Antiresorptive

Antiresorptives are drugs that slow or stop bone resorption, thereby reducing bone turnover and fracture risk. They are used to treat conditions characterized by excessive bone loss, such as osteoporosis, Paget disease, and certain cancers with bone metastases or hypercalcemia. They may be given as oral tablets, injections, or subcutaneous injections.

Most antiresorptives act by inhibiting osteoclast activity or formation. Bisphosphonates bind to bone mineral and disrupt osteoclast function, often triggering osteoclast apoptosis. Denosumab is a monoclonal antibody that targets RANKL, blocking a key signal for osteoclast development and activity. Calcitonin directly inhibits osteoclasts, while selective estrogen receptor modulators and other hormonal strategies can reduce bone resorption by hormonal pathways. Long-standing research has led to a range of agents with varying mechanisms, potencies, and durations of effect.

Common antiresorptives include bisphosphonates such as alendronate, risedronate, ibandronate, and zoledronic acid; denosumab; and, less frequently, calcitonin and certain SERMs like raloxifene. Ongoing monitoring and management consider renal function, calcium levels, and adherence, as well as potential dental risks. Long-term suppression of bone remodeling raises concerns about atypical fractures and osteonecrosis of the jaw, especially after extended use, making treatment duration and drug holidays a consideration in some patients.

Indications typically include prevention and treatment of osteoporotic fractures, relief of bone pain in Paget disease, prevention of skeletal-related events in cancer with bone metastases, and treatment of hypercalcemia of malignancy. Dosing and administration depend on the specific agent, with oral bisphosphonates requiring careful timing relative to meals and hydration, and parenteral agents given by scheduled infusions or injections.