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.