of long term ethanol consumption on liver injury and repair, by Jack R. Wands; (2) Alcohol-induced...

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

    PubMed Central

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

    2013-01-01

    Mucolipidosis type II (MLII) is a severe multi-systemic genetic disorder caused by missorting of lysosomal proteins and the subsequent lysosomal storage of undegraded macromolecules. Although affected children develop disabling skeletal abnormalities, their pathogenesis is not understood. Here we report that MLII knock-in mice, recapitulating the human storage disease, are runted with accompanying growth plate widening, low trabecular bone mass and cortical porosity. Intralysosomal deficiency of numerous acid hydrolases results in accumulation of storage material in chondrocytes and osteoblasts, and impaired bone formation. In osteoclasts, no morphological or functional abnormalities are detected whereas osteoclastogenesis is dramatically increased in MLII mice. The high number of osteoclasts in MLII is associated with enhanced osteoblastic expression of the pro-osteoclastogenic cytokine interleukin-6, and pharmacological inhibition of bone resorption prevented the osteoporotic phenotype of MLII mice. Our findings show that progressive bone loss in MLII is due to the presence of dysfunctional osteoblasts combined with excessive osteoclastogenesis. They further underscore the importance of a deep skeletal phenotyping approach for other lysosomal diseases in which bone loss is a prominent feature. PMID:24127423

  20. Role of carbonic anhydrase in bone - Plasma acetazolamide concentrations associated with inhibition of bone loss

    NASA Technical Reports Server (NTRS)

    Kenny, A. D.

    1985-01-01

    The effects of acetazolamide and benzolamide on bone formation are examined. Solutions of acetazolamide and benzolamide with 1 M THAM/tris(hydromethyl)aminoethane/ or without 1 M THAM were injected subcutaneous with a minipump and into the food of Sprague-Dawley rats. The data reveal that for 8-day and 12-day infusions only acetazolamide combined with 1 M THAM caused any reduction in bone loss and there were no changes in body weights, food consumption and plasma calcium and phosphorus values. Following 8 days of infusion of acetazolamide with 1 M THAM at infusion rates of 0.5, 5.0, and 50 micrograms/hr, no reduction was detected at 0.5 microgram/hr, a 30 percent reduction occurred at 5.0 micrograms/hr and a 49 percent decrease at 50 micrograms/hr. In the benzolamide experiment it was observed that 0.5 percent of the solution in the food caused no reduction in bone loss; however, infusions with benzolamide plus 1 M THAM resulted in a bone loss reduction of 30 percent at 5.0 micrograms/hr, and a 49 percent decrease at 50 micrograms/hr. Acetazolamide levels in the plasma at 50 micrograms/hr doses are calculated as ranging from 99 ng/ml-223 ng/ml and as 46 ng/ml at 5 micrograms/hr doses.

  1. Morsellized bone grafting compensates for femoral bone loss in revision total knee arthroplasty. An experimental study.

    PubMed

    van Loon, C J; de Waal Malefijt, M C; Verdonschot, N; Buma, P; van der Aa, A J; Huiskes, R

    1999-01-01

    This study was undertaken to examine the contribution of uncontained morsellized bone graft to the structural properties of a femoral reconstruction in total knee arthroplasty and to serve as a basis for an in vivo animal study. Ten human distal femora with a standard unicondylar uncontained medial bone defect were prepared to fit a femoral component of a cruciate sacrificing TKA. A cyclic axial load of 750 N was applied to the medial part of the femoral component in the presence of impacted morsellized bone graft. After removal of the bone graft, the cyclic loading was repeated for the unsupported situation. None of the grafts collapsed and all cement mantles stayed intact during the experiments. Elastic deformation during cyclic loading was significantly less when graft was added while time-dependent deformation was not affected. We conclude that impacted morsellized bone graft, used for reconstruction of uncontained femoral bone loss in revision knee arthroplasty, may improve the structural resistance against loading. Further animal experimentation for in vivo application is warranted. PMID:9916775

  2. Prostaglandin E2 Prevents Bone Loss and Adds Extra Bone to Immobilized Distal Femoral Metaphysis in Female Rats

    NASA Technical Reports Server (NTRS)

    Akamine, T.; Jee, W. S. S.; Ke, H. Z.; Li, X. J.; Lin, B. Y.

    1992-01-01

    The object of this study was to determine whether prostaglandin E2 (PGE2) can prevent disuse (underloading)-induced cancellous bone loss. Thirteen-month-old retired female Sprague-Dawley breeders served as controls or were subjected to right hindlimb immobilization by bandaging and simultaneously treated subcutaneously daily with 0, 1, 3, or 6 mg PGE2/kg/d for two and six weeks. Histomorphometric analyses were performed on the cancellous bone using double-fluorescent labeled, 20 micron thick, undecalcified distal femoral metaphysis sections. We found that PGE2 administration not only prevented disuse-induced bone loss, but also added extra bone to disuse cancellous bone in a dose-response manner. PGE2 prevented the disuse-induced osteopenia by stimulating more bone formation than and shortening the period of bone remodeling. It activated woven bone formation, stimulated lamellar bone formation, and increased the eroded bone surface above that caused by disuse alone. While underloading increased the remodeling period (sigma), PGE2 treatment of underloaded bone shortened the time for osteoclastic bone resorption and bone remodeling, and thus reduced the remodeling space. The study shows that PGE2 is a powerful anabolic agent that prevents disuse-induced osteopenia and adds extra bone to these same bones.

  3. GLENOHUMERAL INSTABILITY AND GLENOID BONE LOSS IN A THROWING ATHLETE

    PubMed Central

    Mair, Scott; Lattermann, Christian

    2013-01-01

    This case presents the challenges of management associated with a young throwing athlete presenting with a history of bilateral anterior shoulder instability. This athlete had multiple surgical interventions over a three‐year period. The imaging modalities provided partial elucidation (at best) of the true picture of the pathology. This case report outlines the decision making process utilized to provide individualized care to a young throwing athlete with bilateral glenohumeral joint instability, recurrent dislocations, and resultant glenoid bone loss. Level of Evidence: 5 (Single Case report) PMID:23593558

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

    PubMed Central

    Kim, Tae-Ho; Park, Eui Kyun; Huh, Man-Il; Kim, Hong Kyun; Kim, Shin-Yoon; Lee, Sang-Han

    2016-01-01

    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. PMID:27313644

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  6. Bone marrow monocyte PECAM-1 deficiency elicits increased osteoclastogenesis resulting in trabecular bone loss.

    PubMed

    Wu, Yue; Tworkoski, Kathryn; Michaud, Michael; Madri, Joseph A

    2009-03-01

    In our investigations of the bone marrow (BM) of PECAM-1 null (knockout, KO) mice, we observed that the trabecular bone volume and number of trabeculae were significantly reduced in femoral and tibial long bones. Further studies in vitro revealed increased numbers and size of osteoclasts, enhanced bone resorption on dentin substrates, and hypersensitivity to macrophage CSF and receptor activator of NF-kappaB ligand in BM-derived osteoclast precursor cultures from KO mice. Associations among PECAM-1, Syk, and SHP-1 were found in wild-type BM monocyte derived osteoclast-like cells. The absence of PECAM-1 and SHP-1 interactions in the KO cells leads to the dysregulation of Syk kinases and/or phosphatases, possibly SHP-1. Indeed, KO derived osteoclast-like cells exhibited increased Syk tyrosine phosphorylation levels compared with WT cells. Lastly, WT mice engrafted with marrow from KO kindred showed loss of trabecular bone analogous to KO mice, consistent with increased osteoclastogenesis. PMID:19234161

  7. Phytoestrogens for menopausal bone loss and climacteric symptoms.

    PubMed

    Lagari, Violet S; Levis, Silvina

    2014-01-01

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

  8. Role of microRNAs in Alcohol-Induced Multi-Organ Injury

    PubMed Central

    Natarajan, Sathish Kumar; Pachunka, Joseph M.; Mott, Justin L.

    2015-01-01

    Alcohol consumption and its abuse is a major health problem resulting in significant healthcare cost in the United States. Chronic alcoholism results in damage to most of the vital organs in the human body. Among the alcohol-induced injuries, alcoholic liver disease is one of the most prevalent in the United States. Remarkably, ethanol alters expression of a wide variety of microRNAs that can regulate alcohol-induced complications or dysfunctions. In this review, we will discuss the role of microRNAs in alcoholic pancreatitis, alcohol-induced liver damage, intestinal epithelial barrier dysfunction, and brain damage including altered hippocampus structure and function, and neuronal loss, alcoholic cardiomyopathy, and muscle damage. Further, we have reviewed the role of altered microRNAs in the circulation, teratogenic effects of alcohol, and during maternal or paternal alcohol consumption. PMID:26610589

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  10. Comparison of single- and dual-photon absorptiometry in postmenopausal bone mineral loss

    SciTech Connect

    Nilas, L.; Borg, J.; Gotfredsen, A.; Christiansen, C.

    1985-11-01

    The authors describe a single photon absorptiometric (SPA) technique, which enables differential estimation of the rates of loss from trabecular and cortical bone. Ten scans are obtained in the forearm: six in an area with about 7% trabecular bone and four scans in the adjacent distal area with a trabecular bone content of 25%. By comparing bone masses of these two sites in 19 postmenopausal and 53 premenopausal women, the postmenopausal trabecular bone loss was estimated to be approximately seven times greater than cortical loss within the first years of cessation of regular vaginal bleeding. On a group basis the bone loss at the distal forearm scan site (by SPA) corresponded closely to the spinal bone loss (by dual-photon absorptiometry). The reproducibility of the two scan sites in the forearm was 1-1.5% (CV%), which makes the method suitable for longitudinal studies. Corrections for variations in fatty tissue covering can be made without deterioration of the reproducibility.

  11. The science and practice of bone health in oncology: managing bone loss and metastasis in patients with solid tumors.

    PubMed

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

    2009-10-01

    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

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

    PubMed Central

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

    2015-01-01

    Bone remodeling is a lifelong process in vertebrates that relies on the correct balance between bone resorption by osteoclasts and bone formation by osteoblasts. Bone loss and fracture risk are implicated in inflammatory autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, and systemic lupus erythematosus. The network of inflammatory cytokines produced during chronic inflammation induces an uncoupling of bone formation and resorption, resulting in significant bone loss in patients with inflammatory autoimmune diseases. Here, we review and discuss the involvement of the inflammatory cytokine network in the pathophysiological aspects and the therapeutic advances in inflammatory autoimmune diseases. PMID:26065006

  13. High-fat diet causes bone loss in young mice by promoting osteoclastogenesis through alteration of the bone marrow environment.

    PubMed

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

    2015-04-01

    Obesity is a severe health problem in children, afflicting several organ systems including bone. However, the role of obesity on bone homeostasis and bone cell function in children has not been studied in detail. Here we used young mice fed a high-fat diet (HFD) to model childhood obesity and investigate the effect of HFD on the phenotype of cells within the bone marrow environment. Five-week-old male mice were fed a HFD for 3, 6, and 12 weeks. Decreased bone volume was detected after 3 weeks of HFD treatment. After 6 and 12 weeks, HFD-exposed mice had less bone mass and increased osteoclast numbers. Bone marrow cells, but not spleen cells, from HFD-fed mice had increased osteoclast precursor frequency, elevated osteoclast formation, and bone resorption activity, as well as increased expression of osteoclastogenic regulators including RANKL, TNF, and PPAR-gamma. Bone formation rate and osteoblast and adipocyte numbers were also increased in HFD-fed mice. Isolated bone marrow cells also had a corresponding elevation in the expression of positive regulators of osteoblast and adipocyte differentiation. Our findings indicate that in juvenile mice, HFD-induced bone loss is mainly due to increased osteoclast bone resorption by affecting the bone marrow microenvironment. Thus, targeting osteoclast formation may present a new therapeutic approach for bone complications in obese children. PMID:25673503

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

    PubMed Central

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

    2015-01-01

    Background: Sclerostin, encoded by the SOST gene, has been implicated in the response to mechanical loading in bone. Some studies demonstrated that unloading leads to up-regulated SOST expression, which may induce bone loss. Purpose: Most reported studies regarding the changes caused by mechanical unloading were only based on a single site. Considering that the longitudinal bone growth leads to cells of different age with different sensitivity to unloading, we hypothesized that bone turnover in response to unloading is site specific. Methods: We established a disuse rat model by sciatic neurectomy in tibia. In various regions at two time-points, we evaluated the bone mass and microarchitecture in surgically-operated rats and control rats by micro-Computed Tomography (micro-CT) and histology, sclerostin/SOST by immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and quantitative reverse transcription polymerase chain reaction (qPCR), tartrate resistant acid phosphatase 5b (TRAP 5b) by ELISA and TRAP staining, and other bone markers by ELISA. Results: Micro-CT and histological analysis confirmed bone volume in the disuse rats was significantly decreased compared with those in the time-matched control rats, and microarchitecture also changed 2 and 8 weeks after surgery. Compared with the control groups, SOST mRNA expression in the diaphysis was down-regulated at both week 2 and 8. On the contrary, the percentage of sclerostin-positive osteocytes showed an up-regulated response in the 5 - 6 mm region away from the growth plate, while in the 2.5 - 3.5 mm region, the percentage was no significant difference. Nevertheless, in 0.5 - 1.5 mm region, the percentage of sclerostin-positive osteocytes decreased after 8 weeks, consistent with serum SOST level. Besides, the results of TRAP also suggested that the expression in response to unloading may be opposite in different sites or system. Conclusion: Our data indicated that unloading-induced changes in bone

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

    PubMed

    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. PMID:23970373

  16. Bisphosphonate treatment of type I diabetic mice prevents early bone loss but accentuates suppression of bone formation

    PubMed Central

    Coe, Lindsay M.; Tekalur, Srinivasan Arjun; Shu, Yutian; Baumann, Melissa J.; McCabe, Laura R.

    2016-01-01

    Type I (T1) diabetes is an autoimmune and metabolic disease associated with bone loss. Previous studies demonstrate that T1-diabetes decreases osteoblast activity and viability. Bisphosphonate therapy, commonly used to treat osteoporosis, is demonstrated to inhibit osteoclast activity as well as osteoblast apoptosis. Therefore, we examined the effect of weekly alendronate treatments on T1-diabetes induced osteoblast apoptosis and bone loss. Bone TUNEL assays identified that alendronate therapy prevents the diabetes-induced osteoblast death observed during early stages of diabetes development. Consistent with this, alendronate treatment for 40 days was able to prevent diabetes-induced trabecular bone loss. Alendronate was also able to reduce marrow adiposity in both control diabetic mice compared to untreated mice. Mechanical testing indicated that 40 days of alendronate treatment increased bone stiffness but decreased the work required for fracture in T1-diabetic and alendronate treated mice. Of concern at this later time point, bone formation rate and osteoblast markers, which were already decreased in diabetic mice, were further suppressed in alendronate treated diabetic mice. Taken together, our results suggest that short term alendronate treatment can prevent T1-diabetes-induced bone loss in mice, possibly in part by inhibiting diabetes onset associated osteoblast death, while longer treatment enhanced bone density but at the cost of further suppressing bone formation in diabetic mice. PMID:25641511

  17. Mineralization defects in cementum and craniofacial bone from loss of bone sialoprotein

    PubMed Central

    Foster, B.L.; Ao, M.; Willoughby, C.; Soenjaya, Y.; Holm, E.; Lukashova, L.; Tran, A. B.; Wimer, H.F.; Zerfas, P.M.; Nociti, F.H.; Kantovitz, K.R.; Quan, B.D.; Sone, E.D.; Goldberg, H.A.; Somerman, M.J.

    2015-01-01

    Bone sialoprotein (BSP) is a multifunctional extracellular matrix protein found in mineralized tissues, including bone, cartilage, tooth root cementum (both acellular and cellular types), and dentin. In order to define the role BSP plays in the process of biomineralization of these tissues, we analyzed cementogenesis, dentinogenesis, and osteogenesis (intramembranous and endochondral) in craniofacial bone in Bsp null mice and wild-type (WT) controls over a developmental period (1-60 days post natal; dpn) by histology, immunohistochemistry, undecalcified histochemistry, microcomputed tomography (microCT), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and quantitative PCR (qPCR). Regions of intramembranous ossification in the alveolus, mandible, and calvaria presented delayed mineralization and osteoid accumulation, assessed by von Kossa and Goldner's trichrome stains at 1 and 14 dpn. Moreover, Bsp−/− mice featured increased cranial suture size at the early time point, 1 dpn. Immunostaining and PCR demonstrated that osteoblast markers, osterix, alkaline phosphatase, and osteopontin were unchanged in Bsp null mandibles compared to WT. Bsp−/− mouse molars featured a lack of functional acellular cementum formation by histology, SEM, and TEM, and subsequent loss of Sharpey's collagen fiber insertion into the tooth root structure. Bsp−/− mouse alveolar and mandibular bone featured equivalent or fewer osteoclasts at early ages (1 and 14 dpn), however, increased RANKL immunostaining and mRNA, and significantly increased number of osteoclast-like cells (2-5 fold) were found at later ages (26 and 60 dpn), corresponding to periodontal breakdown and severe alveolar bone resorption observed following molar teeth entering occlusion. Dentin formation was unperturbed in Bsp−/− mouse molars, with no delay in mineralization, no alteration in dentin dimensions, and no differences in odontoblast markers analyzed. No defects were identified

  18. Mineralization defects in cementum and craniofacial bone from loss of bone sialoprotein.

    PubMed

    Foster, B L; Ao, M; Willoughby, C; Soenjaya, Y; Holm, E; Lukashova, L; Tran, A B; Wimer, H F; Zerfas, P M; Nociti, F H; Kantovitz, K R; Quan, B D; Sone, E D; Goldberg, H A; Somerman, M J

    2015-09-01

    Bone sialoprotein (BSP) is a multifunctional extracellular matrix protein found in mineralized tissues, including bone, cartilage, tooth root cementum (both acellular and cellular types), and dentin. In order to define the role BSP plays in the process of biomineralization of these tissues, we analyzed cementogenesis, dentinogenesis, and osteogenesis (intramembranous and endochondral) in craniofacial bone in Bsp null mice and wild-type (WT) controls over a developmental period (1-60 days post natal; dpn) by histology, immunohistochemistry, undecalcified histochemistry, microcomputed tomography (microCT), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and quantitative PCR (qPCR). Regions of intramembranous ossification in the alveolus, mandible, and calvaria presented delayed mineralization and osteoid accumulation, assessed by von Kossa and Goldner's trichrome stains at 1 and 14 dpn. Moreover, Bsp(-/-) mice featured increased cranial suture size at the early time point, 1 dpn. Immunostaining and PCR demonstrated that osteoblast markers, osterix, alkaline phosphatase, and osteopontin were unchanged in Bsp null mandibles compared to WT. Bsp(-/-) mouse molars featured a lack of functional acellular cementum formation by histology, SEM, and TEM, and subsequent loss of Sharpey's collagen fiber insertion into the tooth root structure. Bsp(-/-) mouse alveolar and mandibular bone featured equivalent or fewer osteoclasts at early ages (1 and 14 dpn), however, increased RANKL immunostaining and mRNA, and significantly increased number of osteoclast-like cells (2-5 fold) were found at later ages (26 and 60 dpn), corresponding to periodontal breakdown and severe alveolar bone resorption observed following molar teeth entering occlusion. Dentin formation was unperturbed in Bsp(-/-) mouse molars, with no delay in mineralization, no alteration in dentin dimensions, and no differences in odontoblast markers analyzed. No defects were identified in

  19. Corticosteroid-induced bone loss. Prevention and management.

    PubMed

    Picado, C; Luengo, M

    1996-11-01

    Osteoporosis is one of the most serious adverse effects experienced by patients receiving long term corticosteroid therapy. Bone loss occurs soon after corticosteroid therapy is initiated and results from a complex mechanism involving osteoblastic suppression and increased bone resorption. There are a number of factors that may increase the risk of corticosteroid-induced osteoporosis [smoking, excessive alcohol (ethanol) consumption, amenorrhoea, relative immobilisation, chronic obstructive pulmonary disease, inflammatory bowel disease, hypogonadism in men, organ transplantation]. The initial assessment of patients about to start taking corticosteroids should include measurement of spinal bone density, urinary calcium level and plasma calcifediol (25-hydroxycholecalciferol) level; serum testosterone levels should also be measured when hypogonadism is suspected. Many different drugs have been used to prevent osteoporosis in patients receiving long-term corticosteroid therapy, including thiazide diuretics, cholecalciferol (vitamin D) metabolites, bisphosphonates, calcitonin, fluoride, estrogens, anabolic steroids and progesterone. At present, however, published studies have failed to demonstrate a reduction in the rate of fracture using different preventive pharmacological therapies in patients being treated with corticosteroids on a continuous basis. Among the drugs studied, bisphosphonates (pamidronic acid and etidronic acid) and calcitonin appear to be effective in increasing bone density. Cholecalciferol preparations have been reported to be effective in some, but not all, studies. Limited data have shown positive results with thiazide diuretics, estrogen, progesterone and nandrolone. When treating patients with corticosteroids, the lowest effective dose should be used, with topical corticosteroids used whenever possible. Auranofin may be considered in patients with corticosteroid-dependent asthma. Patients should take as much physical activity as possible

  20. Periotest for measuring periodontal characteristics--correlation with periodontal bone loss.

    PubMed

    Schulte, W; d'Hoedt, B; Lukas, D; Maunz, M; Steppeler, M

    1992-05-01

    The Periotest measures the reaction of the periodontium to a defined percussive force. The percussion is applied to the tooth by an electronically controlled tapping head. Information on structural change is obtained by measurement of both the elastic and viscous characteristics of the periodontium. The latter prevent oscillations of the tooth in the alveolar bone. A value is calculated and is displayed as a "Periotest value". The following research report shows the relation of Periotest values to bone loss. Bone loss was quantitatively determined for 2312 teeth from orthopantomographic radiographs and for 900 teeth exposed to intra-oral films using the standard paralleling technique. A differentiation was made between vertical and horizontal bone loss. Clinical mobility index, pocket depth, gingival recession and papillary hemorrhagic index were also measured. There was a strong association between the Periotest value and bone loss. These results suggest that Periotest evaluation provides an objective indication of the extent of periodontal bone loss. PMID:1608031

  1. Suppression of wnt /beta-catenin signaling in bone of female rats exposed to ethanol post-lactation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic alcohol abuse is a major risk factor for development of osteoporosis. However, the mechanisms through which chronic alcohol intake induces bone loss remain unclear. Alcohol-induced oxidative stress might be the key event in tissue injury. In this report, we chronically infused EtOH (12g/kg/d...

  2. 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.

    PubMed

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

    2016-08-01

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

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

    MedlinePlus

    ... Pub. No. 16–7887 NIH Osteoporosis and Related Bone Diseases ~ National Resource Center 2 AMS Circle Bethesda, MD ... another language, contact the NIH Osteoporosis and Related Bone Diseases ~ National Resource Center at NIHBoneInfo@mail.nih.gov . ...

  4. A positive correlation between occlusal trauma and peri-implant bone loss: literature support.

    PubMed

    Misch, Carl E; Suzuki, Jon B; Misch-Dietsh, Francine M; Bidez, Martha W

    2005-06-01

    The relationship between occlusal overload and peri-implant bone loss remains a controversial topic in implant dentistry. A causal relationship between the incidence of marginal bone loss next to an implant and occlusal overload implies a treatment plan and occlusal scheme would benefit from a force management approach. A MEDLINE-assisted and hand search of peer-reviewed English literature and relative textbooks were used for a selective review of articles addressing biomechanical stress and bone loss in cellular biomechanics, engineering principles, mechanical properties of bone, animal studies, clinical reports, bone physiology, and implant design biomechanics. These papers demonstrate occlusal overload on implants may increase the incidence of marginal bone loss. PMID:15968181

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

    NASA Technical Reports Server (NTRS)

    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

  6. Hydrogen Sulfide Is a Novel Regulator of Bone Formation Implicated in the Bone Loss Induced by Estrogen Deficiency.

    PubMed

    Grassi, Francesco; Tyagi, Abdul Malik; Calvert, John W; Gambari, Laura; Walker, Lindsey D; Yu, Mingcan; Robinson, Jerid; Li, Jau-Yi; Lisignoli, Gina; Vaccaro, Chiara; Adams, Jonathan; Pacifici, Roberto

    2016-05-01

    Hydrogen sulfide (H2 S) is a gasotransmitter known to regulate bone formation and bone mass in unperturbed mice. However, it is presently unknown whether H2 S plays a role in pathologic bone loss. Here we show that ovariectomy (ovx), a model of postmenopausal bone loss, decreases serum H2 S levels and the bone marrow (BM) levels of two key H2 S-generating enzymes, cystathione β-synthase (CBS) and cystathione γ-lyase (CSE). Treatment with the H2 S-donor GYY4137 (GYY) normalizes serum H2 S in ovx mice, increases bone formation, and completely prevents the loss of trabecular bone induced by ovx. Mechanistic studies revealed that GYY increases murine osteoblastogenesis by activating Wnt signaling through increased production of the Wnt ligands Wnt16, Wnt2b, Wnt6, and Wnt10b in the BM. Moreover, in vitro treatment with 17β-estradiol upregulates the expression of CBS and CSE in human BM stromal cells (hSCs), whereas an H2 S-releasing drug induces osteogenic differentiation of hSCs. In summary, regulation of H2 S levels is a novel mechanism by which estrogen stimulates osteoblastogenesis and bone formation in mice and human cells. Blunted production of H2 S contributes to ovx-induced bone loss in mice by limiting the compensatory increase in bone formation elicited by ovx. Restoration of H2 S levels is a potential novel therapeutic approach for postmenopausal osteoporosis. © 2015 American Society for Bone and Mineral Research. PMID:26614970

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

    PubMed

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

    2014-11-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    NASA Technical Reports Server (NTRS)

    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.

  10. Prognosis of implant longevity in terms of annual bone loss: a methodological finite element study.

    PubMed

    Demenko, Vladyslav; Linetskiy, Igor; Linetska, Larysa; Nesvit, Vitalij; Shevchenko, Andrii; Yefremov, Oleg; Weisskircher, Hans-Werner

    2016-01-01

    Dental implant failure is mainly the consequence of bone loss at peri-implant area. It usually begins in crestal bone. Due to this gradual loss, implants cannot withstand functional force without bone overload, which promotes complementary loss. As a result, implant lifetime is significantly decreased. To estimate implant success prognosis, taking into account 0.2 mm annual bone loss for successful implantation, ultimate occlusal forces for the range of commercial cylindrical implants were determined and changes of the force value for each implant due to gradual bone loss were studied. For this purpose, finite element method was applied and von Mises stresses in implant-bone interface under 118.2 N functional occlusal load were calculated. Geometrical models of mandible segment, which corresponded to Type II bone (Lekholm & Zarb classification), were generated from computed tomography images. The models were analyzed both for completely and partially osseointegrated implants (bone loss simulation). The ultimate value of occlusal load, which generated 100 MPa von Mises stresses in the critical point of adjacent bone, was calculated for each implant. To estimate longevity of implants, ultimate occlusal loads were correlated with an experimentally measured 275 N occlusal load (Mericske-Stern & Zarb). These findings generally provide prediction of dental implants success. PMID:25847087

  11. Staphylococcus aureus Protein A Plays a Critical Role in Mediating Bone Destruction and Bone Loss in Osteomyelitis

    PubMed Central

    Widaa, Amro; Claro, Tania; Foster, Timothy J.; O’Brien, Fergal J.; Kerrigan, Steven W.

    2012-01-01

    Staphylococcus aureus is the most frequent causative organism of osteomyelitis. It is characterised by widespread bone loss and bone destruction. Previously we demonstrated that S. aureus protein A (SpA) is capable of binding to tumour necrosis factor receptor-1 expressed on pre-osteoblastic cells, which results in signal generation that leads to cell apoptosis resulting in bone loss. In the current report we demonstrate that upon S. aureus binding to osteoblasts it also inhibits de novo bone formation by preventing expression of key markers of osteoblast growth and division such as alkaline phosphatase, collagen type I, osteocalcin, osteopontin and osteocalcin. In addition, S. aureus induces secretion of soluble RANKL from osteoblasts which in turn recruits and activates the bone resorbing cells, osteoclasts. A strain of S. aureus defective in SpA failed to affect osteoblast growth or proliferation and most importantly failed to recruit or activate osteoclasts. These results suggest that S. aureus SpA binding to osteoblasts provides multiple coordinated signals that accounts for bone loss and bone destruction seen in osteomyelitis cases. A better understanding of the mechanisms through which S. aureus leads to bone infection may improve treatment or lead to the development of better therapeutic agents to treat this notoriously difficult disease. PMID:22792377

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

    PubMed

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

    2016-07-01

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

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

    PubMed Central

    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

  14. Circadian Modulation of Alcohol-Induced Sedation and Recovery in Male and Female Drosophila.

    PubMed

    De Nobrega, Aliza K; Lyons, Lisa C

    2016-04-01

    Delineating the factors that affect behavioral and neurological responses to alcohol is critical to facilitate measures for preventing or treating alcohol abuse. The high degree of conserved molecular and physiological processes makes Drosophila melanogaster a valuable model for investigating circadian interactions with alcohol-induced behaviors and examining sex-specific differences in alcohol sensitivity. We found that wild-type Drosophila exhibited rhythms in alcohol-induced sedation under light-dark and constant dark conditions with considerably greater alcohol exposure necessary to induce sedation during the late (subjective) day and peak sensitivity to alcohol occurring during the late (subjective) night. The circadian clock also modulated the recovery from alcohol-induced sedation with flies regaining motor control significantly faster during the late (subjective) day. As predicted, the circadian rhythms in sedation and recovery were absent in flies with a mutation in the circadian gene period or arrhythmic flies housed in constant light conditions. Flies lacking a functional circadian clock were more sensitive to the effects of alcohol with significantly longer recovery times. Similar to other animals and humans, Drosophila exhibit sex-specific differences in alcohol sensitivity. We investigated whether the circadian clock modulated the rhythms in the loss-of-righting reflex, alcohol-induced sedation, and recovery differently in males and females. We found that both sexes demonstrated circadian rhythms in the loss-of-righting reflex and sedation with the differences in alcohol sensitivity between males and females most pronounced during the late subjective day. Recovery of motor reflexes following alcohol sedation also exhibited circadian modulation in male and female flies, although the circadian clock did not modulate the difference in recovery times between the sexes. These studies provide a framework outlining how the circadian clock modulates alcohol-induced

  15. Low Dose Parathyroid Hormone Maintains Normal Bone Formation in Adult Male Rats During Rapid Weight Loss

    PubMed Central

    Turner, Russell T.; Iwaniec, Urszula T.

    2011-01-01

    A persistent negative energy balance results in bone loss. It is not clear whether the bone loss associated with chronic negative energy balance can be prevented. The objective of this study was to assess the efficacy of intermittent low dose parathyroid hormone (PTH) treatment in maintaining normal bone formation during severe energy restriction. Six-month-old male Fisher 344 rats were divided into 4 treatment groups: (1) baseline, (2) ad libitum (ad lib)-fed control, (3) energy-restricted (to consume 40% ad lib caloric intake), or (4) energy-restricted + low dose (1 μg/kg/d) PTH. Severe energy restriction for 14 days decreased body weight and serum leptin levels. Compared to ad lib-fed controls, energy-restricted rats had lower cancellous bone formation, higher osteoclast perimeter/bone perimeter and higher bone marrow adiposity in the proximal tibial metaphysis. Also, the energy-restricted rats had a lower periosteal bone formation rate at the tibia-fibula synostosis. Administration of PTH to energy-restricted rats had no effect on weight loss or osteoclast perimeter/bone perimeter. In contrast, energy-restricted rats treated with PTH had higher rates of cancellous and cortical bone formation compared to energy-restricted rats, and did not differ from the ad lib-fed control animals. Furthermore, PTH treatment maintained normal bone marrow adiposity. In conclusion, rapid weight loss in adult male rats was accompanied by decreased bone formation and increased bone marrow adiposity and these changes were prevented by low dose PTH treatment. Taken together, the results suggest that the energy cost of bone formation in adult rats is low and PTH therapy is effective in preventing the reduced bone formation associated with rapid weight loss. PMID:21215827

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

    NASA Technical Reports Server (NTRS)

    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

  17. Delay of natural bone loss by higher intakes of specific minerals and vitamins.

    PubMed

    Schaafsma, A; de Vries, P J; Saris, W H

    2001-05-01

    For early prevention or inhibition of postmenopausal and age-related bone loss, nutritional interventions might be a first choice. For some vitamins and minerals an important role in bone metabolism is known or suggested. Calcium and vitamin D support bone mineral density and are basic components in most preventive strategies. Magnesium is involved in a number of activities supporting bone strength, preservation, and remodeling. Fluorine and strontium have bone-forming effects. However, high amounts of both elements may reduce bone strength. Boron is especially effective in case of vitamin D, magnesium, and potassium deficiency. Vitamin K is essential for the activation of osteocalcin. Vitamin C is an important stimulus for osteoblast-derived proteins. Increasing the recommended amounts (US RDA 1989), adequate intakes (US DRI 1997), or assumed normal intakes of mentioned food components may lead to a considerable reduction or even prevention of bone loss, especially in late postmenopausal women and the elderly. PMID:11401244

  18. Annual bone loss and success rates of dental implants based on radiographic measurements

    PubMed Central

    Zhang, L; Liu, Y; Wismeijer, D

    2014-01-01

    Objectives: Bone loss around dental implants is generally measured by monitoring changes in marginal bone level using radiographs. After the first year of implantation, an implant should have <0.2 mm annual loss of marginal bone level to satisfy the criteria of success. However, the process of measuring marginal bone level on radiographs has a precision of 0.2 mm (or more) owing to variations in exposure geometry, exposure time and observer perception. Therefore, the value of the annual loss may vary considerably, especially when short intervals are considered. This study investigates how the success rate of dental implants depends on the way annual bone loss is calculated. Methods: Panoramic radiographs of 82 implant patients with an average follow-up of 10.4 years were analysed. Marginal bone levels near the implants were indicated by one observer. The annual loss of marginal bone level was determined according to four different calculation methods. Results: The methods yielded success rates of 9%, 45%, 81% and 89%. Conclusions: The success rate of dental implants measured on radiographs greatly depends on the details of the calculation method. Without rigorous standardization, annual bone loss and implant success rate are not well defined. PMID:25030551

  19. Zoledronate prevents lactation induced bone loss and results in additional post-lactation bone mass in mice.

    PubMed

    Wendelboe, Mette Høegh; Thomsen, Jesper Skovhus; Henriksen, Kim; Vegger, Jens Bay; Brüel, Annemarie

    2016-06-01

    In rodents, lactation is associated with a considerable and very rapid bone loss, which almost completely recovers after weaning. The aim of the present study was to investigate whether the bisphosphonate Zoledronate (Zln) can inhibit lactation induced bone loss, and if Zln interferes with recovery of bone mass after lactation has ceased. Seventy-six 10-weeks-old NMRI mice were divided into the following groups: Baseline, Pregnant, Lactation, Lactation+Zln, Recovery, Recovery+Zln, and Virgin Control (age-matched). The lactation period was 12days, then the pups were removed, and thereafter recovery took place for 28days. Zln, 100μg/kg, was given s.c. on the day of delivery, and again 4 and 8days later. Mechanical testing, μCT, and dynamic histomorphometry were performed. At L4, lactation resulted in a substantial loss of bone strength (-55% vs. Pregnant, p<0.01), BV/TV (-40% vs. Pregnant, p<0.01), and trabecular thickness (Tb.Th) (-29% vs. Pregnant, p<0.001). Treatment with Zln completely prevented lactation induced loss of bone strength, BV/TV, and Tb.Th at L4. Full recovery of micro-architectural and mechanical properties was found 28days after weaning in vehicle-treated mice. Interestingly, the recovery group treated with Zln during the lactation period had higher BV/TV (+45%, p<0.01) and Tb.Th (+16%, p<0.05) compared with virgin controls. Similar results were found at the proximal tibia and femur. This indicates that Zln did not interfere with the bone formation taking place after weaning. On this background, we conclude that post-lactation bone formation is not dependent on a preceding lactation induced bone loss. PMID:27021151

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

    NASA Technical Reports Server (NTRS)

    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

  1. Bone Marrow Transplantation Improves Autoinflammation and Inflammatory Bone Loss in SH3BP2 Knock-In Cherubism Mice

    PubMed Central

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

    2014-01-01

    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 (Sh3bp2KI/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 Sh3bp2KI/KI mice. Bone marrow (BM) cells from wild-type (Sh3bp2+/+) mice were transplanted to 6-week-old Sh3bp2KI/KI mice with developing inflammation and to 10-week-old Sh3bp2KI/KI mice with established inflammation. Six-week-old Sh3bp2KI/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 10 weeks after BMT compared to Sh3bp2KI/KI mice transplanted with Sh3bp2KI/KI BM cells. Elevation of serum TNF-α levels was not detected after BMT. BMT was effective for up to 20 weeks in 6-week-old Sh3bp2KI/KI mice transplanted with Sh3bp2+/+ BM cells. BMT also ameliorated the inflammation and bone loss in 10-week-old Sh3bp2KI/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. PMID:25445458

  2. Anti-Transforming Growth Factor ß Antibody Treatment Rescues Bone Loss and Prevents Breast Cancer Metastasis to Bone

    PubMed Central

    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 (p<0.01). In addition, treatment 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. PMID:22096521

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

    NASA Technical Reports Server (NTRS)

    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.

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

    NASA Technical Reports Server (NTRS)

    Ellman, Rachel; Sibonga, Jean; Bouxsein, Mary

    2010-01-01

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

  5. Stemmed femoral knee prostheses: effects of prosthetic design and fixation on bone loss.

    PubMed

    van Lenthe, G Harry; Willems, Marieke M M; Verdonschot, Nico; de Waal Malefijt, Maarten C; Huiskes, Rik

    2002-12-01

    Although the revision rates for modern knee prostheses have decreased drastically, the total number of revisions a year is increasing because many more primary knee replacements are being done. At the time of revision, bone loss is common, which compromises prosthetic stability. To improve stability, intramedullary stems are often used. The aim of this study was to estimate the effects of a stem, its diameter and the interface bonding conditions on patterns of the bone remodeling in the distal femur. We created finite element models of the distal half of a femur in which 4 types of knee prostheses were placed. The bone remodeling process was simulated using a strain-adaptive bone remodeling theory. The amount of such remodeling was determined by calculating the changes in bone mineral density in 9 regions of interest from simulated DEXA scans. The computer simulation model showed that revision prostheses tend to cause more bone resorption than primary ones, especially in the most distal regions. Predicted long-term bone loss due to a revision prosthesis with a thin stem equalled that around a prosthesis with an intercondylar box. However, strong regional differences were found--the stemmed prostheses having more bone loss in the most distal areas and some bone gain in the more proximal ones. A prosthesis with a thick stem led to an increase in bone loss. When the prosthesis-cement interface was bonded, more bone loss was predicted than with an unbonded interface. These results suggest that a stem which increases stability initially may reduce stability in the long term. This is due to an increase in stress shielding and bone resorption. PMID:12553509

  6. Alfacalcidol prevents aromatase inhibitor (Letrozole)-induced bone mineral loss in young growing female rats.

    PubMed

    Mohamed, Idris; Yeh, James K

    2009-08-01

    Long-term aromatase inhibitor use causes bone loss and increases fracture risk secondary to induced estrogen deficiency. We postulated that alfacalcidol (A; vitamin D(3) analog) could help prevent the Letrozole (L)-induced mineral bone loss. Fifty intact 1-month-old female rats were randomly divided into basal group; age-matched control group (AMC); L group: oral administration of 2 mg/kg per day; A group: oral administration of 0.1 microg/kg per day; and group L+A for a period of 8 weeks. Eight-week administration of L resulted in a significant increase in body weight, bone length, bone area, bone formation, and bone resorption activities when compared with the AMC group. However, the bone mass and bone mineral density (BMD) were significantly lower than the AMC group. Serum levels of testosterone, LH, FSH, and IGF-1 were significantly higher and serum estrone and estradiol were lower along with a decrease in ovary+uterus horn weight, when compared with the AMC groups. None of those parameters were affected by A treatment, except suppression of bone resorption activities and increased trabecular bone mass and femoral BMD, when compared with the AMC group. Results of L+A combined intervention showed that bone length, bone area, and bone formation activities were higher than the AMC group, and the bone resorption activities were lower and BMD was significantly higher than that of the L group. This study demonstrates that the combined intervention of L and A not only enhances bone growth, but also increases bone density, and the effects of L and A are independent and additive. PMID:19420010

  7. Non-steroidal anti-inflammatory drugs in the reduction of human alveolar bone loss.

    PubMed

    Feldman, R S; Szeto, B; Chauncey, H H; Goldhaber, P

    1983-03-01

    Aspirin (ASA) and indomethacin are inhibitors of prostaglandin synthesis and reduce bone resorption in tissue culture stimulated by preparations obtained from human gingival tissue. In a retrospective study, we attempted to determine whether ASA or ASA plus indomethacin exert a bone resorption inhibiting effect on human alveolar bone. Dental radiographs of 75 patients with a history of arthritis and long-term ingestion (greater than 5 years) of ASA were compared with dental radiographs of 75 healthy male volunteers from the VA Dental Longitudinal Study (DLS). Proximal bone loss was measured using a Schei Ruler graded on a 10-point scale. The data indicated that the ASA population presented with significantly fewer sites of 10% or greater mesial and distal bone loss than the healthy control population (P less than 0.05). Mean percentage bone loss for the entire dentition was also lower in the ASA group, although the difference was not statistically significant. As there is no evidence to suggest that inhibition of alveolar bone loss is a natural concomitant of the arthritic process, we conclude that the inhibition of bone loss found in this study was due to the chronic ingestion of ASA or ASA and indomethacin. PMID:6573339

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

    PubMed Central

    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

  9. Oxidative stress and gamma radiation-induced cancellous bone loss with musculoskeletal disuse

    PubMed Central

    Kondo, Hisataka; Yumoto, Kenji; Alwood, Joshua S.; Mojarrab, Rose; Wang, Angela; Almeida, Eduardo A. C.; Searby, Nancy D.; Limoli, Charles L.

