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Altered Hydroxylation of Estrogen in Patients with Postmenopausal Osteopenia

Department of Internal Medicine, Yonsei University College of Medicine (S.K.L., Y.J.W., J.H.L., S.H.K., E.J.L., K.R.K., H.C.L., K.B.H.); and the Doping Control Center, Korean Institute of Science and Technology (B.C.C.), Seoul, Korea

Address all correspondence and requests for reprints to: Sung Kil Lim, M.D., Department of Internal Medicine, Yonsei University College of Medicine, 134 Shin-chon Dong Sue Dae Moon Gu, 120–752 Seoul, Korea.

To study the possible contributions of the differences in estrogen metabolism to bone mass in postmenopausal osteopenia, spinal and femoral bone mineral densities (BMD) were measured, and 18 urinary metabolites of estrogen were analyzed by a gas chromatography-mass spectrometry assay system in 59 postmenopausal women (5–10 yr after menopause). The BMD of the spine and femoral neck showed positive correlations with body weight, height, and body mass index as we expected. Compared to nonosteopenic subjects, there were no significant differences in serum estrone (E₁) and estradiol (E₂) levels in patients with osteopenia. However, the urinary 16-hydroxyestrone [16-(OH)E₁] level was significantly lower in patients with spinal osteopenia (P < 0.001). Among the 18 urinary metabolites of estrogen, the 16-(OH)E₁ and 16-(OH)E₁/2-hydroxyestrone [2-(OH)E₁) ratio showed positive correlations with spinal BMD (P < 0.05), whereas 2-(OH)E₂ showed a negative correlation with femoral neck BMD (P < 0.05). The urinary 16-(OH)E₁ level also revealed a positive correlation with the age-matched z score of BMD in the spine (P < 0.05). In multiple stepwise regression analysis, weight, 16-(OH)E₁, interaction between 16-(OH)E₁ and 2-(OH)E₂, 2-(OH)E₂, and years after menopause were statistically significant for spinal BMD (r² = 0.4968). For femoral neck BMD and weight, 16-(OH)E₁ and 2-(OH)E₂ were the independent determinants (r² = 0.3369). In conclusion, the activity of estrogen 16-hydroxylase was decreased and/or the activity of estrogen 2-hydroxylase was enhanced in postmenopausal osteopenia. We speculated that these derangements may serve as contributing factors for the acceleration of bone loss in postmenopausal osteoporosis.

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