Participants In Study Of Osteoporotic Fractures Research Articles

Assessing the Role of Selection Bias in the Protective Relationship Between Caregiving and Mortality.

Caregivers have lower mortality rates than noncaregivers in population-based studies, which contradicts the caregiver-stress model and raises speculation about selection bias influencing these findings. We examined possible selection bias due to 1) sampling decisions and 2) selective participation among women (baseline mean age = 79 years) in the Caregiver-Study of Osteoporotic Fractures (Caregiver-SOF) (1999-2009), an ancillary study to the Study of Osteoporotic Fractures (SOF). Caregiver-SOF includes 1,069 SOF participants (35% caregivers) from 4 US geographical areas (Baltimore, Maryland; Minneapolis, Minnesota; the Monongahela Valley, Pennsylvania; and Portland, Oregon). Participants were identified by screening all SOF participants for caregiver status (1997-1999; n = 4,036; 23% caregivers) and rescreening a subset of caregivers and noncaregivers matched on sociodemographic factors 1-2 years later. Adjusted hazard ratios related caregiving to 10-year mortality in all women initially screened, subsamples representing key points in constructing Caregiver-SOF, and Caregiver-SOF. Caregivers had better functioning than noncaregivers at each screening. The association between caregiving and mortality among women invited to participate in Caregiver-SOF (41% died; adjusted hazard ratio (aHR) = 0.73, 95% confidence interval (CI): 0.61, 0.88) was slightly more protective than that in all initially screened women (37% died; aHR = 0.83, 95% CI: 0.73, 0.95), indicating little evidence of selection bias due to sampling decisions, and was similar to that in Caregiver-SOF (39% died; aHR = 0.71, 95% CI: 0.57, 0.89), indicating no participation bias. These results add to a body of evidence that informal caregiving may impart health benefits.

ASSESSING THE ROLE OF SELECTION BIAS IN THE PROTECTIVE RELATIONSHIP BETWEEN CAREGIVING AND MORTALITY

Caregivers have lower mortality rates than noncaregivers in population-based studies, which contradicts the caregiver-stress model and raises speculation about selection bias influencing these findings. We examined possible selection bias due to 1) sampling decisions and 2) selective participation among women (baseline mean age = 79 years) in the Caregiver-Study of Osteoporotic Fractures (Caregiver-SOF) (1999-2009), an ancillary study to the Study of Osteoporotic Fractures (SOF). Caregiver-SOF includes 1,069 SOF participants (35% caregivers) from 4 US geographical areas (Baltimore, Maryland; Minneapolis, Minnesota; the Monongahela Valley, Pennsylvania; and Portland, Oregon). Participants were identified by screening all SOF participants for caregiver status (1997-1999; n = 4,036; 23% caregivers) and rescreening a subset of caregivers and noncaregivers matched on sociodemographic factors 1-2 years later. Adjusted hazard ratios related caregiving to 10-year mortality in all women initially screened, subsamples representing key points in constructing Caregiver-SOF, and Caregiver-SOF. Caregivers had better functioning than noncaregivers at each screening. The association between caregiving and mortality among women invited to participate in Caregiver-SOF (41% died; adjusted hazard ratio (aHR) = 0.73, 95% confidence interval (CI): 0.61, 0.88) was slightly more protective than that in all initially screened women (37% died; aHR = 0.83, 95% CI: 0.73, 0.95), indicating little evidence of selection bias due to sampling decisions, and was similar to that in Caregiver-SOF (39% died; aHR = 0.71, 95% CI: 0.57, 0.89), indicating no participation bias. These results add to a body of evidence that informal caregiving may impart health benefits.

Cross-Sectional and Longitudinal Associations of Diffuse Idiopathic Skeletal Hyperostosis and Thoracic Kyphosis in Older Men and Women.

To investigate cross-sectional and longitudinal associations of diffuse idiopathic skeletal hyperostosis (DISH) and thoracic kyphosis in older persons. DISH 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. DISH 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), after adjustment for covariates. After approximately 4 years of followup, there was no significant difference in annualized percent change in Cobb angle in those with DISH compared to those without DISH (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. Prevalent 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.

Weight Trajectory over 20 Years and Likelihood of Mild Cognitive Impairment or Dementia Among Older Women.

