Non‐Steroidal Anti‐Inflammatory Drugs, Cyclooxygenase‐2 and the Bone Healing Process

Abstract

Traditional non-steroidal anti-inflammatory drugs (NSAID) and selective cyclooxygenase-2 (COX-2) inhibitors are widely used in the treatment of pain, including bone fracture pain and orthopaedic post-operative pain. The gastrointestinal and cardiovascular adverse effects of NSAIDs are acknowledged, but their effects on bone are less widely known.Prostaglandins play an important role in the regulation of osteoblast and osteoclast functions, and inhibition of prostaglandin production retards bone formation. Therefore, NSAIDs could be expected to have significant consequences in divergent clinical situations where bone formation or remodelling is a contributing factor. The present survey reviews current experimental and clinical evidence related to two of those conditions (i.e. on ectopic bone formation and on bone fracture healing). NSAIDs are used clinically to prevent ectopic bone formation (also known as heterotopic ossification) (e.g. after total hip arthroplasty or trauma). The efficacy of NSAIDs in the avoidance of heterotopic ossification has been documented in controlled clinical trials, but the inherent risks (e.g. on healing processes and on loosening of prostheses) need further studies. At the same time, NSAIDs are widely used in the treatment of fracture pain, and their inhibitory effects on the ongoing bone healing process have raised concerns. Results of fracture healing studies in animals treated with NSAIDs or in mice lacking COX-2 gene show that inhibition or deficiency of COX-2 impairs the bone healing process. The limited clinical data also support the assumption that inhibition of COX-2 by non-selective or COX-2-selective NSAIDs delays fracture healing. However, the clinical significance of the effect in various patient groups needs to be carefully assessed and further investigations are needed to characterize the patients at the highest risk for NSAID-induced delayed fracture healing and its complications. In the meantime, use of NSAIDs in fracture patients should be cautious, keeping in mind the benefits of pain relief and inhibition of ectopic bone formation on one hand, and the risks of non-union and retarded union on the other hand.

A systematic review of the therapeutic interventions for heterotopic ossification after spinal cord injury

“…Another NSAID used in HO prevention, celecoxib, has been shown in other populations to be as effective an antiinflammatory medication as indomethacin with fewer gastrointestinal adverse effects. 39 Hence, it is reasonable to assume that it may be as effective in patients with SCI and should be further studied in this population. Radiotherapy for prevention of HO after SCI also acts through the inhibition of mesenchymal cell differentiation.…”

Conservative Treatment with Continuous Cryotherapy as a Japanese Judo Therapy for Jones Fracture: A Case Report

“…These phenomena are often observed in the healing process of adult fractures irrespective of the use of cryotherapy. It has been reported that osteoclasts in the healing process of fractures are absorbed in the damaged bones to rebuild new bones [14]. Therefore, it is possible that the spreading out of the fracture site on the radiographic image in this case results in osteoclast production to remove the damaged bone, which does not correlate to the patient's symptoms, especially pain.…”

The case “Scott Reuben”

“…Laut [2]. Prospektive randomisierte klinische Studien zu Knochenheilungsstö-rungen nach tNSAR und speziell COX-2-Hemmer-Gabe nach Operationen fehlen bisher [8].…”