New Challenges: Use and Interpretation of Radius Bone Mineral Density.

CONTEXT: It is unknown if isolated low bone mineral density (BMD) "osteoporosis" at the radius is associated with increased fracture risk, not only at the wrist but elsewhere and whether it reflects more generalized skeletal fragility. OBJECTIVE: To review the association of radius BMD and fracture risk, the epidemiology of wrist fractures, isolated osteoporosis at the radius and the concordance between radial BMD and femoral neck BMD. METHODS: We completed a narrative literature review on radius BMD and fracture risk and current recommendations for measurement of radial BMD. We updated results of radial BMD and fracture results from the Study of Osteoporotic Fractures over 20 years and examined the concordance of BMD at the distal and proximal radius with femoral neck BMD T -scores. RESULTS: Radius BMD is a robust predictor of all types of fractures including hip and wrist but there is insufficient evidence to suggest that radius BMD predicts wrist fractures better than fractures at other sites. Fractures of the wrist tend to occur in younger, healthier women compared with hip and spine fractures. Nevertheless, wrist fractures are associated with an increased risk of future fractures and represent a missed opportunity for intervention. On a population level, the discordance between radius BMD and femoral neck BMD is small. But women with isolated osteoporosis at the radius had biochemical and microarchitecture deterioration that were similar to women with hip osteoporosis. CONCLUSION: Future research should address the clinical implications of isolated osteoporosis at the radius and whether treatment is warranted.

Factors associated with fall risk increasing drug use in older black and white men and women: the Health ABC Study.

BACKGROUND: Most older adults use medications that may increase falls, often defined as fall risk increasing drugs or "FRIDs". Two definitions for FRIDs, the Centers for Disease Control and Prevention's (CDC) Stopping Elderly Accidents, Deaths & Injuries (STEADI-Rx) and Swedish National Board of Health and Welfare (SNBHW) definitions, are widely accepted, though include different FRIDs in their definitions. Whether factors associated with FRID use in older adults differ by definition is unknown. METHODS: We hypothesized that factors for FRID use will vary by FRID definition in 1,352 community-dwelling older Black and White adults with medication information in the Health, Aging and Body Composition Study (Health ABC; 2007-08 clinic visit; 83.4 ± 2.8 years; 54.1% women; 65.1% White). Multivariable logistic regression and multivariable negative binomial regression, progressively entering groups of covariates (demographics, lifestyle/behavior factors, and multimorbidity), modeled FRID use (yes/no) and count. RESULTS: Of 87.0% participants using SNBHW FRIDs, 82.9% used cardiac medications, with lower use of all other FRIDs (range:1.1-12.4%). Of 86.6% participants using STEADI-Rx FRIDs, 80.5% used cardiac medications, with lower use of all other FRIDs (range:1.1-16.1%). Participants with FRID use by either definition were more likely to have chronic health conditions, a hospitalization in the prior year, higher non-FRIDs medication counts, higher Center for Epidemiologic Studies Depression Scale (CES-D) scores, and less physical activity (all p < 0.05). Participants with STEADI-Rx FRID use had poorer vision and higher Modified Mini-Mental State (3MS) scores. In multivariable logistic regression for SNBHW use, hypertension, body mass index (BMI), 3MS scores, and non-FRID count were positively associated with FRID use and poorer vision and Digit Symbol Substitution Test (DSST) scores were negatively associated. In addition to SNBHW factors, higher CES-D scores were associated with STEADI-Rx FRID use. In multivariable negative binomial regression, hypertension, higher BMI, CES-D scores, and non-FRID count were associated with higher FRID count and sleep problems with lower FRID count for both definitions. Higher 3MS and lower DSST scores were associated with higher STEADI-Rx FRID count. Women had lower SNBHW FRID count after adjustments. CONCLUSIONS: Risk factors for FRID use in older adults differ slightly by STEADI-Rx and SNBHW FRIDs definition, but are largely similar.

24-Hour Activity Composition is Associated with Lower Fall and Fracture Risk in Older Men.

Physical activity (PA), sedentary behavior (SB), and sleep are each individually associated with falls and fractures, but often are not examined simultaneously. Compositional data analysis examined the combined prospective associations between the proportion of time in PA, SB, and sleep relative to the remaining behaviors with recurrent falls (2+ falls in any year), any fractures, and major osteoporotic fracture (MOF) from tri-annual questionnaires, with adjudication for fractures, in 2918 older men aged 78.9 ± 5.1 years in the Osteoporotic Fractures in Men (MrOS) Study. Accelerometers were worn on the right tricep for seven consecutive 24-hour periods and measured PA (>1.5 METs), SB (≤1.5 METs), and sleep. Generalized Estimating Equations evaluated associations with recurrent falls. Cox proportional hazards regression estimated any incident fracture and MOF risk separately. Over four years of follow-up 1025 (35.2%) experienced recurrent falls; over 10 ± 4 years of follow-up, 669 (22.9%) experienced incident fractures and 370 (12.7%) experienced a MOF. Higher proportions of PA relative to SB and sleep were associated with a lower odds of recurrent falls [Odds Ratio (OR): 0.87, 95% CI: 0.76-0.99]. Higher proportions of SB relative to PA and sleep were associated with a higher odds of recurrent falls (OR: 1.38, 95% CI: 1.06-1.81) and higher risk of any fracture [Hazard Ratio (HR): 1.42, 95% CI: 1.05-1.92]. Higher proportions of sleep relative to PA and SB were associated with a lower risk of fracture (HR: 0.74, 95% CI: 0.54-0.99). No associations of activity composition with MOF were observed. When accounting for the co-dependence of daily activities, higher proportions of SB relative to the proportion of PA and sleep were associated with higher odds of recurrent falls and fracture risk. Results suggest reducing SB (and increasing PA) may lower fall and fracture risk in older men, which could inform future interventions.

