ESTROGEN PROTECTION AGAINST BONE RESORBING EFFECTS OF PARATHYROID-HORMONE INFUSION - ASSESSMENT BY USE OF BIOCHEMICAL MARKERS

Objective: Because parathyroid hormone (PTH) stimulates bone resorption, resistance to its actions might help maintain bone mass. We tested the hypothesis that the effects of estrogen on bone are accomplished in part by decreasing the sensitivity of the skeleton to the resorbing effects of PTH. Study Design: Comparison of response to PTH infusion in untreated and estrogen-treated postmenopausal women with osteoporosis. Intervention: (1-34) human PTH, 0.55 U/(kg.h), was infused intravenously over 20 hours. Setting: The inpatient clinical research unit of a referral hospital. Patients: Women with primary postmenopausal osteoporosis who were untreated (n = 15) or treated with estrogen (n = 17). Main Outcome Measures: Skeletal turnover indices including hydroxyproline, deoxypyridinoline, pyridinoline, tartrate-resistant acid phosphatase, alkaline phosphatase, bone Gla protein, and insulin-like growth factor-1. Results: All basal indices were higher in untreated than in estrogen-treated women, but statistical differences were seen only for deoxypyridinoline and pyridinoline. During the 20-hour infusion, hydroxyproline/creatinine increased 0.023 mumol/mumol in untreated women but only 0.010 mumol/mumol in estrogen-treated women (P < 0.05). Corresponding changes for deoxypyridinoline/creatinine were 14.6 mumol/mumol and 3.5 mumol/mumol (P = 0.06). Tartrate-resistant acid phosphatase and pyridinoline increased only in the untreated group. A circadian rhythm in circulating bone Gla protein was seen in both groups without clear PTH-induced effects or differences between groups. Alkaline phosphatase levels and insulin-like growth factor-1 decreased in both groups with no distinction between untreated and estrogen-treated women. Conclusion: The estrogenized postmenopausal osteoporotic skeleton is less sensitive to the bone resorbing effects of acutely administered PTH. There are no differential effects on bone formation.