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.

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).

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.

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.

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 concentrations and risk for hip fractures.

BACKGROUND: The relationship between serum 25-hydroxyvitamin D [25(OH) vitamin D] concentration and hip fractures is unclear. OBJECTIVE: To see whether low serum 25(OH) vitamin D concentrations are associated with hip fractures in community-dwelling women. DESIGN: Nested case-control study. SETTING: 40 clinical centers in the United States. PARTICIPANTS: 400 case-patients with incident hip fracture and 400 control participants matched on the basis of age, race or ethnicity, and date of blood draw. Both groups were selected from 39 795 postmenopausal women who were not using estrogens or other bone-active therapies and who had not had a previous hip fracture. MEASUREMENTS: Serum 25(OH) vitamin D was measured and patients were followed for a median of 7.1 years (range, 0.7 to 9.3 years) to assess fractures. RESULTS: Mean serum 25(OH) vitamin D concentrations were lower in case-patients than in control participants (55.95 nmol/L [SD, 20.28] vs. 59.60 nmol/L [SD, 18.05]; P = 0.007), and lower serum 25(OH) vitamin D concentrations increased hip fracture risk (adjusted odds ratio for each 25-nmol/L decrease, 1.33 [95% CI, 1.06 to 1.68]). Women with the lowest 25(OH) vitamin D concentrations (< or =47.5 nmol/L) had a higher fracture risk than did those with the highest concentrations (> or =70.7 nmol/L) (adjusted odds ratio, 1.71 [CI, 1.05 to 2.79]), and the risk increased statistically significantly across quartiles of serum 25(OH) vitamin D concentration (P for trend = 0.016). This association was independent of number of falls, physical function, frailty, renal function, and sex-steroid hormone levels and seemed to be partially mediated by bone resorption. LIMITATIONS: Few case-patients were nonwhite women. Bone mineral density and parathyroid hormone levels were not accounted for in the analysis. CONCLUSION: Low serum 25(OH) vitamin D concentrations are associated with a higher risk for hip fracture.

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.

Bone mineral density changes during the menopause transition in a multiethnic cohort of women.

CONTEXT: Rates of bone loss across the menopause transition and factors associated with variation in menopausal bone loss are poorly understood. OBJECTIVE: Our objective was to assess rates of bone loss at each stage of the transition and examine major factors that modify those rates. DESIGN, SETTING, AND PARTICIPANTS: We conducted a longitudinal cohort study of 1902 African-American, Caucasian, Chinese, or Japanese women participating in The Study of Women's Health Across the Nation. Women were pre- or early perimenopausal at baseline. OUTCOME MEASURE: We assessed bone mineral density (BMD) of the lumbar spine and total hip across a maximum of six annual visits. RESULTS: There was little change in BMD during the pre- or early perimenopause. BMD declined substantially in the late perimenopause, with an average loss of 0.018 and 0.010 g/cm2.yr from the spine and hip, respectively (P<0.001 for both). In the postmenopause, rates of loss from the spine and hip were 0.022 and 0.013 g/cm2.yr, respectively (P<0.001 for both). During the late peri- and postmenopause, bone loss was approximately 35-55% slower in women in the top vs. the bottom tertile of body weight. Apparent ethnic differences in rates of spine bone loss were largely explained by differences in body weight. CONCLUSIONS: Bone loss accelerates substantially in the late perimenopause and continues at a similar pace in the first postmenopausal years. Body weight is a major determinant of the rate of menopausal BMD loss, whereas ethnicity, per se, is not. Healthcare providers should consider this information when deciding when to screen women for osteoporosis.

Inflammatory markers and incident fracture risk in older men and women: the Health Aging and Body Composition Study.

UNLABELLED: The inflammation of aging hypothesis purports that aging is the accumulation of damage, which results, in part, from chronic activation of inflammation process. We tested this hypothesis in relationship to fractures in 2985 men and women enrolled in the Health ABC study. Results showed that subjects with the greatest number of inflammatory markers have the highest risk of fracture. INTRODUCTION: Cytokines play major roles in regulating bone remodeling in the bone microenvironment, but their relationship to fractures is uncertain. MATERIALS AND METHODS: The study population includes 2985 well-functioning white and black women and men (42%, black; 51%, women) 70-79 yr of age enrolled in the Health Aging and Body Composition Study. Inflammatory markers were measured in frozen serum using standardized assays. We measured interleukin (IL-6), TNFalpha, C-reactive protein (CRP), and soluble receptors (IL-2 sR, IL-6 sR, TNF sR1and TNF sR2).Cytokine-soluble receptors were measured in a subset (n = 1430). Total hip BMD was measured by DXA. During 5.8 +/- 1.6 yr of 95% complete follow-up, incident fractures were confirmed in 268 subjects. The risk of fracture was compared among subjects with the highest inflammatory markers (quartile 4) versus lower levels (quartiles 1, 2, and 3) using proportional hazard models. RESULTS AND CONCLUSIONS: Subjects who fractured were more likely to be white and female. Baseline markers of inflammation were higher among subjects who subsequently experienced an incident fracture. In multivariate models, the relative risk of fracture (95% CIs) for subjects with the highest inflammatory markers (quartile 4) compared with those with lower inflammatory markers (quartiles 1, 2, and 3) was 1.34 (0.99, 1.82) for CRP; 1.28 (0.95-1.74) for IL-6; 1.28 (0.97-1.70) for TNFalpha; 1.52 (1.04-2.21) for IL-2 sR; 1.33 (0.90-1.96) for IL-6 sR; 1.73 (1.18-2.55) for TNF sR1 and 1.48 (1.01-2.20) for TNF sR2. In subjects with three or more (out of seven) high inflammatory markers, the relative risk of fracture was 2.65 (1.44-4.89) in comparison with subjects with no elevated markers. (p trend = 0.001). We conclude that elevated inflammatory markers are prognostic for fractures, extending the inflammation hypothesis of aging to osteoporotic fractures.

