Search

Objective: The aim of this study was to determine whether older postmenopausal women with a history of bilateral oophorectomy before natural menopause (surgical menopause) have a higher risk of nonvertebral postmenopausal fracture than women with natural menopause., Methods: We used 21 years of prospectively collected incident fracture data from the ongoing Study of Osteoporotic Fractures, a cohort study of community-dwelling women without previous bilateral hip fracture who were 65 years or older at enrollment, to determine the risk of hip, wrist, and any nonvertebral fracture. χ(2) and t tests were used to compare the two groups on important characteristics. Multivariable Cox proportional hazards regression models stratified by baseline oral estrogen use status were used to estimate the risk of fracture., Results: Baseline characteristics differed significantly among the 6,616 women within the Study of Osteoporotic Fractures who underwent either surgical (1,157) or natural (5,459) menopause, including mean age at menopause (44.3 ± 7.4 vs 48.9 ± 4.9 y, P < 0.001) and current use of oral estrogen (30.2% vs 6.5%, P < 0.001). Fracture rates were not significantly increased for surgical versus natural menopause, even among women who had never used oral estrogen (hip fracture: hazard ratio [HR], 0.87; 95% CI, 0.63-1.21; wrist fracture: HR, 1.10; 95% CI, 0.78-1.57; any nonvertebral fracture: HR, 1.11; 95% CI, 0.93-1.32)., Conclusions: These data provide some reassurance that the long-term risk of nonvertebral fracture is not substantially increased for postmenopausal women who experienced premenopausal bilateral oophorectomy, compared with postmenopausal women with intact ovaries, even in the absence of postmenopausal estrogen therapy.

Bone mineral density (BMD) is a strong predictor of fracture, yet most fractures occur in women without osteoporosis by BMD criteria. To improve fracture risk prediction, the World Health Organization recently developed a country-specific fracture risk index of clinical risk factors (FRAX) that estimates 10-year probabilities of hip and major osteoporotic fracture. Within differing baseline BMD categories, we evaluated 6252 women aged 65 or older in the Study of Osteoporotic Fractures using FRAX 10-year probabilities of hip and major osteoporotic fracture (ie, hip, clinical spine, wrist, and humerus) compared with incidence of fractures over 10 years of follow-up. Overall ability of FRAX to predict fracture risk based on initial BMD T-score categories (normal, low bone mass, and osteoporosis) was evaluated with receiver-operating-characteristic (ROC) analyses using area under the curve (AUC). Over 10 years of follow-up, 368 women incurred a hip fracture, and 1011 a major osteoporotic fracture. Women with low bone mass represented the majority (n = 3791, 61%); they developed many hip (n = 176, 48%) and major osteoporotic fractures (n = 569, 56%). Among women with normal and low bone mass, FRAX (including BMD) was an overall better predictor of hip fracture risk (AUC = 0.78 and 0.70, respectively) than major osteoporotic fractures (AUC = 0.64 and 0.62). Simpler models (eg, age + prior fracture) had similar AUCs to FRAX, including among women for whom primary prevention is sought (no prior fracture or osteoporosis by BMD). The FRAX and simpler models predict 10-year risk of incident hip and major osteoporotic fractures in older US women with normal or low bone mass., (Copyright © 2011 American Society for Bone and Mineral Research.)

Use of antidepressant medications has been associated with increased risk of fracture, but prior studies have been limited by incomplete control of confounders or a limited number of fractures. Use of antidepressant medications by 8,217 community-dwelling women aged 69 and older from a population-based prospective cohort study at four US clinical centers was assessed by interview at four examinations over a 10-year period, beginning in 1992-1994. Use was coded as a time-dependent variable. Incident fractures occurring after the initial medication assessment until July 2007 were confirmed by radiographic reports. Potential confounders were included in multivariable models and updated at each follow-up visit. Compared to nonusers of antidepressant medications, women using SSRIs experienced a higher risk of nonspine fracture in age-adjusted models (HR = 1.36, 95% CI 1.11-1.67) and in multivariable models controlling for potential confounders (HR = 1.30, 95% CI 1.04-1.62). SSRI use was not associated with an increased risk of first hip fracture (HR = 1.01, 95% CI 0.71-1.44) but was associated with an increased risk of wrist fracture (HR = 1.54, 95% CI 1.01-2.36). TCA use was associated with an increased risk of nonspine fracture in age-adjusted models, but in multivariable models this risk was attenuated. SSRI use was associated with a higher risk of any nonspine fracture, but not hip fracture, in this cohort of older women. TCA use was associated with a higher risk of nonspine fracture, but this association was in part explained by confounding factors.

