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Purpose A three-drug combination of cyclophosphamide, bortezomib, and dexamethasone (CVD) shows significant efficacy and manageable toxicity as induction therapy in patients with multiple myeloma. Materials and Methods In this phase II study, we enrolled 45 patients who achieved a very good partial response (VGPR) or partial response (PR) after autologous stem cell transplantation (ASCT) and evaluated the efficacy and toxicity of CVD consolidation. CVD consolidation comprised three cycles of cyclophosphamide 300 mg/m2 orally on days 1, 8, and 15, and bortezomib 1.3 mg/m2 subcutaneously on days 1, 8, 15, and 22, along with dexamethasone 20 mg orally or intravenously on days 1 and 2, 8 and 9, 15 and 16, and 22 and 23. Results At enrollment, 39 patients (86.7%) showed VGPR, and nine (13.3%) presented with PR. Nineteen patients (45.2%) achieved a complete response or better as their best response after the end of consolidation. Overall, 22 of 42 patients (52.4%) experienced an improved response status with CVD consolidation. Three-year overall survival and progression-free survival rates were 89.0% and 42.7%, respectively. The most common non-hematologic toxicities were peripheral neuropathy and infection (20.5%), with no grade = 3 neuropathy observed. Conclusion These results showed that CVD consolidation therapy improved the response with reasonable toxicity in patients with residual disease after ASCT. This trial was registered with the Clinical Research Information Service, Republic of Korea (KCT0001327). [ABSTRACT FROM AUTHOR]

Vitamin D plays a major role in bone health and probably also in multiple extraskeletal acute and chronic diseases. Although supplementation with calcifediol, a vitamin D metabolite, has demonstrated efficacy and safety in short‐term clinical trials, its effects after long‐term monthly administration have been studied less extensively. This report describes the results of a 1‐year, phase III‐IV, double‐blind, randomized, controlled, parallel, multicenter superiority clinical trial to assess the efficacy and safety of monthly calcifediol 0.266 mg versus cholecalciferol 25,000 IU (0.625 mg) in postmenopausal women with vitamin D deficiency (25(OH)D < 20 ng/mL). A total of 303 women were randomized and 298 evaluated. Patients were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months (Group A1), calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months (Group A2), and cholecalciferol 25,000 IU/month (0.625 mg/month) for 12 months (Group B). By month 4, stable 25(OH)D levels were documented with both calcifediol and cholecalciferol (intention‐to‐treat population): 26.8 ± 8.5 ng/mL (Group A1) and 23.1 ± 5.4 ng/mL (Group B). By month 12, 25(OH)D levels were 23.9 ± 8.0 ng/mL (Group A1) and 22.4 ± 5.5 ng/mL (Group B). When calcifediol treatment was withdrawn in Group A2, 25(OH)D levels decreased to baseline levels (28.5 ± 8.7 ng/mL at month 4 versus 14.4 ± 6.0 ng/mL at month 12). No relevant treatment‐related safety issues were reported in any of the groups. The results confirm that long‐term treatment with monthly calcifediol in vitamin D‐deficient patients is effective and safe. The withdrawal of treatment leads to a pronounced decrease of 25(OH)D levels. Calcifediol presented a faster onset of action compared to monthly cholecalciferol. Long‐term treatment produces stable and sustained 25(OH)D concentrations with no associated safety concerns. © 2023 Faes Farma SA. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Although bone mineral density (BMD) is a predictor of fracture, many fractures occur in women with T‐scores > −2.5. Bone microarchitecture, assessed by trabecular bone score (TBS), predicts fracture risk independent of BMD. We evaluated whether abaloparatide improves TBS and whether TBS trends were associated with vertebral fracture risk reduction. Women with osteoporosis randomized to abaloparatide or placebo for 18 months (ACTIVE), followed by alendronate for 24 months (ACTIVExtend), with evaluable TBS, were included in this post hoc analysis (N = 911). TBS was calculated from spine BMD scans using an algorithm adjusted for tissue thickness (TBSth) at baseline, 6, 18, and 43 months. Mean increments in TBSth from baseline within and between treatment groups, proportion of women with TBSth increments above least significant change (LSC) and proportion with degraded TBSth (<1.027) were calculated. Risk estimates for vertebral fracture were compared using binary logistic regressions adjusted for baseline age and spine BMD. At baseline, 42% had degraded TBSth. Mean TBSth increased 4% after 18 months abaloparatide (p < 0.001) and was unchanged with placebo. After 2 subsequent years of alendronate, the total cumulative TBSth increase was 4.4% with abaloparatide/alendronate and 1.7% with placebo/alendronate (group difference, p < 0.001). At 43 months, the proportion of women with degraded TBSth had declined to 21% with abaloparatide/alendronate and 37% with placebo/alendronate (p < 0.05). An increase in TBSth ≥ LSC was observed in 50% of abaloparatide‐treated women at 18 months and was associated with decreased odds (odds ratio [OR]; 95% confidence interval [CI]) of vertebral fracture (0.19; 95% CI, 0.04–0.80, 6 months; 0.30; 95% CI, 0.11–0.79, 43 months). In conclusion, abaloparatide increased TBSth rapidly and progressively over 18 months and increments were maintained over 2 years with alendronate. TBSth increase was associated with vertebral fracture risk reduction. Microarchitectural improvement may be one mechanism by which abaloparatide strengthens vertebral bone. © 2023 Radius Health, Inc and The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Background: Osteoporosis is often considered to be a disease of women. Over the last few years, owing to the increasing clinical and economic burden, the awareness and imperative for identifying and managing osteoporosis in men have increased substantially. With the approval of agents to treat men with osteoporosis, more economic evaluations have been conducted to assess the potential economic benefits of these interventions. Despite this concern, there is no specific overview of cost-effectiveness analyses for the treatment of osteoporosis in men. Objectives: This study aims (1) to systematically review economic evaluations of interventions for osteoporosis in men; (2) to critically appraise the quality of included studies and the source of model input data; and (3) to investigate the comparability of results for studies including both men and women. Methods: A literature search mainly using MEDLINE (via Ovid) and Embase databases was undertaken to identify original articles published between 1 January, 2000 and 30 June, 2022. Studies that assessed the cost effectiveness of interventions for osteoporosis in men were included. The Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases and the International Osteoporosis Foundation osteoporosis-specific guideline was used to assess the quality of design, conduct, and reporting of included studies. Results: Of 2973 articles identified, 25 studies fulfilled the inclusion criteria, classified into economic evaluations of active drugs (n = 8) or nutritional supplements (n = 4), intervention thresholds (n = 5), screening strategies (n = 6), and post-fracture care programs (n = 2). Most studies were conducted in European countries (n = 15), followed by North America (n = 9). Bisphosphonates (namely alendronate) and nutritional supplements were shown to be generally cost effective compared with no treatment in men over 60 years of age with osteoporosis or prior fractures. Two other studies suggested that denosumab was cost effective in men aged 75 years and older with osteoporosis compared with bisphosphates and teriparatide. Intervention thresholds at which bisphosphonates were found to be cost effective varied among studies with a 10-year probability of a major osteoporotic fracture that ranged from 8.9 to 34.2% for different age categories. A few studies suggested cost effectiveness of screening strategies and post-fracture care programs in men. Similar findings regarding the cost effectiveness of drugs and intervention thresholds in women and men were captured, with slightly greater incremental cost-effectiveness ratios in men. The quality of the studies included had an average score of 18.8 out of 25 (range 13–23.5). Hip fracture incidence and mortality risk were mainly derived from studies in men, while fracture cost, treatment efficacy, and disutility were commonly derived from studies in women or studies combining both sexes. Conclusions: Anti-osteoporosis drugs and nutritional supplements are generally cost effective in men with osteoporosis. Screening strategies and post-fracture care programs also showed economic benefits for men. Cost-effectiveness and intervention thresholds were generally similar in studies conducted in both men and women, with slightly greater incremental cost-effectiveness ratios in men. [ABSTRACT FROM AUTHOR]

