ROCKVILLE, Maryland—In a January 7 "FDA Alert" the US Food and Drug Administration (FDA) warned doctors that severe musculoskeletal pain in patients taking bisphosphonates might be due to the drug. The warning noted that problems have been associated with both intravenous and oral formulations.

"Although severe musculoskeletal pain is included in the prescribing information for all bisphosphonates, the association between bisphosphonates and severe musculoskeletal pain may be overlooked by healthcare professionals, delaying diagnosis, prolonging pain and/or impairment, and necessitating the use of analgesics," the agency said.

The bulletin links these problems to bisphosphonates marketed as Actonel, Actonel+Ca, Aredia, Boniva, Didronel, Fosamax, Fosamax+D, Reclast, Skelid, and Zometa. "Healthcare professionals should consider whether bisphosphonate use might be responsible for severe musculoskeletal pain in patients who present with these symptoms and consider temporary or permanent discontinuation of the drug," the FDA warned.

The agency notes that onset of severe musculoskeletal pain may be within days, months, or years of the patient starts taking a bisphosphonate. Discontinuation resulted in complete relief of symptoms for some patients but in slow or incomplete resolution in other patients.

The severe musculoskeletal pain described in the FDA Alert differs from the acute phase response characterized by fever, chills, bone pain, myalgias, and arthralgias that sometimes accompanies initial administration of intravenous bisphosphonates. The acute-phase problems associated with intravenous bisphosphonates tend to resolve within several days of continued use.

According to the FDA, more debilitating musculoskeletal problems and may occur with initial exposure to once-weekly or once-monthly doses of oral bisphosphonates. The risk factors for and incidence of severe musculoskeletal pain associated with bisphosphonates are unknown.

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