OBJECTIVE: To study the causes and consequences of radiologically confirmed rib fractures (seldom considered in the context of osteoporosis) in community dwelling older men. DESIGN: Prospective cohort study (Osteoporotic Fractures in Men (MrOS) Study). SETTING AND PARTICIPANTS: 5995 men aged 65 or over recruited in 2000-2 from six US sites; 99% answered mailed questionnaires about falls and fractures every four months for a mean 6.2 (SD 1.3) year follow-up. MAIN OUTCOME MEASURES: New fractures validated by radiology reports; multivariate Cox proportional hazard ratios were used to evaluate factors independently associated with time to incident rib fracture; associations between baseline rib fracture and incident hip and wrist fracture were also evaluated. RESULTS: The incidence of rib fracture was 3.5/1000 person years, and 24%(126/522) of all incident non-spine fractures were rib fractures. Nearly half of new rib fractures (48%; n=61) followed falling from standing height or lower. Independent risk factors for an incident rib fracture were age 80 or above, low bone density, difficulty with instrumental activities of daily living, and a baseline history of rib/chest fracture. Men with a history of rib/chest fracture had at least a twofold increased risk of an incident rib fracture (adjusted hazard ratio 2.71, 95% confidence interval 1.86 to 3.95), hip fracture (2.05, 1.33 to 3.15), and wrist fracture (2.06, 1.14 to 3.70). Only 14/82 of men reported being treated with bone specific drugs after their incident rib fracture. CONCLUSIONS: Rib fracture, the most common incident clinical fracture in men, was associated with classic risk markers for osteoporosis, including old age, low hip bone mineral density, and history of fracture. A history of rib fracture predicted a more than twofold increased risk of future fracture of the rib, hip, or wrist, independent of bone density and other covariates. Rib fractures should be considered to be osteoporotic fractures in the evaluation of older men for treatment to prevent future fracture.

BMD was compared across race/ethnic groups. There were substantial race/ethnic differences in BMD even within African or Asian origin. Additional adjustment for body size greatly attenuated or reversed the differences between US Caucasian men vs Asian men. It illustrates the role of body size on the difference between these groups. INTRODUCTION: There is insufficient epidemiologic information about men's bone mineral density (BMD) levels across race/ethnic groups and geographic locations. METHODS: In a cross-sectional design, we compared BMD in older men across seven race/ethnic groups in four countries. Femoral neck, total hip, and lumbar spine BMD were measured in men (age 65 to 78 years) from the Osteoporotic Fractures in Men (MrOS) Study (4,074 Caucasian, 208 African-American, 157 Asian, and 116 Hispanic men in USA), Tobago Bone Health Study (422 Afro-Caribbean men), MrOS Hong Kong Study (1,747 Hong Kong Chinese men), and the Namwon Study (1,079 South Korean men). BMD was corrected according to the cross-site calibration results for all scanners. RESULTS: When compared with US Caucasian men, Afro-Caribbean and African-American men had, respectively, 8-20% and 6-11% higher age-adjusted mean BMD at all three bone sites. Hip BMD was similar in US Caucasian and Hispanic men, US Asian, Hong Kong Chinese, and Korean men had 3-14% lower BMD at all bone sites except femoral neck in Korean men. Additional adjustment for weight and height greatly attenuated or reversed the differences between US Caucasian men vs Asian men including US Asian, Hong Kong Chinese, and South Korean men. Among Asian groups, Korean men had higher femoral neck BMD and lower total hip BMD. CONCLUSION: These findings show substantial race/ethnic differences in BMD even within African or Asian origin and illustrate the important role of body size on the difference between Asian men and others.

