Emily A Rosenberg1, Petra Bůžková2, Howard A Fink3, John A Robbins4, Molly M Shores5, Alvin M Matsumoto6, Kenneth J Mukamal7. 1. Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, MA, United States of America; Harvard Medical School, Boston, MA, United States of America. Electronic address: earosenberg@bwh.harvard.edu. 2. Department of Biostatistics, University of Washington, Seattle, WA, United States of America. 3. Geriatric Research Education and Clinical Center, VA Health Care System, Minneapolis, MN, United States of America. 4. Department of Medicine, University of California Davis, Sacramento, CA, United States of America. 5. Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States of America; Mental Health Service, VA Puget Sound Health Care System, Seattle, WA, United States of America. 6. Department of Medicine, University of Washington, Seattle, WA, United States of America; Geriatric Research, Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, United States of America. 7. Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States of America.
Abstract
BACKGROUND: Little is known about the relationships of dihydrotestosterone (DHT), a more potent androgen than testosterone (T), with bone mineral density (BMD) and fracture risk. Our objectives were to evaluate the relationships of T, DHT and sex hormone binding globulin (SHBG) with BMD, fracture risk, and lean body mass (LBM). METHODS: We evaluated 1128 older men free of cardiovascular disease in a prospective cohort study using data from the Cardiovascular Health Study. T and DHT were measured by liquid chromatography-tandem mass spectrometry and SHBG by fluoroimmunoassay. Our outcomes included incident hip fracture (n = 106) over a median of 10.2 years and BMD and LBM by dual-energy x-ray absorptiometry (n = 439). RESULTS: In Cox regression models mutually adjusted for T, SHBG, and covariates, each standard deviation increment in DHT (0.23 ng/ml) was associated with a 26% lower risk of hip fracture (adjusted hazard ratio [aHR] 0.74, 95% confidence interval (CI) 0.55-1.00, p = 0.049). Similarly, SHBG was associated with fracture in mutually adjusted models (aHR HR 1.26, 95% CI, 1.01-1.58, p = 0.045). In contrast, T (aHR, 1.16, 95% CI, 0.86-1.56, p = 0.324) was not significantly associated with fracture in mutually adjusted models. T, DHT and SHBG were not associated with BMD. T and DHT were both positively associated with LBM in individual models. CONCLUSIONS: In older men, DHT was inversely associated with hip fracture risk and SHBG was positively associated with hip fracture risk, while T was not. Future studies should elucidate the mechanisms by which DHT affects bone health.
BACKGROUND: Little is known about the relationships of dihydrotestosterone (DHT), a more potent androgen than testosterone (T), with bone mineral density (BMD) and fracture risk. Our objectives were to evaluate the relationships of T, DHT and sex hormone binding globulin (SHBG) with BMD, fracture risk, and lean body mass (LBM). METHODS: We evaluated 1128 older men free of cardiovascular disease in a prospective cohort study using data from the Cardiovascular Health Study. T and DHT were measured by liquid chromatography-tandem mass spectrometry and SHBG by fluoroimmunoassay. Our outcomes included incident hip fracture (n = 106) over a median of 10.2 years and BMD and LBM by dual-energy x-ray absorptiometry (n = 439). RESULTS: In Cox regression models mutually adjusted for T, SHBG, and covariates, each standard deviation increment in DHT (0.23 ng/ml) was associated with a 26% lower risk of hip fracture (adjusted hazard ratio [aHR] 0.74, 95% confidence interval (CI) 0.55-1.00, p = 0.049). Similarly, SHBG was associated with fracture in mutually adjusted models (aHR HR 1.26, 95% CI, 1.01-1.58, p = 0.045). In contrast, T (aHR, 1.16, 95% CI, 0.86-1.56, p = 0.324) was not significantly associated with fracture in mutually adjusted models. T, DHT and SHBG were not associated with BMD. T and DHT were both positively associated with LBM in individual models. CONCLUSIONS: In older men, DHT was inversely associated with hip fracture risk and SHBG was positively associated with hip fracture risk, while T was not. Future studies should elucidate the mechanisms by which DHT affects bone health.
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