Risk of Fracture in Women with Sarcopenia, Low Bone Mass, or Both.
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ABSTRACT:
SUBMITTER: Harris R
PROVIDER: S-EPMC5729083 | biostudies-literature | 2017 Dec
REPOSITORIES: biostudies-literature
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Risk of Fracture in Women with Sarcopenia, Low Bone Mass, or Both.
Harris Rebekah R Chang Yuefang Y Beavers Kristen K Laddu-Patel Deepika D Bea Jennifer J Johnson Karen K LeBoff Meryl M Womack Catherine C Wallace Robert R Li Wenjun W Crandall Carolyn C Cauley Jane J
Journal of the American Geriatrics Society 20170927 12
<h4>Objectives</h4>To determine whether women with sarcopenia and low bone mineral density (BMD) are at greater risk of clinical fractures than those with sarcopenia or low BMD alone.<h4>Design</h4>Women's Health Initiative (WHI) Observational and Clinical trials.<h4>Setting</h4>Three U.S. clinical centers (Pittsburgh, PA; Birmingham, AL; Phoenix/Tucson, AZ).<h4>Participants</h4>Women (mean age 63.3 ± 0.07) with BMD measurements (N = 10,937).<h4>Measurements</h4>Sarcopenia was defined as appendi ...[more]
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Project description:PurposeA major challenge in osteoporosis is to identify individuals at high fracture risk. We investigated six bone turnover markers (BTMs) to determine association with specific fracture types; the time-frame for risk prediction and whether these are influenced by age at assessment.MethodsPopulation-based OPRA cohort (n = 1044) was assessed at ages 75, 80, 85 and fractures documented for up to 15 years. Six BTMs were analyzed at each time-point (N-terminal propeptide of type I collagen, PINP; total osteocalcin, OC; bone-specific alkaline phosphatase, BALP; C-terminal telopeptide of type I collagen, CTX; tartrate-resistant acid phosphatase 5b, TRAcP5b; urinary osteocalcin). Hazard ratios (HR) for any, major osteoporotic, vertebral and hip fractures were calculated as short (1, 2, 3 years) and long-term risk (5, 10, 15 years).ResultsAt 75 year, high CTX levels were associated with an increased risk of all fractures, including major osteoporotic fractures, across most time-frames (HRs ranging: 1.28 to 2.28). PINP was not consistently associated. Urinary osteocalcin was consistently associated with elevated short-term risk (HRs ranging: 1.83-2.72). Other BTMs were directionally in accordance, though not all statistically significant. BTMs were not predictive for hip fractures. Association of all BTMs attenuated over time; at 80 year none were associated with an increased fracture risk.ConclusionCTX, urinary OC and TRAcP5b are predictive for fracture in a 1 to 3 year, perspective, whereas in the long-term or above age 80 years, BTMs appear less valuable. Resorption markers, particularly CTX, were more consistently associated with fracture risk than formation markers in the very elderly.
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Project description:Objective:To study the association between osteoporosis and sarcopenia and determine the prevalence of osteosarcopenia in patients who attended a rheumatology center in Ecuador. Methods:A cross-sectional study was conducted in a population of patients who had a densitometric study. The diagnosis of sarcopenia was determined by the DXA standard gold test, screening, and conventional methods (bioimpedance, anthropometric measurements, SARC-F, muscle function, and gait test). Results:A total of 92 patients were studied. The median age was 66?±?10, 90% females. Using the criteria of SMI, 65% had sarcopenia of which 9% had only sarcopenia and 56% had osteosarcopenia; 22% had only osteopenia/osteoporosis; and 13% none of these conditions. The prevalence of sarcopenia according to handgrip strength was 60%, gait speed 45%, and SARC-F score 40%. The prevalence of osteosarcopenia according to handgrip strength was 51%, gait speed 34%, and SARC-F score 32%. Osteoporosis was associated with a higher prevalence of sarcopenia using the criteria of SMI since 40% had sarcopenia in the normal DXA group, 64% in the osteopenia group, and 76% in the osteoporosis group (p=0.017). Of the women, 69% had sarcopenia compared to 33% of the men (p=0.034). The BMI was lower in the group with sarcopenia (25.1?±?4.1?kg/m2) compared to the group without sarcopenia (29.4?±?4.1?kg/m2, p < 0.001). Patients with osteosarcopenia and sarcopenia had lower BMI, handgrip strength, ASM, SMI, and total-body skeletal muscle mass than those with osteopenia/osteoporosis or normal patients. Conclusion:65% of the studied population had sarcopenia. It is clear that the prevalence of sarcopenia is higher in patients with greater loss of bone mass. Identifying pathways that affect both bone and muscle could facilitate the development of treatments that simultaneously improve osteoporosis and sarcopenia.
