Tien N. Vo

Prediction of Incident Major Osteoporotic and Hip Fractures by Trabecular Bone Score (TBS) and Prevalent Radiographic Vertebral Fracture in Older Men

Trabecular bone score (TBS) has been shown to predict major osteoporotic (clinical vertebral, hip, humerus, and wrist) and hip fractures in postmenopausal women and older men, but the association of TBS with these incident fractures in men independent of prevalent radiographic vertebral fracture is unknown. TBS was estimated on anteroposterior (AP) spine dual-energy X-ray absorptiometry (DXA) scans obtained at the baseline visit for 5979 men aged ≥65 years enrolled in the Osteoporotic Fractures in Men (MrOS) Study and its association with incident major osteoporotic and hip fractures estimated with proportional hazards models. Model discrimination was tested with Harrells C-statistic and with a categorical net reclassification improvement index, using 10-year risk cutpoints of 20% for major osteoporotic and 3% for hip fractures. For each standard deviation decrease in TBS, there were hazard ratios of 1.27 (95% confidence interval [CI] 1.17 to 1.39) for major osteoporotic fracture, and 1.20 (95% CI 1.05 to 1.39) for hip fracture, adjusted for FRAX with bone mineral density (BMD) 10-year fracture risks and prevalent radiographic vertebral fracture. In the same model, those with prevalent radiographic vertebral fracture compared with those without prevalent radiographic vertebral fracture had hazard ratios of 1.92 (95% CI 1.49 to 2.48) for major osteoporotic fracture and 1.86 (95% CI 1.26 to 2.74) for hip fracture. There were improvements of 3.3%, 5.2%, and 6.2%, respectively, of classification of major osteoporotic fracture cases when TBS, prevalent radiographic vertebral fracture status, or both were added to FRAX with BMD and age, with minimal loss of correct classification of non-cases. Neither TBS nor prevalent radiographic vertebral fracture improved discrimination of hip fracture cases or non-cases. In conclusion, TBS and prevalent radiographic vertebral fracture are associated with incident major osteoporotic fractures in older men independent of each other and FRAX 10-year fracture risks, and these data support their use in conjunction with FRAX for fracture risk assessment in older men.

The Association Between Trabecular Bone Score and Lumbar Spine Volumetric BMD is Attenuated Among Older Men with High Body Mass Index.

Trabecular bone score (TBS) has been proposed as a dual‐energy X‐ray absorptiometry (DXA) derived measure of underlying quality of trabecular bone; however, TBS is not considered valid for those with body mass index (BMI) >37 kg/m2. Our objective was to determine the association between TBS and lumbar spine (trabecular) volumetric BMD (LS‐VBMD) and to examine whether the association varied by BMI and body composition among older men below this clinical threshold. We used regression models to study 3479 men age ≥65 years enrolled in the Osteoporotic Fractures in Men (MrOS) study who had TBS from spine DXA scans, LS‐VBMD from central quantitative computed tomography, measures of trunk fat and lean mass from DXA, and BMI <37 kg/m2. TBS was categorized as normal (n = 925), partially degraded (n = 1747), and degraded (n = 807). TBS was inversely related to BMI, trunk fat mass, and trunk lean mass (all p < 0.001). The relationship between TBS and LS‐VBMD was nonlinear with magnitude of effect (slope of regression line using standardized variables) ranging from 0.07 (95% CI, –0.02 to 0.15) among those with degraded TBS up to 0.71 (95% CI, 0.54 to 0.89) among those with normal TBS. The relationship was still nonlinear after adjusting for age, clinical site, and either BMI, trunk lean mass, or trunk fat mass. The magnitude of effect relating TBS and LS‐VBMD also decreased with increasing BMI (interaction, p = 0.090) and increasing trunk lean mass (interaction, p = 0.001), but not with increasing trunk fat mass (interaction, p = 0.224). In summary, the strength of the association between TBS and LS‐VBMD among older men was variable and dependent on BMI and body composition, particularly trunk lean mass. The clinical utility of TBS among older men may be somewhat limited among men with high BMI or high trunk lean mass.

