Osteoporosis.

Osteoporosis is a common systemic skeletal disorder resulting in bone fragility and increased fracture risk. Evidence-based screening strategies improve identification of patients who are most likely to benefit from drug treatment to prevent fracture. In addition, careful consideration of when pharmacotherapy should be started, choice of medication, and duration of treatment maximizes the benefits of fracture prevention while minimizing potential harms of long-term drug exposure.

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.

Neighborhood Socioeconomic Deprivation and Health Care Costs in Older Community-Dwelling Adults: Importance of Functional Impairment and Frailty.

BACKGROUND: Low neighborhood socioeconomic status is associated with adverse health outcomes, but its association with health care costs in older adults is uncertain. OBJECTIVES: To estimate the association of neighborhood Area Deprivation Index (ADI) with total, inpatient, outpatient, skilled nursing facility (SNF), and home health care (HHC) costs among older community-dwelling Medicare beneficiaries, and determine whether these associations are explained by multimorbidity, phenotypic frailty, or functional impairments. DESIGN: Four prospective cohort studies linked with each other and with Medicare claims. PARTICIPANTS: In total, 8165 community-dwelling fee-for-service beneficiaries (mean age 79.2 years, 52.9% female). MAIN MEASURES: ADI of participant residence census tract, Hierarchical Conditions Category multimorbidity score, self-reported functional impairments (difficulty performing four activities of daily living), and frailty phenotype. Total, inpatient, outpatient, post-acute SNF, and HHC costs (US 2020 dollars) for 36 months after the index examination. KEY RESULTS: Mean incremental annualized total health care costs adjusted for age, race/ethnicity, and sex increased with ADI ($3317 [95% CI 1274 to 5360] for the most deprived vs least deprived ADI quintile, and overall p-value for ADI variable 0.009). The incremental cost for the most deprived vs least deprived ADI quintile was increasingly attenuated after separate adjustment for multimorbidity ($2407 [95% CI 416 to 4398], overall ADI p-value 0.066), frailty phenotype ($1962 [95% CI 11 to 3913], overall ADI p-value 0.22), or functional impairments ($1246 [95% CI -706 to 3198], overall ADI p-value 0.29). CONCLUSIONS: Total health care costs are higher for older community-dwelling Medicare beneficiaries residing in the most socioeconomically deprived areas compared to the least deprived areas. This association was not significant after accounting for the higher prevalence of phenotypic frailty and functional impairments among residents of socioeconomically deprived neighborhoods.

Association of back pain with all-cause and cause-specific mortality among older men: a cohort study.

OBJECTIVE: We evaluated whether more severe back pain phenotypes-persistent, frequent, or disabling back pain-are associated with higher mortality rate among older men. METHODS: In this secondary analysis of a prospective cohort, the Osteoporotic Fractures in Men (MrOS) study, we evaluated mortality rates by back pain phenotype among 5215 older community-dwelling men (mean age, 73 years, SD = 5.6) from 6 sites in the United States. The primary back pain measure used baseline and Year 5 back pain questionnaire data to characterize participants as having no back pain, nonpersistent back pain, infrequent persistent back pain, or frequent persistent back pain. Secondary measures of back pain from the Year 5 questionnaire included disabling back pain phenotypes. The main outcomes measured were all-cause and cause-specific death. RESULTS: After the Year 5 exam, during up to 18 years of follow-up (mean follow-up = 10.3 years), there were 3513 deaths (1218 cardiovascular, 764 cancer, 1531 other). A higher proportion of men with frequent persistent back pain versus no back pain died (78% versus 69%; sociodemographic-adjusted HR = 1.27, 95% CI = 1.11-1.45). No association was evident after further adjustment for health-related factors, such as self-reported general health and comorbid chronic health conditions (fully adjusted HR = 1.00; 95% CI = 0.86-1.15). Results were similar for cardiovascular deaths and other deaths, but we observed no association of back pain with cancer deaths. Secondary back pain measures, including back-related disability, were associated with increased mortality risk that remained statistically significant in fully adjusted models. CONCLUSION: Although frequent persistent back pain was not independently associated with risk of death in older men, additional secondary disabling back pain phenotypes were independently associated with increased mortality rate. Future investigations should evaluate whether improvements in disabling back pain affect general health and well-being or risk of death.

