Friday, June 1, 2018

Does Celebrex interfere with tendon healing?

Do Selective COX-2 Inhibitors Affect Pain Control and Healing After Arthroscopic Rotator Cuff Repair?

These authors evaluated the efficacy of a selective COX-2 inhibitor in early postoperative pain control, satisfaction with pain management, and incidence of systemic adverse effects in 180 patients undergoing arthroscopic rotator cuff repair.  Patients were randomly allocated in equal numbers (60 each) to receive a selective COX-2 inhibitor (celecoxib, Celebrex 200 mg twice a day), a traditional NSAID (ibuprofen,  385 mg 3 times a day), or an opioid drug (tramadol 50 mg twice a day) for 2 weeks from the first day after surgery.

Magnetic resonance and ultrasonography images of 82 patients were retrospectively reviewed at least 24 months after surgery, along with the range of motion and pain VAS and functional scores.

There were no significant differences among the 3 groups in terms of pain intensity, incidence of adverse effects, or dosage of rescue medication at 3 days or 2 weeks after surgery. Pain VAS and functional scores at the final follow-up were also comparable among the 3 groups. 

However, the retear rate in the celecoxib group (11/30 [37%]) was significantly higher than those in the ibuprofen (2/27 [7%]) and tramadol (1/25 [4%]) groups (P = .009).

The authors conclude that selective COX-2 inhibitors should not be used for postoperative analgesia because they might negatively affect tendon-tobone healing after surgical repair.

Comment: This is an important randomized clinical trial. 
While this study concerns rotator cuff repair, we must be concerned that its conclusion may be applicable to other tendon to bone repairs, such as the subscapularis repair after shoulder arthroplasty. This is especially relevant because of the widespread use of Celebrex as a part of multimodal pain management in a wide range of shoulder procedures. On one hand, celecoxib is known to produce fewer gastrointestinal adverse effects than do traditional NSAIDs and fewer adverse effects, such as nausea, vomiting, and somnolence than opioid drugs, on the other hand these advantages may be offset by drug-related problems with tendon healing.

Non steroidal drugs are believed to have a negative effect on bone and tendon healing, possibly because COX-2 inhibition may lead to reduced prostaglandin synthesis and inhibition of osteoblast function in the early phase of bone formation.  COX-2-specific NSAIDs have been shown to inhibit enthesis formation after tendon repair in animal models with higher rates of healing failure with COX-2 inhibitors in comparison to nonselective COX inhibitors. The pro-inflammatory COX-2/prostaglandin E2 (PGE-2) pathway is thought to be important in stimulating tenocyte proliferation, adhesion, and migration during the early stage of healing. 

Thus while inflammation is associated with pain, it appears to be an important component of tendon to bone healing as well. Balancing the pros and cons of NSAIDs and especially selective COX-2 inhibitors is now a challenge for shoulder surgeons.


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