Increased trabecular bone mass in rats treated with human synthetic parathyroid hormone

Although PTH inhibits bone collagen synthesis acutely, prolonged administration of PTH increases trabecular bone mass. The objectives of this study were to develop a simple method to quantitate the anabolic response of cortical and trabecular bone, to determine if the trabecular bone response is at the expense of cortical bone, and to correlate the bone response with changes in serum calcium or phosphate. Subcutaneous injections of 2 to 16 micrograms/100 g body weight hPTH(1-34) were given daily to weanling rats for 12 days. The trabecular and cortical bone were manually separated from the distal femur, and calcium, hydroxyproline, and extracted dry weight were measured. Growth and renal function were not impaired. Serum calcium (range: 8.9-9.5 mg%) and serum phosphate (range: 7.7-8.5 mg%) did not differ significantly from control serum calcium, 9.1 mg%, or serum phosphate, 8.1 mg%. A dose-related anabolic response was observed in calcium, hydroxyproline, and dry weight of trabecular bone. At the highest dose of hPTH for 12 days, these values were increased above control by 26%, 33%, and 26%, respectively (P less than .01). While cortical bone values increased over 12 days, only the dry weight increase was significant (P less than .01). Our method showed an increase in trabecular bone mass after daily subcutaneous injections of hPTH (1-34) at doses that were neither toxic nor hypercalcemic. Although the absolute change of cortical bone mass was greater than that of trabecular bone, it was more variable and not statistically significant. Nevertheless, these results indicate that trabecular bone mass did not increase at the expense of cortical bone.