Program Factors Affecting Weight Loss and Mobility in Older Adults: Evidence From the Mobility and Vitality Lifestyle Program (MOVE UP).

Background. The Mobility and Vitality Lifestyle Program (MOVE UP) is a behavioral weight-management intervention for improving mobility among community-dwelling older adults. We examined program factors that affect implementation outcomes and participant-level health outcomes. Methods. The MOVE UP program was implemented in the greater Pittsburgh area from January 2015 to June 2019 to improve lower extremity performance in community-dwelling older adults who were overweight or obese. Thirty-two sessions were delivered over 13 months. All sessions were designed to be 1-hour in length, on-site, group-based, and led by trained and supported community health workers (CHWs). Participants completed weekly Lifestyle Logs for self-monitoring of body weight, diet, and physical activity. We evaluated the MOVE UP program using the RE-AIM framework, and collected quantitative data at baseline, 5-, 9-, and 13-months. Multilevel linear regression models assessed the impacts of program factors (site, CHW, and participant characteristics) on implementation outcomes and participant-level health outcomes. Results. Twenty-two CHWs delivered MOVE UP program to 303 participants in 26 cohorts. Participants were similar to the target source population in weight but differed in some demographic characteristics. The program was effective for weight loss and lower extremity function in both intervention and maintenance periods (Ps < .01), with an independent effect for Lifestyle Logs submission but not session attendance. Discussion. CHWs were able to deliver a multi-component weight loss intervention effectively in community settings. CHW and site characteristics had independent impacts on participants' adherence. Lifestyle Log submission may be a more potent measure of adherence in weight loss interventions than attendance.

The Study of Muscle, Mobility and Aging (SOMMA): A Unique Cohort Study About the Cellular Biology of Aging and Age-related Loss of Mobility.

BACKGROUND: The Study of Muscle, Mobility and Aging (SOMMA) aims to understand the biological basis of many facets of human aging, with a focus on mobility decline, by creating a unique platform of data, tissues, and images. METHODS: The multidisciplinary SOMMA team includes 2 clinical centers (University of Pittsburgh and Wake Forest University), a biorepository (Translational Research Institute at Advent Health), and the San Francisco Coordinating Center (California Pacific Medical Center Research Institute). Enrollees were age ≥70 years, able to walk ≥0.6 m/s (4 m); able to complete 400 m walk, free of life-threatening disease, and had no contraindications to magnetic resonance or tissue collection. Participants are followed with 6-month phone contacts and annual in-person exams. At baseline, SOMMA collected biospecimens (muscle and adipose tissue, blood, urine, fecal samples); a variety of questionnaires; physical and cognitive assessments; whole-body imaging (magnetic resonance and computed tomography); accelerometry; and cardiopulmonary exercise testing. Primary outcomes include change in walking speed, change in fitness, and objective mobility disability (able to walk 400 m in 15 minutes and change in 400 m speed). Incident events, including hospitalizations, cancer diagnoses, fractures, and mortality are collected and centrally adjudicated by study physicians. RESULTS: SOMMA exceeded its goals by enrolling 879 participants, despite being slowed by the COVID-19 pandemic: 59.2% women; mean age 76.3 ± 5.0 years (range 70-94); mean walking speed 1.04 ± 0.20 m/s; 15.8% identify as other than Non-Hispanic White. Over 97% had data for key measurements. CONCLUSIONS: SOMMA will provide the foundation for discoveries in the biology of human aging and mobility.

Effectiveness of a behavioral lifestyle intervention on weight management and mobility improvement in older informal caregivers: a secondary data analysis.

BACKGROUND: Older informal caregivers are prone to sedentary behavior and obesity. With great caregiving burdens and frequent physical and mental distress, older informal caregivers may have low adherence and poor results in behavioral intervention for weight management. This study examined whether overweight or obese older informal caregivers could benefit from a behavioral weight management program as much as non-caregivers. METHODS: The Mobility and Vitality Lifestyle Program (MOVE UP) was a pre-post, community-based, 13-month lifestyle intervention study to help older adults improve physical function performance and lose weight. We identified a subset of informal caregivers (n = 29) and non-caregivers (n = 65) from the MOVE UP participants retrospectively. Changes in lower extremity function, weight, depressive symptoms, and self-efficacy from baseline were compared between caregivers and non-caregivers using paired t-tests and ANCOVA. RESULTS: Older informal caregivers had significantly lower session attendance rates than non-caregivers (67.7% vs 76.8%, P < 0.05), however, both informal caregivers and non-caregivers improved significantly in lower extremity function, weight loss, and self-efficacy in diet (Ps < 0.05). For each outcome, changes from baseline to the 13-month endpoint were the same among informal caregivers and non-caregivers. CONCLUSION: This study provides evidence that older informal caregivers can benefit from behavioral weight management interventions despite the challenge caregiving poses for effective self-care. Future behavioral intervention studies for older informal caregivers should adopt self-monitoring tools and extend the on-site delivery to home-based settings for higher adherence and greater flexibility. TRIAL REGISTRATION: Registered at clinicaltrials.gov (NCT02657239).