The association between weight change and cognition is controversial. We examined the association between 20-year weight change and cognitive function in late life. Cohort study. Study of Osteoporotic Fractures (SOF). One thousand two hundred eighty-nine older, community-dwelling women (mean baseline age 68 (65-81) and 88 (82-102) at cognitive testing). Study 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. Women 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. Rate 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.

Estimation of Standardized Hospital Costs from Medicare Claims That Reflect Resource Requirements for Care: Impact for Cohort Studies Linked to Medicare Claims

To compare cost estimates for hospital stays calculated using diagnosis-related group (DRG) weights to actual Medicare payments. Medicare MedPAR files and DRG tables linked to participant data from the Study of Osteoporotic Fractures (SOF) from 1992 through 2010. Participants were women age 65 and older recruited in three metropolitan and one rural area of the United States. Costs were estimated using DRG payment weights for 1,397 hospital stays for 795 SOF participants for 1year following a hip fracture. Medicare cost estimates included Medicare and secondary insurer payments, and copay and deductible amounts. The mean (SD) of inpatient DRG-based cost estimates per person-year were $16,268 ($10,058) compared with $19,937 ($15,531) for MedPAR payments. The correlation between DRG-based estimates and MedPAR payments was 0.71, and 51 percent of hospital stays were in different quintiles when costs were calculated based on DRG weights compared with MedPAR payments. DRG-based cost estimates of hospital stays differ significantly from Medicare payments, which are adjusted by Medicare for facility and local geographic characteristics. DRG-based cost estimates may be preferable for analyses when facility and local geographic variation could bias assessment of associations between patient characteristics and costs.

Common Genetic Variants inARNTLandNPAS2and at Chromosome 12p13 are Associated with Objectively Measured Sleep Traits in the Elderly

To determine the association between common genetic variation in the clock gene pathway and objectively measured acti-graphic sleep and activity rhythm traits. Genetic association study in two population-based cohorts of elderly participants: the Study of Osteoporotic Fractures (SOF) and the Osteoporotic Fractures in Men (MrOS) study. Population-based. SOF participants (n = 1,407, 100% female, mean age 84 years) and MrOS participants (n = 2,527, 100% male, mean age 77 years) with actigraphy and genotype data. N/A. Common genetic variation in 30 candidate genes was captured using 529 single nucleotide polymorphisms (SNPs). Sleep and activity rhythm traits were objectively measured using wrist actigraphy. In a region of high linkage disequilibrium on chromosome 12p13 containing the candidate gene GNB3, the rs1047776 A allele and the rs2238114 C allele were significantly associated with higher wake after sleep onset (meta-analysis: rs1047776 PADD = 2 × 10(-5), rs2238114 PADD = 5 × 10(-5)) and lower LRRC23 gene expression (rs1047776: ρ = -0.22, P = 0.02; rs2238114: ρ = -0.50, P = 5 × 10(-8)). In MrOS participants, SNPs in ARNTL and NPAS2, genes coding for binding partners, were associated with later sleep and wake onset time (sleep onset time: ARNTL rs3816358 P2DF = 1 × 10(-4), NPAS2 rs3768984 P2DF = 5 × 10(-5); wake onset time: rs3816358 P2DF = 3 × 10(-3), rs3768984 P2DF = 2 × 10(-4)) and the SNP interaction was significant (sleep onset time PINT = 0.003, wake onset time PINT = 0.001). A SNP association in the CLOCK gene replicated in the MrOS cohort, and rs3768984 was associated with sleep duration in a previously reported study. Cluster analysis identified four clusters of genetic associations. These findings support a role for common genetic variation in clock genes in the regulation of inter-related sleep traits in the elderly. Evans DS; Parimi N; Nievergelt CM; Blackwell T; Redline S; Ancoli-Israel S; Orwoll ES; Cummings SR; Stone KL; Tranah GJ. Common genetic variants in ARNTL and NPAS2 and at chromosome 12p13 are associated with objectively measured sleep traits in the elderly. SLEEP 2013;36(3):431-446.

