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Current guidelines for the prevention of cardiovascular disease (CVD) recommend diabetes as a CVD risk equivalent. However, reports that have examined the risk of diabetes in comparison to pre-existing CVD are lacking among older women. We aimed to assess whether diabetes was associated with a similar risk of total and cause-specific mortality as a history of CVD in older women.We studied 9218 women aged 68 years or older enrolled in a prospective cohort study (Study of Osteoporotic Fracture) during a mean follow-up period of 11.7 years and compared all-cause, cardiovascular and coronary heart disease mortality among 4 groups: non-diabetic women with and without existing CVD, diabetic women with and without existing CVD. Mean (SD) age of the participants was 75.2 (5.3) years, 3.5% reported diabetes and 6.8% reported existing CVD. During follow-up, 5117 women died with 36% from CVD. The multivariate adjusted risk of cardiovascular mortality was increased among both non-diabetic women with CVD (hazard ratio (HR) 2.32, 95% CI: 1.97-2.74, P

ObjectivesTo determine the association between weight trajectory, health status, and mortality in older women.DesignCohort study.SettingStudy of Osteoporotic Fractures.ParticipantsOlder community-dwelling women (age: baseline (1986-88), mean 68, range 65-81; Year 20 (2006-08), mean 88, range 83-102 (N = 1,323)).MeasurementsBody weight measured repeatedly over 20 years (mean 8 times). Logistic and Cox proportional hazard models were used to evaluate whether 20-year weight trajectory measures were associated with hip fracture, falls, physical performance, and mortality.ResultsIn models adjusted for age, clinic, calcium use, Year 20 weight, walking speed, comorbidity score, smoking, self-reported health, and walking for exercise, women with moderate weight loss (>9.0 kg) over 20 years had a 74% greater risk of death (hazard ratio (HR) = 1.74, 95% confidence interval (CI) = 1.37-2.20) in the 5 years after the Year 20 visit than those with no weight loss and more than twice the risk of hip fracture (HR = 2.56, 95% CI = 1.39-4.70). They were 3.6 times (odds ratio (OR) = 3.60, 95% CI = 1.86-6.95) as likely to have poor physical function at the Year 20 visit as women with no weight loss but no greater risk of 2 or more falls in the 1.5 years after the Year 20 visit. Weight variability and abrupt weight decline were not associated with adverse health oucomes (falls, fractures, mortality), but those in the highest quartile of variability were 2.3 times (OR = 2.26, 95% CI = 1.34-3.80) as likely to have poor physical function scores.ConclusionIn women surviving past 80 years of age, moderate weight loss over 20 years was associated with greater risk of hip fracture, poor physical function, and mortality but not of falls. Future work should separate voluntary from involuntary weight loss.

Bone loss following a fracture could increase the risk of future fractures. In this study, we found that elderly women who had an upper body fracture or multiple fractures lost more bone at the hip than those who did not fracture. This suggests a possible systemic bone loss response initiated by fracture.IntroductionA prior fracture is one of the strongest predictors of subsequent fracture risk, but the etiology of this phenomenon remains unclear. Systemic bone loss post-fracture could contribute to increased risk of subsequent fractures. Therefore, in this study, we investigated whether incident fractures, including those distant to the hip, are associated with accelerated loss of hip bone mineral density (BMD) in elderly women.MethodsWe analyzed data from 3956 Caucasian women aged ≥ 65 years who were enrolled in the Study of Osteoporotic Fractures and completed hip BMD measurements at study visit 4 (year 6) and visit 6 (year 10). Clinical fractures between visits 4 and 6 were ascertained from triannual questionnaires and centrally adjudicated by review of community radiographic reports. Subjects provided questionnaire information and clinical variables at examinations for known and potential covariates. Generalized linear models were used to calculate average annual percent change in total hip BMD between visits 4 and 6 for each incident fracture type and for upper body and lower body fractures combined. A subset of women (n = 3783) was analyzed for annual total hip BMD change between study visits 4 and 5 and between study visits 5 and 6 to evaluate change in total hip BMD during these 2-year intervals.ResultsWomen with incident upper body fracture or incident lower body fracture exhibited reductions in total hip BMD of 0.89 and 0.77% per year, respectively, while women who did not fracture exhibited reductions in total hip BMD of 0.66% per year during the 4-year period. Accelerated loss of hip BMD was isolated to the 2-year time interval that included the fracture. Loss of total hip BMD was not affected by the number of days from fracture to follow up DXA.ConclusionsSystemic bone loss following fracture may increase the risk of future fractures at all skeletal sites. There is a need for improved understanding of mechanisms leading to apparent accelerated bone loss following a fracture in order to reduce subsequent fracture risk.

Previous studies examining the association of cognitive impairment and dementia with fracture outcomes in older adults have usually used standard approaches that did not take into account the competing risk of mortality. However, ignoring mortality may not provide accurate estimates of risk of fracture because dementia in older adults strongly predicts death, making mortality a competing risk. A total of 1491 women (mean age 87.6 years) participating in the prospective Study of Osteoporotic Fractures (SOF) Year 20 exam were cognitively assessed and followed to ascertain vital status (deaths verified by death certificates) and hip fractures (confirmed by radiographic reports). Cognitive status was categorized as normal, mild cognitive impairment (MCI), or dementia, based on a standardized evaluation. Absolute probability of hip fracture by category of cognitive function was estimated using traditional Kaplan-Meier method and cumulative incidence function accounting for competing mortality risk. Risk of hip fracture by cognitive function category was determined using conventional Cox proportional hazards regression and subdistribution hazards models with death as a competing risk. During an average follow-up of 5.6 years, 139 (9.3%) women experienced a hip fracture and 990 (66.4%) died before experiencing this outcome. Among women with dementia, the risk of hip fracture was 11.7% (95% confidence interval [CI] 7.3-17.2) at 5 years and 18.6% (95% CI 9.1-30.9) at 10 years using traditional survival analysis versus 7.9% (95% CI 5.1-11.6) at 5 years and 8.8% (95% CI 5.8-12.8) at 9.8 years using a competing risk approach. Results were similar for women with MCI. Women with MCI and dementia have a higher risk of hip fractures than women with normal cognition. However, not taking into account the competing risk of mortality significantly overestimates the risk of hip fracture in women in the ninth and tenth decades of life with cognitive impairment. © 2018 American Society for Bone and Mineral Research.

