Eric S. Orwoll

Frailty in Older Men: Prevalence, Progression, and Relationship with Mortality

OBJECTIVES: To describe the association between frailty and health status, the progression of frailty, and the relationship between frailty and mortality in older men.

25-Hydroxyvitamin D levels and cognitive performance and decline in elderly men

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

Biochemical markers of bone turnover, hip bone loss, and fracture in older men: the MrOS study.

We used data from the Osteoporotic Fractures in Men (MrOS) study to test the hypothesis that men with higher levels of bone turnover would have accelerated bone loss and an elevated risk of fracture. MrOS enrolled 5995 subjects >65 yr; hip BMD was measured at baseline and after a mean follow‐up of 4.6 yr. Nonspine fractures were documented during a mean follow‐up of 5.0 yr. Using fasting serum collected at baseline and stored at −190°C, bone turnover measurements (type I collagen N‐propeptide [PINP]; β C‐terminal cross‐linked telopeptide of type I collagen [βCTX]; and TRACP5b) were obtained on 384 men with nonspine fracture (including 72 hip fractures) and 947 men selected at random. Among randomly selected men, total hip bone loss was 0.5%/yr among those in the highest quartile of PINP (>44.3 ng/ml) and 0.3%/yr among those in the lower three quartiles (p = 0.01). Fracture risk was elevated among men in the highest quartile of PINP (hip fracture relative hazard = 2.13; 95% CI: 1.23, 3.68; nonspine relative hazard = 1.57, 95% CI: 1.21, 2.05) or βCTX (hip fracture relative hazard = 1.76, 95 CI: 1.04, 2.98; nonspine relative hazard = 1.29, 95% CI: 0.99, 1.69) but not TRACP5b. Further adjustment for baseline hip BMD eliminated all associations between bone turnover and fracture. We conclude that higher levels of bone turnover are associated with greater hip bone loss in older men, but increased turnover is not independently associated with the risk of hip or nonspine fracture.

Sex Steroid Hormones in Older Men: Longitudinal Associations with 4.5-Year Change in Hip Bone Mineral Density—The Osteoporotic Fractures in Men Study

CONTEXT There is limited information on the association between sex hormones and bone loss in older men. OBJECTIVE Our objective was to determine the longitudinal association between sex steroid hormones and bone mineral density (BMD). DESIGN AND SETTING We conducted a prospective study of 5995 men aged at least 65 yr old at six U.S. clinical centers. PARTICIPANTS Sex steroid hormones were measured in a random sample of 1602 men. After exclusions, 1238 men were included in cross-sectional analyses and 969 in longitudinal analyses. Baseline sex hormones were measured using liquid chromatography-mass spectrometry. Bioavailable (Bio) estradiol (BioE2) and testosterone (BioT) were calculated from mass action equations. SHBG was measured using chemiluminescent substrate. MAIN OUTCOME MEASURES BMD of the total hip, measured at baseline and once or twice afterward over 4.6 yr of follow-up, was evaluated. RESULTS The annualized percent change in hip BMD increased with decreasing BioE2 (P trend = 0.03). Men with the lowest BioE2 (<39.7 pmol/liter) compared with the highest BioE2 (> or =66.0 pmol/liter) experienced 38% faster rate of BMD loss (P < 0.05). There was no association between BioT and hip BMD loss. Men with lowest BioE2, lowest BioT, and highest SHBG experienced a 3-fold faster rate of BMD loss compared with men with higher levels (P = 0.02). A threshold effect of SHBG was observed; the rate of hip BMD loss increased in men with SHBG of 49-60 nM. CONCLUSIONS Low BioE2 and high SHBG levels were associated with lower BMD and faster hip BMD loss. The combination of low BioE2, low BioT, and high SHBG was associated with significantly faster rates of BMD loss.

Association Between Parkinson's Disease and Low Bone Density and Falls in Older Men: The Osteoporotic Fractures in Men Study

Objectives: To examine the association between Parkinsons disease (PD) and bone mineral density (BMD) and risk of falls.

Alcohol use, physical performance, and functional limitations in older men

OBJECTIVES: To describe associations between recent alcohol intake, physical performance, and functional limitations in older men.

Circulating vitamin D, supplement use, and cardiovascular disease risk: the MrOS Sleep Study.

CONTEXT Evidence suggests an inverse association between circulating 25(OH) vitamin D and cardiovascular disease (CVD). OBJECTIVE To determine the association between serum 25(OH) vitamin D and risk for CVD events. SETTING AND DESIGN From March 2000 to April 2002, participants were recruited for the Osteoporotic Fractures in Men (MrOS) study. Between December 2003 and March 2005, members of the MrOS cohort were invited to participate in the MrOS Sleep Study. Participants were recruited from 6 clinical centers across the United States and followed for a mean of 5.9 years. Three-thousand-one-hundred-thirty-five men ages 65 and older were included from the MrOS cohort, of whom 116 were excluded for missing vitamin D or CVD data. Participants were divided into two groups based on serum 25(OH) vitamin D levels, <20 ng/mL and ≥20 ng/mL. Participants were followed for CVD endpoints including coronary heart disease (CHD) and cerebrovascular events. Age- and multivariable-adjusted hazard ratios were calculated and stratified by use of vitamin D containing supplements. RESULTS We observed no significant association between circulating 25(OH) vitamin D and risk of CVD event (HR, 0.91; 95% confidence interval (CI), 0.73-1.13) and CHD event (HR, 0.81; 95% CI, 0.61-1.07). For cerebrovascular events, men with vitamin D deficiency exhibited a higher risk (HR, 1.44; 95% CI, 1.00-2.08) using the minimally adjusted model and after excluding supplement users (HR, 1.70; 95% CI, 1.02-2.83). CONCLUSIONS 25(OH) vitamin D was not associated with risk of CVD and CHD events. However, vitamin D deficiency may be associated with an increased risk of cerebrovascular events.