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 yr (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, body mass index, 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 nonsignificant (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 coinfluenced at least to a small degree by shared latent familial or environmental factors; however, up to approximately one-half of the covariation between usual-paced walking speed and rapid step-ups may be due to a common set of genes.

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.

Context: Type 2 diabetes is associated with higher fracture risk at a given bone mineral density. Advanced glycation endproducts (AGEs) accumulate in bone collagen with age and diabetes and may weaken bone., Objective: The aim was to determine whether urine pentosidine, an AGE, was associated with fractures in older adults with and without diabetes., Design: We performed an observational cohort study., Setting: We used data from the Health, Aging and Body Composition prospective study of white and black, well-functioning men and women ages 70-79 yr., Participants: Participants with (n = 501) and without (n = 427) diabetes were matched on gender, race, and study site., Predictor: Urine pentosidine was assayed from frozen stored baseline specimens., Main Outcome Measures: Incident clinical fractures and baseline vertebral fractures were measured., Results: Despite higher bone mineral density, clinical fracture incidence (14.8 vs. 12.6%) and vertebral fracture prevalence (2.3 vs. 2.9%) were not lower in those with diabetes (P > 0.05). In multivariable models, pentosidine was associated with increased clinical fracture incidence in those with diabetes [relative hazard, 1.42; 95% confidence interval (CI), 1.10, 1.83, for 1 sd increase in log pentosidine] but not in those without diabetes (relative hazard, 1.08; 95% CI, 0.79, 1.49; P value for interaction = 0.030). In those with diabetes, pentosidine was associated with increased vertebral fracture prevalence (adjusted odds ratio, 5.93; 95% CI, 2.08, 16.94, for 1 sd increase in log pentosidine) but not in those without diabetes (adjusted odds ratio, 0.74; 95% CI, 0.30, 1.83; P value for interaction = 0.005)., Conclusions: Higher pentosidine levels are a risk factor for fracture in older adults with diabetes and may account in part for reduced bone strength in type 2 diabetes.

Successful aging is multidimensional, and many phenotypes have been proposed. We examined a biomarker of aging based on repeated measures of BMD for up to 15 yr and hypothesized that maintenance of BMD will be associated with low fracture risk and disability and improved survival. We studied 9704 women recruited at four U.S. clinical centers and enrolled in the Study of Osteoporotic Fractures, a longitudinal cohort study. Of these, 8224 women had at least one hip BMD measurement. Hip BMD was measured a maximum of five times over 15 yr. Random effects regression was used to determine a BMD slope for each subject. Three groups were formed-"maintained" BMD: slope >or=0, n = 724 (9%); "expected" BMD loss: slope <0 to <1 SD below mean, n = 6478 (79%); and "accelerated" BMD loss: slope >or=1 SD below mean, n = 1022 (12%). Cox proportional hazards models were used to compare the relative hazard (RH; 95% CI) of fracture, incident mobility disability, and mortality in the maintained and accelerated groups compared with the expected. A 1 SD decrease in the BMD slope was associated with an increased risk of all outcomes. In multivariate models, the RH of nonspine fracture was 0.81 (0.71-0.93) and of hip fracture was 0.36 (0.25-0.53) for women in the maintained compared with the expected group. The incidence of mobility disability was lower in the maintained versus expected group (RH = 0.70; 95% CI = 0.59-0.83), but this was largely explained by other factors. Women who experienced accelerated bone loss were more likely to develop disability (RH = 1.56; 95% CI: 1.33-1.84). Mortality risks were lower in the maintained compared with the expected group (RH = 0.49; 95% CI: 0.42-0.58). In conclusion, a subset of older women maintained their BMD up to 15 yr, suggesting that bone loss is not an inevitable consequence of aging. These women experienced a lower risk of fractures, disability, and mortality, suggesting that this phenotype may be a marker of successful aging.

