Teriparatide (DB06285): A Comprehensive Monograph on the First-in-Class Anabolic Agent for Osteoporosis

Executive Summary

Teriparatide represents a landmark achievement in the management of osteoporosis, establishing a new therapeutic class of bone-forming (anabolic) agents. As a recombinant form of the biologically active 1-34 N-terminal fragment of human parathyroid hormone (hPTH), its mechanism of action is fundamentally distinct from the prevalent antiresorptive therapies. Administered via once-daily subcutaneous injection, teriparatide generates a pulsatile hormonal signal that preferentially stimulates osteoblastic bone formation over osteoclastic resorption. This unique "anabolic window" leads to substantial improvements in bone mass, microarchitecture, and strength.

Clinical evidence, anchored by the pivotal Fracture Prevention Trial and numerous subsequent studies, has unequivocally demonstrated its efficacy in significantly reducing the risk of vertebral fractures in high-risk populations, including postmenopausal women, men with primary or hypogonadal osteoporosis, and patients with glucocorticoid-induced osteoporosis. Head-to-head trials have further established its superiority over oral bisphosphonates in increasing bone mineral density (BMD) and reducing vertebral fracture incidence.

The therapeutic journey of teriparatide has been shaped by a decades-long concern regarding a preclinical finding of osteosarcoma in rats. This led to a "black box" warning and a two-year lifetime treatment limit. However, extensive post-marketing surveillance and real-world data from millions of patients have not substantiated this risk in humans, culminating in the removal of the boxed warning by the U.S. Food and Drug Administration (FDA) in 2020. This regulatory evolution has reshaped the risk-benefit assessment, allowing for more flexible use in patients with sustained high fracture risk.