Background Identifying late-life men who might benefit from treatment to prevent fracture is challenging given high mortality. Our objective was to evaluate risks of clinical fracture, hip fracture, and mortality prior to fracture among men aged at least 80 years. Methods Study participants included 3 145 community-dwelling men (mean [standard deviation] age 83 [2.8] years) from the Osteoporotic Fractures in Men (MrOS) Study. We used separate multivariable Fine-Gray competing risk models with prespecified risk factors (age, hip bone mineral density [BMD], recent fracture [<5 years], fall history [previous year], and multimorbidity [# conditions]) to estimate subdistribution hazard ratios and absolute 5-year risks of any clinical fracture and mortality prior to clinical fracture. Secondary analysis considered a hip fracture. Results There were 414 incident clinical fractures and 595 deaths without prior fracture within 5 years. BMD, fall history, and recent fracture were strong predictors of clinical fracture. Age and multimorbidity were strong predictors of mortality before fracture. After accounting for competing risks, age, BMD, and fall history were each associated with both risks of hip fracture and mortality before hip fracture. Model discrimination varied from 0.65 (mortality before fracture) to 0.79 (hip fracture). Estimated mortality differed substantially among men with similar clinical fracture risk due to a modest correlation between fracture risk and competing mortality risk = 0.37. Conclusion In late-life men, strong risk factors for clinical fracture and hip fracture include fall history, BMD, and recent fracture. Osteoporosis drug treatment decisions may be further enhanced by consideration of fracture risk versus overall life expectancy. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Osteoporosis & Mineral Metabolism / Revista de Osteoporosis y Metabolismo Mineral (English edition) is the property of Ibanez y Plaza and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: to evaluate the application of intervention thresholds based on FRAX in Chilean women. Recategorize the risk of osteoporotic fracture to optimize the selection of eligible women for intervention. Methods: we selected 1782 women aged 50 and older from the 2016-2017 National Health Survey (third version). We estimated the probability of major osteoporotic fractures and hip fractures using the Chilean FRAX model. We estimated the percentage of women eligible for treatment and assessment of bone mineral density by applying specific intervention thresholds by age from 50 to 90 years and a hybrid threshold that combines age-dependent thresholds up to 75 years and, thereafter, a fixed threshold with a single fracture probability up to 90 years. Results: twenty-two women (1.23 %) had a previous fracture and were eligible for treatment for this reason. Using age-specific thresholds, another 33 women were eligible for treatment because the probability of major osteoporotic fracture was above the upper assessment threshold. In 1107 (62.12 %) women, bone mineral density measurement is recommended to recalculate FRAX with the inclusion of femoral neck bone mineral density. With the hybrid threshold, an additional 44 (3.69 %) women were eligible for treatment, and bone density measurement was advised in 1169 women (65.50 %). If treatment was assigned based on FRAX without bone mineral density alone, the number of women eligible for treatment was 70 (5.15 %) with an age-specific intervention threshold and 120 (6.72 %) with the hybrid threshold. Conclusions: the hybrid threshold identifies more women eligible for treatment compared to age-specific thresholds. The average fracture probability was higher with the hybrid threshold. Based on this, our position is to recommend the hybrid threshold. [ABSTRACT FROM AUTHOR]

Background: High-density lipoprotein cholesterol (HDL-C) has long been viewed as a protective factor for cardiovascular health. Yet, higher HDL-C was not necessarily beneficial. The purpose of this study was to investigate the relationship between HDL-C levels and intertrochanter bone mineral density. Methods: The study collected the most recent data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES). Weighted multiple regression analysis was used to evaluate the relationship between HDL-C and intertrochanter BMD, and further subgroup analysis and threshold effect analysis were conducted. Finally, the relationship between HDL-C and intertrochanter BMD was analyzed by fitting smooth curves. Results: The study included 3,345 people ranging in age from 50 to 80. HDL-C was discovered to be negatively correlated with intertrochanter BMD (b = -0.03, 95%CI: -0.04, -0.01, P = 0.0002). In subgroup analysis, the negative correlation was found among 60-70-year-olds (b = -0.04, 95%CI: -0.06, -0.02, P = 0.0010), additionally, non-Hispanic whites (b = -0.03, 95%CI: -0.05, -0.01, P = 0.0140), and obese individuals (b = -0.03, 95%CI: -0.05, -0.01, P = 0.0146). The negative correlation, on the other hand, remained significant and consistent across genders, menstruation status, hormone usage, and long-term use of steroids. The relationship between HDL-C and intertrochanter BMD was an inverted Ushaped curve in men and hormone users, with inflection points of 1.01 mmol/L and 1.71 mmol/L, and an U-shaped curve in other Hispanic and premenopausal individuals, with inflection points of 0.96 mmol/L and 1.89 mmol/L. Conclusions: HDL-C was negatively associated with intertrochanter BMD in people over 50 years of age, non-Hispanic whites, and obesity. [ABSTRACT FROM AUTHOR]

Summary: Appropriate use of FRAX reduces the number of people requiring DXA scans, while contemporaneously determining those most at risk. We compared the results of FRAX with and without inclusion of BMD. It suggests clinicians to carefully consider the importance of BMD inclusion in fracture risk estimation or interpretation in individual patients. Purpose: FRAX is a widely accepted tool to estimate the 10-year risk of hip and major osteoporotic fracture in adults. Prior calibration studies suggest this works similarly with or without the inclusion of bone mineral density (BMD). The purpose of the study is to compare within-subject differences between FRAX estimations derived using DXA and Web software with and without the inclusion of BMD. Method: A convenience cohort was used for this cross-sectional study, consisting of 1254 men and women aged between 40 and 90 years who had a DXA scan and complete validated data available for analysis. FRAX 10-year estimations for hip and major osteoporotic fracture were calculated using DXA software (DXA-FRAX) and the Web tool (Web-FRAX), with and without BMD. Agreements between estimates within each individual subject were examined using Bland–Altman plots. We performed exploratory analyses of the characteristics of those with very discordant results. Results: Overall median DXA-FRAX and Web-FRAX 10-year hip and major osteoporotic fracture risk estimations which include BMD are very similar: 2.9% vs. 2.8% and 11.0% vs. 11% respectively. However, both are significantly lower than those obtained without BMD: 4.9% and 14% respectively, P < 0.001. Within-subject differences between hip fracture estimates with and without BMD were < 3% in 57% of cases, between 3 and 6% in 19% of cases, and > 6% in 24% of cases, while for major osteoporotic fractures such differences are < 10% in 82% of cases, between 10 and 20% in 15% of cases, and > 20% in 3% of cases. Conclusions: Although there is excellent agreement between the Web-FRAX and DXA-FRAX tools when BMD is incorporated, sometimes there are very large differences for individuals between results obtained with and without BMD. Clinicians should carefully consider the importance of BMD inclusion in FRAX estimations when assessing individual patients. [ABSTRACT FROM AUTHOR]