ObjectivesResearch is limited and findings conflict regarding anxiety as a predictor of future cognitive decline in the oldest old persons. We examined the relationship between levels of and changes in anxiety symptoms, and subsequent dementia and mild cognitive impairment (MCI) in the oldest old women.MethodWe conducted secondary analyses of data collected from 1425 community-dwelling women (mean age = 82.8, SD ±3.1 years) followed on average for five years. The Goldberg Anxiety Scale was used to assess anxiety symptoms at baseline, and an expert clinical panel adjudicated dementia and MCI at follow-up. Participants with probable cognitive impairment at baseline were excluded.ResultsAt baseline, 190 (13%) women had moderate/severe anxiety symptoms and 403 (28%) had mild anxiety symptoms. Compared with those with no anxiety symptoms at baseline, women with mild anxiety symptoms were more likely to develop dementia at follow-up (multivariable-adjusted odds ratio = 1.66, 95% confidence interval 1.12-2.45). No significant association was observed between anxiety symptoms and MCI.ConclusionIn the oldest old women, our findings suggest that mild anxiety symptoms may predict future risk of dementia, but not MCI. Future studies should explore potential biological mechanisms underlying associations of anxiety with cognitive impairment.

ObjectiveTo investigate cross-sectional and longitudinal associations of diffuse idiopathic skeletal hyperostosis (DISH) and thoracic kyphosis in older persons.MethodsDISH and kyphosis were assessed in 1,500 men from the Osteoporotic Fractures in Men (MrOS) study and in 1,267 women from the Study of Osteoporotic Fractures (SOF). DISH was assessed using baseline lateral spine radiographs, and Cobb angle of kyphosis was measured from baseline and followup radiographs, a mean 4.6 years later in men, and 3.7 and 15 years later in women. Linear regression was used to analyze associations of DISH with baseline Cobb angle and with percent annualized change in Cobb angle. We tested for heterogeneity among studies.ResultsDISH was identified in 222 participants in MrOS (15%) and in 156 participants in SOF (12%). Participants with DISH in both cohorts had higher baseline Cobb angles (P  0.05) for men or women. Women with DISH had less kyphosis progression over 15 years (0.25% less annualized change in Cobb) than those without DISH.ConclusionPrevalent DISH is associated with greater kyphosis in older men and women, and is not significantly associated with a change in kyphosis over 4-5 years. However, in women followed over 15 years, DISH was associated with less progression of kyphosis. These results suggest that DISH influences kyphosis and may slow progression over the long term. Additional studies of DISH/kyphosis associations are warranted to understand the functional implications of this finding.

Determine the associations of sleep disturbances with hospitalization risk among older women. One thousand eight hundred and twenty-seven women (mean age 83.6 years) participating in Study of Osteoporotic Fractures Year 16 (Y16) examination (2002-2004) linked with Medicare and/or HMO claims. At Y16 examination, sleep/wake parameters were measured by actigraphy (total sleep time [TST], sleep efficiency [SE], sleep latency [SL], and wake after sleep onset [WASO]) and subjective sleep measures (sleep quality [Pittsburgh Sleep Quality Index] and daytime sleepiness [Epworth Sleepiness Scale]) were assessed by questionnaire. Measures except TST were dichotomized based on clinical thresholds. Incident hospitalizations were determined from claims data. Nine hundred and seventy-six women (53%) had ≥1 hospitalization in the 3 years after the Year 16 examination. Reduced SE (odds ratio [OR] = 2.39, 95% confidence interval [CI] 1.69-3.39), prolonged SL (OR = 1.41, 95% CI 1.11-1.78), greater WASO (OR = 1.57, 95% CI 1.28-1.93), shorter TST (OR = 1.98, 95% CI 1.42-2.77) and poorer sleep quality (OR = 1.33, 95% CI 1.07-1.65) were each associated with a higher age and site-adjusted odds of hospitalization; associations were attenuated after multivariable adjustment for traditional prognostic factors with the OR for reduced SE (OR = 1.60, 95% CI 1.08-2.38) and shorter TST (OR = 1.63, 95% CI 1.12-2.37) remaining significant. Among women who were hospitalized, greater WASO (rate ratio [RR] = 1.20, 95% CI 1.04-1.37) and poorer sleep quality (RR = 1.18, 95% CI 1.02-1.35) were each associated with a greater age and site-adjusted RR of inpatient days, but associations did not persist after multivariate adjustment. Older women with sleep disturbances have an increased risk of hospitalization partially attributable to demographics, poorer health status, and comorbidities.