The Association Between Protein Intake by Source and Osteoporotic Fracture in Older Men: A Prospective Cohort Study

Dietary protein is a potentially modifiable risk factor for fracture. Our objectives were to assess the association of protein intake with incident fracture among older men and whether these associations varied by protein source or by skeletal site. We studied a longitudinal cohort of 5875 men (mean age 73.6 ± 5.9 years) in the Osteoporotic Fractures in Men (MrOS) study. At baseline, protein intake was assessed as percent of total energy intake (TEI) with mean intake from all sources = 16.1%TEI. Incident clinical fractures were confirmed by physician review of medical records. There were 612 major osteoporotic fractures, 806 low‐trauma fractures, 270 hip fractures, 193 spine fractures, and 919 non‐hip non‐spine fractures during 15 years of follow‐up. We used Cox proportional hazards models with age, race, height, clinical site, TEI, physical activity, marital status, osteoporosis, gastrointestinal surgery, smoking, oral corticosteroids use, alcohol consumption, and calcium and vitamin D supplements as covariates to compute hazard ratios (HRs) with 95% confidence intervals (CIs), all expressed per unit (SD = 2.9%TEI) increase. Higher protein intake was associated with a decreased risk of major osteoporotic fracture (HR = 0.92; 95% CI, 0.84 to 1.00) with a similar association found for low‐trauma fracture. The association between protein and fracture varied by protein source; eg, increased dairy protein and non‐dairy animal protein were associated with a decreased risk of hip fracture (HR = 0.80 [95% CI, 0.65 to 0.98] and HR = 0.84 [95% CI, 0.72 to 0.97], respectively), whereas plant‐source protein was not (HR = 0.99 [95% CI, 0.78 to 1.24]). The association between protein and fracture varied by fracture site; total protein was associated with a decreased risk of hip fracture (HR = 0.84 [95% CI, 0.73 to 0.95]), but not clinical spine fracture (HR = 1.06 [95% CI, 0.92 to 1.22]). In conclusion, those with high protein intake (particularly high animal protein intake) as a percentage of TEI have a lower risk of major osteoporotic fracture.

Association of Trabecular Bone Score (TBS) With Incident Clinical and Radiographic Vertebral Fractures Adjusted for Lumbar Spine BMD in Older Men: A Prospective Cohort Study

The association of trabecular bone score (TBS) with incident clinical and radiographic vertebral fractures in older men is uncertain. TBS was estimated from baseline spine dual‐energy X‐ray absorptiometry (DXA) scans for 5831 older men (mean age 73.7 years) enrolled in the Osteoporotic Fractures in Men (MrOS) study. Cox proportional hazard models were used to determine the association of TBS (per 1 SD decrease) with incident clinical vertebral fractures. Logistic regression was used to determine the association between TBS (per 1 SD decrease) and incident radiographic vertebral fracture among the subset of 4309 men with baseline and follow‐up lateral spine radiographs (mean 4.6 years later). We also examined whether any associations varied by body mass index (BMI) category. TBS was associated with a 1.41‐fold (95% confidence interval [CI] 1.23 to 1.63) higher aged‐adjusted odds of incident radiographic fracture, and this relationship did not vary by BMI (p value = 0.22 for interaction term). This association was no longer significant with further adjustment for lumbar spine bone mineral density (BMD; odds ratio [OR] = 1.11, 95% CI 0.94 to 1.30). In contrast, the age‐adjusted association of TBS with incident clinical vertebral fracture was stronger in men with lower BMI (≤ median value of 26.8 kg/m2; hazard ratio [HR] = 2.28, 95% CI 1.82 to 2.87) than in men with higher BMI (> median; HR = 1.60, 95% CI 1.31 to 1.94; p value = 0.0002 for interaction term). With further adjustment for lumbar spine BMD, the association of TBS with incident clinical vertebral fracture was substantially attenuated in both groups (HR = 1.30 [95% CI 0.99 to 1.72] among men with lower BMI and 1.11 [95% CI 0.87 to 1.41] among men with higher BMI). In conclusion, TBS is not associated with incident clinical or radiographic vertebral fracture after consideration of age and lumbar spine BMD, with the possible exception of incident clinical vertebral fracture among men with lower BMI.

