ALTERED HYDROXYLATION OF ESTROGEN IN PATIENTS WITH POSTMENOPAUSAL OSTEOPENIA

To study the possible contributions of the differences in estrogen met abolism 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 a ssay system in 59 postmenopausal women (5-10 yr after menopause). The BMD of the spine and femoral neck showed positive correlations with bo dy weight, height, and body mass index as we expected. Compared to non osteopenic subjects, there were no significant differences in serum es trone (E(1)) and estradiol (E(2)) levels in patients with osteopenia. However, the urinary 16 alpha-hydroxyestrone [16 alpha-(OH)E(1)] level was significantly lower in patients with spinal osteopenia (P < 0.001 ). Among the 18 urinary metabolites of estrogen, the 16 alpha-(OH)E(1) and 16 alpha-(OH)E(1)/2-hydroxyestrone [2-(OH)E(1)) ratio showed posi tive correlations with spinal BMD (P < 0.05), whereas 2-(OH)E(2) showe d a negative correlation with femoral neck BMD (P < 0.05). The urinary 16 alpha-(OH)E(1) level also revealed a positive correlation with the age-matched z score of BMD in the spine (P < 0.05). In multiple stepw ise regression analysis, weight, 16 alpha-((OH)E(1), interaction betwe en 16 alpha-(OH)E(1) and 2-(OH)E(2), 2-(OH)E(2), and years after menop ause were statistically significant for spinal BMD (r(2) = 0.4968). Fo r femoral neck BMD and weight, 16 alpha(-(OH)E(1) and 2-(OH)E(2) were the independent determinants (r(2) = 0.3369). In conclusion, the activ ity of estrogen 16 alpha-hydroxylase was decreased and/or the activity of estrogen 2-hydroxylase was enhanced in post menopausal osteopenia. We speculated that these derangements may serve as contributing facto rs for the acceleration of bone loss in postmenopausal osteoporosis.