Repetition of continuous PTH treatments followed by periodic withdrawals exerts anabolic effects on rat bone

Various animal experiments and human studies have shown that intermittent injections of parathyroid hormone (PTH) exert anabolic effects on bone, whereas continuous PTH treatment decreases the bone mass and causes hypercalcemia in animals. However, limited data are available with regard to the effects of a repetitive regimen of continuous treatments of PTH followed by periodic withdrawals on the bone metabolism. We investigated the effects of this regimen by comparing the findings of intermittent and continuous PTH treatments in rats. Infusions of PTH for 24 h followed by 6-day withdrawal periods from PTH transiently increased the serum calcium levels on day 1, but these levels were within the normocalcemic range. The repetition of 4 cycles of continuous PTH infusions followed by PTH withdrawals as well as intermittent PTH treatment increased the trabecular bone thickness, osteoblast surface, and bone formation rate. Continuous PTH infusions followed by PTH withdrawals also increased the cortical thickness of the femoral diaphysis and the osteoid volume in trabecular bones, whereas the continuous treatment failed to induce these changes. These findings suggest that continuous PTH treatment followed by PTH withdrawal is a potential regimen that can induce the anabolic effects of PTH in bone metabolism without inducing hypercalcemia.