ObjectivesThe association between weight change and cognition is controversial. We examined the association between 20-year weight change and cognitive function in late life.DesignCohort study.SettingStudy of Osteoporotic Fractures (SOF).ParticipantsOne thousand two hundred eighty-nine older, community-dwelling women (mean baseline age 68 (65-81) and 88 (82-102) at cognitive testing).MeasurementsStudy of Osteoporotic Fractures participants had body weight measured repeatedly over 20 years (mean 8 weights). Adjudicated cognitive status was classified as normal (n = 775) or mild cognitive impairment (MCI)/dementia (n = 514) at Year 20. Logistic models were used to evaluate whether absolute weight change, rate of weight loss per year, presence of abrupt, unrecovered weight loss, and weight variability were associated with MCI or dementia.ResultsWomen with greater rate of weight loss over 20 years had increased chance of developing MCI or dementia. In age/education/clinic-adjusted "base" models, each 0.5 kg/yr decrease resulted in 30% increased odds of MCI/dementia (OR = 1.30 [95% CI: 1.14, 1.49]). After adjustment for age, education, clinic, depression, and walking speed, there was 17% (OR = 1.17 [95% CI: 1.02, 1.35]) increased odds of MCI/dementia for each 0.5 kg/yr decrease in weight. In base models, variability in weight was significant. Each 1% average deviation from each woman's predicted weight curve was associated with 11% increased odds of MCI/dementia (OR = 1.11 [95% CI: 1.04, 1.18]). The estimate was attenuated after full adjustment (OR = 1.06 [95% CI: 0.99, 1.14]). The presence of an abrupt weight decline was not associated with MCI/dementia.ConclusionsRate of weight loss over 20 years was associated with development of MCI or dementia in women surviving past 80 years, suggesting that nutritional status, social-environmental factors, and/or adipose tissue function and structure may affect cognitive function with aging.

BackgroundThis study examines effects of mobility and cognition on hospitalization and inpatient days among women late in life.MethodsProspective study of 663 women (mean age 87.7 years) participating in the Study of Osteoporotic Fractures Year 20 examination (2006-2008) linked with their inpatient claims data. At Year 20, mobility ascertained by Short Physical Performance Battery categorized as poor, intermediate, or good. Cognitive status adjudicated based on neuropsychological tests and classified as normal, mild cognitive impairment, or dementia. Hospitalizations (n = 182) during 12 months following Year 20.ResultsReduced mobility and poorer cognition were each associated in a graded manner with higher inpatient health care utilization, even after accounting for each other and traditional prognostic indicators. For example, adjusted mean inpatient days per year were 0.94 (95% confidence interval [CI] 0.52-1.45) among women with good mobility increasing to 2.80 (95% CI 1.64-3.89) among women with poor mobility and 1.59 (95% CI 1.08-2.03) among women with normal cognition increasing to 2.53 (95% CI 1.55-3.40) among women with dementia. Women with poor mobility/dementia had a nearly sixfold increase in mean inpatient days per year (4.83, 95% CI 2.73-8.54) compared with women with good mobility/normal cognition (0.84, 95% CI 0.49-1.44).ConclusionsAmong women late in life, mobility limitations and cognitive deficits were each independent predictors of higher inpatient health care utilization even after considering each other and conventional predictors. Additive effects of reduced mobility and poorer cognition may be important to consider in medical decision making and health care policy planning for the growing population of adults aged ≥85 years.

BackgroundThis study examines the effects of mobility and cognition on mortality risk in women late in life.MethodsA prospective study was conducted among 1,495 women (mean age 87.6 years) participating in the Study of Osteoporotic Fractures Year 20 examination (2006-2008). Mobility (ascertained by Short Physical Performance Battery [SPPB]) was categorized as poor (SPPB 0-3, n = 312), intermediate (SPPB 4-9, n = 799), or good (SPPB 10-12, n = 384). Cognitive status (adjudicated based on neuropsychological tests) was classified as normal (n = 873), mild cognitive impairment (n = 354), or dementia (n = 268). Deaths (n = 749) were identified from Year 20 through July 31, 2014 (average follow-up 4.9 years).ResultsThere was not strong evidence of an interaction between mobility and cognition for prediction of mortality risk (p interaction term .16). Compared to women with good mobility, mortality risks were increased among women with intermediate mobility (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.02-1.57) and those with poor mobility (HR 1.64, 95% CI 1.24-2.16) after consideration of cognition and other mortality risk factors. Similarly, mortality risks were higher among women with mild cognitive impairment (HR 1.46, 95% CI 1.21-1.76) and those with dementia (HR 1.88, 95% CI 1.54-2.31) compared to women with normal cognition after consideration of mobility and other mortality risk factors.ConclusionsAmong women late in life, 5-year mortality risk was substantially increased among women with deficits in mobility even after accounting for cognition and traditional prognostic indicators. Similarly, deficits in cognition were associated with increased 5-year mortality despite consideration of mobility and conventional risk factors.

To examine the degree of trauma in major osteoporotic fractures (MOF) in men versus women, we used data from 15,698 adults aged ≥65 years enrolled in the Osteoporotic Fractures in Men (MrOS) study (5994 men) and the Study of Osteoporotic Fractures (SOF) (9704 women). Participants were contacted tri-annually to ascertain incident fractures, which were confirmed by radiographic reports and coded according to degree of self-reported trauma. Trauma was classified as low (fall from ≤ standing height; fall on stairs, steps, or curb; minimal trauma other than fall [coughing, turning over]); moderate (collisions with objects during normal activity without associated fall); or high (fall from > standing height; severe trauma [motor vehicle accident, assault]). MOF included hip, clinical vertebral, wrist, and humerus fractures. Mean fracture follow-up was 9.1 years in SOF and 8.7 years in MrOS. A total of 14.6% of the MOF in men versus 6.3% of the MOF in women were classified as high trauma (p < 0.001); men versus women more often experienced fractures resulting from severe trauma as well as from fall > standing height. High-trauma fractures were more significantly common in men versus women at the hip (p = 0.002) and wrist (p < 0.001) but not at the spine or humerus. Among participants with MOF, the odds ratio of a fracture related to high-trauma fracture among men versus women was 3.12 (95% confidence interval [CI] 1.70-5.71) after adjustment for traditional risk factors. Findings were similar in analyses limited to participants with hip fractures (odds ratio [OR] = 3.34, 95% CI 1.04-10.67) and those with wrist fracture (OR = 5.68, 95% CI 2.03-15.85). Among community-dwelling older adults, MOF are more likely to be related to high trauma in men than in women. These findings are not explained by sex differences in conventional risk factors and may reflect a greater propensity among men to engage in risky behavior. © 2015 American Society for Bone and Mineral Research.