Diabetes and Change in Bone Mineral Density at the Hip, Calcaneus, Spine, and Radius in Older Women

Older women with type 2 diabetes mellitus (DM) have higher bone mineral density (BMD) but also have higher rates of fracture compared to those without DM. Limited evidence suggests that DM may also be associated with more rapid bone loss. To determine if bone loss rates differ by DM status in older women, we analyzed BMD data in the Study of Osteoporotic Fractures (SOF) between 1986 and 1998. SOF participants were women ≥65 years at baseline who were recruited from four regions in the U.S. DM was ascertained by self-report. BMD was measured with dual-energy x-ray absorptiometry (DXA) at baseline and at least one follow-up visit at the hip (N = 6624) and calcaneus (N = 6700) and, on a subset of women, at the spine (N = 396) and distal radius (N = 306). Annualized percent change in BMD was compared by DM status, using random effects models. Of 6,867 women with at least one follow-up DXA scan, 409 had DM at baseline. Mean age was 70.8 (SD 4.7) years. Baseline BMD was higher in women with DM at all measured sites. In models adjusted for age and clinic, women with prevalent DM lost bone more rapidly than those without DM at the femoral neck (−0.96 vs. −0.59%/year, p < 0.001), total hip (−0.98 vs. −0.70%/year, p < 0.001), calcaneus (−1.64 vs. −1.40%/year, p = 0.005), and spine (−0.33 vs. +0.33%/year, p = 0.033), but not at the distal radius (−0.97 vs. −0.90%/year, p = 0.91). These findings suggest that despite higher baseline BMD, older women with DM experience more rapid bone loss than those without DM at the hip, spine, and calcaneus, but not the radius. Higher rates of bone loss may partially explain higher fracture rates in older women with DM.

Magnitude and consequences of misclassification of incident hip fractures in large cohort studies: the Study of Osteoporotic Fractures and Medicare claims data

In the Study of Osteoporotic Fractures (SOF), 18.5 % of incident hip fractures identified in Medicare Fee-for-Service claims data were not reported to or confirmed by the cohort. Cognitive impairment was a modest risk factor for false-negative hip fracture ascertainment via self-report. Prospective cohort studies of fractures that rely on participant self-report to be the initial signal of an incident fracture could be prone to bias if a significant proportion of fractures are not self-reported. We used data from the SOF merged with Medicare Fee-for-Service claims data to estimate the proportion of participants who had an incident hip fracture identified in Medicare claims that was either not self-reported or confirmed (by review of radiographic reports) in SOF. Between 1/1/1991 and 12/31/2007, 647 SOF participants had a hip fracture identified in Medicare claims, but 120 (18.5 %) were either not reported to or confirmed by the cohort. False-negative hip fracture ascertainment was associated with a reduced modified Mini-Mental State Exam (MMSE) score (odds ratio 1.31 per SD decrease, 95 % C.I. 1.06-1.63). Point estimates of associations of predictors of incident hip fracture were changed minimally when the misclassification of incident hip fracture status was corrected with use of claims data. A substantial minority of incident hip fractures were not reported to or confirmed in the SOF. Cognitive impairment was modestly associated with false-negative hip fracture ascertainment. While there was no evidence to suggest that misclassification of incident hip fracture status resulted in biased associations of potential predictors with hip fracture in this study, false-negative incident fracture ascertainment in smaller cohort studies with limited power may increase the risk of type 2 error (not finding significant associations of predictors with incident fractures).

Association of Osteocalcin and Abdominal Aortic Calcification in Older Women: The Study of Osteoporotic Fractures

Osteocalcin (OC) is produced by osteoblasts and vascular smooth muscle cells. In animal models, serum OC levels are strongly correlated with vascular calcium content, however, the association of OC with vascular calcification in humans is uncertain. The Study of Osteoporotic Fractures (SOF) enrolled community-living women, age ≥65 years. The present study included a subsample of 363 randomly selected SOF participants. Serum total OC was measured by ELISA, and abdominal aortic calcification (AAC) was evaluated on lateral lumbar radiographs. We examined the cross-sectional association between serum OC and AAC. The mean serum OC level was 24 ± 11 ng/ml and AAC was present in 188 subjects (52%). We observed no association of OC and AAC in either unadjusted or adjusted analyses. For example, each standard deviation higher OC level was associated with an odds ratio (OR) for AAC prevalence (AAC score >0) near unity (OR = 1.06; 95% CI, 0.82–1.36) in models adjusted for CVD risk factors. Further adjustment for intact parathyroid hormone, bone-specific alkaline phosphatase, 25-hydroxyvitamin D, and hip and spine bone mineral density did not materially change the results (OR = 1.22; 95% CI, 0.86–1.75). Similarly, higher OC levels were not associated with severity of AAC (P = 0.87). In conclusion, among community-living older women, serum OC is not associated with AAC. These findings suggest that serum OC levels may more closely reflect bone formation than vascular calcification in humans.

