Bisphosphonate Therapy
Linked to Risk for Severe
Musculoskeletal Pain
Yael Waknine
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
