New indication: Zoledronic acid (Reclast), a bisphosphonate, was approved on May 29, 2009, for the prevention of osteoporosis in postmenopausal women
Zoledronic acid is a bisphosphonate that inhibits osteoclast-mediated bone resorption. This agent was approved on May 29, 2009, for the prevention of osteoporosis in postmenopausal women.
Efficacy. The efficacy of zoledronic acid for the prevention of postmenopausal osteoporosis was assessed in a 2-year, randomized, multicenter, double-blind, placebo-controlled trial of 581 postmenopausal women with osteopenia. Patients were stratified by the number of years since menopause (Stratum I, <5 years since menopause; Stratum II, ≥5 years since menopause). Patients were randomized to treatment with zoledronic acid (5-mg infusion) at randomization and at Month 12, to treatment with zoledronic acid (5-mg infusion) at randomization and placebo at Month 12, or to treatment with placebo at randomization and at Month 12. All women also received supplemental calcium and vitamin D. The primary end point was the percentage change from baseline in bone mineral density (BMD) at 24 months. Zoledronic acid administered at randomization (with placebo at Month 12) was associated with a 6.3% increase in lumbar spine BMD in Stratum 1 and a 5.4% increase in lumbar spine BMD in Stratum II relative to placebo at 24 months (P<.0001). Zoledronic acid at randomization (with placebo at Month 12) was also associated with a 4.7% increase in total hip BMD in Stratum I and a 3.2% increase in total hip BMD in Stratum II relative to placebo at 24 months (P<.0001).
Safety. Hypocalcemia and mineral metabolism disturbances must be treated before initiation of zoledronic acid therapy. Monitoring of calcium and mineral levels is recommended for these patients. This agent should not be used in patients with severe renal impairment. Cases of renal impairment have been reported in patients treated with zoledronic acid; these cases have more commonly occurred in patients with pre-existing renal compromise or other risk factors. Healthcare professionals should measure serum creatinine levels before every dose of zoledronic acid, and interim monitoring may be warranted in patients at high risk. Bisphosphonate treatment has been associated with osteonecrosis of the jaw. An oral examination should be performed before initiation of bisphosphonate therapy, and patients with concomitant risk factors should avoid invasive dental procedures during bisphosphonate therapy if possible. Zoledronic acid should not be used during pregnancy, as this agent may cause fetal harm. Infrequently, patients taking bisphosphonates have experienced severe and occasionally incapacitating bone, joint, and/or muscle pain. Zoledronic acid should be used with caution in aspirin-sensitive patients, as there have been reports of bronchoconstriction in these patients during zoledronic acid treatment. The most common adverse events associated with zoledronic acid when used for the prevention of postmenopausal osteoporosis include arthralgia, pyrexia, myalgia, pain, chills, headache, and back pain.
Dosing. For the prevention of osteoporosis in postmenopausal women, a 5-mg infusion of zoledronic acid should be administered intravenously over ≥15 minutes every 2 years. Healthcare professionals should ensure that patients are also adequately supplemented with calcium and vitamin D if dietary intake is not sufficient.