Background: To inform recommendations by the Canadian Task Force on Preventive Health Care, we reviewed evidence on the benefits, harms, and acceptability of screening and treatment, and on the accuracy of risk prediction tools for the primary prevention of fragility fractures among adults aged 40 years and older in primary care. Methods: For screening effectiveness, accuracy of risk prediction tools, and treatment benefits, our search methods involved integrating studies published up to 2016 from an existing systematic review. Then, to locate more recent studies and any evidence relating to acceptability and treatment harms, we searched online databases (2016 to April 4, 2022 [screening] or to June 1, 2021 [predictive accuracy]; 1995 to June 1, 2021, for acceptability; 2016 to March 2, 2020, for treatment benefits; 2015 to June 24, 2020, for treatment harms), trial registries and gray literature, and hand-searched reviews, guidelines, and the included studies. Two reviewers selected studies, extracted results, and appraised risk of bias, with disagreements resolved by consensus or a third reviewer. The overview of reviews on treatment harms relied on one reviewer, with verification of data by another reviewer to correct errors and omissions. When appropriate, study results were pooled using random effects meta-analysis; otherwise, findings were described narratively. Evidence certainty was rated according to the GRADE approach. Results: We included 4 randomized controlled trials (RCTs) and 1 controlled clinical trial (CCT) for the benefits and harms of screening, 1 RCT for comparative benefits and harms of different screening strategies, 32 validation cohort studies for the calibration of risk prediction tools (26 of these reporting on the Fracture Risk Assessment Tool without [i.e., clinical FRAX], or with the inclusion of bone mineral density (BMD) results [i.e., FRAX + BMD]), 27 RCTs for the benefits of treatment, 10 systematic reviews for the harms of treatment, and 12 studies for the acceptability of screening or initiating treatment. In females aged 65 years and older who are willing to independently complete a mailed fracture risk questionnaire (referred to as "selected population"), 2-step screening using a risk assessment tool with or without measurement of BMD probably (moderate certainty) reduces the risk of hip fractures (3 RCTs and 1 CCT, n = 43,736, absolute risk reduction [ARD] = 6.2 fewer in 1000, 95% CI 9.0–2.8 fewer, number needed to screen [NNS] = 161) and clinical fragility fractures (3 RCTs, n = 42,009, ARD = 5.9 fewer in 1000, 95% CI 10.9–0.8 fewer, NNS = 169). It probably does not reduce all-cause mortality (2 RCTs and 1 CCT, n = 26,511, ARD = no difference in 1000, 95% CI 7.1 fewer to 5.3 more) and may (low certainty) not affect health-related quality of life. Benefits for fracture outcomes were not replicated in an offer-to-screen population where the rate of response to mailed screening questionnaires was low. For females aged 68–80 years, population screening may not reduce the risk of hip fractures (1 RCT, n = 34,229, ARD = 0.3 fewer in 1000, 95% CI 4.2 fewer to 3.9 more) or clinical fragility fractures (1 RCT, n = 34,229, ARD = 1.0 fewer in 1000, 95% CI 8.0 fewer to 6.0 more) over 5 years of follow-up. The evidence for serious adverse events among all patients and for all outcomes among males and younger females (<65 years) is very uncertain. We defined overdiagnosis as the identification of high risk in individuals who, if not screened, would never have known that they were at risk and would never have experienced a fragility fracture. This was not directly reported in any of the trials. Estimates using data available in the trials suggest that among "selected" females offered screening, 12% of those meeting age-specific treatment thresholds based on clinical FRAX 10-year hip fracture risk, and 19% of those meeting thresholds based on clinical FRAX 10-year major osteoporotic fracture risk, may be overdiagnosed as being at high risk of fracture. Of those identified as being at high clinical FRAX 10-year hip fracture risk and who were referred for BMD assessment, 24% may be overdiagnosed. One RCT (n = 9268) provided evidence comparing 1-step to 2-step screening among postmenopausal females, but the evidence from this trial was very uncertain. For the calibration of risk prediction tools, evidence from three Canadian studies (n = 67,611) without serious risk of bias concerns indicates that clinical FRAX-Canada may be well calibrated for the 10-year prediction of hip fractures (observed-to-expected fracture ratio [O:E] = 1.13, 95% CI 0.74–1.72, I2 = 89.2%), and is probably well calibrated for the 10-year prediction of clinical fragility fractures (O:E = 1.10, 95% CI 1.01–1.20, I2 = 50.4%), both leading to some underestimation of the observed risk. Data from these same studies (n = 61,156) showed that FRAX-Canada with BMD may perform poorly to estimate 10-year hip fracture risk (O:E = 1.31, 95% CI 0.91-2.13, I2 = 92.7%), but is probably well calibrated for the 10-year prediction of clinical fragility fractures, with some underestimation of the observed risk (O:E 1.16, 95% CI 1.12–1.20, I2 = 0%). The Canadian Association of Radiologists and Osteoporosis Canada Risk Assessment (CAROC) tool may be well calibrated to predict a category of risk for 10-year clinical fractures (low, moderate, or high risk; 1 study, n = 34,060). The evidence for most other tools was limited, or in the case of FRAX tools calibrated for countries other than Canada, very uncertain due to serious risk of bias concerns and large inconsistency in findings across studies. Postmenopausal females in a primary prevention population defined as <50% prevalence of prior fragility fracture (median 16.9%, range 0 to 48% when reported in the trials) and at risk of fragility fracture, treatment with bisphosphonates as a class (median 2 years, range 1–6 years) probably reduces the risk of clinical fragility fractures (19 RCTs, n = 22,482, ARD = 11.1 fewer in 1000, 95% CI 15.0–6.6 fewer, [number needed to treat for an additional beneficial outcome] NNT = 90), and may reduce the risk of hip fractures (14 RCTs, n = 21,038, ARD = 2.9 fewer in 1000, 95% CI 4.6–0.9 fewer, NNT = 345) and clinical vertebral fractures (11 RCTs, n = 8921, ARD = 10.0 fewer in 1000, 95% CI 14.0–3.9 fewer, NNT = 100); it may not reduce all-cause mortality. There is low certainty evidence of little-to-no reduction in hip fractures with any individual bisphosphonate, but all provided evidence of decreased risk of clinical fragility fractures (moderate certainty for alendronate [NNT=68] and zoledronic acid [NNT=50], low certainty for risedronate [NNT=128]) among postmenopausal females. Evidence for an impact on risk of clinical vertebral fractures is very uncertain for alendronate and risedronate; zoledronic acid may reduce the risk of this outcome (4 RCTs, n = 2367, ARD = 18.7 fewer in 1000, 95% CI 25.6–6.6 fewer, NNT = 54) for postmenopausal females. Denosumab probably reduces the risk of clinical fragility fractures (6 RCTs, n = 9473, ARD = 9.1 fewer in 1000, 95% CI 12.1–5.6 fewer, NNT = 110) and clinical vertebral fractures (4 RCTs, n = 8639, ARD = 16.0 fewer in 1000, 95% CI 18.6–12.1 fewer, NNT=62), but may make little-to-no difference in the risk of hip fractures among postmenopausal females. Denosumab probably makes little-to-no difference in the risk of all-cause mortality or health-related quality of life among postmenopausal females. Evidence in males is limited to two trials (1 zoledronic acid, 1 denosumab); in this population, zoledronic acid may make little-to-no difference in the risk of hip or clinical fragility fractures, and evidence for all-cause mortality is very uncertain. The evidence for treatment with denosumab in males is very uncertain for all fracture outcomes (hip, clinical fragility, clinical vertebral) and all-cause mortality. There is moderate certainty evidence that treatment causes a small number of patients to experience a non-serious adverse event, notably non-serious gastrointestinal events (e.g., abdominal pain, reflux) with alendronate (50 RCTs, n = 22,549, ARD = 16.3 more in 1000, 95% CI 2.4–31.3 more, [number needed to treat for an additional harmful outcome] NNH = 61) but not with risedronate; influenza-like symptoms with zoledronic acid (5 RCTs, n = 10,695, ARD = 142.5 more in 1000, 95% CI 105.5–188.5 more, NNH = 7); and non-serious gastrointestinal adverse events (3 RCTs, n = 8454, ARD = 64.5 more in 1000, 95% CI 26.4–13.3 more, NNH = 16), dermatologic adverse events (3 RCTs, n = 8454, ARD = 15.6 more in 1000, 95% CI 7.6–27.0 more, NNH = 64), and infections (any severity; 4 RCTs, n = 8691, ARD = 1.8 more in 1000, 95% CI 0.1–4.0 more, NNH = 556) with denosumab. For serious adverse events overall and specific to stroke and myocardial infarction, treatment with bisphosphonates probably makes little-to-no difference; evidence for other specific serious harms was less certain or not available. There was low certainty evidence for an increased risk for the rare occurrence of atypical femoral fractures (0.06 to 0.08 more in 1000) and osteonecrosis of the jaw (0.22 more in 1000) with bisphosphonates (most evidence for alendronate). The evidence for these rare outcomes and for rebound fractures with denosumab was very uncertain. Younger (lower risk) females have high willingness to be screened. A minority of postmenopausal females at increased risk for fracture may accept treatment. Further, there is large heterogeneity in the level of risk at which patients may be accepting of initiating treatment, and treatment effects appear to be overestimated. Conclusion: An offer of 2-step screening with risk assessment and BMD measurement to selected postmenopausal females with low prevalence of prior fracture probably results in a small reduction in the risk of clinical fragility fracture and hip fracture compared to no screening. These findings were most applicable to the use of clinical FRAX for risk assessment and were not replicated in the offer-to-screen population where the rate of response to mailed screening questionnaires was low. Limited direct evidence on harms of screening were available; using study data to provide estimates, there may be a moderate degree of overdiagnosis of high risk for fracture to consider. The evidence for younger females and males is very limited. The benefits of screening and treatment need to be weighed against the potential for harm; patient views on the acceptability of treatment are highly variable. Systematic review registration: International Prospective Register of Systematic Reviews (PROSPERO): CRD42019123767. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) has been linked with a number of extra hepatic diseases and could be a potential risk factor of decreasing bone mineral density. To determine whether Upper Egyptian patients with NAFLD are at risk of developing osteoporosis. Cross sectional study was done on a total 100 individuals; 50 patients diagnosed with NAFLD (based on ultrasound imaging) crossed-matched with 50 individuals without NAFLD based on age, sex and body mass index. Bone mineral density, serum calcium and phosphorus levels, serum parathyroid hormone, serum vitamin D and fasting insulin level were assessed. Osteoporosis was prevalent in NAFLD patients versus to controls (19/50 vs. 0/50; P < 0.001). There was significant decrease in bone mineral density in NAFLD patients than controls (− 2.29 ± 0.4 vs. − 1.53 ± 0.1; P < 0.001). There was a statistical significance decrease in serum vitamin D and calcium levels in NAFLD patients than controls. Furthermore, vitamin D levels in the NAFLD group was a predictor for osteoporosis (OR 0.614; 95% CI 0.348–0.825). Patients with NAFLD tend to have a significant decrease in bone density, vitamin D, and serum calcium levels than controls. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this research is to provide national estimates of the prevalence of health condition diagnoses among age-entitled transgender and cisgender Medicare beneficiaries. Quantification of the health burden across sex assigned at birth and gender can inform prevention, research, and allocation of funding for modifiable risk factors. Methods: Using 2009-2017 Medicare fee-for-service data, we implemented an algorithm that leverages diagnosis, procedure, and pharmacy claims to identify age-entitled transgender Medicare beneficiaries and stratify the sample by inferred gender: trans feminine and nonbinary (TFN), trans masculine and nonbinary (TMN), and unclassified. We selected a 5% random sample of cisgender individuals for comparison. We descriptively analyzed (means and frequencies) demographic characteristics (age, race/ethnicity, US census region, months of enrollment) and used chi-square and t-tests to determine between- (transgender vs. cisgender) and within-group gender differences (e.g., TMN, TFN, unclassified) difference in demographics (p<0.05). We then used logistic regression to estimate and examine within- and between-group gender differences in the predicted probability of 25 health conditions, controlling for age, race/ethnicity, enrollment length, and census region. Results: The analytic sample included 9,975 transgender (TFN n=4,198; TMN n=2,762; unclassified n=3,015) and 2,961,636 cisgender (male n=1,294,690, female n=1,666,946) beneficiaries. The majority of the transgender and cisgender samples were between the ages of 65 and 69 and White, non-Hispanic. The largest proportion of transgender and cisgender beneficiaries were from the South. On average, transgender individuals had more months of enrollment than cisgender individuals. In adjusted models, aging TFN or TMN Medicare beneficiaries had the highest probability of each of the 25 health diagnoses studied relative to cisgender males or females. TFN beneficiaries had the highest burden of health diagnoses relative to all other groups. Discussion: These findings document disparities in key health condition diagnoses among transgender Medicare beneficiaries relative to cisgender individuals. Future application of these methods will enable the study of rare and anatomy-specific conditions among hard-to-reach aging transgender populations and inform interventions and policies to address documented disparities. [ABSTRACT FROM AUTHOR]

