Do non-steroidal anti-inflammatory drugs adversely affect stress fracture healing?

Illustraion: British Journal of Sports Medicine

A short review

P Wheeler and M E Batt

British Journal of Sports Medicine

February 2005, Volume 39, Pages 65-69

Sports medicine doctors in the UK have published a literature review to examine whether non-steroidal anti-inflammatory drugs (NSAIDs) adversely affect the healing of stress fractures. Previous laboratory studies using animal subjects indicated that NSAIDs can affect fracture healing. This link has not been established in human subjects, particularly for stress fractures. Overall, this study is extremely useful given the high usage of NSAIDs in treatment musculoskeletal disorders.

NSAIDs are used primarily for reducing the pain, heat, swelling and redness that is associated with inflammation. The three most commonly used NSAIDs are aspirin (salicylate), acetaminophen and ibuprofen. Aspirin has many trade names by which it is also known. Acetaminophen is manufactured under the trade name Paracetamol, as well as Tylenol and Datril. Other NSAIDs used in sports medicine include Flurbiprofen (Ansaid), Indomethacin (Indocin), Ibuprofen (Advil, Motrin, Nuprin, Nurofen), Naproxen (Naprosyn) and Diclofenac (Voltaren). In the United Kingdom, a few NSAIDs are on restricted sale to the public, but most have a prescription only medicine licence.

Wheeler and Batt cited historical research and an article by Penman in the New Scientist in 2002, which highlighted the effects of NSAIDs on bone healing and put it once more into the public domain. On the basis of previously published animal and human research, Penman discussed whether NSAIDs could interfere with fracture healing. The article states that NSAIDs, including ibuprofen and indomethacin, delay fracture healing by one or two weeks in rats, which is the equivalent to slowing healing by 20–25%, but the trials from which these figures were gleaned are not readily identified. The article concludes with the suggestion that people with healing fractures should avoid NSAIDs and that further investigation is required.

The authors performed literature searches for original publications and reviews. Although no studies were found that examined stress fractures specifically, the authors extended their search to examine the effects of NSAIDs on all types of healing. There are few studies investigating the effects of NSAIDs on bone healing, although it is widely accepted that there is a theoretical risk.

Wheeler and Batt reported that animal studies have shown that NSAIDs, including indomethacin, aspirin, and ibuprofen can all affect healing of a variety of fractures, including those affecting the rat forelimb, vertebra, or femur. All doses of indomethacin appear to cause delayed bone healing, but aspirin only delays healing at levels approaching toxicity.

Prospective studies on the effects of NSAIDs in humans show mixed results. One study showed that patients who received indomethacin had a greater risk of non-union of the long bones than those who received either radiotherapy or no preventative treatment. Retrospective studies of healing and recovery after fractures all showed an adverse effect on bone healing, either delayed bone healing or an increased rate of non-union, by the administration of NSAIDs.

The authors made the conclusion that further studies are required. Until the results of this research are available, they felt that the option of least risk is to avoid the use of NSAIDs in the treatment of patients who are suspected of having stress fractures.

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