Weight Loss through Lifestyle Intervention Improves Mobility in Older Adults.

BACKGROUND AND OBJECTIVES: The high prevalence of overweight or obesity in older adults is a public health concern because obesity affects health, including the risk of mobility disability. RESEARCH DESIGN AND METHODS: The Mobility and Vitality Lifestyle Program, delivered by community health workers (CHWs), enrolled 303 community-dwelling adults to assess the impact of a 32-session behavioral weight management intervention. Participants completed the program at 26 sites led by 22 CHWs. Participation was limited to people aged 60-75 who had a body mass index (BMI) of 27-45 kg/m2. The primary outcome was the performance on the Short Physical Performance Battery (SPPB) over 12 months. RESULTS: Participants were aged 67.7 (SD 4.1) and mostly female (87%); 22.7% were racial minorities. The mean (SD) BMI at baseline was 34.7 (4.7). Participants attended a median of 24 of 32 sessions; 240 (80.3%) completed the 9- or 13-month outcome assessment. Median weight loss in the sample was 5% of baseline body weight. SPPB total scores improved by +0.31 units (p < .006), gait speed by +0.04 m/s (p < .0001), and time to complete chair stands by -0.95 s (p < .0001). Weight loss of at least 5% was associated with a gain of +0.73 in SPPB scores. Increases in activity (by self-report or device) were not independently associated with SPPB outcomes but did reduce the effect of weight loss. DISCUSSION AND IMPLICATIONS: Promoting weight management in a community group setting may be an effective strategy for reducing the risk of disability in older adults.

Longitudinal changes in hip geometry in relation to the final menstrual period: Study of Women's Health Across the Nation (SWAN).

BACKGROUND: In SWAN, we showed that accelerated loss of bone mineral density (BMD) begins 1 year before the final menstrual period (FMP) to 2 years after the FMP and slows thereafter. However, the risk of fracture depends on both BMD and bone geometry. The hip structural analysis (HSA) measures important geometric properties of bone. Changes in HSA parameters across the menopausal transition have not been previously assessed. METHODS: The current analysis uses data from SWAN, 5 years before to 5 years after FMP (N = 900, Age (mean(SD)) = 46.85(2.60), 44% White). HSA parameters at the femoral narrow neck were obtained from 2D DXA scans and normalized to baseline values. FMP was determined from annual interviews. Changes in HSA were assessed over 3 periods, 5 to 2 years before FMP (pre-transmenopausal), 2 years before to 1 years after FMP (transmenopausal), 1 to 5 years after FMP (postmenopausal). Mixed linear models with random slopes were used to estimate the rate of change in HSA parameters relative to FMP. RESULTS: Loss of BMD, cross-sectional area (CSA), and section modulus (SM) and increases in outer diameter (OD) were greatest in the transmenopausal period (p for all<0.05). Changes continued in the postmenopausal period but were not statistically significant. The cumulative percentage changes over 10 years in BMD (-10.67%), CSA (-9.01), SM (-7.03) and OD (+1.95) were statistically significant. CONCLUSION: Changes in hip geometry across the menopause transition parallel changes in BMD and provide insight into mechanisms that may increase risk of fragility fracture.

Using the Infrastructure of State Aging Services to Promote Prevention Behavior.