Summary: Key statements of the Russian clinical guidelines on the diagnosis and treatment of osteoporosis are summarized. They were developed by a task force representing the key Russian professional associations involved in the management of osteoporosis and approved by the Russian Ministry of Health. Purpose: To summarize key statements of the Russian clinical practice guidelines for the diagnosis and treatment of osteoporosis. Methods: The Russian clinical guidelines on the diagnosis and treatment of osteoporosis were developed by a task force representing the key Russian professional associations involved in the management of osteoporosis: These comprised the Russian Association of Endocrinologists, the Russian Association for Osteoporosis, the Association of Rheumatologists of Russia, the Association of Orthopedic surgeons and Traumatologists of Russia, the Russian Association of Gynecologists-Endocrinologists, and the Russian Association of Gerontologists and Geriatrics. The guidelines are based on a systematic literature review and principles of evidence-based medicine and were compiled in accordance with the requirements for clinical recommendations developed by the Ministry of Health of the Russian Federation. Results: Key statements included in the Russian guidelines of osteoporosis approved by the Russian Ministry of Health in 2021 are summarized. The statements are graded based on levels of evidence and supported by short comments. The guidelines are focused on the current approach to screening, diagnosis, differential diagnosis, and treatment of osteoporosis. Conclusion: These guidelines are a practical tool for general practitioners, as well as medical specialists, primarily endocrinologists, rheumatologists, orthopedic surgeons, and other physicians who are involved in the management of patients with osteoporosis. [ABSTRACT FROM AUTHOR]

Summary: Osteoporosis care in men is suboptimal due to low rates of testing and treatment. Applying biomechanical computed tomography (BCT) analysis to existing CT scans, we found a high proportion of men with osteoporosis have never been diagnosed or treated. BCT may improve identification of patients at high risk of fracture. Purpose: Osteoporosis care in men is suboptimal due to low rates of DXA testing and treatment. Biomechanical computed tomography analysis (BCT) can be applied "opportunistically" to prior hip-containing CT scans to measure femoral bone strength and hip BMD. Methods : In this retrospective, cross-sectional study, we used BCT in male veterans with existing CT scans to investigate the prevalence of osteoporosis, defined by hip BMD (T-score ≤ − 2.5) or fragile bone strength (≤ 3500 N). 577 men, age ≥ 65 with abdominal/pelvic CTs performed in 2017–2019, were randomly selected for BCT analysis. Clinical data were collected via electronic health records and used with the femoral neck BMD T-score from BCT to estimate 10-year hip fracture risks by FRAX. Results: Prevalence of osteoporosis by BCT increased with age (13.5% age 65–74; 18.2% age 75–84; 34.3% age ≥ 85), with an estimated overall prevalence of 18.3% for men age ≥ 65. In those with osteoporosis (n = 108/577), only 38.0% (41/108) had a prior DXA and 18.6% (7/108) had received osteoporosis pharmacotherapy. Elevated hip fracture risk by FRAX (≥ 3%) did not fully capture those with fragile bone strength. In a multivariate logistic regression model adjusted for age, BMI, race, and CT location, end stage renal disease (odds ratio 7.4; 95% confidence interval 2.3–23.9), COPD (2.2; 1.2–4.0), and high-dose inhaled corticosteroid use (3.7; 1.2–11.8) were associated with increased odds of having osteoporosis by BCT. Conclusion: Opportunistic BCT in male veterans provides an additional avenue to identify patients who are at high risk of fractures. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Tissue Engineering Research / Zhongguo Zuzhi Gongcheng Yanjiu is the property of Chinese Journal of Tissue Engineering Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: To determine the proportion of postmenopausal Thai women who would be classified as having high risk of fracture and eligible for anti-osteoporosis therapy according to the National Osteoporosis Foundation (NOF) criteria. Methods: Postmenopausal Thai women aged 40–90 years who had been screened for osteoporosis during 2014–2019 were recruited. Demographic data and osteoporosis risk factors were collected based on the Fracture Risk Assessment Tool (FRAX) questionnaire. Bone mineral density (BMD) at the femoral neck and lumbar spine measured using dual energy X-ray absorptiometry. Ten-year probabilities of hip and major osteoporotic fracture (MOF) were calculated based on the Thai FRAX model with BMD. The study's protocol was approved by the Institutional Ethical Committee (HE581241). Results: A total of 3,280 postmenopausal women were included. The mean ± SD age was 63.6 ± 10.1 years. A total of 170 (5.2%) participants had a history of hip and/or vertebral fracture. After excluding these participants with fracture history, 699 (21.3%) had osteoporosis, 355 (10.8%) had osteopenia with high risk of fracture (FRAX 10-year probability of hip fracture ≥ 3% and/or MOF ≥ 20%), 1192 (36.3%) had osteopenia with low risk of fracture (FRAX 10-year probability of hip fracture < 3% and MOF < 20%) and 864 (26.3%) had normal BMD. Taken together, a total of 1,224 (37.3%) participants would be eligible for anti-osteoporosis therapy (prior fracture, osteoporosis or osteopenia with high risk of fracture). Conclusion: The prevalence of Thai postmenopausal women who would be eligible for anti-osteoporosis therapy was 37.3%. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Rheumatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Osteoporosis is a bone disorder characterised by low bone mineral density, reduced bone strength, increased bone fragility, and impaired mineralisation of bones causing an increased risk of bone fracture. Several therapies are available for treating osteoporosis which include bisphosphonates, anti-resorptive agents, oestrogen modulators, etc. These therapies primarily focus on decreasing bone resorption and do not assist in bone regeneration or offering permanent curative solutions. Additionally, these therapies are associated with severe adverse events like thromboembolism, increased risk of stroke, and hypocalcaemia. To overcome these limitations, bone regenerative pathways and approaches are now considered to manage osteoporosis. The bone regenerative pathways involved in bone regeneration include wingless-related integration site/β-catenin signalling pathway, notch signalling pathway, calcium signalling, etc. The various regenerative approaches which possess potential to heal and replace the bone defect site include scaffolds, cements, cell therapy, and other alternative medicines. The review focuses on describing the challenges and opportunities in bone regeneration for osteoporosis. [ABSTRACT FROM AUTHOR]