Physical activity, sedentary behavior, and sleep are each individually associated with falls and fractures. However, there is only a finite amount of time for each activity in a 24-hour day and the ideal structure of the day for these activities is unknown. We evaluated the association between the combination of physical activity, sedentary behavior, and sleep together with recurrent falls and fractures in older men. Spending a higher proportion of the day in physical activity was associated with a lower risk of falls, while a higher proportion of sedentary behavior was associated with a higher risk of falls and fractures. For sleep, higher proportions of the day spent sleeping were associated with a lower risk of fractures. These results can inform future physical activity interventions aimed at lowering falls and fracture risk in older men by focusing on increasing the amount of time in physical activity by specifically lowering the amount of time in sedentary behavior.

Weight change, variability, and trajectories and risk of hip fracture among older adults with Dysglycemia: the cardiovascular health study.

BACKGROUND: Type 2 diabetes mellitus and lower weight are both associated with osteoporotic fractures, but the roles of variability and trajectory are less clear.1 The associations of these factors among older adults with dysglycemia, who are at highest risk of fracture, with fracture risk and bone mineral density (BMD) remains uncertain. METHODS: We followed 775 men and 1080 women from the Cardiovascular Health Study (mean age 77.4 years) with abnormal oral glucose tolerance testing in 1989-1990. We measured their weights yearly through 1994-1995 and derived intra-individual mean weight, weight slope, and weight variability. We also used growth mixture modelling to derive four latent body-mass index trajectories over time. We used Cox proportional hazards models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for subsequent hip fracture through 2015 and linear regression models to estimate cross-sectional associations with bone mineral density (BMD) of the hip. RESULTS: Each 10 kg higher mean weight was associated with a lower risk of subsequent hip fracture overall (HR 0.81; CI 0.70-0.94) and among women (HR 0.76; CI 0.64-0.91) and with higher BMD (P-value <0.001). Higher weight variability was directly associated with incident hip fracture among women (HR 1.18; CI: 1.03-1.35). Compared with a stable trajectory, a "progressive overweight" trajectory was associated with lower risk of hip fracture (HR 0.66; CI: 0.44-0.99). An uncommon trajectory of "accelerating obesity" was associated with higher BMD. CONCLUSIONS: Among older adults with dysglycemia at high risk for fracture, lower mean weight is associated with higher fracture risk, but variability and trajectory may also contribute. These results highlight the complex effects of weight in older age.

Older adults with diabetes are susceptible to falls and fractures, but how their weight affects their bone strength and fractures remains uncertain. We followed 1855 men and women age 65 years and older with abnormal glucose in The Cardiovascular Health Study and used yearly measured weights to calculate average weight, change in weight over time, and variability in weight. Higher mean weight was associated with lower risk of hip fracture and higher bone density. Weight variability was associated with higher fracture risk among older women. Using trajectories, a group that slowly gained weight over time had a lower risk of hip fracture compared to a group with stable weight.

Fall Trajectories in Older Men: Trajectories of Change by Age and Predictors for Future Fall Risk.

BACKGROUND: Very little is known about specific trajectories or patterns of falls over time. Using the well-characterized cohort of the Osteoporotic Fractures in Men Study (MrOS), we classified individuals by fall trajectories across age and identified predictors of group assignment based on characteristics at baseline. METHODS: Using an analysis sample of 5 976 MrOS participants and 15 years of follow-up data on incident falls, we used group-based trajectory models (PROC TRAJ in SAS) to identify trajectories of change. We assessed the association of baseline characteristics with group assignment using 1-way analysis of variance and chi-square tests. Multivariable logistic regression was used to analyze the outcome of the high-risk fall trajectory groups compared to the low-risk groups. RESULTS: Changes in rates of falls were relatively constant or increasing with 5 distinct groups identified. Mean posterior probabilities for all 5 trajectories were similar and consistently above 0.8 indicating a reasonable model fit. Among the 5 fall trajectory groups, 2 were deemed high risk, those with steeply increasing fall risk and persistently high fall risk. Factors associated with fall risk included body mass index, use of central nervous agents, prior history of diabetes and Parkinson's disease, back pain, grip strength, and physical and mental health scores. CONCLUSIONS: Two distinct groups of high fall risk individuals were identified among 5 trajectory groups, those with steeply increasing fall risk and persistently high fall risk. Statistically significant characteristics for group assignment suggest that future fall risk of older men may be predictable at baseline.