INTRODUCTION: State infrastructure for aging services, such as programs in county senior centers, can help promote prevention of chronic disease and reach large numbers of older adults. The objective of our study was to assess how well such infrastructure can support prevention efforts. METHODS: The University of Pittsburgh CDC Prevention Research Center partnered with the Pennsylvania Department of Aging APPRISE program to deliver the 10 Keys to Healthy Aging program. APPRISE is a Medicare counseling program offered at senior centers; the 10 Keys is a series of behavior-activation workshops for people aged 50 or older that cover recommendations of the US Preventive Services Task Force and other evidence-based recommendations for health promotion. We assessed implementation, increases in prevention knowledge, and maintenance of prevention behavior. RESULTS: From 2013 through 2016, 1,534 adults at 83 sites participated in the program; 1,044 (68.1%) completed at least 8 of 10 Keys workshops. A total of 736 adults (mean [standard deviation] age, 74.9 [8.3] y) voluntarily completed a 14-item pretest and posttest of prevention knowledge; respondents' knowledge score increased from 61.5% to 78.5% correct (P < .001). In a subsample (n = 339) reporting on their own prevention behaviors at baseline, quiz scores and prevention behaviors were correlated (r = 0.30, P < .001). In monthly telephone follow-up with 147 respondents over 6 months, maintenance of prevention behaviors was strong in the areas of physical activity and hypertension management and significantly higher for people completing a greater number of Keys workshops. CONCLUSION: Prevention behavior can be activated in aging services settings and can be incorporated into daily routines.

Sex Steroid Hormones and Fracture in a Multiethnic Cohort of Women: The Women's Health Initiative Study (WHI).

Context: We hypothesize that endogenous sex steroids are associated with fracture risk independent of race/ethnicity. Design and Setting: We performed a nested case-control study within the prospective Women's Health Initiative Observational Study. Incident nonspine fractures were identified in 381 black, 192 Hispanic, 112 Asian, and 46 Native American women over an average of 8.6 years. A random sample of 400 white women who experienced an incident fracture was chosen. One control was selected per case and matched on age, race/ethnicity, and blood draw date. Bioavailable estradiol (BioE2), bioavailable testosterone (BioT), and sex hormone-binding globulin (SHBG) were measured using baseline fasting serum. Conditional logistic regression models calculated the odds ratio (OR) and 95% confidence interval (CI) of fracture across tertiles of hormone. Results: In multivariable and race/ethnicity-adjusted models, higher BioE2 (>8.25 pg/mL) and higher BioT (>13.3 ng/dL) were associated with decreased risk of fracture (OR, 0.65; 95% CI, 0.50 to 0.85; P trend = 0.001 and OR, 0.76; 95% CI, 0.60 to 0.96; P trend = 0.02, respectively). The interaction term between race/ethnicity and either BioE2 or BioT was not significant. There was no association between SHBG and fracture risk. In models stratifying by race/ethnicity, higher BioE2 was associated with a lower risk of fracture in both white women (OR, 0.56; 95% CI, 0.36 to 0.87) and black women (OR, 0.61; 95% CI, 0.39 to 0.96). Higher BioT was associated with a significantly lower fracture risk in only black women (OR, 0.65; 95% CI, 0.43 to 1.00), P trend = 0.03. Conclusions: Serum BioE2 and BioT are associated with fracture risk in older women irrespective of race/ethnicity and independent of established risk factors for fracture.

Vertebral bone marrow fat, bone mineral density and diabetes: The Osteoporotic Fractures in Men (MrOS) study.

Elevated vertebral bone marrow fat (BMF) among individuals with osteoporosis has been established in histomorphometric studies. Several studies have found a negative correlation between BMF and bone mineral density (BMD) at the spine in men and women across different age groups. Animal studies have also observed bone loss with increased BMF in mice with induced diabetes. Our study objective was to test the hypothesis that the association between BMF and BMD varies by diabetic status. We performed a cross-sectional study of 156 men aged 74-96years from the Osteoporotic Fractures in Men study at the Pittsburgh clinical site. All men had spine BMF scans using proton magnetic resonance spectroscopy and spine and hip BMD scans by dual-energy X-ray absorptiometry. BMF was expressed as lipid to "lipid+water" ratio (%). Men were considered diabetic if they self-reported a physician diagnosis of diabetes, diabetes medication or had a fasting glucose ≥126mg/dl. Men with diabetes (n=38) had a significantly higher spine BMF (58.9 vs. 54.6%, p=0.0035), spine BMD (1.20 vs. 1.10g/cm2, P=0.007) and total hip BMD (1.00 vs. 0.94g/cm2, p=0.04) than those without, while no differences were observed for body weight, body mass index or waist circumference. Pearson correlation tests showed no significant correlation of spine BMF with age or BMD in non-diabetics. Significant inverse correlations were observed between BMF and BMD (-0.30 for femoral neck and -0.39 for total hip) among diabetic men. In conclusion, men with diabetes had a higher BMF compared to non-diabetic men. The correlation between BMF and BMD differed by diabetes status. Further investigation of the association of diabetes with BMF and BMD may provide a better understanding of the high fracture rates among individuals with diabetes despite their higher BMD.