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Project description:Individuals with Down syndrome (DS), the result of trisomy of human chromosome Hsa21 (Ts21), present with an array of skeletal abnormalities typified by altered craniofacial features, short stature and low bone mineral density (BMD). While bone deficits progress with age in both sexes, low bone mass is more pronounced in DS men than women and osteopenia appears earlier. In the current study, the reproductive hormone status (FSH, LH, testosterone) of 17 DS patients (males, ages range 19-52 years) was measured. Although testosterone was consistently low, the hypothalamic-pituitary-gonadal axis was intact with corresponding rises in FSH and LH. To provide further insight into the heterogeneity of the bone mass in DS, the skeletal phenotypes of three of the most used murine DS models, Ts65Dn (Ts65), TC1, and Dp16(Yey1) (Dp16) were characterized and contrasted. Evaluation of the bone phenotype of both male and female 3-month-old Dp16 mice demonstrated sexual dimorphism, with low bone mass apparent in males, as it is in Ts65, but not in female Dp16. In contrast, male TC1 mice had no apparent bone phenotype. To determine whether low bone mass in DS impacted fracture healing, fractures of the middle phalanx (P2) digits were generated in both male and female Dp16 mice at 15 weeks of age, an age where the sexually dimorphic low BMD persisted. Fracture healing was assessed via in vivo microCT over (13 weeks) 93 days post fracture (DPF). At 93 DPF, 0 % of DS male (n = 12) or female (n = 8) fractures healed, compared to 50 % of the male (n = 28) or female (n = 8) WT littermate fractures. MicroCT revealed periosteal unbridged mineralized callus formation across the fracture gap in Dp16 mice, which was confirmed by subsequent histology. These studies provide the first direct evidence of significantly impaired fracture healing in the setting of DS.
| S-EPMC9356441 | biostudies-literature
Project description:ImportanceRepeated bone mineral density (BMD) testing to screen for osteoporosis requires resources. For patient counseling and optimal resource use, it is important for clinicians to know whether repeated BMD measurement (compared with baseline BMD measurement alone) improves the ability to discriminate between postmenopausal women who will and will not experience a fracture.ObjectiveTo assess whether a second BMD measurement approximately 3 years after the initial assessment is associated with improved ability to estimate fracture risk beyond the baseline BMD measurement alone.Design, setting, and participantsThe Women's Health Initiative is a prospective observational study. Participants in the present cohort study included 7419 women with a mean (SD) follow-up of 12.1 (3.4) years between 1993 and 2010 at 3 US clinical centers. Data analysis was conducted between May 2019 and December 2019.Main outcomes and measuresIncident major osteoporotic fracture (ie, hip, clinical spine, forearm, or shoulder fracture), hip fracture, baseline BMD, and absolute change in BMD were assessed. The area under the receiver operating characteristic curve (AU-ROC) for baseline BMD, absolute change in BMD, and the combination of baseline BMD and change in BMD were calculated to assess incident fracture risk discrimination during follow-up.ResultsOf 7419 participants, the mean (SD) age at baseline was 66.1 (7.2) years, the mean (SD) body mass index was 28.7 (6.0), and 1720 (23%) were nonwhite individuals. During the study follow-up (mean [SD] 9.0 [3.5] years after the second BMD measurement), 139 women (1.9%) experienced hip fractures, and 732 women (9.9%) experienced major osteoporotic fracture. In discriminating between women who experience hip fractures and those who do not, AU-ROC values were 0.71 (95% CI, 0.67-0.75) for baseline total hip BMD, 0.61 (95% CI, 0.56-0.65) for change in total hip BMD, and 0.73 (95% CI, 0.69-0.77) for the combination of baseline total hip BMD and change in total hip BMD. Femoral neck and lumbar spine BMD values had similar discrimination for hip fracture. For discrimination of major osteoporotic fracture, AU-ROC values were 0.61 (95% CI, 0.59-0.63) for baseline total hip BMD, 0.53 (95% CI, 0.51-0.55) for change in total hip BMD, and 0.61 (95% CI, 0.59-0.63) for the