Effects of cyclooxygenase inhibitors on bone and cartilage metabolism--a review

In this era of increeasing use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) for treatment of painful/inflammatory disorders, it is necessary to review the effect of these drugs on bone and cartilage metabolism. Inflammation is an essential component of the healing process in bone, and cyclooxygenase (cox-1 and cox-2) enzymes play important roles in fracture repair. Therefore, there is concern that NSAIDs, which have anti-inflammatory and analgesic properties that are mediated by inhibition of cox-1 and cox-2 may delay the healing of bone injuries. Also as newer drugs, selective cox-2 inhibitors are being developed to avert the gastrointestinal symptoms of the non-specific NSAIDs, it is imperative that these substances are studied for any deleterious effect on bone and cartilage metabolism.

Literature on the subject was reviewed using manual library search, articles in journals and internet search. The search words were: NSAIDs and bone metabolism, cyclooxygenase inhibitors and bone metabolism. The search was done using medscape, ortolink and pubmed search engines. The search covered a period of 35 years (1970-2005).

NSAIDs can either reversibly or irreversibly block the cyclooxygenase pathway thereby inhibiting prostaglandin synthesis. These cox inhibitors especially the cox-2 have been found to inhibit the production of prostaglandins which are necessary in bone healing. Prostaglandins play a role in both osteoblastogenesis and bone resorption, and so, cox inhibitors suppress these functions.

NSAIDs especially the cox-2 inhibitors should be avoided following fractures or implant surgery. They should be reserved for other painful inflammatory disorders in which bone resorption and formation mediated by prostaglandins are not required.