Reliability and Validity of Abbreviated Surveys Derived from the National Eye Institute Visual Function Questionnaire: The Study of Osteoporotic Fractures

To test the reliability and validity of questionnaires shortened from the National Eye Institute 25-item Vision Function Questionnaire (NEI VFQ-25). Cross-sectional, multicenter cohort study. 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. 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. 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.

Differences in Site-Specific Fracture Risk Among Older Women with Discordant Results for Osteoporosis at Hip and Spine: Study of Osteoporotic Fractures

To examine the fracture pattern in older women whose bone mineral density (BMD) T-score criteria for osteoporosis at hip and spine disagree, hip and spine BMD were measured in Study of Osteoporotic Fractures participants using dual energy X-ray absorptiometry (DXA). Hip osteoporosis was defined as T-score ≤−2.5 at femoral neck or total hip, and spine osteoporosis as T-score ≤−2.5 at lumbar spine. Incident clinical fractures were self-reported and centrally adjudicated. Incident radiographic spine fractures were defined morphometrically. Compared to women with osteoporosis at neither hip nor spine, those osteoporotic only at hip had a 3.0-fold age- and weight-adjusted increased risk for hip fracture (95% confidence interval [CI]: 2.4–3.6), and smaller increases in risk of nonhip nonspine (hazard ratios [HR] = 1.6), clinical spine (odds ratio [OR] = 2.2), and radiographic spine fractures (OR = 1.5). Women osteoporotic only at spine had a 2.8-fold increased odds of radiographic spine fracture (95% CI: 2.1–3.8), and smaller increases in risk of clinical spine (OR = 1.4), nonhip nonspine (HR = 1.6), and hip fractures (HR = 1.2). Discordant BMD results predict different fracture patterns. DXA fracture risk estimation in these patients should be site specific. Women osteoporotic only at spine would not have been identified from hip BMD measurement alone, and may have a sufficiently high fracture risk to warrant preventive treatment.

Bone Mineral Density and Age‐Related Maculopathy in Older Women

To determine whether bone mineral density (BMD) is associated with age-related maculopathy (ARM) risk in older women. Cross-sectional analysis at Year 10 (1997/98) of the Study of Osteoporotic Fractures (SOF). Four clinical centers in the United States. One thousand forty-two randomly sampled SOF participants who attended the Year 10 clinic visit. ARM 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. The 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). Higher 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.

Postmenopausal Bilateral Oophorectomy Is Not Associated With Increased Fracture Risk in Older Women

We studied whether oophorectomy performed after menopause is associated with an increased risk of hip or vertebral fractures in 6295 Study of Osteoporotic Fractures participants. There was no association between postmenopausal oophorectomy and the risk of hip or vertebral fractures. Bilateral oophorectomy after natural menopause has been associated with an increased risk of osteoporotic fractures, potentially because of a decline in serum estradiol and testosterone levels after the oophorectomy. We prospectively tested this hypothesis in the Study of Osteoporotic Fractures (SOF). We studied 6295 white women 65 years of age participating in the SOF who were not taking estrogen therapy at baseline. Hip fracture analyses included 708 hip fractures; vertebral fracture analyses included 267 incident vertebral fractures. Baseline serum estradiol and free testosterone values were available in a small subset of participants. There were no significant differences in age, weight, or BMD between the women who underwent postmenopausal oophorectomy (n = 583) and those who did not (n = 5712). Free testosterone levels were significantly lower among women who had a postmenopausal oophorectomy. A history of postmenopausal oophorectomy was not associated with an increased risk of hip (hazard ratio [HR] = 1.1; 95% CI = 0.9-1.5) or vertebral fracture (HR = 0.7; 95% CI = 0.5-1.2). The relationship between oophorectomy and hip fracture was not altered by adding serum estradiol level (HR = 1.3; 95% CI = 0.5-3.2) or serum free testosterone level (HR = 1.7; 95% CI = 0.8-3.7) to the model. In summary, postmenopausal oophorectomy was not associated with an increased risk of hip or vertebral fracture in this cohort. These results are in contrast to previous findings, suggesting that the relationship between postmenopausal oophorectomy and fractures is not fully elucidated and that incidental oophorectomy after menopause should still be considered carefully in each potential patient.