Inflammatory Markers and the Risk of Hip and Vertebral Fractures in Men: the Osteoporotic Fractures in Men (MrOS).

Cytokines play major roles in regulating bone remodeling, but their relationship to incident fractures in older men is uncertain. We tested the hypothesis that men with higher concentrations of pro-inflammatory markers have a higher risk of fracture. We used a case-cohort design and measured inflammatory markers in a random sample of 961 men and in men with incident fractures including 120 clinical vertebral, 117 hip, and 577 non-spine fractures; average follow-up 6.13 years (7.88 years for vertebral fractures). We measured interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor alpha (TNFα), soluble receptors (SR) of IL-6 (IL-6SR) and TNF (TNFαSR1 and TNFαSR2), and IL-10. The risk of non-spine, hip, and clinical vertebral fracture was compared across quartiles (Q) of inflammatory markers using Cox proportional hazard models with tests for linear trend. In multivariable-adjusted models, men with the highest (Q4) TNFa cytokine concentrations and their receptors had a 2.0-4.2-fold higher risk of hip and clinical vertebral fracture than men with the lowest (Q1). Results were similar for all non-spine fractures, but associations were smaller. There was no association between CRP and IL-6SR and fracture. Men in the highest Q of IL-10 had a 49% lower risk of vertebral fracture compared with men in Q1. Among men with ≥3 inflammatory markers in the highest Q, the hazard ratio (HR) for hip fractures was 2.03 (95% confidence interval [CI] 1.11-3.71) and for vertebral fracture 3.06 (1.66-5.63). The HRs for hip fracture were attenuated by 27%, 27%, and 15%, respectively, after adjusting for appendicular lean mass (ALM), disability, and bone density, suggesting mediating roles. ALM also attenuated the HR for vertebral fractures by 10%. There was no association between inflammation and rate of hip BMD loss. We conclude that inflammation may play an important role in the etiology of fractures in older men. © 2016 American Society for Bone and Mineral Research.

Objective measures of physical activity, fractures and falls: the osteoporotic fractures in men study.

OBJECTIVES: To determine the association between objectively measured physical activity (PA), fractures, and falls. DESIGN: Longitudinal cohort study. SETTING: Six U.S. clinical sites. PARTICIPANTS: Two thousand seven hundred thirty-one men with a mean age of 79. MEASUREMENTS: Total and active energy expenditure (EE) and minutes per day spent in sedentary and moderate intensity activities were measured for at least 5 days. Energy expended at a metabolic equivalent of greater than three was termed active EE. Incident nonspine fractures and falls were identified every 4 months. RESULTS: Seven hundred fifty-nine (28.2%) men fell at least once over 12 months of follow-up; 186 (6.8%) experienced one or more fractures over an average follow-up of 3.5 ± 0.9 years. The association between PA and falling varied according to age (P interaction = .02). Men younger than 80 with the lowest active EE had a lower risk of falling than men with the highest active EE (relative risk (RR) = 0.75; P trend = .08), whereas men aged 80 and older with the lowest active EE had a higher risk of falling than men with the highest active EE (RR = 1.43, P trend = .09). In multivariate models including health status, men in the lowest quintile of active EE had a significantly higher risk of fracture (hazard ratio (HR) = 1.82, 95% confidence interval (CI) = 1.10-3.00, P trend = .04) than men in highest quintile. Men with <33 min/d of moderate activity had a 70% greater risk of fracture (HR = 1.70, 95% CI = 1.03-2.80). CONCLUSION: Age modifies the association between PA and falling. Interventions aimed at obtaining more than 30 minutes of moderate PA per day may reduce fractures, extending PA guidelines to the oldest old, the fastest-growing proportion of those aged 65 and older.

Sclerostin and bone strength in women in their 10th decade of life.