    2010-01-01

    Exposure of astronauts in space to radiation during weightlessness may contribute to subsequent bone loss. Gamma irradiation of postpubertal mice rapidly increases the number of bone-resorbing osteoclasts and causes bone loss in cancellous tissue; similar changes occur in skeletal diseases associated with oxidative stress. Therefore, we hypothesized that increased oxidative stress mediates radiation-induced bone loss and that musculoskeletal disuse changes the sensitivity of cancellous tissue to radiation exposure. Musculoskeletal disuse by hindlimb unloading (1 or 2 wk) or total body gamma irradiation (1 or 2 Gy of 137Cs) of 4-mo-old, male C57BL/6 mice each decreased cancellous bone volume fraction in the proximal tibiae and lumbar vertebrae. The extent of radiation-induced acute cancellous bone loss in tibiae and lumbar vertebrae was similar in normally loaded and hindlimb-unloaded mice. Similarly, osteoclast surface in the tibiae increased 46% as a result of irradiation, 47% as a result of hindlimb unloading, and 64% as a result of irradiation + hindlimb unloading compared with normally loaded mice. Irradiation, but not hindlimb unloading, reduced viability and increased apoptosis of marrow cells and caused oxidative damage to lipids within mineralized tissue. Irradiation also stimulated generation of reactive oxygen species in marrow cells. Furthermore, injection of α-lipoic acid, an antioxidant, mitigated the acute bone loss caused by irradiation. Together, these results showed that disuse and gamma irradiation, alone or in combination, caused a similar degree of acute cancellous bone loss and shared a common cellular mechanism of increased bone resorption. Furthermore, irradiation, but not disuse, may increase the number of osteoclasts and the extent of acute bone loss via increased reactive oxygen species production and ensuing oxidative damage, implying different molecular mechanisms. The finding that α-lipoic acid protected cancellous tissue from the

  10. The effect of whey acidic protein fractions on bone loss in the ovariectomised rat.

    PubMed

    Kruger, Marlena C; Plimmer, Gabrielle G; Schollum, Linda M; Haggarty, Neill; Ram, Satyendra; Palmano, Kate

    2005-08-01

    Bovine milk has been shown to contain bioactive components with bone-protective properties. Earlier studies on bovine milk whey protein showed that it suppressed bone resorption in the female ovariectomised rat. A new osteotropic component was subsequently identified in the whey basic protein fraction, but bone bioactivity may also be associated with other whey fractions. In the present study, we investigated whether acidic protein fractions isolated from bovine milk whey could prevent bone loss in mature ovariectomised female rats. Six-month-old female rats were ovariectomised (OVX) or left intact (sham). The OVX rats were randomised into four groups. One group remained the control (OVX), whereas three groups were fed various whey acidic protein fractions from milk whey as 3 g/kg diet for 4 months. Outcomes were bone mineral density, bone biomechanics and markers of bone turnover. Bone mineral density of the femurs indicated that one of the whey AF over time caused a recovery of bone lost from OVX. Plasma C-telopeptide of type I collagen decreased significantly in all groups except OVX control over time, indicating an anti-resorptive effect of whey acidic protein. Biomechanical data showed that the AF may affect bone architecture as elasticity was increased by one of the whey AF. The femurs of AF-supplemented rats all showed an increase in organic matter. This is the first report of an acidic whey protein fraction isolated from milk whey that may support the recovery of bone loss in vivo. PMID:16115359

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

    PubMed

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

    2009-01-01

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

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

    PubMed

    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

  13. Inflammation, bone loss and fracture risk in spondyloarthritis

    PubMed Central

    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

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

    PubMed

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

    2016-06-01

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

  15. Accuracy of Cone Beam Computed Tomography for Detection of Bone Loss

    PubMed Central

    Goodarzi Pour, Daryoush; Soleimani Shayesteh, Yadollah

    2015-01-01

    Objectives: Bone assessment is essential for diagnosis, treatment planning and prediction of prognosis of periodontal diseases. However, two-dimensional radiographic techniques have multiple limitations, mainly addressed by the introduction of three-dimensional imaging techniques such as cone beam computed tomography (CBCT). This study aimed to assess the accuracy of CBCT for detection of marginal bone loss in patients receiving dental implants. Materials and Methods: A study of diagnostic test accuracy was designed and 38 teeth from candidates for dental implant treatment were selected. On CBCT scans, the amount of bone resorption in the buccal, lingual/palatal, mesial and distal surfaces was determined by measuring the distance from the cementoenamel junction to the alveolar crest (normal group: 0–1.5mm, mild bone loss: 1.6–3mm, moderate bone loss: 3.1–4.5mm and severe bone loss: >4.5mm). During the surgical phase, bone loss was measured at the same sites using a periodontal probe. The values were then compared by McNemar’s test. Results: In the buccal, lingual/palatal, mesial and distal surfaces, no significant difference was observed between the values obtained using CBCT and the surgical method. The correlation between CBCT and surgical method was mainly based on the estimation of the degree of bone resorption. CBCT was capable of showing various levels of resorption in all surfaces with high sensitivity, specificity, positive predictive value and negative predictive value compared to the surgical method. Conclusion: CBCT enables accurate measurement of bone loss comparable to surgical exploration and can be used for diagnosis of bone defects in periodontal diseases in clinical settings. PMID:26877741

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  17. ESTRADIOL PROTECTS AGAINST ETHANOL-INDUCED BONE LOSS BY INHIBITING UP REGULATION OF RANKL IN OSTEOBLASTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lactation-induced bone loss is promptly restored in the post-weaning period by a process of anabolic rebuilding, the endocrine and molecular basis of which still remains enigmatic. Ethanol (EtOH) consumption during this post-weaning period prevents the recovery of bone density and may be a significa...

  18. NADPH oxidases are critical targets for prevention of ethanol-induced bone loss

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The molecular mechanisms through which chronic alcohol consumption induce bone loss and osteoporosis are largely unknown. Ethanol increases expression and activates NADPH (nicotinamide adenine dinucleotide phosphate) oxidase enzymes (Nox) in osteoblasts leading to accumulation of reactive oxygen spe...

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

    PubMed

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

    2014-10-01

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

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

    PubMed Central

    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

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

    PubMed

    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. PMID:25575469

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

    PubMed Central

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

    2014-01-01

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

  3. Adipose-Derived Mesenchymal Stem Cells Prevent Systemic Bone Loss in Collagen-Induced Arthritis.

    PubMed

    Garimella, Manasa G; Kour, Supinder; Piprode, Vikrant; Mittal, Monika; Kumar, Anil; Rani, Lekha; Pote, Satish T; Mishra, Gyan C; Chattopadhyay, Naibedya; Wani, Mohan R

    2015-12-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammatory synovitis leading to joint destruction and systemic bone loss. The inflammation-induced bone loss is mediated by increased osteoclast formation and function. Current antirheumatic therapies primarily target suppression of inflammatory cascade with limited or no success in controlling progression of bone destruction. Mesenchymal stem cells (MSCs) by virtue of their tissue repair and immunomodulatory properties have shown promising results in various autoimmune and degenerative diseases. However, the role of MSCs in prevention of bone destruction in RA is not yet understood. In this study, we investigated the effect of adipose-derived MSCs (ASCs) on in vitro formation of bone-resorbing osteoclasts and pathological bone loss in the mouse collagen-induced arthritis (CIA) model of RA. We observed that ASCs significantly inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis in both a contact-dependent and -independent manner. Additionally, ASCs inhibited RANKL-induced osteoclastogenesis in the presence of proinflammatory cytokines such as TNF-α, IL-17, and IL-1β. Furthermore, treatment with ASCs at the onset of CIA significantly reduced clinical symptoms and joint pathology. Interestingly, ASCs protected periarticular and systemic bone loss in CIA mice by maintaining trabecular bone structure. We further observed that treatment with ASCs reduced osteoclast precursors in bone marrow, resulting in decreased osteoclastogenesis. Moreover, ASCs suppressed autoimmune T cell responses and increased the percentages of peripheral regulatory T and B cells. Thus, we provide strong evidence that ASCs ameliorate inflammation-induced systemic bone loss in CIA mice by reducing osteoclast precursors and promoting immune tolerance. PMID:26538398

  4. Precision bone and muscle loss measurements by advanced, multiple projection DEXA (AMPDXA) techniques for spaceflight applications

    NASA Technical Reports Server (NTRS)

    Charles, H. K. Jr; Beck, T. J.; Feldmesser, H. S.; Magee, T. C.; Spisz, T. S.; Pisacane, V. L.

    2001-01-01

    An advanced, multiple projection, dual energy x-ray absorptiometry (AMPDXA) scanner system is under development. The AMPDXA is designed to make precision bone and muscle loss measurements necessary to determine the deleterious effects of microgravity on astronauts as well as develop countermeasures to stem their bone and muscle loss. To date, a full size test system has been developed to verify principles and the results of computer simulations. Results indicate that accurate predictions of bone mechanical properties can be determined from as few as three projections, while more projections are needed for a complete, three-dimensional reconstruction. c 2001. Elsevier Science Ltd. All rights reserved.

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

    PubMed Central

    Mendonça, Maira L.; Batista, Sérgio L.; Nogueira-Barbosa, Marcello H.; Salmon, Carlos E.G.; de Paula, Francisco J.A.

    2016-01-01

    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.

  6. Myeloid thrombomodulin lectin-like domain inhibits osteoclastogenesis and inflammatory bone loss

    PubMed Central

    Cheng, Tsung-Lin; Lai, Chao-Han; Shieh, Shyh-Jou; Jou, Yin-Bo; Yeh, Jwu-Lai; Yang, Ai-Lun; Wang, Yan-Hsiung; Wang, Chau-Zen; Chen, Chung-Hwan; Shi, Guey-Yueh; Ho, Mei-Ling; Wu, Hua-Lin

    2016-01-01

    Osteoclastogenesis is an essential process during bone metabolism which can also be promoted by inflammatory signals. Thrombomodulin (TM), a transmembrane glycoprotein, exerts anti-inflammatory activities such as neutralization of proinflammatory high-mobility group box 1 (HMGB1) through TM lectin-like domain. This study aimed to identify the role of myeloid TM (i.e., endogenous TM expression on the myeloid lineage) in osteoclastogenesis and inflammatory bone loss. Using human peripheral blood mononuclear cells and mouse bone marrow-derived macrophages, we observed that the protein levels of TM were dramatically reduced as these cells differentiated into osteoclasts. In addition, osteoclastogenesis and extracellular HMGB1 accumulation were enhanced in primary cultured monocytes from myeloid-specific TM-deficient mice (LysMcre/TMflox/flox) and from TM lectin-like domain deleted mice (TMLeD/LeD) compared with their respective controls. Micro-computerized tomography scans showed that ovariectomy-induced bone loss was more pronounced in TMLeD/LeD mice compared with controls. Finally, the inhibiting effects of recombinant TM lectin-like domain (rTMD1) on bone resorption in vitro, and bone loss in both the ovariectomized model and collagen antibody-induced arthritis model has been detected. These findings suggested that the myeloid TM lectin-like domain may inhibit osteoclastogenesis by reducing HMGB1 signaling, and rTMD1 may hold therapeutic potential for inflammatory bone loss. PMID:27311356

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  9. TLR5, a novel mediator of innate immunity-induced osteoclastogenesis and bone loss.

    PubMed

    Kassem, Ali; Henning, Petra; Kindlund, Bert; Lindholm, Catharina; Lerner, Ulf H

    2015-11-01

    Accumulating evidence points to the importance of the innate immune system in inflammation-induced bone loss in infectious and autoimmune diseases. TLRs are well known for being activated by ligands expressed by bacteria, viruses, and fungi. Recent findings indicate that also endogenous ligands in inflammatory processes are important, one being a TLR5 agonist present in synovial fluid from patients with rheumatoid arthritis (RA). We found that activation of TLR5 by its specific ligand, flagellin, caused robust osteoclast formation and bone loss in cultured mouse neonatal parietal bones dependent on increased receptor activator of NF-κB ligand (RANKL):osteoprotegerin ratio, with half-maximal stimulation at 0.01 μg/ml. Flagellin enhanced Rankl mRNA in isolated osteoblasts by a myeloid differentiation primary response gene 88 and NF-κB-dependent mechanism. Injection of flagellin locally over skull bones in 5-wk-old mice resulted in increased mRNA expression of Rankl and osteoclastic genes, robust osteoclast formation, and bone loss. The effects in vitro and in vivo were absent in Tlr5(-/-) mice. These data show that TLR5 is a novel activator of RANKL and osteoclast formation and, therefore, a potential key factor in inflammation-induced bone erosions in diseases like RA, reactive arthritis, and periodontitis. TLR5 might be a promising novel treatment target for prevention of inflammatory bone loss. PMID:26207027

  10. Myeloid thrombomodulin lectin-like domain inhibits osteoclastogenesis and inflammatory bone loss.

    PubMed

    Cheng, Tsung-Lin; Lai, Chao-Han; Shieh, Shyh-Jou; Jou, Yin-Bo; Yeh, Jwu-Lai; Yang, Ai-Lun; Wang, Yan-Hsiung; Wang, Chau-Zen; Chen, Chung-Hwan; Shi, Guey-Yueh; Ho, Mei-Ling; Wu, Hua-Lin

    2016-01-01

    Osteoclastogenesis is an essential process during bone metabolism which can also be promoted by inflammatory signals. Thrombomodulin (TM), a transmembrane glycoprotein, exerts anti-inflammatory activities such as neutralization of proinflammatory high-mobility group box 1 (HMGB1) through TM lectin-like domain. This study aimed to identify the role of myeloid TM (i.e., endogenous TM expression on the myeloid lineage) in osteoclastogenesis and inflammatory bone loss. Using human peripheral blood mononuclear cells and mouse bone marrow-derived macrophages, we observed that the protein levels of TM were dramatically reduced as these cells differentiated into osteoclasts. In addition, osteoclastogenesis and extracellular HMGB1 accumulation were enhanced in primary cultured monocytes from myeloid-specific TM-deficient mice (LysMcre/TM(flox/flox)) and from TM lectin-like domain deleted mice (TM(LeD/LeD)) compared with their respective controls. Micro-computerized tomography scans showed that ovariectomy-induced bone loss was more pronounced in TM(LeD/LeD) mice compared with controls. Finally, the inhibiting effects of recombinant TM lectin-like domain (rTMD1) on bone resorption in vitro, and bone loss in both the ovariectomized model and collagen antibody-induced arthritis model has been detected. These findings suggested that the myeloid TM lectin-like domain may inhibit osteoclastogenesis by reducing HMGB1 signaling, and rTMD1 may hold therapeutic potential for inflammatory bone loss. PMID:27311356

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

    NASA Technical Reports Server (NTRS)

    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.

  12. Twelve-Minute Daily Yoga Regimen Reverses Osteoporotic Bone Loss

    PubMed Central

    Lu, Yi-Hsueh; Rosner, Bernard; Chang, Gregory

    2016-01-01

    Objective: Assess the effectiveness of selected yoga postures in raising bone mineral density (BMD). Methods: Ten-year study of 741 Internet-recruited volunteers comparing preyoga BMD changes with postyoga BMD changes. Outcome Measures: Dual-energy x-ray absorptiometric scans. Optional radiographs of hips and spine and bone quality study (7 Tesla). Results: Bone mineral density improved in spine, hips, and femur of the 227 moderately and fully compliant patients. Monthly gain in BMD was significant in spine (0.0029 g/cm2, P = .005) and femur (0.00022 g/cm2, P = .053), but in 1 cohort, although mean gain in hip BMD was 50%, large individual differences raised the confidence interval and the gain was not significant for total hip (0.000357 g/cm2). No yoga-related serious injuries were imaged or reported. Bone quality appeared qualitatively improved in yoga practitioners. Conclusion: Yoga appears to raise BMD in the spine and the femur safely. PMID:27226695

  13. Conception on the Cell Mechanisms of Bone Tissue Loss

    NASA Astrophysics Data System (ADS)

    Rodionova, N. V.

    2008-06-01

    Basing on the analysis of available literature, the results of our own electron microscopic and radioautographic researches the data are presented about the morphofunctional peculiarities and succession of cellular interactions in adaptive remodeling of bone structures after exposure of animals (rats, monkeys) to microgravity (station SLS-2, Bion-11). The probable cellular mechanisms of the development of osteopenia and osteoporosis are considered.

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

    PubMed

    Mei, Lin; Mochizuki, Miyako; Hasegawa, Noboru

    2012-01-01

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

  15. Tenofovir treatment of primary osteoblasts alters gene expression profiles: implications for bone mineral density loss

    PubMed Central

    Grigsby, Iwen F.; Pham, Lan; Mansky, Louis M.; Gopalakrishnan, Raj; Carlson, Ann E.; Mansky, Kim C.

    2010-01-01

    There is strong clinical evidence that implicates tenofovir in the loss of bone mineral density during treatment of human immunodeficiency virus infection. In this study, we sought to test the hypothesis that tenofovir treatment of osteoblasts causes changes in the gene expression profile that would impact osteoblast function during bone formation. Primary osteoblasts were isolated and then treated with the tenofovir prodrug, tenofovir disoproxil fumarate (TDF). Total RNA from TDF-treated and untreated osteoblasts were extracted and used for microarray analysis to assess TDF-associated changes in the gene expression profile. Strikingly, the changes in gene expression profiles involved in cell signaling, cell cycle and amino acid metabolism, which would likely impact osteoblast function in bone formation. Our findings demonstrate for the first time that tenofovir treatment of primary osteoblasts results in gene expression changes that implicate loss of osteoblast function in tenofovir-associated bone mineral density loss. PMID:20171173

  16. Sex steroid deficiency–associated bone loss is microbiota dependent and prevented by probiotics

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-06-01

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

  18. Low Magnitude, High Frequency Signals Could Reduce Bone Loss During Spaceflight

    NASA Astrophysics Data System (ADS)

    Hawkey, A.

    The removal of gravitational loading results in a loss of homeostasis of the skeleton. This leads to significant losses of bone mass during long-duration missions in space. Conventional exercise countermeasures, such as running and resistance training, have only limited effectiveness in reducing the rate at which bone is demineralised in microgravity. Bone loss, therefore, remains a major concern and if not annulled could be so severe as to jeopardise an extended human presence in space. In addition, current exercise regimes occupy valuable crew time, and astronauts often find the equipment cumbersome and uncomfortable to use. Recent studies suggest that exposing the body to short periods (<20mins) of low magnitude (<1g), high frequency (15-35Hz) signals (vibration) everyday could reduce, even prevent, bone loss during conditions such as osteoporo- sis on earth. The new vibration therapy treatment could also have several advantages over existing exercise countermeasures used in spaceflight due to it being very simple to operate, relatively inexpensive, and requiring only short periods of time `training', unlike the complicated, expensive and time-consuming devices currently used. This review highlights the detrimen- tal effects that microgravity has on the strength and integrity of bone, how current countermeasures are ineffective at stemming this level of deterioration, and how new vibration techniques could significantly reduce space-induced bone loss.

  19. Baseline observations from the POSSIBLE EU® study: characteristics of postmenopausal women receiving bone loss medications

    PubMed Central

    Cooper, Cyrus; Roux, Christian; Díez-Pérez, Adolfo; Guillemin, Francis; Jonsson, Bengt; Ortolani, Sergio; Pfeilschifter, Johannes; Horne, Rob; Kakad, Shilpa; Shepherd, Susan; Möller, Gerd; Marciniak, Anne; Martinez, Luc

    2010-01-01

    Summary Prospective Observational Scientific Study Investigating Bone Loss Experience in Europe (POSSIBLE EU®) is an ongoing longitudinal cohort study that utilises physician- and patient-reported measures to describe the characteristics and management of postmenopausal women on bone loss therapies. We report the study design and baseline characteristics of 3,402 women recruited from general practice across five European countries. Purpose The POSSIBLE EU® is a study describing the characteristics and management of postmenopausal women receiving bone loss medications. Methods Between 2005 and 2008, general practitioners enrolled postmenopausal women initiating, switching or continuing treatment with bone loss treatment in France, Germany, Italy, Spain and the UK. Patients and physicians completed questionnaires at study entry and at 3-month intervals, for 1 year. Results Of 3,402 women enrolled (mean age 68.2 years [SD] 9.83), 96% were diagnosed with low bone mass; 55% of these using dual energy X-ray absorptiometry. Most women (92%) had comorbidities. Mean minimum T score (hip or spine) at diagnosis was −2.7 (SD 0.89; median −2.7 [interquartile range, −3.2, −2.2]) indicating low bone mineral density. Almost 40% of the women had prior fractures in adulthood, mostly non-vertebral, non-hip in nature, 30% of whom had at least two fractures and more than half experienced moderate/severe pain or fatigue. Bisphosphonates were the most common type of bone loss treatment prescribed in the 12 months preceding the study. Conclusions POSSIBLE EU® characterises postmenopausal women with low bone mass, exhibiting a high rate of prevalent fracture, substantial bone fragility and overall comorbidity burden. Clinical strategies for managing osteoporosis in this population varied across the five participating European countries, reflecting their different guidelines, regulations and standards of care. PMID:21258637

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

    PubMed

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

    2010-11-01

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

  1. Does a high dietary acid content cause bone loss, and can bone loss be prevented with an alkaline diet?

    PubMed

    Hanley, David A; Whiting, Susan J

    2013-01-01

    A popular concept in nutrition and lay literature is that of the role of a diet high in acid or protein in the pathogenesis of osteoporosis. A diet rich in fruit and vegetable intake is thought to enhance bone health as the result of its greater potassium and lower "acidic" content than a diet rich in animal protein and sodium. Consequently, there have been a number of studies of diet manipulation to enhance potassium and "alkaline" content of the diet to improve bone density or other parameters of bone health. Although acid loading or an acidic diet featuring a high protein intake may be associated with an increase in calciuria, the evidence supporting a role of these variables in the development of osteoporosis is not consistent. Similarly, intervention studies with a more alkaline diet or use of supplements of potassium citrate or bicarbonate have not consistently shown a bone health benefit. In the elderly, inadequate protein intake is a greater problem for bone health than protein excess. PMID:24094472

  2. Polar bears (Ursus maritimus), the most evolutionary advanced hibernators, avoid significant bone loss during hibernation.

    PubMed

    Lennox, Alanda R; Goodship, Allen E

    2008-02-01

    Some hibernating animals are known to reduce muscle and bone loss associated with mechanical unloading during prolonged immobilisation,compared to humans. However, here we show that wild pregnant polar bears (Ursus maritimus) are the first known animals to avoid significant bone loss altogether, despite six months of continuous hibernation. Using serum biochemical markers of bone turnover, we showed that concentrations for bone resorption are not significantly increased as a consequence of hibernation in wild polar bears. This is in sharp contrast to previous studies on other hibernating species, where for example, black bears (Ursus americanus), show a 3-4 fold increase in serum bone resorption concentrations posthibernation,and must compensate for this loss through rapid bone recovery on remobilisation, to avoid the risk of fracture. In further contrast to black bears, serum concentrations of bone formation markers were highly significantly increased in pregnant female polar bears compared to non-pregnant,thus non-hibernating females both prior to and after hibernation. However, bone formation concentrations in new mothers were significantly reduced compared to pre-hibernation concentrations. The de-coupling of bone turnover in favour of bone formation prior to hibernation, suggests that wild polar bears may posses a unique physiological mechanism for building bone in protective preparation against expected osteopenia associated with disuse,starvation, and hormonal drives to mobilise calcium for reproduction, during hibernation. Understanding this physiological mechanism could have profound implications for a natural solution for the prevention of osteoporosis in animals subjected to captivity with inadequate space for exercise,humans subjected to prolonged bed rest while recovering from illness, or astronauts exposed to antigravity during spaceflight.© 2008 Elsevier Inc. All rights reserved. PMID:18249018

  3. The Role of IL-1β in the Bone Loss during Rheumatic Diseases

    PubMed Central

    Ruscitti, Piero; Cipriani, Paola; Carubbi, Francesco; Liakouli, Vasiliki; Di Benedetto, Paola; Berardicurti, Onorina; Alesse, Edoardo; Giacomelli, Roberto

    2015-01-01

    Several inflammatory diseases have been associated with increased bone resorption and fracture rates and different studies supported the relation between inflammatory cytokines and osteoclast activity. The main factor required for osteoclast activation is the stimulation by receptor activator of nuclear factor kappa-B ligand (RANKL) expressed on osteoblasts. In this context, interleukin- (IL-) 1β, one of the most powerful proinflammatory cytokines, is a strong stimulator of in vitro and in vivo bone resorption via upregulation of RANKL that stimulates the osteoclastogenesis. The resulting effects lead to an imbalance in bone metabolism favouring bone resorption and osteoporosis. In this paper, we review the available literature on the role of IL-1β in the pathogenesis of bone loss. Furthermore, we analysed the role of IL-1β in bone resorption during rheumatic diseases and, when available, we reported the efficacy of anti-IL-1β therapy in this field. PMID:25954061

  4. Comparative study between two techniques for alveolar bone loss assessment: A pilot study

    PubMed Central

    Lira-Júnior, Ronaldo; Freires, Irlan de Almeida; de Oliveira, Isabelle LinsMacêdo; da Silva, Ennyo Sobral Crispim; da Silva, SeverinoCelestino; de Brito, Roberto Lira

    2013-01-01

    Objective: To conduct a comparative study between two techniques for assessment of alveolar bone loss. Materials and Methods: Absolute and relative techniques were evaluated. The sample consisted of 16 radiographs supposed to meet a single criterion: The reference points applied (Cementum-enamel junction (CEJ) alveolar bone crest and root apex) should be visible. Bone height was measured in the selected radiographs as the percentage of root length through both techniques. Data were submitted to the Statistical Package for Social Science software. Results obtained by both methods were converted into bone loss index values and then categorized. Sensitivity and specificity of the relative technique, compared to the absolute technique, were calculated. Wilcoxon test and the Bland and Altman's method were employed for comparisons. Significance level was set at 5%. Results: For the absolute and relative techniques, means of bone loss index were respectively of 4.81 (±2.25) and 4.75 (±1.80). Bone loss index ≥6 (alveolar bone loss ≥50%) was found in 5 (31.2%) teeth, in the absolute technique, and in 4 (25%) teeth, according to the relative technique. There was no statistically significant difference between both methods (P>0.05). According to the Bland and Altman's method, it was verified a bias of 0.06, and limits of upper and lower agreement of, respectively, 1.58 and –1.45. Sensitivity of 0.8 and specificity of 1 were found for the relative technique compared to the absolute one. Conclusion: There was no significant difference between the techniques evaluated, and the relative technique was found to be reliable for measuring alveolar bone loss. PMID:23633780

  5. Weight-Loss Surgery Doesn't Boost Bone Health: Study

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_160161.html Weight-Loss Surgery Doesn't Boost Bone Health: Study Increased ... 29, 2016 FRIDAY, July 29, 2016 (HealthDay News) -- Weight-loss surgery helps severely obese patients shed pounds and ...

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

    PubMed

    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. PMID:19703606

  7. Structural basis of growth-related gain and age-related loss of bone strength

    PubMed Central

    2008-01-01

    If bone strength was the only requirement of skeleton, it could be achieved with bulk, but bone must also be light. During growth, bone modelling and remodelling optimize strength, by depositing bone where it is needed, and minimize mass, by removing it from where it is not. The population variance in bone traits is established before puberty and the position of an individual's bone size and mass tracks in the percentile of origin. Larger cross-sections have a comparably larger marrow cavity, which results in a lower volumetric BMD (vBMD), thereby avoiding bulk. Excavation of a marrow cavity thus minimizes mass and shifts the cortex radially, increasing rigidity. Smaller cross-sections are assembled by excavating a smaller marrow cavity leaving a relatively thicker cortex producing a higher vBMD, avoiding the fragility of slenderness. Variation in cellular activity around the periosteal and endocortical envelopes fashions the diverse shapes of adjacent cross-sections. Advancing age is associated with a decline in periosteal bone formation, a decline in the volume of bone formed by each basic multicellular unit (BMU), continued resorption by each BMU, and high remodelling after menopause. Bone loss in young adulthood has modest structural and biomechanical consequences because the negative BMU balance is driven by reduced bone formation, remodelling is slow and periosteal apposition continues shifting the thinned cortex radially. But after the menopause, increased remodelling, worsening negative BMU balance and a decline in periosteal apposition accelerate cortical thinning and porosity, trabecular thinning and loss of connectivity. Interstitial bone, unexposed to surface remodelling becomes more densely mineralized, has few osteocytes and greater collagen cross-linking, and accumulates microdamage. These changes produce the material and structural abnormalities responsible for bone fragility. PMID:18556646

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

    PubMed

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

    2016-10-01

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

  9. A losing battle: weight regain does not restore weight loss-induced bone loss in postmenopausal women.

    PubMed

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

    2011-12-01

    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/m(2). 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

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

    PubMed Central

    Xu, Dan; Zhao, Xin; Li, Yi; Ji, Yinli; Zhang, Jiangyan; Wang, Jufang; Xie, Xiaodong; Zhou, Guangming

    2014-01-01

    Outer space is a complex environment with various phenomena that negatively affect bone metabolism, including microgravity and highly energized ionizing radiation. In the present study, we used four groups of male Wistar rats treated with or without four-week hindlimb suspension after 4 Gy of X-rays to test whether there is a combined effect for hindlimb suspension and X-ray radiation. We tested trabecular parameters and some cytokines of the bone as leading indicators of bone metabolism. The results showed that hindlimb suspension and X-ray radiation could cause a significant increase in bone loss. Hindlimb suspension caused a 56.6% bone loss (P = 0.036), while X-ray radiation caused a 30.7% (P = 0.041) bone loss when compared with the control group. The combined factors of hindlimb suspension and X-rays exerted a combined effect on bone mass, with a reduction of 64.8% (P = 0.003). PMID:24699002

  11. Alendronate and Resistive Exercise Countermeasures Against Bed Rest-Induced Bone Loss: Biochemical Markers of Bone and Calcium Metabolism

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Nillen, Jeannie L.; Davis-Street, Janis E.; DeKerlegand, Diane E.; LeBlanc, Adrian; Shackelford, Linda C.

    2001-01-01

    Weightlessness-induced bone loss must be counteracted to ensure crew health during extendedduration space missions. Studies were conducted to assess two bone loss countermeasures in a ground-based model: horizontal bed rest. Following a 3-wk ambulatory adaptation period, male and female subjects (aged 21-56 y) completed a 17-wk bed rest protocol. Subjects were assigned to one of three treatments: alendronate (ALEN; 10 mg/d, n=6), resistive exercise (RE; 1.5 h/d, 6 d/wk, n=8), or control (CN; no countermeasure, n=8). Dietary intake was adjusted to maintain body weight. Endocrine and biochemical indices were measured in blood and urine using standard laboratory methods. All data reported are expressed as percent change from individual pre-bedrest data. Serum calcium changed little during bed rest, and tended to decrease (4-8%) in ALEN subjects. In RE subjects, bone alkaline phosphatase and osteocalcin were increased >65 and >30%, respectively, during bed rest, while these were unchanged or decreased in ALEN and CN subjects. Urinary calcium was increased 50% in CN subjects, but was unchanged or decreased in both ALEN and RE groups. Urinary n-telopeptide excretion was increased 40-50% in CN and RE subjects, but decreased 20% in ALEN subjects. Pyridinium crosslink and deoxypyridinoline excretion were increased 20-50% during bed rest. These data suggest that RE countermeasures are effective at increasing markers of bone formation in an analog of weightlessness, while ALEN reduces markers of bone resorption. Counteracting the bone loss of space flight may require both pharmacologic and exercise countermeasures.

  12. Combined Oral Administration of Bovine Collagen Peptides with Calcium Citrate Inhibits Bone Loss in Ovariectomized Rats

    PubMed Central

    Liu, JunLi; Wang, YiHu; Song, ShuJun; Wang, XiJie; Qin, YaYa; Si, ShaoYan; Guo, YanChuan

    2015-01-01

    Purpose 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. Methods 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. Results 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. Conclusions 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. PMID:26258559

  13. Ladder-Climbing Training Prevents Bone Loss and Microarchitecture Deterioration in Diet-Induced Obese Rats.

    PubMed

    Tang, Liang; Gao, Xiaohang; Yang, Xiaoying; Liu, Chentao; Wang, Xudan; Han, Yanqi; Zhao, Xinjuan; Chi, Aiping; Sun, Lijun

    2016-01-01

    Resistance exercise has been proved to be effective in improving bone quality in both animal and human studies. However, the issue about whether resistance exercise can inhibit obesity-induced bone loss has not been previously investigated. In the present study, we have evaluated the effects of ladder-climbing training, one of the resistance exercises, on bone mechanical properties and microarchitecture in high-fat (HF) diet-induced obese rats. Twenty-four rats were randomly assigned to the Control, HF + sedentary (HF-S) and HF + ladder-climbing training (HF-LCT) groups. Rats in the HF-LCT group performed ladder-climbing training for 8 weeks. The results showed that ladder-climbing training significantly reduced body and fat weight, and increased muscle mass along with a trend toward enhanced muscle strength in diet-induced obese rats. MicroCT analysis demonstrated that obesity-induced bone loss and architecture deterioration were significantly mitigated by ladder-climbing training, as evidenced by increased trabecular bone mineral density, bone volume over total volume, trabecular number and thickness, and decreased trabecular separation and structure model index. However, neither HF diet nor ladder-climbing training had an impact on femoral biomechanical properties. Moreover, ladder-climbing training significantly increased serum adiponectin, decreased serum leptin, TNF-α, IL-6 levels, and downregulated myostatin (MSTN) expression in diet-induced obese rats. Taken together, ladder-climbing training prevents bone loss and microarchitecture deterioration in diet-induced obese rats through multiple mechanisms including increasing mechanical loading on bone due to improved skeletal muscle mass and strength, regulating the levels of myokines and adipokines, and suppressing the release of pro-inflammatory cytokines. It indicates that resistance exercise may be a promising therapy for treating obesity-induced bone loss. PMID:26410845

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

    PubMed

    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. PMID:26450018

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

    PubMed

    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. PMID:21663481

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

    PubMed Central

    Rasouli Ghahroudi, AAR.; Talaeepour, AR; Mesgarzadeh, A.; Rokn, AR.; Khorsand, A.; Mesgarzadeh, NN.; Kharazi Fard, MJ.

    2010-01-01

    Objective: Vertical bone loss evaluations in the Nobel Biocare Replace® Select Tapered ™ implant system in the human after one-year loading time. Materials and Methods: This retrospective cross-sectional study was performed on 31 patients (14 men, 17 women; mean age, 60.39 years) receiving 170 implants (mean, 5.48 for each patient) of Groovy and Non-groovy designs in the Nobel Biocare Replace® Select Tapered ™ system. The marginal bone loss was measured at mesial and distal aspects of the implants on OPG x-rays after one-year follow-up. The data regarding the patient’s gender, age, history of disease, smoking, bone type at implant location, loading time of prosthesis and implant, implant design, diameter and length were recorded by the patients’ records and interview. The data were subjected to multiple linear regression and Pearson coefficient ratio regarding different factors. Results: The mean (standard deviation) distal, mesial and overall bone loss was 0.688 mm (0.851), 0.665 mm (0.849) and 0.935 mm (0.905), respectively in the studied implants. No significant differences were found regarding implant location, bone quality at the implant region, implant design and bone graft reception. In addition, no significant correlation was found between the occurred bone loss and implant diameter, length and number of used splints. Conclusion: Due to the criteria mentioned for implant success in term of bone loss values after one-year loading time, Noble Biocare Replace® Select Tapered ™ implant system is an acceptable treatment option for implant restorations in this regard. PMID:21998781

  17. Decursin from Angelica gigas suppresses RANKL-induced osteoclast formation and bone loss.

    PubMed

    Wang, Xin; Zheng, Ting; Kang, Ju-Hee; Li, Hua; Cho, Hyewon; Jeon, Raok; Ryu, Jae-Ha; Yim, Mijung

    2016-03-01

    Osteoclasts are the only cells capable of breaking down bone matrix, and excessive activation of osteoclasts is responsible for bone-destructive diseases. In this study, we investigated the effects of decursin from extract of Angelica gigas root on receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast formation using mouse bone marrow-derived macrophages (BMMs). Decursin inhibited RANKL-induced osteoclast formation without cytotoxicity. In particular, decursin maintains the characteristics of macrophages by blocking osteoclast differentiation by RANKL. Furthermore, the RANKL-stimulated bone resorption was diminished by decursin. Mechanistically, decursin blocked the RANKL-triggered ERK mitogen-activated protein kinases (MAPK) phosphorylation, which results in suppression of c-Fos and the nuclear factor of activated T cells (NFATc1) expression. In accordance with the in vitro study, decursin reduced lipopolysaccharide (LPS)- or ovariectomy (OVX)-induced bone loss in vivo. Therefore, decursin exerted an inhibitory effect on osteoclast formation and bone loss in vitro and in vivo. Decursin could be useful for the treatment of bone diseases associated with excessive bone resorption. PMID:26825541

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

    NASA Technical Reports Server (NTRS)

    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 (<10 µg/dL) have indicated associations of blood lead level with lower cognitive test scores in children, later onset of puberty in girls, and increased blood pressure and cardiovascular mortality rates in adults. Cognitive effects are considered by regulatory agencies to be the most sensitive endpoint at low doses. Although 95% of the body burden of lead is stored in the bones, the adverse effects of lead correlate with the concentration of lead in the blood better than with that in the bones. NASA has found that prolonged exposure to microgravity during spaceflight results in a significant loss of bone minerals, the extent of which varies from individual to individual and from bone to bone, but generally averages about 0.5% per month. During such bone loss, lead that had been stored in bones would be released along with calcium. The effects on the concentration of lead in the blood (PbB) of various concentrations of lead in drinking water (PbW) and of lead released from bones due to accelerated osteoporosis in microgravity, as well as changes in exposure to environmental lead before, during, and after spaceflight were evaluated using a physiologically based pharmacokinetic (PBPK) model that incorporated exposure to environmental lead both on earth and in flight and included temporarily increased rates of osteoporosis during spaceflight.