Quantitative computed tomography (QCT) can estimate volumetric bone mineral density (vBMD) and distinguish trabecular from cortical bone. Few comprehensive studies have examined correlates of volumetric bone mineral density (vBMD) in older men. This study evaluated the impact of demographic, anthropometric, lifestyle, and medical factors on vBMD in 1172 men, aged 69-97, and enrolled in The Osteoporotic Fractures in Men Study (MrOS). Peripheral quantitative computed tomography (pQCT) was used to measure vBMD of the radius and tibia. The multivariable linear regression models explained up to 10% of the variance in trabecular vBMD and up to 9% of the variance in cortical vBMD. Age was not correlated with radial trabecular vBMD. Correlates associated with both cortical and trabecular vBMD were age (-), caffeine intake (-), total calcium intake (+), non-trauma fracture (-), and hypertension (+). Higher body weight was related to greater trabecular vBMD and lower cortical vBMD. Height (-), education (+), diabetes with TZD use (+), rheumatoid arthritis (+), using arms to stand from a chair (-), and anti-androgen use (-) were only associated with trabecular vBMD. Factors only associated with cortical vBMD included clinic site (-), androgen use (+), grip strength (+), past smoker (-) and time to complete 5 chair stands (-). Certain correlates of trabecular and cortical volumetric BMD differed among older men. An ascertainment of risk factors associated with trabecular and cortical vBMD may lead to better understanding and preventive efforts for osteoporosis in men.(c) 2010 American Society for Bone and Mineral Research.

The new US National Osteoporosis Foundation Clinician's Guide to Prevention and Treatment of Osteoporosis includes criteria for recommending pharmacologic treatment based on history of hip or vertebral fracture, femoral neck (FN) or spine BMD T-scores </=-2.5, and presence of low bone mass at the FN or spine plus a 10 year risk of hip fracture >/=3% or of major osteoporotic fracture >/= 20%. The proportion of men who would be recommended for treatment by these guidelines is not known. We applied the NOF criteria for treatment to men participating in the Osteoporotic Fractures in Men Study (MrOS). To determine how the MrOS population differs from the general US population of Caucasian men aged 65 years and older, we compared men in MrOS to men who participated in the National Health and Nutrition Examination Survey (NHANES) III on criteria included in the NOF treatment guidelines that were common to both cohorts. Compared with NHANES III, men in MrOS had higher femoral neck BMD. Application of NOF guidelines to MrOS data estimated that at least 34% of U.S. white men >/= age 65 and 49% of those >/= age 75 years would be recommended for drug treatment. Application of the new NOF Guidelines would result in recommending a very large proportion of white men in the United States for pharmacologic treatment of osteoporosis, for whom many the efficacy of treatment is unknown.(c) 2010 American Society for Bone and Mineral Research.

In the FIT Long Term Extension (FLEX) trial, 10 years of alendronate (ALN) did not significantly reduce the risk of non-vertebral fractures (NVF), compared with 5 years of ALN. Continuing ALN reduced the risk of clinical, but not morphometric, vertebral fractures, regardless of baseline vertebral fracture status. In previous studies, ALN efficacy for NVF prevention in women without prevalent vertebral fracture was limited to those with femoral neck (FN) T-score </=-2.5. To determine whether the effect of long-term ALN on fracture differs by vertebral fracture status and femoral neck (FN) T-score, we performed a post hoc analysis using FLEX data, a randomized double-blind placebo-controlled trial among 1,099 postmenopausal women originally randomized to ALN in FIT with mean ALN use of 5 years. In FLEX women were randomized to placebo (40%) or ALN 5 (30%) or 10 (30%) mg/d for an additional 5 years. Among women without vertebral fracture at FLEX baseline (N = 720), continuation of ALN reduced NVF in women with FLEX baseline FN T-score </=-2.5 (RR 0.50; 95% CI 0.26-0.96) but not with T-score >-2.5 and </=-2 (RR 0.79; 95% CI 0.37-1.66) or with T-score >-2 (RR 1.41; 95% CI 0.75-2.66)(p for interaction 0.019). Continuing alendronate for 10 years instead of stopping after 5 years reduces non-vertebral fracture risk in women without prevalent vertebral fracture whose FN T-score, achieved after 5 years of ALN, is </=-2.5, but does not reduce risk of NVF in women whose T-score is >-2.(c) 2010 American Society for Bone and Mineral Research.

