Teriparatide

Teriparatide is a recombinant form of the first 34 amino acids of human parathyroid hormone (PTH 1-34) and the first anabolic osteoporosis treatment approved by the FDA. Sold under the brand name Forteo, it stimulates new bone formation on trabecular and cortical surfaces and is indicated for postmenopausal women, men with osteoporosis, and patients with glucocorticoid-induced osteoporosis at high fracture risk. It became generic (Bonsity) in 2019.

Teriparatide binds to the PTH1 receptor (PTH1R) on osteoblasts and osteoblast precursors, activating the Gs-protein/cAMP/PKA and Gq-protein/PLC/PKC pathways. Intermittent once-daily administration creates transient PTH1R stimulation that preferentially activates osteoblasts over osteoclasts, resulting in net bone formation. The drug increases osteoblast number by promoting differentiation from precursors and inhibiting osteoblast apoptosis, increases periosteal bone formation, and enhances cancellous connectivity. Continuous PTH exposure (unlike once-daily pulses) stimulates both formation and resorption; the pulsatile dosing exploits the anabolic window. Bone mineral density increases are seen at spine and hip within 3–6 months of treatment.

The pivotal Fracture Prevention Trial (n=1,637) demonstrated teriparatide reduced vertebral fractures by 65% and non-vertebral fractures by 53% versus placebo over 21 months. Significant BMD increases occur at the lumbar spine (+9%) and femoral neck (+3%) within 18 months. Studies confirm superiority to antiresorptives for spine BMD gains. The drug is approved for up to 2 years of cumulative lifetime use due to osteosarcoma risk observed in rat carcinogenicity studies (high dose, lifetime exposure); no osteosarcoma cases attributable to teriparatide have been reported in humans after 20+ years of clinical use.