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Am Fam Physician. 2008;78(4):508-509

Author disclosure: Nothing to disclose.

Zoledronic acid (Reclast) is a parenteral, once-yearly bisphosphonate labeled for the treatment of osteoporosis in postmenopausal women.

NameDosageDose formApproximate cost*
Zoledronic acid (Reclast)5-mg intravenous infusion over at least 15 minutes once a year5 mg per 100 mL solution$1,250


Serious adverse effects with zoledronic acid are infrequent. Osteonecrosis of the jaw is a rare condition reported with all bisphosphonates, but mostly in patients with cancer receiving intravenous bisphosphonates who subsequently have dental procedures. It has been reported less often in patients without cancer. The manufacturer and the American Dental Association recommend that major dental work be completed before treatment is started and that invasive dental procedures be avoided during treatment1,2 ; however, one study with more than 3,000 patients receiving zoledronic acid did not demonstrate any instance of osteonecrosis following a dental procedure.3

An acute phase reaction characterized by fever, bone pain, myalgias, and arthralgias may occur shortly after the drug is administered. It tends to resolve within several days and with continued use. In contrast, a syndrome of severe, incapacitating bone, joint, or musculoskeletal pain in patients taking bisphosphonates, including zoledronic acid, may occur days, months, or years after starting therapy. Symptoms may resolve upon discontinuation of therapy, but slow or incomplete resolution has been reported. The risk factors and incidence have not been identified at this time.1,4 Bisphosphonates may remain in bone for years and accumulate the longer they are used. This long duration of activity may explain why osteonecrosis and joint and musculoskeletal pain can occur years after treatment is discontinued.

Although most adverse effects involve the musculoskeletal system, atrial fibrillation may occur slightly more often in patients receiving zoledronic acid.1,5 A causal relationship has not been established.


Influenza-like symptoms, such as fever, myalgia, arthralgia, and headache, can occur following administration. These symptoms may begin within three days of administration, with resolution in three to 14 days. Acetaminophen or ibuprofen (Motrin) may reduce these symptoms.1


Zoledronic acid has been shown to decrease spine and hip fractures in two studies.5,6 It has been studied in women with a mean age of 73 years who are at high risk of fracture (three-year risk of any fracture of 12.8 percent). In combination with calcium and vitamin D, yearly treatment with zoledronic acid decreases the risk of hip fracture, with one fracture prevented for every 107 patients treated for three years (number needed to treat [NNT] = 107; 95% confidence interval [CI], 64.7 to 290.7). Clinically apparent vertebral fractures are also decreased (NNT = 59; 95% CI 44.9 to 84.2).5 There have been no studies with patient-oriented outcomes that compare other bisphosphonates with zoledronic acid for the treatment of osteoporosis.

Zoledronic acid also decreases subsequent fractures and overall mortality in patients treated after an initial hip fracture. In these patients with a much higher likelihood of a subsequent fracture (14 percent), one fracture is prevented for every 23 patients treated for two years (NNT = 23; 95% CI, 14.1 to 55.3). One death (from any cause) is prevented for every 27 patients who received zoledronic acid instead of placebo (NNT = 27; 95% CI, 15.4 to 96.3).6


Zoledronic acid costs approximately $1,250 per dose, given once a year. This course of treatment costs less than one year of intravenous ibandronate (Boniva) given every three months ($1,940), but costs more than one year of any of the oral bisphosphonates given monthly.


Zoledronic acid is administered as a 5-mg, 15-minute infusion once a year. It should not be used in women with a creatinine clearance of less than 35 mL per minute (0.58 mL per second), and patients should be well hydrated before the infusion is given, especially if receiving diuretic treatment. Patients need to take usual daily dosages of calcium (1,000 to 1,500 mg) and vitamin D (800 to 1,000 IU).1

Bottom Line

Zoledronic acid, in combination with calcium and vitamin D, will reduce the risk of vertebral fractures, and to a lesser extent, hip fractures in women with osteoporosis. It decreases subsequent fractures and mortality in high-risk patients who have had a hip fracture. Zoledronic acid may be most useful for women who are unable to tolerate, or have difficulty remembering to take, oral bisphosphonates.

STEPS new drug reviews cover Safety, Tolerability, Effectiveness, Price, and Simplicity. Each independent review is provided by authors who have no financial association with the drug manufacturer.

This series is coordinated by Allen F. Shaughnessy, PharmD, assistant medical editor.

A collection of STEPS published in AFP is available at

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