Indomethacin does not inhibit the anabolic effect of parathyroid hormone on the long bones of rats

Abstract

Chronic administration of parathyroid hormone, hPTH 1-34, increased bone mass in normocalcemic, young rats. Since PTH can stimulate prostaglandin E2 (PGE2) production in bone in vitro, and since PGE2 can stimulate bone formation, the anabolic effect of PTH could be mediated by PGE2. To test this hypothesis, experiments were done to determine if indomethacin, which blocks endogenous PG production, would inhibit the anabolic response of bone to PTH. In the first experiment, male Sprague-Dawley rats, 70-100 g, in groups of five, were treated for 12 days with either hPTH 1-34, 8 micrograms/100g/day; PTH vehicle; indomethacin, 2 mg/kg/day; or a combination of PTH and indomethacin. In the second experiment, groups of 6 rats each were given vehicle or hPTH 1-34, 8 micrograms/100g/day, in combination with indomethacin, 0, 1, 2, or 4 mg/kg/day. Subcutaneous injections of PTH wee given once daily and indomethacin was given orally in divided doses, twice a day. Rats were killed on day 12 in both experiments; their sera were analyzed and the trabecular and cortical bone of distal femurs processed to determine calcium (Ca) and hydroxyproline content and dry weight. PTH and indomethacin had no significant effect on serum Ca, phosphate, alkaline phosphatase, urea nitrogen and creatinine, or systemic and long-bone linear growth. In rats treated with PTH alone or in combination with indomethacin, bone Ca of distal femurs increased by 28-44%; dry weight by 29-41%, and hydroxyproline by 17-45%. Indomethacin alone had no effect on bone growth.(ABSTRACT TRUNCATED AT 250 WORDS)