Incremental Health Care Costs of Self-Reported Functional Impairments and Phenotypic Frailty in Community-Dwelling Older Adults : A Prospective Cohort Study.

BACKGROUND: Health care systems need better strategies to identify older adults at risk for costly care to select target populations for interventions to reduce health care burden. OBJECTIVE: To determine whether self-reported functional impairments and phenotypic frailty are associated with incremental health care costs after accounting for claims-based predictors. DESIGN: Prospective cohort study. SETTING: Index examinations (2002 to 2011) of 4 prospective cohort studies linked with Medicare claims. PARTICIPANTS: 8165 community-dwelling fee-for-service beneficiaries (4318 women, 3847 men). MEASUREMENTS: Weighted (Centers for Medicare & Medicaid Services Hierarchical Condition Category index) and unweighted (count of conditions) multimorbidity and frailty indicators derived from claims. Self-reported functional impairments (difficulty performing 4 activities of daily living) and frailty phenotype (operationalized using 5 components) derived from cohort data. Health care costs ascertained for 36 months after index examinations. RESULTS: Average annualized costs (2020 U.S. dollars) were $13 906 among women and $14 598 among men. After accounting for claims-based indicators, average incremental costs of functional impairments versus no impairment in women (men) were $3328 ($2354) for 1 impairment increasing to $7330 ($11 760) for 4 impairments; average incremental costs of phenotypic frailty versus robust in women (men) were $8532 ($6172). Mean predicted costs adjusted for claims-based indicators in women (men) varied by both functional impairments and the frailty phenotype ranging from $8124 ($11 831) among robust persons without impairments to $18 792 ($24 713) among frail persons with 4 impairments. Compared with the model with claims-derived indicators alone, this model resulted in more accurate cost prediction for persons with multiple impairments or phenotypic frailty. LIMITATION: Cost data limited to participants enrolled in the Medicare fee-for-service program. CONCLUSION: Self-reported functional impairments and phenotypic frailty are associated with higher subsequent health care expenditures in community-dwelling beneficiaries after accounting for several claims-based indicators of costs. PRIMARY FUNDING SOURCE: National Institutes of Health.

The association between multimorbidity and osteoporosis investigation and treatment in high-risk fracture patients in Australia: A prospective cohort study.

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.

Relation Between Dietary Protein Intake and Gut Microbiome Composition in Community-Dwelling Older Men: Findings from the Osteoporotic Fractures in Men Study (MrOS).

BACKGROUND: Little is known about the association of specific nutrients, especially proteins, on age-related gut dysbiosis. OBJECTIVES: To determine the associations between the quantity and sources (vegetable and animal) of dietary protein intake and gut microbiome composition in community-dwelling older men. METHODS: We performed a cross-sectional analysis on 775 older men from the Osteoporotic Fractures in Men Study (MrOS) (age 84.2 ± 4.0 y) with available dietary information and stool samples at visit 4 (2014-2016). Protein intake was estimated from a brief FFQ and adjusted to total energy intake. The gut microbiome composition was determined by 16S (v4) sequencing (processed by DADA2 and SILVA). A total of 11,534 amplicon sequence variants (ASVs) were identified and assigned to 21 phyla with dominance of Firmicutes (45%) and Bacteroidetes (43%). We performed α-diversity, ß-diversity, and taxa abundance (by Analysis of Compositions of Microbiomes with Bias Correction [ANCOM-BC]) to determine the associations between protein intake and the gut microbiome. RESULTS: Median protein intake was 0.7 g/(kg body weight · d). Participants with higher energy-adjusted protein intakes had higher Shannon and Chao1 α-diversity indices (P < 0.05). For ß-diversity analysis, participants with higher protein intakes had a different center in weighted and unweighted UniFrac Principal Co-ordinates Analysis (PCoA) compared with those with lower intake (P < 0.05), adjusted for age, race, education, clinical center, batch number, fiber and energy intake, weight, height, and medications. Similarly, higher protein consumptions from either animal or vegetable sources were associated with higher gut microbiome diversity. Several genus-level ASVs, including Christensenellaceae, Veillonella, Haemophilus, and Klebsiella were more abundant in participants with higher protein intakes, whereas Clostridiales bacterium DTU089 and Desulfovibrio were more abundant in participants with lower protein intake (Bonferroni corrected P < 0.05). CONCLUSIONS: We observed significant associations between protein intake and gut microbiome diversity in community-living older men. Further studies are needed to elucidate the mediation role of the gut microbiome on the relation between protein intake and health outcomes in older adults.