  19. Targeting Pin1 Protects Mouse Cardiomyocytes from High-Dose Alcohol-Induced Apoptosis

    PubMed Central

    Wang, Yuehong; Li, Zizhuo; Zhang, Yu; Yang, Wei; Sun, Jiantao; Shan, Lina; Li, Weimin

    2016-01-01

    Long-term heavy alcohol consumption is considered to be one of the main causes of left ventricular dysfunction in alcoholic cardiomyopathy (ACM). As previously suggested, high-dose alcohol induces oxidation stress and apoptosis of cardiomyocytes. However, the underlying mechanisms are yet to be elucidated. In this study, we found that high-dose alcohol treatment stimulated expression and activity of Pin1 in mouse primary cardiomyocytes. While siRNA-mediated knockdown of Pin1 suppressed alcohol-induced mouse cardiomyocyte apoptosis, overexpression of Pin1 further upregulated the numbers of apoptotic mouse cardiomyocytes. We further demonstrated that Pin1 promotes mitochondria oxidative stress and loss of mitochondrial membrane potential but suppresses endothelial nitric oxide synthase (eNOS) expression in the presence of alcohol. Taken together, our results revealed a pivotal role of Pin1 in regulation of alcohol-induced mouse cardiomyocytes apoptosis by promoting reactive oxygen species (ROS) accumulation and repressing eNOS expression, which could be potential therapeutic targets for ACM. PMID:26697133

  20. Peroxisome Proliferator-Activated Receptor γ Regulates Chronic Alcohol-Induced Alveolar Macrophage Dysfunction.

    PubMed

    Yeligar, Samantha M; Mehta, Ashish J; Harris, Frank L; Brown, Lou Ann S; Hart, C Michael

    2016-07-01

    Peroxisome proliferator-activated receptor (PPAR) γ is critical for alveolar macrophage (AM) function. Chronic alcohol abuse causes AM phagocytic dysfunction and susceptibility to respiratory infections by stimulating nicotinamide adenine dinucleotide oxidases (Nox), transforming growth factor-β1, and oxidative stress in the AM. Because PPARγ inhibits Nox expression, we hypothesized that alcohol reduces PPARγ, stimulating AM dysfunction. AMs were examined from: (1) patients with alcoholism or control patients; (2) a mouse model of chronic ethanol consumption; (3) PPARγ knockout mice; or (4) MH-S cells exposed to ethanol in vitro. Alcohol reduced AM PPARγ levels and increased Nox1, -2, and -4, transforming growth factor-β1, oxidative stress, and phagocytic dysfunction. Genetic loss of PPARγ recapitulated, whereas stimulating PPARγ activity attenuated alcohol-mediated alterations in gene expression and phagocytic function, supporting the importance of PPARγ in alcohol-induced AM derangements. Similarly, PPARγ activation in vivo reduced alcohol-mediated impairments in lung bacterial clearance. Alcohol increased levels of microRNA-130a/-301a, which bind to the PPARγ 3' untranslated region to reduce PPARγ expression. MicroRNA-130a/-301a inhibition attenuated alcohol-mediated PPARγ reductions and derangements in AM gene expression and function. Alcohol-induced Toll-like receptor 4 endocytosis was reversed by PPARγ activation. These findings demonstrate that targeting PPARγ provides a novel therapeutic approach for mitigating alcohol-induced AM derangements and susceptibility to lung infection. PMID:26677910

  1. Microglial AGE-albumin is critical in promoting alcohol-induced neurodegeneration in rats and humans.

    PubMed

    Byun, Kyunghee; Bayarsaikhan, Delger; Bayarsaikhan, Enkhjargal; Son, Myeongjoo; Oh, Seyeon; Lee, Jaesuk; Son, Hye-In; Won, Moo-Ho; Kim, Seung U; Song, Byoung-Joon; Lee, Bonghee

    2014-01-01

    Alcohol is a neurotoxic agent, since long-term heavy ingestion of alcohol can cause various neural diseases including fetal alcohol syndrome, cerebellar degeneracy and alcoholic dementia. However, the molecular mechanisms of alcohol-induced neurotoxicity are still poorly understood despite numerous studies. Thus, we hypothesized that activated microglial cells with elevated AGE-albumin levels play an important role in promoting alcohol-induced neurodegeneration. Our results revealed that microglial activation and neuronal damage were found in the hippocampus and entorhinal cortex following alcohol treatment in a rat model. Increased AGE-albumin synthesis and secretion were also observed in activated microglial cells after alcohol exposure. The expressed levels of receptor for AGE (RAGE)-positive neurons and RAGE-dependent neuronal death were markedly elevated by AGE-albumin through the mitogen activated protein kinase pathway. Treatment with soluble RAGE or AGE inhibitors significantly diminished neuronal damage in the animal model. Furthermore, the levels of activated microglial cells, AGE-albumin and neuronal loss were significantly elevated in human brains from alcoholic indivisuals compared to normal controls. Taken together, our data suggest that increased AGE-albumin from activated microglial cells induces neuronal death, and that efficient regulation of its synthesis and secretion is a therapeutic target for preventing alcohol-induced neurodegeneration. PMID:25140518

  2. Short-Term Hypoxia Accelerates Bone Loss in Ovariectomized Rats by Suppressing Osteoblastogenesis but Enhancing Osteoclastogenesis.

    PubMed

    Wang, Guixin; Wang, Jia; Sun, Dawei; Xin, Jingyi; Wang, Liping; Huang, Dong; Wu, Weichi; Xian, Cory J

    2016-01-01

    BACKGROUND Although it has been reported that hypoxic exposure can attenuate hypertension, heart disease, diabetes, and some other diseases, effects of hypoxia on osteoporosis are still unknown. MATERIAL AND METHODS The current study investigated whether short-term hypoxic exposure (in comparison with normoxic conditions) affects bone metabolism in normal or ovariectomized (OVX) adult female rats in an vivo study. Micro-computed tomography bone volume/structural analyses, histological examination, and serum bone turnover biochemical assays were used. In addition, the expressions of some associated major regulatory molecules were measured in osteoblastic cultures. RESULTS While the 14-day hypoxic exposure did not change the bone-remodeling process in normal adult female rats, it decreased bone volume, osteoclast density, and serum bone formation marker (alkaline phosphatase) level, but increased osteoclast density and serum bone resorption marker (C-telopeptide of collagen) level in OVX rats. The bone marrow adipocyte number and serum fatty acid binding protein-4 level were increased in OVX-hypoxic rats compared with OVX-normoxic rats. Consistently, in human MG-63 osteoblastic cultures, the hypoxic condition suppressed protein expression of osteogenic transcriptional factors Runx2 and osterix, elevated protein expression of osteoclastogenic cytokine receptor activator of nuclear factor kappa-B ligand, but reduced that of osteoclastogenic inhibitor osteoprotegerin. CONCLUSIONS Our results suggest that, although no change occurred in the bone-remodeling process in normal adult female rats after hypoxic exposure, under the estrogen-deficient osteoporotic condition, the hypoxic condition can alter the bone microenvironment so that it may further impair osteoblastic differentiation and enhance osteoclastic formation, and thus reduce bone formation, enhance bone resorption, and accelerate bone loss. PMID:27550548

  3. Short-Term Hypoxia Accelerates Bone Loss in Ovariectomized Rats by Suppressing Osteoblastogenesis but Enhancing Osteoclastogenesis

    PubMed Central

    Wang, Guixin; Wang, Jia; Sun, Dawei; Xin, Jingyi; Wang, Liping; Huang, Dong; Wu, Weichi; Xian, Cory J.

    2016-01-01

    Background Although it has been reported that hypoxic exposure can attenuate hypertension, heart disease, diabetes, and some other diseases, effects of hypoxia on osteoporosis are still unknown. Material/Methods The current study investigated whether short-term hypoxic exposure (in comparison with normoxic conditions) affects bone metabolism in normal or ovariectomized (OVX) adult female rats in an vivo study. Micro-computed tomography bone volume/structural analyses, histological examination, and serum bone turnover biochemical assays were used. In addition, the expressions of some associated major regulatory molecules were measured in osteoblastic cultures. Results While the 14-day hypoxic exposure did not change the bone-remodeling process in normal adult female rats, it decreased bone volume, osteoclast density, and serum bone formation marker (alkaline phosphatase) level, but increased osteoclast density and serum bone resorption marker (C-telopeptide of collagen) level in OVX rats. The bone marrow adipocyte number and serum fatty acid binding protein-4 level were increased in OVX-hypoxic rats compared with OVX-normoxic rats. Consistently, in human MG-63 osteoblastic cultures, the hypoxic condition suppressed protein expression of osteogenic transcriptional factors Runx2 and osterix, elevated protein expression of osteoclastogenic cytokine receptor activator of nuclear factor kappa-B ligand, but reduced that of osteoclastogenic inhibitor osteoprotegerin. Conclusions Our results suggest that, although no change occurred in the bone-remodeling process in normal adult female rats after hypoxic exposure, under the estrogen-deficient osteoporotic condition, the hypoxic condition can alter the bone microenvironment so that it may further impair osteoblastic differentiation and enhance osteoclastic formation, and thus reduce bone formation, enhance bone resorption, and accelerate bone loss. PMID:27550548

  4. Effect of venlafaxine on bone loss associated with ligature-induced periodontitis in Wistar rats

    PubMed Central

    2010-01-01

    Background The present study investigated the effects of venlafaxine, an antidepressant drug with immunoregulatory properties on the inflammatory response and bone loss associated with experimental periodontal disease (EPD). Materials and Methods Wistar rats were subjected to a ligature placement around the second upper left molar. The treated groups received orally venlafaxine (10 or 50 mg/kg) one hour before the experimental periodontal disease induction and daily for 10 days. Vehicle-treated experimental periodontal disease and a sham-operated (SO) controls were included. Bone loss was analyzed morphometrically and histopathological analysis was based on cell influx, alveolar bone, and cementum integrity. Lipid peroxidation quantification and immunohistochemistry to TNF-α and iNOS were performed. Results Experimental periodontal disease rats showed an intense bone loss compared to SO ones (SO = 1.61 ± 1.36; EPD = 4.47 ± 1.98 mm, p < 0.001) and evidenced increased cellular infiltration and immunoreactivity for TNF-α and iNOS. Venlafaxine treatment while at low dose (10 mg/kg) afforded no significant protection against bone loss (3.25 ± 1.26 mm), a high dose (50 mg/kg) caused significantly enhanced bone loss (6.81 ± 3.31 mm, p < 0.05). Venlafaxine effectively decreased the lipid peroxidation but showed no significant change in TNF-α or iNOS immunoreactivity. Conclusion The increased bone loss associated with high dose venlafaxine may possibly be a result of synaptic inhibition of serotonin uptake. PMID:20546603

  5. Effects of increased hypothalamic leptin gene expression on ovariectomy-induced bone loss in rats

    PubMed Central

    Jackson, M.A.; Iwaniec, U.T.; Turner, R.T.; Wronski, T.J.; Kalra, S.P.

    2011-01-01

    Estrogen deficiency results in accelerated bone turnover with a net increase in bone resorption. Subcutaneous administration of leptin attenuates bone loss in ovariectomized (ovx) rats by reducing bone resorption. However, in addition to its direct beneficial effects, leptin has been reported to have indirect (central nervous system-mediated) antiosteogenic effects on bone, which may limit the efficacy of elevated serum leptin to prevent estrogen deficiency-associated bone loss. The present study evaluated the long-term effects of increased hypothalamic leptin transgene expression, using recombinant adeno-associated virus-leptin (rAAV-Lep) gene therapy, on bone mass, architecture, and cellular endpoints in sexually mature ovx Sprague-Dawley rats. Ovx rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either rAAV-Lep or rAAV-GFP (control vector encoding green fluorescent protein) and maintained for 10 weeks. Additional controls consisted of ovary-intact rats and ovx rats pair-fed to rAAV-Lep rats. Lumbar vertebrae were analyzed by micro-computed tomography and tibiae by histomorphometry. Cancellous bone volume was lower and osteoclast perimeter, osteoblast perimeter, and bone marrow adipocyte density were greater in ovx rats compared to ovary-intact controls. In contrast, differences among ovx groups were not detected for any endpoint evaluated. In conclusion, whereas estrogen deficiency resulted in marked cancellous osteopenia, increased bone turnover and marrow adiposity, increasing hypothalamic leptin transgene expression in ovx rats had neither detrimental nor beneficial effects on bone mass, architecture, or cellular endpoints. These findings demonstrate that the antiresorptive effects of subcutaneous leptin administration in ovx rats are mediated through leptin targets in the periphery. PMID:21640774

  6. Radiation activated CHK1/MEPE pathway may contribute to microgravity-induced bone density loss

    NASA Astrophysics Data System (ADS)

    Zhang, Xiangming; Wang, Ping; Wang, Ya

    2015-11-01

    Bone density loss in astronauts on long-term space missions is a chief medical concern. Microgravity in space is the major cause of bone density loss (osteopenia), and it is believed that high linear energy transfer (LET) radiation in space exacerbates microgravity-induced bone density loss; however, the mechanism remains unclear. It is known that acidic serine- and aspartate-rich motif (ASARM) as a small peptide released by matrix extracellular phosphoglycoprotein (MEPE) promotes osteopenia. We previously discovered that MEPE interacted with checkpoint kinase 1 (CHK1) to protect CHK1 from ionizing radiation promoted degradation. In this study, we addressed whether the CHK1-MEPE pathway activated by radiation contributes to the effects of microgravity on bone density loss. We examined the CHK1, MEPE and secreted MEPE/ASARM levels in irradiated (1 Gy of X-ray) and rotated cultured human osteoblast cells. The results showed that radiation activated CHK1, decreased the levels of CHK1 and MEPE in human osteoblast cells and increased the release of MEPE/ASARM. These results suggest that the radiation-activated CHK1/MEPE pathway exacerbates the effects of microgravity on bone density loss, which may provide a novel targeting factor/pathway for a future countermeasure design that could contribute to reducing osteopenia in astronauts.

  7. Arthritis-induced alveolar bone loss is associated with changes in the composition of oral microbiota.

    PubMed

    Corrêa, Jôice Dias; Saraiva, Adriana Machado; Queiroz-Junior, Celso Martins; Madeira, Mila Fernandes Moreira; Duarte, Poliana Mendes; Teixeira, Mauro Martins; Souza, Danielle Glória; da Silva, Tarcília Aparecida

    2016-06-01

    Rheumatoid arthritis (RA) and periodontitis (PD) are chronic inflammatory disorders that cause bone loss. PD tends to be more prevalent and severe in RA patients. Previous experimental studies demonstrated that RA triggers alveolar bone loss similarly to PD. The aim of this study was to investigate if arthritis-induced alveolar bone loss is associated with modification in the oral microbiota. Checkerboard DNA-DNA hybridization was employed to analyze forty oral bacterial species in 3 groups of C57BL/6 mice: control (n = 12; without any challenge); Y4 (n = 8; received oral inoculation of Aggregatibacter Actinomycetemcomitans strain FDC Y4) and AIA group (n = 12; chronic antigen-induced arthritis). The results showed that AIA and Y4 group exhibited similar patterns of bone loss. The AIA group exhibited higher counts of most bacterial species analyzed with predominance of Gram-negative species similarly to infection-induced PD. Prevotella nigrescens and Treponema denticola were detected only in the Y4 group whereas Campylobacter showae, Streptococcus mitis and Streptococcus oralis were only found in the AIA group. Counts of Parvimonas micra, Selenomonas Noxia and Veillonella parvula were greater in the AIA group whereas Actinomyces viscosus and Neisseira mucosa were in large proportion in Y4 group. In conclusion, AIA is associated with changes in the composition of the oral microbiota, which might account for the alveolar bone loss observed in AIA mice. PMID:26996070

  8. Characteristics and prediction of the alveolar bone loss: essay of modeling.

    PubMed

    Ruquet, M; Bonfil, J J; Tardivo, D; Tavitian, P; Sastre, J; Tosello, A; Foti, B

    2009-12-01

    The alveolar bone loss is a phenomenon which intervenes throughout the life and which can be aggravated by the action of individual and behavioural factors. From this observation we shall try to characterize it and to propose formulas of prediction of the alveolar bone loss according to the age of the patient. We shall expose an analysis of factors bound to the alveolar bone loss and propose a modeling of the alveolar bone loss according to the age in an essentially predictive purpose. The methodology is based on the medical exploitation of CT-dentascanners and medical questionnaire as well as administrative questionnaire used in odontology. Measures of the distance ECJ and the summit of crest are made on the radiology and the individual factors and behavioural factors are scored. The descriptive analysis of the data allowed us to characterize the phenomenon of alveolar bone loss in a therapeutic purpose. The statistical treatment of these data will establish various models according to gender. The described method is simple and its applications seem numerous in the several domains: prevention, improvement of prosthetic and periodontal therapeutics. PMID:20614694

  9. Dietary Sodium Effects on Bone Loss and Calcium Metabolism During Bed Rest

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Arnaud, Sara B.; Abrams, Steven A.; Paloski, W. H. (Technical Monitor)

    2000-01-01

    The acceleration of age-related bone loss is one of the most detrimental effects of space flight. The ability to understand and counteract this loss will be critical for crew health and safety during and after long-duration missions. Studies in healthy ambulatory individuals have linked high salt (sodium) diets, hypercalciuria, and increased renal stone risk. Dietary salt may modulate bone loss through changes in calcium metabolism and the calcium endocrine system. The research proposed here will determine the role of dietary salt in the loss of bone during simulated space flight. Calcium metabolism will be determined through calcium kinetics studies, endocrine and biochemical measurements; and estimates of the mass, distribution and mechanical properties of bone, in subjects fed low (100 mmol sodium/day) or high (250 mmol sodium/day) levels of dietary salt during 28 days of headdown tilt bedrest. This research addresses the role of dietary salt in the loss of bone and calcium in space flight, and integrates the changes in calcium metabolism with those occurring in other physiologic systems. These data will be critical for both countermeasure development, and in determination of nutritional requirements for extended-duration space flight. The potential countermeasures resulting from this research will reduce health risks due to acceleration of age-related osteoporosis and increased risk of renal stone formation..

  10. Radiation activated CHK1/MEPE pathway may contribute to microgravity-induced bone density loss.

    PubMed

    Zhang, Xiangming; Wang, Ping; Wang, Ya

    2015-11-01

    Bone density loss in astronauts on long-term space missions is a chief medical concern. Microgravity in space is the major cause of bone density loss (osteopenia), and it is believed that high linear energy transfer (LET) radiation in space exacerbates microgravity-induced bone density loss; however, the mechanism remains unclear. It is known that acidic serine- and aspartate-rich motif (ASARM) as a small peptide released by matrix extracellular phosphoglycoprotein (MEPE) promotes osteopenia. We previously discovered that MEPE interacted with checkpoint kinase 1 (CHK1) to protect CHK1 from ionizing radiation promoted degradation. In this study, we addressed whether the CHK1-MEPE pathway activated by radiation contributes to the effects of microgravity on bone density loss. We examined the CHK1, MEPE and secreted MEPE/ASARM levels in irradiated (1 Gy of X-ray) and rotated cultured human osteoblast cells. The results showed that radiation activated CHK1, decreased the levels of CHK1 and MEPE in human osteoblast cells and increased the release of MEPE/ASARM. These results suggest that the radiation-activated CHK1/MEPE pathway exacerbates the effects of microgravity on bone density loss, which may provide a novel targeting factor/pathway for a future countermeasure design that could contribute to reducing osteopenia in astronauts. PMID:26553637

  11. Radiation activated CHK1/MEPE pathway may contribute to microgravity-induced bone density loss

    PubMed Central

    Zhang, Xiangming; Wang, Ping; Wang, Ya

    2016-01-01

    Bone density loss in astronauts on long-term space missions is a chief medical concern. Microgravity in space is the major cause of bone density loss (osteopenia), and it is believed that high linear energy transfer (LET) radiation in space exacerbates microgravity-induced bone density loss; however, the mechanism remains unclear. It is known that acidic serine- and aspartate-rich motif (ASARM) as a small peptide released by matrix extracellular phosphoglycoprotein (MEPE) promotes osteopenia. We previously discovered that MEPE interacted with checkpoint kinase 1 (CHK1) to protect CHK1 from ionizing radiation promoted degradation. In this study, we addressed whether the CHK1-MEPE pathway activated by radiation contributes to the effects of microgravity on bone density loss. We examined the CHK1, MEPE and secreted MEPE/ASARM levels in irradiated (1 Gy of X-ray) and rotated cultured human osteoblast cells. The results showed that radiation activated CHK1, decreased the levels of CHK1 and MEPE in human osteoblast cells and increased the release of MEPE/ASARM. These results suggest that the radiation-activated CHK1/MEPE pathway exacerbates the effects of microgravity on bone density loss, which may provide a novel targeting factor/pathway for a future countermeasure design that could contribute to reducing osteopenia in astronauts. PMID:26553637

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

    PubMed

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

    2015-07-01

    Increased fracture risk is commonly reported in cancer patients receiving radiotherapy, particularly at sites within the field of treatment. The direct and systemic effects of ionizing radiation on bone at a therapeutic dose are not well-characterized in clinically relevant animal models. Using 20-week-old male C57Bl/6 mice, effects of irradiation (right hindlimb; 2 Gy) on bone volume and microarchitecture were evaluated prospectively by microcomputed tomography and histomorphometry and compared to contralateral-shielded bone (left hindlimb) and non-irradiated control bone. One week postirradiation, trabecular bone volume declined in irradiated tibias (-22%; p < 0.0001) and femurs (-14%; p = 0.0586) and microarchitectural parameters were compromised. Trabecular bone volume declined in contralateral tibias (-17%; p = 0.003), and no loss was detected at the femur. Osteoclast number, apoptotic osteocyte number, and marrow adiposity were increased in irradiated bone relative to contralateral and non-irradiated bone, whereas osteoblast number was unchanged. Despite no change in osteoblast number 1 week postirradiation, dynamic bone formation indices revealed a reduction in mineralized bone surface and a concomitant increase in unmineralized osteoid surface area in irradiated bone relative to contralateral and non-irradiated control bone. Further, dose-dependent and time-dependent calvarial culture and in vitro assays confirmed that calvarial osteoblasts and osteoblast-like MC3T3 cells were relatively radioresistant, whereas calvarial osteocyte and osteocyte-like MLO-Y4 cell apoptosis was induced as early as 48 hours postirradiation (4 Gy). In osteoclastogenesis assays, radiation exposure (8 Gy) stimulated murine macrophage RAW264.7 cell differentiation, and coculture of irradiated RAW264.7 cells with MLO-Y4 or murine bone marrow cells enhanced this effect. These studies highlight the multifaceted nature of radiation-induced bone loss by demonstrating direct

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

    PubMed Central

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

    2015-01-01

    Increased fracture risk is commonly reported in cancer patients receiving radiotherapy, particularly at sites within the field of treatment. The direct and systemic effects of ionizing radiation on bone at a therapeutic dose are not well characterized in clinically relevant animal models. Using twenty-week male C57Bl/6 mice, effects of irradiation (right hindlimb; 2 Gy) on bone volume and microarchitecture were evaluated prospectively by microcomputed tomography and histomorphometry and compared to contralateral-shielded bone (left hindlimb) and non-irradiated control bone. One-week post-irradiation, trabecular bone volume declined in irradiated tibiae (−22%; p<0.0001) and femora (−14%; p=0.0586) and microarchitectural parameters were compromised. Trabecular bone volume declined in contralateral tibiae (−17%; p=0.003), and no loss was detected at the femur. Osteoclast number, apoptotic osteocyte number and marrow adiposity were increased in irradiated bone relative to contralateral and non-irradiated bone, while osteoblast number was unchanged. Despite no change in osteoblast number one-week post-irradiation, dynamic bone formation indices revealed a reduction in mineralized bone surface and a concomitant increase in unmineralized osteoid surface area in irradiated bone relative to contralateral and non-irradiated control bone. Further, dose- and time-dependent calvarial culture and in vitro assays confirmed that calvarial osteoblasts and osteoblast-like MC3T3 cells were relatively radioresistant, while calvarial osteocyte and osteocyte-like MLO-Y4 cell apoptosis was induced as early as 48h post-irradiation (4 Gy). In osteoclastogenesis assays, radiation exposure (8 Gy) stimulated murine macrophage RAW264.7 cell differentiation and co-culture of irradiated RAW264.7 cells with MLO-Y4 or murine bone marrow cells enhanced this effect. These studies highlight the multi-faceted nature of radiation-induced bone loss by demonstrating direct and systemic effects on

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

    PubMed

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

    1995-10-01

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

  15. Supraphysiological testosterone enanthate administration prevents bone loss and augments bone strength in gonadectomized male and female rats.

    PubMed

    Yarrow, Joshua F; Conover, Christine F; Purandare, Amol V; Bhakta, Ashish M; Zheng, Naiquan; Conrad, Bryan; Altman, Molly K; Franz, Sarah E; Wronski, Thomas J; Borst, Stephen E

    2008-11-01

    High-dose testosterone enanthate (TE) may prevent hypogonadism-induced osteopenia. For this study, 3-mo-old male and female Fisher SAS rats underwent sham surgery, gonadectomy (GX), or GX plus 28 days TE administration (7.0 mg/wk). GX reduced serum sex hormones (i.e., testosterone, dihydrotestosterone, and estradiol) (P < 0.05) in both sexes and bone concentrations of testosterone (males only), and estradiol (females only). GX also elevated urine deoxypyridinoline/creatinine in both sexes and serum osteocalcin (females only), findings that are consistent with high-turnover osteopenia. GX reduced cancellous bone volume (CBV) and increased osteoid surfaces in tibia of both sexes. GX males also experienced reduced trabecular number and width and increased trabecular separation, whereas GX females experienced increased osteoblast and osteoid surfaces. Bone biomechanical characteristics remained unaffected by GX, except that femoral stiffness was reduced in females. In contrast, TE administration to GX rats elevated serum and bone androgens to supraphysiological concentrations in both sexes but altered neither serum nor bone estradiol in males. Additionally, TE did not prevent GX-induced reductions in serum or bone estradiol in females. TE also reduced markers of high-turnover osteopenia in both sexes. In males, TE prevented GX-induced changes in trabecular number and separation, CBV, and osteoid surfaces while diminishing osteoblast and osteoclast surfaces; however, these changes were not fully prevented in females. In both sexes, TE increased femoral length and femoral maximal strength to above that of Sham and GX animals while preventing the loss of femoral stiffness in females. In conclusion, TE administration appears protective of cancellous bone in male rats and augments cortical bone strength in both sexes. PMID:18780767

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

    NASA Astrophysics Data System (ADS)

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

    2014-02-01

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

  17. Men and women in space: bone loss and kidney stone risk after long-duration spaceflight.

    PubMed

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

    2014-07-01

    Bone loss, a key concern for long-duration space travelers, is typically considered a female issue. The number of women who have flown long-duration space missions is now great enough to allow a quantitative comparison of changes in bone and renal stone risk by sex. Participants were 42 astronauts (33 men and 9 women) on long-duration missions to the International Space Station. Bone mineral density (by dual-energy X-ray absorptiometry) and biochemical markers of bone metabolism (from blood and urine samples) were evaluated before and after flight. Data were analyzed in two groups, based on available resistance exercise equipment. Missions were 49 to 215 days in duration, flown between 2000 and 2012. The bone density response to spaceflight was the same for men and women in both exercise groups. The bone mineral density response to flight was the same for men and women, and the typical decrease in bone mineral density (whole body and/or regional) after flight was not observed for either sex for those using an advanced resistive exercise device. Biochemical markers of bone formation and resorption responded similarly in male and female astronauts. The response of urinary supersaturation risk to spaceflight was not significantly different between men and women, although risks were typically increased after flight in both groups, and risks were greater in men than in women before and after flight. The responses of men and women to spaceflight with respect to these measures of bone health were not different. PMID:24470067

  18. Swimming Activity Prevents the Unloading Induced Loss of Bone Mass, Architecture, and Strength in Rats

    PubMed Central

    Falcai, Maurício J.; Leoni, Graziela Bianchi; de Sousa Neto, Manoel Damião; Volpon, Jose B.

    2015-01-01

    We investigated whether swimming activity associated with a three-week period of hypoactivity could prevent the deleterious effects of disuse on the tibias of tail-suspended rats. Forty Wistar rats were divided into five groups: (HS) permanently hindlimb suspension rats; (HS + Swim) rats submitted to unloading interrupted by swimming exercise; (HS + WB) hindlimb suspension rats with interruption for regular weight bearing for the same length of time as the HS+Swim rats; (Control) control rats that were allowed regular cage activities; and (Control + Swim) control rats that underwent swimming exercise. At the end of the experiment, bone mineral density, bone strength, and trabecular quantification were analyzed. The hindlimb-suspended rats exhibited bone quality loss (significant decrease in BMD, bone strength, and deterioration of trabecular and cortical bone architecture; decrease in BV/TV, TbN, TbTh, ConnD, CtV, and CtTh; and increase in TbSp) when compared to control rats. In contrast, trained rats showed a significant increase of 43% in bone mass, 29% in bone strength, 58% in trabecular thickness, 85% in bone volume, 27% in trabeculae number, and 30% in cortical volume, when compared to the hindlimb-suspended rats. We conclude that swimming activity not only ameliorates but also fully prevents the deleterious effects on bone quality in osteopenic rats. PMID:26090414

  19. Vitamin D Supplementation Protects Against Bone Loss Following Inhalant Organic Dust and Lipopolysaccharide Exposures in Mice

    PubMed Central

    Dusad, Anand; Thiele, Geoffrey M.; Klassen, Lynell W.; Wang, Dong; Duryee, Michael J.; Mikuls, Ted R.; Staab, Elizabeth B.; Wyatt, Todd A.; West, William W.; Reynolds, Stephen J.; Romberger, Debra J.; Poole, Jill A.

    2015-01-01

    Systemic bone loss is associated with airway inflammatory diseases; yet, strategies to halt disease progression from inhalant exposures are not clear. Vitamin D might be a potentially protective approach against noxious respirable environmental exposures. We sought to determine whether vitamin D supplementation represents a viable lung and bone protective strategy following repetitive inhalant treatments with organic dust extract (ODE) or lipopolysaccharide (LPS) in mice. C57BL/5 mice were maintained on diets with low (1 IU/D/g) or high (10 IU/D/g) vitamin D for 5 weeks, and treated with ODE from swine confinement facilities, LPS, or saline daily for 3 weeks per established intranasal inhalation protocol. Lungs, hind limbs, and sera were harvested for experimental outcomes. Serum 25-hydroxy vitamin D levels were 10-fold different between low/high vitamin D treatment groups with no differences between inhalant agents/saline treatments. Serum calcium levels were not affected. There was no difference in the magnitude of ODE- or LPS-induced inflammatory cell influx or lung histopathology between high/low vitamin D treatment groups. However, high vitamin D treatment reversed the loss of bone mineral density, bone volume, and bone microarchitecture deterioration induced by ODE or LPS as determined by micro-CT analysis. Bone-resorbing osteoclasts were also reduced by high vitamin D treatment. In the low vitamin D treatment groups, ODE induced the greatest degree of airway inflammatory consequences, and LPS induced the greatest degree of bone loss. Collectively, high concentration vitamin D was protective against systemic bone loss, but not airway inflammation, resulting from ODE- or LPS-induced airway injury. PMID:25759026

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

    PubMed

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

    2004-01-01

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

  1. The efficacy of calcitriol therapy in the management of bone loss and fractures: a qualitative review

    PubMed Central

    Hebl, S.; Purnell, J. Q.; Reid, M. E.; Rosier, R. N.; Mustian, K. M.; Palesh, O. G.; Huston, A. J.; Ling, M. N.; Morrow, G. R.

    2010-01-01

    Summary Osteoporosis, a skeletal disorder characterized by a reduction in bone strength, increases fracture risk. Primary osteoporosis is usually a result of reduced bone mineral density as a consequence of natural aging. Secondary osteoporosis is usually a result of a disease, such as cystic fibrosis, or medical treatment, such as corticosteroids or cancer treatment. Introduction Currently, ten million Americans are osteoporotic and an additional 34 million have the precursor condition, osteopenia. Osteoporosis leads to 1.5 million fractures and 500,000 hospitalizations annually. Osteoporosis-related fractures increase mortality and reduce quality of life. Calcitriol, the active form of vitamin D, regulates intestinal calcium absorption, among other actions. During the past four decades, many clinical trials investigating the effect of calcitriol on bone loss have been performed. Methods We conducted a systematic qualitative review of clinical trials that assessed calcitriol for the treatment of osteoporosis and bone loss. In these clinical trials, calcitriol was used as a monotherapy and in combination with other therapeutic bone agents. Results and conclusion Studies using calcitriol monotherapy, although not conclusive, found that calcitriol slowed the rate of bone loss in a variety of populations. Calcitriol in combination with other therapeutic bone agents was shown to have additional bone-preserving effects when compared to the use of therapeutic bone agents alone. A common side-effect of calcitriol therapy was hypercalcemia and hypercalciuria, but the degree of hypercalcemia was mild. Recent research found that intermittent dosing can reduce hypercalcemia rates. Calcitriol, alone or in combination with other agents, should be considered for the therapy of osteoporosis. PMID:19960185

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

    NASA Technical Reports Server (NTRS)

    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.

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

    PubMed Central

    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. PMID:23024690

  4. Bone Loss in Space: Shuttle/MIR Experience and Bed Rest Countermeasure Program

    NASA Technical Reports Server (NTRS)

    Shackelford, L. C.; LeBlanc, A.; Feiveson, A.; Oganov, V.

    1999-01-01

    Loss of bone mineral during space flight was documented in the 1970's Skylab missions. The USSR space program made similar observations in the 1980's. The Institute of Biomedical Problems in Moscow and NASA JSC in 1989 began to collect pre- and post-flight bone mineral density (BMD) using Hologic QDR 1000 DEXA scanners transferred from JSC to Moscow and Star City. DEXA whole body, hip, and lumbar spine scans were performed prior to and during the first week after return from 4- to 6-month missions (plus one 8-month mission and one 14- month mission) on the Mir space station. These data documented the extent and regional nature of bone loss during long duration space flight. Of the 18 cosmonauts participating in this study between 1990 and 1995, seven flew two missions. BMD scans prior to the second flight compared to the first mission preflight scans indicated that recovery was possibly delayed or incomplete. Because of these findings, NASA and IBMP initiated the study "Bone Mineral Loss and Recovery After Shuttle/Mir Flights" in 1995 to evaluate bone recovery during a 3-year post-flight period. All of the 14 participants thus far evaluated lost bone in at least one region of the spine and lower extremities during flight. Of the 14, only one to date has exhibited full return to baseline BNM values in all regions. The current study will continue until the last participant has reached full bone recovery in all regions, has reached a plateau, or until three years after the flight (2001 for the last mission of the program). Bone mineral density losses in space and difficulty in returning to baseline indicate a need for countermeasure development. In late 1996 NASA JSC and Baylor College of Medicine were approved to conduct two countermeasure studies during 17 weeks of bed rest. In 1997 the studies were begun in the bed rest facility established by NASA, Baylor College of Medicine, and The Methodist Hospital in Houston. To date, three bed rest controls, five resistive

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

    PubMed Central

    Rusen, Jamie; Leiter, Jeff; Chahal, Jaskarndip; 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. PMID:25136461

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

    NASA Technical Reports Server (NTRS)

    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

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

    PubMed

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

    2013-06-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Matsushima, Hisashi

    2016-07-01

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

  10. Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin

    PubMed Central

    Harre, Ulrike; Georgess, Dan; Bang, Holger; Bozec, Aline; Axmann, Roland; Ossipova, Elena; Jakobsson, Per-Johan; Baum, Wolfgang; Nimmerjahn, Falk; Szarka, Eszter; Sarmay, Gabriella; Krumbholz, Grit; Neumann, Elena; Toes, Rene; Scherer, Hans-Ulrich; Catrina, Anca Irinel; Klareskog, Lars; Jurdic, Pierre; Schett, Georg

    2012-01-01

    Autoimmunity is complicated by bone loss. In human rheumatoid arthritis (RA), the most severe inflammatory joint disease, autoantibodies against citrullinated proteins are among the strongest risk factors for bone destruction. We therefore hypothesized that these autoantibodies directly influence bone metabolism. Here, we found a strong and specific association between autoantibodies against citrullinated proteins and serum markers for osteoclast-mediated bone resorption in RA patients. Moreover, human osteoclasts expressed enzymes eliciting protein citrullination, and specific N-terminal citrullination of vimentin was induced during osteoclast differentiation. Affinity-purified human autoantibodies against mutated citrullinated vimentin (MCV) not only bound to osteoclast surfaces, but also led to robust induction of osteoclastogenesis and bone-resorptive activity. Adoptive transfer of purified human MCV autoantibodies into mice induced osteopenia and increased osteoclastogenesis. This effect was based on the inducible release of TNF-α from osteoclast precursors and the subsequent increase of osteoclast precursor cell numbers with enhanced expression of activation and growth factor receptors. Our data thus suggest that autoantibody formation in response to citrullinated vimentin directly induces bone loss, providing a link between the adaptive immune system and bone. PMID:22505457

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

    PubMed Central

    Azuma, Kagaku; Furuzawa, Manabu; Fujiwara, Shu; Yamada, Kumiko; Kubo, Kin-ya

    2015-01-01

    Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a wooden stick to chew during the experimental period. Quantitative micro-computed tomography, histologic analysis, and biochemical markers were used to evaluate the bone response. The stress/chewing group exhibited significantly attenuated stress-induced increases in serum corticosterone levels, suppressed bone formation, enhanced bone resorption, and decreased trabecular bone mass in the vertebrae and distal femurs, compared with mice in the stress group. Active mastication during exposure to chronic stress alleviated chronic stress-induced bone density loss in B6 mice. Active mastication during chronic psychologic stress may thus be an effective strategy to prevent and/or treat chronic stress-related osteopenia. PMID:26664256

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

    PubMed

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

    1991-12-01

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

  13. Effect of Cistanches Herba Aqueous Extract on Bone Loss in Ovariectomized Rat

    PubMed Central

    Liang, Haidong; Yu, Fang; Tong, Zhihong; Huang, Zaiguo

    2011-01-01

    To assess the ability of traditional Chinese medicine Cistanches Herba extract (CHE) to prevent bone loss in the ovariectomized (OVX) rat, Cistanches Herba extract (CHE) was administered intragastrically to the rats. Female rats were anesthetized with pentobarbital sodium (40 mg kg−1, i.p.), and their ovaries were removed bilaterally. The rats in the sham-operated group were anesthetized, laparotomized, and sutured without removing their ovaries. After 1 week of recovery from surgery, the OVX rats were randomly divided into three groups and orally treated with H2O (OVX group) or CHE (100 or 200 mg kg−1 daily) for 3 months. The sham-operated group (n = 8) was orally treated with H2O. After 3 months, the total body bone mineral density (BMD), bone mineral content (BMC), Bone biomechanical index, blood mineral levels and blood antioxidant enzymes activities were examined in sham-operated, ovariectomized and Cistanches Herba extract treated rats. Results showed that Cistanches Herba extract treatment significantly dose-dependently enhanced bone mineral density (BMD), bone mineral content (BMC), maximum load, displacement at maximum load, stress at maximum load, load at auto break, displacement at auto break, and stress at auto break, and blood antioxidant enzymes activities, decreased blood Ca, Zn and Cu levels compared to the OVX group. This experiment demonstrates that the administration of Cistanches Herba extract to ovariectomized rats reverses bone loss and prevents osteoporosis. PMID:21954345

  14. Rhizoma Dioscoreae extract protects against alveolar bone loss in ovariectomized rats via microRNAs regulation.

    PubMed

    Zhang, Zhiguo; Song, Changheng; Zhang, Fangzhen; Xiang, Lihua; Chen, Yanjing; Li, Yan; Pan, Jinghua; Liu, Hong; Xiao, Gary Guishan; Ju, Dahong

    2015-01-01

    The aim of this study was to evaluate the osteoprotective effect of aqueous Rhizoma Dioscoreae extract (RDE) on the alveolar bone of rats with ovariectomy-induced bone loss. Female Wistar rats underwent either ovariectomy or sham operation (SHAM). The ovariectomized (OVX) rats were treated with vehicle (OVX), estradiol valerate (EV), or RDE. After treatments, the bone mineral density (BMD) and the three-dimensional microarchitecture of the alveolar bone were analyzed to assess bone mass. Microarrays were used to evaluate microRNA expression profiles in alveolar bone from RDE-treated and OVX rats. The differential expression of microRNAs was validated using real-time quantitative RT-PCR (qRT-PCR), and the target genes of validated microRNAs were predicted and further analyzed using Ingenuity Pathway Analysis (IPA). The key findings were verified using qRT-PCR. Our results show that RDE inhibits alveolar bone loss in OVX rats. Compared to the OVX rats, the RDE-treated rats showed upregulated expression levels of 8 microRNAs and downregulated expression levels of 8 microRNAs in the alveolar bone in the microarray analysis. qRT-PCR helped validate 13 of 16 differentially expressed microRNAs, and 114 putative target genes of the validated microRNAs were retrieved. The IPA showed that these putative target genes had the potential to code for proteins that were involved in the transforming growth factor (TGF)-β/bone morphogenetic proteins (BMPs)/Smad signaling pathway (Tgfbr2/Bmpr2, Smad3/4/5, and Bcl-2) and interleukin (IL)-6/oncostatin M (OSM)/Jak1/STAT3 signaling pathway (Jak1, STAT3, and Il6r). These experiments revealed that RDE could inhibit ovariectomy-induced alveolar bone loss in rats. The mechanism of this anti-osteopenic effect in alveolar bone may involve the simultaneous inhibition of bone formation and bone resorption, which is associated with modulation of the TGF-β/BMPs/Smad and the IL-6/OSM/Jak1/STAT3 signaling pathways via microRNA regulation. PMID

  15. Rhizoma Dioscoreae Extract Protects against Alveolar Bone Loss in Ovariectomized Rats via microRNAs Regulation

    PubMed Central

    Zhang, Zhiguo; Song, Changheng; Zhang, Fangzhen; Xiang, Lihua; Chen, Yanjing; Li, Yan; Pan, Jinghua; Liu, Hong; Xiao, Gary Guishan; Ju, Dahong

    2015-01-01

    The aim of this study was to evaluate the osteoprotective effect of aqueous Rhizoma Dioscoreae extract (RDE) on the alveolar bone of rats with ovariectomy-induced bone loss. Female Wistar rats underwent either ovariectomy or sham operation (SHAM). The ovariectomized (OVX) rats were treated with vehicle (OVX), estradiol valerate (EV), or RDE. After treatments, the bone mineral density (BMD) and the three-dimensional microarchitecture of the alveolar bone were analyzed to assess bone mass. Microarrays were used to evaluate microRNA expression profiles in alveolar bone from RDE-treated and OVX rats. The differential expression of microRNAs was validated using real-time quantitative RT-PCR (qRT-PCR), and the target genes of validated microRNAs were predicted and further analyzed using Ingenuity Pathway Analysis (IPA). The key findings were verified using qRT-PCR. Our results show that RDE inhibits alveolar bone loss in OVX rats. Compared to the OVX rats, the RDE-treated rats showed upregulated expression levels of 8 microRNAs and downregulated expression levels of 8 microRNAs in the alveolar bone in the microarray analysis. qRT-PCR helped validate 13 of 16 differentially expressed microRNAs, and 114 putative target genes of the validated microRNAs were retrieved. The IPA showed that these putative target genes had the potential to code for proteins that were involved in the transforming growth factor (TGF)-β/bone morphogenetic proteins (BMPs)/Smad signaling pathway (Tgfbr2/Bmpr2, Smad3/4/5, and Bcl-2) and interleukin (IL)-6/oncostatin M (OSM)/Jak1/STAT3 signaling pathway (Jak1, STAT3, and Il6r). These experiments revealed that RDE could inhibit ovariectomy-induced alveolar bone loss in rats. The mechanism of this anti-osteopenic effect in alveolar bone may involve the simultaneous inhibition of bone formation and bone resorption, which is associated with modulation of the TGF-β/BMPs/Smad and the IL-6/OSM/Jak1/STAT3 signaling pathways via microRNA regulation. PMID

  16. COMPARISON BETWEEN INVERTED AND UNPROCESSED DIGITIZED RADIOGRAPHIC IMAGING IN PERIODONTAL BONE LOSS MEASUREMENTS

    PubMed Central

    Scaf, Gulnara; Morihisa, Olívia; Loffredo, Leonor de Castro Monteiro

    2007-01-01

    The advances in digital imaging technology in dentistry have provided an alternative to film-based radiography and have given new options to detect periodontal bone loss. The purpose of this study was to compare inverted and unprocessed digitized radiographic imaging in periodontal bone loss measurements. Thirty-five film-based periapical radiographs of patients suffering from moderate to advanced untreated periodontal bone loss associated to lower premolar and molars was selected from the department files, with 40 bone loss areas. The film-based radiographs were digitized with a flatbed scanner with a transparency and radiograph adapter used for transilluminating the radiograph imaging. Digitization was performed at 600 dpi and in gray scale. The images were digitized using Image Tool software by applying image inversion, that is, transformation of radiopaque structures into radiolucent structures and vice-versa. The digital data were saved as JPEG files. The images were displayed on a 15-inch and 24-bit video monitor under reduced room lighting. One calibrated examiner performed all radiographic measurements, three times, from the cementoenamel junction to the most apical extension of the bone loss, in both types of image (inverted and unprocessed). Brightness and contrast were adjusted according to the examiner's individual demand. Intraclass correlation coefficient was used to compare the measurements from both types of images. The means of radiographic measurements, in mm, for inverted and unprocessed digitized imaging were 6.4485 and 6.3790, respectively. The intraclass correlation coefficient was significant (0.99) The inverted and unprocessed digitized radiographic images were reliable and there was no difference in the diagnostic accuracy between these images regarding periodontal bone loss measurements. PMID:19089186

  17. Arthroscopic Distal Clavicular Autograft for Treating Shoulder Instability With Glenoid Bone Loss

    PubMed Central

    Tokish, John M.; Fitzpatrick, Kelly; Cook, Jay B.; Mallon, William J.