Data concerning the link between severity of abdominal aortic calcification (AAC) and fracture risk in postmenopausal women are discordant. This association may vary by skeletal site and duration of follow-up. Our aim was to assess the association between the AAC severity and fracture risk in older women over the short- and long term. This is a case-cohort study nested in a large multicenter prospective cohort study. The association between AAC and fracture was assessed using Odds Ratios (OR) and 95% confidence intervals (95%CI) for vertebral fractures and using Hazard Risks (HR) and 95%CI for non-vertebral and hip fractures. AAC severity was evaluated from lateral spine radiographs using Kauppila's semiquantitative score. Severe AAC (AAC score 5+) was associated with higher risk of vertebral fracture during 4 years of follow-up, after adjustment for confounders (age, BMI, walking, smoking, hip bone mineral density, prevalent vertebral fracture, systolic blood pressure, hormone replacement therapy) (OR=2.31, 95%CI: 1.24-4.30, p

BackgroundDepressive symptoms are common in older adults and associated with poor outcomes. Although circadian genes have been implicated in depression, the relationship between circadian genes and depressive symptoms in older adults is unclear.MethodsA cross-sectional genetic association study of 529 single nucleotide polymorphisms (SNPs) representing 30 candidate circadian genes was performed in two population-based cohorts: the Osteoporotic Fractures in Men Study (MrOS; N=270, age: 76.58±5.61 years) and the Study of Osteoporotic Fractures (SOF) in women (N=1740, 84.05±3.53 years) and a meta-analysis was performed. Depressive symptoms were assessed with the Geriatric Depression Scale categorizing participants as having none-few symptoms (0-2), some depressive symptoms (>2 to

ObjectiveTo determine the risk of all-cause and disease-specific mortality among older women with hip osteoarthritis (OA) and to identify mediators in the causal pathway.MethodsData were from the Study of Osteoporotic Fractures, a US population-based cohort study of 9,704 white women age ≥65 years. The analytic sample included women with hip radiographs at baseline (n = 7,889) and year 8 (n = 5,749). Mortality was confirmed through October 2013 by death certificates and hospital discharge summaries. Radiographic hip OA (RHOA) was defined as a Croft grade of ≥2 in at least 1 hip (definite joint space narrowing or osteophytes plus 1 other radiographic feature).ResultsThe mean ± SD followup time was 16.1 ± 6.2 years. The baseline and year 8 prevalence of RHOA were 8.0% and 11.0%, respectively. The cumulative incidence (proportion of deaths during the study period) was 67.7% for all-cause mortality, 26.3% for cardiovascular disease (CVD) mortality, 11.7% for cancer mortality, 1.9% for gastrointestinal disease mortality, and 27.8% for all other mortality causes. RHOA was associated with an increased risk of all-cause mortality (hazard ratio 1.14 [95% confidence interval 1.05-1.24]) and CVD mortality (hazard ratio 1.24 [95% confidence interval 1.09-1.41]) adjusted for age, body mass index, education, smoking, health status, diabetes, and stroke. These associations were partially explained by the mediating variable of physical function.ConclusionRHOA was associated with an increased risk of all-cause and CVD mortality among older white women followed up for 16 years. Dissemination of evidence-based physical activity and self-management interventions for hip OA in community and clinical settings can improve physical function and might also contribute to lower mortality.

ObjectivesTo examine the association between age-related macular degeneration (AMD) and all-cause and cause-specific mortality in a population of older women.DesignProspective cohort study.SettingFour U.S. clinical centers.ParticipantsA random sample of 1,202 women with graded fundus photographs at the Year 10 visit of the Study of Osteoporotic Fractures (mean age 79.5).MeasurementsForty-five-degree stereoscopic fundus photographs were graded for presence and severity (early vs late) of AMD. Vital status was adjudicated from death certificates. Cox proportional hazards models, adjusted for appropriate confounders, were used to estimate mortality hazards ratios.ResultsPrevalence of any AMD was 40.5% at baseline, with 441 (36.7%) having early AMD and 46 (3.8%) having late AMD. Cumulative mortality was 51.6% over 15 years of follow-up. Overall, there was no significant association between AMD presence or severity and all-cause or cause-specific mortality. Because there was a significant interaction between AMD and age in predicting mortality (P

Multiple lines of evidence support an immunologic basis and genetic disposition for the development of age-related macular degeneration (AMD). Comprehensive human leukocyte antigens (HLA) class II typing at four loci (DRB1, DQA1, DQB1, and DPB1) was assessed using next generation sequencing methods and tested for association with age-related macular degeneration (AMD) in a case-control study of 456 AMD cases and 499 controls from the population-based Study of Osteoporotic Fractures (SOF) cohort. No statistically significant associations were identified for any of the class II loci and a previously identified association between DRB1*13:01 was not replicated in this dataset. These results reported here suggest that common HLA class II genetic variation does not contribute to AMD disease risk.