Recent studies have suggested an increased fracture risk with acid-suppressive medication use. We studied two cohorts of men and women over age 65 who were enrolled in the Osteoporotic Fractures in Men Study (MrOS) and the Study of Osteoporotic Fractures (SOF), respectively. We used dual-energy X-ray absorptiometry and assessed baseline use of proton pump inhibitors (PPIs) and/or H2 receptor antagonists (H2RAs) in 5,755 men and 5,339 women. Medication use and bone mineral density (BMD) were assessed, and hip and other nonspine fractures were documented. On multivariate analysis, men using either PPIs or H2RAs had lower cross-sectional bone mass. No significant BMD differences were observed among women. However, there was an increased risk of nonspine fracture among women using PPIs (relative hazard [RH] = 1.34, 95% confidence interval [CI] 1.10-1.64). PPI use was also associated with an increased risk of nonspine fracture in men but only among those who were not taking calcium supplements (RH = 1.49, 95% CI 1.04-2.14). H2RA use was not associated with nonspine fractures, and neither H2RA use nor PPI use was associated with incident hip fractures in men or women. The use of PPIs in older women, and perhaps older men with low calcium intake, may be associated with a modestly increased risk of nonspine fracture.

Candidate osteoporosis gene variants were examined for associations with fracture risk and bone mineral density (BMD). A total of 9,704 white women were recruited at four U.S. clinical centers and enrolled into the Study of Osteoporotic Fractures, a longitudinal cohort study. Genotyping of 31 polymorphisms from 18 candidate osteoporosis genes was performed in 6,752 women. Incident radiographic fractures were identified at the third and eighth examinations compared with the baseline examination. BMD was measured at the total hip by dual-energy X-ray absorptiometry. Analyses were adjusted for age, clinic site, and self-reported ethnicity. During a mean follow-up of 14.5 years, a total of 849 hip, 658 vertebral, and 2,496 nonhip/nonvertebral fractures occurred in 6,752 women. Women carrying the ALOX15&#95;G48924T T/T genotype had a higher rate of hip fracture (hazard ratio [HR] = 1.33;95% confidence interval [95% CI] = 1.00-1.77) compared with the G/G genotype. Compared with those carrying the PRL&#95;T228C T/T genotype, women with either the C/C (HR = 0.80; 95% CI = 0.67-0.95) or C/T (HR = 0.81; 95% CI = 0.68-0.97) genotype had a lower rate of nonvertebral/nonhip fractures. Women carrying the BMP2&#95;A125611G G/G genotype had a higher rate of vertebral fracture (odds ratio [OR] = 1.51; 95% CI = 1.03-2.23) compared with the A/A genotype. Women with the ESR1&#95;C1335G G/G genotype had a higher rate of vertebral fracture (OR = 1.64; 95% CI = 1.07-2.50) compared with the C/C genotype. Compared with those with the MMP2&#95;C595T C/C genotype, women with the C/T (OR = 0.79; 95% CI = 0.65-0.96) or T/T (OR = 0.44; 95% CI = 0.27-0.72) genotype had a lower rate of vertebral fracture. In conclusion, polymorphisms in several candidate genes were associated with hip, vertebral, and nonhip/nonvertebral fractures but not with total hip BMD in this large population based cohort study.