    2014-01-01

    Glenoid bone loss is a significant risk factor for failure after arthroscopic shoulder stabilization. Multiple options are available to reconstruct this bone loss, including coracoid transfer, iliac crest bone graft, and osteoarticular allograft. Each technique has strengths and weaknesses. Coracoid grafts are limited to anterior augmentation and, along with iliac crest, do not provide an osteochondral reconstruction. Osteochondral allografts do provide a cartilage source but are challenged by the potential for graft rejection, infection, cost, and availability. We describe the use of a distal clavicular osteochondral autograft for bony augmentation in cases of glenohumeral instability with significant bone loss. This graft has the advantages of being readily available and cost-effective, it provides an autologous osteochondral transplant with minimal donor-site morbidity, and it can be used in both anterior and posterior bone loss cases. The rationale and technical aspects of arthroscopic performance will be discussed. Clinical studies are warranted to determine the outcomes of the use of the distal clavicle as a graft in shoulder instability. PMID:25264509

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

    PubMed

    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. PMID:18037367

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

    PubMed

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

    2015-01-01

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

  20. Menatetrenone rescues bone loss by improving osteoblast dysfunction in rats immobilized by sciatic neurectomy.

    PubMed

    Iwasaki-Ishizuka, Yoshiko; Yamato, Hideyuki; Murayama, Hisashi; Ezawa, Ikuko; Kurokawa, Kiyoshi; Fukagawa, Masafumi

    2005-02-25

    Menatetrenone (MK-4) is a vitamin K2 homologue that has been used as a therapeutic agent for osteoporosis in Japan. However, there is no far any reported evidence that MK-4 ameliorates a pre-existing condition of reduced bone mineral density (BMD) in vivo. In this study, we evaluated the effect of MK-4 in a rat model of established bone loss through immobilization caused by sciatic neurectomy. Unilateral sciatic neurectomy (SNx) was performed in rats, and 10 or 30 mg/kg of MK-4 or vehicle was administered to the rats three weeks after operation. Seven weeks after operation, the rats were sacrificed and BMD and bone histomorphometric parameters were measured to assess the effects of MK-4. While BMD of the distal femoral metaphysis was significantly decreased after SNx, MK-4 administration increased BMD in the neurectomized rats. Bone formation was decreased continuously and bone resorption was initially increased in SNx rats. Four weeks treatment of MK-4 increased bone formation and suppressed bone resorption. In addition, increased carboxylated osteocalcin and decreased undercarboxylated osteocalcin in serum were observed in MK-4-administered rats. These results indicated that MK-4 rescued bone volume by improving osteoblast dysfunction and accelerating gamma carboxylation of osteocalcin. MK-4 may be useful for treating disuse osteopenia. PMID:15698851

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

    PubMed Central

    Thrailkill, Kathryn; Bunn, R. Clay; Lumpkin, Charles; Cockrell, Gael; Kahn, C. Ronald; Fowlkes, John; Nyman, Jeffry S.

    2014-01-01

    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. PMID:24963495

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

    PubMed Central

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

    2016-01-01

    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 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. PMID:26840705

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

    PubMed

    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 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. PMID:26840705

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

    PubMed

    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 < 0.05). Both obese groups had similar percentages of fat (P = nonsignificant); however, alveolar bone loss was significantly greater in animals that were on the PA-enriched HFD (P < 0.05). TNF-α levels were highest in the PA group (P < 0.001) and increased in all groups in response to P. gingivalis inoculation (P < 0.01), whereas bone remodeling markers OC, CTX, and P1NP were lowest in the PA group (P < 0.001) and highest in the C group. Bacterial challenge decreased bone metabolism markers in all groups (P < 0.01). Further, osteoclasts showed an augmented inflammatory response to P. gingivalis in the presence of hyperlipidemic PA levels as opposed to OA cultures, which responded similarly to controls. These findings indicate that the specific FA profile of

  5. Depressive Symptoms, Bone Loss, and Fractures in Postmenopausal Women

    PubMed Central

    Scholes, Delia; Brunner, Robert L.; Robbins, John; Reed, Susan D.; Newton, Katherine M.; Melville, Jennifer L.; LaCroix, Andrea Z.

    2008-01-01

    Background Osteoporosis and depression may be associated through common physiologic systems or risk factors. Objective To assess the associations between depressive symptoms (Burnam’s scale) or antidepressant use and bone outcomes. Design Prospective cohort study. Participants A total of 93,676 postmenopausal women (50 to 79 years old) enrolled in the Women’s Health Initiative Observational Study. Measurements Self-reported fractures (n = 14,982) (hip [adjudicated], spine, wrist, and “other”). Analyses included 82,410 women with complete information followed on average for 7.4 years. Bone mineral density (BMD) of the hip (n = 4539), spine (n = 4417), and whole body (n = 4502) was measured at baseline and 3 years in women enrolled at 3 densitometry study sites. Results Overall, there were no statistically significant associations between depressive symptoms or antidepressant therapy and 3-year change in BMD. In a subset of women not using antidepressants, there was a significant difference in whole-body BMD change between women with and without depressive symptoms (P = .05). Depressive symptoms (hazard ratio [HR] 1.08; 95% CI = 1.02 to 1.14) and antidepressant therapy (HR = 1.22; CI = 1.15 to 1.30) independently increased risk of any fracture, the majority of which occurred at “other” anatomic sites. Antidepressant therapy increased the risk of spine fracture (HR = 1.36; CI = 1.14 to 1.63). No associations were observed between depressive symptoms or antidepressant therapy and hip or wrist fracture. Conclusion In this study of postmenopausal women, average age 64, we observed minimal association between depressive symptoms and 3-year changes in either BMD or fracture risk. Antidepressant use was not associated with changes in BMD, but was associated with increased risk of fractures at the spine and “other ” anatomic sites. PMID:18286345

  6. Prostaglandin synthesis inhibitors block alcohol-induced fetal hypoplasia.

    PubMed

    Pennington, S; Allen, Z; Runion, J; Farmer, P; Rowland, L; Kalmus, G

    1985-01-01

    Alcohol-induced growth retardation is a fetal effect consistently associated with maternal ethanol consumption. In humans, those infants whose mothers consume even a limited amount of ethanol during pregnancy have a significant incidence of growth inhibition. The molecular mechanism responsible for this growth deficiency is unknown, and prevention depends on maternal abstinence during pregnancy. The data reported here suggest that ethanol-mediated increases in tissue prostaglandin (PG) E levels (PGE1 plus PGE2) are correlated with the growth retardation. Further, simultaneous administration of PG synthesis inhibitors with the alcohol blocks the rise in tissue PG levels and protects against the alcohol-induced hypoplasia. PMID:3904508

  7. Dietary fat level and alcohol-induced pancreatic injury

    SciTech Connect

    Towner, S.J.; Inomata, T.; Largman, C.; French, S.W.

    1986-03-01

    Effects of dietary fat levels on alcohol-induced pancreatic injury were studied in a rat model which achieves sustained blood alcohol levels and maximal nutritional control. A diet containing 5, 25, or 35% of fat (corn oil; % total calories) and either ethanol or isocaloric dextrose were intragastrically infused in male Wistar rats for 30-120 days. Following intoxication, the pancreatic pathology was examined light-microscopically. None of pair-fed controls showed abnormal pancreas histology. These results indicate potentiation of alcohol-induced pancreatic injury. Particularly higher incidence of chronic interstitial pancreatitis with increased dietary fat.

  8. Obesity-mediated inflammatory microenvironment stimulates osteoclastogenesis and bone loss in mice

    PubMed Central

    Halade, Ganesh V; Jamali, Amina El; Williams, Paul J; Fajardo, Roberto J; Fernandes, Gabriel

    2010-01-01

    Clinical evidence indicates that fat is inversely proportional to bone mass in elderly obese women. However, it remains unclear whether obesity accelerates bone loss. In this report we present evidence that increased visceral fat leads to inflammation and subsequent bone loss in 12-month-old C57BL/6J mice that were fed 10% corn oil (CO)-based diet and a control lab chow (LC) for 6 months. As expected from our previous work, CO-fed mice demonstrated increased visceral fat and enhanced total body fat mass compared to LC. The adipocyte-specific PPARγ and bone marrow (BM) adiposity were increased in CO-fed mice. In correlation with those modifications, inflammatory cytokines (IL-1β, IL-6, TNF-α) were significantly elevated in COfed mice compared to LC-fed mice. This inflammatory BM microenvironment resulted in increased superoxide production in osteoclasts and undifferentiated BM cells. In CO-fed mice, the increased number of osteoclasts per trabecular bone length and the increased osteoclastogenesis assessed ex-vivo suggest that CO diet induces bone resorption. Additionally, the up-regulation of osteoclast-specific cathepsin k and RANKL expression and down-regulation of osteoblast-specific RUNX2/Cbfa1 supports this bone resorption in CO-fed mice. Also, COfed mice exhibited lower trabecular bone volume in the distal femoral metaphysis and had reduced OPG expression. Collectively, our results suggest that increased bone resorption in mice fed a CO-enriched diet is possibly due to increased inflammation mediated by the accumulation of adipocytes in the BM microenvironment. This inflammation may consequently increase osteoclastogenesis, while reducing osteoblast development in CO-fed mice. PMID:20923699

  9. Disruption of NF-κB1 prevents bone loss caused by mechanical unloading.

    PubMed

    Nakamura, Hitomi; Aoki, Kazuhiro; Masuda, Wataru; Alles, Neil; Nagano, Kenichi; Fukushima, Hidefumi; Osawa, Kenji; Yasuda, Hisataka; Nakamura, Ichiro; Mikuni-Takagaki, Yuko; Ohya, Keiichi; Maki, Kenshi; Jimi, Eijiro

    2013-06-01

    Mechanical unloading, such as in a microgravity environment in space or during bed rest (for patients who require prolonged bed rest), leads to a decrease in bone mass because of the suppression of bone formation and the stimulation of bone resorption. To address the challenges presented by a prolonged stay in space and the forthcoming era of a super-aged society, it will be important to prevent the bone loss caused by prolonged mechanical unloading. Nuclear factor κB (NF-κB) transcription factors are activated by mechanical loading and inflammatory cytokines. Our objective was to elucidate the role of NF-κB pathways in bone loss that are caused by mechanical unloading. Eight-week-old wild-type (WT) and NF-κB1-deficient mice were randomly assigned to a control or mechanically unloaded with tail suspension group. After 2 weeks, a radiographic analysis indicated a decrease in bone mass in the tibias and femurs of the unloaded WT mice but not in the NF-κB1-deficient mice. An NF-κB1 deficiency suppressed the unloading-induced reduction in bone formation by maintaining the proportion and/or potential of osteoprogenitors or immature osteoblasts, and by suppression of bone resorption through the inhibition of intracellular signaling through the receptor activator of NF-κB ligand (RANKL) in osteoclast precursors. Thus, NF-κB1 is involved in two aspects of rapid reduction in bone mass that are induced by disuse osteoporosis in space or bed rest. PMID:23322687

  10. Effect of calcium on skeletal development, bone loss, and risk of fractures.

    PubMed

    Heaney, R P

    1991-11-25

    In assessing the role of calcium, it must be stressed that calcium is not the cause of bone health but simply a necessary condition for it. It is mechanical usage that is of primary importance for bone. In just the same way iron is essential for hemoglobin synthesis and protein is essential for muscle mass, but neither is sufficient by itself. What, then, ought we to expect from a high calcium intake? Can we prevent estrogen-withdrawal bone loss? No. Calcium is not a substitute for estrogen, anymore than it is a substitute for exercise. Will calcium slow the remodeling loss that occurs with aging? Yes, to some extent; as calcium slows remodeling, it will inevitably slow remodeling-related loss. But most importantly, a high calcium intake will prevent calcium-deficiency bone loss. The only question, therefore, is the extent to which calcium deficiency loss may contribute significantly to bone fragility in various populations. The bone loss and fracture data reviewed briefly here indicate that an important portion of the osteoporotic fracture burden is calcium-related. What that portion is will be a function of the fraction of the population with inadequate intakes in any given country. Better than half of all adult American women have calcium intakes less than 500 mg/day, whereas only a small fraction of Dutch or Danish women, for example, would be under that level. Hence, a population-wide program to increase calcium intake in the United States would be likely to yield a greater benefit than in either the Netherlands or Denmark. That does not mean, of course, that there could not be substantial benefit to individuals with low intakes in all countries. Calcium intakes of greater than or equal to 1,500 mg are both safe and natural. While not all bone loss and low trauma fractures are due to low calcium intake, some almost certainly are. Adaptation to low intakes does occur, but it is seldom sufficient to compensate for the low intake. We cannot easily distinguish

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

    DOE PAGESBeta

    Schreurs, A. -S.; Shirazi-Fard, Y.; Shahnazari, M.; Alwood, J. S.; Truong, T. A.; Tahimic, C. G. T.; Limoli, C. L.; Turner, N. D.; Halloran, B.; Globus, R. K.

    2016-02-11

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

  12. Prevention of Bone Loss in a Model of Postmenopausal Osteoporosis through Adrenomedullin Inhibition

    PubMed Central

    Martínez-Herrero, Sonia; Larrayoz, Ignacio M.; Ochoa-Callejero, Laura; Fernández, Luis J.; Allueva, Alexis; Ochoa, Ignacio; Martínez, Alfredo

    2016-01-01

    Despite recent advances in the understanding and treatment options for osteoporosis, this condition remains a serious public health issue. Adrenomedullin (AM) is a regulatory peptide with reported activity on bone remodeling. To better understand this relationship we built an inducible knockout for AM. An outstanding feature of knockout mice is their heavier weight due, in part, to the presence of denser bones. The femur of knockout animals was denser, had more trabeculae, and a thicker growth plate than wild type littermates. The endocrine influence of AM on bone seems to be elicited through an indirect mechanism involving, at least, the regulation of insulin, glucose, ghrelin, and calcitonin gene-related peptide (CGRP). To confirm the data we performed a pharmacological approach using the AM inhibitor 16311 in a mouse model of osteoporosis. Ovariectomized females showed significant bone mass loss, whereas ovariectomized females treated with 16311 had similar bone density to sham operated females. In conclusion, we propose the use of AM inhibitors for the treatment of osteoporosis and other conditions leading to the loss of bone mass. PMID:27445864

  13. Increased EZH2 and decreased osteoblastogenesis during local irradiation-induced bone loss in rats

    PubMed Central

    Guo, Changjun; Li, Changwei; Yang, Kai; Kang, Hui; Xu, Xiaoya; Xu, Xiangyang; Deng, Lianfu

    2016-01-01

    Radiation therapy is commonly used to treat cancer patients but exhibits adverse effects, including insufficiency fractures and bone loss. Epigenetic regulation plays an important role in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Here, we reported local bone changes after single-dose exposure to 137CS irradiation in rats. Femur bone mineral density (BMD) and trabecular bone volume in the tibia were significantly decreased at 12 weeks after irradiation. Micro-CT results showed that tBMD, Tb.h and Tb.N were also significantly reduced at 12 weeks after irradiation exposure. ALP-positive OB.S/BS was decreased by 42.3% at 2 weeks after irradiation and was decreased by 50.8% at 12 weeks after exposure. In contrast to the decreased expression of Runx2 and BMP2, we found EZH2 expression was significantly increased at 2 weeks after single-dose 137CS irradiation in BMSCs. Together, our results demonstrated that single-dose 137CS irradiation induces BMD loss and the deterioration of bone microarchitecture in the rat skeleton. Furthermore, EZH2 expression increased and osteoblastogenesis decreased after irradiation. The underlying mechanisms warrant further investigation. PMID:27499068

  14. Increased EZH2 and decreased osteoblastogenesis during local irradiation-induced bone loss in rats.

    PubMed

    Guo, Changjun; Li, Changwei; Yang, Kai; Kang, Hui; Xu, Xiaoya; Xu, Xiangyang; Deng, Lianfu

    2016-01-01

    Radiation therapy is commonly used to treat cancer patients but exhibits adverse effects, including insufficiency fractures and bone loss. Epigenetic regulation plays an important role in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Here, we reported local bone changes after single-dose exposure to (137)CS irradiation in rats. Femur bone mineral density (BMD) and trabecular bone volume in the tibia were significantly decreased at 12 weeks after irradiation. Micro-CT results showed that tBMD, Tb.h and Tb.N were also significantly reduced at 12 weeks after irradiation exposure. ALP-positive OB.S/BS was decreased by 42.3% at 2 weeks after irradiation and was decreased by 50.8% at 12 weeks after exposure. In contrast to the decreased expression of Runx2 and BMP2, we found EZH2 expression was significantly increased at 2 weeks after single-dose (137)CS irradiation in BMSCs. Together, our results demonstrated that single-dose (137)CS irradiation induces BMD loss and the deterioration of bone microarchitecture in the rat skeleton. Furthermore, EZH2 expression increased and osteoblastogenesis decreased after irradiation. The underlying mechanisms warrant further investigation. PMID:27499068

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

    PubMed Central

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

    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 microstructural 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. PMID:26273512

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

    PubMed

    Schreurs, A-S; Shirazi-Fard, Y; Shahnazari, M; Alwood, J S; Truong, T A; Tahimic, C G T; Limoli, C L; Turner, N D; Halloran, B; Globus, R K

    2016-01-01

    Bone loss caused by ionizing radiation is a potential health concern for radiotherapy patients, radiation workers and astronauts. In animal studies, exposure to ionizing radiation increases oxidative damage in skeletal tissues, and results in an imbalance in bone remodeling initiated by increased bone-resorbing osteoclasts. Therefore, we evaluated various candidate interventions with antioxidant or anti-inflammatory activities (antioxidant cocktail, dihydrolipoic acid, ibuprofen, dried plum) both for their ability to blunt the expression of resorption-related genes in marrow cells after irradiation with either gamma rays (photons, 2 Gy) or simulated space radiation (protons and heavy ions, 1 Gy) and to prevent bone loss. Dried plum was most effective in reducing the expression of genes related to bone resorption (Nfe2l2, Rankl, Mcp1, Opg, TNF-α) and also preventing later cancellous bone decrements caused by irradiation with either photons or heavy ions. Thus, dietary supplementation with DP may prevent the skeletal effects of radiation exposures either in space or on Earth. PMID:26867002

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

    PubMed Central

    Schreurs, A.-S.; Shirazi-Fard, Y.; Shahnazari, M.; Alwood, J. S.; Truong, T. A.; Tahimic, C. G. T.; Limoli, C. L.; Turner, N. D.; Halloran, B.; Globus, R. K.

    2016-01-01

    Bone loss caused by ionizing radiation is a potential health concern for radiotherapy patients, radiation workers and astronauts. In animal studies, exposure to ionizing radiation increases oxidative damage in skeletal tissues, and results in an imbalance in bone remodeling initiated by increased bone-resorbing osteoclasts. Therefore, we evaluated various candidate interventions with antioxidant or anti-inflammatory activities (antioxidant cocktail, dihydrolipoic acid, ibuprofen, dried plum) both for their ability to blunt the expression of resorption-related genes in marrow cells after irradiation with either gamma rays (photons, 2 Gy) or simulated space radiation (protons and heavy ions, 1 Gy) and to prevent bone loss. Dried plum was most effective in reducing the expression of genes related to bone resorption (Nfe2l2, Rankl, Mcp1, Opg, TNF-α) and also preventing later cancellous bone decrements caused by irradiation with either photons or heavy ions. Thus, dietary supplementation with DP may prevent the skeletal effects of radiation exposures either in space or on Earth. PMID:26867002

  18. Effect of loading time on marginal bone loss around hydroxyapatite-coated implants

    PubMed Central

    Kim, Young-Kyun; Ahn, Kyo-Jin; Yun, Pil-Young; Kim, Minkyoung; Yang, Hong-So; Yi, Yang-Jin

    2013-01-01

    Objectives The objective of this study is compare the rate of marginal bone resorption around hydroxyapatite-coated implants given different loading times in order to evaluate their stability. Materials and Methods The study was conducted retrospectively for one year, targeting 41 patients whose treatment areas were the posterior maxilla and the mandible. Osstem TS III HA (Osstem Implant Co., Busan, Korea) and Zimmer TSV-HA (Zimmer Dental, Carlsbad, CA, USA), which employ the new hydroxyapatite coating technique, were used. The patients were divided into two groups - immediate and delayed loading - and the bone level at the time of loading commencement and after one year of loading was measured using periapical radiography. Differences between the groups were evaluated using Mann-Whitney (α=0.05). Results For all patients as a single group, the survival rate of the implants was 100%, and the mean marginal bone loss was 0.26±0.59 mm. In comparison of the differences by loading, mean marginal bone loss of 0.32±0.69 mm was recorded for the immediate loading group whereas the delayed loading group had mean marginal bone loss of 0.16±0.42 mm. However, the difference was not significant (P>0.05). Conclusion Within the limited observation period of one year, predictable survival rates can be expected when using immediately loaded hydroxyapatite-coated implants. PMID:24471037

  19. OOPHORECTOMY-INDUCED BONE LOSS IS ATTENUATED IN MAGP1-DEFICIENT MICE

    PubMed Central

    Craft, Clarissa S.; Broekelmann, Thomas J.; Zou, Wei; Chappel, Jean C.; Teitelbaum, Steven L.; Mecham, Robert P.

    2011-01-01

    Microfibril-associated glycoprotein-1 (MAGP1)¶, together with the fibrillins, are constitutive components of vertebrate microfibrils. Mice deficient in MAGP1 (MAGP1Δ) develop progressive osteopenia and reduced whole-bone strength, and have elevated numbers of osteoclasts lining the bone surface. Our previous studies suggested that the increased osteoclast population was associated with elevated levels of RANKL, a positive regulator of osteoclast differentiation. To explore the relationship between RANKL expression and osteoclast differentiation in MAGP1 deficiency, oophorectomy (OVX) was used to stimulate RANKL expression in both WT and MAGP1Δ animals. Bone loss following OVX was monitored using whole body DEXA and in vivo μCT. While WT mice exhibited significant bone loss following OVX, percent bone loss was reduced in MAGP1Δ mice. Further, serum RANKL levels rose significantly in OVX WT mice whereas there was only a modest increase in RANKL following OVX in the mutant mice due to already high baseline levels. Elevated RANKL expression was normalized when cultured MAGP1Δ osteoblasts were treated with a neutralizing antibody targeting free TGFβ. These studies provide support for increased RANKL expression associated with MAGP1 deficiency and provide a link to altered TGF-β signaling as a possible causative signaling pathway regulating RANKL expression in MAGP1Δ osteoblasts. PMID:21898536

  20. Evaluation of peri-implant bone loss around platform-switched implants.

    PubMed

    Cappiello, Michele; Luongo, Roberto; Di Iorio, Donato; Bugea, Calogero; Cocchetto, Roberto; Celletti, Renato

    2008-08-01

    This clinical and radiographic prospective study evaluated bone loss around two-piece implants that were restored according to the platform-switching protocol. One hundred thirty-one implants were consecutively placed in 45 patients following a nonsubmerged surgical protocol. On 75 implants, a healing abutment 1 mm narrower than the implant platform was placed at the time of surgery. On the remaining implants, a healing abutment of the same diameter as the implant was inserted. All implants were positioned at the crestal level. Clinical and radiographic examinations were performed prior to surgery, at the end of surgery, 8 weeks after implant placement, at the time of provisional prosthesis insertion, at the time of definitive prosthesis insertion, and 12 months after loading. The data collected showed that vertical bone loss for the test cases varied between 0.6 mm and 1.2 mm (mean: 0.95 +/- 0.32 mm), while for the control cases, bone loss was between 1.3 mm and 2.1 mm (mean: 1.67 +/- 0.37 mm). These data confirm the important role of the microgap between the implant and abutment in the remodeling of the peri-implant crestal bone. Platform switching seems to reduce peri-implant crestal bone resorption and increase the long-term predictability of implant therapy. PMID:18717373

  1. A Hypomagnetic Field Aggravates Bone Loss Induced by Hindlimb Unloading in Rat Femurs

    PubMed Central

    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. PMID:25157571

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

    PubMed

    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. PMID:18791351

  3. Constitutively Elevated Blood Serotonin Is Associated with Bone Loss and Type 2 Diabetes in Rats.

    PubMed

    Erjavec, Igor; Bordukalo-Niksic, Tatjana; Brkljacic, Jelena; Grcevic, Danka; Mokrovic, Gordana; Kesic, Maja; Rogic, Dunja; Zavadoski, William; Paralkar, Vishwas M; Grgurevic, Lovorka; Trkulja, Vladimir; Cicin-Sain, Lipa; Vukicevic, Slobodan

    2016-01-01

    Reduced peripheral serotonin (5HT) in mice lacking tryptophan hydroxylase (TPH1), the rate limiting enzyme for 5HT synthesis, was reported to be anabolic to the skeleton. However, in other studies TPH1 deletion either had no bone effect or an age dependent inhibition of osteoclastic bone resorption. The role of 5HT in bone therefore remains poorly understood. To address this issue, we used selective breeding to create rat sublines with constitutively high (high-5HT) and low (low-5HT) platelet 5HT level (PSL) and platelet 5HT uptake (PSU). High-5HT rats had decreased bone volume due to increased bone turnover characterized by increased bone formation and mineral apposition rate, increased osteoclast number and serum C-telopeptide level. Daily oral administration of the TPH1 inhibitor (LX1032) for 6 weeks reduced PSL and increased the trabecular bone volume and trabecular number of the spine and femur in high-5HT rats. High-5HT animals also developed a type 2 diabetes (T2D) phenotype with increased: plasma insulin, glucose, hemoglobin A1c, body weight, visceral fat, β-cell pancreatic islets size, serum cholesterol, and decreased muscle strength. Serum calcium accretion mediated by parathyroid hormone slightly increased, whereas treatment with 1,25(OH)2D3 decreased PSL. Insulin reduction was paralleled by a drop in PSL in high-5HT rats. In vitro, insulin and 5HT synergistically up-regulated osteoblast differentiation isolated from high-5HT rats, whereas TPH1 inhibition decreased the number of bone marrow-derived osteoclasts. These results suggest that constitutively elevated PSL is associated with bone loss and T2D via a homeostatic interplay between the peripheral 5HT, bone and insulin. PMID:26907598

  4. Constitutively Elevated Blood Serotonin Is Associated with Bone Loss and Type 2 Diabetes in Rats

    PubMed Central

    Brkljacic, Jelena; Grcevic, Danka; Mokrovic, Gordana; Kesic, Maja; Rogic, Dunja; Zavadoski, William; Paralkar, Vishwas M.; Grgurevic, Lovorka; Trkulja, Vladimir; Cicin-Sain, Lipa; Vukicevic, Slobodan

    2016-01-01

    Reduced peripheral serotonin (5HT) in mice lacking tryptophan hydroxylase (TPH1), the rate limiting enzyme for 5HT synthesis, was reported to be anabolic to the skeleton. However, in other studies TPH1 deletion either had no bone effect or an age dependent inhibition of osteoclastic bone resorption. The role of 5HT in bone therefore remains poorly understood. To address this issue, we used selective breeding to create rat sublines with constitutively high (high-5HT) and low (low-5HT) platelet 5HT level (PSL) and platelet 5HT uptake (PSU). High-5HT rats had decreased bone volume due to increased bone turnover characterized by increased bone formation and mineral apposition rate, increased osteoclast number and serum C-telopeptide level. Daily oral administration of the TPH1 inhibitor (LX1032) for 6 weeks reduced PSL and increased the trabecular bone volume and trabecular number of the spine and femur in high-5HT rats. High-5HT animals also developed a type 2 diabetes (T2D) phenotype with increased: plasma insulin, glucose, hemoglobin A1c, body weight, visceral fat, β-cell pancreatic islets size, serum cholesterol, and decreased muscle strength. Serum calcium accretion mediated by parathyroid hormone slightly increased, whereas treatment with 1,25(OH)2D3 decreased PSL. Insulin reduction was paralleled by a drop in PSL in high-5HT rats. In vitro, insulin and 5HT synergistically up-regulated osteoblast differentiation isolated from high-5HT rats, whereas TPH1 inhibition decreased the number of bone marrow-derived osteoclasts. These results suggest that constitutively elevated PSL is associated with bone loss and T2D via a homeostatic interplay between the peripheral 5HT, bone and insulin. PMID:26907598

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

    NASA Technical Reports Server (NTRS)

    OMalley, Bert W.

    1999-01-01

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

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

    PubMed

    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. PMID:18504147

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

    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

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

    PubMed Central

    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 association of CCAP with the mandibular cortical index and periodontal bone loss, respectively. Results 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. Conclusion 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. PMID:24380062

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

    PubMed

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

    2012-07-01

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

  11. Feeding Blueberry Diets in Early Life Prevent Senescence of Osteoblasts and Bone Loss in Ovariectomized Adult Female Rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Appropriate nutrition during early development is essential for optimal bone mass accretion; however, linkage between early nutrition, childhood bone mass and prevention of bone loss later in life has not been extensively studied. In this report, we show that feeding a high quality diet supplemented...

  12. Feeding blueberry diets during early development is sufficient to prevent senescence of osteoblasts and bone loss in adulthood

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Appropriate nutrition during early development is essential for optimal bone mass accretion; however, linkage between early nutrition, childhood bone mass and prevention of bone loss later in life has not been extensively studied. In this report, we show that feeding a high quality diet supplemented...

  13. Oolong tea drinking could help prevent bone loss in postmenopausal Han Chinese women.

    PubMed

    Wang, Guibin; Liu, Guibin; Liu, Liu Hongmei; Zhao, Huanli; Zhang, Fengfang; Li, Shufa; Chen, Yang; Zhang, Zhenchun

    2014-11-01

    The aim of this study was to analyze the relationship between oolong tea drinking and bone mineral density in postmenopausal Han Chinese women, while living and diet habits, fertility, disease elements and other baseline conditions were controlled. One group included 124 cases who routinely drank oolong tea, and the other included 556 who did not drink tea. Data were collected on participant age, lifestyle habits, fertility condition, disease elements, and lumbar, and hip bone densities. It was found that the bone densities of the greater trochanteric bone in tea drinkers were higher (0.793 ± 0.119 kg/cm(2)) than that in non-tea drinkers (0.759 ± 0.116 kg/cm(2), F = 6.248, p = 0.013). Similarly, the bone density of Ward's triangular bone in tea drinkers was higher (0.668 ± 0.133 kg/cm(2)) than that in non-tea drinkers (0.637 ± 0.135 kg/cm(2), F = 6.152, p = 0.013). Oolong tea drinking could help prevent bone loss in postmenopausal Chinese women. PMID:24989680

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

    PubMed

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

    2007-05-01

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

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

    PubMed

    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 (P<0.1) in rAAV-GFP-treated rats (13.5 months old) compared to baseline control rats (9 months old). Significant differences in cancellous bone or biomarkers of bone turnover were not detected between rAAV-Leptin 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. PMID:26487675

  16. Bone Grafts

    MedlinePlus

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

  17. Alcohol-Induced Myocardial Fibrosis in Metallothionein-Null Mice

    PubMed Central

    Wang, Lipeng; Zhou, Zhanxiang; Saari, Jack T.; Kang, Y. James

    2005-01-01

    Alcohol-induced cardiomyopathy including fibrosis has been recognized clinically for a long time, but its pathogenesis is incompletely understood. Studies using experimental animals have not fully duplicated the pathological changes in humans, and animal models of alcoholic cardiac fibrosis are not available. In the present study, we have developed a mouse model in which cardiac hypertrophy and fibrosis were produced in metallothionein-knockout (MT-KO) mice fed an alcohol-containing liquid diet for 2 months. The same alcohol feeding did not produce cardiac fibrosis in the wild-type (WT) control mice, although there was no difference in the alcohol-induced heart hypertrophy between the WT controls and the MT-KO mice. Zinc supplementation prevented cardiac fibrosis but did not affect heart hypertrophy in the alcohol-fed MT-KO mice, suggesting a specific link between zinc homeostasis and cardiac fibrosis. Serum creatine phosphokinase activity was significantly higher in the alcohol-administered MT-KO mice than in the WT mice, and zinc supplementation decreased serum creatine phosphokinase activities and eliminated the difference between the groups. Thus, disturbance in zinc homeostasis due to the lack of MT associates with alcohol-induced cardiac fibrosis and more severe cardiac injury, making the MT-KO mouse model of alcohol-induced cardiac fibrosis a useful tool to investigate specific factors involved in the alcoholic cardiomyopathy. PMID:16049321

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

    PubMed Central

    Dutta, D; Dharmshaktu, P; Aggarwal, A; Gaurav, K; Bansal, R; Devru, N; Garga, UC; Kulshreshtha, B

    2016-01-01

    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. PMID:27241810

  19. Interdependence of Muscle Atrophy and Bone Loss Induced by Mechanical Unloading

    PubMed Central

    Lloyd, Shane A.; Lang, Charles H.; Zhang, Yue; Paul, Emmanuel M.; Laufenberg, Lacee J.; Lewis, Gregory S.; Donahue, Henry J.

    2014-01-01

    Mechanical unloading induces muscle atrophy and bone loss; however, the time course and interdependence of these effects is not well defined. We subjected 4-month-old C57BL/6J mice to hindlimb suspension (HLS) for three weeks, sacrificing 12-16 mice on day (D) 0, 7, 14, and 21. Lean mass was 7-9% lower for HLS vs. control from D7-21. Absolute mass of the gastrocnemius (gastroc) decreased 8% by D7, and was maximally decreased 16% by D14 of HLS. mRNA levels of Atrogin-1 in the gastroc and quad were increased 99% and 122%, respectively, at D7 of HLS. Similar increases in MuRF1 mRNA levels occurred at D7. Both atrogenes returned to baseline by D14. Protein synthesis in gastroc and quad was reduced 30% from D7-14 of HLS, returning to baseline by D21. HLS decreased phosphorylation of SK61, a substrate of mammalian target of rapamycin (mTOR), on D7-21, while 4E-BP1 was not lower until D21. Cortical thickness of the femur and tibia did not decrease until D14 of HLS. Cortical bone of controls did not change over time. HLS mice had lower distal femur bone volume fraction (−22%) by D14; however, the effects of HLS were eliminated by D21 due to the decline of trabecular bone mass of controls. Femur strength was decreased approximately 13% by D14 of HLS, with no change in tibia mechanical properties at any time point. This investigation reveals that muscle atrophy precedes bone loss during unloading and may contribute to subsequent skeletal deficits. Countermeasures that preserve muscle may reduce bone loss induced by mechanical unloading or prolonged disuse. Trabecular bone loss with age, similar to that which occurs in mature astronauts, is superimposed on unloading. Preservation of muscle mass, cortical structure, and bone strength during the experiment suggests muscle may have a greater effect on cortical than trabecular bone. PMID:24127218

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  3. OPG Treatment Prevents Bone Loss During Lactation But Does Not Affect Milk Production or Maternal Calcium Metabolism.