Bone quality is increasingly being recognized in the assessment of fracture risk. Nonenzymatic collagen cross‐linking with the accumulation of advanced glycation end products stiffens and embrittles collagen fibers thus increasing bone fragility. Echogenicity is an ultrasound (US) parameter that provides information regarding the skin collagen structure. We hypothesized that both skin and bone collagen degrade in parallel fashion. Prospectively collected data of 110 patients undergoing posterior lumbar fusion was analyzed. Preoperative skin US measurements were performed in the lumbar region to assess dermal thickness and echogenicity. Intraoperative bone biopsies from the posterior superior iliac spine were obtained and analyzed with confocal fluorescence microscopy for fluorescent advanced glycation endproducts (fAGEs). Pearson's correlation was calculated to examine relationships between (1) US and fAGEs, and (2) age and fAGEs stratified by sex. Multivariable linear regression analysis with adjustments for age, sex, body mass index (BMI), diabetes mellitus, and hemoglobin A1c (HbA1c) was used to investigate associations between US and fAGEs. One hundred and ten patients (51.9% female, 61.6 years, BMI 29.8 kg/m2) were included in the analysis. In the univariate analysis cortical and trabecular fAGEs decreased with age, but only in women (cortical: r = −0.32, p = 0.031; trabecular: r = −0.32; p = 0.031). After adjusting for age, sex, BMI, diabetes mellitus, and HbA1c, lower dermal (β = 1.01; p = 0.012) and subcutaneous (β = 1.01; p = 0.021) echogenicity increased with increasing cortical fAGEs and lower dermal echogenicity increased with increasing trabecular fAGEs (β = 1.01; p = 0.021). This is the first study demonstrating significant associations between skin US measurements and in vivo bone quality parameters in lumbar fusion patients. As a noninvasive assessment tool, skin US measurements might be incorporated into future practice to investigate bone quality in spine surgery patients. [ABSTRACT FROM AUTHOR]

Summary: International variations in osteoporosis and fracture rates have been reported, with temporal trends differing between populations. We observed higher BMD and lower fracture prevalence in a recently recruited cohort compared to that of a cohort recruited 20 years ago, even after adjusting for multiple covariates. Purpose: We explored sex-specific differences in femoral neck bone mineral density (FN-BMD) and in prevalent major osteoporotic fractures (MOF) using two Canadian cohorts recruited 20 years apart. Methods: We included men and women aged 50–85 years from the Canadian Multicentre Osteoporosis Study (CaMos, N = 6,479; 1995–1997) and the Canadian Longitudinal Study on Aging (CLSA, N = 19,534; 2012–2015). We created regression models to compare FN-BMD and fracture risk between cohorts, adjusting for important covariates. Among participants with prevalent MOF, we compared anti-osteoporosis medication use. Results: Mean (SD) age in CaMos (65.4 years [8.6]) was higher than in CLSA (63.8 years [9.1]). CaMos participants had lower mean body mass index and higher prevalence of smoking (p < 0.001). Adjusted linear regression models (estimates [95%CI]) demonstrated lower FN-BMD in CaMos women (− 0.017 g/cm2 [− 0.021; − 0.014]) and men (− 0.006 g/cm2 [− 0.011; 0.000]), while adjusted odds ratios (95%CI) for prevalent MOF were higher in CaMos women (1.99 [1.71; 2.30]) and men (2.33 [1.82; 3.00]) compared to CLSA. In women with prevalent MOF, menopausal hormone therapy use was similar in both cohorts (43.3% vs 37.9%, p = 0.076), but supplements (32.0% vs 48.3%, p < 0.001) and bisphosphonate use (5.8% vs 17.3%, p < 0.001) were lower in CaMos. The proportion of men with MOF who received bisphosphonates was below 10% in both cohorts. Conclusion: Higher BMD and lower fracture prevalence were noted in the more recently recruited CLSA cohort compared to CaMos, even after adjusting for multiple covariates. We noted an increase in bisphosphonate use in the recent cohort, but it remained very low in men. [ABSTRACT FROM AUTHOR]

BACKGROUND: There is paucity in the literature regarding physical therapy (PT) utilization for postoperative management following balloon kyphoplasty (BKP). CASE PRESENTATION: A 74-year-old female with osteoporosis and multiple sclerosis presented with a vertebral burst fracture following a fall. The patient was successfully treated with transforaminal epidural for radiculopathy but underwent a BKP due to worsening low back pain. The patient was referred to PT and began 6 weeks after BKP due to residual low back pain and limitations in functional mobility. OUTCOME AND FOLLOW-UP: Significant improvements in Oswestry Disability Index, Patient-Specific Functional Scale, numeric pain-rating scale, and 5 times sit-to-stand were demonstrated following 16 weeks of postoperative PT without adverse events. DISCUSSION: Physical therapy following BKP may reduce pain and fall risk while improving quality of life without adverse events in patients with vertebral burst fracture on an individual basis. [ABSTRACT FROM AUTHOR]

Catch a Break (CaB) is a secondary fracture prevention program that uses medical understandings of osteoporosis to assess first fractures and determine appropriateness for secondary fracture prevention. In this study, we interviewed CaB program participants to identify the understandings that patients themselves used to make sense of first fractures and the osteoporosis suggestion as cause. Semi-structured interviews were conducted with female and male participants of the CaB program in Canada. An interpretive practice approach was used to analyze the data. A random sample of 20 individuals, 12 women, and eight men all aged 50 years and over participated. First fractures were produced as meaningful in the context of osteoporosis only for seniors of very advanced age, and for people of any age with poor nutrition. The trauma events that led to a first fracture were produced as meaningful only if perceived as accidents, and having an active lifestyle was produced as beneficial only for mental health and well-being unrelated to osteoporosis. Cultural knowledge shapes, but does not determine, how individuals make sense of their health and illness experiences. Risk prevention program designers should include patients on the design team and be more aware of the presumptive knowledge used to identify individuals at risk of disease. [ABSTRACT FROM AUTHOR]