Sclerostin is a potent inhibitor of bone formation but has been shown to correlate positively with areal bone mineral density (aBMD). Little is known about its relationship to parameters of bone strength and volumetric BMD (vBMD) as measured by peripheral quantitative computed tomography (pQCT). We measured both serum sclerostin and parameters of tibial bone size and strength by pQCT to characterize this relationship. Our study population consisted of 223 white and 35 African American women (mean age 87 years) from the Study of Osteoporotic Fractures (SOF) cohort, who had usable pQCT scans of the tibia at sites 4% (T4%), 33% (T33%), and 66% (T66%) from the ankle. Analysis of covariance was used to test for differences in age-adjusted means of aBMD, pQCT variables, and serum biomarkers across sclerostin quartiles. African American women had significantly lower median sclerostin (34.3 pmol/L) than white women (48.5 pmol/L) (p = 0.05). Women in the highest sclerostin quartile had 7% to 14.5% higher hip aBMD and pQCT parameters of vBMD and bone size than those in the lowest quartile in multivariate models adjusting for age, race, weight, height, and diabetes status. The association of sclerostin with parameters of bone strength differed dramatically between T33% and T66% sites. At T66%, women in the highest sclerostin quartile had pQCT strength parameters 9.4% to 15.3% greater than the lowest quartile, whereas no trend was found for the T33% site. Our results suggest paradoxical associations between circulating sclerostin and bone size, density, and strength.

C-reactive protein, bone strength, and nine-year fracture risk: data from the Study of Women's Health Across the Nation (SWAN).

Higher levels of C-reactive protein (CRP), an inflammatory marker, are associated with increased fracture risk, although previous studies on CRP and bone mineral density (BMD) have yielded conflicting results. We aimed to test the hypotheses that composite indices of femoral neck strength relative to load, which are inversely associated with fracture risk, would also be inversely associated with CRP, and would explain part of the association between CRP and fracture risk. We analyzed data from a multisite, multiethnic prospective cohort of 1872 community-dwelling women, premenopausal or early perimenopausal at baseline. Femoral neck composite strength indices in three failure modes were calculated using dual-energy X-ray absorptiometry (DXA)-derived femoral neck width (FNW), femoral neck axis length (FNAL), femoral neck BMD and body size at baseline, as BMD*FNW/weight for compression strength, BMD*(FNW)(2) /(FNAL*weight) for bending strength, and BMD*FNW*FNAL/(height*weight) for impact strength. Incident nondigital, noncraniofacial fractures were ascertained annually over a median follow-up of 9 years. In analyses adjusted for age, race/ethnicity, diabetes, menopause transition stage, body mass index, smoking, alcohol use, physical activity, medications, prior fracture, and study site, CRP was associated inversely with each composite strength index (0.035-0.041 SD decrement per doubling of CRP, all p < 0.001), but not associated with femoral neck or lumbar spine BMD. During the follow-up, 194 women (10.4%) had fractures. In Cox proportional hazards analyses, fracture hazard increased linearly with loge (CRP), only for CRP levels ≥ 3 mg/L. Addition of femoral neck or lumbar spine BMD to the model did not attenuate the CRP-fracture association. However, addition of any of the composite strength indices attenuated the CRP-fracture association and made it statistically nonsignificant. We conclude that fracture risk increases with increasing CRP, only above the threshold of 3 mg/L. Unlike BMD, composite strength indices are inversely related to CRP levels, and partially explain the increased fracture risk associated with inflammation.

Ethnic variability in bone geometry as assessed by hip structure analysis: findings from the hip strength across the menopausal transition study.

Racial/ethnic origin plays an important role in fracture risk. Racial/ethnic differences in fracture rates cannot be fully explained by bone mineral density (BMD). Studies examining the influence of bone geometry and strength on fracture risk have focused primarily on older adults and have not included people from diverse racial/ethnic backgrounds. Our goal was to explore racial/ethnic differences in hip geometry and strength in a large sample of midlife women. We performed hip structure analysis (HSA) on hip dual-energy X-ray absorptiometry (DXA) scans from 1942 premenopausal and early perimenopausal women. The sample included white (50%), African American (27%), Chinese (11%), and Japanese (12%) women aged 42 to 52 years. HSA was performed using software developed at Johns Hopkins University. African American women had higher conventional (8.4% to 9.7%) and HSA BMD (5.4% to 19.8%) than other groups with the exception being Japanese women, who had the highest HSA BMD (9.7% to 31.4%). HSA indices associated with more favorable geometry and greater strength and resistance to fracture were more prevalent in African American and Japanese women. Femurs of African American women had a smaller outer diameter, a larger cross-sectional area and section modulus, and a lower buckling ratio. Japanese women presented a different pattern with a higher section modulus and lower buckling ratio, similar to African American women, but a wider outer diameter; this was offset by a greater cross-sectional area and a more centrally located centroid. Chinese women had similar conventional BMD as white women but a smaller neck region area and HSA BMD at both regions. They also had a smaller cross-sectional area and section modulus, a more medially located centroid, and a higher buckling ratio than white women. The observed biomechanical differences may help explain racial/ethnic variability in fracture rates. Future research should explore the contribution of hip geometry to fracture risk across all race/ethnicities.