In generally healthy adults, supplemental vitamin D3 did not reduce fractures vs. placebo at 5 y.

SOURCE CITATION: LeBoff MS, Chou SH, Ratliff KA, et al. Supplemental vitamin D and incident fractures in midlife and older adults. N Engl J Med. 2022;387:299-309. 35939577.

Physical functioning and mental health treatment initiation and retention for veterans with posttraumatic stress disorder: a prospective cohort study.

BACKGROUND: Most US adults with posttraumatic stress disorder (PTSD) do not initiate mental health treatment within a year of diagnosis. Increasing treatment uptake can improve health and quality of life for those with PTSD. Individuals with PTSD are more likely to report poor physical functioning, which may contribute to difficulty with treatment initiation and retention. We sought to determine the effects of poor physical functioning on mental health treatment initiation and retention for individuals with PTSD. METHODS: We used data for a national cohort of veterans in VA care; diagnosed with PTSD in June 2008-July 2009; with no mental health treatment in the prior year; and who responded to baseline surveys on physical functioning and PTSD symptoms (n = 6,765). Physical functioning was assessed using Veterans RAND 12-item Short Form Health Survey, and encoded as limitations in physical functioning and role limitations due to physical health. Treatment initiation (within 6 months of diagnosis) was determined using VA data and categorized as none (reference), only medications, only psychotherapy, or both. Treatment retention was defined as having ≥ 4 months of appropriate antidepressant or ≥ 8 psychotherapy encounters. RESULTS: In multinomial models, greater limitations in physical functioning were associated with lower odds of initiating only psychotherapy (OR 0.82 [95 % CI 0.68, 0.97] for limited a little and OR 0.74 [0.61, 0.90] for limited a lot, compared to reference "Not limited at all"). However, it was not associated with initiation of medications alone (OR 1.04 [0.85, 1.28] for limited a little and OR 1.07 [0.86, 1.34] for limited a lot) or combined with psychotherapy (OR 1.03 [0.85, 1.25] for limited a little and OR 0.95 [0.78, 1.17] for limited a lot). Greater limitations in physical functioning were also associated with lower odds of psychotherapy retention (OR 0.69 [0.53, 0.89] for limited a lot) but not for medications (e.g., OR 0.96 [0.79, 1.17] for limited a lot). Role limitations was only associated with initiation of both medications and psychotherapy, but there was no effect gradient (OR 1.38 [1.03, 1.86] for limitations a little or some of the time, and OR 1.18 [0.63, 1.06] for most or all of the time, compared to reference "None of the time"). Accounting for chronic physical health conditions did not attenuate associations between limitations in physical functioning (or role limitations) and PTSD treatment; having more chronic conditions was associated with lower odds of both initiation and retention for all treatments (e.g., for 2 + conditions OR 0.53 [0.41, 0.67] for initiation of psychotherapy). CONCLUSIONS: Greater limitations in physical functioning may be a barrier to psychotherapy initiation and retention. Future interventions addressing physical functioning may enhance uptake of psychotherapy.