Background A possible familial component to fracture risk may be mediated through a genetic liability to fall recurrently. Methods Our analysis sample included 186 female sibling-ships (N=401) of mean age =71.9 years (SD=5.0). Using variance component models, we estimated residual upper-limit heritabilities in fall-risk mobility phenotypes (e.g., chair-stand time, rapid step-ups, and usual-paced walking speed) and in recurrent falls. We also estimated familial and environmental (unmeasured) correlations between pairs of fall-risk mobility phenotypes. All models were adjusted for age, height, BMI, and medical and environmental factors. Results Residual upper-limit heritabilities were all moderate (p<0.05), ranging from 0.27 for usual-paced walking speed to 0.58 for recurrent falls. A strong familial correlation between usual-paced walking speed and rapid step-ups of 0.65 (p<0.01) was identified. Familial correlations between usual-paced walking speed and chair-stand time (-0.02) and between chair-stand time and rapid step-ups (-0.27) were both non-significant (p>0.05). Environmental correlations ranged from 0.35 to 0.58 (absolute values), p<0.05 for all. Conclusions There exists moderate familial resemblance in fall-risk mobility phenotypes and recurrent falls among older female siblings, which we expect is primarily genetic given that adult siblings live separate lives. All fall-risk mobility phenotypes may be co-influenced at least to a small degree by shared latent familial or environmental factors; however, up to approximately half of the covariation between usual-paced walking speed and rapid step-ups may be due to a common set of genes. Key words: falls, familial correlation, genetics, heritability.

PURPOSE: To test the reliability and validity of questionnaires shortened from the National Eye Institute 25-item Vision Function Questionnaire (NEI VFQ-25). DESIGN: Cross-sectional, multicenter cohort study. METHODS: Reliability was assessed by Cronbach alpha coefficients. Validity was evaluated by studying the association of vision-targeted quality-of-life composite scores with objective visual function measurements. A total of 5482 women between the ages of 65 and 100 years participated in the year-10 clinic visit in the Study of Osteoporotic Fractures (SOF). A total of 3631 women with complete data were included in the visual acuity (VA) and visual field (VF) analyses of the 9-item NEI VFQ (NEI VFQ-9), which is defined for those who care to drive, and a total of 5311 women with complete data were included in the VA and VF in the analyses of the 8-item NEI VFQ (NEI VFQ-8). To assess differences in prevalent eye diseases, which were ascertained for a random sample of SOF participants, 853 and 1237 women were included in the NEI VFQ-9 and the NEI VFQ-8 analyses, respectively. RESULTS: The Cronbach alpha coefficient for the NEI VFQ-9 scale was 0.83, and that of the NEI VFQ-8 was 0.84. Using both questionnaires, women with VA worse than 20/40 had lower composite scores compared with those with VA of 20/40 or better (P <.001). Participants with mild, moderate, and severe binocular VF loss had lower composite scores compared with those with no binocular VF loss (P <.001). Compared with women without chronic eye diseases in both eyes, women with at least 1 chronic eye disease in at least 1 eye had lower composite scores. CONCLUSIONS: Both questionnaires showed high reliability across items and validity with respect to clinical markers of eye disease. Future research should compare the properties of these shortened surveys with those of the NEI VFQ-25.

BACKGROUND: A Web-based risk assessment tool (FRAX) using clinical risk factors with and without femoral neck bone mineral density (BMD) has been incorporated into clinical guidelines regarding treatment to prevent fractures. However, it is uncertain whether prediction with FRAX models is superior to that based on parsimonious models. METHODS: We conducted a prospective cohort study in 6252 women 65 years or older to compare the value of FRAX models that include BMD with that of parsimonious models based on age and BMD alone for prediction of fractures. We also compared FRAX models without BMD with simple models based on age and fracture history alone. Fractures (hip, major osteoporotic [hip, clinical vertebral, wrist, or humerus], and any clinical fracture) were ascertained during 10 years of follow-up. Area under the curve (AUC) statistics from receiver operating characteristic curve analysis were compared between FRAX models and simple models. RESULTS: The AUC comparisons showed no differences between FRAX models with BMD and simple models with age and BMD alone in discriminating hip (AUC, 0.75 for the FRAX model and 0.76 for the simple model; P =.26), major osteoporotic (AUC, 0.68 for the FRAX model and 0.69 for the simple model; P =.51), and clinical fracture (AUC, 0.64 for the FRAX model and 0.63 for the simple model; P =.16). Similarly, performance of parsimonious models containing age and fracture history alone was nearly identical to that of FRAX models without BMD. The proportion of women in each quartile of predicted risk who actually experienced a fracture outcome did not differ between FRAX and simple models (P > or =.16). CONCLUSION: Simple models based on age and BMD alone or age and fracture history alone predicted 10-year risk of hip, major osteoporotic, and clinical fracture as well as more complex FRAX models.