Effects of Mobility and Multimorbidity on Inpatient and Postacute Health Care Utilization

Background This study examines effects of mobility and multimorbidity on hospitalization and inpatient and postacute care (PAC) facility days among older men. Methods Prospective study of 1,701 men (mean age 79.3 years) participating in Osteoporotic Fractures in Men (MrOS) Study Year 7 (Y7) examination (2007-2008) linked with their Medicare claims. At Y7, mobility ascertained by usual gait speed and categorized as poor, intermediate, or good. Multimorbidity quantified by applying Elixhauser algorithm to inpatient and outpatient claims and categorized as none, mild-moderate, or high. Hospitalizations and PAC facility stays ascertained during 12 months following Y7. Results Reduced mobility and greater multimorbidity burden were independently associated with a higher risk of inpatient and PAC facility utilization, after accounting for each other and traditional indicators. Adjusted mean total facility days per year were 1.13 (95% confidence interval [CI] = 0.74-1.40) among men with good mobility increasing to 2.43 (95% CI = 1.17-3.84) among men with poor mobility, and 0.67 (95% CI = 0.38-0.91) among men without multimorbidity increasing to 2.70 (95% CI = 1.58-3.77) among men with high multimorbidity. Men with poor mobility and high multimorbidity had a ninefold increase in mean total facility days per year (5.50, 95% CI = 2.78-10.87) compared with men with good mobility without multimorbidity (0.59, 95% CI = 0.37-0.95). Conclusions Among older men, mobility limitations and multimorbidity were independent predictors of higher inpatient and PAC utilization after considering each other and conventional predictors. Marked combined effects of reduced mobility and multimorbidity burden may be important to consider in clinical decision-making and planning health care delivery strategies for the growing aged population.

Comparison of Associations of DXA and CT Visceral Adipose Tissue Measures With Insulin Resistance, Lipid Levels, and Inflammatory Markers

Visceral adipose tissue (VAT) measured by computed tomography (CT) is related to insulin resistance, lipids, and serum inflammatory markers. Our objective was to compare the strength of the associations of VAT measured using dual-energy X-ray absorptiometry (DXA-VAT) and CT (CT-VAT) with insulin resistance, serum lipids, and serum markers of inflammation. For 1117 men aged 65 and older enrolled in the Osteoporotic Fractures in Men Study, the cross-sectional associations of DXA-VAT and CT-VAT with homeostasis model assessment of insulin resistance (homa2ir), C-reactive protein, and high-density lipoprotein (HDL) cholesterol were estimated with regression models and compared using a Hausman test. Adjusted for age and body mass index, DXA-VAT was moderately associated with homa2ir (effect size 0.38, 95% confidence interval [CI]: 0.28-0.47) and modestly associated with HDL cholesterol (DXA effect size -0.29, 95% CI: -0.38 to -0.21). These associations were significantly greater than those for CT-VAT with homa2ir (0.30, 95% CI: 0.24-0.37; p value for effect size difference 0.03) and CT-VAT with HDL cholesterol (-0.22, 95% CI: -0.29 to -0.15; p value for difference 0.005). Neither DXA-VAT nor CT-VAT was associated with C-reactive protein after adjustment for age and body mass index (DXA-VAT effect size 0.14, 95% CI: -0.04 to 0.32; CT-VAT effect size 0.08, 95% CI: -0.08 to 0.25; p value for difference 0.35). DXA-VAT has similar or greater associations with insulin resistance and HDL cholesterol as does CT-VAT in older men, confirming the concurrent validity of DXA-VAT. Investigations of how well DXA measurements of VAT predict incident cardiovascular disease events are warranted.

Which sleep health characteristics predict all-Cause mortality in older men? An application of flexible multivariable approaches