Fractures by race and ethnicity in a diverse sample of postmenopausal women: a current evaluation among Hispanic and Asian origin groups.

Using 1998-2022 Women's Health Initiative (WHI) data, our study provides contemporary fracture data by race and ethnicity, specifically focusing on Hispanic and Asian women. Fractures of interest included any clinical, hip, and major osteoporotic fractures (MOFs). We utilized the updated race and ethnicity information collected in 2003, which included seven Asian and five Hispanic origin groups. We computed crude and age-standardized fracture incidence rates per 10 000 woman-years across race and ethnic categories and by Asian and Hispanic origin. We used Cox proportional hazards model, adjusting for age and WHI clinical trial arm, to evaluate the risk of fracture (1) by race compared to White women, (2) Asian origin compared to White women, (3) Hispanic compared to non-Hispanic women, and (4) Asian and Hispanic origins compared the most prevalent origin group. Over a median (interquartile range) follow-up of 19.4 (9.2-24.2) years, 44.2% of the 160 824 women experienced any clinical fracture, including 36 278 MOFs and 8962 hip fractures. Compared to White women, Black, Pacific Islander, Asian, and multiracial women had significantly lower risk of any clinical and MOFs, while only Black and Asian women had significantly lower hip fracture risk. Within Asian women, Filipina women had 24% lower risk of any clinical fracture compared to Japanese women. Hispanic women had significantly lower risk of any clinical, hip, and MOF fractures compared to non-Hispanic women, with no differences in fracture risk observed within Hispanic origin groups. In this diverse sample of postmenopausal women, we confirmed racial and ethnic differences in fracture rates and risk, with novel findings among within Asian and Hispanic subgroups. These data can aid in future longitudinal studies evaluate contributors to racial and ethnic differences in fractures.

We provided contemporary fracture rates by race and ethnicity, specifically focusing on multiple Hispanic and Asian subgroups, using 1998-2022 data from the Women's Health Initiative. Over a median follow-up of 19.4 years, 43.4% of the 154 948 women experienced any clinical fracture, including 8679 hip and 34 546 major osteoporotic fractures. Compared to White women, Black, Pacific Islander, Asian, and multiracial women had significantly lower risk of any clinical and major osteoporotic fractures (MOFs); while only Black and Asian women had significantly lower hip fracture risk when compared to White women. Within Asian women, Filipina women had 24% lower risk of any clinical fracture compared to Japanese women. Hispanic women had significantly lower risk of any clinical, hip, and MOF fractures compared to non-Hispanic women, with no differences in fracture risk observed within Hispanic women. In this diverse sample of postmenopausal women, we confirmed racial and ethnic differences in fracture rates and risk, with novel findings among Pacific Islander women and within Asian and Hispanic subgroups.

Skeletal Muscle Composition, Power, and Mitochondrial Energetics in Older Men and Women With Knee Osteoarthritis.

OBJECTIVE: Our objective was to investigate the overall and sex-specific relationships between the presence and severity of knee osteoarthritis (KOA) and muscle composition, power, and energetics in older adults. METHODS: Male and female patients (n = 655, mean ± SD age 76.1 ± 4.9 years; 57% female) enrolled in the Study of Muscle, Mobility, and Aging completed standing knee radiographs and knee pain assessments. Participants were divided into three groups using Kellgren-Lawrence grade (KLG) of KOA severity (0-1, 2, or 3-4). Outcome measures included whole-body muscle mass, thigh fat-free muscle (FFM) volume and muscle fat infiltration (MFI), leg power, specific power (power normalized to muscle volume), and muscle mitochondrial energetics. RESULTS: Overall, the presence and severity of KOA is associated with greater MFI, lower leg power and specific power, and reduced oxidative phosphorylation (P trend < 0.036). Sex-specific analysis revealed reduced energetics only in female patients with KOA (P trend < 0.007) compared to female patients without KOA. In models adjusted for age, sex, race, nonsteroidal anti-inflammatory drug administration, site or technician, physical activity, height, and participants with abdominal adiposity with KLG 3 to 4 had greater MFI (mean 0.008%, 95% confidence interval [CI] 0.004%-0.011%) and lower leg power (mean -51.56 W, 95% CI -74.03 to -29.10 W) and specific power (mean -5.38 W/L, 95% CI -7.31 to -3.45 W/L) than those with KLG 0 to 1. No interactions were found between pain and KLG status. Among those with KOA, MFI and oxidative phosphorylation were associated with thigh FFM volume, leg power, and specific power. CONCLUSION: Muscle health is associated with the presence and severity of KOA and differs by sex. Although muscle composition and power are lower in both male and female patients with KOA, regardless of pain status, mitochondrial energetics is reduced only in female patients.