combination of baseline total hip BMD and change in total hip BMD. Femoral neck and lumbar spine BMD values had similar ability to discriminate between women who experienced major osteoporotic fracture and those who did not. Associations between change in bone density and fracture risk did not differ by subgroup, including diabetes, age, race/ethnicity, body mass index, or baseline BMD T score.Conclusions and relevanceThe findings of this study suggest that a second BMD assessment approximately 3 years after the initial measurement was not associated with improved discrimination between women who did and did not experience subsequent hip fracture or major osteoporotic fracture beyond the baseline BMD value alone and should not routinely be performed.
| S-EPMC7385675 | biostudies-literature
Project description:Osteoporosis is a skeletal disorder characterized by compromised bone strength and increased risk of fracture. Low bone mass and/or pre-existing bone fragility fractures serve as diagnostic criteria in deciding when to start medication for osteoporosis. Although osteoporosis is a metabolic disorder, metabolic markers to predict reduced bone mass are unknown. Here, we show serum metabolomics profiles of women grouped as pre-menopausal with normal bone mineral density (BMD) (normal estrogen and normal BMD; NN), post-menopausal with normal BMD (low estrogen and normal BMD; LN) or post-menopausal with low BMD (low estrogen and low BMD; LL) using comprehensive metabolomics analysis. To do so, we enrolled healthy volunteer and osteoporosis patient female subjects, surveyed them with a questionnaire, measured their BMD, and then undertook a comprehensive metabolomics analysis of sera of the three groups named above. We identified 24 metabolites whose levels differed significantly between NN/LN and NN/LL groups, as well as 18 or 10 metabolites whose levels differed significantly between NN/LN and LN/LL, or LN/LL and NN/LN groups, respectively. Our data shows metabolomics changes represent useful markers to predict estrogen deficiency and/or bone loss.
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Project description:INTRODUCTION:Antiresorptive medications increase bone density and decrease vertebral fracture, while high-intensity resistance and impact training (HiRIT) increases balance, bone and muscle strength decreasing risk for falls and fractures. Medications are typically prescribed by doctors and exercise by exercise specialists, frequently in isolation. OBJECTIVE:Our primary aim is to determine the effect of an 8-month HiRIT programme with or without osteoporosis medications on bone mineral density (BMD) of the spine and hip in postmenopausal women with low bone mass. METHODS AND ANALYSIS:One hundred and sixty postmenopausal women with low bone mass will be recruited from the community to participate in an 8-month randomised controlled trial. Participants will be on stable doses of antiresorptive bone medication for at least 12 months (n=80) or have not taken bone medications for at least 12 months (n=80). Participants will be block randomised, stratified by medication intake, to twice-weekly 40-min supervised sessions of HiRIT or a low-intensity exercise programme (control). Primary outcomes include change in lumbar spine and total hip areal bone mineral density. Secondary outcomes include whole body, femoral neck and forearm BMD, proximal femur bone geometry and volumetric density, vertebral morphology, body composition, anthropometry, physical function, posture, rate of falls, osteoarthritis symptoms, pelvic floor health, quality of life, physical activity enjoyment, resting blood pressure, safety and compliance. All outcomes will be assessed at baseline and 8 months and intention-to-treat and per-protocol analyses will be conducted. Repeated measure analysis of covariance will be used to determine intervention effects on outcome measures, controlling for initial values, compliance and other variables found to differ between groups at baseline. ETHICS AND DISSEMINATION:The study has been approved by Griffith University Human Research Ethics Committee (Ref: 2017/739). Results will be reported in peer-reviewed journals and at conferences. TRIAL REGISTRATION NUMBER:Australian New Zealand Clinical Trials Registry (ACTRN12617001511325).