    PubMed

    Ardeshirpour, Laleh; Dumitru, Cristina; Dann, Pamela; Sterpka, John; VanHouten, Joshua; Kim, Wonnam; Kostenuik, Paul; Wysolmerski, John

    2015-08-01

    Lactation is associated with increased bone turnover and rapid bone loss, which liberates skeletal calcium used for milk production. Previous studies suggested that an increase in the skeletal expression of receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells ligand (RANKL) coupled with a decrease in osteoprotegerin (OPG) levels likely triggered bone loss during lactation. In this study, we treated lactating mice with recombinant OPG to determine whether bone loss during lactation was dependent on RANKL signaling and whether resorption of the maternal skeleton was required to support milk production. OPG treatment lowered bone resorption rates and completely prevented bone loss during lactation but, surprisingly, did not decrease osteoclast numbers. In contrast, OPG was quite effective at lowering osteoblast numbers and inhibiting bone formation in lactating mice. Furthermore, treatment with OPG during lactation prevented the usual anabolic response associated with reversal of lactational bone loss after weaning. Preventing bone loss had no appreciable effect on milk production, milk calcium levels, or maternal calcium homeostasis when mice were on a standard diet. However, when dietary calcium was restricted, treatment with OPG caused maternal hypocalcemia, maternal death, and decreased milk production. These studies demonstrate that RANKL signaling is a requirement for bone loss during lactation, and suggest that osteoclast activity may be required to increase osteoblast numbers during lactation in preparation for the recovery of bone mass after weaning. These data also demonstrate that maternal bone loss is not absolutely required to supply calcium for milk production unless dietary calcium intake is inadequate. PMID:25961842

  4. OPG Treatment Prevents Bone Loss During Lactation But Does Not Affect Milk Production or Maternal Calcium Metabolism

    PubMed Central

    Ardeshirpour, Laleh; Dumitru, Cristina; Dann, Pamela; Sterpka, John; VanHouten, Joshua; Kim, Wonnam; Kostenuik, Paul

    2015-01-01

    Lactation is associated with increased bone turnover and rapid bone loss, which liberates skeletal calcium used for milk production. Previous studies suggested that an increase in the skeletal expression of receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells ligand (RANKL) coupled with a decrease in osteoprotegerin (OPG) levels likely triggered bone loss during lactation. In this study, we treated lactating mice with recombinant OPG to determine whether bone loss during lactation was dependent on RANKL signaling and whether resorption of the maternal skeleton was required to support milk production. OPG treatment lowered bone resorption rates and completely prevented bone loss during lactation but, surprisingly, did not decrease osteoclast numbers. In contrast, OPG was quite effective at lowering osteoblast numbers and inhibiting bone formation in lactating mice. Furthermore, treatment with OPG during lactation prevented the usual anabolic response associated with reversal of lactational bone loss after weaning. Preventing bone loss had no appreciable effect on milk production, milk calcium levels, or maternal calcium homeostasis when mice were on a standard diet. However, when dietary calcium was restricted, treatment with OPG caused maternal hypocalcemia, maternal death, and decreased milk production. These studies demonstrate that RANKL signaling is a requirement for bone loss during lactation, and suggest that osteoclast activity may be required to increase osteoblast numbers during lactation in preparation for the recovery of bone mass after weaning. These data also demonstrate that maternal bone loss is not absolutely required to supply calcium for milk production unless dietary calcium intake is inadequate. PMID:25961842

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    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. Selection of an appropriate animal model for study of bone loss in weightlessness

    NASA Technical Reports Server (NTRS)

    Wolinsky, I.

    1986-01-01

    Prolonged weightlessness in space flight results in a slow progressive demineralization of bone accompanied by an increased calcium output in the urine resulting in negative calcium balances. This possibly irreversible bone loss may constitute a serious limiting factor to long duration manned space flight. A number of preventative measures have been suggested, i.e., exercise during flight, dietary calcium supplements, use of specific prophylactic drugs. In order to facilitate research in these areas it is necessary to develop appropriate ground-based animal models that simulate the human condition of osteoporsis. An appropriate animal model would permit bone density studies, calcium balance studies, biochemical analyses, ground-based simulation models of weightlessness (bed rest, restraint, immobilization) and the planning of inflight experiments. Several animal models have been proposed in the biomedical research literature, but have inherent deficiencies. The purpose of this project was to evaluate models in the literature and determine which of these most closely simulates the phenomenon of bone loss in humans with regard to growth, bone remodeling, structural, chemical and mineralization similarities to human. This was accomplished by a comprehensive computer assisted literature search and report. Three animal models were examined closely for their relative suitability: the albino rat, monkey, and Beagle.

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

    PubMed

    Ramhamadany, Eamon; Modi, Chetan S

    2016-06-18

    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

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

    PubMed

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

    2016-03-16

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

  10. Association of osteoprotegerin and bone loss after adjuvant chemotherapy in early-stage breast cancer

    PubMed Central

    Oostra, Drew R.; Lustberg, Maryam B.; Reinbolt, Raquel E.; Pan, Xueliang; Wesolowski, Robert; Shapiro, Charles L.

    2015-01-01

    Purpose Chemotherapy induced ovarian failure (CIOF) results in rapid bone loss. Receptor Activator of Nuclear Factor Kappa-B (RANK)-RANK ligand (RANK-L) signaling balances bone resorption and formation. Osteoprotegerin (OPG) acts as a decoy receptor for RANK, interrupting osteoclast activation and bone resorption. This study examined the relationship between OPG and bone loss in women with CIOF. Methods Premenopausal women with stage I/II breast cancers receiving adjuvant chemotherapy were evaluated at chemotherapy initiation, 6 and 12 months. Bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), follicle stimulating hormone (FSH), ionized calcium, osteocalcin, and OPG were serially measured. CIOF was defined as a negative pregnancy test, FSH levels >30 MIU/mL, and ≥3 months of amenorrhea. Results Forty women were enrolled; 31 (77.5%) met CIOF criteria. BMD significantly decreased (p < 0.001) in the CIOF group at both time points: LS BMD decreased from a median of 0.993 g/cm2 to 0.976 g/cm2 and 0.937 g/cm2 at 6 and 12 months, respectively. OPG was significantly elevated at 6 months (median increase 0.30 pmol/L, p = 0.015) and then decreased at 12 months to levels still above baseline (median difference 0.2 pmol/L, p = 0.70). Conclusions In what was likely a compensatory response to rapid bone loss, CIOF patients’ OPG levels increased at 6 months and then decreased at 12 months to values greater than baseline assessments. This phenomenon is described in other diseases, but never before in CIOF. PMID:25575458

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

    PubMed Central

    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% (p<0.02), subtrochanter aBMD and BMC decreased by −2.1±2.0% and −3.3±3.7% (p<0.01). There was a significant decrease in lumbar spine BMC (−1.1±1.9%; p=0.03). There were no significant bone changes in the tibia (p>0.11). 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

  12. Androgen-deprivation therapy and bone loss in prostate cancer patients: a clinical review

    PubMed Central

    Bienz, Marc; Saad, Fred

    2015-01-01

    Androgen-deprivation therapy (ADT) has become a standard of care in the management of advanced prostate cancer or as an adjunct therapy. However, ADT is associated with a well-known deleterious effect on bone health, resulting in a decrease in bone-mass density (BMD) and increased risk for fracture. With the longer life expectancy of prostate cancer patients, improvement of the quality of life has become increasingly important. Therefore, adequate screening, prevention and treatment of BMD loss is paramount. Zoledronic acid and denosumab have shown promising results in recent studies, which has led to the Food and Drug Administration approval of these treatment options in various settings throughout the course of the disease, including the prevention of ADT-associated bone loss. This review focuses on the various parameters that impact BMD loss in men initiating ADT, on the specific effect of ADT on bone health and on various lifestyle modifications and treatment options such as bisphosphonates, osteoclast-targeted therapy and selective estrogen-receptor modulators that have shown promising results in recent studies. PMID:26131363

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

    PubMed Central

    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. PMID:26136808

  14. Odanacatib, A Cathepsin K-Specific Inhibitor, Inhibits Inflammation and Bone Loss Caused by Periodontal Diseases

    PubMed Central

    Hao, Liang; Chen, Jianwei; Zhu, Zheng; Reddy, Michael S.; Mountz, John D.; Chen, Wei; Li, Yi-Ping

    2015-01-01

    Background Periodontitis is a bacteria-induced inflammatory disease mainly affecting periodontal tissues, leading to periodontal inflammation, bone breakdown, and loss of the tooth. The main obstacle for treating periodontitis effectively is the difficulty in finding a target that can inhibit bone loss and inflammation simultaneously. Recent studies showed that cathepsin K (CTSK) might have functions in the immune system besides its role in osteoclasts. Thus, targeting CTSK would have a potential therapeutic effect in both the bone system and the immune system during the progression of periodontitis. Methods In the current study, a small molecular inhibitor (odanacatib [ODN]) is explored to inhibit the function of CTSK in a bacteria-induced periodontitis mouse model. Results The application of ODN decreased the number of osteoclasts, macrophages, and T cells, as well as the expression of Toll-like receptors (TLRs) in the periodontitis lesion area. Furthermore, lack of CTSK inhibited the expression of TLR4, TLR5, and TLR9 and their downstream cytokine signaling in the gingival epithelial cells in periodontitis lesions, demonstrating that the innate immune response was inhibited in periodontitis. Conclusion The present results show that inhibition of CTSK can prevent bone loss and the immune response during the progression of periodontitis, indicating that CTSK is a promising target for treating inflammatory diseases such as periodontitis by affecting both osteoclasts and the immune system. PMID:25879791

  15. Vitamin K catabolite inhibition of ovariectomy-induced bone loss: Structure–activity relationship considerations

    PubMed Central

    Soper, Robin J.; Oguz, Cenk; Emery, Roger; Pitsillides, Andrew A.; Hodges, Stephen J.

    2016-01-01

    Scope The potential benefit of vitamin K as a therapeutic in osteoporosis is controversial and the vitamin K regimen being used clinically (45 mg/day) employs doses that are many times higher than required to ensure maximal gamma-carboxylation of the vitamin K-dependent bone proteins. We therefore tested the hypothesis that vitamin K catabolites, 5-carbon (CAN5C) and 7-carbon carboxylic acid (CAN7C) aliphatic side-chain derivatives of the naphthoquinone moiety exert an osteotrophic role consistent with the treatment of osteoporosis. Methods and results Osteoblast-like MG63 cell cultures were challenged with lipopolysaccharide and the levels of interleukin-6, an osteoclastogenic cytokine, measured with and without catabolites; low concentrations of CAN7C significantly inhibited interleukin-6 release, but CAN5C did not. In models of bone loss induced by ovariectomy or sciatic neurectomy in C57BL/6 mice, we found that the rarer CAN7C catabolite markedly restricted ovariectomy-induced bone loss and possibly limited sciatic neurectomy-induced bone loss. CAN7C activity depends on a free carboxylic acid and its particular side-chain structure. Conclusion These in vivo data indicate for the first time that the clinical utility of vitamin K for osteoporosis may reside in an unusual catabolite. PMID:25044634

  16. Serum sclerostin and DKK1 in relation to exercise against bone loss in experimental bed rest.

    PubMed

    Belavý, Daniel L; Baecker, Natalie; Armbrecht, Gabriele; Beller, Gisela; Buehlmeier, Judith; Frings-Meuthen, Petra; Rittweger, Jörn; Roth, Heinz J; Heer, Martina; Felsenberg, Dieter

    2016-05-01

    The impact of effective exercise against bone loss during experimental bed rest appears to be associated with increases in bone formation rather than reductions of bone resorption. Sclerostin and dickkopf-1 are important inhibitors of osteoblast activity. We hypothesized that exercise in bed rest would prevent increases in sclerostin and dickkopf-1. Twenty-four male subjects performed resistive vibration exercise (RVE; n = 7), resistive exercise only (RE; n = 8), or no exercise (control n = 9) during 60 days of bed rest (2nd Berlin BedRest Study). We measured serum levels of BAP, CTX-I, iPTH, calcium, sclerostin, and dickkopf-1 at 16 time-points during and up to 1 year after bed rest. In inactive control, after an initial increase in both BAP and CTX-I, sclerostin increased. BAP then returned to baseline levels, and CTX-I continued to increase. In RVE and RE, BAP increased more than control in bed rest (p ≤ 0.029). Increases of CTX-I in RE and RVE did not differ significantly to inactive control. RE may have attenuated increases in sclerostin and dickkopf-1, but this was not statistically significant. In RVE there was no evidence for any impact on sclerostin and dickkopf-1 changes. Long-term recovery of bone was also measured and 6-24 months after bed rest, and proximal femur bone mineral content was still greater in RVE than control (p = 0.01). The results, while showing that exercise against bone loss in experimental bed rest results in greater bone formation, could not provide evidence that exercise impeded the rise in serum sclerostin and dickkopf-1 levels. PMID:26056021

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

    PubMed

    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. PMID:26285046

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

    PubMed

    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. PMID:25404554

  19. Cadmium-induced bone loss: Increased susceptibility in female beagles after ovariectomy

    SciTech Connect

    Bhattacharyya, M.H.; Sacco-Gibson, N.A.; Peterson, D.P.

    1991-01-01

    Bone resorption, as measured by release of bone {sup 45}Ca, was significantly increased in elderly female beagles within 96 h of exposure to 15 mg/L Cd in drinking water. The {sup 45}Ca response was greater in ovariecotomized (OV) animals than in sham-operated (SO) controls and was not mediated by changes in calciotropic hormone concentrations. Mean blood Cd concentrations were 3--8 {mu}g/L during the earliest bone resorption response and 13--15 {mu}g/L at the end of the study. During 7 mo of Cd exposure, bone mineral densities decreased most in the OV animals exposed to Cd: {minus}15.4 {plus minus} 4.3% for the tibia distal end and {minus}7.2 {plus minus} 1.2% for the lumbar vertebrae (L2-L4) (mean {plus minus} SE, n=4). Results indicate that Cd may act directly on bone and that postmenopausal women exposed to Cd in industry or via cigarette smoke may be at increased risk of Cd-induced bone loss. 21 refs., 4 figs.

  20. Bone mineral loss and recovery after 17 weeks of bed rest

    NASA Technical Reports Server (NTRS)

    Leblanc, A. D.; Schneider, V. S.; Evans, H. J.; Engelbretson, D. A.; Krebs, J. M.; LaBlanc, A. D. (Principal Investigator)

    1990-01-01

    The purpose of this work was to determine the rate and extent of bone loss and recovery from long-term disuse and in particular from disuse after exposure to weightlessness. For this purpose, bed rest is used to simulate the reduced stress and strain on the skeleton. This study reports on the bone loss and recovery after 17 weeks of continuous bed rest and 6 months of reambulation in six normal male volunteers. Bone regions measured were the lumbar spine, hip, tibia, forearm, calcaneus, total body, and segmental regions from the total-body scan. The total body, lumbar spine, femoral neck, trochanter, tibia, and calcaneus demonstrated significant loss, p less than 0.05. Expressed as the percentage change from baseline, these were 1.4, 3.9, 3.6, 4.6, 2.2, and 10.4, respectively. Although several areas showed positive slopes during reambulation, only the calcaneus was significant (p less than 0.05), with nearly 100% recovery. Segmental analysis of the total-body scans showed significant loss (p less than 0.05) in the lumbar spine, total spine, pelvis, trunk, and legs. During reambulation, the majority of the regions demonstrated positive slopes, although only the pelvis and trunk were significant (p less than 0.05). Potential redistribution of bone mineral was observed: during bed rest the bone mineral increased in the skull of all subjects. The change in total BMD and calcium from calcium balance were significantly (p less than 0.05) correlated, R = 0.88.

  1. Comparison of Diagnostic Accuracy of Conventional Intraoral Periapical and Direct Digital Radiographs in Detecting Interdental Bone Loss

    PubMed Central

    Suragimath, Girish; Jaishankar, H.P.; Kulkarni, Prasad; Bijjaragi, Shobha C.; Sangle, Varsha Ajit

    2015-01-01

    Background: Periodontitis is an inflammatory disease of the supporting tissues of the teeth caused by specific microorganisms, resulting in destruction of the periodontal ligament and alveolar bone. Progressive loss of alveolar bone is the salient feature of periodontal disease. Accurate detection of periodontal disease with the use of radiographs helps in diagnosis, treatment and prognosis. Aims: The present study aims to compare the efficacy of conventional intraoral periapical (IOPA) and direct digital radiographs (RVG) in detecting interdental alveolar bone loss using intrasurgical (IS) measurements as the gold standard. Materials and Methods: Thirty patients elected to undergo periodontal flap surgery with periodontitis computing to 60 interdental alveolar defects on mandibular first molars were considered. IOPA and RVG were captured using standardized techniques. Bone loss measurements in IOPA and RVG were compared to the IS measurements. Statistical Analysis: Statistical analysis was carried out using student t test and ANOVA with the help of SPSS software and p-value <0.05 was considered as significant. Results: Both IOPA and RVG underestimated the bone loss measurements when compared to IS measurements which was statistically significant (p<0.0001). Bone loss measurements in RVG were closer to IS measurements than IOPA. Conclusion: Both the radiographic techniques IOPA and RVG underestimated bone loss by 1.5–2.5 mm. RVG was superior to IOPA for the detection of interdental bone loss due to reduced time and radiation exposure to obtain the same diagnostic information. PMID:25859522

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

    PubMed Central

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

    2011-01-01

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

  3. Poncirin prevents bone loss in glucocorticoid-induced osteoporosis in vivo and in vitro.

    PubMed

    Yoon, Hyung-Young; Won, Ye-Yeon; Chung, Yoon-Sok

    2012-09-01

    Poncirin, a flavonoid isolated from the fruit of Poncirus trifoliata, possesses anti-bacterial and anti-inflammatory activities. However, the action of poncirin in bone biology is unclear. In this study, the in vivo and in vitro effects of poncirin in a glucocorticoid-induced osteoporosis (GIO) mouse model were investigated. Seven-month-old male mice were assigned to the following five groups: (1) sham-implantation (sham), (2) prednisolone 2.1 mg/kg/day (GC), (3) GC treated with 10 mg/kg/day of genistein, (4) GC treated with 3 mg/kg/day of poncirin, (5) and GC treated with 10 mg/kg/day of strontium (GC + SrCl(2)). After 8 weeks, bone loss was measured by microcomputed tomography. Osteocalcin (OC) and C-terminal telopeptides of type I collagen (CTX) were evaluated in sera. Runx2 protein, OC and osteoprotegerin (OPG) mRNA expression, alkaline phosphatase (ALP) activity, and mineral nodule assay were performed in C3H10T1/2 or primary bone marrow stromal cells. Poncirin significantly increased the bone mineral density and improved the microarchitecture. Poncirin increased serum OC, Runx2 protein production, expression of OC and OPG mRNA, ALP activity, and mineral nodule formation; and decreased serum CTX. These effects were more prominent in the poncirin group compared to the other positive control groups (genistein and strontium). The poncirin-mediated restoration of biochemical bone markers, increased bone mineral density, and improved trabecular microarchitecture likely reflect increased bone formation and decreased bone resorption in GIO mice. PMID:22407507

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

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

    The human zero-gravity locomotion simulator and the cadaver simulator offer a powerful combination for the study of the implications of exercise for maintaining bone quality during space flight. Such studies, when compared with controlled in-flight exercise programs, could help in the identification of a strain threshold for the prevention of bone loss during space flight.

  5. Image registration of proximal femur with substantial bone changes: application in 3D visualization of bone loss of astronauts after long-duration spaceflight

    NASA Astrophysics Data System (ADS)

    Li, Wenjun; Sode, Miki; Saeed, Isra; Lang, Thomas

    2006-03-01

    We recently studied bone loss in crewmembers making 4 to 6 months flights on the International Space Station. We employed Quantitative Computed Tomography (QCT) technology (Lang et. al., J Bone Miner Res. 2004; v. 19, p. 1006), which made measurements of both cortical and trabecular bone loss that could not be obtained by using 2-dimensional dual x-ray absorptiometry (DXA) imaging technology. To further investigate the bone loss after spaceflight, we have developed image registration technologies to align serial scans so that bone changes can be directly visualized in a subregional level, which can provide more detailed information for understanding bone physiology during long-term spaceflight. To achieve effective and robust registration when large bone changes exist, we have developed technical adaptations to standard registration methods. Our automated image registration is mutual-information based. We have applied an automatically adaptive binning method in calculating the mutual information. After the pre- and post-flight scans are geometrically aligned, the interior bone changes can be clearly visualized. Image registration can also be applied to Finite Element Modeling (FEM) to compare bone strength change, where consistent loading conditions must be applied to serial scans.

  6. The Role of Mechanical Stimulation in Recovery of Bone Loss-High versus Low Magnitude and Frequency of Force.

    PubMed

    Nagaraja, Mamta Patel; Jo, Hanjoong

    2014-01-01

    Musculoskeletal pathologies associated with decreased bone mass, including osteoporosis and disuse-induced bone loss, affect millions of Americans annually. Microgravity-induced bone loss presents a similar concern for astronauts during space missions. Many pharmaceutical treatments have slowed osteoporosis, and recent data shows promise for countermeasures for bone loss observed in astronauts. Additionally, high magnitude and low frequency impact such as running has been recognized to increase bone and muscle mass under normal but not microgravity conditions. However, a low magnitude and high frequency (LMHF) mechanical load experienced in activities such as postural control, has also been shown to be anabolic to bone. While several clinical trials have demonstrated that LMHF mechanical loading normalizes bone loss in vivo, the target tissues and cells of the mechanical load and underlying mechanisms mediating the responses are unknown. In this review, we provide an overview of bone adaptation under a variety of loading profiles and the potential for a low magnitude loading as a way to counteract bone loss as experienced by astronauts. PMID:25370188

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  9. Osteoprotegerin is an effective countermeasure for spaceflight-induced bone loss in mice.

    PubMed

    Lloyd, Shane A; Morony, Sean E; Ferguson, Virginia L; Simske, Steven J; Stodieck, Louis S; Warmington, Kelly S; Livingston, Eric W; Lacey, David L; Kostenuik, Paul J; Bateman, Ted A

    2015-12-01

    Bone loss associated with microgravity exposure poses a significant barrier to long-duration spaceflight. Osteoprotegerin-Fc (OPG-Fc) is a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor that causes sustained inhibition of bone resorption after a single subcutaneous injection. We tested the ability of OPG-Fc to preserve bone mass during 12 days of spaceflight (SF). 64-day-old female C57BL/6J mice (n=12/group) were injected subcutaneously with OPG-Fc (20mg/kg) or an inert vehicle (VEH), 24h prior to launch. Ground control (GC) mice (VEH or OPG-Fc) were maintained under environmental conditions that mimicked those in the space shuttle middeck. Age-matched baseline (BL) controls were sacrificed at launch. GC/VEH, but not SF/VEH mice, gained tibia BMD and trabecular volume fraction (BV/TV) during the mission (P<0.05 vs. BL). SF/VEH mice had lower BV/TV vs. GC/VEH mice, while SF/OPG-Fc mice had greater BV/TV than SF/VEH or GC/VEH. SF reduced femur elastic and maximum strength in VEH mice, with OPG-Fc increasing elastic strength in SF mice. Serum TRAP5b was elevated in SF/VEH mice vs. GC/VEH mice. Conversely, SF/OPG-Fc mice had lower TRAP5b levels, suggesting that OPG-Fc preserved bone during spaceflight via inhibition of osteoclast-mediated bone resorption. Decreased bone formation also contributed to the observed osteopenia, based on the reduced femur periosteal bone formation rate and serum osteocalcin level. Overall, these observations suggest that the beneficial effects of OPG-Fc during SF are primarily due to dramatic and sustained suppression of bone resorption. In growing mice, this effect appears to compensate for the SF-related inhibition of bone formation, while preventing any SF-related increase in bone resorption. We have demonstrated that the young mouse is an appropriate new model for SF-induced osteopenia, and that a single pre-flight treatment with OPG-Fc can effectively prevent the deleterious effects of SF on mouse bone. PMID

  10. PULSED FOCUSED ULTRASOUND TREATMENT OF MUSCLE MITIGATES PARALYSIS-INDUCED BONE LOSS IN THE ADJACENT BONE: A STUDY IN A MOUSE MODEL

    PubMed Central

    Poliachik, Sandra L.; Khokhlova, Tatiana D.; Wang, Yak-Nam; Simon, Julianna C.; Bailey, Michael R.

    2015-01-01

    Bone loss can result from bed rest, space flight, spinal cord injury or age-related hormonal changes. Current bone loss mitigation techniques include pharmaceutical interventions, exercise, pulsed ultrasound targeted to bone and whole body vibration. In this study, we attempted to mitigate paralysis-induced bone loss by applying focused ultrasound to the midbelly of a paralyzed muscle. We employed a mouse model of disuse that uses onabotulinumtoxinA-induced paralysis, which causes rapid bone loss in 5 d. A focused 2 MHz transducer applied pulsed exposures with pulse repetition frequency mimicking that of motor neuron firing during walking (80 Hz), standing (20 Hz), or the standard pulsed ultrasound frequency used in fracture healing (1 kHz). Exposures were applied daily to calf muscle for 4 consecutive d. Trabecular bone changes were characterized using micro-computed tomography. Our results indicated that application of certain focused pulsed ultrasound parameters was able to mitigate some of the paralysis-induced bone loss. PMID:24857416

  11. Heat shock protein 60 protects skeletal tissue against glucocorticoid-induced bone mass loss by regulating osteoblast survival.

    PubMed

    Wang, Feng-Sheng; Wu, Re-Wen; Ko, Jih-Yang; Tai, Ming-Hong; Ke, Huei-Ching; Yeh, Da-Wei; Wu, Shin-Long; Chen, Ming-Wen

    2011-11-01

    Excessive glucocorticoid administration accelerates osteoblast apoptosis and skeletal deterioration. Heat shock proteins (HSPs) regulate metabolic activities in osteoblastic cells. This study characterized the biological significance of HSP60 in glucocorticoid-induced bone loss. Rats were treated with glucocorticoid, HSP60 antisense oligonucleotides, or adenovirus-mediated HSP60 gene transfer. Bone mineral density, metaphyseal trabecular micro-architecture, and fragility were analyzed by dual X-ray absorptiometry, micro-computed tomography, and material testing, respectively. Differential proteomic profiles of bone tissue extracts were detected by bi-dimensional electrophoresis and mass spectrometry. Survival and proapoptotic signal transduction were quantified by immunoblotting. Glucocorticoid-treated rats had low bone mineral density and metaphyseal trabecular microstructure in association with downregulation of collagen 1α1 and HSP60 expressions in bone tissue. Gain of HSP60 function by adenovirus-mediated HSP60 gene transfer abrogated the deleterious effects of glucocorticoid treatment on bone mass, trabecular microstructure, and mechanical strength. Enhancement of HSP60 signaling attenuated the glucocorticoid-induced loss of trabecular bone volume, mineral acquisition reactions and osteoblast surface. HSP60 gene transfer activated ERK and Akt and reduced Bax and cytochrome c release, as well as caspase-3 cleavage, which attenuated the inhibitory effects of glucocorticoid treatment on osteoblast survival. Loss of HSP60 function by HSP60 antisense oligonucleotides accelerated mitochondrial apoptotic programs and osteoblast apoptosis. Knockdown of HSP60 induced loss of bone mass, micro-architecture integrity, and mechanical property. Taken together, loss of HSP60 signaling contributes to the glucocorticoid-induced enhancement of pro-apoptotic reactions, thereby accelerating osteoblast apoptosis and bone mass loss. Enhancement of HSP60 function is beneficial for

  12. sFRP4-dependent Wnt signal modulation is critical for bone remodeling during postnatal development and age-related bone loss

    PubMed Central

    Haraguchi, Ryuma; Kitazawa, Riko; Mori, Kiyoshi; Tachibana, Ryosuke; Kiyonari, Hiroshi; Imai, Yuuki; Abe, Takaya; Kitazawa, Sohei

    2016-01-01

    sFRP4 is an extracellular Wnt antagonist that fine-tunes its signal activity by direct binding to Wnts. Bone fragility under oxidative stress by diabetes and aging is partly related to the suppression of the Wnt signal through upregulated sFRP4. Here, to explore the functions of sFRP4 as a balancer molecule in bone development and remodeling, we analyzed the sFRP4 knock-in mouse strain. X-gal and immunohistochemically stained signals in sFRP4-LacZ heterozygous mice were detectable in restricted areas, mostly in osteoblasts and osteoclasts, of the femoral diaphysis after neonatal and postnatal stages. Histological and μCT analyses showed increased trabecular bone mass with alteration of the Wnt signal and osteogenic activity in sFRP4 mutants; this augmented the effect of the buildup of trabecular bone during the ageing period. Our results indicate that sFRP4 plays a critical role in bone development and remodeling by regulating osteoblasts and osteoclasts, and that its functional loss prevents age-related bone loss in the trabecular bone area. These findings imply that sFRP4 functions as a key potential endogenous balancer of the Wnt signaling pathway by efficiently having direct influence on both bone formation and bone absorption during skeletal bone development and maintenance through remodeling. PMID:27117872

  13. sFRP4-dependent Wnt signal modulation is critical for bone remodeling during postnatal development and age-related bone loss.

    PubMed

    Haraguchi, Ryuma; Kitazawa, Riko; Mori, Kiyoshi; Tachibana, Ryosuke; Kiyonari, Hiroshi; Imai, Yuuki; Abe, Takaya; Kitazawa, Sohei

    2016-01-01

    sFRP4 is an extracellular Wnt antagonist that fine-tunes its signal activity by direct binding to Wnts. Bone fragility under oxidative stress by diabetes and aging is partly related to the suppression of the Wnt signal through upregulated sFRP4. Here, to explore the functions of sFRP4 as a balancer molecule in bone development and remodeling, we analyzed the sFRP4 knock-in mouse strain. X-gal and immunohistochemically stained signals in sFRP4-LacZ heterozygous mice were detectable in restricted areas, mostly in osteoblasts and osteoclasts, of the femoral diaphysis after neonatal and postnatal stages. Histological and μCT analyses showed increased trabecular bone mass with alteration of the Wnt signal and osteogenic activity in sFRP4 mutants; this augmented the effect of the buildup of trabecular bone during the ageing period. Our results indicate that sFRP4 plays a critical role in bone development and remodeling by regulating osteoblasts and osteoclasts, and that its functional loss prevents age-related bone loss in the trabecular bone area. These findings imply that sFRP4 functions as a key potential endogenous balancer of the Wnt signaling pathway by efficiently having direct influence on both bone formation and bone absorption during skeletal bone development and maintenance through remodeling. PMID:27117872

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

    PubMed

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

    2013-06-01

    It has been generally accepted that calcium intake prevents bone loss, and frequent fracture resulted from osteoporosis. However, it is still elusive as to how effective sole calcium intake is in preventing or attenuating the severity of osteoporosis. Here, we demonstrate the effects of eggshell-casein phosphopeptide (ES-CPP), and compared these effects those of calcium supplement, for restoring ovariectomy-mediated bone loss. CPP, synthesized from the hydrolysis of casein (0.5%) using trypsin, was added to the grinded ES and was then administered to the ovariectomized (OVX) rat at 100 mg/kg for 4 weeks. Urine and feces from each group were collected each day, and were used to calculate the apparent calcium absorption rate in a day. After 4 weeks incubation, blood and femoral bones were isolated for the analysis of parameters representing osteoporosis. The apparent calcium absorption rate was significantly increased in the ES-CPP treated groups, in comparison to both the OVX and the commercial calcium supplement (CCS) treated group. Notably, treatment with ES-CPP markedly enhanced the calcium content in femoral bone and the relative weight of femoral bone to body weight, though calcium content in serum was barely changed by treatment with ES-CPP. Parameters of osteoporosis, such as osteocalcin in serum and bone mineral density, were rescued by treatment with ES-CPP, compared to treatment with commercial calcium supplement. This finding strongly suggests the possible use of ES-CPP in preventing or attenuating the severity of postmenopausal osteoporosis. PMID:23825479

  15. Loss of Gi G-Protein-Coupled Receptor Signaling in Osteoblasts Accelerates Bone Fracture Healing.

    PubMed

    Wang, Liping; Hsiao, Edward C; Lieu, Shirley; Scott, Mark; O'Carroll, Dylan; Urrutia, Ashley; Conklin, Bruce R; Colnot, Celine; Nissenson, Robert A

    2015-10-01

    G-protein-coupled receptors (GPCRs) are key regulators of skeletal homeostasis and are likely important in fracture healing. Because GPCRs can activate multiple signaling pathways simultaneously, we used targeted disruption of G(i) -GPCR or activation of G(s) -GPCR pathways to test how each pathway functions in the skeleton. We previously demonstrated that blockade of G(i) signaling by pertussis toxin (PTX) transgene expression in maturing osteoblastic cells enhanced cortical and trabecular bone formation and prevented age-related bone loss in female mice. In addition, activation of G(s) signaling by expressing the G(s) -coupled engineered receptor Rs1 in maturing osteoblastic cells induced massive trabecular bone formation but cortical bone loss. Here, we test our hypothesis that the G(i) and G(s) pathways also have distinct functions in fracture repair. We applied closed, nonstabilized tibial fractures to mice in which endogenous G(i) signaling was inhibited by PTX, or to mice with activated G(s) signaling mediated by Rs1. Blockade of endogenous G(i) resulted in a smaller callus but increased bone formation in both young and old mice. PTX treatment decreased expression of Dkk1 and increased Lef1 mRNAs during fracture healing, suggesting a role for endogenous G(i) signaling in maintaining Dkk1 expression and suppressing Wnt signaling. In contrast, adult mice with activated Gs signaling showed a slight increase in the initial callus size with increased callus bone formation. These results show that G(i) blockade and G(s) activation of the same osteoblastic lineage cell can induce different biological responses during fracture healing. Our findings also show that manipulating the GPCR/cAMP signaling pathway by selective timing of G(s) and G(i) -GPCR activation may be important for optimizing fracture repair. PMID:25917236

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

    PubMed Central

    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

  17. Dietary quercetin inhibits bone loss without effect on the uterus in ovariectomized mice.

    PubMed

    Tsuji, Mitsuyoshi; Yamamoto, Hironori; Sato, Tadatoshi; Mizuha, Yoko; Kawai, Yoshichika; Taketani, Yutaka; Kato, Shigeaki; Terao, Junji; Inakuma, Takahiro; Takeda, Eiji

    2009-01-01

    Quercetin is a major dietary flavonoid found in onions and other vegetables, and potentially has beneficial effects on disease prevention. In the present study, we demonstrate for the first time the effects of dietary quercetin on bone loss and uterine weight loss by ovariectomy in vivo. Female mice were ovariectomized (OVX) and were randomly allocated to 3 groups: a control diet or a diet with 0.25% (LQ) or 2.5% quercetin (HQ). After 4 weeks, dietary quercetin had no effects on uterine weight in OVX mice, but bone mineral density of the lumbar spine L4 and femur measured by peripheral quantitative computed tomography (pQCT) was higher in both the sham and the HQ groups than in the OVX group. Histomorphometric analysis showed that the HQ group restored bone volume (BV/TV) completely in distal femoral cancellous bone, but did not reduce the osteoclast surface area and osteoclast number when compared with the OVX group. In in-vitro experiments using mouse monocyte/macrophage cell line RAW264.7 cells, however, quercetin and its conjugate, quercetin-3-O-beta-D: -glucuronide dose-dependently inhibited the receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast differentiation, and the RANKL-stimulated expression of osteoclast related genes was also inhibited by quercetin. The luciferase reporter assay showed that quercetin did not appear to have estrogenic activity through estrogen receptors. These results suggest that dietary quercetin inhibits bone loss without effect on the uterus in OVX mice and does not act as a potent inhibitor of osteoclastogenesis or as a selective estrogen receptor modulator in vivo. PMID:19495926

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

    NASA Astrophysics Data System (ADS)

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

    2008-06-01

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

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

    PubMed

    Panseriya, Bhrugesh J; Hungund, Shital

    2011-07-01

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

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

    PubMed

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

    2016-08-01

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

  1. Epidemiologic Analyses of Risk Factors for Bone Loss and Recovery Related to Long-Duration Space Flight

    NASA Technical Reports Server (NTRS)

    Sibonga, Jean; Amin, Shreyasee

    2010-01-01

    AIM 1: To investigate the risk of microgravity exposure on long-term changes in bone health and fracture risk. compare data from crew members ("observed") with what would be "expected" from Rochester Bone Health Study. AIM 2: To provide a summary of current evidence available on potential risk factors for bone loss, recovery & fracture following long-duration space flight. integrative review of all data pre, in-, and post-flight across disciplines (cardiovascular, nutrition, muscle, etc.) and their relation to bone loss and recovery

  2. Accelerated bone mineral loss following a hip fracture: a prospective longitudinal study.

    PubMed

    Dirschl, D R; Henderson, R C; Oakley, W C

    1997-07-01

    The purpose of this prospective study was to monitor the bone mineral density (BMD) of the lumbar spine and contralateral femoral neck in the first year following an osteoporosis-related fracture of the hip. Eighty-three elderly patients (mean age 77 years) who had sustained a hip fracture had determinations of BMD made at the time of fracture; 49 of these patients were available for reassessment of BMD 1 year later. The change in BMD was correlated with pre- and postinjury variables, such as ambulatory ability, dietary intake of calcium, serum vitamin D levels, mental status, and routine serologies. The mean decrease in BMD in the year following fracture was 5.4% from the contralateral femoral neck and 2.4% from the lumbar spine. Calcium intake correlated with the loss of BMD from the femoral neck (p = 0.015), but not the lumbar spine. Patients with daily calcium intakes of less than 500 mg/day had a more than 10% decrease in femoral neck BMD in the year following their hip fracture. Serum 1,25-dihydroxy vitamin D level correlated with loss of MBD from the lumbar spine (p = 0.001), but not from the femoral neck. There was no correlation between the loss of bone mineral from either measurement site and age, sex, level of ambulation, or mental status. The loss of BMD from the femoral neck in the year following a hip fracture is more than five times that reported in the nonfractured population. This accelerated rate of loss can have drastic consequences in an elderly population already exhibiting osteopenia and propensity to fall. Investigation of pharmacologic or other interventions in the first critical year following a hip fracture may potentially blunt this accelerated rate of bone loss and lessen the risk of subsequent fractures. PMID:9213011

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2015-12-10

    Osteoclasts are responsible for bone erosion in diseases such as osteoporosis and rheumatoid arthritis. In the present study, we investigate the effects of eriodictyol, a flavonoid found naturally in citrus fruits, on the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation using mouse bone marrow macrophages (BMMs). Eriodictyol inhibited RANKL-induced osteoclast formation in a dose-dependent manner without cytotoxicity. In addition, eriodictyol suppressed bone resorption activity of differentiated osteoclasts. The inhibitory effect of eriodictyol was associated with impaired activation of multiple signaling events downstream of RANK, including extracellular signal-regulated kinase, p38, and c-Jun terminal kinase phosphorylation, followed by decreased nuclear factor of activated T cells (NFAT)c1 expression. Ectopic overexpression of a constitutively active form of NFATc1 completely rescued the anti-osteoclastogenic effect of eriodictyol, suggesting that the anti-osteoclastogenic effect was mainly attributed to the reduction in NFATc1 expression. Consistent with the in vitro anti-osteoclastogenic effect, eriodictyol suppressed lipopolysaccharide-induced osteoclast formation in the calvarial model and ovariectomy-induced bone loss in vivo. Taken together, our data demonstrate that eriodictyol is a new therapeutic agent with the potential to prevent bone destructive diseases by reducing both osteoclast differentiation and function. PMID:26450448