Fracture risk assessment without race/ethnicity information.

CONTEXT: Dual-energy x-ray absorptiometry-derived bone mineral density (BMD) does not explain interracial differences in fracture risk; thus, BMD-based fracture risk assessment requires patient race/ethnicity information and ethnicity-specific BMD reference databases. OBJECTIVE: The objective of the study was to investigate whether composite femoral neck strength indices, which integrate dual-energy x-ray absorptiometry-derived femoral neck size, femoral neck BMD, and body size, will allow fracture risk assessment without requiring race/ethnicity information. DESIGN: This was a prospective cohort study. SETTING AND PARTICIPANTS: A total of 1940 community-dwelling women aged 42-53 yr from four race/ethnicity groups (968 Caucasian, 512 African-American, 239 Japanese, and 221 Chinese) were followed up for 9 yr. OUTCOME MEASUREMENTS: Self-reported, nondigital, noncraniofacial fractures were measured. RESULTS: Two hundred and two women (10.4%) sustained fractures and 82 (4.3%) had minimum-trauma fractures. Each sd increment in any of the strength indices was associated with a 34-41% reduction in fracture hazard over 9 yr (each P<0.001). Race/ethnicity predicted fracture hazard independent of BMD (P=0.02) but did not predict fracture hazard independent of any of the composite indices (P=0.11-0.22). Addition of race/ethnicity did not improve risk discrimination ability of the strength indices, but did significantly improve the discrimination ability of BMD. The discrimination ability of BMD with race/ethnicity was not statistically different from that of any of the strength indices without race/ethnicity. CONCLUSIONS: Composite strength indices of the femoral neck can predict fracture risk without race/ethnicity information as accurately as bone mineral density does in combination with race/ethnicity information and therefore would allow risk prediction in people of mixed race/ethnicity and in groups without a BMD reference database.

Bone resorption and fracture across the menopausal transition: the Study of Women's Health Across the Nation.

OBJECTIVE: Bone turnover markers (BTMs) predict fracture in older women, whereas data on younger women are lacking. To test the hypothesis that BTMs measured before and after menopause predict fracture risk, we performed a cohort study of 2,305 women. METHODS: Women attended up to nine clinic visits for an average of 7.6 ± 1.6 years; all were aged 42 to 52 years and were premenopausal or early perimenopausal at baseline. Incident fractures were self-reported. Serum osteocalcin and urinary cross-linked N-telopeptide of type I collagen (NTX) were measured at baseline. NTX was measured at each annual follow-up. Interval-censored survival models or generalized estimating equations were used to test whether baseline BTMs and changes in NTX, respectively, were associated with fracture risk. Hazard ratios (HRs) or odds ratios were calculated with 95% CIs. RESULTS: Women who experienced fractures (n = 184) had about a 10% higher baseline median NTX (34.4 vs 31.5 nanomoles of bone collagen equivalents per liter per nanomole of creatinine per liter; P = 0.001), but there was no difference in osteocalcin. A 1-SD decrease in lumbar spine bone mineral density (BMD) measured premenopausally was associated with a higher fracture risk during menopause (HR, 1.50; 95% CI, 1.28-1.68). Women with a baseline NTX greater than the median had a 45% higher risk of fracture, multivariable-adjusted (HR, 1.46; 95% CI, 1.05-2.26). The HR of fracture among women with both the lowest spine BMD (quartile 1) and the highest NTX (quartile 4) at baseline was 2.87 (95% CI, 1.61-6.01), compared with women with lower NTX and higher BMD. Women whose NTX increased more than the median had a higher risk of fracture (odds ratio, 1.51; 95% CI, 1.08-2.10). Women who had baseline NTX greater than the median experienced greater loss of spine and hip BMD. CONCLUSIONS: A higher urinary NTX excretion measured before menopause and across menopause is associated with a higher risk of fracture. Our results are consistent with the pathophysiology of transmenopausal changes in bone strength.

Inflammatory markers and the risk of hip fracture: the Women's Health Initiative.

