Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men

Abstract

Young adult males who cannot produce or respond to estrogen (E) are osteopenic, suggesting that E may regulate bone turnover in men, as well as in women. Both bioavailable E and testosterone (T) decrease substantially in aging men, but it is unclear which deficiency is the more important factor contributing to the increased bone resorption and impaired bone formation that leads to their bone loss. Thus, we addressed this issue directly by eliminating endogenous T and E production in 59 elderly men (mean age 68 years), studying them first under conditions of physiologic T and E replacement and then assessing the impact on bone turnover of withdrawing both T and E, withdrawing only T, or only E, or continuing both. Bone resorption markers increased significantly in the absence of both hormones and were unchanged in men receiving both hormones. By two-factor ANOVA, E played the major role in preventing the increase in the bone resorption markers, whereas T had no significant effect. By contrast, serum osteocalcin, a bone formation marker, decreased in the absence of both hormones, and both E and T maintained osteocalcin levels. We conclude that in aging men, E is the dominant sex steroid regulating bone resorption, whereas both E and T are important in maintaining bone formation.

Figure 1

Schematic representation of the study design. Following the base-line visit, the subjects were randomized into one of four groups, as indicated.

Figure 2

Changes in urinary Dpd (top panel) and NTx (bottom panel) excretion in the four groups between the base-line and final visits. ^AP < 0.05, ^BP < 0.005, and ^CP < 0.001 for change from base line. The overall effect of E and T on the bone markers was analyzed using the two-factor ANOVA model described in Methods.

Figure 3

Changes in serum osteocalcin (top panel) and PINP (bottom panel) levels in the four groups between the base-line and final visits. ^AP < 0.005 and ^BP < 0.001 for change from base line. The overall effect of E and T on the bone markers was analyzed using the two-factor ANOVA model described in Methods.