Chemokine CXCL9, a marker of inflammaging, is associated with changes of muscle strength and mortality in older men.

Our study examined associations of the CXC motif chemokine ligand 9 (CXCL9), a pro-inflammatory protein implicated in age-related inflammation, with musculoskeletal function in elderly men. We found in certain outcomes both cross-sectional and longitudinal significant associations of CXCL9 with poorer musculoskeletal function and increased mortality in older men. This requires further investigation. PURPOSE: We aim to determine the relationship of (CXCL9), a pro-inflammatory protein implicated in age-related inflammation, with both cross-sectional and longitudinal musculoskeletal outcomes and mortality in older men. METHODS: A random sample from the Osteoporotic Fractures in Men (MrOS) Study cohort (N = 300) was chosen for study subjects that had attended the third and fourth clinic visits, and data was available for major musculoskeletal outcomes (6 m walking speed, chair stands), hip bone mineral density (BMD), major osteoporotic fracture, mortality, and serum inflammatory markers. Serum levels of CXCL9 were measured by ELISA, and the associations with musculoskeletal outcomes were assessed by linear regression and fractures and mortality with Cox proportional hazards models. RESULTS: The mean CXCL9 level of study participants (79.1 ± 5.3 years) was 196.9 ± 135.2 pg/ml. There were significant differences for 6 m walking speed, chair stands, physical activity scores, and history of falls in the past year across the quartiles of CXCL9. However, higher CXCL9 was only significantly associated with changes in chair stands (ß = - 1.098, p < 0.001) even after adjustment for multiple covariates. No significant associations were observed between CXCL9 and major osteoporotic fracture or hip BMD changes. The risk of mortality increased with increasing CXCL9 (hazard ratio quartile (Q)4 vs Q1 1.98, 95% confidence interval 1.25-3.14; p for trend < 0.001). CONCLUSIONS: Greater serum levels of CXCL9 were significantly associated with a decline in chair stands and increased mortality. Additional studies with a larger sample size are needed to confirm our findings.

Hip Fracture Risk Assessment Tools for Adults Aged 80 Years and Older.

Importance: While adults aged 80 years and older account for 70% of hip fractures in the US, performance of fracture risk assessment tools in this population is uncertain. Objective: To compare performance of the Fracture Risk Assessment Tool (FRAX), Garvan Fracture Risk Calculator, and femoral neck bone mineral density (FNBMD) alone in 5-year hip fracture prediction. Design, Setting and Participants: Prognostic analysis of 3 prospective cohort studies including participants attending an index examination (1997 to 2016) at age 80 years or older. Data were analyzed from March 2023 to April 2024. Main Outcomes and Measures: Participants contacted every 4 or 6 months after index examination to ascertain incident hip fractures and vital status. Predicted 5-year hip fracture probabilities calculated using FRAX and Garvan models incorporating FNBMD and FNBMD alone. Model discrimination assessed by area under receiver operating characteristic curve (AUC). Model calibration assessed by comparing observed vs predicted hip fracture probabilities within predicted risk quintiles. Results: A total of 8890 participants were included, with a mean (SD) age at index examination of 82.6 (2.7) years; 4906 participants (55.2%) were women, 866 (9.7%) were Black, 7836 (88.1%) were White, and 188 (2.1%) were other races and ethnicities. During 5-year follow-up, 321 women (6.5%) and 123 men (3.1%) experienced a hip fracture; 818 women (16.7%) and 921 men (23.1%) died before hip fracture. Among women, AUC was 0.69 (95% CI, 0.67-0.72) for FRAX, 0.69 (95% CI, 0.66-0.72) for Garvan, and 0.72 (95% CI, 0.69-0.75) for FNBMD alone (FNBMD superior to FRAX, P = .01; and Garvan, P = .01). Among men, AUC was 0.71 (95% CI, 0.66-0.75) for FRAX, 0.76 (95% CI, 0.72-0.81) for Garvan, and 0.77 (95% CI, 0.72-0.81) for FNBMD alone (P < .001 Garvan and FNBMD alone superior to FRAX). Among both sexes, Garvan greatly overestimated hip fracture risk among individuals in upper quintiles of predicted risk, while FRAX modestly underestimated risk among those in intermediate quintiles of predicted risk. Conclusions and Relevance: In this prognostic study of adults aged 80 years and older, FRAX and Garvan tools incorporating FNBMD compared with FNBMD alone did not improve 5-year hip fracture discrimination. FRAX modestly underpredicted observed hip fracture probability in intermediate-risk individuals. Garvan markedly overpredicted observed hip fracture probability in high-risk individuals. Until better prediction tools are available, clinicians should prioritize consideration of hip BMD, life expectancy, and patient preferences in decision-making regarding drug treatment initiation for hip fracture prevention in late-life adults.

