Effect of COX-2 inhibition on tendon-to-bone healing and PGE2 concentration after anterior cruciate ligament reconstruction

Abstract

BackgroundNon-steroidal anti-inflammatory drugs are commonly used to reduce pain and inflammation in orthopaedic patients. Selective cyclooxygenase-2 (COX-2) inhibitors have been developed to minimize drug-specific side effects. However, they are suspected to impair both bone and tendon healing. The objective of this study is to evaluate the effect of COX-2 inhibitor administration on tendon-to-bone healing and prostaglandin E (PGE2) concentration.MethodsThirty-two New Zealand white rabbits underwent reconstructions of the anterior cruciate ligaments and were randomized into four groups: Two groups postoperatively received a selective COX-2 inhibitor (Celecoxib) on a daily basis for 3 weeks, the two other groups received no postoperative COX-2 inhibitors at all and were examined after three or 6 weeks. The PGE2 concentration of the synovial fluid, the osseous integration of the tendon graft at tunnel aperture and midtunnel section, as well as the stability of the tendon graft were examined via biomechanic testing.ResultsAfter 3 weeks, the PGE2 content of the synovial fluid in the COX-2 inhibitor recipients was significantly lower than that of the control group (p = 0.018). At the same time, the COX-2 inhibitor recipients had a significantly lower bone density and lower amount of new bone formation than the control group (p = 0.020; p = 0.028) in the tunnel aperture. At the 6-week examination, there was a significant increase in the PGE2 content within synovial fluid of the COX-2 inhibitor recipients (p = 0.022), whose treatment with COX-2 inhibitors had ended 3 weeks earlier; in contrast, the transplant stability decreased and was reduced by 37% compared to the controls.ConclusionsSelective COX-2 inhibitors cause impaired tendon-to-bone healing, weaken mechanical stability and decrease PGE2 content of the synovial fluid. The present study suggests a reluctant use of COX-2 inhibitors when tendon-to-bone healing is intended.

Evaluation of the Rheologic and Physicochemical Properties of a Novel Hyaluronic Acid Filler Range with eXcellent Three-Dimensional Reticulation (XTR™) Technology

“…Therefore, additional hyaluronidase sessions are usually needed for patients receiving fillers with higher HA concentration [ 10 ]. However, different studies have demonstrated contradictory results attributed to disparities in hyaluronidase source (bovine, ovine, recombinant human), doses used, as well as diverse experimental formats [ 9 ].…”

“…HA filler degradability by hyaluronidase can be considered as a “safety-feature” and gives a filler a potential edge over its competitors [ 9 ]. Technical errors, such as overfilling/overcorrection or filler placement at the wrong soft tissue plane or misplacement, may be reversed by hyaluronidase administration.…”

“…Thus, it is important for practitioners to find that delicate balance between stability and degradability to determine which fillers are best suited for their patients. Degradability studies have highlighted that HA content, cohesivity and crosslinking properties may play a role in the sensitivity of these fillers to enzymatic degradation [ 9 , 11 ].…”

Do Nonsteroidal Anti-Inflammatory Drugs Affect Tissue Healing After Arthroscopic Anterior Cruciate Ligament Reconstruction?

“…Although NSAIDs have so many advantages, these drugs have been reported to potentially impair musculoskeletal healing in several previous basic experimental studies [ 12 , 13 , 28 , 29 ]. These experimental studies found that NSAIDs could have a negative effect in decreasing inflammatory cell signaling during inflammatory and proliferative phase of tendon healing.…”

“…In recent years, selective COX-2 inhibitors, including celecoxib, have become more popular because they can provide similar effect in pain control and reduce incidence of side effects of traditional NSAIDs and opioid [ 11 ]. However, recent basic science studies have reported selective COX-2 inhibitors could impair tendon-to-bone healing, weakening mechanical stability of joints [ 12 , 13 ]. Whether selective COX-2 inhibitors postpone healing of ACL resulting in reduced functional outcomes remains unclear.…”