Background: Multimorbidity is common among fracture patients. However, its association with osteoporosis investigation and treatment to prevent future fractures is unclear. This limited knowledge impedes optimal patient care. This study investigated the association between multimorbidity and osteoporosis investigation and treatment in persons at high risk following an osteoporotic fracture. Methods and findings: The Sax Institute's 45 and Up Study is a prospective population-based cohort of 267,153 people in New South Wales, Australia, recruited between 2005 and 2009. This analysis followed up participants until 2017 for a median of 6 years (IQR: 4 to 8). Questionnaire data were linked to hospital admissions (Admitted Patients Data Collection (APDC)), emergency presentations (Emergency Department Data Collection (EDDC)), Pharmaceutical Benefits Scheme (PBS), and Medicare Benefits Schedule (MBS). Data were linked by the Centre for Health Record Linkage and stored in a secured computing environment. Fractures were identified from APDC and EDDC, Charlson Comorbidity Index (CCI) from APDC, Dual-energy X-ray absorptiometry (DXA) investigation from MBS, and osteoporosis treatment from PBS. Out of 25,280 persons with index fracture, 10,540 were classified as high-risk based on 10-year Garvan Fracture Risk (age, sex, weight, prior fracture and falls) threshold ≥20%. The association of CCI with likelihood of investigation and treatment initiation was determined by logistic regression adjusted for education, socioeconomic and lifestyle factors). The high-risk females and males averaged 77 ± 10 and 86 ± 5 years, respectively; >40% had a CCI ≥2. Only 17% of females and 7% of males received a DXA referral, and 22% of females and 14% males received osteoporosis medication following fracture. A higher CCI was associated with a lower probability of being investigated [adjusted OR, females: 0.73 (95% CI, 0.61 to 0.87) and 0.43 (95% CI, 0.30 to 0.62); males: 0.47 (95% CI, 0.33 to 0.68) and 0.52 (0.31 to 0.85) for CCI: 2 to 3, and ≥4 versus 0 to 1, respectively] and of receiving osteoporosis medication [adjusted OR, females: 0.85 (95% CI, 0.74 to 0.98) and 0.78 (95% CI, 0.61 to 0.99); males: 0.75 (95% CI, 0.59 to 0.94) and 0.37 (95% CI, 0.23 to 0.53) for CCI: 2 to 3, and ≥4 versus 0 to 1, respectively]. The cohort is relatively healthy; therefore, the impact of multimorbidity on osteoporosis management may have been underestimated. Conclusions: Multimorbidity contributed significantly to osteoporosis treatment gap. This suggests that fracture risk is either underestimated or underprioritized in the context of multimorbidity and highlights the need for extra vigilance and improved fracture care in this setting. Dana Bliuc and team investigate the association between multimorbidity and osteoporosis investigation and treatment in persons at high risk following an osteoporotic fracture. Author summary: Why was this study done?: Osteoporotic fractures are common, costly, and associated with increased risk of future fracture and premature mortality. Effective preventive treatment is available and recommended for high-risk patients with a 10-year fracture risk >20%, but its uptake in this group is suboptimal. High-risk patients often have multiple chronic conditions, and it is important to know to what degree the other chronic conditions might alter the uptake of fracture prevention medication in order to optimise patient care. What did the researchers do and find?: We conducted a prospective study including over 10,000 adults aged 50+ with an osteoporotic fracture and high-risk of future fracture to investigate the association between multimorbidity and osteoporosis investigation and treatment. In this high-risk group, the vast majority of adults were not investigated or treated for osteoporosis following an osteoporotic fracture. Adults with multiple chronic conditions were significantly less likely to be investigated [adjusted OR, females: 0.73 (95% CI, 0.61 to 0.87) and 0.43 (95% CI, 0.30 to 0.62); males: 0.47 (95% CI, 0.33 to 0.68) and 0.52 (0.31 to 0.85) for CCI: 2 to 3, and ≥4 versus 0 to 1, respectively] or treated for osteoporosis [adjusted OR, females: 0.85 (95% CI, 0.74 to 0.98) and 0.78 (95% CI, 0.61 to 0.99); males: 0.75 (95% CI, 0.59 to 0.94) and 0.37 (95% CI, 0.23 to 0.53) for CCI: 2 to 3, and ≥4 versus 0 to 1, respectively] compared to those without chronic conditions. What do these findings mean?: The presence of additional chronic conditions was associated with a lower likelihood of being investigated and treated for osteoporosis. These findings suggest that fracture preventing treatment is either underprioritised or underestimated in the presence of other chronic conditions. There is a need for more awareness of increased fracture risk in complex patients with multiple chronic conditions. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cell transplantation (HSCT) is an established therapeutic strategy for the treatment of malignant (leukemia and lymphoma) and non-malignant (thalassemia, anemia, and immunodeficiency) hematopoietic diseases. Thanks to the improvement in patient care and the development of more tolerable conditioning treatments, which has extended the applicability of therapy to the elderly, a growing number of patients have successfully benefited from HSCT therapy and, more importantly, HSCT transplant-related mortality has consistently reduced in recent years. However, concomitantly to long term patient survival, a growing incidence of late HSCT-related sequelae has been reported, being variably associated with negative effects on quality of life of patients and having a non-negligible impact on healthcare systems. The most predominantly observed HSCT-caused complications are chronic alterations of the endocrine system and metabolism, which endanger postoperative quality of life and increase morbidity and mortality of transplanted patients. Here, we specifically review the current knowledge on HSCT-derived side-effects on the perturbation of mineral metabolism; in particular, the homeostasis of calcium, focusing on current reports regarding osteoporosis and recurrent renal dysfunctions that have been observed in a percentage of HSC-transplanted patients. Possible secondary implications of conditioning treatments for HSCT on the physiology of the parathyroid glands and calcium homeostasis, alone or in association with HSCT-caused renal and bone defects, are critically discussed as well. [ABSTRACT FROM AUTHOR]

Introduction: Fracture Liaison Services (FLS) has been proven effective in reducing subsequent fractures and related mortality. However, more research is needed on the impact of FLS on the 30-day readmission rate and its effectiveness in rural hospitals. This study aims to assess the impact of FLS on clinical outcomes including readmission rates, subsequent fractures, and fracture-related mortality in rural areas of an Asain country. Materials and methods: In a rural hospital in Taiwan, we conducted a two-year prospective cohort study on elderly individuals with fragility hip fractures. The study compared the clinical outcomes between the control group and the FLS-cohort group. Logistic regression analysis was used to identify factors contributing to 1-year mortality after injury. Results: 556 patients were enrolled. (304 in the control group and 252 in the FLS group) The mean age was 79.8 years. The findings revealed that the introduction of FLS did not result in significant differences in mortality, readmission, complication, subsequent fractures, or secondary hip fractures. However, there were notable improvements in the length of hospital stay and the proportion of patients receiving surgery within 48 h following the implementation of FLS. Subgroup analysis showed that FLS patients who received anti-osteoporotic treatment had lower mortality and 30-day readmission rates. Factors associated with higher 1-year mortality included male, high ASA level, and delayed surgery. Discussion: This study provides the real-life evidence of the effect of intensive FLS model in a rural hospital in an Asian country. Conclusion: While FLS did not show significant differences in certain clinical outcomes, it led to shorter hospital stays and increased timely surgeries. FLS patients receiving anti-osteoporotic treatment had better mortality and readmission rates. Further research is necessary to gain a comprehensive understanding of the impact of FLS care in rural areas of Asia. [ABSTRACT FROM AUTHOR]

Patients who undergo shoulder surgery are frequently affected by osteoporosis and osteopenia, and the prevalence of this association is expected to increase due to the growing number of elderly individuals undergoing these procedures. It may be advisable to conduct a preoperative DXA scan for orthopedic surgical candidates at high risk, to detect those who could benefit from early intervention and avoid any related adverse events. Some of these complications include periprosthetic fractures, infection, subsequent fragility fractures, and have an all-cause revision arthroplasty at 2 years post-op. Some studies analyzed the beneficence of antiresorptive medications pre-operatively but the latter did not show favorable outcomes. Surgical management may include cementing components of the prosthesis as well as modifying the diameter of the shoulder stem. Nevertheless, more studies are needed to evaluate the efficacy of any intervention, whether medical or surgical, to avoid any shoulder arthroplasty related-complication that may be precipitated by the reduced bone mineral density. [ABSTRACT FROM AUTHOR]

Osteoporosis and fragility fractures (FFs) are considered critical health problems by the World Health Organization (WHO) because of high morbidity, mortality, and healthcare costs. The occurrence of a FF raises the risk of a subsequent fracture (refracture). The hip is the most common site of fragility refracture, and its onset is associated with a further increase in patient's morbidity, mortality, and socioeconomic burden. Therefore, the prevention of refracture is essential. In this context, fracture liaison service (FLS) demonstrated to be able to reduce FF risk and also improve patients' adherence to anti-osteoporotic treatments, particularly for bisphosphonates (BPs). However, long-term and high adherence to BPs may lead to atypical femoral fractures (AFFs). These latter are tensile side stress fractures of the femur, with high rates of complications, including delayed and non-healing. An effective FLS should be able to prevent both FF and AFF. A comprehensive and interdisciplinary approach, through the involvement and education of a dedicated team of healthcare professionals (i.e. orthopedic, geriatrician, primary care physician, rehabilitation team, and bone nurse) for evaluating both FF and AFF risks might be useful to improve the standard of care. [ABSTRACT FROM AUTHOR]

