Teriparatide

Teriparatide is a recombinant form of the biologically active N-terminal fragment (amino acids 1-34) of human parathyroid hormone (PTH). While continuous PTH elevation (as in hyperparathyroidism) causes bone loss, the intermittent administration of PTH paradoxically stimulates new bone formation — a phenomenon that has been exploited therapeutically. Approved by the FDA in 2002 and marketed as Forteo, teriparatide was the first anabolic (bone-building) agent approved for the treatment of osteoporosis.

The anabolic effect of intermittent PTH administration is mediated through direct stimulation of osteoblasts (bone-forming cells). When PTH levels rise briefly and then fall (as occurs with daily teriparatide injection), it preferentially activates osteoblast activity over osteoclast (bone-resorbing) activity, resulting in net bone formation. This is fundamentally different from antiresorptive agents (bisphosphonates, denosumab), which work by slowing bone breakdown rather than building new bone.

The pivotal Fracture Prevention Trial demonstrated that teriparatide 20 mcg daily reduced the risk of new vertebral fractures by 65% and non-vertebral fractures by 53% over a median of 19 months in postmenopausal women with severe osteoporosis. These results represented unprecedented fracture risk reduction and established teriparatide as the treatment of choice for patients with severe osteoporosis, particularly those with multiple fractures or very low bone density who need rapid bone density improvement.

An important clinical consideration is the "anabolic window" concept — teriparatide is most effective when used as the first-line injectable therapy, as prior bisphosphonate use may blunt the early anabolic response. After completing a course of teriparatide (maximum 2 years), patients should transition to an antiresorptive agent to maintain the bone density gains. Failure to follow teriparatide with antiresorptive therapy results in rapid bone loss.