Antiresorptive agents inhibit osteoclast activity and slow bone remodeling, allowing better mineralization of bone matrix and stabilization of the trabecular microarchitecture. These agents include bisphosphonates, selective estrogen-receptor modulators (SERMs), calcitonin, and postmenopausal estrogen. Bisphosphonates are considered the firstline therapy for osteoporosis. Randomized placebo-controlled trials have shown that bisphosphonates, SERMs, estrogen, calcitonin, and PTH significantly reduce risks for vertebral fractures in postmenopausal women; evidence is less conclusive for nonvertebral fractures, and there are no trial data for treating men.

Estrogen therapy is now contraindicated due to associated risks of breast cancer and vascular thrombosis. Bisphosphonates have been linked to rare risks of osteonecrosis of the jaw and atypical femur fractures, and SERMs increase the risk for thromboembolic events.

Anabolic agents such as PTH stimulate bone formation by acting primarily on osteoblasts but require subcutaneous administration and monitoring for hypercalcemia. PTH is reserved for patients with severe osteoporosis (T scores < −3.5 or < −2.5 with a fragility fracture) or those who have failed or not tolerated other therapies.

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