Background: T-score discordance is common in osteoporosis diagnosis and leads to problems for clinicians formulating treatment plans. Objectives: This study investigated the potential predictors of T-score discordance and compared fracture risk among individuals with varying T-score discordance status. Design: This was a single-center cross-sectional study conducted at Wan Fang Hospital, Taipei City, between 1 February 2020 and 31 January 2022. Methods: The present study enrolled patients aged ≥50 years who received advanced bone health examination. Participants with a history of fracture surgery or underlying musculoskeletal diseases were excluded. Bioelectrical impedance analysis and dual-energy X-ray absorptiometry were used to determine the body composition and T-score, respectively. Discordance was defined as different T-score categories between the lumbar spine and hip. The impact of discordance on an individual's fracture risk was assessed using the Fracture Risk Assessment Tool (FRAX). Results: This study enrolled 1402 participants (181 men and 1221 women). Of the 912 participants diagnosed with osteoporosis, 47 (5%) and 364 (40%) were categorized as having major and minor discordance, respectively. Multinomial logistic regression revealed that decreased walking speed was significantly correlated with major discordance but not osteoporosis in both the hip and lumbar spine (odds ratio of 0.25, p = 0.04). The adjusted FRAX scores for the major osteoporotic fracture risks of the major and minor discordance groups were approximately 14%, which was significantly lower than that of people having osteoporosis in both the hip and lumbar spine. Conclusions: Walking speed exhibited the most significant correlation with major discordance in patients with osteoporosis. Although adjusted major fracture risks were similar between the major and minor discordance groups, further longitudinal studies are warranted to confirm this finding. Registrations: This study was approved by the Ethics Committee of Taipei Medical University on 01/04/2022 (TMU-JIRB N202203088). [ABSTRACT FROM AUTHOR]

Given the aging population, with a peak age-specific prevalence that is shifting beyond the age of 50, several women currently living with MS are very close to menopause. Menopause is usually characterized by several specific symptoms with adverse impacts on different aspects of a woman's quality of life, such as fatigue, and cognitive, mood and bladder disorders, which overlap with symptoms of MS. Generally, after this biological transition, women with MS appear to be subject to less inflammatory activity. However, several studies have reported an increase of disability accumulation after menopause, suggesting that it is a turning point to a more progressive phase of the disease. This may be attributable to the hormonal and immunological changes associated with menopause, with several effects on neuroinflammation and neurodegeneration increasing due to the immunosenescence of aging. This review summarizes the hormonal and immunological changes associated with menopause, detailing the effects on MS symptoms, outcomes, and the aging process. Furthermore, possible interventions to improve patients' quality of life are evaluated. In fact, it is increasingly necessary to improve the global management of MS women, as well as their lives, at this multifaceted turning point. [ABSTRACT FROM AUTHOR]

Summary: This study evaluates a novel, simple bone health screening protocol composed of patient sex, age, fracture history, and FRAX risk to identify total knee arthroplasty patients for preoperative DXA. Findings supported effectiveness, with sensitivity of 1.00 (CI 0.92–1.00) and specificity of 0.54 (CI 0.41–0.68) when evaluating for clinical osteoporosis. Purpose: Bone health optimization is a process where osteoporotic patients are identified, evaluated via modalities such as dual-energy X-ray absorptiometry (DXA), and treated when indicated. There are currently no established guidelines to determine who needs presurgical DXA. This study evaluates the effectiveness of a simple screening protocol to identify TKA patients for preoperative DXA. Methods: This prospective cohort study began on September 1, 2019, and included 100 elective TKA patients. Inclusion criteria were ≥ 50 years and primary TKA. All patients obtained routine clinical DXA. The screening protocol defining who should obtain DXA included meeting any of the following: female ≥ 65, male ≥ 70, fracture history after age 50, or FRAX major osteoporotic fracture risk without bone mineral density (BMD) adjustments ≥ 8.4%. Osteoporosis was defined by the World Health Organization (WHO) criteria (T-score ≤ − 2.5) or clinically (T-score ≤ − 2.5, elevated BMD-adjusted FRAX risk, or prior hip/spine fracture). Sensitivity and specificity were calculated. Results: The study included 68 females and 32 males, mean age 67.2 ± 7.7. T-score osteoporosis was observed in 16 patients while 43 had clinical osteoporosis. Screening criteria recommending DXA was met by 69 patients. Screening sensitivity was 1.00 (CI 0.79–1.00) and specificity was 0.37 (CI 0.27–0.48) for identifying patients with T-score osteoporosis. Similar sensitivity of 1.00 (CI 0.92–1.00) and specificity of 0.54 (CI 0.41–0.68) were found for clinical osteoporosis. Conclusions: A simple screening protocol identifies TKA patients with T-score and clinical osteoporosis for preoperative DXA with high sensitivity in this prospective cohort study. [ABSTRACT FROM AUTHOR]

This position paper of the International Osteoporosis Foundation (IOF) and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) addresses the rationale for separate diagnostic and intervention thresholds in osteoporosis. We conclude that the current BMD-based diagnostic criteria for osteoporosis be retained whilst clarity is brought to bear on the distinction between diagnostic and intervention thresholds. [ABSTRACT FROM AUTHOR]

Osteoporosis screening, diagnosis, and treatment have gained much attention in the health care community over the past 2 decades. During this time, creation of multispecialty awareness programs (eg, "Own the Bone," American Orthopedic Association; "Capture the Fracture," International Osteoporosis Foundation) and improvements in diagnostic protocols have been evident. Significant advances in technology have elucidated elements of genetic predisposition for decreased bone mineral density in the aging population. Additionally, several novel drug therapies have entered the market and provide more options for primary care and osteoporosis specialists to medically manage patients at risk for fragility fractures. Despite this, adherence to osteoporosis screening and treatment protocols has been surprisingly low by health care practitioners, including orthopedic surgeons. Continued awareness and education of this skeletal disorder is crucial to effectively care for our aging population. [Orthopedics. 2023;46(1):e20–e26.] [ABSTRACT FROM AUTHOR]

Objective: Zoledronic acid (ZA) is an antiosteoporotic drug that has been proven to reduce mortality after a hip fracture (HF). ZA is however underused with older HF patients. One possible cause may be the high prevalence of severe renal failure and hypocalcemia which contraindicate ZA administration. The aim of this study was to assess the prevalence of these 2 contraindications in patients aged 75 years or older admitted into an orthogeriatric (OG) unit after a low-energy HF. The secondary objective was to assess the prevalence of situations in which ZA must be used with caution.Methods: Our retrospective descriptive monocentric study was performed in an OG unit on a cohort of elderly patients hospitalized for HF from August 2015 to August 2017. Prevalence of hypocalcemia lower than 2 mmol/L and Cockcroft creatinine clearance lower than 35 mL/min was recorded.Results: Among the 194 patients admitted for HF, 136 patients (mean age 86 ± 5.6 years; 101 women) were included. The mean length of hospital stay was 15 ± 9 days. 111 (81.5%) had no contraindications to ZA administration. More than 80% presented situations in which ZA had to be used with caution, including 25(OH)D deficiency (20%).Conclusion: The majority of subjects aged 75 years or older admitted to hospital after an HF seem to have no contraindication for ZA administration during their immediate postoperative hospital stay. The hospitalization period after HF repair gives the opportunity to give most of them this treatment to improve their prognosis, taking into account situations in which ZA must be used with caution. [ABSTRACT FROM AUTHOR]

Aim: Elagolix, a gonadotropin‐releasing hormone receptor antagonist, was recently approved for heavy menstrual bleeding associated with uterine fibroids (UF, Oriahnn) at a dose of 300 mg twice daily (BID) in combination with add‐back therapy (oestradiol 1 mg/norethindrone acetate 0.5 mg [E2/NETA] once daily) for 24 months use. The limited duration of treatment is related to elagolix dose‐ and duration‐dependent decrease in oestrogen that is mechanistically linked to changes in bone mineral density (BMD). The work herein supported the extended treatment duration of 24 months. Methods: An integrated exposure‐response and epidemiological modelling framework of elagolix effects on femoral neck BMD (FN‐BMD), informed by real‐world data and phase 3 clinical trials data, was developed to predict the time course and magnitude of changes in BMD and its relation to risk of bone fracture in women with UF. Results: Model results indicated that women treated with elagolix 300 mg BID + E2/NETA in the long term (ie, >24 months) may experience less than 1% loss in FN‐BMD per year, relative to placebo. The exposure‐response model simulations and clinical risk factors were used to estimate 10‐year risk of fractures using the clinically validated Fracture Risk Assessment Tool (FRAX). The impact of elagolix 300 mg BID + E2/NETA treatment on the 10‐year risk of hip or major osteoporotic fractures estimated from the FRAX model was minimal compared to that of placebo. Conclusion: The elagolix integrated exposure‐BMD analysis and translation to fracture risk provided an interdisciplinary model‐informed drug development framework for clinical benefit‐risk evaluation and enabled approval of longer treatment duration to benefit the patient. [ABSTRACT FROM AUTHOR]

