FDA Warns of Potential Side Effect of Bisphosphonate Use

Earlier this week, the FDA issued an alert highlighting the possibility of severe and sometimes incapacitating bone, joint and/or muscle pain in patients taking bisphosphonates. The agency is encouraging health care professionals to assess whether severe musculoskeletal pain in patients taking bisphosphonates, which are frequently prescribed to treat or prevent osteoporosis, could be attributed to their use of these drugs and to consider temporarily or permanently discontinuing their use.

The severe musculoskeletal pain that prompted the alert may occur within days, months, or years after starting a bisphosphonate and should not be confused with the acute phase response that sometimes accompanies initial administration of intravenous bisphosphonates and that also may occur with initial exposure to once-weekly or once-monthly doses of oral bisphosphonates, say FDA officials. The symptoms related to the acute phase response, which may include fever, chills, bone pain, myalgias and arthralgias, typically resolve within several days with continued drug use.

In contrast, the musculoskeletal pain symptoms described in the FDA alert may or may not resolve after discontinuing bisphosphonate use. Some patients have reported complete relief of symptoms after discontinuing the bisphosphonate, whereas others have reported slow or incomplete resolution.

The risk factors for and incidence of severe musculoskeletal pain associated with bisphosphonates are unknown.

Bisphosphonates decrease bone resorption by inhibiting osteoclast activity or through other mechanisms. Among the agents included in this class of drugs are alendronate sodium, marketed both as a generic and under the brand name Fosamax; ibandronate sodium, marketed as Boniva; and risedronate sodium, marketed as Actonel. Each of these drugs is indicated and widely prescribed for the treatment or prevention of osteoporosis in postmenopausal women.

Additional bisphosphonates currently approved for use in the United States are etidronate disodium, sold as Didronel; pamidronate disodium, sold as Aredia; tiludronate disodium, sold as Skelid; and zoledronic acid, sold (for different indications) under the brand names Reclast and Zometa.

Other indications for which agents in this class of drugs are used include:

Further background information, as well as additional recommendations and considerations for physicians and other health care providers, is available online from the FDA's Center for Drug Evaluation and Research.

Adverse events associated with use of these or any other drugs should be reported to the FDA's MedWatch program.