ACCRETION OF BONE MASS AND STRENGTH WITH PARATHYROID-HORMONE PRIOR TOTHE ONSET OF ESTROGEN DEFICIENCY CAN PROVIDE TEMPORARY BENEFICIAL-EFFECTS IN SKELETALLY MATURE RATS

Intermittent administration of parathyroid hormone (PTH) has been show n to be an anabolic agent for animal and human skeletons. In previous studies, PTH has been used concurrent with, or subsequent to, the onse t of bone loss. However, it is entirely possible that PTH may be used as an anabolic agent in a situation where there is stable skeletal rem odeling. Increasing bone mass at this time might confer long-lasting b eneficial effects when bone loss begins, for example, subsequent to th e loss of ovarian function. To test this hypothesis, we evaluated the effects of administering rat PTH(1-34) (80 mu g/kg/day, subucutaneousl y [sc]) to 6-month-old rats for a 2-week period prior to ovariectomy, and followed the natural occurrence of bone loss over a 14-week period . To determine the effects of estrogen intervention on bone gained by PTH treatment, one group was repleted with 17 alpha-estradiol (10 mu g /kg/day via sc implant), Serial measurements of bone mass in vivo at t he distal femur were obtained at 2-week intervals using dual-energy X- ray absorptiometry, while histologic and mechanical strength data were obtained from excised proximal tibiae and distal femurs after sacrifi ce. Two weeks of PTH treatment resulted in an increase of bone mineral density (BRID), mechanical strength, and cancellous bone volume (CnBV /TV). Four weeks after PTH withdrawal, significant residual beneficial effects on BMD and strength, irrespective of ovarian status, were obs erved, However, 14 weeks after PTH withdrawal, although there were sti ll residual effects on CnBV/TV in ovariectomized animals pretreated wi th PTH, the PTH effects on BMD and mechanical strength had been lost. Estradiol repletion during the rapid bone loss phase following ovariec tomy prevented the reduction in BMD associated with either ovariectomy or PTH withdrawal, Our results suggest that: treatment of rats with P TH prior to ovariectomy produces an increase in BMD and strength, thes e beneficial effects extend for a period of at least three times the t reatment duration, the BMD that is lost when PTH is discontinued equat es to the amount accrued during the PTH treatment, estrogen replacemen t can be used to maintain the bone gained as a result of PTH treatment .