Associations of empirically derived dietary patterns and cognitive performance in older men: Results of the Osteoporotic Fractures in Men (MrOS) study.

OBJECTIVE: The aim of this study was to examine associations between empirically derived dietary pattern scores and cognition, as well as risk of cognitive decline, over an average of 4.6 (± 0.3) years in older men. MATERIALS AND METHODS: This analysis was conducted as part of the Osteoporotic Fractures in Men (MrOS) prospective cohort study. Diet was assessed at Visit 1 (3/2000-4/2002) by food frequency questionnaire, and dietary patterns (Western and Prudent) were derived by factor analysis. The analytic cohort comprised 4231 community-dwelling American men who were aged 65 years or more. Cognitive function was assessed with the Modified Mini-Mental State exam (3MS) and the Trails B test at Visit 1 and at Visit 2 (3/2005-5/2006). Associations between dietary pattern score and cognition and risk of cognitive decline were estimated using mixed effects regression models. Model 1 was adjusted for age, clinic site and total energy intake (TEI). Model 2 was further adjusted for calcium and vitamin D supplement use, body mass index (BMI), physical activity, smoking, diabetes and hypertension (Western diet group) and education, calcium and vitamin D supplement use, depression, BMI, physical activity, smoking and stroke (Prudent diet group). RESULTS: Adherence to the Western dietary pattern was associated with higher 3MS scores and shorter Trails B test time at Visit 1 in Model 2. Adherence to the Prudent dietary pattern was associated with higher 3MS scores in Model 1 but not Model 2. There were no independent associations between dietary pattern scores and risk of cognitive decline 4.6 (± 0.3) years later at Visit 2. CONCLUSION: The results do not support a robust protective effect of the Prudent dietary pattern on cognition in the MrOS cohort. Associations between the Western dietary pattern and better cognitive scores should be interpreted with caution. Further research is needed to understand the complex interactions between dietary patterns and cognition in older men.

Predictive value of sarcopenia components for all-cause mortality: findings from population-based cohorts.

BACKGROUND: Low grip strength and gait speed are associated with mortality. However, investigation of the additional mortality risk explained by these measures, over and above other factors, is limited. AIM: We examined whether grip strength and gait speed improve discriminative capacity for mortality over and above more readily obtainable clinical risk factors. METHODS: Participants from the Health, Aging and Body Composition Study, Osteoporotic Fractures in Men Study, and the Hertfordshire Cohort Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over 2.4-6 m. Verified deaths were recorded. Associations between sarcopenia components and mortality were examined using Cox regression with cohort as a random effect; discriminative capacity was assessed using Harrell's Concordance Index (C-index). RESULTS: Mean (SD) age of participants (n = 8362) was 73.8(5.1) years; 5231(62.6%) died during a median follow-up time of 13.3 years. Grip strength (hazard ratio (95% CI) per SD decrease: 1.14 (1.10,1.19)) and gait speed (1.21 (1.17,1.26)), but not ALM index (1.01 (0.95,1.06)), were associated with mortality in mutually-adjusted models after accounting for age, sex, BMI, smoking status, alcohol consumption, physical activity, ethnicity, education, history of fractures and falls, femoral neck bone mineral density (BMD), self-rated health, cognitive function and number of comorbidities. However, a model containing only age and sex as exposures gave a C-index (95% CI) of 0.65(0.64,0.66), which only increased to 0.67(0.67,0.68) after inclusion of grip strength and gait speed. CONCLUSIONS: Grip strength and gait speed may generate only modest adjunctive risk information for mortality compared with other more readily obtainable risk factors.

Medicare Fee-For-Service Spending for Fall Injury and Nonfall Events: The Health, Aging, and Body Composition Study.

Background and Objectives: Fall injuries are prevalent in older adults, yet whether higher spending occurs after nonfracture (NFFI) and fracture is unknown. We examined whether incident fall injuries, including NFFI and fractures, were associated with higher Medicare spending in 12 months after incident events in older adults. Research Design and Methods: The Health, Aging, and Body Composition Study included 1 595 community-dwelling adults (53% women, 37% Black; 76.7 ±â€…2.9 years) with linked Medicare Fee-For-Service (FFS) claims at 2000/01 exam. Incident outpatient and inpatient fall injuries (N = 448) from 2000/01 exam to December 31, 2008 were identified using the first claim with a nonfracture injury diagnosis code with a fall E-code, or a fracture diagnosis code with/without an E-code. Up to 3 participants without fall injuries (N = 1 147) were matched on nonfall events to 448 participants in the fall injury month. We calculated the change in monthly FFS spending in 12 months before versus after index events in both groups. Generalized linear regression with centered outcomes and gamma distributions examined the association of prepost expenditure changes with fall injuries (including NFFI and fractures) adjusting for related covariates. Results: Monthly spending increased after versus before fall injuries (USD$2 261 vs $981), nonfracture (N = 105; USD$2 083 vs $1 277), and fracture (N = 343; USD$2 315 vs $890) injuries (all p < .0001). However, after adjusting for covariates in final models, fall injuries were not significantly associated with larger increases in spending/month versus nonfall events (differential increase: USD$399.58 [95% CI: -USD$44.95 to $844.11]). Fracture prepost change in monthly spending was similar versus NFFI (differential increase: USD$471.93 [95% CI: -USD$21.17 to $965.02]). Discussion and Implications: Although substantial increases occurred after injuries, with fracture and NFFI increasing similarly, changes in monthly spending after fall injury were not different compared to nonfall events. Our results contribute to the understanding of subsequent spending after fall injury that may inform further research on fall injury-related health care spending.

