Effect of treatment for 3 months with human parathyroid hormone 1-34 peptide in ovariectomized cynomolgus monkeys (Macaca fascicularis).

Abstract

Clinical data suggest that PTH may increase cancellous bone mass at the expense of cortical bone in human beings. In this study, the effects of PTH on whole body, axial and appendicular bone mass were studied in an animal model with Haversian cortical bone remodelling. Ovariectomized, young adult, female cynomolgus monkeys were assigned to Placebo (n = 9) or PTH groups (n = 10). The PTH group received 10 micrograms/kg synthetic human PTH(1-34) peptide by SC injection, 3 days/week for 3 months and the Placebo group received vehicle. Spinal and whole body bone mass were measured by DXA, and proximal tibia, distal radius and mid-radius bone mass were measured by quantitative computed tomography (QCT) at baseline and 3 months. Small, transient increases in serum calcium were observed 4 hours after injection with PTH. Compared to placebo-treated animals, PTH-treated monkeys had no change in whole body bone mass, but a 5% increase in spinal bone mineral density. Cortical bone mass measured by QCT at appendicular sites was not affected by PTH treatment, but there were significant increases in cancellous bone mass in the proximal tibia, and a similar trend in distal radius. PTH stimulated dramatic bone gain in the lumbar spine and at appendicular trabecular bone sites during three months' treatment. There was no evidence of cortical bone loss during the same period.