Study Objectives Sleep is multidimensional, with domains including duration, timing, continuity, regularity, rhythmicity, quality, and sleepiness/alertness. Individual sleep characteristics representing these domains are known to predict health outcomes. However, most studies consider sleep characteristics in isolation, resulting in an incomplete understanding of which sleep characteristics are the strongest predictors of health outcomes. We applied three multivariable approaches to robustly determine which sleep characteristics increase mortality risk in the osteoporotic fractures in men sleep study. Methods In total, 2,887 men (mean 76.3 years) completed relevant assessments and were followed for up to 11 years. One actigraphy or self-reported sleep characteristic was selected to represent each of seven sleep domains. Multivariable Cox models, survival trees, and random survival forests were applied to determine which sleep characteristics increase mortality risk. Results Rhythmicity (actigraphy pseudo-F statistic) and continuity (actigraphy minutes awake after sleep onset) were the most robust sleep predictors across models. In a multivariable Cox model, lower rhythmicity (hazard ratio, HR [95%CI] =1.12 [1.04, 1.22]) and lower continuity (1.16 [1.08, 1.24]) were the strongest sleep predictors. In the random survival forest, rhythmicity and continuity were the most important individual sleep characteristics (ranked as the sixth and eighth most important among 43 possible sleep and non-sleep predictors); moreover, the predictive importance of all sleep information considered simultaneously followed only age, cognition, and cardiovascular disease. Conclusions Research within a multidimensional sleep health framework can jumpstart future research on causal pathways linking sleep and health, new interventions that target specific sleep health profiles, and improved sleep screening for adverse health outcomes.

Sleep disturbances and risk of hospitalization and inpatient days among older women

Study Objectives Determine the associations of sleep disturbances with hospitalization risk among older women. Methods 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. Results 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. Conclusions Older women with sleep disturbances have an increased risk of hospitalization partially attributable to demographics, poorer health status, and comorbidities.

Association of Increased Urinary Albumin with Risk of Incident Clinical Fracture and Rate of Hip Bone Loss: The Osteoporotic Fractures in Men Study.

Prior studies suggest that increased urine albumin is associated with a heightened fracture risk in women, but results in men are unclear. We used data from Osteoporotic Fractures in Men (MrOS), a prospective cohort study of community‐dwelling men aged ≥65 years, to evaluate the association of increased urine albumin with subsequent fractures and annualized rate of hip bone loss. We calculated albumin/creatinine ratio (ACR) from urine collected at the 2003–2005 visit. Subsequent clinical fractures were ascertained from triannual questionnaires and centrally adjudicated by review of radiographic reports. Total hip BMD was measured by DXA at the 2003–2005 visit and again an average of 3.5 years later. We estimated risk of incident clinical fracture using Cox proportional hazards models, and annualized BMD change using ANCOVA. Of 2982 men with calculable ACR, 9.4% had ACR ≥30 mg/g (albuminuria) and 1.0% had ACR ≥300 mg/g (macroalbuminuria). During a mean of 8.7 years of follow‐up, 20.0% of men had an incident clinical fracture. In multivariate‐adjusted models, neither higher ACR quintile (p for trend 0.75) nor albuminuria (HR versus no albuminuria, 0.89; 95% CI, 0.65 to 1.20) was associated with increased risk of incident clinical fracture. Increased urine albumin had a borderline significant, multivariate‐adjusted, positive association with rate of total hip bone loss when modeled in ACR quintiles (p = 0.06), but not when modeled as albuminuria versus no albuminuria. Macroalbuminuria was associated with a higher rate of annualized hip bone loss compared to no albuminuria (–1.8% more annualized loss than in men with ACR <30 mg/g; p < 0.001), but the limited prevalence of macroalbuminuria precluded reliable estimates of its fracture associations. In these community‐dwelling older men, we found no association between urine albumin levels and risk of incident clinical fracture, but found a borderline significant, positive association with rate of hip bone loss.

Associations of recent weight loss with health care costs and utilization among older women

The association of weight loss with health care costs among older women is uncertain. Our study aim was to examine the association of objectively measured weight change with subsequent total health care (THC) costs and other health care utilization among older women. Our study population included 2,083 women (mean age 80.2 years) enrolled in the Study of Osteoporotic Fractures and U.S. Medicare Fee for Service. Weight loss and gain were defined, respectively, as ≥5% decrease and ≥5% increase in body weight, and weight maintenance as <5% change in body weight over a period of 4.5 years. THC costs, outpatient costs, hospitalizations, and skilled nursing facility [SNF] utilization were estimated from Medicare claims for 1 year after the period during which weight change was measured. The associations of weight change with THC and outpatient costs were estimated using generalized linear models with gamma variance and log link functions, and with hospitalizations and SNF utilization using logistic models. Adjusted for age and current body mass index (BMI), weight loss compared with weight maintenance was associated with a 35% increase in THC costs (