The Women's Health Initiative Randomized Trials and Clinical Practice: A Review.

Importance: Approximately 55 million people in the US and approximately 1.1 billion people worldwide are postmenopausal women. To inform clinical practice about the health effects of menopausal hormone therapy, calcium plus vitamin D supplementation, and a low-fat dietary pattern, the Women's Health Initiative (WHI) enrolled 161 808 postmenopausal US women (N = 68 132 in the clinical trials) aged 50 to 79 years at baseline from 1993 to 1998, and followed them up for up to 20 years. Observations: The WHI clinical trial results do not support hormone therapy with oral conjugated equine estrogens plus medroxyprogesterone acetate for postmenopausal women or conjugated equine estrogens alone for those with prior hysterectomy to prevent cardiovascular disease, dementia, or other chronic diseases. However, hormone therapy is effective for treating moderate to severe vasomotor and other menopausal symptoms. These benefits of hormone therapy in early menopause, combined with lower rates of adverse effects of hormone therapy in early compared with later menopause, support initiation of hormone therapy before age 60 years for women without contraindications to hormone therapy who have bothersome menopausal symptoms. The WHI results do not support routinely recommending calcium plus vitamin D supplementation for fracture prevention in all postmenopausal women. However, calcium and vitamin D are appropriate for women who do not meet national guidelines for recommended intakes of these nutrients through diet. A low-fat dietary pattern with increased fruit, vegetable, and grain consumption did not prevent the primary outcomes of breast or colorectal cancer but was associated with lower rates of the secondary outcome of breast cancer mortality during long-term follow-up. Conclusions and Relevance: For postmenopausal women, the WHI randomized clinical trials do not support menopausal hormone therapy to prevent cardiovascular disease or other chronic diseases. Menopausal hormone therapy is appropriate to treat bothersome vasomotor symptoms among women in early menopause, without contraindications, who are interested in taking hormone therapy. The WHI evidence does not support routine supplementation with calcium plus vitamin D for menopausal women to prevent fractures or a low-fat diet with increased fruits, vegetables, and grains to prevent breast or colorectal cancer. A potential role of a low-fat dietary pattern in reducing breast cancer mortality, a secondary outcome, warrants further study.

Gender and age differences in the associations between cortical thickness and hand osteoarthritis severity: data from the Osteoarthritis Initiative.

OBJECTIVE: To evaluate gender differences in the association between metacarpal cortical thickness (Tcort)-a surrogate for bone density-and severity of radiographic hand osteoarthritis (HOA) in a longitudinal observational study. METHOD: Hand radiographs of 3575 participants (2039 F/1536 M) from the Osteoarthritis Initiative were assessed at baseline and 48 months. A reader used a semi-automated software tool to calculate Tcort, a measurement of the cortical thickness, for metacarpals 2-4. Average Tcort at baseline and change in Tcort from baseline to 48 months was determined and stratified by gender and age for 7 5-year age groups. Spearman's rank correlation coefficients were calculated for the association of baseline Tcort and 2 measures of baseline HOA severity: the sum of Kellgren-Lawrence (KL) grade and total number of joints with radiographic HOA. Longitudinally, logistic regression was used to assess the relationship of Tcort loss to new finger joint radiographic HOA, increase in KL grades, and incident hand pain. RESULTS: Male Tcort was higher than females. Significant correlations between Tcort and radiographic severity were noted for women but not men, with stronger associations among women >60 years (rho = -0.25; 95% confidence interval (CI) = -0.31 to -0.19). Statistically significant associations were seen between Tcort change and radiographic osteoarthritis change among women but not men, with substantial gender differences for Tcort change, particularly ages 50 to 70 years (p < 0.01; e.g., Tcort change ages 55 to <60: males = -0.182 (0.118), females = -0.219 (0.124)). CONCLUSION: We found significant HOA-related gender differences in Tcort, suggesting the involvement of female bone loss during and after menopause.

The American Society for Bone and Mineral Research Task Force on clinical algorithms for fracture risk report.