BackgroundReduced sleep duration has been increasingly reported to predict obesity. However, timing and regularity of sleep may also be important. In this study, the cross-sectional association between objectively measured sleep patterns and obesity was assessed in two large cohorts of older individuals.MethodsWrist actigraphy was performed in 3053 men (mean age: 76.4 years) participating in the Osteoporotic Fractures in Men Study and 2985 women (mean age: 83.5 years) participating in the Study of Osteoporotic Fractures. Timing and regularity of sleep patterns were assessed across nights, as well as daytime napping.ResultsGreater night-to-night variability in sleep duration and daytime napping were associated with obesity independent of mean nocturnal sleep duration in both men and women. Each 1 h increase in the standard deviation of nocturnal sleep duration increased the odds of obesity 1.63-fold (95% confidence interval: 1.31-2.02) among men and 1.22-fold (95% confidence interval: 1.01-1.47) among women. Each 1 h increase in napping increased the odds of obesity 1.23-fold (95% confidence interval: 1.12-1.37) in men and 1.29-fold (95% confidence interval: 1.17-1.41) in women. In contrast, associations between later sleep timing and night-to-night variability in sleep timing with obesity were less consistent.ConclusionsIn both older men and women, variability in nightly sleep duration and daytime napping were associated with obesity, independent of mean sleep duration. These findings suggest that characteristics of sleep beyond mean sleep duration may have a role in weight homeostasis, highlighting the complex relationship between sleep and metabolism.

It is unknown how well prediction models incorporating multiple risk factors identify women with radiographic prevalent vertebral fracture (PVFx) compared with simpler models and what their value might be in clinical practice to select older women for lateral spine imaging. We compared 4 regression models for predicting PVFx in women aged 68 y and older enrolled in the Study of Osteoporotic Fractures with a femoral neck T-score ≤ -1.0, using area under receiving operator characteristic curves (AUROC) and a net reclassification index. The AUROC for a model with age, femoral neck bone mineral density, historical height loss (HHL), prior nonspine fracture, body mass index, back pain, and grip strength was only minimally better than that of a more parsimonious model with age, femoral neck bone mineral density, and historical height loss (AUROC 0.689 vs 0.679, p values for difference in 5 bootstrapped samples

ObjectivesAging is associated with changes in circadian rhythms. Current evidence supports a role for circadian rhythms in the pathophysiology of depression. However, little is known about the relationship between depressive symptoms and circadian activity rhythms in older adults. We examined this association in community-dwelling older women.MethodsWe performed a cross-sectional analysis of 3,020 women (mean age: 83.55 ± 3.79 years) enrolled in the Study of Osteoporotic Fractures. Depressive symptoms were assessed with the Geriatric Depression Scale categorizing participants as "normal" (0-2; referent group, N = 1,961), "some depressive symptoms" (3-5, N = 704), or "depressed" (≥6, N = 355). Circadian activity rhythm variables were measured using wrist actigraphy.ResultsIn age-adjusted and Study of Osteoporotic Fractures site-adjusted models, greater levels of depressive symptoms were associated with decreased amplitude (height; df = 3,014, t = -11.31, p for linear trend

ObjectivesTo determine whether older women with diabetes mellitus have a greater longitudinal decline in physical performance than those without and whether any decline differs according to insulin sensitizer use.DesignProspective cohort study.SettingBaltimore, Maryland; Minneapolis, Minnesota; Portland, Oregon; and the Monongahela, Pennsylvania.ParticipantsCommunity-dwelling women (mean age 78.5 ± 3.6) enrolled in the Study of Osteoporotic Fractures in 1997-98 and restudied 4.9 ± 0.6 years later (N = 2,864).MeasurementsWomen were categorized as having no diabetes mellitus (n = 2,680) or having diabetes mellitus (n = 184). A prescription medication inventory was used to determine use of insulin sensitizers (metformin and thiazolidinedione). The outcomes were longitudinal changes in physical performance measures, including grip strength, usual walk speed, and rapid walk speed.ResultsEstimates from fully adjusted models showed that women with diabetes mellitus had greater declines in usual walk speed (-0.16 m/s, 95% confidence interval (CI) = -0.19 to -0.14) and rapid walk speed (-0.21 m/s, 95% CI = -0.24 to -0.17) than those without (usual walk speed -0.11 m/s, 95% CI = -0.12 to -0.11, P < .001; rapid walk speed -0.15 m/s, 95% CI = -0.16 to -0.14; P = .005). Women with diabetes mellitus taking insulin sensitizers had less decline in usual walk speed than those not taking insulin sensitizers (P < .001). Declines in grip strength did not differ significantly by diabetes mellitus status or insulin sensitizer use.ConclusionOlder women with diabetes mellitus have a greater decline in walk speed, but not grip strength, than older women without diabetes mellitus. Clinical studies in older adults to determine whether diabetes mellitus treatments such as insulin sensitizers can prevent loss in walk speed and mobility are needed.

Recent studies indicate that obesity is not protective against fracture in postmenopausal women and increases the risk of fracture at some sites. Risk factors for fracture in obese women may differ from those in the nonobese. We aimed to compare the ability of FRAX with and without bone mineral density (BMD) to predict fractures in obese and nonobese older postmenopausal women who were participants in the Study of Osteoporotic Fractures. Data for FRAX clinical risk factors and femoral neck BMD were available in 6049 women, of whom 18.5% were obese. Hip fractures, major osteoporotic fractures, and any clinical fractures were ascertained during a mean follow-up period of 9.03 years. Receiving operator curve (ROC) analysis, model calibration, and decision curve analysis were used to compare fracture prediction in obese and nonobese women. ROC analysis revealed no significant differences between obese and nonobese women in fracture prediction by FRAX, with or without BMD. Predicted hip fracture risk was lower than observed risk in both groups of women, particularly when FRAX + BMD was used, but there was good calibration for FRAX + BMD in prediction of major osteoporotic fracture in both groups. Decision curve analysis demonstrated that both FRAX models were useful for hip fracture prediction in obese and nonobese women for threshold 10-year fracture probabilities in the range of 4% to 10%, although in obese women FRAX + BMD was superior to FRAX alone. For major osteoporotic fracture, both FRAX models were useful in both groups of women for threshold probabilities in the range of 10% to 30%. For all clinical fractures, the FRAX models were not useful at threshold probabilities below 30%. We conclude that FRAX is of value in predicting hip and major osteoporotic fractures in obese postmenopausal women, particularly when used with BMD.

