antiresorptives

Antiresorptives are medications that reduce bone resorption by osteoclasts, slowing bone remodeling and helping to strengthen bone and lower fracture risk. They are used in conditions characterized by increased bone turnover, most notably osteoporosis, but also in certain cancers with bone involvement and other metabolic bone diseases.

Mechanisms of action vary among agents. Bisphosphonates bind to hydroxyapatite in bone and inhibit osteoclast activity, often inducing osteoclast apoptosis. Denosumab is a monoclonal antibody that targets RANKL, preventing osteoclast formation and activity. Calcitonin directly inhibits osteoclast function. Other drugs, such as selective estrogen receptor modulators, reduce bone resorption by influencing hormonal pathways that regulate osteoclasts. Many antiresorptives have long-lasting effects on bone, but some require periodic dosing or injections, and oral formulations may interact with food or require specific timing.

Common agents include bisphosphonates (oral alendronate, risedronate, ibandronate; intravenous zoledronic acid), denosumab (subcutaneous), calcitonin (nasal or injectable), and selective estrogen receptor modulators (raloxifene). They are used to prevent fractures in postmenopausal osteoporosis and to treat osteoporosis in men, glucocorticoid-induced osteoporosis, Paget’s disease, and hypercalcemia of malignancy. In cancer, antiresorptives help manage bone metastases and reduce skeletal-related events.

Safety considerations include reduced kidney function with some bisphosphonates, hypocalcemia, and rare but serious complications such as osteonecrosis of the jaw and atypical femoral fractures. Rebound increases in bone turnover can occur after stopping denosumab, requiring monitoring and, in some cases, a follow-up treatment plan. Dental evaluation is often recommended before initiating therapy with potent antiresorptives.