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The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 7 2266-2274
Copyright © 1998 by The Endocrine Society

Original Studies

Relationship of Serum Sex Steroid Levels and Bone Turnover Markers with Bone Mineral Density in Men and Women: A Key Role for Bioavailable Estrogen1

Sundeep Khosla, L. Joseph Melton, III, Elizabeth J. Atkinson, W. M. O’Fallon, George G. Klee and B. Lawrence Riggs

Endocrine Research Unit (S.K., B.L.R.); Division of Endocrinology, Metabolism, and Nutrition; Departments of Internal Medicine, Health Sciences Research (L.J.M., E.J.A., W.M.O.), and Laboratory Medicine and Pathology (G.G.K.), Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Sundeep Khosla, M.D., Mayo Clinic, 200 First Street SW, 5–164 West Joseph, Rochester, Minnesota 55905. E-mail: khosla.sundeep{at}mayo.edu

Estrogen (E) deficiency associated with the menopause is the major cause of bone loss in aging women. However, men also lose significant amounts of bone with age, but they do not have the equivalent of menopause, and serum total testosterone (T) and E levels decline only marginally 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 population-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%, respectively. In these men and in a parallel cohort of 304 women, aged 21–94 yr, serum PTH increased 84% and 64% over the life span, and urinary N-telopeptide of type I collagen (NTx) excretion, a bone resorption marker, increased 77% and 80% between age 50–85 yr in the men and women, respectively. By univariate analyses, serum bioavailable T and E levels correlated positively with bone mineral density (BMD) at the total body, spine, proximal femur, and distal radius and negatively with urinary NTx excretion in men and women. Urinary NTx excretion was also negatively associated with BMD in both sexes. By multivariate analyses, however, serum bioavailable E level was the consistent independent predictor 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 deficiency not just in postmenopausal women, but also in men.




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