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

    PubMed Central

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

    2016-01-01

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

  6. Effect of neutral zone technique on marginal bone loss around implant-supported overdentures

    PubMed Central

    Darwish, Mahmoud; Nassani, Mohammad Zakaria; Baroudi, Kusai

    2015-01-01

    Aim: The aim of this study was to compare changes in marginal bone height around immediately loaded implants supporting a mandibular overdenture constructed according to the neutral zone technique with changes around overdentures constructed according to the conventional methods. Materials and Methods: Twelve completely edentulous male patients were randomly allocated to two equal groups of patients. Patients in the first group received conventionally constructed complete dentures and patients in the second group received complete dentures constructed using the neutral zone record. All the patients received two single-piece titanium implants placed bilaterally in the mandibular canine regions using flapless surgery, which were then immediately loaded by the dentures. Marginal bone height was radiographically evaluated at baseline and 6, 12, and 18 months after implant loading. Results: There was a significant loss in marginal bone height around the supporting implants in each study group. However, no significant differences in marginal bone height were recorded between the study groups over the observation period (P > 0.05). Conclusion: Marginal bone height changes induced by overdentures constructed with neutral zone technique on immediately loaded implants are not different from those changes induced by overdentures constructed with a conventional method. PMID:26942118

  7. Simulated Interventions to Ameliorate Age-Related Bone Loss Indicate the Importance of Timing.

    PubMed

    Proctor, Carole J; Gartland, Alison

    2016-01-01

    Bone remodeling is the continuous process of bone resorption by osteoclasts and bone formation by osteoblasts, in order to maintain homeostasis. The activity of osteoclasts and osteoblasts is regulated by a network of signaling pathways, including Wnt, parathyroid hormone (PTH), RANK ligand/osteoprotegrin, and TGF-β, in response to stimuli, such as mechanical loading. During aging there is a gradual loss of bone mass due to dysregulation of signaling pathways. This may be due to a decline in physical activity with age and/or changes in hormones and other signaling molecules. In particular, hormones, such as PTH, have a circadian rhythm, which may be disrupted in aging. Due to the complexity of the molecular and cellular networks involved in bone remodeling, several mathematical models have been proposed to aid understanding of the processes involved. However, to date, there are no models, which explicitly consider the effects of mechanical loading, the circadian rhythm of PTH, and the dynamics of signaling molecules on bone remodeling. Therefore, we have constructed a network model of the system using a modular approach, which will allow further modifications as required in future research. The model was used to simulate the effects of mechanical loading and also the effects of different interventions, such as continuous or intermittent administration of PTH. Our model predicts that the absence of regular mechanical loading and/or an impaired PTH circadian rhythm leads to a gradual decrease in bone mass over time, which can be restored by simulated interventions and that the effectiveness of some interventions may depend on their timing. PMID:27379013

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

    PubMed

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

    2005-06-01

    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. PMID:16038092

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

    NASA Astrophysics Data System (ADS)

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

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

  10. Simulated Interventions to Ameliorate Age-Related Bone Loss Indicate the Importance of Timing

    PubMed Central

    Proctor, Carole J.; Gartland, Alison

    2016-01-01

    Bone remodeling is the continuous process of bone resorption by osteoclasts and bone formation by osteoblasts, in order to maintain homeostasis. The activity of osteoclasts and osteoblasts is regulated by a network of signaling pathways, including Wnt, parathyroid hormone (PTH), RANK ligand/osteoprotegrin, and TGF-β, in response to stimuli, such as mechanical loading. During aging there is a gradual loss of bone mass due to dysregulation of signaling pathways. This may be due to a decline in physical activity with age and/or changes in hormones and other signaling molecules. In particular, hormones, such as PTH, have a circadian rhythm, which may be disrupted in aging. Due to the complexity of the molecular and cellular networks involved in bone remodeling, several mathematical models have been proposed to aid understanding of the processes involved. However, to date, there are no models, which explicitly consider the effects of mechanical loading, the circadian rhythm of PTH, and the dynamics of signaling molecules on bone remodeling. Therefore, we have constructed a network model of the system using a modular approach, which will allow further modifications as required in future research. The model was used to simulate the effects of mechanical loading and also the effects of different interventions, such as continuous or intermittent administration of PTH. Our model predicts that the absence of regular mechanical loading and/or an impaired PTH circadian rhythm leads to a gradual decrease in bone mass over time, which can be restored by simulated interventions and that the effectiveness of some interventions may depend on their timing. PMID:27379013

  11. Loss of transcription factor early growth response gene 1 results in impaired endochondral bone repair

    PubMed Central

    Reumann, Marie K.; Strachna, Olga; Yagerman, Sarah; Torrecilla, Daniel; Kim, Jihye; Doty, Steven B.; Lukashova, Lyudmila; Boskey, Adele L.; Mayer-Kuckuk, Philipp

    2011-01-01

    Transcription factors that play a role in ossification during development are expected to participate in postnatal fracture repair since the endochondral bone formation that occurs in embryos is recapitulated during fracture repair. However, inherent differences exist between bone development and fracture repair, including a sudden disruption of tissue integrity followed by an inflammatory response. This raises the possibility that repair-specific transcription factors participate in bone healing. Here, we assessed the consequence of loss of early growth response gene 1 (EGR-1) on endochondral bone healing because this transcription factor has been shown to modulate repair in vascularized tissues. Model fractures were created in ribs of wild type (wt) and EGR-1−/− mice. Differences in tissue morphology and composition between these two animal groups were followed over 28 post fracture days (PFDs). In wt mice, bone healing occurred in healing phases characteristic of endochondral bone repair. A similar healing sequence was observed in EGR-1−/− mice but was impaired by alterations. A persistent accumulation of fibrin between the disconnected bones was observed on PFD7 and remained pronounced in the callus on PFD14. Additionally, the PFD14 callus was abnormally enlarged and showed increased deposition of mineralized tissue. Cartilage ossification in the callus was associated with hyper-vascularity and -proliferation. Moreover, cell deposits located in proximity to the callus within skeletal muscle were detected on PFD14. Despite these impairments, repair in EGR-1−/− callus advanced on PFD28, suggesting EGR-1 is not essential for healing. Together, this study provides genetic evidence that EGR-1 is a pleiotropic regulator of endochondral fracture repair. PMID:21726677

  12. Reduction of Dietary Acid Load as a Potential Countermeasure for Bone Loss Associated with Spaceflight

    NASA Technical Reports Server (NTRS)

    Zwart, S. R.; Watts, S. M.; Sams, C. F.; Whitson, P. A.; Smith, S. M.

    2006-01-01

    In several studies we tested the concepts that diet can alter acid-base balance and that reducing the dietary acid load has a positive effect on maintenance of bone. In study 1, (n = 11, 60-90 d bed rest), the renal acid load of the diet was estimated from its chemical composition, and was positively correlated with urinary markers of bone resorption (P less than 0.05); that is, the greater the acid load, the greater the excretion of bone resorption markers. In study 2, in males (n = 8, 30 d bed rest), an estimate of the ratio of nonvolatile acid precursors to base precursors in the diet was positively correlated (P less than 0.05) with markers of bone resorption. In study 3, for 28 d subjects received either a placebo (n = 6) or an essential amino acid supplement (n = 7) that included methionine, a known acid precursor. During bed rest (28 d), urinary calcium was greater than baseline levels in the supplemented group but not the control group (P less than 0.05), and in the supplemented group, urinary pH decreased (P less than 0.05). In study 4, less bone resorption occurred in space crew members who received potassium citrate (n = 6) during spaceflight of 4-6 months than in crew members who received placebo or were not in the study (n = 8) (P less than 0.05). Reducing acid load has the potential to mitigate increased bone resorption during spaceflight, and may serve as a bone loss countermeasure.

  13. Conception on the cell mechanisms of bone tissue loss under spase flight conditions

    NASA Astrophysics Data System (ADS)

    Rodionova, Natalia; Oganov, Victor; Kabitskaya, Olga

    in rehabilitation of the resorbed bone tissue. This sequence of events is considered as a mechanism of bone tissue loss which underlies the development of osteopenia and osteoporosis under the mechanical loading deficit.

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

    NASA Technical Reports Server (NTRS)

    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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27011174

  16. Low-dosage micronized 17 beta-estradiol prevents bone loss in postmenopausal women

    NASA Technical Reports Server (NTRS)

    Ettinger, B.; Genant, H. K.; Steiger, P.; Madvig, P.

    1992-01-01

    With the use of a double-blind, randomized, dose-ranging design, we tested during an 18-month period the degree of protection against postmenopausal bone loss afforded by micronized 17 beta-estradiol in dosages of 0.5, 1.0, and 2.0 mg. All subjects received supplementation to ensure a minimum of 1500 mg calcium daily. Fifty-one subjects completed at least 1 year of follow-up bone density measurements by quantitative computed tomography and by single- and dual-photon absorptiometry. In the placebo group spinal trabecular bone density decreased 4.9% annually (p less than 0.001), whereas in those taking micronized 17 beta-estradiol bone density tended to increase (annual increases of 0.3% in the 0.5 mg micronized 17 beta-estradiol group, 1.8% in the 1.0 mg micronized 17 beta-estradiol group, and 2.5% in the 2.0 mg micronized 17 beta-estradiol group). After completing the double-blind phase, 41 subjects completed an additional 18 months of follow-up while taking 1.0 mg micronized 17 beta-estradiol. During this time one third of the subjects were randomly assigned to discontinue calcium supplements. Among those who previously received placebo, trabecular bone density increased 4.3% annually, whereas among those who had used micronized 17 beta-estradiol, trabecular bone density response was inversely related to the dosage previously used. Additionally and independently, the level of calcium intake showed a statistically significant correlation with the change in spinal trabecular bone density (r = 0.37, p = 0.02). We conclude that micronized 17 beta-estradiol has a continuous skeletal dose-response effect in the range of 0.5 to 2.0 mg and that calcium intake positively modifies the skeletal response to 1.0 mg micronized 17 beta-estradiol.

  17. Longitudinal study of dental caries, tooth mortality and interproximal bone loss in adults with intellectual disability.

    PubMed

    Gabre, P; Martinsson, T; Gahnberg, L

    2001-02-01

    The investigation focused on longitudinal changes of oral health in a group of adults with intellectual disability. A number of 124 individuals, aged 21-40 yr in 1990, were followed during 8.5 yr. The incidence and prevalence of caries, incidence of tooth mortality, and interproximal bone loss were registered from clinical examinations and bite-wing radiographs. The subjects visited the dental clinic for preventive dental care on average every third month during the period. The caries incidence was low, on average 0.51 new lesions per yr. Persons with mild intellectual disability experienced more caries than other subjects. During the 8.5 yr, the subjects had lost on average 1.82 teeth, with periodontitis dominating as the reason for tooth mortality. Individuals who cooperated poorly with dental treatment had lost the most teeth. The average annual bone loss in all subjects was 0.03 mm. Subjects with Down syndrome had a higher bone loss compared to those with other diagnoses of intellectual disability. Thus, the major part of the persons with intellectual disability showed satisfactory oral health. However, subjects with poor ability to cooperate with dental treatment and subjects with Down syndrome showed an increased risk for impaired oral health. PMID:11330930

  18. Predictors of Higher Bone Mineral Density Loss and Use of Depot Medroxyprogesterone Acetate

    PubMed Central

    Rahman, Mahbubur; Berenson, Abbey B.

    2009-01-01

    Objective To identify possible predictive factors of higher bone loss, defined as at least 5%, at the spine or femoral neck, over time in depot medroxyprogesterone (DMPA) users. Methods Bone mineral density (BMD) was measured at the lumbar spine and femoral neck every 6 months in 240 white, black, and Hispanic women using DMPA. For purpose of analysis, an arbitrary value of at least 5% BMD loss from the baseline value after 24 months of DMPA use at either the lumbar spine or femoral neck was considered as higher BMD loss. Logistic regression analysis was then used to examine factors predictive of at least 5% BMD loss at either site. Results Of the initial 240 DMPA users, 95 completed 24 months of follow-up. Forty-five of the 95 DMPA users (47.4%) had at least 5% BMD loss at the lumbar spine or femoral neck by 24 months. Multivariable logistic regression model showed that at least 5% BMD loss was associated with current smoking (adjusted odds ratio [OR] 3.88, 95% confidence interval [CI], 1.26–11.96), calcium intake (in 100 mg) (OR 0.81, 95% CI, 0.65–0.99), and parity (OR 0.49, 95% CI, 0.29–0.82). Age, race or ethnicity, previous contraceptive use and body mass index were not associated with higher BMD loss. Conclusions The risk of higher BMD loss associated with DMPA use may be reduced by quitting smoking and increasing calcium intake. Having had a child is also protective. PMID:20027031

  19. Post-Translational Loss of Renal TRPV5 Calcium Channel Expression, Ca2+ Wasting, and Bone Loss in Experimental Colitis

    PubMed Central

    Radhakrishnan, V. M.; Ramalingam, R.; Larmonier, C. B.; Thurston, R. D.; Laubitz, D.; Midura-Kiela, M. T.; McFadden, R-M. T.; Kuro-o, Makoto; Kiela, P. R.; Ghishan, F. K.

    2013-01-01

    Background & Aims Dysregulated Ca2+ homeostasis likely contributes to the etiology of IBD-associated loss of bone mineral density (BMD). Experimental colitis leads to decreased expression of Klotho, a protein which supports renal Ca2+ reabsorption by stabilizing TRPV5 channel on the apical membrane of distal tubule epithelial cells. Methods Colitis was induced in mice via administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS) or transfer of CD4+IL10−/− and CD4+, CD45RBhi T cells. We investigated changes in bone metabolism, renal processing of Ca2+, and expression of TRPV5. Results Mice with colitis had normal serum levels of Ca2+ and parathormone. Computed tomography analysis demonstrated decreased density of cortical and trabecular bone, and there was biochemical evidence for reduced bone formation and increased bone resorption. Increased fractional urinary excretion of Ca2+ was accompanied by reduced levels of TRPV5 protein in distal convoluted tubules, with a concomitant increase in TRPV5 sialylation. In mIMCD3 cells transduced with TRPV5 adenovirus, the inflammatory cytokines tumor necrosis factor (TNF), interferon (IFN)γ, and interleukin 1β reduced levels of TRPV5 on the cell surface, leading to its degradation. Cytomix induced interaction between TRPV5 and UBR4, an E3 ubiquitin ligase; knockdown of UBR4 with small interfering RNAs prevented cytomix-induced degradation of TRPV5. The effects of cytokines on TRPV5 were not observed in cells stably transfected with membrane-bound Klotho; TRPV5 expression was preserved when colitis was induced with TNBS in transgenic mice that overexpress Klotho or in mice with T-cell transfer colitis injected with soluble recombinant Klotho. Conclusion Following induction of colitis in mice via TNBS administration or T-cell transfer, TNF and IFNγ reduce expression and activity of Klotho, which would otherwise protect TRPV5 from hyper-sialylation and cytokine-induced TRPV5 endocytosis, UBR4-dependent ubiquitination

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

    PubMed Central

    Hubert, Patrice A.; Lee, Sang Gil; Lee, Sun-Kyeong; Chun, Ock K.

    2014-01-01

    Bone loss during aging has become an increasing public health concern as average life expectancy has increased. One of the most prevalent forms of age-related bone disease today is osteoporosis in which the body slows down bone formation and existing bone is increasingly being resorbed by the body to maintain the calcium balance. Some causes of this bone loss can be attributed to dysregulation of osteoblast and osteoclast activity mediated by increased oxidative stress through the aging process. Due to certain serious adverse effects of the currently available therapeutic agents that limit their efficacy, complementary and alternative medicine (CAM) has garnered interest as a natural means for the prevention of this debilitating disease. Natural antioxidant supplementation, a type of CAM, has been researched to aid in reducing bone loss caused by oxidative stress. Naturally occurring polyphenols, such as anthocyanins rich in berries, are known to have anti-oxidative properties. Several studies have been reviewed to determine the impact polyphenol intake—particularly that of berries—has on bone health. Studies reveal a positive association of high berry intake and higher bone mass, implicating berries as possible inexpensive alternatives in reducing the risk of age related bone loss. PMID:26784669

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

    PubMed

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

    2016-06-28

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

  2. Treatment with curcumin alleviates sublesional bone loss following spinal cord injury in rats.

    PubMed

    Yang, Xiaobin; He, Baorong; Liu, Peng; Yan, Liang; Yang, Ming; Li, Dichen

    2015-10-15

    This work aimed to investigate the therapeutic effect of curcumin on sublesional bone loss induced by spinal cord injury (SCI) in rats. SCI model in this work was generated in rats by surgical transaction of the cord at the T10-12 level. After the surgery, animals were treated with curcumin (110 mg/kg body mass/day, via oral gavages) for 2 weeks. Treatment of SCI rats with curcumin prevented the reduction of bone mass in tibiae and femurs, preserved bone microstructure including trabecular bone volume fraction, trabecular number, and trabecular thickness in proximal tibiae, and preserved mechanical properties of femoral midshaft. Treatment of SCI rats with curcumin increased osteoblast surface and reduced osteoclast surface in proximal tibiae. Treatment of SCI rats with curcumin increased osteocalcin mRNA expression and reduced mRNA levels of tartrate-resistant acid phosphatase and mRNA ratio of receptor activator of NF-κB ligand/osteoprotegerin in distal femurs. Treatment of SCI rats with curcumin reduced serum and femoral levels of thiobarbituric acid reactive substances. Treatment of SCI rats with curcumin had no significant effect on serum 25(OH)D, but enhanced mRNA and protein expression of vitamin D receptor (VDR) in distal femurs. Treatment of SCI rats with curcumin enhanced mRNA levels of Wnt3a, Lrp5, and ctnnb1 and upregulated protein expression of β-catenin in distal femurs. In conclusions, treatment with curcumin abated oxidative stress, activated VDR, and enhanced Wnt/β-catenin pathway, which might explain its beneficial effect against sublesional bone loss following SCI in rats, at least in part. PMID:26300394

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

    PubMed

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

    2012-06-01

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

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

    PubMed Central

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

    2012-01-01

    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. PMID:23082080

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

    PubMed

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

    2016-03-01

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

  6. Toll-Like Receptor 9-Mediated Inflammation Triggers Alveolar Bone Loss in Experimental Murine Periodontitis

    PubMed Central

    Kim, Paul D.; Xia-Juan, Xia; Crump, Katie E.; Abe, Toshiharu; Hajishengallis, George

    2015-01-01

    Chronic periodontitis is a local inflammatory disease induced by a dysbiotic microbiota and leading to destruction of the tooth-supporting structures. Microbial nucleic acids are abundantly present in the periodontium, derived through release after phagocytic uptake of microbes and/or from biofilm-associated extracellular DNA. Binding of microbial DNA to its cognate receptors, such as Toll-like receptor 9 (TLR9), can trigger inflammation. In this study, we utilized TLR9 knockout (TLR9−/−) mice and wild-type (WT) controls in a murine model of Porphyromonas gingivalis-induced periodontitis and report the first in vivo evidence that TLR9 signaling mediates the induction of periodontal bone loss. P. gingivalis-infected WT mice exhibited significantly increased bone loss compared to that in sham-infected WT mice or P. gingivalis-infected TLR9−/− mice, which were resistant to bone loss. Consistent with this, the expression levels of interleukin 6 (IL-6), tumor necrosis factor (TNF), and receptor-activator of nuclear factor kappa B ligand (RANKL) were significantly elevated in the gingival tissues of the infected WT mice but not in infected TLR9−/− mice compared to their levels in controls. Ex vivo studies using splenocytes and bone marrow-derived macrophages revealed significantly diminished cytokine production in TLR9−/− cells relative to the cytokine production in WT cells in response to P. gingivalis, thereby implicating TLR9 in inflammatory responses to this organism. Intriguingly, compared to the cytokine production in WT cells, TLR9−/− cells exhibited significantly decreased proinflammatory cytokine production upon challenge with lipopolysaccharide (LPS) (TLR4 agonist) or Pam3Cys (TLR2 agonist), suggesting possible cross talk between TLR9, TLR4, and TLR2. Collectively, our results provide the first proof-of-concept evidence implicating TLR9-triggered inflammation in periodontal disease pathogenesis, thereby identifying a new potential

  7. Toll-Like Receptor 9-Mediated Inflammation Triggers Alveolar Bone Loss in Experimental Murine Periodontitis.

    PubMed

    Kim, Paul D; Xia-Juan, Xia; Crump, Katie E; Abe, Toshiharu; Hajishengallis, George; Sahingur, Sinem E

    2015-07-01

    Chronic periodontitis is a local inflammatory disease induced by a dysbiotic microbiota and leading to destruction of the tooth-supporting structures. Microbial nucleic acids are abundantly present in the periodontium, derived through release after phagocytic uptake of microbes and/or from biofilm-associated extracellular DNA. Binding of microbial DNA to its cognate receptors, such as Toll-like receptor 9 (TLR9), can trigger inflammation. In this study, we utilized TLR9 knockout (TLR9(-/-)) mice and wild-type (WT) controls in a murine model of Porphyromonas gingivalis-induced periodontitis and report the first in vivo evidence that TLR9 signaling mediates the induction of periodontal bone loss. P. gingivalis-infected WT mice exhibited significantly increased bone loss compared to that in sham-infected WT mice or P. gingivalis-infected TLR9(-/-) mice, which were resistant to bone loss. Consistent with this, the expression levels of interleukin 6 (IL-6), tumor necrosis factor (TNF), and receptor-activator of nuclear factor kappa B ligand (RANKL) were significantly elevated in the gingival tissues of the infected WT mice but not in infected TLR9(-/-) mice compared to their levels in controls. Ex vivo studies using splenocytes and bone marrow-derived macrophages revealed significantly diminished cytokine production in TLR9(-/-) cells relative to the cytokine production in WT cells in response to P. gingivalis, thereby implicating TLR9 in inflammatory responses to this organism. Intriguingly, compared to the cytokine production in WT cells, TLR9(-/-) cells exhibited significantly decreased proinflammatory cytokine production upon challenge with lipopolysaccharide (LPS) (TLR4 agonist) or Pam3Cys (TLR2 agonist), suggesting possible cross talk between TLR9, TLR4, and TLR2. Collectively, our results provide the first proof-of-concept evidence implicating TLR9-triggered inflammation in periodontal disease pathogenesis, thereby identifying a new potential therapeutic target

  8. Suberoylanilide hydroxamic acid (SAHA; vorinostat) causes bone loss by inhibiting immature osteoblasts

    PubMed Central

    McGee-Lawrence, Meghan E.; McCleary-Wheeler, Angela L.; Secreto, Frank J.; Razidlo, David F.; Zhang, Minzhi; Stensgard, Bridget A.; Li, Xiaodong; Stein, Gary S.; Lian, Jane B.; Westendorf, Jennifer J.

    2011-01-01

    Histone deacetylase (Hdac) inhibitors are used clinically to treat cancer and epilepsy. Although Hdac inhibition accelerates osteoblast maturation and suppresses osteoclast maturation in vitro, the effects of Hdac inhibitors on the skeleton are not understood. The purpose of this study was to determine how the pan-Hdac inhibitor, suberoylanilide hydroxamic acid (SAHA; a.k.a. vorinostat or Zolinza™) affects bone mass and remodeling in vivo. Male C57BL/6 mice received daily SAHA (100 mg/kg) or vehicle injections for three to four weeks. SAHA decreased trabecular bone volume fraction and trabecular number in the distal femur. Cortical bone at the femoral midshaft was not affected. SAHA reduced serum levels of P1NP, a bone formation marker, and also suppressed tibial mRNA levels of type I collagen, osteocalcin and osteopontin, but did not alter Runx2 or osterix transcripts. SAHA decreased histological measures of osteoblast number but interestingly increased indices of osteoblast activity including mineral apposition rate and bone formation rate. Neither serum (TRAcP 5b) nor histological markers of bone resorption were affected by SAHA. P1NP levels returned to baseline in animals which were allowed to recover for four weeks after four weeks of daily SAHA injections, but bone density remained low. In vitro, SAHA suppressed osteogenic colony formation, decreased osteoblastic gene expression, induced cell cycle arrest, and caused DNA damage in bone marrow-derived adherent cells. Collectively, these data demonstrate that bone loss following treatment with SAHA is primarily due to a reduction in osteoblast number. Moreover, these decreases in osteoblast number can be attributed to the deleterious effects of SAHA on immature osteoblasts, even while mature osteoblasts are resistant to the harmful effects and demonstrate increased activity in vivo, indicating that the response of osteoblasts to SAHA is dependent upon their differentiation state. These studies suggest that

  9. Moderate weight loss in obese and overweight men preserves bone quality12345

    PubMed Central

    Pop, L Claudia; Sukumar, Deeptha; Tomaino, Katherine; Schlussel, Yvette; Schneider, Stephen H; Gordon, Chris L; Wang, Xiangbing; Shapses, Sue A

    2015-01-01

    Background: Weight loss (WL) negatively affects bone mineral density (BMD) in older populations and has specifically been shown in women. Objective: In this prospective controlled trial, we examined variables of bone quality and endocrine changes after intentional WL in men. Design: Thirty-eight overweight and obese [mean ± SD body mass index (in kg/m2): 31.9 ± 4.4; age: 58 ± 6 y] men were recruited to either WL through caloric restriction or weight maintenance (WM) for 6 mo. Results: There was a −7.9 ± 4.4% and +0.2 ± 1.6% change in body weight in the WL and WM groups, respectively. There was a greater increase in femoral neck and total body BMD and bone mineral content (BMC) in the WM group than in the WL group (P-interaction effect < 0.05). In contrast, there was a trend for the tibia cortical thickness and area to decrease more in the WM group than in the WL group (P ≤ 0.08). There was a decrease in the periosteal circumference in both groups over time (P < 0.01) and no statistically significant changes in trabecular bone. Circulating total, free, and bioavailable estradiol decreased in the WL group compared with the WM group, and changes were different between groups (P < 0.05). Serum total and bioavailable testosterone increased in both groups (P < 0.01). Serum 25-hydroxyvitamin D increased to a similar extent in both groups (P < 0.05). Conclusions: Moderate WL in overweight and obese men did not decrease BMD at any anatomical site or alter cortical and trabecular bone and geometry. Also, despite increased BMD at some sites when maintaining excess body weight, cortical bone showed a trend in the opposite direction. This trial was registered at clinicaltrials.gov as NCT00472745. PMID:25733651

  10. Andrographolide suppresses RANKL-induced osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo

    PubMed Central

    Zhai, Z J; Li, H W; Liu, G W; Qu, X H; Tian, B; Yan, W; Lin, Z; Tang, T T; Qin, A; Dai, K R

    2014-01-01

    Background and Purpose Osteoclasts play a pivotal role in diseases such as osteoporosis, rheumatoid arthritis and tumour bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. Here, we examined changes in osteoclastogenesis and LPS-induced osteolysis in response to andrographolide (AP), a diterpenoid lactone isolated from the traditional Chinese and Indian medicinal plant Andrographis paniculata. Experimental Approach Effects of AP on osteoclast differentiation and bone resorption were measured in vitro. Western blots and RT-PCR techniques were used to examine the underlying molecular mechanisms. The bone protective activity of AP in vivo was assessed in a mouse model of osteolysis. Key Results AP concentration-dependently suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro and reduced the expression of osteoclast-specific markers, including tartrate-resistant acid phosphatase, calcitonin receptors and cathepsin K. Further molecular analysis revealed that AP impaired RANKL-induced NF-κB signalling by inhibiting the phosphorylation of TGF-β-activated kinase 1, suppressing the phosphorylation and degradation of IκBα, and subsequently preventing the nuclear translocation of the NF-κB p65 subunit. AP also inhibited the ERK/MAPK signalling pathway without affecting p38 or JNK signalling. Conclusions and Implications AP suppressed RANKL-induced osteoclastogenesis through attenuating NF-κB and ERK/MAPK signalling pathways in vitro, thus preventing bone loss in vivo. These data indicated that AP is a promising natural compound for the treatment of osteoclast-related bone diseases. PMID:24125472

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

    PubMed

    Gelaude, Frederik; Clijmans, Tim; Delport, Hendrik

    2011-01-01

    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. PMID:22013539

  12. Effect of trabecular bone loss on cortical strain rate during impact in an in vitro model of avian femur

    PubMed Central

    Reich, Tal; Gefen, Amit

    2006-01-01

    Background Osteoporotic hip fractures occur due to loss of cortical and trabecular bone mass and consequent degradation in whole bone strength. The direct cause of most fractures is a fall, and hence, characterizing the mechanical behavior of a whole osteopenic bone under impact is important. However, very little is known about the mechanical interactions between cortical and trabecular bone during impact, and it is specifically unclear to what extent epiphyseal trabecular bone contributes to impact resistance of whole bones. We hypothesized that trabecular bone serves as a structural support to the cortex during impact, and hence, loss of a critical mass of trabecular bone reduces internal constraining of the cortex, and, thereby, decreases the impact tolerance of the whole bone. Methods To test this hypothesis, we conducted cortical strain rate measurements in adult chicken's proximal femora subjected to a Charpy impact test, after removing different trabecular bone core masses to simulate different osteopenic severities. Results We found that removal of core trabecular bone decreased by ~10-fold the cortical strain rate at the side opposite to impact (p < 0.01), i.e. from 359,815 ± 1799 μm/m per second (mean ± standard error) for an intact (control) specimen down to 35,997 ± 180 μm/m per second where 67% of the total trabecular bone mass (~0.7 grams in adult chicken) were removed. After normalizing the strain rate by the initial weight of bone specimens, a sigmoid relation emerged between normalized strain rate and removed mass of trabecular bone, showing very little effect on the cortex strain rate if below 10% of the trabecular mass is removed, but most of the effect was already apparent for less than 30% trabecular bone loss. An analytical model of the experiments supported this behavior. Conclusion We conclude that in our in vitro avian model, loss of over 10% of core trabecular bone substantially altered the deformation response of whole bone to impact

  13. Probiotics (Bifidobacterium longum) Increase Bone Mass Density and Upregulate Sparc and Bmp-2 Genes in Rats with Bone Loss Resulting from Ovariectomy

    PubMed Central

    Parvaneh, Kolsoom; Ebrahimi, Mahdi; Sabran, Mohd Redzwan; Karimi, Golgis; Hwei, Angela Ng Min; Abdul-Majeed, Saif; Ahmad, Zuraini; Ibrahim, Zuriati; Jamaluddin, Rosita

    2015-01-01

    Probiotics are live microorganisms that exert beneficial effects on the host, when administered in adequate amounts. Mostly, probiotics affect the gastrointestinal (GI) tract of the host and alter the composition of gut microbiota. Nowadays, the incidence of hip fractures due to osteoporosis is increasing worldwide. Ovariectomized (OVX) rats have fragile bone due to estrogen deficiency and mimic the menopausal conditions in women. Therefore, this study aimed to examine the effects of Bifidobacterium longum (B. longum) on bone mass density (BMD), bone mineral content (BMC), bone remodeling, bone structure, and gene expression in OVX rats. The rats were randomly assigned into 3 groups (sham, OVX, and the OVX group supplemented with 1 mL of B. longum 108–109 colony forming units (CFU)/mL). B. longum was given once daily for 16 weeks, starting from 2 weeks after the surgery. The B. longum supplementation increased (p < 0.05) serum osteocalcin (OC) and osteoblasts, bone formation parameters, and decreased serum C-terminal telopeptide (CTX) and osteoclasts, bone resorption parameters. It also altered the microstructure of the femur. Consequently, it increased BMD by increasing (p < 0.05) the expression of Sparc and Bmp-2 genes. B. longum alleviated bone loss in OVX rats and enhanced BMD by decreasing bone resorption and increasing bone formation. PMID:26366421

  14. Probiotics (Bifidobacterium longum) Increase Bone Mass Density and Upregulate Sparc and Bmp-2 Genes in Rats with Bone Loss Resulting from Ovariectomy.

    PubMed

    Parvaneh, Kolsoom; Ebrahimi, Mahdi; Sabran, Mohd Redzwan; Karimi, Golgis; Hwei, Angela Ng Min; Abdul-Majeed, Saif; Ahmad, Zuraini; Ibrahim, Zuriati; Jamaluddin, Rosita

    2015-01-01

    Probiotics are live microorganisms that exert beneficial effects on the host, when administered in adequate amounts. Mostly, probiotics affect the gastrointestinal (GI) tract of the host and alter the composition of gut microbiota. Nowadays, the incidence of hip fractures due to osteoporosis is increasing worldwide. Ovariectomized (OVX) rats have fragile bone due to estrogen deficiency and mimic the menopausal conditions in women. Therefore, this study aimed to examine the effects of Bifidobacterium longum (B. longum) on bone mass density (BMD), bone mineral content (BMC), bone remodeling, bone structure, and gene expression in OVX rats. The rats were randomly assigned into 3 groups (sham, OVX, and the OVX group supplemented with 1 mL of B. longum 10(8)-10(9) colony forming units (CFU)/mL). B. longum was given once daily for 16 weeks, starting from 2 weeks after the surgery. The B. longum supplementation increased (p < 0.05) serum osteocalcin (OC) and osteoblasts, bone formation parameters, and decreased serum C-terminal telopeptide (CTX) and osteoclasts, bone resorption parameters. It also altered the microstructure of the femur. Consequently, it increased BMD by increasing (p < 0.05) the expression of Sparc and Bmp-2 genes. B. longum alleviated bone loss in OVX rats and enhanced BMD by decreasing bone resorption and increasing bone formation. PMID:26366421

  15. The relationship between blood lead levels and periodontal bone loss in the United States, 1988-1994.

    PubMed Central

    Dye, Bruce A; Hirsch, Rosemarie; Brody, Debra J

    2002-01-01

    An association between bone disease and bone lead has been reported. Studies have suggested that lead stored in bone may adversely affect bone mineral metabolism and blood lead (PbB) levels. However, the relationship between PbB levels and bone loss attributed to periodontal disease has never been reported. In this study we examined the relationship between clinical parameters that characterize bone loss due to periodontal disease and PbB levels in the U.S. population. We used data from the Third National Health and Nutritional Examination Survey (NHANES III), 1988-1994, for the analyses. A total of 10,033 participants 20-69 years of age who completed a periodontal examination and had whole blood tested for lead were examined. Four types of periodontal disease measures were used to indicate oral bone loss: periodontal pocket depth, attachment loss extent, attachment loss severity, and the presence of dental furcations. We found that dental furcations were the best periodontal bone loss indicator for PbB levels (p = 0.005) in a multivariate linear regression model adjusting for sex, age, race/ethnicity, educational attainment, poverty status, smoking, and age of home. Furthermore, after additional modeling, we found a smoking and dental furcation interaction (p = 0.034). Subsequent stratified analyses indicated that current and past smoking is an effect modifier for dental furcations on PbB levels. These findings indicate that increased PbB levels may be associated with advanced periodontal bone loss, particularly among people with a history of smoking. PMID:12361924

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 (...

  18. Resistance exercise as a countermeasure to disuse-induced bone loss

    NASA Technical Reports Server (NTRS)

    Shackelford, L. C.; LeBlanc, A. D.; Driscoll, T. B.; Evans, H. J.; Rianon, N. J.; Smith, S. M.; Spector, E.; Feeback, D. L.; Lai, D.

    2004-01-01

    During spaceflight, skeletal unloading results in loss of bone mineral density (BMD). This occurs primarily in the spine and lower body regions. This loss of skeletal mass could prove hazardous to astronauts on flights of long duration. In this study, intense resistance exercise was used to test whether a training regimen would prevent the loss of BMD that accompanies disuse. Nine subjects (5 men, 4 women) participated in a supine maximal resistance exercise training program during 17 wk of horizontal bed rest. These subjects were compared with 18 control subjects (13 men, 5 women) who followed the same bed rest protocol without exercise. Determination of treatment effect was based on measures of BMD, bone metabolism markers, and calcium balance obtained before, during, and after bed rest. Exercisers and controls had significantly (P < 0.05) different means, represented by the respective following percent changes: lumbar spine BMD, +3% vs. -1%; total hip BMD, +1% vs. -3%; calcaneus BMD, +1% vs. -9%; pelvis BMD, -0.5% vs. -3%; total body BMD, 0% vs. -1%; bone-specific alkaline phosphatase, +64% vs. 0%; alkaline phosphatase, +31% vs. +5%; osteocalcin, +43% vs. +10%; 1,25 dihydroxyvitamin D, +12% vs. -15%; parathyroid hormone intact molecule, +18% vs. -25%; and serum and ionized calcium, -1% vs. +1%. The difference in net calcium balance was also significant (+21 mg/day vs. -199 mg/day, exercise vs. control). The gastrocnemius and soleus muscle volumes decreased significantly in the exercise group, but the loss was significantly less than observed in the control group. The results indicate that resistance exercise had a positive treatment effect and thus might be useful as a countermeasure to prevent the deleterious skeletal changes associated with long-duration spaceflight.

  19. Resistance exercise as a countermeasure to disuse-induced bone loss.

    PubMed

    Shackelford, L C; LeBlanc, A D; Driscoll, T B; Evans, H J; Rianon, N J; Smith, S M; Spector, E; Feeback, D L; Lai, D

    2004-07-01

    During spaceflight, skeletal unloading results in loss of bone mineral density (BMD). This occurs primarily in the spine and lower body regions. This loss of skeletal mass could prove hazardous to astronauts on flights of long duration. In this study, intense resistance exercise was used to test whether a training regimen would prevent the loss of BMD that accompanies disuse. Nine subjects (5 men, 4 women) participated in a supine maximal resistance exercise training program during 17 wk of horizontal bed rest. These subjects were compared with 18 control subjects (13 men, 5 women) who followed the same bed rest protocol without exercise. Determination of treatment effect was based on measures of BMD, bone metabolism markers, and calcium balance obtained before, during, and after bed rest. Exercisers and controls had significantly (P < 0.05) different means, represented by the respective following percent changes: lumbar spine BMD, +3% vs. -1%; total hip BMD, +1% vs. -3%; calcaneus BMD, +1% vs. -9%; pelvis BMD, -0.5% vs. -3%; total body BMD, 0% vs. -1%; bone-specific alkaline phosphatase, +64% vs. 0%; alkaline phosphatase, +31% vs. +5%; osteocalcin, +43% vs. +10%; 1,25 dihydroxyvitamin D, +12% vs. -15%; parathyroid hormone intact molecule, +18% vs. -25%; and serum and ionized calcium, -1% vs. +1%. The difference in net calcium balance was also significant (+21 mg/day vs. -199 mg/day, exercise vs. control). The gastrocnemius and soleus muscle volumes decreased significantly in the exercise group, but the loss was significantly less than observed in the control group. The results indicate that resistance exercise had a positive treatment effect and thus might be useful as a countermeasure to prevent the deleterious skeletal changes associated with long-duration spaceflight. PMID:15220316

  20. Circulating osteogenic cells: characterization and relationship to rates of bone loss in postmenopausal women.

    PubMed

    Undale, Anita; Srinivasan, Bhuma; Drake, Matthew; McCready, Louise; Atkinson, Elizabeth; Peterson, James; Riggs, B Lawrence; Amin, Shreyasee; Modder, U I; Moedder, U I; Khosla, Sundeep

    2010-07-01

    There is increasing evidence that osteogenic cells are present not only in bone marrow (BM) but also in peripheral blood (PB). Since staining for alkaline phosphatase (AP) identifies osteoprogenitor cells in BM, we sought to further characterize BM versus PB hematopoietic lineage negative (lin-)/AP+ cells and to compare gene expression in PB lin-/AP+ cells from postmenopausal women undergoing rapid versus slow bone loss. PB lin-/AP+ cells were smaller than their BM counterparts, and both were negative for the pan-hematopoietic marker, CD45. BM and PB lin-/AP+ cells were capable of mineralization in vitro. Using whole genome linear amplification followed by quantitative polymerase chain reaction (QPCR) analysis, we found that relative to the BM cells, PB lin-/AP+ cells expressed similar levels of a number of key osteoblast marker genes (runx2, osterix, osteopontin, OPG, periostin), consistent with the PB cells being in the osteoblastic lineage. Importantly, however, compared to the BM cells, PB lin-/AP+ cells expressed lower levels of mRNAs for AP, type I collagen, and for a panel of proliferation markers, but higher levels of osteocalcin, osteonectin, and PTHR1 mRNAs, as well as those for RANKL and ICAM-1, both of which are important in supporting osteoclastogenesis. Using microarray followed by QPCR analysis, we further demonstrated that, compared to postmenopausal women undergoing slow bone loss, PB lin-/AP+ cells from women undergoing rapid bone loss expressed lower levels of mRNAs for hydroxyprostaglandin dehydrogenase, interferon regulator factor 3, Wnt1-induced secreted protein 1, and TGFbeta2, but higher levels of the Smad3 interacting protein, zinc finger DHHC-type containing 4 and col1alpha2. These data thus demonstrate that while PB lin-/AP+ cells express a number of osteoblastic genes and are capable of mineralization, they are a relatively quiescent cell population, both in terms of cell proliferation and matrix synthesis. However, their higher

  1. Circulating Osteogenic Cells: Characterization and Relationship to Rates of Bone Loss in Postmenopausal Women

    PubMed Central

    Undale, Anita; Srinivasan, Bhuma; Drake, Matthew; McCready, Louise; Atkinson, Elizabeth; Peterson, James; Riggs, B. Lawrence; Amin, Shreyasee; Mödder, Ulrike; Khosla, Sundeep

    2010-01-01

    There is increasing evidence that osteogenic cells are present not only in bone marrow (BM) but also in peripheral blood (PB). Since staining for alkaline phosphatase (AP) identifies osteoprogenitor cells in BM, we sought to further characterize BM versus PB hematopoietic lineage negative (lin−)/AP+ cells and to compare gene expression in PB lin−/AP+ cells from postmenopausal women undergoing rapid versus slow bone loss. PB lin−/AP+ cells were smaller than their BM counterparts, and both were negative for the pan-hematopoietic marker, CD45. BM and PB lin−/AP+ cells were capable of mineralization in vitro. Using whole genome linear amplification followed by quantitative polymerase chain reaction (QPCR) analysis, we found that relative to the BM cells, PB lin−/AP+ cells expressed similar levels of a number of key osteoblast marker genes (runx2, osterix, osteopontin, OPG, periostin), consistent with the PB cells being in the osteoblastic lineage. Importantly, however, compared to the BM cells, PB lin−/AP+ cells expressed lower levels of mRNAs for AP, type I collagen, and for a panel of proliferation markers, but higher levels of osteocalcin, osteonectin, and PTHR1 mRNAs, as well as those for RANKL and ICAM-1, both of which are important in supporting osteoclastogenesis. Using microarray followed by QPCR analysis, we further demonstrated that, compared to postmenopausal women undergoing slow bone loss, PB lin−/AP+ cells from women undergoing rapid bone loss expressed lower levels of mRNAs for hydroxyprostaglandin dehydrogenase, interferon regulator factor 3, Wnt1-induced secreted protein 1, and TGFβ2, but higher levels of the Smad3 interacting protein, zinc finger DHHC-type containing 4 and col1α2. These data thus demonstrate that while PB lin−/AP+ cells express a number of osteoblastic genes and are capable of mineralization, they are a relatively quiescent cell population, both in terms of cell proliferation and matrix synthesis. However, their

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

    PubMed

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

    2015-09-30

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

  3. Prosthetic Abutment Height is a Key Factor in Peri-implant Marginal Bone Loss

    PubMed Central

    Galindo-Moreno, P.; León-Cano, A.; Ortega-Oller, I.; Monje, A.; Suárez, F.; ÓValle, F.; Spinato, S.; Catena, A.

