Estrogen Plays a Major Role in Bone Resorption in Normal Elderly Men
Because testosterone (T) is the dominant sex steroid secreted in men, it was thought to be the major sex steroid regulating bone metabolism in men. However, this concept has been challenged. In a recently published study (J Clin Invest 106:1553, 2000), Falahati-Nini, et al studied the role of T and E on biological markers of bone resorption and bone formation in older, otherwise healthy, men.
Endogenous testosterone (T) and estrogen (E) were depleted in 59 elderly men (mean age 68 years) by treatment with 7.5 mg Leupolide (Lupron depot). Exogenous T and E were reintroduced at doses aimed at achieving physiological levels (5mg/d T patch and 0.0375 mg/d E patch) and continued for 3 weeks. After 3 weeks, patients were randomized to one of fours groups: A) T and E both discontinued (-T, -E); B) T discontinued (-T, +E); C) E discontinued (+T, -E); and, D) no discontinuations (+T, +E). All patients were treated with 2.5mg/d Letrozole, an aromatase inhibitor, throughout the study to prevent conversion of T to E. Bone resorption was assessed by measurement of urinary total deoxypyridinoline (Dpd) and N-telopeptide of type I collagen ( NTx). Bone formation was assessed by serum osteocalcin (OC), amino-terminal propeptide of type I procollagen (PINP), and bone-specific alkaline phosphatase (BSAP). Measurements were taken at weeks 3 and 6.
With regard to bone resorption markers, urinary Dpd excretion increased in groups A (26%), B (9%), and C (22%), whereas no significant increase occurred in group D. Nearly identical trends were observed for NTx (35%, 9%, and 22% for Groups A, B and C). Using a two-factor ANOVA model, there was a clear effect of E, but not T, on urinary Dpd excretion (p 0.005 and 0.232 for E and T, respectively) and on NTx excretion (p 0.0002 and 0.085 for E and T, respectively). With regard to markers of bone formation, serum OC decreased significantly (16%) in Group A only. Using the ANOVA model, both E and T had significant effects in maintaining OC levels (p 0.002 and 0.013 for E and T, respectively). Similar findings were observed for PINP levels. No significant differences in serum BSAP were observed among the four groups.
These data indicate that E clearly exerts a dominant regulatory effect on bone resorption in normal elderly men. T may have small effect, although not significant. Both E and T are important in maintaining bone formation.
Editorial Comment: This study challenges the traditional concept that testosterone is the critical sex hormone for maintaining bone density. There may be a role for low dose estrogen or selective estrogen receptor modulators (SERMs) in the treatment of osteoporosis in aging men.
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