BackgroundResults of prospective studies examining the association between 25 hydroxyvitamin D (25[OH]D) levels and cognitive decline have been inconsistent. We tested the hypothesis that lower 25(OH)D levels are associated with a greater likelihood of cognitive impairment and risk of cognitive decline.MethodsThe study is a cross-sectional and longitudinal analysis of a prospective cohort of 6,257 community-dwelling elderly women followed for 4 years. Global cognitive function was measured by the Modified Mini-Mental State Examination and executive function was measured by Trail Making Test Part B (Trails B). Cognitive impairment at baseline was defined as a score >1.5 SD below the sample mean; cognitive decline was defined as decline from baseline to follow-up >1 SD from mean change in score.ResultsWomen with very low vitamin D levels had an increased odds of global cognitive impairment at baseline: odds ratio (95% confidence interval), 1.60 (1.05-2.42) for women with 25(OH)D

PurposeTo estimate the incidence of age-related macular degeneration (AMD) and the association of smoking and alcohol in a population of older women.DesignProspective cohort study.MethodsSubjects were women who attended the Study of Osteoporotic Fractures year-10 and year-15 follow-up clinic visits and had fundus photographs taken at both visits (n = 1958; 245 Black and 1713 White subjects; mean age at year 10 visit, 78.2 years). Forty-five degree stereoscopic fundus photographs were graded for AMD. Logistic regression was used to test whether risk factors were associated with incident AMD.ResultsThe overall 5-year AMD incidence was 24.1% (95% confidence interval [CI], 21.7 to 26.6) for early and 5.7% (95% CI, 4.6 to 6.8) for late. Early AMD incidence in White subjects ranged from 21.9% in those aged 74 to 79 years to 33.2% in those 80 to 84 years, but was observed at the slightly lower rate of 29.0% in subjects > or =85 years (trend P < .0001). After confounder adjustment, alcohol consumption was significantly associated with an elevated risk of incident early AMD (odds ratio [OR], 1.57; 95% CI, 1.18 to 2.11). There was an increased risk of early AMD among subjects aged 80 years or older who were smoking compared to those younger than 80 years who were not smoking (OR, 5.49; 95% CI, 1.57 to 19.20; P for interaction = .026).ConclusionsThe magnitude of the greater-than-additive effect of smoking on the age-adjusted risk of AMD reinforces recommendations to quit smoking even for older individuals.

SummaryMany falls occur among older adults with no traditional risk factors. We examined potential independent effects of lifestyle on fall risk. Not smoking and going outdoors frequently or infrequently were independently associated with more falls, indicating lifestyle-related behavioral and environmental risk factors are important causes of falls in older women.IntroductionPhysical and lifestyle risk factors for falls and population attributable risks (PAR) were examined.MethodsWe conducted a 4-year prospective study of 8,378 community-dwelling women (mean age = 71 years, SD = 3) enrolled in the Study of Osteoporotic Fractures. Data on number of falls were self-reported every 4 months. Fall rates were calculated (# falls/woman-years). Poisson regression was used to estimate relative risks (RR).ResultsPhysical risk factors (p < or = 0.05 for all) included tall height (RR = 0.89 per 5 in.), dizziness (RR = 1.16), fear of falling (RR = 1.20), self-reported health decline (RR = 1.19), difficulty with Instrumental Activities of Daily Living (IADLs) (RR = 1.12, per item), fast usual-paced walking speed (RR = 1.18, per 2 SD), and use of antidepressants (RR = 1.20), benzodiazepines (RR = 1.11), or anticonvulsants (RR = 1.62). Protective physical factors (p < or = 0.05 for all) included good visual acuity (RR = 0.87, per 2 SD) and good balance (RR = 0.85 vs. poor). Lifestyle predicted fewer falls including current smoking (RR = 0.76), going outdoors at least twice weekly but not more than once a day (RR = 0.89 and vs. twice daily). High physical activity was associated with more falls but only among IADL impaired women. Five potentially modifiable physical risk factors had PAR > or = 5%.ConclusionsFall interventions addressing modifiable physical risk factors with PAR > or = 5% while considering environmental/behavioral risk factors are indicated.

ObjectivesTo evaluate the associations between visual field loss and nonspine fractures.DesignProspective cohort study.SettingCommunity.ParticipantsFour thousand seven hundred seventy-three community-dwelling white and African-American women aged 65 and older with no previous history of hip fracture at the time of recruitment.MeasurementsRadiographically confirmed hip and nonspine, nonhip fractures identified from September 1997 to April 2008. Visual field loss was measured using a Humphrey Field Analyzer suprathreshold screening test of the peripheral and central vision of each eye and was classified into an ordinal rating of no, mild, moderate, or severe binocular visual field (BVF) loss.ResultsFor hip and nonspine, nonhip fractures and in unadjusted and covariate-adjusted analyses, the highest incidence of fractures was seen in women with the most-severe BVF loss. In covariate-adjusted analysis, women with mild, moderate, and severe BVF loss had a 49% (hazard ratio (HR)=1.49, 95% confidence interval (CI)=1.18-1.88), 25% (HR=1.25, 95% CI=0.87-1.80), and 66% (HR=1.66, 95% CI=1.19-2.32) greater risk, respectively, for hip fractures than women without BVF loss. Similarly, women with mild visual field loss had a 12% (HR=0.88, 95% CI=0.75-1.04) lower risk for nonspine, nonhip fractures, whereas women with moderate and severe visual field loss had a 18% (HR=1.18, 95% CI=0.92-1.52) and 59% (HR=1.59, 95% CI=1.24-2.03) greater risk of nonspine, nonhip fractures than women without BVF loss.ConclusionBVF loss is independently associated with hip and nonspine, nonhip fractures in older female volunteers.