Frailty: implications for clinical practice and public health.

Frailty is an emerging global health burden, with major implications for clinical practice and public health. The prevalence of frailty is expected to rise alongside rapid growth in the ageing population. The course of frailty is characterised by a decline in functioning across multiple physiological systems, accompanied by an increased vulnerability to stressors. Having frailty places a person at increased risk of adverse outcomes, including falls, hospitalisation, and mortality. Studies have shown a clear pattern of increased health-care costs and use associated with frailty. All older adults are at risk of developing frailty, although risk levels are substantially higher among those with comorbidities, low socioeconomic position, poor diet, and sedentary lifestyles. Lifestyle and clinical risk factors are potentially modifiable by specific interventions and preventive actions. The concept of frailty is increasingly being used in primary, acute, and specialist care. However, despite efforts over the past three decades, agreement on a standard instrument to identify frailty has not yet been achieved. In this Series paper, we provide an overview of the global impact and burden of frailty, the usefulness of the frailty concept in clinical practice, potential targets for frailty prevention, and directions that need to be explored in the future.

Interventions to Prevent or Delay Long-Term Nursing Home Placement for Adults with Impairments-a Systematic Review of Reviews.

BACKGROUND: With continued growth in the older adult population, US federal and state costs for long-term care services are projected to increase. Recent policy changes have shifted funding to home and community-based services (HCBS), but it remains unclear whether HCBS can prevent or delay long-term nursing home placement (NHP). METHODS: We searched MEDLINE (OVID), Sociological Abstracts, PsycINFO, CINAHL, and Embase (from inception through September 2018); and Cochrane Database of Systematic Reviews, Joanna Briggs Institute Database, AHRQ Evidence-based Practice Center, and VA Evidence Synthesis Program reports (from inception through November 2018) for English-language systematic reviews. We also sought expert referrals. Eligible reviews addressed HCBS for community-dwelling adults with, or at risk of developing, physical and/or cognitive impairments. Two individuals rated quality (using modified AMSTAR 2) and abstracted review characteristics, including definition of NHP and interventions. From a prioritized subset of the highest-quality and most recent reviews, we abstracted intervention effects and strength of evidence (as reported by review authors). RESULTS: Of 47 eligible reviews, most focused on caregiver support (n = 10), respite care and adult day programs (n = 9), case management (n = 8), and preventive home visits (n = 6). Among 20 prioritized reviews, 12 exclusively included randomized controlled trials, while the rest also included observational studies. Prioritized reviews found no overall benefit or inconsistent effects for caregiver support (n = 2), respite care and adult day programs (n = 3), case management (n = 4), and preventive home visits (n = 2). For caregiver support, case management, and preventive home visits, some reviews highlighted that a few studies of higher-intensity models reduced NHP. Reviews on other interventions (n = 9) generally found a lack of evidence examining NHP. DISCUSSION: Evidence indicated no benefit or inconsistent effects of HCBS in preventing or delaying NHP. Demonstration of substantial impacts on NHP may require longer-term studies of higher-intensity interventions that can be adapted for a variety of settings. Registration PROSPERO # CRD42018116198.

Individual and joint trajectories of change in bone, lean mass and physical performance in older men.