Lead is stored in the skeleton and can serve as an endogenous source for many years. Lead may influence the risk of fracture, through direct effects on bone strength or indirectly by disturbing neuromuscular function and increasing the risk of falls. The objective of this analysis is to test the hypothesis that women with higher blood lead levels experience higher rates of falls and fracture. This was a prospective cohort study of 533 women 65-87 yr of age enrolled in the Study of Osteoporotic Fractures at two U.S. research centers (Baltimore, MD; Monongahela Valley, PA) from 1986 to 1988. Blood lead levels (in microg/dl) were measured in 1990-1991 by atomic absorption spectrophotometry and classified as "low" (or=8; upper 15th percentile). Total hip BMD was measured by DXA twice, 3.55 yr apart. Information on falls was collected every 4 mo for 4 yr. Incident nonspine fractures were identified and confirmed over 10 yr. Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% CI of fracture. Generalized estimating equations were used to calculate the incident rate ratio of falls (95% CI). The mean blood lead level was 5.3 +/- 2.3 (SD) microg/dl (range, 1-21 microg/dl). Baseline BMD was 7% lower in total hip and 5% lower in femoral neck in the highest compared with lowest blood lead group (p < 0.02). Hip bone loss tended to be greater in the high lead group, but differences were not significant. In multivariable adjusted models, women with high blood lead levels had an increased risk of nonspine fracture (HR = 2.50; 95% CI = 1.25, 5.03; p trend = 0.016) and higher risk of falls (incident rate ratio = 1.62; 95% CI = 1.07, 2.45; p trend = 0.014) compared with women with lowest lead level. Blood lead levels are associated with an increased risk of falls and fractures, extending the negative health consequences of lead to include osteoporotic fractures.

Background: Frailty, as defined by the index derived from the Cardiovascular Health Study (CHS index), predicts risk of adverse outcomes in older adults. Use of this index, however, is impractical in clinical practice., Methods: We conducted a prospective cohort study in 6701 women 69 years or older to compare the predictive validity of a simple frailty index with the components of weight loss, inability to rise from a chair 5 times without using arms, and reduced energy level (Study of Osteoporotic Fractures [SOF index]) with that of the CHS index with the components of unintentional weight loss, poor grip strength, reduced energy level, slow walking speed, and low level of physical activity. Women were classified as robust, of intermediate status, or frail using each index. Falls were reported every 4 months for 1 year. Disability (> or =1 new impairment in performing instrumental activities of daily living) was ascertained at 4(1/2) years, and fractures and deaths were ascertained during 9 years of follow-up. Area under the curve (AUC) statistics from receiver operating characteristic curve analysis and -2 log likelihood statistics were compared for models containing the CHS index vs the SOF index., Results: Increasing evidence of frailty as defined by either the CHS index or the SOF index was similarly associated with an increased risk of adverse outcomes. Frail women had a higher age-adjusted risk of recurrent falls (odds ratio, 2.4), disability (odds ratio, 2.2-2.8), nonspine fracture (hazard ratio, 1.4-1.5), hip fracture (hazard ratio, 1.7-1.8), and death (hazard ratio, 2.4-2.7) (P < .001 for all models). The AUC comparisons revealed no differences between models with the CHS index vs the SOF index in discriminating falls (AUC = 0.61 for both models; P = .66), disability (AUC = 0.64; P = .23), nonspine fracture (AUC = 0.55; P = .80), hip fracture (AUC = 0.63; P = .64), or death (AUC = 0.72; P = .10). Results were similar when -2 log likelihood statistics were compared., Conclusion: The simple SOF index predicts risk of falls, disability, fracture, and death as well as the more complex CHS index and may provide a useful definition of frailty to identify older women at risk of adverse health outcomes in clinical practice.