Using race and ethnicity in clinical algorithms potentially contributes to health inequities. The American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee convened the ASBMR Task Force on Clinical Algorithms for Fracture Risk to determine the impact of race and ethnicity adjustment in the US Fracture Risk Assessment Tool (US-FRAX). The Task Force engaged the University of Minnesota Evidence-based Practice Core to conduct a systematic review investigating the performance of US-FRAX for predicting incident fractures over 10 years in Asian, Black, Hispanic, and White individuals. Six studies from the Women's Health Initiative (WHI) and Study of Osteoporotic Fractures (SOF) were eligible; cohorts only included women and were predominantly White (WHI > 80% and SOF > 99%), data were not consistently stratified by race and ethnicity, and when stratified there were far fewer fractures in Black and Hispanic women vs White women rendering area under the curve (AUC) estimates less stable. In the younger WHI cohort (n = 64 739), US-FRAX without bone mineral density (BMD) had limited discrimination for major osteoporotic fracture (MOF) (AUC 0.53 (Black), 0.57 (Hispanic), and 0.57 (White)); somewhat better discrimination for hip fracture in White women only (AUC 0.54 (Black), 0.53 (Hispanic), and 0.66 (White)). In a subset of the older WHI cohort (n = 23 918), US-FRAX without BMD overestimated MOF. The Task Force concluded that there is little justification for estimating fracture risk while incorporating race and ethnicity adjustments and recommends that fracture prediction models not include race or ethnicity adjustment but instead be population-based and reflective of US demographics, and inclusive of key clinical, behavioral, and social determinants (where applicable). Research cohorts should be representative vis-à-vis race, ethnicity, gender, and age. There should be standardized collection of race and ethnicity; collection of social determinants of health to investigate impact on fracture risk; and measurement of fracture rates and BMD in cohorts inclusive of those historically underrepresented in osteoporosis research.

Using race or ethnicity when calculating disease risk may contribute to health disparities. The ASBMR Task Force on Clinical Algorithms for Fracture Risk was created to understand the impact of the US Fracture Risk Assessment Tool (US-FRAX) race and ethnicity adjustments. The Task Force reviewed the historical development of FRAX, including the assumptions underlying selection of race and ethnicity adjustment factors. Furthermore, a systematic review of literature was conducted, which revealed an overall paucity of data evaluating the performance of US-FRAX in racially and ethnically diverse groups. While acknowledging the existence of racial and ethnic differences in fracture epidemiology, the Task Force determined that currently there is limited evidence to support the use of race and ethnicity­specific adjustments in US-FRAX. The Task Force also concluded that research is needed to create generalizable fracture risk calculators broadly applicable to current US demographics, which do not include race and ethnicity adjustments. Until such population­based fracture calculators are available, clinicians should consider providing fracture risk ranges for Asian, Black, and/or Hispanic patients and should engage in shared decision-making with patients about fracture risk interpretation. Future studies are required to evaluate fracture risk tools in populations inclusive of those historically underrepresented in research.

Physical function trajectory after wrist or lower arm fracture in postmenopausal women: results from the Women's Health Initiative Study.

Long-term physical functioning trajectories following distal forearm fracture are unknown. We found that women with versus those without distal forearm fracture were more likely to experience a 5-year decline in physical functioning, independent of initial physical functioning level. This association was most evident among women 80 years and older. INTRODUCTION: Physical functioning trajectory following lower arm or wrist fracture is not well understood. PURPOSE: This study is to evaluate physical functioning trajectory before vs. after lower arm or wrist fracture, stratified by age. METHODS: We performed a nested case-control study of prospective data from the Women's Health Initiative Study (n = 2097 cases with lower arm or wrist fracture, 20,970 controls). Self-reported fractures and the physical functioning subscale of the RAND 36-item Short-Form Health Survey were assessed annually. We examined three physical functioning trajectory groups: stable, improving, and declining. RESULTS: Mean (SD) number of physical functioning measurements was 5.2 (1.5) for cases and 5.0 (1.4) for controls. Declining physical functioning was observed among 20.4% of cases and 16.0% of controls. Compared to women without lower arm or wrist fracture, women with lower arm or wrist fracture were 33% more likely to experience declining physical functioning (adjusted odds ratio [aOR] 1.33 95% confidence interval [CI] 1.19-1.49, reference group stable or improving physical functioning trajectory). Associations varied by age: age ≥ 80 years aOR 1.56 (95% CI 1.29-1.88); age 70-79 years aOR 1.29 (95% CI 1.09-1.52); age < 70 years aOR 1.15 (95% CI 0.86-1.53) (pinteraction = 0.06). Associations between lower arm or wrist fracture and odds of declining physical functioning did not vary by baseline physical functioning or physical activity level. CONCLUSIONS: Women with lower arm or wrist fracture, particularly those aged 80 and older, were more likely to experience declines in physical functioning than women without such fractures, independent of baseline physical functioning level.

Balancing fracture risk versus risk of mortality before fracture among women aged 80 years or older.