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Project description:The Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH) trial (NCT01631214; https://clinicaltrials.gov/ct2/show/NCT01631214) showed that romosozumab for 1 year followed by alendronate led to larger areal bone mineral density (aBMD) gains and superior fracture risk reduction versus alendronate alone. aBMD correlates with bone strength but does not capture all determinants of bone strength that might be differentially affected by various osteoporosis therapeutic agents. We therefore used quantitative computed tomography (QCT) and finite element analysis (FEA) to assess changes in lumbar spine volumetric bone mineral density (vBMD), bone volume, bone mineral content (BMC), and bone strength with romosozumab versus alendronate in a subset of ARCH patients. In ARCH, 4093 postmenopausal women with severe osteoporosis received monthly romosozumab 210 mg sc or weekly oral alendronate 70 mg for 12 months, followed by open-label weekly oral alendronate 70 mg for ≥12 months. Of these, 90 (49 romosozumab, 41 alendronate) enrolled in the QCT/FEA imaging substudy. QCT scans at baseline and at months 6, 12, and 24 were assessed to determine changes in integral (total), cortical, and trabecular lumbar spine vBMD and corresponding bone strength by FEA. Additional outcomes assessed include changes in aBMD, bone volume, and BMC. Romosozumab caused greater gains in lumbar spine integral, cortical, and trabecular vBMD and BMC than alendronate at months 6 and 12, with the greater gains maintained upon transition to alendronate through month 24. These improvements were accompanied by significantly greater increases in FEA bone strength (p < 0.001 at all time points). Most newly formed bone was accrued in the cortical compartment, with romosozumab showing larger absolute BMC gains than alendronate (p < 0.001 at all time points). In conclusion, romosozumab significantly improved bone mass and bone strength parameters at the lumbar spine compared with alendronate. These results are consistent with greater vertebral fracture risk reduction observed with romosozumab versus alendronate in ARCH and provide insights into structural determinants of this differential treatment effect. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
| S-EPMC9292813 | biostudies-literature
Project description:Background & aims Sarcopenia is an age-related disease that increases the risk of falls and fractures in older adults. However, there is no blood biochemical marker to help to predict or diagnose sarcopenia in clinical practice. Soluble interleukin 2 receptor (sIL-2R) was reported to be associated with muscle satellite cell dysfunction which played an important role in the pathogenesis of sarcopenia. Thereby, we aimed to explore the association between serum sIL-2R and sarcopenia in older adults at high risk of fractures. Methods A total of 429 hospitalized older adults (age ≥55 years) were enrolled in this cross-sectional study (mean age = 66.62 ± 6.59 years; 62.7% female). Logistic regression analysis was performed to assess the association of sIL-2R with sarcopenia, muscle mass, muscle strength, and physical performance, respectively. The optimal models for the diagnosis of sarcopenia and low hand grip strength (HGS) were established by multivariable binary logistic regression analysis with backward selection, and further were evaluated for the diagnostic values by receiver operating characteristic (ROC) curve. Results Higher sIL-2R levels were found in sarcopenia than no-sarcopenia group in male (median 421 U/mL (interquartile range [IQR] 217 U/mL) vs median 362 U/mL (IQR 157 U/mL); n = 77 vs 83; p < 0.01). Compared to the lowest sIL-2R tertile, the highest tertile of sIL-2R was independently associated with the risk of low HGS (odds ratio [OR] 4.608, 95% confidence interval [CI] 1.673–12.695) and the risk of sarcopenia (OR 3.306, 95% CI 1.496–7.302) in men. ROC curves revealed that the Area Under the Curve (AUC) of the optimal models for diagnosing sarcopenia and low HGS was 0.752 and 0.846. Conclusion Our results suggest that serum sIL-2R is the independent risk factor for sarcopenia and low muscle strength only in men. sIL-2R may be developed to be a biochemical marker for sarcopenia and low muscle strength diagnoses in older men at high risk of fractures, but more prospective studies are needed to prove it. The translational potential of this article Our results showed that the highest tertile of sIL-2R was independent of low risk of HGS and sarcopenia in men, compared to the lowest tertile. As the population ages, sIL-2R may become a potential diagnostic tool for predicting low HGS and sarcopenia among men at high risk of fractures.
