Bisphosphonate Therapy

 Linked to Risk for Severe

 Musculoskeletal Pain

January 8, 2008 — Temporary or permanent discontinuation of bisphosphonate therapy should be considered in patients who present with severe musculoskeletal pain, the US Food and Drug Administration (FDA) warned healthcare professionals yesterday. Overlooking bisphosphonate therapy as a causal factor may delay diagnosis, thereby prolonging pain and/or impairment and the use of analgesics. In contrast with the acute-phase response that sometimes accompanies initial exposure to bisphosphonate therapy, some patients experience severe and sometimes incapacitating bone, joint, and/or muscle pain that begins months or years later.

The incidence rate and risk factors for this reaction remain unknown, according to an alert sent from MedWatch, the FDA's safety information and adverse event reporting program. Moreover, discontinuation of therapy may not lead to complete relief — some patients have reported slow or incomplete resolution of symptoms.

Over the next 6 months, the FDA will be evaluating reports of severe musculoskeletal pain associated with bisphosphonate use. In the interim, patients reporting these symptoms should be monitored, and alternative causes for pain should be considered for those who do not experience a lessening or resolution of symptoms after bisphosphonate withdrawal.

Bisphosphonates are indicated for the prevention and treatment of osteoporosis and for treating hypercalcemia of malignancy and Paget's disease. They also are beneficial in patients with multiple myeloma and bone metastases from solid tumors.

Currently marketed oral bisphosphonates include risedronate sodium tablets (Actonel and Actonel + Ca, Proctor & Gamble Pharmaceuticals, Inc), alendronate sodium tablets (Fosamax and Fosamax + D, Merck & Company, Inc), ibandronate sodium tablets (Boniva, Roche), etidronate disodium tablets (Didronel, Proctor & Gamble), and tiludronate disodium tablets (Skelid, sanofi-aventis US, LLC).

Injectable bisphosphonates include pamidronate disodium injection (Aredia, Novartis Pharmaceuticals Corp) and zoledronic acid injection (Reclast and Zometa, Novartis).

Adverse events related to bisphosphonate use should be reported to the FDA's MedWatch reporting program by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787.