NSAIDs Inhibit Tendon-to-Bone Healing in Rotator Cuff Repair
Authors: Medscape - 2005
References: AOSSM 2004 Annual Meeting. Presented June 25, 2004.
A two-week course of indomethacin or celecoxib significantly inhibits tendon-to-bone healing in rotator cuff repair for eight weeks, according to the results of a preliminary study presented at the annual meeting of the American Orthopaedic Society for Sports Medicine in Quebec City, Canada.
"Rotator cuff healing involves bone growing into the tendon (bone formation at that junction)...and failure rates of healing are pretty high," Scott A. Rodeo, MD, lead author of the study and orthopaedic surgeon and sports medicine specialist at the Hospital for Special Surgery at Cornell Medical Center in New York City, told Medscape. "There's good data now demonstrating that nonsteroidal anti-inflammatory drugs (NSAIDs) can have adverse effects on bone healing...we hypothesized that they may have an adverse effect on rotator cuff repairs."
The study involved 180 rats that underwent acute rotator cuff repair surgery. For two weeks postsurgery, 60 rats were treated with indomethacin (a nonspecific NSAID), 60 with celecoxib (a cyclooxygenase 2 [COX-2] inhibitor NSAID), and the remaining 60 rats received standard rat chow. The animals were then sacrificed at two, four, and eight weeks.
While all tendons in the control group healed, four tendons in the celecoxib group and one tendon in the indomethacin group failed to heal. Biomechanical testing demonstrated significantly lower failure loads in the celecoxib and indomethacin groups compared with the control group at two, four, and eight weeks (P < .001) with no significant difference between the NSAID groups at any time.
Histological analysis showed that the celecoxib and indomethacin groups displayed similar morphology at the tendon-bone attachment site at all time points, remaining poorly organized at eight weeks compared with the control group. The fibrocartilage zone between tendon and bone did not consistently form in these groups.
Birefringence of collagen under polarized light was used to detect differences in collagen deposition and maturation in the healing tendons over time. Significant differences were found between subjects in the control group and the indomethacin group at two weeks (P = .007) and between the control group and both the indomethacin and celecoxib groups at four and eight weeks (P < .001). Birefringence increased over time in the control group but not in the NSAID groups over all time points to eight weeks (P < .001).
"Given that NSAID administration was discontinued after 14 days yet affected load-to-failure eight weeks following repair, it appears that inhibition of the early events in the inflammatory cascade has a lasting negative effect on tendon-to-bone healing," Dr. Rodeo said. "The fact that [indomethacin and celecoxib] had equal effects demonstrates that it's the COX-2 enzyme that probably has a critical role. Studies in bone physiology and bone metabolism have shown that COX-2 has a critical effect in turning on genes in bone cells to create bone."
"Though NSAID use is common following rotator cuff repair and other procedures, it's premature to extrapolate this information to humans," Dr. Rodeo added. "We have some convincing data; however, this should be verified in a larger animal trial before we make recommendations for changes in clinical practice."