Context: It is widely believed that fractures resulting from high trauma are not osteoporotic; however, this assumption has not been studied prospectively., Objective: To examine the association between bone mineral density (BMD) and high-trauma fracture and between high-trauma fracture and subsequent fracture in older women and men., Design, Setting, and Participants: Two prospective US cohort studies in community-dwelling adults 65 years or older from geographically diverse sites. The Study of Osteoporotic Fractures followed up 8022 women for 9.1 years (1988-2006). The Osteoporotic Fractures in Men Study followed up 5995 men for 5.1 years (2000-2007)., Main Outcome Measures: Hip and spine BMD were assessed by dual-energy x-ray absorptiometry. Incident nonspine fractures were confirmed by radiographic report. Fractures were classified, without knowledge of BMD, as high trauma (due to motor vehicle crashes and falls from greater than standing height) or as low trauma (due to falls from standing height and less severe trauma)., Results: Overall, 264 women and 94 men sustained an initial high-trauma fracture and 3211 women and 346 men sustained an initial low-trauma fracture. For women, each 1-SD reduction in total hip BMD was similarly associated with an increased risk of high-trauma fracture (multivariate relative hazard [RH], 1.45; 95% confidence interval [CI], 1.23-1.72) and low-trauma fracture (RH, 1.49; 95% CI, 1.42-1.57). Results were consistent in men (high-trauma fracture RH, 1.54; 95% CI, 1.20-1.96; low-trauma fracture RH, 1.69; 95% CI, 1.49-1.91). Risk of subsequent fracture was 34% (95% CI, 7%-67%) greater among women with an initial high-trauma fracture and 31% (95% CI, 20%-43%) greater among women with an initial low-trauma fracture, compared with women having no high- or low-trauma fracture, respectively. Risk of subsequent fracture was not modeled for men., Conclusions: Similar to low-trauma nonspine fractures, high-trauma nonspine fractures are associated with low BMD and increased risk of subsequent fracture in older adults. High-trauma nonspine fractures should be included as outcomes in osteoporosis trials and observational studies.

Unlabelled: We evaluated the association between the VDR translation start site polymorphism and osteoporotic phenotypes among 6698 older white women. Women with the C/C genotype had lower wrist BMD and an increased risk of wrist and all non-spine/low-trauma fractures. The high frequency of this variant confers a population attributable risk that is similar to several established risk factors for fracture., Introduction: The vitamin D receptor (VDR) is a nuclear receptor that regulates bone formation, bone resorption, and calcium homeostasis. A common C to T polymorphism in exon 2 of the VDR gene introduces a new translation start site and a protein that differs in length by three amino acids (T = 427aa, C = 424aa; rs10735810)., Materials and Methods: We conducted genetic association analyses of this polymorphism, BMD, and fracture outcomes in a prospective cohort of 6698 white American women >or=65 years of age. Incident fractures were confirmed by physician adjudication of radiology reports. There were 2532 incident nontraumatic/nonvertebral fractures during 13.6 yr of follow-up including 509 wrist and 703 hip fractures., Results: Women with the C/C genotype had somewhat lower distal radius BMD compared with those with the T/T genotype (CC=0.358 g/cm(2), CT=0.361 g/cm(2), TT=0.369 g/cm(2), p=0.003). The C/C genotype was also associated with increased risk of non-spine, low traumatic fractures (HR: 1.18; 95% CI: 1.04, 1.33) and wrist fractures (HR: 1.33; 95% CI: 1.01, 1.75) compared with the T/T genotype in age-adjusted models. Further adjustments for distal radius BMD only slightly attenuated these associations. The VDR polymorphism was not associated with hip fracture. The population attributable risk (PAR) of the C/C genotype for incident fractures was 6.1%. The PAR for established risk factors for fracture were: low femoral neck BMD (PAR=16.3%), maternal history of fracture (PAR=5.1%), low body weight (PAR=5.3%), corticosteroid use (PAR=1.3%), and smoking (PAR=1.6%). Similar PAR results were observed for wrist fractures., Conclusions: The common and potentially functional VDR translation start site polymorphism confers a modestly increased relative risk of fracture among older white women. However, the high frequency of this variant confers a population attributable risk that is similar to or greater than several established risk factors for fracture.

Background: Whether repeat bone mineral density (BMD) measurement adds benefit beyond the initial BMD measurement in predicting fractures in older women is unknown., Methods: We prospectively measured total hip BMD in 4124 older women (mean +/- SD age, 72 +/- 4 years) from 1989 to 1990 and again 8 years later. Incident nontraumatic hip and nonspine fractures were validated by radiology reports (>95% follow-up). In addition, spine fractures were defined morphometrically in 2129 of these women by lateral spine x-ray films from 1991 to 1992 and then again 11.4 years later. Prediction of fracture risk was assessed with proportional hazards models and receiver operating characteristic curves for BMD measures., Results: Over a mean of 5 years after the repeat BMD measure, 877 women experienced an incident nontraumatic nonspine fracture (275 hip fractures). In addition, 340 women developed a spine fracture. After adjustment for age and weight change, initial and repeat BMD measurements were similarly associated with fracture risk (per unit standard deviation lower in BMD) for nonspine (hazard ratio, 1.6), spine (odds ratio, 1.8-1.9), and hip (hazard ratio, 2.0-2.2) fractures (P<.001 for all models). Areas under the receiver operating characteristic curves (AUC) revealed no significant differences to discriminate nonspine (AUC, 0.65), spine (AUC, 0.67-0.68), or hip (AUC, 0.73-0.74) fractures between models with initial BMD, repeat BMD, or initial BMD plus change in BMD. Stratification by initial BMD t scores (normal, osteopenic, or osteoporotic), high bone loss, or hormone therapy did not alter results., Conclusion: In healthy, older, postmenopausal women, repeating a measurement of BMD up to 8 years later provides little additional value besides the initial BMD measurement for predicting incident fractures.

