Once daily subcutaneous injections of human or bovine parathyroid hormone cure estrogen deficiency osteoporosis in rats, increasing trabecular and cortical bone mass and strength to normal or supra-normal levels. When daily subcutaneous injections of PTH are administered to humans, the increases in trabecular bone mass are much less dramatic than the increases in trabecular bone in PTH-treated rats. Furthermore, cortical bone mass does not increase at all in PTH-treated humans. It is not clear whether therapeutic results differ in rats and humans because their skeletons differ, or because their extra-skeletal responses to PTH injections differ, or because PTH pharmacokinetics and PTH doses differ in rats and humans. It is difficult to investigate all these possibilities in humans and we have therefore been testing whether non-human primates can be used to study the skeletal effects of PTH. We selected 30 healthy, adult, non-pregnant, non-lactating female Macaca mulatta and measured their lumbar spine and forearm cortical bone mineral density (BMD) by DXA in consultation with scientists at Hologic, Inc., manufacturer of our DXA equipment. We then separated the monkeys into three groups, matched for lumbar spine BMD, forearm cortical (diaphyseal) BMD and body weight and randomly assigned groups to receive once-daily subcutaneous injections of vehicle or human parathyroid hormone for six months. We repeated DXA measurements every month, and at the same times measured the concentrations of calcium, inorganic phosphate, alkaline phosphatase and osteocalcin in the monkeys' serum. Neither dose of hPTH 1-38 altered spine or fore mass. Further studies indicate that hPTH administered to monkeys is more bioavailable than in rats, with prolonged absorption following subcutaneous administration. These considerations suggest that the effects of hPTH treatment on bone mass depend critically on the hormone's pharmacokinetics. Furthermore, conventional pharmacokinetic analyses (Cmac
Showing the most recent 10 out of 365 publications
