Indomethacin and celecoxib improve tendon healing in rats.
Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the formation of bone. However, they have been shown to increase tensile strength in healing tendons. Most NSAIDs inhibit two isoforms of cyclooxygenases called Cox-1 and Cox-2. Thanks to fewer side-effects, the recently introduced selective cyclooxygenase-2 (Cox-2) inhibitors will probably promote more widespread use of this kind of drug. To clarify the effects on tendon healing of a general Cox-inhibitor (indomethacin) as well as a selective Cox-2 inhibitor (celecoxib), we resected 3 mm of the Achilles tendon in rats and measured the strength of the tendon regenerate. Indomethacin given as daily injections in doses of 1.5, 3.0 and 5.0 mg/kg reduced the thickness (cross-sectional area) of the tendon regenerate at 14 days, as compared to controls, but there was no difference in the failure load or stiffness. In another series of measurements, indomethacin in a dose of 3.0 mg/kg reduced the cross-sectional area at 10, 14 and 18 days after transsection. Failure load was not affected, but tensile stress at failure was increased by indomethacin at 14 and 18 days. Indomethacin (3 mg/kg) was then compared to celecoxib (4.5 mg/kg) and controls 14 days after tendon transsection. No difference between the drugs was seen. Again, the transverse area was smaller in the treated tendons than in the controls. Failure load was unchanged and the tensile stress was higher in the treated tendons than in the controls. Because of the reduction in cross-sectional area without an effect on failure load, the use of Cox-inhibitors may be beneficial in clinical situations where thickening of a healing tendon is a problem--e.g., in the hand or shoulder.
Forslund
Carina
C
Orthopedic Department, Lund University Hospital, Lund, Sweden.
Bylander
Birger
B
Aspenberg
Per
P
D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000068579:Celecoxib; D003430:Cross-Sectional Studies; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D007213:Indomethacin / Q000494:pharmacology*; D011720:Pyrazoles; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012680:Sensitivity and Specificity; D013449:Sulfonamides / Q000494:pharmacology*; D013708:Tendon Injuries / Q000188:drug therapy*; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D007213:Indomethacin