BACKGROUND: Declines in bone, muscle and physical performance are associated with adverse health outcomes in older adults. However, few studies have described concurrent age-related patterns of change in these factors. The purpose of this study was to characterize change in four properties of muscle, physical performance, and bone in a prospective cohort study of older men. METHODS: Using repeated longitudinal data from up to four visits across 6.9 years from up to 4681 men (mean age at baseline 72.7 yrs. ±5.3) participating in the Osteoporotic Fractures in Men (MrOS) Study, we used group-based trajectory models (PROC TRAJ in SAS) to identify age-related patterns of change in four properties of muscle, physical performance, and bone: total hip bone mineral (BMD) density (g/m2) and appendicular lean mass/ht2 (kg/m2), by DXA; grip strength (kg), by hand dynamometry; and walking speed (m/s), by usual walking pace over 6 m. We also described joint trajectories in all pair-wise combinations of these measures. Mean posterior probabilities of placement in each trajectory (or joint membership in latent groups) were used to assess internal reliability of the model. The number of trajectories for each individual factor was limited to three, to ensure that the pair-wise determination of joint trajectories would yield a tractable number of groups as well as model fit considerations. RESULTS: The patterns of change identified were generally similar for all measures, with three district groups declining over time at roughly similar rates; joint trajectories revealed similar patterns with no cross-over or convergence between groups. Mean posterior probabilities for all trajectories were similar and consistently above 0.8 indicating reasonable model fit to the data. CONCLUSIONS: Our description of trajectories of change with age in bone mineral density, grip strength, walking speed and appendicular lean mass found that groups identified by these methods appeared to have little crossover or convergence of change with age, even when considering joint trajectories of change in these factors.

Long-Term Drug Therapy and Drug Discontinuations and Holidays for Osteoporosis Fracture Prevention: A Systematic Review.

Background: Optimal long-term osteoporosis drug treatment (ODT) is uncertain. Purpose: To summarize the effects of long-term ODT and ODT discontinuation and holidays. Data Sources: Electronic bibliographic databases (January 1995 to October 2018) and systematic review bibliographies. Study Selection: 48 studies that enrolled men or postmenopausal women aged 50 years or older who were being investigated or treated for fracture prevention, compared long-term ODT (>3 years) versus control or ODT continuation versus discontinuation, reported incident fractures (for trials) or harms (for trials and observational studies), and had low or medium risk of bias (ROB). Data Extraction: Two reviewers independently rated ROB and strength of evidence (SOE). One extracted data; another verified accuracy. Data Synthesis: Thirty-five trials (9 unique studies) and 13 observational studies (11 unique studies) had low or medium ROB. In women with osteoporosis, 4 years of alendronate reduced clinical fractures (hazard ratio [HR], 0.64 [95% CI, 0.50 to 0.82]) and radiographic vertebral fractures (both moderate SOE), whereas 4 years of raloxifene reduced vertebral but not nonvertebral fractures. In women with osteopenia or osteoporosis, 6 years of zoledronic acid reduced clinical fractures (HR, 0.73 [CI, 0.60 to 0.90]), including nonvertebral fractures (high SOE) and clinical vertebral fractures (moderate SOE). Long-term bisphosphonates increased risk for 2 rare harms: atypical femoral fractures (low SOE) and osteonecrosis of the jaw (mostly low SOE). In women with unspecified osteoporosis status, 5 to 7 years of hormone therapy reduced clinical fractures (high SOE), including hip fractures (moderate SOE), but increased serious harms. After 3 to 5 years of treatment, bisphosphonate continuation versus discontinuation reduced radiographic vertebral fractures (zoledronic acid; low SOE) and clinical vertebral fractures (alendronate; moderate SOE) but not nonvertebral fractures (low SOE). Limitation: No trials studied men, clinical fracture data were sparse, methods for estimating harms were heterogeneous, and no trials compared sequential treatments or different durations of drug holidays. Conclusion: Long-term alendronate and zoledronic acid therapies reduce fracture risk in women with osteoporosis. Long-term bisphosphonate treatment may increase risk for rare adverse events, and continuing treatment beyond 3 to 5 years may reduce risk for vertebral fractures. Long-term hormone therapy reduces hip fracture risks but has serious harms. Primary Funding Source: National Institutes of Health and Agency for Healthcare Research and Quality. (PROSPERO: CRD42018087006).

Implications of Frailty among Men with Implantable Cardioverter Defibrillators.