    2014-01-01

    In this study, we analyzed the influence of prosthetic abutment height on marginal bone loss (MBL) around implants in the posterior maxilla. In this retrospective cohort study, the radiographically determined MBL was related to the height of the abutments of internal conical connection implants at 6 and 18 months post-loading. Data were gathered on age, sex, bone substratum, smoking habit, history of periodontitis, and prosthetic features, among other variables. A linear mixed model was used for statistical analysis. The study included 131 patients receiving 315 implants. MBL rates at 6 and 18 months were mainly affected by the abutment height but were also significantly influenced by the bone substratum, periodontitis, and smoking habit. MBL rates were higher for prosthetic abutment < 2 mm vs. ≥ 2 mm, for periodontal vs. non-periodontal patients, for grafted vs. pristine bone, and for a heavier smoking habit. The abutment height is a key factor in MBL. MBL rates followed a non-linear trend, with a greater MBL rate during the first 6 months post-loading than during the next 12 months. PMID:24621670

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

    PubMed

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

    2015-12-01

    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)-1β, 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 κB 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. PMID:26674426

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

    PubMed Central

    Guo, Yuchen; Sun, Ningyuan; Duan, Xiaobo; Xu, Xin; Zheng, Liwei; Seriwatanachai, Dutmanee; Wang, Yongyue; Yuan, Quan

    2016-01-01

    Background 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. Methods 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. Results 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. Conclusion In summary, our findings indicate that estrogen deficiency leads to further mandibular bone loss in CKD mice. PMID:26886008

  6. Apigenin inhibits osteoblastogenesis and osteoclastogenesis and prevents bone loss in ovariectomized mice.

    PubMed

    Goto, Tadashi; Hagiwara, Keitaro; Shirai, Nobuaki; Yoshida, Kaoru; Hagiwara, Hiromi

    2015-03-01

    Polyphenol have been reported to have physiological effects with respect to alleviating diseases such as osteoporosis and osteopetrosis. We recently reported that the olive polyphenol hydroxytyrosol accelerates bone formation both in vivo and in vitro. The present study was designed to evaluate the in vivo and in vitro effects of apigenin (4',5,7-trihydroxyflavone), one of the major polyphenols in olives and parsley, on bone formation by using cultured osteoblasts and osteoclasts and ovariectomized (OVX) mice, respectively. Apigenin markedly inhibited cell proliferation and indices of osteoblast differentiation, such as collagen production, alkaline phosphatase activity, and calcium deposition in osteoblastic MC3T3-E1 cells at concentrations of 1-10 μM. At 10 μM, apigenin completely inhibited the formation of multinucleated osteoclasts from mouse splenic cells. Moreover, injection of apigenin at 10 mg kg(-1) body weight significantly suppressed trabecular bone loss in the femurs of OVX mice. Our findings indicate that apigenin may have critical effects on bone maintenance in vivo. PMID:24500394

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

    NASA Astrophysics Data System (ADS)

    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

  8. Marginal bone loss and dental implant failure may be increased in smokers.

    PubMed

    Veitz-Keenan, Analia

    2016-03-01

    Data sourcesAn electronic search was performed in PubMed, Web of Science and the Cochrane Central Register of Controlled Trials up to February 2015. References of included studies were also searched. No language restrictions were appliedStudy selectionProspective, retrospective and randomised clinical trials that compared marginal bone loss and failure rates between smokers and non-smokers. Implant failure was considered as total loss of the implant. Studies with patients who had periodontal disease prior to treatment or who had metabolic diseases were excluded.Data extraction and synthesisTwo reviewers were involved in the research and screening process and disagreements were resolved by discussion. The quality of the studies was analysed using the Newcastle-Ottawa scale for non-randomised clinical trials. Data extracted from the studies included, when available: follow up period, number of subjects, smoking status, number of implants placed, implant system, implant length and diameter, healing period, antibiotics and mouth-rinse use, marginal bone loss, failure rate and drop-outs. For binary outcomes (implant failure) the estimate of the intervention effect was expressed in the form of an odds ratio (OR) with the confidence interval (CI) of 95%. For continuous outcomes (marginal bone loss) the average and standard deviation (SD) were used to calculate the standardised mean difference with a 95% CI. Meta-analysis was performed for studies with similar outcomes, I(2) a statistical test was used to express the heterogeneity among the studies. Publication bias was explored as well.ResultsA total of 15 observational studies were included in the review. The number of participants ranged from 60 to 1727 and the average age was 52.5 years. The follow-up period ranged from eight to 240 months. The total number of implants placed was 5840 in smokers and 14,683 in non-smokers. The Branemak system, (Noble Biocare AB, Goteborg, Sweden), was the most commonly used implant

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

    NASA Astrophysics Data System (ADS)

    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

  10. Progressive femoral cortical and cancellous bone density loss after uncemented tapered-design stem fixation

    PubMed Central

    Nowak, Tobias E; Haeberle, Lothar; Mueller, Lars P; Kress, Alexander; Voelk, Michael; Pfander, David; Forst, Raimund; Schmidt, Rainer

    2010-01-01

    Background Aseptic implant loosening and periprosthetic bone loss are major problems after total hip arthroplasty (THA). We present an in vivo method of computed tomography (CT) assisted osteodensitometry after THA that differentiates between cortical and cancellous bone density (BD) and area around the femoral component. Method Cortical and cancellous periprosthetic femoral BD (mg CaHA/mL), area (mm2) and contact area between the prothesis and cortical bone were determined prospectively in 31 patients 10 days, 1 year, and 6 years after uncemented THA (mean age at implantation: 55 years) using CT-osteodensitometry. Results 6 years postoperatively, cancellous BD had decreased by as much as 41% and cortical BD by up to 27% at the metaphyseal portion of the femur; this decrease was progressive between the 1-year and 6-year examinations. Mild cortical hypertrophy was observed along the entire length of the diaphysis. No statistically significant changes in cortical BD were observed along the diaphysis of the stem. Interpretation Periprosthetic CT-assisted osteodensitometry has the technical ability to discriminate between cortical and cancellous bone structures with respect to strain-adapted remodeling. Continuous loss of cortical and cancellous BD at the femoral metaphysis, a homeostatic cortical strain configuration, and mild cortical hypertrophy along the diaphysis suggest a diaphyseal fixation of the implanted stem. CT-assisted osteodensitometry has the potential to become an effective instrument for quality control in THA by means of in vivo determination of periprosthetic BD, which may be a causal factor in implant loosening after THA. PMID:20180716

  11. Expression of SOFAT by T- and B-lineage cells may contribute to bone loss

    PubMed Central

    JARRY, CHRISTIAN R.; MARTINEZ, ELIZABETH F.; PERUZZO, DAIANE C.; CARREGARO, VANESSA; SACRAMENTO, LAÍS A.; ARAÚJO, VERA C.; WEITZMANN, M. NEALE; NAPIMOGA, MARCELO H.

    2016-01-01

    A novel T cell-secreted cytokine, termed secreted osteoclastogenic factor of activated T cells (SOFAT) that induces osteoclastic bone resorption in a RANKL-independent manner, has been described. Our group have previously reported that SOFAT is highly expressed in gingival tissues of patients with chronic periodontitis suggesting a putative role in the bone loss associated with periodontal disease. The aim of the present study was to identify other potential cellular sources of SOFAT in the bone resorptive lesions of patients with periodontal disease. Gingival tissues were biopsied from systemically healthy subjects without periodontal disease (n=5) and patients with chronic periodontitis (n=5), and the presence of SOFAT was analyzed by immunohistochemistry and immunofluorescence staining. The present data demonstrated marked SOFAT staining in diseased periodontal tissues that was predominantly associated with the lymphocytic infiltration of gingival tissues. Notably, in addition to CD3+ T cells, B-lineage cells including plasma cells also exhibited strong staining for SOFAT. As SOFAT has not previously been reported in B-lineage cells, splenic T cells and B cells were further purified from BALB/c mice and activated using CD3/CD28 and lipopolysaccharide, respectively. SOFAT was quantified by reverse transcription-quantitative polymerase chain reaction and was shown to be significantly expressed (P<0.05) in both activated T cells and B cells compared with unstimulated cells. These data support a putative role of SOFAT in the bone loss associated with chronic periodontal disease. In addition, to the best of our knowledge, this study demonstrates for the first time that in addition to T cells, B-lineage cells may also be a significant source of SOFAT in inflammatory states. PMID:27035849

  12. Experimental estrogen-induced hyperprolactinemia results in bone-related hearing loss in the guinea pig.

    PubMed

    Horner, Kathleen C; Cazals, Yves; Guieu, Régis; Lenoir, Marc; Sauze, Nicole

    2007-11-01

    Our group (Horner KC, Guieu R, Magnan J, Chays A, Cazals Y. Neuropsychopharmacology 26: 135-138, 2002) has earlier described hyperprolactinemia in some patients presenting inner ear dysfunction. However, in that study, it was not possible to determine whether hyperprolactinemia was a cause or an effect of the symptoms. To investigate the effect of hyperprolactinemia on inner ear function, we first developed a model of hyperprolactinemia in estrogen-primed Fischer 344 rats and then performed functional studies on pigmented guinea pigs. Hyperprolactinemia induced, after 2 mo, a hearing loss of approximately 30-40 dB across all frequencies, as indicated by the compound action potential audiogram. During the 3rd mo, the hearing loss continued to deteriorate. The threshold shifts were more substantial in males than in females. Observations under a dissection microscope revealed bone dysmorphology of the bulla and the cochlea. Light microscopy observations of cryostat sections confirmed bone-related pathology of the bony cochlear bulla and the cochlear wall and revealed morphopathology of the stria vascularis and spiral ligament. Scanning electron microscopy revealed loss of hair cells and stereocilia damage, in particular in the upper three cochlear turns and the two outermost hair cell rows. The data provide the first evidence of otic capsule and hair cell pathology associated with estrogen-induced prolonged hyperprolactinemia and suggest that conditions such as pregnancy, anti-psychotic drug treatment, aging, and/or stress might lead to similar ear dysfunctions. PMID:17711987

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

    PubMed

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

    2015-03-01

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

  14. Igfbp2 Deletion in Ovariectomized Mice Enhances Energy Expenditure but Accelerates Bone Loss.

    PubMed

    DeMambro, Victoria E; Le, Phuong T; Guntur, Anyonya R; Maridas, David E; Canalis, Ernesto; Nagano, Kenichi; Baron, Roland; Clemmons, David R; Rosen, Clifford J

    2015-11-01

    Previously, we reported sexually dimorphic bone mass and body composition phenotypes in Igfbp2(-/-) mice (-/-), where male mice exhibited decreased bone and increased fat mass, whereas female mice displayed increased bone but no changes in fat mass. To investigate the interaction between IGF-binding protein (IGFBP)-2 and estrogen, we subjected Igfbp2 -/- and +/+ female mice to ovariectomy (OVX) or sham surgery at 8 weeks of age. At 20 weeks of age, mice underwent metabolic cage analysis and insulin tolerance tests before killing. At harvest, femurs were collected for microcomputed tomography, serum for protein levels, brown adipose tissue (BAT) and inguinal white adipose tissue (IWAT) adipose depots for histology, gene expression, and mitochondrial respiration analysis of whole tissue. In +/+ mice, serum IGFBP-2 dropped 30% with OVX. In the absence of IGFBP-2, OVX had no effect on preformed BAT; however, there was significant "browning" of the IWAT depot coinciding with less weight gain, increased insulin sensitivity, lower intraabdominal fat, and increased bone loss due to higher resorption and lower formation. Likewise, after OVX, energy expenditure, physical activity and BAT mitochondrial respiration were decreased less in the OVX-/- compared with OVX+/+. Mitochondrial respiration of IWAT was reduced in OVX+/+ yet remained unchanged in OVX-/- mice. These changes were associated with significant increases in Fgf21 and Foxc2 expression, 2 proteins known for their insulin sensitizing and browning of WAT effects. We conclude that estrogen deficiency has a profound effect on body and bone composition in the absence of IGFBP-2 and may be related to changes in fibroblast growth factor 21. PMID:26230658

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

    PubMed Central

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

    2013-01-01

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

  16. Prevention of aromatase inhibitor-induced bone loss with alendronate in postmenopausal women: The BATMAN Trial

    PubMed Central

    Lomax, Anna J.; Yee Yap, Saw; White, Karen; Beith, Jane; Abdi, Ehtesham; Broad, Adam; Sewak, Sanjeev; Lee, Chooi; Sambrook, Philip; Pocock, Nicholas; Henry, Margaret J.; Yeow, Elaine G.; Bell, Richard

    2013-01-01

    Postmenopausal women on aromatase inhibitors (AI) are at risk of aromatase inhibitor-associated bone loss (AIBL) and fractures. In 2005 Osteoporosis Australia proposed an algorithm for bisphosphonate intervention. Three hundred and three postmenopausal women with early breast cancer (EBC) were enrolled (osteoporotic, n=25; osteopaenic, n=146; normal bone mineral density (BMD), n=126). Weekly alendronate (70 mg) treatment efficacy as triggered by the algorithm in preventing bone loss was evaluated. All patients received anastrozole (1 mg daily), calcium and vitamin D. Results All osteoporotic patients received alendronate at baseline. Eleven out of the 146 (7.5%) osteopaenic patients commenced alendronate within 18 months of participation and eleven commenced after. One hundred and twenty four out of the 146 (84.9%) osteopaenic patients and all 126 with normal baseline BMD did not trigger the algorithm. At three years, lumbar spine mean BMD increased (15.6%, p<0.01) in the osteoporotic group. BMD in the osteopaenic group with early intervention significantly increased at three years (6.3%, p=0.02). No significant change was seen in the late intervention group. No change was observed in those with osteopaenia without alendronate. There was a significant drop in lumbar spine (−5.4%) and hip (−4.5%) mean BMD, in the normal BMD group, none of whom received alendronate. Fracture data will be presented. Conclusion In postmenopausal women with endocrine-responsive EBC, BMD improved over time when a bisphosphonate is administered with anastrozole in osteoporotic patients using an osteoporosis schedule. Subjects with normal baseline BMD experienced the greatest BMD loss, although none became osteoporotic. PMID:26909285

  17. Lipopolysaccharide-induced epithelial monoamine oxidase mediates alveolar bone loss in a rat chronic wound model.

    PubMed

    Ekuni, Daisuke; Firth, James D; Nayer, Tarun; Tomofuji, Takaaki; Sanbe, Toshihiro; Irie, Koichiro; Yamamoto, Tatsuo; Oka, Takashi; Liu, Zhenzi; Vielkind, Juergen; Putnins, Edward E

    2009-10-01

    Reactive oxygen species (ROS) production is an antimicrobial response to pathogenic challenge that may, in the case of persistent infection, have deleterious effects on the tissue of origin. A rat periodontal disease model was used to study ROS-induced chronic epithelial inflammation and bone loss. Lipopolysaccharide (LPS) was applied for 8 weeks into the gingival sulcus, and histological analysis confirmed the onset of chronic disease. Junctional epithelium was collected from healthy and diseased animals using laser-capture microdissection, and expression microarray analysis was performed. Of 19,730 genes changed in disease, 42 were up-regulated >/=4-fold. Three of the top 10 LPS-induced genes, monoamine oxidase B (MAO/B) and flavin-containing monooxygenase 1 and 2, are implicated in ROS signaling. LPS-associated induction of the ROS mediator H(2)O(2), as well as MAO/B and tumor necrosis factor (TNF)-alpha levels were validated in the rat histological sections and a porcine junctional epithelial cell culture model. Topical MAO inhibitors significantly counteracted LPS-associated elevation of H(2)O(2) production and TNF-alpha expression in vivo and in vitro, inhibited disease-associated apical migration and proliferation of junctional epithelium and inhibited induced systemic H(2)O(2) levels and alveolar bone loss in vivo. These results suggest that LPS induces chronic wounds via elevated MAO/B-mediated increases in H(2)O(2) and TNF-alpha activity by epithelial cells and is further associated with more distant effects on systemic oxidative stress and alveolar bone loss. PMID:19779138

  18. β2-adrenergic signal transduction plays a detrimental role in subchondral bone loss of temporomandibular joint in osteoarthritis

    PubMed Central

    Jiao, Kai; Niu, Li-Na; Li, Qi-hong; Ren, Gao-tong; Zhao, Chang-ming; Liu, Yun-dong; Tay, Franklin R.; Wang, Mei-qing

    2015-01-01

    The present study tested whether activation of the sympathetic tone by aberrant joint loading elicits abnormal subchondral bone remodeling in temporomandibular joint (TMJ) osteoarthritis. Abnormal dental occlusion was created in experimental rats, which were then intraperitoneally injected by saline, propranolol or isoproterenol. The norepinephrine contents, distribution of sympathetic nerve fibers, expression of β-adrenergic receptors (β-ARs) and remodeling parameters in the condylar subchondral bone were investigated. Mesenchymal stem cells (MSCs) from condylar subchondral bones were harvested for comparison of their β-ARs, pro-osteoclastic gene expressions and pro-osteoclastic function. Increases in norepinephrine level, sympathetic nerve fiber distribution and β2-AR expression were observed in the condylar subchondral bone of experimental rats, together with subchondral bone loss and increased osteoclast activity. β-antagonist (propranolol) suppressed subchondral bone loss and osteoclast hyperfunction while β-agonist (isoproterenol) exacerbated those responses. MSCs from experimental condylar subchondral bone expressed higher levels of β2-AR and RANKL; norepinephrine stimulation further increased their RANKL expression and pro-osteoclastic function. These effects were blocked by inhibition of β2-AR or the PKA pathway. RANKL expression by MSCs decreased after propranolol administration and increased after isoproterenol administration. It is concluded that β2-AR signal-mediated subchondral bone loss in TMJ osteoarthritisis associated with increased RANKL secretion by MSCs. PMID:26219508

  19. Feeding Blueberry Diets in Early Life Prevent Senescence of Osteoblasts and Bone Loss in Ovariectomized Adult Female Rats

    PubMed Central

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

    2011-01-01

    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. PMID:21912699

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

    PubMed Central

    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

  1. Effect of KW-8232, a novel anti-osteoporotic agent, on bone loss in sciatic neurectomized rats.

    PubMed

    Uchii, M; Takashima, M; Sugiyama, T; Kosaka, N

    1998-10-01

    The purpose of this study was to evaluate the effects of 3-[bis(4-hydroxyphenyl)methyl]-2-[4-(2-chlorophenyl)-piperazin-1-+ ++ylcarbonyl]-1-(2-dimethylaminoethyl) indole methanesulfonate (KW-8232), a novel anti-osteoporotic agent, on bone loss in neurectomized rats. We also investigated the effect of KW-8232 on bone resorption in this animal model. Male Sprague-Dawley rats underwent unilateral hind-limb immobilization by sciatic neurectomy. KW-8232 (3, 10 and 30 mg/kg, p.o.) was effective in inhibiting femoral bone loss. KW-8232 decreased urinary pyridinoline and deoxypyridinoline excretion. These results indicate that KW-8232 effectively prevents the bone loss due to immobilization. PMID:9829630

  2. Raloxifene preserves phenytoin and sodium valproate induced bone loss by modulating serum estradiol and TGF-β3 content in bone of female mice.

    PubMed

    Anwar, Md Jamir; Radhakrishna, K V; Sharma, Abhay; Vohora, Divya

    2014-10-01

    Antiepileptic drugs (AEDs)-induced adverse consequences on bone are now well recognized. Despite this, there is limited data on the effect of anti-osteoporotic therapies on AEDs-induced bone loss. We hypothesize that estrogen deprivation following phenytoin (PHT) and sodium valproate (SVP) therapy could lead to adverse bony effects. Both PHT and SVP inhibit human aromatase enzyme and stimulate microsomal catabolism of oestrogens. Estrogen deficiency states are known to reduce the deposition of transforming growth factor-β (TGF-β3), a bone matrix protein, having anti-osteoclastic property. Thus, an attempt was made to investigate the effect of raloxifene, a selective oestrogen receptor modulator, in comparison with calcium and vitamin D3 (CVD) supplementation, on PHT and SVP-induced alterations in bone in mice and to unravel the role of estradiol and TGF-β3 in mediation of bony effects by either AEDs or raloxifene. Further, the effect of raloxifene on seizures and on the antiepileptic efficacy of PHT and SVP was investigated. Swiss strains of female mice were treated with PHT (35 mg/kg, p.o.) and SVP (300 mg/kg, p.o.) for 120 days to induce bone loss as evidenced by reduced bone mineral density (BMD) and altered bone turnover markers (BTMs) in lumbar bones (alkaline phosphatase, tartarate resistant acid phosphatase, hydroxyproline) and urine (calcium). The bone loss was accompanied by reduced serum estradiol levels and bone TGF-β3 content. Preventive and therapeutic treatment with raloxifene ameliorated bony alterations and was more effective than CVD. It also significantly restored estradiol and TGF-β3 levels. Deprived estrogen levels (that in turn reduced lumbar TGF-β3 content) following PHT and SVP, thus, might represent one of the various mechanisms of AEDs-induced bone loss. Raloxifene preserved the bony changes without interfering with antiepileptic efficacy of these drugs, and hence raloxifene could be a potential therapeutic option in the management of

  3. An Increase in Forearm Cortical Bone Size After Menopause May Influence the Estimated Bone Mineral Loss--A 28-Year Prospective Observational Study.

    PubMed

    Karlsson, Magnus K; Ahlborg, Henrik G; Svejme, Ola; Nilsson, Jan-Åke; Rosengren, Björn E

    2016-01-01

    Areal bone mineral density (aBMD) is the most common estimate of bone mass, incorporated in the World Health Organization definition of osteoporosis. However, aBMD depends on not only the amount of mineral but also the bone size. The estimated postmenopausal decline in aBMD could because of this be influenced by changes in bone size.We measured bone mineral content (BMC; mg), aBMD (mg/cm2), and bone width (mm) by single-photon absorptiometry at the cortical site of the forearm in a population-based sample of 105 Caucasian women. We conducted 12 measurements during a 28-yr period from mean 5 yr (range: 2-9) before menopause to mean 24 yr (range: 18-28) after menopause. We calculated individual slopes for changes in the periods before menopause, 0-<8, 8-<16, and 16-28 yr after menopause. Data are presented as means with 95% confidence intervals. The annual BMC changes in the 4 periods were -1.4% (-0.1, -2.6), -1.1% (-0.9, -1.4), -1.2% (-0.9, -1.6), and -1.1% (-0.8, -1.4) and the annual increase in bone width 0.4% (-1.2, 1.9), 0.7% (0.5, 0.9), 0.1% (-0.2, 0.4), and 0.1% (-0.2, 0.4). BMC loss was similar in all periods, whereas the increase in bone width was higher in the first postmenopausal period than in the second (p=0.003) and the third (p=0.01) postmenopausal periods. Menopause is followed by a transient increase in forearm bone size that will influence the by aBMD estimated cortical loss in bone minerals. PMID:25708121

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

    PubMed

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

    2015-06-01

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

  5. The look AHEAD trial: bone loss at four-year follow-up in type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    OBJECTIVE: To determine whether an intensive lifestyle intervention (ILI) designed to sustain weight loss and improve physical fitness in overweight or obese persons with type 2 diabetes was associated with bone loss after 4 years of follow-up. RESEARCH DESIGN AND METHODS: This randomized controlled...

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

    PubMed

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

    2016-09-01

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

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

    PubMed

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

    2016-08-01

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

  8. PTH1-34 alleviates radiotherapy-induced local bone loss by improving osteoblast and osteocyte survival.

    PubMed

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

    2014-10-01

    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

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

    PubMed Central

    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

  10. Genetic susceptibility factors for alcohol-induced chronic pancreatitis.

    PubMed

    Aghdassi, Ali A; Weiss, F Ulrich; Mayerle, Julia; Lerch, Markus M; Simon, Peter

    2015-07-01

    Chronic pancreatitis is a progressive inflammatory disease of the pancreas and frequently associated with immoderate alcohol consumption. Since only a small proportion of alcoholics eventually develop chronic pancreatitis genetic susceptibility factors have long been suspected to contribute to the pathogenesis of the disease. Smaller studies in ethnically defined populations have found that not only polymorphism in proteins involved in the metabolism of ethanol, such as Alcohol Dehydrogenase and Aldehyde Dehydrogenase, can confer a risk for developing chronic pancreatitis but also mutations that had previously been reported in association with idiopathic pancreatitis, such as SPINK1 mutations. In a much broader approach employing genome wide search strategies the NAPS study found that polymorphisms in the Trypsin locus (PRSS1 rs10273639), and the Claudin 2 locus (CLDN2-RIPPLY1-MORC4 locus rs7057398 and rs12688220) confer an increased risk of developing alcohol-induced pancreatitis. These results from North America have now been confirmed by a European consortium. In another genome wide approach polymorphisms in the genes encoding Fucosyltransferase 2 (FUT2) non-secretor status and blood group B were not only found in association with higher serum lipase levels in healthy volunteers but also to more than double the risk for developing alcohol-associated chronic pancreatitis. These novel genetic associations will allow to investigate the pathophysiological and biochemical basis of alcohol-induced chronic pancreatitis on a cellular level and in much more detail than previously possible. PMID:26149858

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

    PubMed Central

    2014-01-01

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

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

    PubMed

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

    2009-09-01

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

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

    PubMed

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

    2016-05-01

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

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

    NASA Technical Reports Server (NTRS)

    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

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

    PubMed Central

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

    2015-01-01

    Context: Pycnogenol® extracted from French maritime pine bark (Pinus pinaster Ait. subsp. atlantica) is functional for its antioxidant activity. Objective: To investigate the effects of Pycnogenol® on bone mineral density (BMD), trabecular microarchitecture and bone metabolism in ovariectomized (OVX) rats. Materials and methods: Thirty Sprague-Dawley rats were randomized into 3 groups: SHAM group (sham-operated rats), OVX group (OVX rats), and treatment group (OVX rats supplemented with 40 mg/kg Pycnogenol® by oral gavage). Serum levels of procollagen type I N-terminal propeptide (PINP), alkaline phosphatase (ALP) and minerals were detected at the end of 9 weeks of gavage. Deoxypyridinoline/creatinine (DPYD/Cr) and N-telopeptide of type I collagen/creatinine (NTX/Cr) rate in urine were also calculated. Left femora were collected for BMD determination, and the right distal femora were made into undecalcified specimens for histomorphometry analysis. Results: At the end of study, PINP level, DPYD/Cr and NTX/Cr rate were significantly increased, and femoral BMD were dramatically decreased in OVX group compared with SHAM group (P < 0.01) while serum minerals and ALP concentrations showed no significant difference. The treatment group had dramatically decreased biomarkers and increased BMD than OVX group (P < 0.01). Histomorphometry analysis showed worse bone microarchitecture parameters in the OVX group compared with the SHAM group which were significantly improved in the treatment group compared with the OVX group (P < 0.01). Discussion and conclusion: Pycnogenol® (40 mg/kg) can inhibit aggravated bone resorption, prevent BMD loss, and restore the impaired trabecular microarchitecture in OVX rats after 9-week-intervention. PMID:26379883

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

    SciTech Connect

    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.

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

    PubMed

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

    2015-12-01

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

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

    SciTech Connect

    Yang, Yuehua Zheng, Xinfeng Li, Bo Jiang, Shengdan Jiang, Leisheng

    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.

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

    PubMed

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

    2016-03-01

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

  20. Involvement of SOCS3 in regulation of CD11c+ dendritic cell-derived osteoclastogenesis and severe alveolar bone loss.

    PubMed

    Zhang, Xiaoxia; Alnaeeli, Mawadda; Singh, Bhagirath; Teng, Yen-Tung A

    2009-05-01

    To investigate the role of suppressor of cytokine signaling (SOCS) molecules in periodontal immunity and RANKL-mediated dendritic cell (DC)-associated osteoclastogenesis, we analyzed SOCS expression profiles in CD4(+) T cells and the effect of SOCS3 expression in CD11c(+) DCs during periodontal inflammation-induced osteoclastogenesis and bone loss in nonobese diabetic (NOD) versus humanized NOD/SCID mice. Our results of ex vivo and in vitro analyses showed that (i) there is significantly higher SOCS3 expression associated with RANKL(+) T-cell-mediated bone loss in correlation with increased CD11c(+) DC-mediated osteoclastogenesis; (ii) the transfection of CD11c(+) DC using an adenoviral vector carrying a dominant negative SOCS3 gene significantly abrogates TRAP and bone-resorptive activity; and (iii) inflammation-induced TRAP expression, bone resorption, and SOCS3 activity are not associated with any detectable change in the expression levels of TRAF6 and mitogen-activated protein kinase signaling adaptors (i.e., Erk, Jnk, p38, and Akt) in RANKL(+) T cells. We conclude that SOCS3 plays a critical role in modulating cytokine signaling involved in RANKL-mediated DC-derived osteoclastogenesis during immune interactions with T cells and diabetes-associated severe inflammation-induced alveolar bone loss. Therefore, the development of SOCS3 inhibitors may have therapeutic potential as the target to halt inflammation-induced bone loss under pathological conditions in vivo. PMID:19255186

  1. Suppressive effects of the leaf of Terminalia catappa L. on osteoclast differentiation in vitro and bone weight loss in vivo.

    PubMed

    Koyama, Tomoyuki; Nakajima, Chie; Nishimoto, Sogo; Takami, Masamichi; Woo, Je-Tae; Yazawa, Kazunaga

    2012-01-01

    Oral administration of Terminalia catappa extract (TCE; 1,000 mg/kg) for 5 wk suppressed bone weight loss and trabecular bone loss in ovariectomized mice. An in vitro experiment showed that TCE (1.3-20 µg/mL) did not increase alkaline phosphatase activity, which would indicate osteoclast formation, in osteoblast-like 3T3-L1 cells. On the other hand, TCE (12.5 µg/mL) markedly decreased the number of tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells, which would indicate osteoclast formation, in a co-culture system (bone marrow cells/osteoblastic UAMS-32 cells). A detailed analysis of the stages of osteoclast differentiation revealed that TCE mainly suppressed the differentiation of bone marrow mononuclear cells into osteoclast progenitor cells in the presence of M-CSF and TGF-β. An additional experiment using fractionated TCE revealed that the water-soluble fraction suppressed the bone weight loss in OVX-mice and osteoclast differentiation in vitro. Therefore, the suppressive effects of TCE on bone weight loss in mice might be due to the suppressive effects of highly polar components on the early stage of osteoclast differentiation. PMID:22790571

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

    PubMed Central

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

    2015-01-01

    BACKGROUND/OBJECFTIVES The effect of St. John's Wort extract (SJW) on MG-63 cell proliferation and trabecular bone loss induced by ovariectomy was examined. MATERIALS/METHODS Proliferation, expression of estrogen receptor (ER) α and ER β, and gene expressions of osteoprotegerin (OPG), osteocalcin (OC) and alkaline phosphatase (ALP) were examined in MG-63 cells treated with or without SJW. Ovariectomized rats were treated with SJW at the dose of 100 or 200 mg/kg/day, β-estradiol-3-benzoate (E2), or vehicle only (OVX-C), and sham operated rats were treated with vehicle only (Sham-C). Serum ALP and C-telopeptide (CTX), and femoral trabecular bone loss were examined. RESULTS SJW increased MG-63 cell proliferation and expression of ER α and ER β, and positive effect was shown on gene expressions of ALP, OC and OPG. SJW also showed estrogen like effect on bone associated with slowing down in trabecular bone loss. Histopathology by H&E showed rats treated with SJW displayed denser structure in metaphyseal region of distal femur compared with rats in OVX-C. SJW was shown to reduce serum CTX in OVX rats. CONCLUSION The present study provides new insight in preventing estrogen deficiency induced bone loss of SJW and possibility for its application in bone health supplement. PMID:26425274

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

    PubMed

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

    2014-03-01

    Postmenopausal osteoporosis due to estrogen deficiency is associated with severe morbidity and mortality. Beneficial effects of conjugated linoleic acid (CLA) on bone mineral density (BMD) have been reported in mice, rats and humans, but the effect of long term CLA supplementation against ovariectomy-induced bone loss in mice and the mechanisms underlying this effect have not been studied yet. Eight-week old ovariectomized (Ovx) and sham operated C57BL/6 mice were fed either a diet containing 0.5 % safflower oil (SFO) or 0.5 % CLA for 24 weeks to examine BMD, bone turn over markers and osteotropic factors. Bone marrow (BM) cells were cultured to determine the effect on inflammation, osteoclastogenesis, and osteoblastogenesis. SFO/Ovx mice had significantly lower femoral, tibial and lumbar BMD compared to SFO/Sham mice; whereas, no difference was found between CLA/Ovx and CLA/Sham mice. CLA inhibited bone resorption markers whereas enhanced bone formation markers in Ovx mice as compared to SFO-fed mice. Reverse transcriptase polymerase chain reaction and fluorescence activated cell sorting analyses of splenocytes revealed that CLA inhibited pro-osteoclastogenic receptor activator of NF-κB (RANKL) and stimulated decoy receptor of RANKL, osteoprotegerin expression. CLA also inhibited pro-inflammatory cytokine and enhanced anti-inflammatory cytokine production of lipopolysaccharide-stimulated splenocytes and BM cells. Furthermore, CLA inhibited osteoclast differentiation in BM and stimulated osteoblast differentiation in BM stromal cells as confirmed by tartrate resistant acid phosphatase and Alizarin Red staining, respectively. In conclusion, CLA may prevent postmenopausal bone loss not only by inhibiting excessive bone resorption due to estrogen deficiency but also by stimulating new bone formation. CLA might be a potential alternative therapy against osteoporotic bone loss. PMID:24338525

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

    NASA Technical Reports Server (NTRS)

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

    2014-01-01

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

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

    PubMed

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

    2016-09-01

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

  6. Evaluation of the relative rates of bone mineral content loss in postmenopause due to both estrogen deficiency and ageing.

    PubMed

    Gnudi, S; Mongiorgi, R; Figus, E; Bertocchi, G

    1990-12-01

    To evaluate the relative rates of bone mineral content loss in postmenopause due to both estrogen deficiency and ageing, three groups of women were studied by computerized bone densitometry at the radius mid-point and at the distal point, modified according to the Abwrey technique. All women were in apparent good health and never had estrogen therapy. In the first group there were 64 women aged between 30 and 50 who were ovariectomized between 25 and 35 years of age. The second group was made up of 309 women between 50 and 55 years. In the third group there were 136 women aged 30-50 with normal ovaric function. The ordinary functions of linear polynomial regression were used to describe the variations in density with age. The percentage of postmenopausal bone loss was determined by calculating the BMC value at the start of the menopause and again twenty years later, according to the linear regression equation of postmenopausal period of each group of women in the study. The women who had natural menopause showed an average bone loss per year of 1.63% at the mid radius and 1.0% at the distal point. The ovariectomized women had an average loss of 0.85% at the mid point and 0.66% at the distal point. No significant decrease of bone mass was found before menopause. From a comparison between the two groups of women with analogous periods of menopause, it comes out that, during the first 20 years of natural menopause, estrogen deficiency is responsible for 52.5%-66.4% of the bone mineral loss, the remaining amount being attributable to other causes, connected with ageing. Estrogen deficiency is therefore, the principal factor causing bone mineral loss in natural menopause. PMID:2100526

  7. Inhibitory effects of Persicariae Rhizoma aqueous extracts on experimental periodontitis and alveolar bone loss in Sprague-Dawley rats

    PubMed Central

    Kang, Su Jin; Lee, Eun Kyung; Han, Chang Hyun; Lee, Bong Hyo; Lee, Young Joon; Ku, Sae Kwang

    2016-01-01

    Persicariae Rhizoma (PR) is the dried stem parts of Persicaria tinctoria H. Gross (Polygonaceae), and has been traditionally used as anti-inflammatory and detoxifying agent. In the present study, the effects of PR aqueous extracts on ligation-induced experimental periodontitis (EPD) and associated alveolar bone loss in rats were examined. Following the induction of EPD in rats, PR extracts were orally administered once a day for 10 days, and the changes and gains in body weight, alveolar bone loss and total aerobic bacterial counts of buccal gingiva were observed with histopathological analysis. In addition, anti-inflammatory effects were evaluated by monitoring myeloperoxidase (MPO) activities, and interleukin (IL)-1β and tumor necrosis factor (TNF)-α contents, and anti-oxidant effects were investigated by measuring inducible nitric oxide synthase (iNOS) activities and malondialdehyde (MDA) levels. Bacterial proliferation, periodontitis and associated alveolar bone loss induced by ligature placement were significantly and dose-dependently inhibited by the treatment with PR extracts. The inhibitory effects of 200 mg/kg PR were similar to those of 5 mg/kg indomethacin on ligation-induced periodontitis and associated alveolar bone losses in this study. The results suggest that PR effectively inhibits ligature placement-induced periodontitis and alveolar bone loss in rats via antibacterial, antioxidative and anti-inflammatory activities. PMID:27588077

  8. Recovery of Spaceflight-induced Bone Loss: Bone Mineral Density after Long-Duration Missions as Fitted with an Exponential Function

    NASA Technical Reports Server (NTRS)

    Sibonga, J. D.; Evans, H. J.; Sung, H. G.; Spector, E. R.; Lang, T. F.; Oganov, V. S.; Bakulin, A. V.; Shackelford, L. C.; LeBlanc, A. D.