PurposeTo explore the association between the consumption of fruits and vegetables and the presence of glaucoma.DesignCross-sectional cohort study.MethodsIn a sample of 1,155 women located in multiple centers in the United States, glaucoma specialists diagnosed glaucoma in at least one eye by assessing optic nerve head photographs and 76-point suprathreshold screening visual fields. Consumption of fruits and vegetables was assessed using the Block Food Frequency Questionnaire. The relationship between selected fruit and vegetable consumption and glaucoma was investigated using adjusted logistic regression models.ResultsAmong 1,155 women, 95 (8.2%) were diagnosed with glaucoma. In adjusted analysis, the odds of glaucoma risk were decreased by 69% (odds ratio [OR], 0.31; 95% confidence interval [CI], 0.11 to 0.91) in women who consumed at least one serving per month of green collards and kale compared with those who consumed fewer than one serving per month, by 64% (OR, 0.36; 95% CI, 0.17 to 0.77) in women who consumed more than two servings per week of carrots compared with those who consumed fewer than one serving per week, and by 47% (OR, 0.53; 95% CI, 0.29 to 0.97) in women who consumed at least one serving per week of canned or dried peaches compared with those who consumed fewer than one serving per month.ConclusionsA higher intake of certain fruits and vegetables may be associated with a decreased risk of glaucoma. More studies are needed to investigate this relationship.

ObjectivesTo determine whether bone mineral density (BMD) is associated with age-related maculopathy (ARM) risk in older women.DesignCross-sectional analysis at Year 10 (1997/98) of the Study of Osteoporotic Fractures (SOF).SettingFour clinical centers in the United States.ParticipantsOne thousand forty-two randomly sampled SOF participants who attended the Year 10 clinic visit.MeasurementsARM status was determined from fundus photographs using a modification of the Wisconsin Age-Related Maculopathy Grading System 6-level severity scale used in the National Health and Nutrition Examination Survey III. Total hip BMD was measured at Year 10 using dual-energy x-ray absorptiometry. Information on potential confounders, including age, reproductive hormone exposures, body mass index, smoking, alcohol consumption, nutrition, education, diabetes mellitus, hypertension, and physical activity, was ascertained with questionnaires.ResultsThe prevalence of ARM was 50% (46% had early ARM and 4% had late ARM). After potential confounder adjustment, greater BMD was associated with lower odds of ARM (odds ratio (OR) per 1 standard deviation increase in BMD=0.82, 95% confidence interval (CI)=0.70-0.96). Women in the highest quartile of BMD had lower odds of ARM than those in the lowest quartile (OR=0.63, 95% CI=0.41-0.97) and those in the lowest three quartiles combined (OR=0.66, 95% CI=0.48-0.91).ConclusionHigher levels of BMD may be associated with lower risk for ARM. The underlying mechanism is unknown, although BMD may be a marker for lifetime endogenous estrogen exposure. Future studies are needed to replicate these findings and further investigate the nature of the relationship between BMD and ARM.

ObjectivesTo determine whether poorer visual acuity and contrast sensitivity are independent risk factors for all-cause and traumatic mortality in older women.DesignTwelve-year prospective cohort study (1986-2003).SettingFour U.S. clinical centers.ParticipantsNine thousand seven hundred four postmenopausal white women aged 65 and older.MeasurementsHabitually 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.ResultsDuring 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).ConclusionPoorer 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.

ObjectivesTo determine the association between vision and hearing impairment and subsequent cognitive and functional decline in community-residing older women.DesignProspective cohort study.SettingFour metropolitan areas of the United States.ParticipantsA total of 6,112 women aged 69 and older participating in the Study of Osteoporotic Fractures (SOF) between 1992 and 1994.MeasurementsFive thousand three hundred forty-five participants had hearing measured, 1,668 had visual acuity measured, and 1,636 had both measured. Visual impairment was defined as corrected vision worse than 20/40. Hearing impairment was defined as the inability to hear a tone of 40 dB or greater at 2,000 hertz. Participants completed the modified Mini-Mental State Examination and/or a functional status assessment at baseline and follow-up. Cognitive and functional decline were defined as the amount of decline from baseline to follow-up that exceeded the observed average change in scores by at least 1 standard deviation.ResultsAbout one-sixth (15.7%) of the sample had cognitive decline; 10.1% had functional decline. In multivariate models adjusted for sociodemographic characteristics and chronic conditions, vision impairment at baseline was associated with cognitive (odds ratio (OR)=1.78, 95% confidence interval (CI)=1.21-2.61) and functional (OR=1.79, 95% CI=1.15-2.79) decline. Hearing impairment was not associated with cognitive or functional decline. Combined impairment was associated with the greatest odds for cognitive (OR=2.19, 95% CI=1.26-3.81) and functional (OR=1.87, 95% CI=1.01-3.47) decline.ConclusionSensory impairment is associated with cognitive and functional decline in older women. Studies are needed to determine whether treatment of vision and hearing impairment can decrease the risk for cognitive and functional decline.