Background: This study aimed to develop and validate a lasso regression algorithm model which was established by correlation factors of bone mineral density (BMD) and could be accurately predicted a high-risk population of primary osteoporosis (POP). It provides a rapid, economical and acceptable early screening method for osteoporosis in grass-roots hospitals. Methods: We collected 120 subjects from primary osteoporosis screening population in Zhejiang Quhua Hospital between May 2021 and November 2021 who were divided into three groups (normal, osteopenia and osteoporosis) according to the BMD T-score. The levels of three micro-RNAs in the plasma of these people were detected and assessed by qRT-PCR. At the same time, the levels of β-CTX and t-P1NP in serum of the three groups were determined. Based on the cluster random sampling method, 84 subjects (84/120, 70%) were selected as the training set and the rest were the test set. Lasso regression was used to screen characteristic variables and establish an algorithm model to evaluate the population at high risk of POP which was evaluated and tested in an independent test cohort. The feature variable screening process was used 10-fold cross validation to find the optimal lambda. Results: The osteoporosis risk score was established in the training set: Risk of primary osteoporosis score (RPOPs) = -0.1497785 + 2.52Age − 0.19miR21 + 0.35miR182 + 0.17β-CTx. The sensitivity, precision and accuracy of RPOPs in an independent test cohort were 79.17%, 82.61% and 75%, respectively. The AUC in the test set was 0.80. Some risk factors have a significant impact on the abnormal bone mass of the subjects. These risk factors were female (p = 0.00013), older than 55 (p < 2.2e-16) and BMI < 24 (p = 0.0091) who should pay more attention to their bone health. Conclusion: In this study, we successfully constructed and validated an early screening model of osteoporosis that is able to recognize people at high risk for developing osteoporosis and remind them to take preventive measures. But it is necessary to conduct further external and prospective validation research in large sample size for RPOPs prediction models. [ABSTRACT FROM AUTHOR]

Purpose: Osteoarthritis (OA), osteoporosis, and bone fractures are frequent aging-related conditions. Regardless of the growing research interest in the effects of hip OA on femoral fracture risk, data about the region specificity of osteodensitometric and hip structure analysis (HSA) parameters of the proximal femora are lacking in aged postmenopausal women with hip OA compared to individuals with femoral neck fragility fracture.Methods: This study included 76 postmenopausal women admitted for total hip arthroplasty due to non-traumatic femoral neck fracture (FN_Fx group, n = 39) and hip osteoarthritis (OA group, n = 37).Results: Osteodensitometric parameters differed significantly between the OA and FN_Fx groups, depicting lower bone mineral density in the FN_Fx group (p < 0.05). The most significant increase in these parameters was registered in the intertrochanteric region of the OA group. Moreover, the OA-induced changes in HSA-derived parameters displayed significant regional heterogeneity, with the intertrochanteric region showing the most notable difference between OA and FN_Fx group.Conclusion: Our data may indicate that OA displayed the most prominent positive effect on the intertrochanteric femoral region, revealing the regional heterogeneity in structural geometry and biomechanical indices of proximal femora in OA individuals. Since we did not observe significant differences in the femoral neck region, we may speculate that OA does not have a substantial protective effect on the femoral neck fracture risk in aged postmenopausal women. [ABSTRACT FROM AUTHOR]

To explore the association between the single nucleotide polymorphism (SNP) of leptin receptor (LEPR) gene and the susceptibility to osteoporosis (OP) among Chinese Mulao people. A total of 738 people were involved. Bone mineral density (BMD) was examined by calcaneus ultrasound attenuation measurement. Six SNPs of LEPR were detected. The genotypes, allele frequencies, linkage disequilibrium, and haplotype were analyzed. BMD decreased with age and males had higher BMD than women. The proportion of normal bone mass decreased with age, and morbidity of OP increased. Three out of six SNPs showed a difference between OP and normal group. Individuals with AA genotype of rs1137100 in OP group outnumber the normal group, AA increased the risk of OP. In rs2767485, CT increased the risk of OP, C allele may be susceptible to OP. TT genotype of rs465555 was susceptible genotype of OP, T locus may be associated with OP. Strong linkage disequilibrium was detected among rs1137100, rs1137101, and rs4655555. Four haplotypes were constructed, among which, AACGCT and GGTGTA increased the risk of OP by 3.9 and 4.2 times, respectively, whereas, GGCGTA reduced 74% of OP susceptibility. The rs1137100, rs2767485, and rs465555 of LEPR were associated with OP in Chinese Mulao people. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective cohort study. Purpose: We propose a method for screening for low bone mineral density (BMD) among perimenopausal and postmenopausal women using a self-reported questionnaire. Overview of Literature: Osteoporosis is a major health problem worldwide. However, it is not cost-effective to evaluate BMD in all patients. Although several tools for predicting osteoporosis have been established, they do not focus much on low BMD prior to the development of osteoporosis. Methods: We retrospectively reviewed the medical records of 198 women aged 40-70 years who underwent mass screening for osteoporosis at our hospital between 2016 and 2019. The BMD values and the following data were collected: age, body mass index, fracture history, lower back pain, height loss, kyphosis, history of fragility fracture, family history of vertebral or hip fracture, and menopause. The reliability of each data point for the young adult mean <80% was calculated using discriminant analysis. Variables with large weight coefficients were selected and scored. This scoring tool was examined, and a cutoff score for predicting the young adult mean <80% was determined. Results: Sixty-four participants (32.3%) had a young adult mean <80%. According to the weight coefficients, the following five variables were scored as follows: age =60 years 3 points, body mass index <22 kg/m² 3 points, lower back pain 1 point, height loss (cm) 1 point, and menopause 1 point. The area under the receiver operating characteristic curve was 0.738 (95% confidence interval, 0.669-0.807). At cutoff scores of =5 and <5, the sensitivity was 82.8%, with specificity of 52.0%. Conclusions: The scoring tool performed well for predicting young adult mean <80% among perimenopausal and postmenopausal women in Japan. This tool may be useful to screen for low BMD. [ABSTRACT FROM AUTHOR]

Abaloparatide significantly increased bone mineral density (BMD) in women with postmenopausal osteoporosis and decreased risk of vertebral, nonvertebral, and clinical fractures compared with placebo. The Abaloparatide for the Treatment of Men with Osteoporosis (ATOM; NCT03512262) study evaluated the efficacy and safety of abaloparatide compared with placebo in men. Eligible men aged 40 to 85 years with osteoporosis were randomized 2:1 to daily subcutaneous injections of abaloparatide 80 μg or placebo for 12 months. The primary endpoint was change from baseline in lumbar spine BMD. Key secondary endpoints included BMD change from baseline at the total hip and femoral neck. A total of 228 men were randomized (abaloparatide, n = 149; placebo, n = 79). Baseline characteristics were similar across treatment groups (mean age, 68.3 years; mean lumbar spine BMD T‐score, −2.1). At 12 months, BMD gains were greater with abaloparatide compared with placebo at the lumbar spine (least squares mean percentage change [standard error]: 8.48 [0.54] versus 1.17 [0.72]), total hip (2.14 [0.27] versus 0.01 [0.35]), and femoral neck (2.98 [0.34] versus 0.15 [0.45]) (all p < 0.0001). The most common (≥5%) treatment‐emergent adverse events were injection site reaction, dizziness, nasopharyngitis, arthralgia, bronchitis, hypertension, and headache. During 12 months of abaloparatide treatment, men with osteoporosis exhibited rapid and significant improvements in BMD with a safety profile consistent with previous studies. These results suggest abaloparatide can be considered as an effective anabolic treatment option for men with osteoporosis. © 2022 Radius Health Inc and The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]