Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Their Effect on Musculoskeletal Soft-Tissue Healing: A Scoping Review

Nonsteroidal anti-inflammatory drugs (NSAIDs) are being increasingly employed as a part of multimodal non-opioid strategies to treat postoperative pain. In the present study, we sought to review the effects of short-term NSAID use on musculoskeletal soft-tissue healing.

We performed a scoping review of all studies that included the use of NSAIDs and their effect on healing of soft tissues, which for the purpose of this review refers to non-osseous musculoskeletal tissue such as ligament, tendon, labrum, and meniscus. The inclusion criteria encompassed all studies (human, animal, and in vitro) that evaluated the effect of NSAIDs on soft-tissue healing. Subgroup analyses, wherever applicable, were conducted on the basis of the type of NSAID (cyclooxygenase [COX]-specific or nonspecific) and the type of study (human, animal, or in vitro). Relevant metadata from each study were abstracted, and descriptive statistics were used to summarize the results.

A total of 44 studies met the inclusion criteria, including 3 human studies, 33 animal studies, and 8 in vitro studies. These studies included 4 different NSAIDs in the human subgroup, 16 different NSAIDs in the animal subgroup, and 7 different NSAIDs in the in vitro subgroup. The majority of reported studies (including 1 of 2 human studies, 10 of 14 animal studies, and 3 of 3 in vitro studies) demonstrated that COX-2-selective inhibitors had negative impact on soft-tissue healing. In contrast, the majority of human and animal studies (2 of 2 and 19 of 30, respectively) demonstrated that nonselective COX inhibitors had no negative effect on the healing of labrum, tendons, and ligaments. The majority of in vitro studies demonstrated that NSAIDs have a harmful effect on biological processes involved in tendon-healing and regeneration (tenocyte proliferation, collagen and glycosaminoglycan synthesis).

Current limited evidence demonstrates that selective COX-2 inhibitors can negatively affect healing of musculoskeletal soft tissue after surgical repair. In contrast, the majority of studies demonstrate that nonselective COX inhibitors have no negative effect on musculoskeletal soft-tissue healing. Additional high-quality human clinical trials are necessary to provide more definitive conclusions.