Teriparatide

The body makes endogenous parathyroid hormone (PTH), which has 84 amino acids, and it is the main regulator of calcium and phosphate metabolism in bone and kidney. Its normal actions include regulating bone metabolism, renal tubular reabsorption of calcium and phosphate, and intestinal calcium absorption. Both PTH and teriparatide work by binding to specific high-affinity receptors on the cell surface.

Teriparatide is the same as the first 34 amino acids (the N-terminal end) of PTH. These bind to the receptors with the same affinity and have the same physiological actions on bone and kidney. Teriparatide is not expected to accumulate in bone or other tissues.

How teriparatide affects the skeleton depends on the pattern of systemic exposure. When it is given once daily, it stimulates new bone formation on trabecular and cortical (periosteal and/or endosteal) bone surfaces, because it stimulates osteoblastic activity more than osteoclastic activity. In monkey studies, teriparatide improved trabecular microarchitecture and increased bone mass and strength by stimulating new bone formation in both cancellous and cortical bone. In humans, its anabolic effects show up as an increase in skeletal mass, an increase in markers of bone formation and resorption, and an increase in bone strength.

The picture is different when endogenous PTH stays in continuous excess, as it does in hyperparathyroidism. That may harm the skeleton, because bone resorption may be stimulated more than bone formation.