RELATIONSHIP OF SERUM SEX STEROID-LEVELS AND BONE TURNOVER MARKERS WITH BONE-MINERAL DENSITY IN MEN AND WOMEN - A KEY ROLE FOR BIOAVAILABLEESTROGEN

Estrogen (E) deficiency associated with the menopause is the major cau se of bone loss in aging women. However, men also lose significant amo unts of bone with age, but they do not have the equivalent of menopaus e, and serum total testosterone (T) and E levels decline only marginal ly with age in men. Thus, it has been difficult to attribute bone loss in aging men to either T or E deficiency. Here, we show in a populati on-based, age-stratified sample of 346 men, aged 23-90 yr, that serum total T and E (estradiol plus estrone) levels decreased over the life span by 30% and 12%, respectively, but bioavailable (or nonsex hormone -binding globulin-bound)T and E levels decreased by 64% and 47%, respe ctively. In these men and in a parallel cohort of 304 women, aged 21-9 4 yr, serum PTH increased 84% and 64% over the life span, and urinary N-telopeptide of type I collagen (NTx) excretion, a bone resorption ma rker, increased 77% and 80% between age 50-85 yr in the men and women, respectively. By univariate analyses, serum bioavailable T and E leve ls correlated positively with bone mineral density (BMD) at the total body, spine, proximal femur, and distal radius and negatively with uri nary NTx excretion in men and women. Urinary NTx excretion was also ne gatively associated with BMD in both sexes. By multivariate analyses, however, serum bioavailable E level was the consistent independent pre dictor of BMD in both men and postmenopausal women. Thus, bioavailable E levels decline significantly with age and are important predictors of BMD in men as well as women. These studies suggest that in contrast to traditional belief, age-related bone loss may be the result of E d eficiency not just in postmenopausal women, but also in men.