OBJECTIVES: Frailty is associated with adverse outcomes, but little is known of the impact of frailty on patients with implantable cardioverter defibrillators (ICDs). This study sought to determine the prevalence of frailty, based on quantitative assessment, and assessed its potential impact on outcomes among community-dwelling men with ICDs. METHODS: A total of 124 ICD-treated men presenting for a routine device clinic appointment between May and October 2016 underwent frailty assessment consisting of three components: shrinking (weight loss ≥5% during the past year), weakness (inability to rise from a chair without using their arms), and self-reported poor energy level. Patients who had no components were considered robust, those with 1 component were intermediate stage, and those with ≥2 components were deemed frail. RESULTS: Mean age was 70.4 (±9.7) years. Of the 124 men, 31 (25%) were considered to be frail, 65 (52%) were intermediate, and 28 (23%) were robust. Frail men were older and were more likely to have symptomatic heart failure, chronic kidney disease, and hypertension (P < 0.05 for all) compared with nonfrail men. During a follow-up of 16 months, frail men were significantly more likely to die compared with nonfrail men (29% vs 5.4%, P < 0.0003). The incidence of appropriate ICD shocks (16.1% vs 6.5%) or hospitalizations (38.7% vs 23.7%) tended to be higher among frail versus nonfrail patients, but neither reached statistical significance (P = 0.10). CONCLUSIONS: Almost one-fourth of men with ICD are frail. Almost one-third of frail ICD patients died within 16 months. It may be useful to assess frailty in patients with ICD.

Association between post-stroke disability and 5-year hip-fracture risk: The Women's Health Initiative.

BACKGROUND: Hip fractures are a significant post-stroke complication. We examined predictors of hip fracture risk after stroke using data from the Women's Health Initiative (WHI). In particular, we examined the association between post-stroke disability levels and hip fracture risk. METHODS: The WHI is a prospective study of 161,808 postmenopausal women aged 50-79 years. Trained physicians adjudicated stroke events and hip fractures. Our study included stroke survivors from the observational and clinical trial arms who had a Glasgow Outcome Scale of good recovery, moderately disabled, or severely disabled and survived more than 7 days post-stroke. Hip fracture-free status was compared across disability levels. Secondary analysis examined hip fracture risk while accounting for competing risk of death. RESULTS: Average age at time of stroke was 74.6±7.2 years; 84.3% were white. There were 124 hip fractures among 4,640 stroke survivors over a mean follow-up time of 3.1±1.8 years. Mortality rate was 23.3%. Severe disability at discharge (Hazard Ratio (HR): 2.1 (95% Confidence Interval (CI): 1.4-3.2), but not moderate disability (HR: 1.1 (95%CI: 0.7-1.7), was significantly associated with an increased risk of hip fracture compared to good recovery status. This association was attenuated after accounting for mortality. White race, increasing age and higher Fracture Risk Assessment Tool (FRAX)-predicted hip fracture risk (without bone density information) were associated with an increased hip fracture risk. After accounting for mortality, higher FRAX risk and white race remained significant. CONCLUSION: Severe disability after stroke and a higher FRAX risk score were associated with risk of subsequent hip fracture. After accounting for mortality, only the FRAX risk score remained significant. The FRAX risk score appears to identify stroke survivors at high risk of fractures. Our results suggest that stroke units can consider the incorporation of osteoporosis screening into care pathways.

Effects of Testosterone Treatment in Older Men.

