Molecular, biochemical and cellular biology of PTH anabolic action.

PTH is a single chain polypeptide with 84 amino acids. The N-terminal region, 1-34, is a biologically active fragment. PTH has both anabolic and catabolic actions on bone. Bauer et al. demonstrated that PTH extract increased trabecular bone in some animals and Selye et al. provided histology evidence that parathyroid extract, when administered in very small doses to rat pups, stimulated osteoblasts and increased bone apposition. The first clinical trial conducted with PTH was performed in 21 patients with osteoporosis treated with human PTH (1-34) [hPTH (1-34)]. In this study, the [hPTH (1-34)] was given as once-daily subcutaneous injections with an increase of 70% above mean baseline values of trabecular bone. Intermittent treatment with PTH increases osteoblast number and bone formation. The skeletal effects of PTH depend upon the pattern of systemic exposure. Once-daily administration of PTH stimulates new bone formation on trabecular and cortical bone surfaces by preferential stimulation of osteoblastic activity over osteoclastic activity. By increasing new bone formation, PTH improves bone mass and bone strength, and thereby reduces the risk of fracture. PTH (1-34) is currently being safely and effectively used in osteoporosis, and together with novel PTH derivates agent provides more tools for the clinicians in their armamentarium for the fight against osteoporosis.