EFFECTS OF RECIPROCAL TREATMENT WITH ESTROGEN AND ESTROGEN PLUS PARATHYROID-HORMONE ON BONE-STRUCTURE AND STRENGTH IN OVARIECTOMIZED RATS

Intermittent administration of PTH has been found to be an effective a nabolic agent in cancellous bone. We have reported previously that com bined treatment with PTH and estrogen in estrogen-deficient rats was b eneficial in correcting established osteopenia. To determine if the be neficial effects of PTH therapy can be preserved by estrogen alone and whether PTH therapy can be effective in treating osteopenic subjects stabilized with estrogen, we have undertaken a ''crossover'' study in the rat model of estrogen-deficiency induced osteopenia. Six-month-old female rats were ovariectomized and after 5 wk treated for 8 wk with vehicle, 30 mu g/kg per day of rPTH(1-34) plus 15 mu g/kg per day of l 7 beta-estradiol or 17 beta-estradiol alone. One group from each treat ment regimen was then sacrificed and for an additional 8 weeks the rem aining rats were (a) maintained on their previous treatment; (b) ''cro ssed over'' to their reciprocal treatment; or (c) administered vehicle only. At the end of this second 8-wk treatment period all rats were s acrificed. Bone mineral density of the distal femur, histomorphometric measurements of the proximal tibia and mechanical testing of the dist al femur and selected vertebral bodies were performed. Our results dem onstrated that (a) the gains in bone mass, trabecular connectivity and mechanical strength induced by PTH can be maintained by estrogen alon e, but are reversed when both agents are withdrawn; and (b) rats with established osteopenia, maintained on estrogen treatment alone, can de rive the full beneficial effects from the addition of PTH to the treat ment at a later date. These data indicate that combined and/or sequent ial use of antiresorptive and anabolic agents may be a promising appro ach to the treatment of osteoporosis.