BACKGROUND: Serum testosterone concentrations decrease as men age, but benefits of raising testosterone levels in older men have not been established. METHODS: We assigned 790 men 65 years of age or older with a serum testosterone concentration of less than 275 ng per deciliter and symptoms suggesting hypoandrogenism to receive either testosterone gel or placebo gel for 1 year. Each man participated in one or more of three trials--the Sexual Function Trial, the Physical Function Trial, and the Vitality Trial. The primary outcome of each of the individual trials was also evaluated in all participants. RESULTS: Testosterone treatment increased serum testosterone levels to the mid-normal range for men 19 to 40 years of age. The increase in testosterone levels was associated with significantly increased sexual activity, as assessed by the Psychosexual Daily Questionnaire (P<0.001), as well as significantly increased sexual desire and erectile function. The percentage of men who had an increase of at least 50 m in the 6-minute walking distance did not differ significantly between the two study groups in the Physical Function Trial but did differ significantly when men in all three trials were included (20.5% of men who received testosterone vs. 12.6% of men who received placebo, P=0.003). Testosterone had no significant benefit with respect to vitality, as assessed by the Functional Assessment of Chronic Illness Therapy-Fatigue scale, but men who received testosterone reported slightly better mood and lower severity of depressive symptoms than those who received placebo. The rates of adverse events were similar in the two groups. CONCLUSIONS: In symptomatic men 65 years of age or older, raising testosterone concentrations for 1 year from moderately low to the mid-normal range for men 19 to 40 years of age had a moderate benefit with respect to sexual function and some benefit with respect to mood and depressive symptoms but no benefit with respect to vitality or walking distance. The number of participants was too few to draw conclusions about the risks of testosterone treatment. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00799617.).

Facebook advertising for recruitment of midlife women with bothersome vaginal symptoms: A pilot study.

BACKGROUND: The MsFLASH (Menopause Strategies: Finding Lasting Answers for Symptoms and Health) Network recruited into five randomized clinical trials (n = 100-350) through mass mailings. The fifth trial tested two interventions for postmenopausal vulvovaginal symptoms (itching, pain, irritation, dryness, or pain with sex) and thus required a high level of sensitivity to privacy concerns. For this trial, in addition to mass mailings we pilot tested a social media recruitment approach. We aimed to evaluate the feasibility of recruiting healthy midlife women with bothersome vulvovaginal symptoms to participate in the Vaginal Health Trial through Facebook advertising. METHODS: As part of a larger advertising campaign that enrolled 302 postmenopausal women for the 12-week randomized, double-blind, placebo-controlled Vaginal Health Trial from April 2016 to February 2017, Facebook advertising was used to recruit 25 participants. The target population for recruitment by mailings and by Facebook ads included women aged 50-70 years and living within 20 miles of study sites in Minneapolis, MN and Seattle, WA. Design of recruitment letters and Facebook advertisements was informed by focus group feedback. Facebook ads were displayed in the "newsfeed" of targeted users and included a link to the study website. Response rates and costs are described for both online ads and mailing. RESULTS: Facebook ads ran in Minneapolis for 28 days and in Seattle for 15 days, with ads posted and removed from the site as needed based on clinic flow and a set budget limit. Our estimated Facebook advertising reach was over 200,000 women; 461 women responded and 25 were enrolled at a cost of US$14,813. The response rate per estimated reach was 0.22%; costs were US$32 per response and US$593 per randomized participant. The social media recruitment results varied by site, showing greater effectiveness in Seattle than in Minneapolis. We mailed 277,000 recruitment letters; 2166 women responded and 277 were randomized at a cost of US$98,682. The response rate per letter sent was 0.78%; costs were US$46 per response and US$356 per randomized participant. Results varied little across sites. CONCLUSION: Recruitment to a clinical trial testing interventions for postmenopausal vaginal symptoms is feasible through social media advertising. Variability in observed effectiveness and costs may reflect the small sample sizes and limited budget of the pilot recruitment study.

Osteoporosis.

Osteoporosis is a common systemic skeletal disorder resulting in bone fragility and increased fracture risk. However, management of osteoporosis and fracture prevention strategies are often not addressed by primary care clinicians, even in older patients with recent fractures. Evidence-based screening strategies will improve identification of patients who are most likely to benefit from drug treatment to prevent fracture. In addition, careful consideration of when pharmacotherapy should be started and choice of medication and duration of treatment will maximize the benefits of fracture prevention while minimizing potential harms of long-term drug exposure.

Association of Sleep Disordered Breathing with Erectile Dysfunction in Community Dwelling Older Men.