BACKGROUND: Most fractures occur in women aged ≥80 years but competing mortality unrelated to fracture may limit the benefit of osteoporosis drug therapy for some women in late life. Our primary aim was to develop separate prediction models for non-spine fracture (NSF) and mortality before fracture to identify subsets of women with varying fracture versus mortality risks. METHODS: Separate prediction models were developed for NSF and mortality before NSF for 4895 women aged ≥80 years enrolled in the Study of Osteoporotic Fractures (SOF) or the Health Aging and Body Composition (HABC) study. Proportional hazards models modified to account for competing mortality were used to identify candidate risk factors for each outcome. Predictors associated with NSF or mortality (p < 0.2) were included in separate competing risk models to estimate the cumulative incidence of NSF and mortality before NSF during 5 years of follow-up. This process was repeated to develop separate prediction models for hip fracture and mortality before hip fracture. RESULTS: Significant predictors of NSF (race, total hip BMD, grip strength, prior fracture, falls, and use of selective serotonin reuptake inhibitors, benzodiazepines, or oral/transdermal estrogen) differed from predictors of mortality before NSF (age, walking speed, multimorbidity, weight change, shrinking, smoking, self-rated health, dementia, and use of warfarin). Within nine subsets of women defined by tertiles of risk, 5-year outcomes varied from 28% NSF and 8% mortality in the high-risk NSF/low-risk mortality subset, to 9% NSF and 22% mortality in the low-risk NSF/high-risk mortality subset. Similar results were seen for predictors of hip fracture and mortality before hip fracture. CONCLUSION: Considerable variation in 5-year competing mortality risk is present among women in late life with similar 5-year NSF risk. Both fracture risk and life expectancy should inform shared clinical decision-making regarding initiation or continuation of osteoporosis drug therapy for women aged ≥80 years.

Associations between hypertension with reproductive and menopausal factors: An integrated women's health programme (IWHP) study.

BACKGROUND: Women are less likely to have classic cardiovascular risk factors than men, and events during their reproductive and menopausal years may increase hypertension risk. The aim of this study is to examine woman-specific factors, including menstrual, reproductive and pregnancy complications, in relation to the prevalence of hypertension in mid-life Asian women. METHODS: This is a cross-sectional study of 1146 healthy women aged 45-69 years, from a multi-ethnic Asian cohort. The women completed an extensive questionnaire that included their sociodemographic details, medical history, lifestyle and physical activity, and reproductive and menopausal history. They also underwent objectively measured physical performance tests and a dual X-ray absorptiometry scan. Hypertension was defined as a systolic BP ≥140 and/or diastolic BP ≥90mm Hg, past diagnosis by a physician, or use of antihypertensive medications. Multivariable logistic regression was used to assess the independent risk factors for hypertension. RESULTS: The average age of the 1146 women analysed was 56.3 (SD 6.2) years, and 55.2 percent of them were hypertensive. The prevalence of gestational diabetes and gestational hypertension was 12.6% and 9.4%, respectively. Besides age, abnormal menstrual cycle length at 25 years of age (OR:2.35, CI:1.34-4.13), preeclampsia (OR:2.46, CI:1.06-5.74), increased visceral adiposity (OR:4.21, CI:2.28-7.79) and reduced physical performance (OR:2.83, CI:1.46-5.47) were independently associated with hypertension in Asian women. CONCLUSIONS: Our findings highlight the necessity of including features of menstrual and reproductive history as possible indicators of hypertension risk in cardiovascular disease risk assessment and prevention among Asian women. Reducing visceral adiposity and exercise to improve physical performance may help women avoid developing hypertension.

More rapid bone mineral density loss in older men with diabetes: The Osteoporotic Fractures in Men (MrOS) Study.

CONTEXT: Type 2 diabetes mellitus (T2D) is associated with more rapid bone loss in women, but less evidence is available for men or those with prediabetes. OBJECTIVE: To determine whether bone loss rate is affected by diabetes status in older men, we analyzed data from the Osteoporotic Fractures in Men (MrOS) study. METHODS: The multisite MrOS study enrolled 5,994 men aged ≥65 years. Diabetes status was defined by self-report, diabetes medication use, or elevated fasting serum glucose at baseline. Hip bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DXA) at baseline and a follow-up visit after 4.6 ± 0.4 years. This analysis included 4095 men, excluding those without a follow-up DXA or with unknown diabetes status. Changes in hip BMD in participants with normoglycemia (NG), prediabetes, or T2D, excluding thiazolidinedione (TZD) users, were evaluated using generalized linear models (GLM). Diabetes medication use and BMD loss among those with T2D were also evaluated with GLM. RESULTS: In adjusted models, loss in hip BMD was greater in men with T2D (- 2.23%: 95% CI: -2.54 to -1.91; p<0.001) but not in men with prediabetes (-1.45%; 95% CI -1.63 to -1.26; p=0.33) compared to NG (-1.57%: 95% CI -1.73 to -1.41). Among men with T2D, TZD, insulin and sulfonylurea use were associated with greater hip BMD loss. CONCLUSIONS: Men with T2D, but not prediabetes, experienced an accelerated bone loss compared to participants with normoglycemia. More rapid bone loss predicts increased risk of fractures and mortality in broader populations.