BackgroundUse of central nervous system (CNS) active medications may increase the risk for fractures. Prior studies are limited by incomplete control of confounders.MethodsTo determine whether use of CNS active medications, including benzodiazepines, antidepressants, anticonvulsants, and narcotics, increases fracture risk in elderly, community-dwelling women, we examined use of these 4 categories of medications in a cohort of 8127 older women and followed the participants prospectively for incident nonspine fractures, including hip fractures. Current use of CNS active medications was assessed by interview with verification of use from containers between 1992 and 1994 and between 1995 and 1996. Use was coded as a time-dependent variable. Incident nonspine fractures occurring after the initial medication assessment until May 31, 1999, were confirmed by radiographic reports.ResultsDuring an average follow-up of 4.8 years, 1256 women (15%) experienced at least one nonspine fracture, including 288 (4%) with first hip fractures. Compared with nonusers, women taking narcotics (multivariate hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.06-1.83) and those taking antidepressants (multivariate HR, 1.25; 95% CI, 0.99-1.58) had increases in the risks for any nonspine fractures. Women taking tricyclic antidepressants and those using selective serotonin reuptake inhibitors (SSRIs) had similar fracture rates. There were no independent associations between benzodiazepine use or anticonvulsant use and risk for nonspine fracture. Women taking antidepressants compared with nonusers had a 1.7-fold increase in the risk for hip fracture (multivariate HR, 1.65; 95% CI, 1.05-2.57). We did not observe independent associations between use of any of the other 3 classes of CNS active medications and risk of hip fracture.ConclusionsCommunity-dwelling older women taking narcotics have an increased risk for any nonspine fracture, and those taking antidepressants have a greater risk for nonspine fractures, including hip fracture. Rates of fracture were similar in women taking tricyclic antidepressants and those using SSRIs. Benzodiazepine use and anticonvulsant use were not independently associated with an increased risk of nonspine fractures, including hip fracture.

ObjectivesTo determine whether current use of central nervous system (CNS)-active medications, including benzodiazepines, antidepressants, anticonvulsants, and narcotics, increases the risk for subsequent falls.DesignProspective cohort study.SettingFour clinical centers in Baltimore, Maryland; Portland, Oregon; Minneapolis, Minnesota; and the Monongahela Valley, Pennsylvania.ParticipantsEight thousand one hundred twenty-seven women aged 65 and older participating in the fourth examination of the Study of Osteoporotic Fractures between 1992 and 1994.MeasurementsCurrent use of CNS-active medications was assessed with an interviewer-administered questionnaire with verification of use from medication containers. A computerized dictionary was used to categorize type of medication from product brand and generic names. Incident falls were reported every 4 months for 1 year after the fourth examination.ResultsDuring an average follow-up of 12 months, 2,241 women (28%) reported falling at least once, including 917 women (11%) who experienced two or more (frequent) falls. Compared with nonusers, women using benzodiazepines (multivariate odds ratio (MOR) = 1.51, 95% confidence interval (CI) = 1.14-2.01), those taking antidepressants (MOR = 1.54, 95% CI = 1.14-2.07), and those using anticonvulsants (MOR = 2.56, 95% CI = 1.49-4.41) were at increased risk of experiencing frequent falls during the subsequent year. We found no evidence of an independent association between narcotic use and falls (MOR = 0.99 for frequent falling, 95% CI = 0.68-1.43). Among benzodiazepine users, both women using short-acting benzodiazepines (MOR = 1.42, 95% CI = 0.98-2.04) and those using long-acting benzodiazepines (MOR = 1.56, 95% CI = 1.00-2.43) appeared to be at greater risk of frequent falls than nonusers, although the CIs overlapped 1.0. We found no evidence to suggest that women using selective serotonin-reuptake inhibitors (MOR = 3.45, 95% CI = 1.89-6.30) had a lower risk of frequent falls than those using tricyclic antidepressants (MOR 1.28, 95% CI = 0.90-1.84).ConclusionsCommunity-dwelling older women taking CNS-active medications, including those taking benzodiazepines, antidepressants, and anticonvulsants, are at increased risk of frequent falls. Minimizing use of these CNS-active medications may decrease risk of future falls. Our results suggest that fall risk in women taking benzodiazepines is at best marginally decreased by use of short-acting preparations. Similarly, our findings indicate that preferential use of selective serotonin-reuptake inhibitors is unlikely to reduce fall risk in older women taking antidepressants.

ObjectiveTo examine the relationship between diabetes and the incidence of functional disability and to determine the predictors of functional disability among older women with diabetes.Research design and methodsWe analyzed data from 8,344 women enrolled in the Study of Osteoporotic Fractures, a prospective cohort of women aged > or =65 years. Diabetes (n = 527, 6.3% prevalence) and comorbidities (coronary heart disease, stroke, arthritis, depression, and visual impairment) were assessed by questionnaire and physical examination. Incident disability, defined as onset of inability to do one or more major functional tasks (walking 0.25 mile, climbing 10 steps, performing household chores, shopping, and cooking meals), was assessed by questionnaire over 12 years.ResultsThe yearly incidence of any functional disability was 9.8% among women with diabetes and 4.8% among women without diabetes. The age-adjusted hazard rate ratio (HRR) of disability for specific tasks associated with diabetes ranged from 2.12 (1.82-2.48) for doing housework to 2.50 (2.05-3.04) for walking two to three blocks. After adjustment for potential confounders at baseline (BMI, physical activity, estrogen use, baseline functional status, visual impairment, and marital status) and comorbidities (heart disease, stroke, depression, and arthritis), diabetes remained associated with a 42% increased risk of any incident disability and a 53-98% increased risk of disability for specific tasks. Among women with diabetes, older age, higher BMI, coronary heart disease, arthritis, physical inactivity, and severe visual impairment at baseline were each independently associated with disability.ConclusionsDiabetes is associated with an increased incidence of functional disability, which is likely to further erode health status and quality of life.