Sex steroid hormones in older men: longitudinal associations with 4.5-year change in hip bone mineral density--the osteoporotic fractures in men study

Abstract

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.

Figure 1

A, Change in total hip BMD by quintile of baseline bioavailable estradiol. Results have been adjusted for age, race, clinic, baseline weight, and weight change (P trend = 0.03). B, Change in total hip BMD by quintile of baseline bioavailable testosterone. Results have been adjusted for age, race, clinic, baseline weight, and weight change (P trend = 0.17). C, Change in total hip BMD by quintile of baseline SHBG. Results have been adjusted for age, race, clinic, baseline weight, and weight change.

Figure 2

Spline fit of change in total hip BMD vs. baseline SHBG. Results have been adjusted for age, race, clinic, baseline weight, and weight change.

Figure 3

Combined effect of BioE2, BioT, and SHBG on total hip BMD loss. Results have been adjusted for age, race, clinic, baseline weight, and weight change. *, P < 0.05 vs. the referent group (high BioE2, high BioT, and low SHBG). The number of men in each category is as follows: 1) low BioE2, low BioT, high SHBG, n = 15; 2) low BioE2, low BioT, low SHBG, n = 43; 3) low BioE2, high BioT, high SHBG, n = 24; 4) low BioE2, high BioT, low SHBG, n = 95; 5) high BioE2, low BioT, high SHBG, n = 9; 6) high BioE2, low BioT, low SHBG, n = 107; 7) high BioE2, high BioT, high SHBG, n = 131; and 8) high BioE2, High BioT, low SHBG, n = 545.