Cytokines play a major role in bone remodeling in vitro and in animal models, with evidence supporting the involvement of inflammatory markers in the pathogenesis of osteoporosis. However, less is known about the longitudinal association of inflammatory markers with hip fracture. We tested whether high receptor levels of proinflammatory cytokines are associated with an increased risk of hip fracture in older women. We used a nested case-control study design from the Women's Health Initiative Observational Study (WHI-OS) and selected 400 cases with physician-adjudicated incident hip fractures and 400 controls matched on age, race, and date of blood draw. Participants were chosen from 39,795 postmenopausal women without previous hip fractures, not using estrogens or other bone-active therapies. Incident hip fractures (median follow-up 7.1 years) were verified by review of radiographs and confirmed by blinded central adjudicators. Hip fractures with a pathological cause were excluded. In multivariable models, the risk of hip fracture for subjects with the highest levels of inflammatory markers (quartile 4) compared with those with lower levels (quartiles 1, 2, and 3) was 1.43 (95% confidence interval [CI], 0.98-2.07) for interleukin-6 (IL-6) soluble receptor (SR), 1.40 (95% CI, 0.97-2.03) for tumor necrosis factor (TNF) SR1, and 1.56 (95% CI, 1.09-2.22) for TNF SR2. In subjects with all three markers in the highest quartile, the risk ratio of fracture was 2.76 (95% CI, 1.22-6.25) in comparison with subjects with 0 or 1 elevated marker(s) (p trend = 0.018). Elevated levels of inflammatory markers for all three cytokine-soluble receptors were associated with an increased risk of hip fractures in older women. Future clinical trials should test whether interventions to decrease inflammatory marker levels reduces hip fractures.

Diabetes and femoral neck strength: findings from the Hip Strength Across the Menopausal Transition Study.

CONTEXT: Diabetes mellitus is associated with increased hip fracture risk, despite being associated with higher bone mineral density in the femoral neck. OBJECTIVE: The objective of the study was to test the hypothesis that composite indices of femoral neck strength, which integrate dual-energy x-ray absorptiometry derived femoral neck size, femoral neck areal bone mineral density, and body size and are inversely associated with hip fracture risk, would be lower in diabetics than in nondiabetics and be inversely related to insulin resistance, the primary pathology in type 2 diabetes. DESIGN: This was a cross-sectional analysis. SETTING AND PARTICIPANTS: The study consisted of a multisite, multiethnic, community-dwelling sample of 1887 women in pre- or early perimenopause. OUTCOME MEASUREMENTS: Composite indices for femoral neck strength in different failure modes (axial compression, bending, and impact) were measured. RESULTS: Adjusted for age, race/ethnicity, menopausal stage, body mass index, smoking, physical activity, calcium and vitamin D supplementation, and study site, diabetic women had higher femoral neck areal bone mineral density [+0.25 sd, 95% confidence interval (CI) (+0.06, +0.44) sd] but lower composite strength indices [-0.20 sd, 95% CI (-0.38, -0.03) sd for compression, -0.19 sd, 95% CI (-0.38, -0.003) sd for bending, -0.19 sd, 95% CI (-0.37, -0.02) sd for impact] than nondiabetic women. There were graded inverse relationships between homeostasis model-assessed insulin resistance and all three strength indices, adjusted for the same covariates. CONCLUSIONS: Despite having higher bone density, diabetic women have lower indices of femoral neck strength relative to load, consistent with their documented higher fracture risk. Insulin resistance appears to play an important role in bone strength reduction in diabetes.

Official Positions for FRAX® clinical regarding international differences from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®.

Osteoporosis is a serious worldwide epidemic. Increased risk of fractures is the hallmark of the disease and is associated with increased morbidity, mortality and economic burden. FRAX® is a web-based tool developed by the Sheffield WHO Collaborating Center team, that integrates clinical risk factors, femoral neck BMD, country specific mortality and fracture data and calculates the 10 year fracture probability in order to help health care professionals identify patients who need treatment. However, only 31 countries have a FRAX® calculator at the time paper was accepted for publication. In the absence of a FRAX® model for a particular country, it has been suggested to use a surrogate country for which the epidemiology of osteoporosis most closely approximates the index country. More specific recommendations for clinicians in these countries are not available. In North America, concerns have also been raised regarding the assumptions used to construct the US ethnic specific FRAX® calculators with respect to the correction factors applied to derive fracture probabilities in Blacks, Asians and Hispanics in comparison to Whites. In addition, questions were raised about calculating fracture risk in other ethnic groups e.g., Native Americans and First Canadians. In order to provide additional guidance to clinicians, a FRAX® International Task Force was formed to address specific questions raised by physicians in countries without FRAX® calculators and seeking to integrate FRAX® into their clinical practice. The main questions that the task force tried to answer were the following: The Task Force members conducted appropriate literature reviews and developed preliminary statements that were discussed and graded by a panel of experts at the ISCD-IOF joint conference. The statements approved by the panel of experts are discussed in the current paper.