Objectives: To determine whether poorer visual acuity and contrast sensitivity are independent risk factors for all-cause and traumatic mortality in older women., Design: Twelve-year prospective cohort study (1986-2003)., Setting: Four U.S. clinical centers., Participants: Nine thousand seven hundred four postmenopausal white women aged 65 and older., Measurements: Habitually corrected binocular visual acuity and low- and high-frequency contrast sensitivity were measured at baseline using a standard protocol. A study physician adjudicated the primary cause of death from death certificates and medical record review., Results: During an average of 12.2 years of follow-up, 3,427 women died (35%), 72 (0.7%) from traumatic events. In multivariate models adjusted for age, chronic medical problems, and smoking, all-cause mortality risk was 19% greater for persons in the worst quartile of visual acuity than for those in the best (hazard ratio (HR) = 1.19, P = .008) and 39% greater for persons with the worst contrast sensitivity (HR = 1.39, P < .001) than for those with the best. Traumatic mortality risk was 2.4 times greater for women with the worst contrast sensitivity than for those with the best (HR = 2.44, P = .03)., Conclusion: Poorer visual acuity and contrast sensitivity are associated with greater risk of traumatic and all-cause mortality in older women, even after controlling for demographic and clinical characteristics. Although further research is necessary to determine how treating reversible causes of visual impairment or improving current refraction affects mortality in older women, clinical detection and follow-up of these visual impairments holds promise for identifying those who are at risk of mortality from other systemic conditions.

Objectives: To test the association between self-reported sleep and nap habits and risk of falls and fractures in a large cohort of older women., Design: Study of Osteoporotic Fractures prospective cohort study., Setting: Clinical centers in Baltimore, Maryland; Minneapolis, Minnesota; Portland, Oregon; and the Monongahela Valley, near Pittsburgh, Pennsylvania., Participants: Eight thousand one hundred one community-dwelling Caucasian women aged 69 and older (mean 77.0)., Measurements: Sleep and nap habits were assessed using a questionnaire at the fourth clinic visit (1993/94). Fall frequency during the subsequent year was ascertained using tri-annual questionnaire. Incident hip and nonspinal fractures during 6 years of follow-up were confirmed using radiographic reports., Results: Five hundred fifty-three women suffered hip fractures, and 1,938 suffered nonspinal fractures. In multivariate models, women who reported napping daily had significantly higher odds of suffering two or more falls during the subsequent year (odds ratio=1.32, 95% confidence interval (CI)=1.03-1.69) and were more likely to suffer a hip fracture (hazard ratio (HR)=1.33, 95% CI=0.99-1.78) than women who did not nap daily. Those sleeping at least 10 hours per 24 hours had a higher risk of nonspinal fracture than (HR=1.26, 95% CI=1.00-1.58) and a similar but nonsignificant increased risk of hip fracture to (HR=1.43, 95% CI=0.95-2.15) those who reported sleeping between 8 and 9 hours., Conclusion: Self-reported long sleep and daily napping are associated with greater risk of falls and fractures in older women. Interventions to improve sleep may reduce their risk of falls and fractures. Future research is needed to determine whether specific sleep disorders contribute to these relationships.