    2007-01-01

    The loss of bone mineral in NASA astronauts during spaceflight has been investigated throughout the more than 40 years of space travel. Consequently, it is a medical requirement at NASA Johnson Space Center (JSC) that changes in bone mass be monitored in crew members by measuring bone mineral density (BMD) with dual-energy x-ray absorptiometry (DXA) before and after flight on astronauts who serve on long-duration missions (4-6 months). We evaluated this repository of medical data to track whether there is recovery of bone mineral that was lost during spaceflight. Our analysis was supplemented by BMD data from cosmonauts ( by convention, a space traveler formally employed by the Russia Aviation and Space Agency or by the previous Soviet Union) who had also flown on long-duration missions. Data from a total of 45 individual crew members -- a small number of whom flew on more than one mission -- were used in this analysis. Changes in BMD (between 56 different sets of pre- and postflight measurements) were plotted as a function of time (days after landing). Plotted BMD changes were fitted to an exponential mathematical function that estimated: i) BMD change on landing day (day 0) and ii) the number of days after landing when 50% of the lost bone would be recovered ("50% recovery time") in the lumbar spine, trochanter, pelvis, femoral neck and calcaneus. In sum, averaged losses of bone mineral after long-duration spaceflight ranged between 2-9% across all sites with our recovery model predicting a 50% restoration of bone loss for all sites to be within 9 months.

  9. Premenopausal Trabecular Bone Loss is Associated with a Family History of Fragility Fracture

    PubMed Central

    Prior, J. C.; Hitchcock, C. L.; Vigna, Y. M.; Seifert-Klauss, V.

    2016-01-01

    rate of premenopausal spinal trabecular bone loss. PMID:27582584

  10. A multiscale mechanobiological model of bone remodelling predicts site-specific bone loss in the femur during osteoporosis and mechanical disuse.

    PubMed

    Lerebours, C; Buenzli, P R; Scheiner, S; Pivonka, P

    2016-02-01

    We propose a multiscale mechanobiological model of bone remodelling to investigate the site-specific evolution of bone volume fraction across the midshaft of a femur. The model includes hormonal regulation and biochemical coupling of bone cell populations, the influence of the microstructure on bone turnover rate, and mechanical adaptation of the tissue. Both microscopic and tissue-scale stress/strain states of the tissue are calculated from macroscopic loads by a combination of beam theory and micromechanical homogenisation. This model is applied to simulate the spatio-temporal evolution of a human midshaft femur scan subjected to two deregulating circumstances: (i) osteoporosis and (ii) mechanical disuse. Both simulated deregulations led to endocortical bone loss, cortical wall thinning and expansion of the medullary cavity, in accordance with experimental findings. Our model suggests that these observations are attributable to a large extent to the influence of the microstructure on bone turnover rate. Mechanical adaptation is found to help preserve intracortical bone matrix near the periosteum. Moreover, it leads to non-uniform cortical wall thickness due to the asymmetry of macroscopic loads introduced by the bending moment. The effect of mechanical adaptation near the endosteum can be greatly affected by whether the mechanical stimulus includes stress concentration effects or not. PMID:26239380

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

    PubMed Central

    2013-01-01

    Background Hwangryun-haedok-tang (HRT) is traditional herbal medicine used to treat inflammatory-related diseases in Asia. However, its effect on osteoclastogenesis and bone loss is still unknown. In this study, we evaluated the effect of HRT and its fermented product (fHRT) on the receptor activator for the nuclear factor-κB ligand-induced osteoclastogenesis using murine bone marrow-derived macrophages and postmenopausal bone loss using an ovariectomy (OVX) rat model. Methods Tartrate resistant acid phosphatase (TRAP) staining was employed to evaluate osteoclast formation. mRNA level of transcription factor and protein levels of signaling molecules were determined by real-time quantitative polymerase chain reaction and Western blot analysis, respectively. Effect of HRT or fHRT on OVX-induced bone loss was evaluated using OVX rats orally administered HRT, or fHRT with 300 mg/kg for 12 weeks. Micro-CT analysis of femora was performed to analyze bone parameter. Results HRT or fHRT treatment significantly decreased TRAP activity and the number of TRAP positive multinuclear cells on osteoclastogenesis. Interestingly, these inhibitory effects of HRT were enhanced by fermentation. Furthermore, fHRT significantly inhibited mRNA and protein expression of nuclear factor of activated T cells cytoplasmic 1, which leads to down-regulation of NFATc1-regulated mRNA expressions such as TRAP, the d2 isoform of vacuolar ATPase V(0) domain, and cathepsin K. Administration of fHRT significantly inhibited the decrease of bone mineral density, and improved bone parameter of femora more than that of HRT and vehicle in OVX rats. Conclusions This study demonstrated that lactic bacterial fermentation fortifies the inhibitory effect of HRT on osteoclastogenesis and bone loss. These results suggest that fermented HRT might have the beneficial potential on osteoporosis by inhibiting osteoclastogenesis. PMID:23680047

  12. Implications of compromised zinc status on bone loss associated with chronic inflammation in C57BL/6 mice

    PubMed Central

    Chongwatpol, Pitipa; Rendina-Ruedy, Elizabeth; Stoecker, Barbara J; Clarke, Stephen L; Lucas, Edralin A; Smith, Brenda J

    2015-01-01

    Compromised zinc status and chronic inflammation are independent factors that can contribute to bone loss. However, zinc’s role in regulating lymphoid and myeloid cell populations, combined with the interplay between the immune and skeletal systems raises the question as to the extent to which a low-grade inflammatory challenge in the context of marginal zinc deficiency would exacerbate bone loss. To address this question, young adult C57BL/6 male mice (n=32) were used in a 2×2 factorial design with dietary zinc (adequate or 35 ppm vs inadequate or −Zn =5 ppm) and lipopolysaccharide (LPS, 0 or 0.1 mg/kg body weight). Mice were fed their respective diets for 10 weeks. On the 6th week, mice had a slow release pellet implanted to induce a low-grade inflammation for the final 4 weeks of the study. −Zn induced a decrease in total white cell counts and peripheral lymphocytes, whereas LPS increased blood monocytes. LPS significantly reduced spine bone mineral density and trabecular bone volume and number of the vertebral body compared with both zinc adequate and inadequate without LPS groups. Likewise, the most pronounced effects on bone strength occurred with LPS, however, −Zn also had negative effects on the bone von Mises stresses. LPS induced an increase in TNF-α and this response was further increased with −Zn. Although the marginal zinc deficiency altered immune function, bone loss was not exacerbated with low-grade chronic inflammation in marginally zinc-deficient young adult mice. These findings demonstrate that in young adult animals an immune challenge modestly increases the inflammatory response and worsens bone biomechanics in the context of a marginal zinc deficiency, but not to the extent that more severe adverse outcomes are observed on bone structural parameters. PMID:26203271

  13. Bone Grafts

    MedlinePlus

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

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

    PubMed

    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. PMID:26549245

  15. Review article: Treatments for bone loss in revision total knee arthroplasty.

    PubMed

    Qiu, Yi Yan; Yan, Chun Hoi; Chiu, Kwong Yuen; Ng, Fu Yuen

    2012-04-01

    Bone deficiency hinders implant alignment and stabilisation of the bone-implant interface in revision total knee arthroplasty (TKA). Treatments for bone defects include bone cement, bone cement with screw reinforcement, metal augments, impaction bone grafts, structural allografts, and tantalum, depending on the location and size of the defects. Small defects are usually treated with cement, cement plus screws, or impaction allograft bone. Large defects are repaired with structural allografts or metal augments. Recent developments involve the use of highly porous osteoconductive tantalum. We reviewed the pros and cons of each method for bone defect management in revision TKA. PMID:22535817

  16. Effect of a CCR1 receptor antagonist on systemic trafficking of MSCs and polyethylene particle-associated bone loss

    PubMed Central

    Gibon, Emmanuel; Yao, Zhenyu; Rao, Allison J.; Zwingenberger, Stefan; Batke, Barbara; Valladares, Roberto; Smith, R. Lane; Biswal, Sandip; Gambhir, Sanjiv S.; Goodman, Stuart B.

    2012-01-01

    Particle-associated periprosthetic osteolysis remains a major issue in joint replacement. Ongoing bone loss resulting from wear particle-induced inflammation is accompanied by continued attempts at bone repair. Previously we showed that mesenchymal stem cells (MSCs) are recruited systemically to bone exposed to continuous infusion of ultra high molecular weight polyethylene (UHMWPE) particles. The chemokine-receptor axis that mediates this process is unknown. We tested two hypotheses: (1) the CCR1 receptor mediates the systemic recruitment of MSCs to UHMWPE particles and (2) recruited MSCs are able to differentiate into functional mature osteoblasts and decrease particle-associated bone loss. Nude mice were allocated randomly to four groups. UHMWPE particles were continuously infused into the femoral shaft using a micro-pump. Genetically modified murine wild type reporter MSCs were injected systemically via the left ventricle. Non-invasive imaging was used to assay MSC migration and bone mineral density. Bioluminescence and immunohistochemistry confirmed the chemotaxis of reporter cells and their differentiation into mature osteoblasts in the presence of infused particles. Injection of a CCR1 antagonist decreased reporter cell recruitment to the UHMWPE particle infusion site and increased osteolysis. CCR1 appears to be a critical receptor for chemotaxis of MSCs in the presence of UHMWPE particles. Interference with CCR1 exacerbates particle-induced bone loss. PMID:22364730

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

    NASA Technical Reports Server (NTRS)

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

    2006-01-01

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

  18. Stepping towards prevention of bone loss after stroke: a systematic review of the skeletal effects of physical activity after stroke.

    PubMed

    Borschmann, Karen; Pang, Marco Y C; Bernhardt, Julie; Iuliano-Burns, Sandra

    2012-06-01

    Bone loss after stroke is pronounced, and contributes to increased fracture risk. People who fracture after stroke experience reduced mobility and increased mortality. Physical activity can maintain or improve bone mineral density and structure in healthy older adults, likely reducing fracture risk. The purpose of this systematic review was to investigate the skeletal effects of physical activity in adults affected by stroke. A search of electronic databases was undertaken. Selection criteria of trials were • prospective and controlled • physical activity-based intervention • participants with history of stroke, and • bone-related outcome measures. Effect sizes were calculated for outcomes of paretic and nonparetic limbs. Three of 349 identified records met the inclusion criteria. Small effect sizes were found in favor of physical activity in adults with chronic stroke (n=95, 40% female, average age 63·8 years, more than one-year poststroke). Patients in intervention groups had significantly higher changes in femoral neck bone mineral density, tibial cortical thickness and trabecular bone mineral content of the paretic limb, compared with controls (P<0·05). It is not known whether these benefits reduced fracture risk. There are limited studies investigating the skeletal effect of physical activity for adults poststroke. Given the increased risk of, and poor outcomes following a fracture after stroke, randomized trials are warranted to investigate the benefits of physical activity on bone, after stroke. Interventions are likely to be beneficial if implemented soon after stroke, when bone loss appears to be rapid and pronounced. PMID:21967614

  19. High-Dose α-Tocopherol Supplementation Does Not Induce Bone Loss in Normal Rats

    PubMed Central

    Kasai, Shunji; Ito, Akemi; Shindo, Kaori; Toyoshi, Tohru; Bando, Masahiro

    2015-01-01

    Oxidative stress affects bone turnover. Preventative effects of antioxidants such as vitamin E on reduced bone mineral density and fractures associated with aging, osteoporosis, and smoking have been examined in animals and humans. The effects of vitamin E (α-tocopherol; αT) on bone health have yielded conflicting and inconclusive results from animal studies. In this study, to determine the bone effects of αT, we investigated the in vivo effects of αT on the bone mineral density, bone mass, bone microstructure, bone resorption, and osteogenesis through peripheral quantitative computed tomography (pQCT) measurements, micro-computed tomography (micro-CT) analyses, and bone histomorphometry of lumbar vertebrae and femurs in normal female Wistar rats fed diets containing αT in different quantities (0, 30, 120, or 600 mg/kg diet) for 8 weeks. To validate our hypotheses regarding bone changes, we examined ovariectomized rats as an osteoporosis model and control sham-operated rats in parallel. As expected, ovariectomized rats had reduced bone mineral density in lumbar vertebrae and the distal metaphyses of their femurs, reduced bone mass and deteriorated microstructure of cancellous bones in the vertebral body and distal femur metaphyses, and reduced bone mass due to resorption-dominant enhanced bone turnover in secondary cancellous bones in these sites. In comparison, αT administered to normal rats, even at the highest dose, did not induce reduced bone mineral density of lumbar vertebrae and femurs or a reduced bone mass or fragile microstructure of cancellous bones of the vertebral body and distal femur metaphyses. Instead, αT-fed rats showed a tendency for an osteogenesis-dominant bone mass increase in secondary cancellous bones in the vertebral body, in which active bone remodeling occurs. Thus, αT consumption may have beneficial effects on bone health. PMID:26147575

  20. High-Dose α-Tocopherol Supplementation Does Not Induce Bone Loss in Normal Rats.

    PubMed

    Kasai, Shunji; Ito, Akemi; Shindo, Kaori; Toyoshi, Tohru; Bando, Masahiro

    2015-01-01

    Oxidative stress affects bone turnover. Preventative effects of antioxidants such as vitamin E on reduced bone mineral density and fractures associated with aging, osteoporosis, and smoking have been examined in animals and humans. The effects of vitamin E (α-tocopherol; αT) on bone health have yielded conflicting and inconclusive results from animal studies. In this study, to determine the bone effects of αT, we investigated the in vivo effects of αT on the bone mineral density, bone mass, bone microstructure, bone resorption, and osteogenesis through peripheral quantitative computed tomography (pQCT) measurements, micro-computed tomography (micro-CT) analyses, and bone histomorphometry of lumbar vertebrae and femurs in normal female Wistar rats fed diets containing αT in different quantities (0, 30, 120, or 600 mg/kg diet) for 8 weeks. To validate our hypotheses regarding bone changes, we examined ovariectomized rats as an osteoporosis model and control sham-operated rats in parallel. As expected, ovariectomized rats had reduced bone mineral density in lumbar vertebrae and the distal metaphyses of their femurs, reduced bone mass and deteriorated microstructure of cancellous bones in the vertebral body and distal femur metaphyses, and reduced bone mass due to resorption-dominant enhanced bone turnover in secondary cancellous bones in these sites. In comparison, αT administered to normal rats, even at the highest dose, did not induce reduced bone mineral density of lumbar vertebrae and femurs or a reduced bone mass or fragile microstructure of cancellous bones of the vertebral body and distal femur metaphyses. Instead, αT-fed rats showed a tendency for an osteogenesis-dominant bone mass increase in secondary cancellous bones in the vertebral body, in which active bone remodeling occurs. Thus, αT consumption may have beneficial effects on bone health. PMID:26147575

  1. Puerarin prevents bone loss in ovariectomized mice and inhibits osteoclast formation in vitro.

    PubMed

    Yuan, Si-Yuan; Sheng, Tong; Liu, Lian-Qi; Zhang, Yun-Ling; Liu, Xue-Mei; Ma, Tao; Zheng, Hong; Yan, Yan; Ishimi, Yoshiko; Wang, Xin-Xiang

    2016-04-01

    The present study aimed at investigating the effects of Puerarin (PR), a major isoflavonoid isolated from the Chinese medicinal herb Puerariae radix, on bone metabolism and the underlying mechanism of action. The in vivo assay, female mice were ovariectomized (OVX), and the OVX mice were fed with a diet containing low, middle, and high doses of PR (2, 4, and 8 mg·d(-1), respectively) or 17β-estradiol (E2, 0.03 μg·d(-1)) for 4 weeks. In OVX mice, the uterine weight declined, and intake of PR at any dose did not affect uterine weight, compared with the control. The total femoral bone mineral density (BMD) was significantly reduced by OVX, which was reversed by intake of the diet with PR at any dose, especially at the low dose. In the in vitro assay, RAW264.7 cells were used for studying the direct effect of PR on the formation of osteoclasts. PR reduced the formation of tartrate resistant acid phosphatase (TRAP)-positive multi-nucleated cells in the RAW 264.7 cells induced by receptor activator for nuclear factor-κB Ligand (RANKL). MC3T3-E1 cells were used for studying the effects of PR on the expression of osteoprotegerin (OPG) and RANKL mRNA expression in osteoblasts. The expression of OPG mRNA and RANKL mRNA was detected by RT-PCR on Days of 5, 7, 10, and 12 after PR exposure. PR time-dependently enhanced the expression of OPG mRNA and reduced the expression of RANKL mRNA in MC3T3-E1 cells. In conclusion, our results suggest that PR can effectively prevent bone loss in OVX mice without any hyperplastic effect on the uterus, and the antiosteoporosis activity of PR may be related to its effects on the formation of osteoclasts and the expression of RANKL OPG in osteoblasts. PMID:27114313

  2. Prevention of bone loss and muscle atrophy during manned space flight.

    PubMed

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

    1992-04-01

    This paper reviews the biomedical literature concerning human adaptation to nonterrestrial environments, and focuses on the definition of practical countermeasures necessary for long-term survival on the Moon, Mars and during long-term space missions and exploration. Of particular importance is the development of clinically relevant countermeasures for prevention of pathophysiological changes in the musculoskeletal and cardiopulmonary systems under these conditions. The countermeasures which are proposed are based upon a combination of biomechanical and theoretical analyses. The biomechanical analyses are based upon clinical measurements of human skeletal density changes associated with weight lifting as well as clinical studies of human strength and fitness currently being conducted using an isoinertial trunk dynamometer. The theoretical analysis stems from a mathematical model for bone loss in altered gravity environments that we have begun to develop. These analyses provide guidelines for the development of practical therapeutic treatments (exercise, artificial gravity) designed to minimize musculoskeletal deconditioning associated with less than Earth gravity environments. Our findings suggest that very intensive exercise, which impose high loads on the musculoskeletal system for brief periods, may be more efficient in preserving bone and skeletal muscle conditioning within "safe" limits for longer periods than low intensity activities such as treadmill running and bicycling. A 1/6 to 1/7-g gravitational environment is predicted to be sufficient to preserve bone strength above the fracture risk level. Basic biomedical support of manned space missions, Moon and Mars bases should include routine assessment of skeletal density, muscle strength, cardiac output and total energy expenditure. This information can be used to periodically re-evaluate exercise programs and or artificial gravity requirements for crew members. PMID:11541051

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

    PubMed

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

    2009-08-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  6. No effect of risedronate on femoral periprosthetic bone loss following total hip arthroplasty

    PubMed Central

    Muren, Olle; Akbarian, Ehsan; Salemyr, Mats; Bodén, Henrik; Eisler, Thomas; Stark, André

    2015-01-01

    Background and purpose We have previously shown that during the first 2 years after total hip arthroplasty (THA), periprosthetic bone resorption can be prevented by 6 months of risedronate therapy. This follow-up study investigated this effect at 4 years. Patients and methods A single-center, double-blind, randomized placebo-controlled trial was carried out from 2006 to 2010 in 73 patients with osteoarthritis of the hip who were scheduled to undergo THA. The patients were randomly assigned to receive either 35 mg risedronate or placebo orally, once a week, for 6 months postoperatively. The primary outcome was the percentage change in bone mineral density (BMD) in Gruen zones 1 and 7 in the proximal part of the femur at follow-up. Secondary outcomes included migration of the femoral stem and clinical outcome scores. Results 61 of the 73 patients participated in this 4-year (3.9- to 4.1-year) follow-up study. BMD was similar in the risedronate group (n = 30) and the placebo group (n = 31). The mean difference was −1.8% in zone 1 and 0.5% in zone 7. Migration of the femoral stem, the clinical outcome, and the frequency of adverse events were similar in the 2 groups. Interpretation Although risedronate prevents periprosthetic bone loss postoperatively, a decrease in periprosthetic BMD accelerates when therapy is discontinued, and no effect is seen at 4 years. We do not recommend the use of risedronate following THA for osteoarthritis of the hip. PMID:25885280

  7. Role of IL-17A signalling in psoriasis and associated bone loss.

    PubMed

    Uluçkan, Özge; Wagner, Erwin F

    2016-01-01

    Inflammation is a physiological reaction to tissue injury, pathogen invasion and a natural response to various stress stimuli. Innate and adaptive immune cells are activated and recruited to the site of inflammation to suppress or promote inflammation. The recruitment and activation of immune cells is modulated by cytokines and chemokines, which are regulated by transcription factors, such as AP-1 (Fos/Jun), NF-kB, NFATs and STATs. Moreover, it is now appreciated that chronic inflammation can lead to systemic effects affecting the whole organism by mechanisms which are not well understood.Here we review our recent data obtained from the analyses of psoriasis patient samples as well as from AP-1 (Fos/Jun)-dependent, genetically engineered mouse models. The deletion of two AP-1 factors JunB and c-Jun in an inducible manner in adult mice, specifically in Keratin-5 expressing tissues, leads to a psoriasis-like disease. Importantly, the epidermal proteome of the mutant mice is comparable to psoriasis patient samples. Our analyses revealed that the activation of S100A8/A9-dependent C3 complement as well as a miR-21-dependent TIMP-3/TACE pathway leading to TNF-α shedding, are causally involved in disease development.Epidermal deletion of only JunB in mice leads to chronic skin inflammation with increased levels of pro-inflammatory cytokines and multi-organ involvement. Our recent findings show that chronic skin inflammation induces bone loss through systemic elevated IL-17A signalling. This novel mechanism involves inhibition of osteoblast-mediated bone formation by reduced Wnt signalling with no effect on RANKL-dependent osteoclastic bone resorption. These data have important translational implications; blocking of IL-17A signalling, which is already approved for the treatment of psoriasis, should also be considered to prevent the adverse skeletal consequences of chronic inflammatory diseases. PMID:27586798

  8. Osteoblast Lineage Cells Play an Essential Role in Periodontal Bone Loss Through Activation of Nuclear Factor-Kappa B

    PubMed Central

    Pacios, Sandra; Xiao, Wenmei; Mattos, Marcelo; Lim, Jason; Tarapore, Rohinton S.; Alsadun, Sarah; Yu, Bo; Wang, Cun-Yu; Graves, Dana T.

    2015-01-01

    Bacterial pathogens stimulate periodontitis, the most common osteolytic disease in humans and the most common cause of tooth loss in adults. Previous studies identified leukocytes and their products as key factors in this process. We demonstrate for the first time that osteoblast lineage cells play a critical role in periodontal disease. Oral infection stimulated nuclear localization of NF-κB in osteoblasts and osteocytes in the periodontium of wild type but not transgenic mice that expressed a lineage specific dominant negative mutant of IKK (IKK-DN) in osteoblast lineage cells. Wild-type mice were also susceptible to bacteria induced periodontal bone loss but transgenic mice were not. The lack of bone loss in the experimental group was linked to reduced RANKL expression by osteoblast lineage cells that led to diminished osteoclast mediated bone resorption and greater coupled new bone formation. The results demonstrate that osteoblast lineage cells are key contributors to periodontal bone loss through an NF-κB mediated mechanism. PMID:26666569

  9. A Modest Protective Effect of Thyrotropin against Bone Loss Is Associated with Plasma Triiodothyronine Levels

    PubMed Central

    Kang, Mira; Choi, Sun Kyu; Kim, Kyunga; Jang, Ju Young; Cho, Yoon Young; Min, Yong-Ki; Chung, Jae Hoon; Kim, Sun Wook

    2015-01-01

    Background The independent skeletal effect of thyrotropin (thyroid stimulating hormone, TSH) has been suggested in animal studies. However, clinical data on the association between bone loss and variations in TSH levels is inconsistent. This study aimed to investigate the relationship between TSH levels and bone mineral density (BMD). Methods We conducted a cross-sectional study with 37,431 subjects (33,052 cases with euthyroidism and 4,379 cases with subclinical thyroid dysfunction) aged over 35 years. We performed thyroid function tests and measured BMD at the lumbar spine, femur neck, and total hip. Results Levels of TSH and T3 were positively correlated in women (r = 0.076, P = 0.001) and uncorrelated in men. In both men and women, TSH levels correlated positively and T3 levels correlated negatively with BMD at all skeletal sites in age and body mass index adjusted analyses. BMD increased steadily with TSH levels from the subclinical hyperthyroid to subclinical hypothyroid range in subjects with T3 levels in the highest tertile (119.5–200.0 ng/dL), but was no longer significant in subjects with lower plasma T3 levels. Conclusions The variations in TSH levels within the euthyroid and subclinical range were positively correlated with BMD in healthy men and women. The negative effect of T3 on BMD appears to be compensated for by increased TSH in subjects with plasma T3 levels in the upper normal range. PMID:26679692

  10. Hif1α is required for osteoclast activation and bone loss in male osteoporosis.

    PubMed

    Tando, Toshimi; Sato, Yuiko; Miyamoto, Kana; Morita, Mayu; Kobayashi, Tami; Funayama, Atsushi; Kanaji, Arihiko; Hao, Wu; Watanabe, Ryuichi; Oike, Takatsugu; Nakamura, Masaya; Matsumoto, Morio; Toyama, Yoshiaki; Miyamoto, Takeshi

    2016-02-01

    The number of osteoporosis patients is increasing not only in women but in men. Male osteoporosis occurs due to aging or androgen depletion therapies, leading to fractures. However, molecular mechanisms underlying male osteoporosis remain unidentified. Here, we show that hypoxia inducible factor 1 alpha (Hif1α) is required for development of testosterone deficiency-induced male osteoporosis. We found that in mice Hif1α protein accumulates in osteoclasts following orchidectomy (ORX) in vivo. In vitro, Hif1α protein accumulated in osteoclasts cultured in hypoxic conditions, but Hif1α protein rather than mRNA levels were suppressed by testosterone treatment, even in hypoxia. Administration of a Hif1α inhibitor to ORX mice abrogated testosterone deficiency-induced osteoclast activation and bone loss but did not alter osteoclast activities or bone phenotypes in sham-operated, testosterone-sufficient animals. We conclude that Hif1α protein accumulation due to testosterone-deficiency promotes development of male osteoporosis. Thus Hif1α protein could be targeted to inhibit pathologically-activated osteoclasts under testosterone-deficient conditions to treat male osteoporosis patients. PMID:26792721

  11. Assessment of phalangeal bone loss in patients with rheumatoid arthritis by quantitative ultrasound

    PubMed Central

    Roben, P; Barkmann, R; Ullrich, S; Gause, A; Heller, M; Gluer, C

    2001-01-01

    OBJECTIVE—Periarticular osteopenia is an early radiological sign of rheumatoid arthritis (RA). Quantitative ultrasound (QUS) devices have recently been shown to be useful for assessing osteoporosis. In this study the capability of a transportable and easy to use QUS device to detect skeletal impairment of the finger phalanges in patients with RA was investigated.
METHODS—In a cross sectional study 83 women (30 controls, 29 with glucocorticosteroid (GC) treated RA, and 24 with GC treated vasculitis) were examined. QUS measurements were obtained at the metaphyses of the proximal phalanges II-V and directly at the proximal interphalangeal joints II-IV with a DBM Sonic 1200 (IGEA, Italy) QUS device. Amplitude dependent speed of sound (AD-SoS) was evaluated. In 23 of the patients with RA, hand radiographs were evaluated.
RESULTS—Significant differences between patients with RA and the other groups were found for AD-SoS at both measurement sites. Compared with age matched controls, the AD-SoS of patients with RA was lowered by two and three standard deviations at the metaphysis and joint, respectively. Fingers of patients with RA without erosions (Larsen score 0-I) already had significantly decreased QUS values, which deteriorated further with the development of erosions (Larsen II-V).
CONCLUSION—This study indicates that QUS is sensitive to phalangeal periarticular bone loss in RA. QUS is a quick, simple, and inexpensive method free of ionising radiation that appears to be suited to detection of early stages of periarticular bone loss. Its clinical use in the assessment of early RA should be further evaluated in prospective studies.

 PMID:11406521

  12. Phalangeal quantitative ultrasound and bone mineral density in evaluating cortical bone loss: a study in postmenopausal women with primary hyperparathyroidism and subclinical iatrogenic hyperthyroidism.

    PubMed

    Cipriani, Cristiana; Romagnoli, Elisabetta; Scarpiello, Addolorata; Angelozzi, Maurizio; Montesano, Teresa; Minisola, Salvatore

    2009-01-01

    Twenty-five postmenopausal women with primary hyperparathyroidism (PHPT) and 30 age-matched women with subclinical hyperthyroidism (sHTH) were studied to assess cortical bone loss. One hundred two healthy women were also recruited. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at lumbar spine (LS), femoral neck (FN) and femoral total (FT), and at one-third of the radius (R). Amplitude-dependent speed of sound (ADSoS) and Ultrasound Bone Profile Index (UBPI) were also evaluated using phalangeal quantitative ultrasound (QUS). A significant correlation was found between QUS and BMD at LS (ADSoS, p < 0.05) and R (ADSoS and UBPI, p < 0.001) in controls. QUS significantly correlated with BMD at LS, FN (p < 0.01), and FT (p < 0.001) in sHTH. No correlations were found in the PHPT group. Mean T-score values of all parameters were significantly lower in patients compared with controls (p < 0.001); however, they did not differ between PHPT and sHTH patients. T-score of R, ADSoS, and UBPI was reduced compared with other sites (p < 0.001) in both diseases. In postmenopausal women with PHPT and sHTH, bone loss is mainly detectable at cortical level. However, qualitative and/or structural changes of bone could account for the lack of correlations between these 2 techniques at cortical sites. PMID:19815437

  13. Periprosthetic bone loss in total hip arthroplasty. Polyethylene wear debris and the concept of the effective joint space.

    PubMed

    Schmalzried, T P; Jasty, M; Harris, W H

    1992-07-01

    Thirty-four hips in which there had been prosthetic replacement were selected for study because of the presence of linear (diffuse) or lytic (localized) areas of periprosthetic bone loss. In all hips, there was careful documentation of the anatomical location of the material that had been obtained for histological analysis, and the specific purpose of the removal of the tissue was for examination to determine the cause of the resorption of bone. Specimens from twenty-three hips were retrieved during an operation and from eleven hips, at autopsy. The area of bone loss was linear only in sixteen hips, lytic only in thirteen, and both linear and lytic in five. In all thirty-four hips, intracellular particulate debris was found in the macrophages that were present in the area of bone resorption. All thirty-four had intracellular particles of polyethylene, many of which were less than one micrometer in size. Thirty-one hips had extracellular particles of polyethylene as well. Twenty-two of the thirty-four hips had intracellular metallic debris; in ten, metallic debris was found extracellularly as well. Ten of the sixteen cemented specimens had intracellular and extracellular polymethylmethacrylate debris. In the mechanically stable prostheses--cemented and uncemented--polyethylene wear debris was identified in areas of bone resorption far from the articular surfaces. The number of macrophages in a microscopic field was directly related to the amount of particulate polyethylene debris that was visible by light microscopy. Although the gross radiographic appearances of linear bone loss and lytic bone loss were different, the histological appearance of the regions in which there was active bone resorption was similar. Regardless of the radiographic appearance and anatomical origin of the specimen, bone resorption was found to occur in association with macrophages that were laden with polyethylene debris. In general, the number of macrophages present had a direct

  14. Inhibiting myostatin signaling prevents femoral trabecular bone loss and microarchitecture deterioration in diet-induced obese rats.

    PubMed

    Tang, Liang; Yang, Xiaoying; Gao, Xiaohang; Du, Haiping; Han, Yanqi; Zhang, Didi; Wang, Zhiyuan; Sun, Lijun

    2016-02-01

    Besides resulting in a dramatic increase in skeletal muscle mass, myostatin (MSTN) deficiency has a positive effect on bone formation. However, the issue about whether blocking MSTN can inhibit obesity-induced bone loss has not been previously investigated. In the present study, we have evaluated the effects of MSTN blocking on bone quality in high-fat (HF), diet-induced obese rats using a prepared polyclonal antibody for MSTN (MsAb). Twenty-four rats were randomly assigned to the Control, HF and HF + MsAb groups. Rats in the HF + MsAb group were injected once a week with purified MsAb for eight weeks. The results showed that MsAb significantly reduced body and fat weight, and increased muscle mass and strength in the HF group. MicroCT analysis demonstrated that obesity-induced bone loss and architecture deterioration were significantly mitigated by MsAb treatment, as evidenced by increased bone mineral density, bone volume over total volume, trabecular number and thickness, and decreased trabecular separation and structure model index. However, neither HF diet nor MsAb treatment had an impact on femoral biomechanical properties including maximum load, stiffness, energy absorption and elastic modulus. Moreover, MsAb significantly increased adiponectin concentrations, and decreased TNF-α and IL-6 levels in diet-induced obese rats. Taken together, blocking MSTN by MsAb improves bone quality in diet-induced obese rats through a mechanotransduction pathway from skeletal muscle, and the accompanying changes occurring in the levels of circulating adipokines and pro-inflammatory cytokines may also be involved in this process. It indicates that the administration of MSTN antagonists may be a promising therapy for treating obesity and obesity-induced bone loss. PMID:26438721

  15. The soy-associated phytoestrogen, genistein, does not protect against alcohol induced osteoporosis in male mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Alcohol abuse acts as a risk factor for osteoporosis by increasing osteoclast activity and decreasing osteoblast activity in bone. These effects can be reversed by estradiol. Soy diets are also suggested to have protective effects on bone loss in men and women, as a result of the presence of soy pro...

  16. Arterialized Venous Bicarbonate Is Associated With Lower Bone Mineral Density and an Increased Rate of Bone Loss in Older Men and Women

    PubMed Central

    Tabatabai, L. S.; Cummings, S. R.; Tylavsky, F. A.; Bauer, D. C.; Cauley, J. A.; Kritchevsky, S. B.; Newman, A.; Simonsick, E. M.; Harris, T. B.; Sebastian, A.

    2015-01-01

    Context: Higher dietary net acid loads have been associated with increased bone resorption, reduced bone mineral density (BMD), and increased fracture risk. Objective: The objective was to compare bicarbonate (HCO3) measured in arterialized venous blood samples to skeletal outcomes. Design: Arterialized venous samples collected from participants in the Health, Aging and Body Composition (Health ABC) Study were compared to BMD and rate of bone loss. Setting: The setting was a community-based observational cohort. Participants: A total of 2287 men and women age 74 ± 3 years participated. Intervention: Arterialized venous blood was obtained at the year 3 study visit and analyzed for pH and pCO2. HCO3 was determined using the Henderson-Hasselbalch equation. Main Outcome Measure: BMD was measured at the hip by dual-energy x-ray absorptiometry at the year 1 (baseline) and year 3 study visits. Results: Plasma HCO3 was positively associated with BMD at both year 1 (P = .001) and year 3 (P = .001) in models adjusted for age, race, sex, clinic site, smoking, weight, and estimated glomerular filtration rate. Plasma HCO3 was inversely associated with rate of bone loss at the total hip over the 2.1 ± 0.3 (mean ± SD) years between the two bone density measurements (P < .001). Across quartiles of plasma HCO3, the rate of change in BMD over the 2.1 years ranged from a loss of 0.72%/y in the lowest quartile to a gain of 0.15%/y in the highest quartile of HCO3. Conclusions: Arterialized plasma HCO3 was associated positively with cross-sectional BMD and inversely with the rate of bone loss, implying that systemic acid-base status is an important determinant of skeletal health during aging. Ongoing bone loss was linearly related to arterialized HCO3, even after adjustment for age and renal function. Further research in this area may have major public health implications because reducing dietary net acid load is possible through dietary intervention or through supplementation with

  17. Loss of milk fat globule-epidermal growth factor 8 (MFG-E8) in mice leads to low bone mass and accelerates ovariectomy-associated bone loss by increasing osteoclastogenesis.

    PubMed

    Sinningen, Kathrin; Albus, Elise; Thiele, Sylvia; Grossklaus, Sylvia; Kurth, Thomas; Udey, Mark C; Chavakis, Triantafyllos; Hofbauer, Lorenz C; Rauner, Martina

    2015-07-01

    Milk fat globule-epidermal growth factor 8 (MFG-E8) is a glycoprotein that controls the engulfment of apoptotic cells and exerts inflammation-modulatory effects. Recently, it has been implicated in osteoclastogenesis and the pathogenesis of inflammatory periodontal bone loss, but its role in physiological bone homeostasis is still not well defined. Here, we evaluated the influence of MFG-E8 on osteoblasts and osteoclasts and its impact on bone remodeling in healthy and ovariectomized mice as a model for post-menopausal osteoporosis. Total and trabecular bone mineral densities at the lumbar spine in 6-week-old MFG-E8 KO mice were reduced by 11% (p < 0.05) and 17% (p < 0.01), respectively, as compared to wild-type (WT) mice. Accordingly, serum levels of the bone formation marker P1NP were decreased by 37% (p < 0.01) in MFG-E8 KO mice as were the ex vivo mineralization capacity and expression of osteoblast genes (Runx2, alkaline phosphatase, osteocalcin) in MFG-E8 KO osteoblasts. In contrast, serum bone resorption markers CTX1 and TRAP5b were increased by 30% and 60% (p < 0.05), respectively, in MFG-E8 KO mice. Furthermore, bone marrow macrophages from MFG-E8-KO mice differentiated more effectively into osteoclasts, as compared to WT cells. MFG-E8-deficient osteoclasts displayed increased bone resorption ex vivo, which could be reversed by the presence of recombinant MFG-E8. To determine the significance of the enhanced osteoclastogenesis in MFG-E8 KO mice, we performed an ovariectomy, which is associated with bone loss due to increased osteoclast activity. Indeed, MFG-E8 KO mice lost 12% more trabecular bone density than WT mice after ovariectomy. Together, these data indicate that MFG-E8 controls steady-state and pathological bone turnover and may therefore represent a new target gene in the treatment of bone diseases. PMID:25868798

  18. Operative findings of conductive hearing loss with intact tympanic membrane and normal temporal bone computed tomography.

    PubMed

    Kim, Se-Hyung; Cho, Yang-Sun; Kim, Hye Jeong; Kim, Hyung-Jin

    2014-06-01

    Despite recent technological advances in diagnostic methods including imaging technology, it is often difficult to establish a preoperative diagnosis of conductive hearing loss (CHL) in patients with an intact tympanic membrane (TM). Especially, in patients with a normal temporal bone computed tomography (TBCT), preoperative diagnosis is more difficult. We investigated middle ear disorders encountered in patients with CHL involving an intact TM and normal TBCT. We also analyzed the surgical results with special reference to the pathology. We reviewed the medical records of 365 patients with intact TM, who underwent exploratory tympanotomy for CHL. Fifty nine patients (67 ears, eight bilateral surgeries) had a normal preoperative TBCT findings reported by neuro-radiologists. Demographic data, otologic history, TM findings, preoperative imaging findings, intraoperative findings, and pre- and postoperative audiologic data were obtained and analyzed. Exploration was performed most frequently in the second and fifth decades. The most common postoperative diagnosis was stapedial fixation with non-progressive hearing loss. The most commonly performed hearing-restoring procedure was stapedotomy with piston wire prosthesis insertion. Various types of hearing-restoring procedures during exploration resulted in effective hearing improvement, especially with better outcome in the ossicular chain fixation group. In patients with CHL who have intact TM and normal TBCT, we should consider an exploratory tympanotomy for exact diagnosis and hearing improvement. Information of the common operative findings from this study may help in preoperative counseling. PMID:23744181

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

    PubMed

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

    2015-11-01

    The nutritional benefits of pomegranate have attracted great scientific interest. The pomegranate, including the pomegranate peel, has been used worldwide for many years as a fruit with medicinal activity, mostly antioxidant properties. Among chronic diseases, osteoporosis, which is associated with bone remodelling impairment leading to progressive bone loss, could eventually benefit from antioxidant compounds because of the involvement of oxidative stress in the pathogenesis of osteopenia. In this study, with in vivo and ex vivo experiments, we investigated whether the consumption of pomegranate peel extract