| S-EPMC9674866 | biostudies-literature
Project description:Among 377,561 female Medicare beneficiaries who sustained a fracture, 10% had another fracture within 1 year, 18% within 2 years, and 31% within 5 years. Timely management to reduce risk of subsequent fracture is warranted following all nontraumatic fractures, including nonhip nonvertebral fractures, in older women.IntroductionPrior fracture is a strong predictor of subsequent fracture; however, postfracture treatment rates are low. Quantifying imminent (12-24 month) risk of subsequent fracture in older women may clarify the need for early postfracture management.MethodsThis retrospective cohort study used Medicare administrative claims data. Women ≥ 65 years who sustained a clinical fracture (clinical vertebral and nonvertebral fracture; index date) and were continuously enrolled for 1-year pre-index and ≥ 1-year (≥ 2 or ≥ 5 years for outcomes at those time points) post-index were included. Cumulative incidence of subsequent fracture was calculated from 30 days post-index to 1, 2, and 5 years post-index. For appendicular fractures, only those requiring hospitalization or surgical repair were counted. Death was considered a competing risk.ResultsAmong 377,561 women (210,621 and 10,969 for 2- and 5-year outcomes), cumulative risk of subsequent fracture was 10%, 18%, and 31% at 1, 2, and 5 years post-index, respectively. Among women age 65-74 years with initial clinical vertebral, hip, pelvis, femur, or clavicle fractures and all women ≥ 75 years regardless of initial fracture site (except ankle and tibia/fibula), 7-14% fractured again within 1 year depending on initial fracture site; risk rose to 15-26% within 2 years and 28-42% within 5 years. Risk of subsequent hip fracture exceeded 3% within 5 years in all women studied, except those < 75 years with an initial tibia/fibula or ankle fracture.ConclusionsWe observed a high and early risk of subsequent fracture following a broad array of initial fractures. Timely management with consideration of pharmacotherapy is warranted in older women following all fracture types evaluated.
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Project description:Back pain is a major public health problem due to its high frequency, to the resulting activity constraint, and the need for surgery in many cases. Back pain is more frequent in women than men, mainly in postmenopausal women. High prevalence of hypovitaminosis D has been detected in postmenopausal women, and it is associated with decreased bone mass, sarcopenia, vertebral fractures, and inflammation, which can be related to back pain.The relation between back pain and hypovitaminosis D was evaluated in this study, as well the difference regarding the number of bedridden days, number of days away from work, and daily activities limitation between women with and without hypovitaminosis D. This study reviewed baseline data from an interventional phase III multicenter trial in low bone mass postmenopausal women. The study included demographic data, 25OHD determinations, Newitt/Cummings questionnaire on back pain, and vertebral fracture identified thought X-ray evaluation.The trial included 9354 participants, but only 9305 underwent all the evaluations. The age median was 67 (60 - 85 years old) and age at menopause was 49 (18 - 72 years). Hypovitaminosis D was found in 22.5% of the subjects, 15.3% of them had vertebral fractures, 67.5% with back pain, and 14.8% reduced their daily activities in the previous six months. Subjects with hypovitaminosis D, compared to those without hypovitaminosis D, reported more back pain (69.5 v 66.9%, p: 0.022), more cases of severe back pain (8.5% v 6.8%, p: 0,004), higher limitation in their daily activities (17.2 v 14.0%, p: 0.001), and more fractures (17.4 v 14.6%, p: 0,002); also, they had more trouble to perform daily activities addressed in the Newwit/Cummings questionnaire.Hypovitaminosis D was related to back pain, to its severity, and to difficulty in perform daily activities.ClinicalTrial.gov: NCT00088010.
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