ANABOLIC EFFECTS OF PARATHYROID-HORMONE ON CORTICAL BONE IN OVARIECTOMIZED RATS

The purpose of this study was to determine whether PTH has anabolic effects on cortical bone in ovariectomized (OVX) rats similar to those previously observed in cancellous bone. Groups of OVX rats were untreated for the first 4 weeks postovariectomy followed by treatment for 5-, 10-, or 15-week periods with vehicle, estrogen, the bisphosphonate risedronate (NE-58095), PTH, PTH + estrogen or PTH + NE-58095. A group of sham-operated control rats was treated with vehicle alone. Cross sections of the tibial diaphysis immediately proximal to the tibiofibular junction were subjected to quantitative bone histomorphometry. In comparison to vehicle-treated control rats, the following structural changes were detected in cortical bone of OVX rats after 15 weeks of vehicle treatment: increased cortical bone tissue area, increased cortical bone area, and a trend for increased bone marrow area. Indices of periosteal bone formation were increased in vehicle-treated OVX rats at 5 weeks, but declined to control levels at the later time points. In addition, vehicle-treated OVX rats exhibited a nonsignificant trend for increased endocortical bone formation relative to vehicle-treated control rats throughout most of the study. Estrogen, but not NE-58095, prevented most of the changes in cortical bone structure associated with ovariectomy. In comparison to vehicle treatment of OVX rats, estrogen decreased both periosteal and endocortical bone formation whereas NE-58095 decreased endocortical, but not periosteal, bone formation. Treatment of OVX rats with PTH alone increased cortical bone area and width as well as decreased bone marrow area compared to vehicle-treated OVX rats. The PTH-induced increase in cortical bone mass was associated with a marked increase in periosteal and endocortical bone formation at 5 weeks of treatment. Afterwards, cortical bone formation in PTH-treated OVX rats declined toward the levels of vehicle-treated control and OVX rats. Concurrent treatment of OVX rats with PTH + estrogen or PTH + NE-58095 blunted somewhat the stimulatory effect of PTH on cortical bone formation, but presumably inhibited endocortical bone resorption as well. As a result, the increase in cortical bone area induced by the concurrent treatments was nearly identical to that of PTH alone. The data indicate that PTH, in contrast to estrogen and NE-58095, stimulates cortical bone formation and augments cortical bone mass in the tibial diaphysis of OVX rats. In this animal model, our findings do not support the contention that PTH augments cancellous bone at the expense of cortical bone in the estrogen-deplete skeleton.