Bone-Protective Pharmacotherapy in Endocrine Disease

Bone is constantly remodeled. Osteoclasts remove older bone, and osteoblasts replace it. When these processes remain balanced, bone maintains both mineral density and internal architecture. Estrogen deficiency, excess thyroid hormone, excess parathyroid hormone, glucocorticoids, and some diabetes therapies can shift remodeling toward resorption or impair new bone formation. The result is not merely a lower bone mineral density (BMD). Trabeculae become thinner and less connected, so a fall from standing height can produce a vertebral, hip, wrist, or humeral fracture. Antiresorptive drugs slow osteoclast activity. Bisphosphonates bind to hydroxyapatite in bone and remain there for years, continuing to suppress resorption after the drug is stopped. Denosumab blocks receptor activator of nuclear factor kappa-B ligand (RANKL), the signal needed for osteoclast formation and survival. Its effect is potent but temporary: when injections stop, osteoclast activity can rebound quickly. Anabolic agents are used when fracture risk is especially high. Intermittent teriparatide, a parathyroid hormone analogue, stimulates osteoblast-mediated bone formation. Romosozumab inhibits sclerostin, increasing bone formation while also decreasing resorption. This dual action produces substantial early gains in bone density, but those gains...