Clinical Medicine Reviews in Women's Health

Postmenopausal osteoporosis is a disease associated with increased morbidity and mortality. Oral bisphosphonates administered once weekly are associated with adverse events from the upper gastrointestinal system, leading to poor adherence. Zoledronic acid is a nitrogen containing third-generation bisphosphonate approved for the treatment of postmenopausal osteoporosis. It is a potent antiresorptive agent which expresses high affinity for the hydroxyapatite of the bone and accumulates at sites of increased bone turnover. Adverse events include fever, flu-like symptoms, myalgia, arthralgia, and headache, while rare adverse effects include hypocalcemia, renal dysfunction, atrial fibrillation, and osteonecrosis of the jaw. The drug is excreted intact through kidneys. Until recently, the recommended dosage was 5 mg given as an annual intravenous infusion. In 2009, intravenous zoledronic acid 5 mg was approved for the treatment of postmenopausal osteoporosis as a single infusion every two years. This review summarizes all evidence supporting the efficacy of a single biennial 5 mg dose against postmenopausal osteoporosis. The FDA approval was based on a clinical randomized trial which included osteopenic postmenopausal women and showed that BMD in all measured sites remained increased 24 months after the infusion. Many studies showed similar results concerning BMD and also demonstrated that bone turnover markers remained suppressed for > 12 months. The less frequent administration of zoledronic acid is expected to improve adherence and decrease the adverse events, leading subsequently to improved clinical results.