TNFalpha is a proinflammatory cytokine that promotes osteoclastic bone resorption. We evaluated the association between a G-308A polymorphism (rs1800629) at the TNFA locus and osteoporosis phenotypes in 4306 older women participating in the Study of Osteoporotic Fractures. Femoral neck bone mineral density (BMD) and structural geometry were measured using dual-energy x-ray absorptiometry and hip structural analysis. Incident fractures were confirmed by physician adjudication of radiology reports. Despite similar femoral neck BMD, women with the A/A genotype had greater subperiosteal width (P = 0.01) and endocortical diameter (P = 0.03) than those with the G/G genotype. The net result of these structural differences was that there was a greater distribution of bone mass away from the neutral axis of the femoral neck in women with the A/A genotype, resulting in greater indices of bone bending strength (cross-sectional moment of inertia: P = 0.004; section modulus: P = 0.003). Among 376 incident hip fractures during 12.1 yr of follow-up, a 22% decrease in the risk of hip fracture was seen per copy of the A allele (relative risk 0.78; 95% confidence interval 0.63, 0.96), which was not influenced by adjustments for potential confounding factors, BMD, or bone strength indices. The G-308A polymorphism was not associated with a reduced risk of other fractures. These results suggest a potential role of genetic variation in TNFalpha in the etiology of osteoporosis.

Purpose: To devise, validate, and test a software model that improves how clinicians calculate individual risk for osteoporotic fracture and expected treatment benefit., Methods: We developed a simple model of seven easily ascertained items plus bone mineral density (BMD) that calculates absolute fracture risk and expected absolute risk reduction after treatment. Baseline clinical variables and longitudinal fracture data from two large osteoporosis cohort studies validated the model's accuracy in predicting fracture risk. We then surveyed 298 clinicians to evaluate the likelihood they would prescribe alendronate in three hypothetical cases, first given the clinical data alone and then with model-derived data on fracture risk and expected treatment benefit., Results: We found a strong linear relationship with the model's predicted fracture risk and observed fracture rates in two large observational cohorts but the model overestimated risk 2-3 fold. The model predicted a 1:200 5-year risk for spinal fracture and a 1:40 risk for nonspinal fracture in an index case of a younger, thin, osteopenic woman. Given this hypothetical history with BMD t-scores, 26% of clinicians were likely to prescribe alendronate; when also given model-calculated 5-year fracture risks with or without treatment, only 13% were likely to prescribe alendronate (p < 0.001). For 2 other osteoporosis patients in whom risk was much higher, further information on fracture risk and expected treatment benefit did not alter prescribing., Conclusions: Reporting absolute fracture risk with and without treatment promises to be most useful in women with osteopenia, a common clinical dilemma in younger postmenopausal women.

Whether nulliparity increases fracture risk is unclear from prior studies, which are limited by small samples or lack of measured bone mineral density. No study has evaluated whether the effect of parity differs by skeletal site. We prospectively analyzed the relationship of parity to the risk of incident nontraumatic hip, spine, and wrist fractures in 9704 women aged 65 years or older participating in the Study of Osteoporotic Fractures to determine if parity reduces postmenopausal fracture risk, and if so, if this risk reduction is (1) greater at weight-bearing skeletal sites and (2) independent of bone mineral density. Parity was ascertained by self-report. Incident hip and wrist fractures were determined by physician adjudication of radiology reports (mean follow-up, 9.8 years) and spine fractures by morphometric criteria on serial radiographs. The relationship of parity to hip and wrist fracture was assessed by proportional hazards models. Spine fracture risk was evaluated by logistic regression. Compared with parous women, nulliparous women (n = 1835, 19%) had an increased risk of hip and spine, but not wrist, fractures. In multivariate models, parity remained a significant predictor only for hip fracture. Nulliparous women had a 44% increased risk of hip fractures independent of hip bone mineral density (hazards ratio, 1.44; 95% CI, 1.17-1.78). Among parous women, each additional birth reduced hip fracture risk by 9% (p = 0.03). Additionally, there were no differences in mean total hip, spine, or radial bone mineral density values between nulliparous and parous women after multivariate adjustment. In conclusion, childbearing reduces hip fracture risk by means that may be independent of hip bone mineral density.