PURPOSE: We investigated the association between sleep disordered breathing and erectile dysfunction in older men. MATERIALS AND METHODS: We performed a cross-sectional analysis of community dwelling men age 67 years or older enrolled in the Osteoporotic Fractures in Men Sleep Study. Participants underwent overnight polysomnography (2003 to 2005) and completed sexual health questionnaires (2005 to 2006). We defined sleep disordered breathing using the apnea-hypopnea index or nocturnal hypoxemia. Erectile dysfunction was defined using the MMAS (Massachusetts Male Aging Study) scale and, in sexually active men, the International Index of Erectile Function. We used logistic regression to examine the association between sleep disordered breathing and erectile dysfunction. RESULTS: Mean participant age was 76±5 years. Of the 2,676 men completing the MMAS, 70% had moderate to complete erectile dysfunction. Among 1,099 sexually active men completing the IIEF-5 (5-item International Index of Erectile Function), 26% had moderate to severe erectile dysfunction. A higher apnea-hypopnea index was associated with greater odds of MMAS defined moderate to complete erectile dysfunction after adjusting for age and study site (OR 1.39, 95% CI 1.00-1.92 for severe sleep disordered breathing vs none, p trend=0.008), but not after further adjustment for body mass index, socioeconomic status and comorbidities (OR 1.05, 95% CI 0.75-1.49, p trend=0.452). Greater nocturnal hypoxemia was associated with increased odds of MMAS defined moderate to complete erectile dysfunction (unadjusted OR 1.36, 95% Cl 1.04-1.80 vs none) but this was attenuated after adjustment for age and study site (OR 1.24, 95% CI 0.92-1.66). Sleep disordered breathing was not associated with erectile dysfunction by 5-item International Index of Erectile Function. CONCLUSIONS: In this cross-sectional analysis in older men sleep disordered breathing was associated with higher odds of erectile dysfunction in unadjusted analyses that was largely explained by higher body mass index and increased comorbidity among men with sleep disordered breathing. Prospective studies accounting for obesity and multimorbidity would further clarify the association of sleep disordered breathing and erectile dysfunction.

Screening for Osteoporosis in Older Men: Operating Characteristics of Proposed Strategies for Selecting Men for BMD Testing.

BACKGROUND: The optimal approach for selecting men for bone mineral density (BMD) testing to screen for osteoporosis is uncertain. OBJECTIVE: To compare strategies for selecting older men for screening BMD testing. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 4043 community-dwelling men aged ≥70 years at four US sites. MAIN MEASURES: BMD at the total hip, femoral neck, and lumbar spine using dual-energy x-ray absorptiometry (DXA). Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and area under the receiver operating curve (AUC) of the Osteoporosis Self-Assessment Tool (OST) and Fracture Risk Assessment Tool (FRAX) without BMD to discriminate between those with and without osteoporosis as defined by World Health Organization (WHO) diagnostic criteria, and between those recommended and not recommended for pharmacologic therapy based on the National Osteoporosis Foundation (NOF) guidelines. KEY RESULTS: Among the cohort, 216 (5.3%) had a BMD T-score ≤ -2.5 at the femoral neck, total hip, or lumbar spine, and 1184 (29.2%) met criteria for consideration of pharmacologic therapy according to NOF guidelines. The OST had better discrimination (AUC 0.68) than the FRAX (AUC 0.62; p = 0.004) for identifying T-score-defined osteoporosis. Use of an OST threshold of <2 resulted in sensitivity of 0.83 and specificity of 0.36 for the identification of osteoporosis, compared to sensitivity of 0.59 and specificity of 0.59 for the use of FRAX with a cutoff of 9.3% 10-year risk of major osteoporotic fracture. CONCLUSIONS: The OST performs modestly better than the more complex FRAX in selecting older men for BMD testing to screen for osteoporosis; the use of either tool substantially reduces the proportion of men referred for BMD testing compared to universal screening. Of 1000 men aged 70 and older in this community-based cohort, the use of an OST cutoff of <2 to select men for BMD testing would result in 654 men referred for BMD testing, of whom 44 would be identified as having osteoporosis, and nine with osteoporosis would be missed.