OBJECTIVE: To test the hypothesis that lower 25-hydroxyvitamin D [25(OH)D] levels are associated with a greater likelihood of cognitive impairment and risk of cognitive decline. METHODS: We measured 25(OH)D and assessed cognitive function using the Modified Mini-Mental State Examination (3MS) and Trail Making Test Part B (Trails B) in a cohort of 1,604 men enrolled in the Osteoporotic Fractures in Men Study and followed them for an average of 4.6 years for changes in cognitive function. RESULTS: In a model adjusted for age, season, and site, men with lower 25(OH)D levels seemed to have a higher odds of cognitive impairment, but the test for trend did not reach significance (impairment by 3MS: odds ratio [OR] 1.84, 95% confidence interval [CI] 0.81-4.19 for quartile [Q] 1; 1.41, 0.61-3.28 for Q2; and 1.18, 0.50-2.81 for Q3, compared with Q4 [referent group; p trend = 0.12]; and impairment by Trails B: OR 1.66, 95% CI 0.98-2.82 for Q1; 0.96, 0.54-1.69 for Q2; and 1.30, 0.76-2.22 for Q3, compared with Q4 [p trend = 0.12]). Adjustment for age and education further attenuated the relationships. There was a trend for an independent association between lower 25(OH)D levels and odds of cognitive decline by 3MS performance (multivariable OR 1.41, 95% CI 0.89-2.23 for Q1; 1.28, 0.84-1.95 for Q2; and 1.06, 0.70-1.62 for Q3, compared with Q4 [p = 0.10]), but no association with cognitive decline by Trails B. CONCLUSION: We found little evidence of independent associations between lower 25-hydroxyvitamin D level and baseline global and executive cognitive function or incident cognitive decline.

Context: Early postmenopausal women with higher testosterone (T) levels have increased insulin resistance (IR) and cardiovascular risk factors, but whether this translates into increased cardiovascular disease later in life is unknown. Objective: The objective of the study was to determine whether higher T levels are associated with IR, the metabolic syndrome (MetSyn), and coronary heart disease (CHD) in elderly women. Design: Total T and free T by equilibrium dialysis were measured using ultrasensitive assays in 344 women aged 65-98 yr enrolled in the Cardiovascular Health Study. Cross-sectional analyses were performed to examine the associations between total and free T and IR, MetSyn, and CHD. Results: There was a stepwise increase in the homeostasis model assessment of insulin resistance with increasing total (P = 0.0.003) and free T (P = 0.02) level and a corresponding decrease in Quantitative Insulin Sensitivity Check Index (P < 0.001 and P = 0.002, respectively). In adjusted models, higher levels of both total and free T were strongly associated with abdominal obesity and high fasting glucose, the two MetSyn components most strongly linked to IR. After adjustment, women in the top quartile of total T levels had a 3-fold greater odds of MetSyn (odds ratio 3.15, 95% confidence interval 1.57-6.35) than those in the bottom quartile and a 3-fold greater odds of CHD (odds ratio 2.95, 95% confidence interval 1.2-7.3) than those in second quartile, whereas free T was not significantly associated with MetSyn or CHD. Conclusions: Higher levels of T are associated with IR, MetSyn, and CHD in elderly women. Whether T is a marker or mediator of cardiovascular disease in this population merits further investigation.