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 (≥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 withmenwith 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.
Bibliographical noteFunding Information:
The MrOS is supported by National Institutes of Health (NIH) funding. The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), the National Center for Research Resources (NCRR), and NIH Roadmap for Medical Research provide support under the following grant numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 RR024140 . The National Heart, Lung, and Blood Institute (NHLBI) provides funding for the MrOS Sleep ancillary study, “Outcomes of Sleep Disorders in Older Men,” under the following grant numbers: R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839 .