Serum 25-hydroxyvitamin D and clinical fracture risk in a multiethnic cohort of women: the Women's Health Initiative (WHI).

Low 25-hydroxyvitamin D [25(OH)D] levels have been linked to hip fracture in white women. To study the association of 25(OH)D with risk of fracture in multiethnic women, we performed a nested case-control study within the prospective Women's Health Initiative (WHI) Observational Study. Incident fractures were identified in 381 black, 192 Hispanic, 113 Asian, and 46 Native American women over an average of 8.6 years. A random sample of 400 white women who fractured was chosen. One control individual was selected per case and matched on age, race/ethnicity, and blood draw date. 25(OH)D, parathyroid hormone, and vitamin D-binding protein (DBP) were measured in fasting baseline serum. Conditional logistic regression models were used to calculate the odds ratio (OR) and 95% CI. In multivariable models, higher 25(OH)D levels compared with levels less than 20 ng/mL were associated with a lower risk of fracture in white women (20 to <30 ng/mL: OR = 0.82, 95% CI 0.58-1.16; ≤30.0 ng/mL: OR = 0.56, 95% CI 0.35-0.90; p trend = 0.02). In contrast, higher 25(OH)D (≥20 ng/mL) compared with levels less than 20 ng/mL were associated with a higher risk of fracture in black women (OR = 1.45, 95% CI 1.06-1.98; p trend = 0.043). Higher 25(OH)D (≥30.0 ng/mL) was associated with higher fracture risk in Asian women after adjusting for DBP (OR = 2.78, 95% CI 0.99-7.80; p trend = 0.04). There was no association between 25(OH)D and fracture in Hispanic or Native American women. Our results suggest divergent associations between 25(OH)D and fracture by race/ethnicity. The optimal level of 25(OH)D for skeletal health may differ in white and black women.

A comparison of polycystic ovary syndrome and related factors between lesbian and heterosexual women.

OBJECTIVES: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder associated with infertility, cardiovascular disease and type 2 diabetes. Despite anecdotal evidence that lesbians may have higher PCOS rates than heterosexuals, little empirically based evidence supports this theory. To address this gap, we examined PCOS prevalence and associated factors among a community sample of lesbian and heterosexual women. METHODS: Lesbian (n = 114) and heterosexual (n = 97) women aged 35 to 45 who participated in The Epidemiologic STudy of HEalth Risk (ESTHER) Project (Pittsburgh, PA) were recruited into our PCOS exploratory study between April and October 2008. A reproductive endocrinologist, "blinded" to participant sexual orientation, identified women with PCOS using a modified version of the 2003 Rotterdam Diagnostic Criteria for PCOS. Sexual orientation was defined by self-reported sexual identity, behavior, and attraction. Fisher's exact, chi-square, and Wilcoxon rank-sum tests were used for analysis. RESULTS: Approximately 6.2% (n = 13) of the total sample (n = 211) had PCOS. PCOS rates did not significantly differ between lesbian and heterosexual women ([7.9%, n = 9] vs. [4.1%, n = 4]; p = .256). No significant differences in PCOS-related factors were found between lesbian and heterosexual women: polycystic ovaries ([10.5%, n = 12] vs. [6.2%, n = 6]; p = 0.261), hirsutism ([24.6%, n = 28] vs. [15.5%, n = 15]; p = 0.102), oligomenorrhea ([3.6%, n = 4] vs. [5.4%, n = 5]; p = 0.735), adult acne ([21.1%, n = 24] vs. [24.7%, n = 24], p = 0.524), and median testosterone ([1.69 ng/mL, n = 114] vs. [1.52 ng/mL, n = 97]; p = 0.069) and androstenedione ([1.63 ng/mL, n = 114] vs. [1.51 ng/mL, n = 97]; p = 0.079) concentrations, respectively. CONCLUSION: PCOS and related factors did not differ by sexual orientation. Despite this, our observed rates warrant the need for additional studies to examine the relationship between PCOS diagnoses, PCOS-related factors, and sexual orientation.