PROGRAMMED ADMINISTRATION OF PARATHYROID-HORMONE INCREASES BONE-FORMATION AND REDUCES BONE LOSS IN HINDLIMB-UNLOADED OVARIECTOMIZED RATS

Gonadal insufficiency and reduced mechanical usage are two important r isk factors for osteoporosis. The beneficial effects of PTH therapy to reverse the estrogen deficiency-induced bone loss in the laboratory r at are well known, but the influence of mechanical usage in this respo nse has not been established. In this study, the effects of programed administration of PTH on cancellous bone volume and turnover at the pr oximal tibial metaphysis were determined in hindlimb-unloaded, ovariec tomized (OVX), 3-month-old Sprague-Dawley rats. PTH was administered t o weight-bearing and hindlimb-unloaded OVX rats with osmotic pumps pro gramed to deliver 20 mu g human PTH (similar to 80 mu g/kg.day) during a daily l-h infusion for 7 days. Compared with sham-operated rats, OV X increased longitudinal and radial bone growth, increased indexes of cancellous bone turnover, and resulted in net resorption of cancellous bone. Hindlimb unloading of OVX rats decreased longitudinal and radia l bone growth, decreased osteoblast number, increased osteoclast numbe r, and resulted in a further decrease in cancellous bone volume compar ed with those in weight-bearing OVX rats. Programed administration of PTH had no effect on either radial or longitudinal bone growth in weig ht-bearing and hindlimb-unloaded OVX rats. PTH treatment had dramatic effects on selected cancellous bone measurements; PTH maintained cance llous bone volume in OVX weight-bearing rats and greatly reduced cance llous bone loss in OVX hindlimb-unloaded rats. In the latter animals, PTH treatment prevented the hindlimb unloading-induced reduction in tr abecular thickness, but the hormone was ineffective in preventing eith er the increase in osteoclast number or the loss of trabecular plates. Importantly, PTH treatment increased the retention of a baseline flur ochrome label, osteoblast number, and bone formation in the proximal t ibial metaphysis regardless of the level of mechanical usage. These fi ndings demonstrate that programed administration of PTH is effective i n increasing osteoblast number and bone formation and has beneficial e ffects on bone volume in the absence of weight-bearing and gonadal hor mones. We conclude that the actions of PTH on cancellous bone are inde pendent of the level of mechanical usage.