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.

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.

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.

Energy requirements in the eighth decade of life.

BACKGROUND: Knowledge of energy requirements among relatively healthy elderly is limited. OBJECTIVES: The objectives of the study were to measure total energy expenditure (TEE)-derived energy requirements in a biracial population of older adults without limitations to daily life and to test these empirical measures against national and international recommendations. DESIGN: TEE (measured by the doubly labeled water method), resting metabolic rate (RMR), activity-related energy expenditure (AEE), and body composition were measured in 288 persons aged 70-79 y selected from the Health, Aging, and Body Composition Study. RESULTS: TEE was lower in women (approximately 530 kcal/d; P < 0.0001) than in men because of the women's lower RMR and AEE. Fat-free mass explained the sex difference in RMR, but body weight failed to account for the women's lower AEE (approximately 1 kcal x kg(-1) x d(-1); P = 0.007). Blacks had lower TEE than did whites (approximately 100 kcal/d, P = 0.03), and that was explained by blacks' lower RMR. Physical activity level (TEE/RMR) did not differ significantly between sexes and races (1.70 +/- 0.23). The World Health Organization (WHO) recommendations overestimated TEE by 10 +/- 15% (P < 0.0001) in women but not in men, and the dietary reference intakes (DRIs) were accurate to 0 +/- 14% (P = 0.1). Both WHO and DRI recommendations are based on an underestimated physical activity level, and WHO recommendations are based on overestimated RMR. CONCLUSIONS: This study of well-functioning older adults confirms the racial difference in energy metabolism and supports the use of the 2002 DRIs. Because the DRIs and WHO recommendations underestimated PAL, new predictive equations of energy requirements are proposed.

Vitamin D receptor and aromatase gene interaction and bone mass in older African-American women.

Aromatization of androgens by the CYP19 gene product, aromatase, is the major source of endogenous estrogen in postmenopausal women. We determined whether an Arg(264)Cys polymorphism in the CYP19 gene is associated with bone mineral density (BMD) and bone loss in older women. Because vitamin D regulates CYP19 gene expression, we also tested for an interaction with a translation start site polymorphism in the vitamin D receptor (VDR) gene. Hip BMD was measured twice, an average of 1.9 years apart, in 100 African-American women aged > or =65 years. Neither polymorphism alone was significantly associated with BMD or bone loss. BMD measurements in women with the less frequent allele at both loci were 0.5 to 1.3 SD lower than in women with neither or only a single rare allele (P <.001 for interaction). These women also experienced more rapid hip bone loss than other women (P <.05 for interaction). We conclude that VDR and CYP19 gene polymorphisms may jointly influence bone mass and the rate of bone loss in older African-American women.

Sport and home physical activity are independently associated with bone density.

PURPOSE: To study the relations between four domains of physical activity-sport, home, work, and active living-and bone mineral density (BMD). METHODS: Baseline data from African-American (N = 544), Caucasian (N= 1044), Chinese (N= 230), and Japanese (N= 239) participants, aged 42-52 yr, from the study of Women's Health Across the Nation were analyzed. BMD was measured with Hologic 2000 or 4500A densitometers. Physical activity was assessed with the Kaiser Physical Activity Scale, which rates each domain of activity between 1 (low) and 5 (high). Multiply adjusted linear regression models were used to estimate the relations between each activity domain and BMD. RESULTS: The mean and median values of sport, home, work, and active living each approximated the midpoint of the scale and did not differ substantially among ethnic groups. Scores for each domain of activity were not highly correlated, with r values ranging between -0.03 and 0.33. Independent of age, body mass index, ethnic group, alcohol use, dietary calcium, smoking, menopause status, SWAN site, and other domains of physical activity, higher sport activity was statistically significantly associated with greater BMD at the lumbar spine (P= 0.008), femoral neck (P= 0.0002), and total hip (P< 0.0001). More home physical activity was associated with higher BMD at the spine (P= 0.049) and femoral neck (P= 0.008). Neither work physical activity nor active living was related to BMD at any bone site. CONCLUSIONS: These results highlight the need to consider domain-specific physical activity in relation to health outcomes in women.

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.

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.

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.

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.