What are the possible risks of zoledronic acid (Reclast) for the treatment of osteoporosis?

Updated: Jan 20, 2021
  • Author: Rachel Elizabeth Whitaker Elam, MD, MSc; Chief Editor: Herbert S Diamond, MD  more...
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Answer

In September 2011, the US Food and Drug Administration (FDA) updated the prescribing information for zoledronic acid to provide improved information regarding the risk of kidney failure. Acute kidney injury requiring dialysis and fatal outcomes have been reported to the FDA following the use of zoledronic acid. The drug is contraindicated in patients with moderate to severe renal impairment (ie, creatinine clearance < 35 mL/min) or evidence of acute renal impairment. Risk for renal impairment is also increased by the following [160] :

  • Coadministration of zoledronic acid with nephrotoxic or diuretic medications
  • Severe dehydration before or after administration
  • Advanced patient age

In March 2012, the FDA made safety labeling changes for bisphosphonates, including zoledronic acid, to advise of the risk for atypical subtrochanteric and diaphyseal femoral fractures in patients who have received bisphosphonate therapy, including zoledronic acid. These fractures occur with minimal or no trauma and may present as groin pain weeks to months after fracture. The FDA also includes a safety warning for bisphosphonates, including zoledronic acid, regarding the risk for osteonecrosis of the jaw (ONJ).  [161]  Atypical femur fractures and ONJ are rare events in patients on long term antiresportive agents, including bisphosphonates or denosumab, when used in the treatment of osteoporosis.

The incidence of ONJ in patients on antiresportive therapy for osteoporosis is estimated to be between 1 in 10,000 and 1 in 100,000 per year of use; this risk is only very minimally, if at all, increased compared with the general population. In contrast, the use of IV bisphosphonates and denosumab in cancer patients to reduce complications of metastatic cancer results in substantially higher cumulative doses administered (given increased dose and frequency used for these indications); therefore, atypical femoral fractures and ONJ are more commonly seen when IV bisphosphonates or denosumab are used as part of cancer treatment. [162]

In November 2012, the FDA made safety labeling changes for zoledronic acid to warn against the following adverse reactions [161] :

  • Acute phase reaction within 3 days of zoledronic acid administration: symptoms include pyrexia, fatigue, bone pain and/or arthralgias, myalgias, chills, and influenza-like illness; symptoms usually resolve within 3 days of onset but can take 7-14 days to resolve, and some symptoms may persist for longer 

  • Hypersensitivity reactions presenting as bronchospasms; interstitial lung disease (ILD) with positive re-challenge


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