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From the Clinical Research Centers |
Endocrine Unit, Department of Medicine, Massachusetts General Hospital (J.S.F.), and the Department of Biostatistics, Harvard School of Public Health (D.A.S.), Boston, Massachusetts 02114
Address all correspondence and requests for reprints to: Joel S. Finkelstein, M.D., Endocrine Unit, Bulfinch 327, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114. E-mail: finkelstein{at}helix.mgh.harvard.edu
Although a causal association between estrogen deficiency and bone loss has been established for many years, the mechanism by which estrogen deficiency leads to bone loss is unclear. Estrogen deficiency could induce bone loss either by a direct effect on bone cells to modify the production of bone-resorbing cytokines or by altering the production or response to calcium regulatory hormones such as PTH and 1,25-dihydroxyvitamin D. To assess the effects of ovarian hormones on calcium regulatory hormones, we evaluated the ability of calcium to suppress PTH secretion and the ability of PTH to increase serum 1,25-dihydroxyvitamin D and whole blood ionic calcium levels in women before and after GnRH analog-induced ovarian suppression. Sixteen women with endometriosis underwent iv infusion of calcium (1.1 mg calcium gluconate/cc in 5% dextrose) at a rate of 4 cc/kg·h (n = 7) or human PTH-(134) (Parathar) at a dose of 0.55 U/kg·h (n = 9) before and after 6 months of suppression of ovarian function with the GnRH analog nafarelin acetate (200 µg, intranasally, twice daily). Initial infusions were performed between days 610 of the menstrual cycle. Serum PTH and whole blood ionic calcium levels were measured at -20, -10, and 0 min and then every 10 min for 2 h during iv calcium infusions. Whole blood ionic calcium and 1,25-dihydroxyvitamin D levels were measured every 6 h for 24 h during iv human PTH-(134) infusions.
Serum estradiol levels were markedly suppressed by nafarelin therapy in both groups of women. The relationship between whole blood ionic calcium and serum PTH levels was similar before and during nafarelin-induced ovarian suppression. The net change and rate of rise in serum 1,25-dihydroxyvitamin D levels in response to PTH infusion were similar before and during nafarelin therapy. Peak whole blood ionic calcium and incremental increases in ionic calcium in response to PTH were similar before and during nafarelin therapy.
Our data suggest that ovarian suppression does not alter the regulation of PTH secretion in response to calcium, the ability of PTH to stimulate 1,25-dihydroxyvitamin D formation, or the skeletal sensitivity to PTH. These findings suggest that alterations in calcium regulatory hormones by estrogen deficiency are unlikely to play a major role in the pathogenesis of estrogen deficiency bone loss.
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B. Z. Leder, M. R. Smith, M. A. Fallon, M.-L. T. Lee, and J. S. Finkelstein Effects of Gonadal Steroid Suppression on Skeletal Sensitivity to Parathyroid Hormone in Men J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 511 - 516. [Abstract] [Full Text] |
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