title: The mechanisms of the inhibitory effects of nonsteroidal anti-inflammatory drugs on bone healing: a concise review.
abstract: Nonsteroidal anti-inflammatory drug (NSAID) use continues to expand at a remarkable rate due both to the broad spectrum of clinical applications for these medications and to the relatively recent introduction of the popular COX-2-selective inhibitors. The use of NSAIDs is particularly prevalent in patients with a variety of musculoskeletal conditions and injuries. Reports of impaired bone healing associated with NSAID use, therefore, are a particular cause for concern. Animal and in vitro studies have demonstrated impaired bone healing in the presence of traditional NSAIDs, as measured by a variety of different parameters. More recently, initial studies investigating the effects of COX-2-selective inhibitors on bone healing have yielded similar results. With mounting evidence that NSAIDs do in fact interfere with proper bone healing in various animal models, questions have arisen regarding the potential mechanism through which NSAIDs produce this outcome and whether these results can be translated to clinical settings. A likely pathway for these observed effects results from an understanding of the steps involved in bone healing itself. These steps include an inflammatory response, bone resorption, and new bone formation. Investigations over the past several decades have elucidated a role for prostaglandins (PGs) in each of these areas. Specifically, PGs have been shown to elicit and participate in inflammatory responses, increase osteoclast activity and subsequent bone resorption, and increase osteoblast activity and new bone formation. This apparent integral role for PGs in the process of bone healing, coupled with the knowledge that NSAIDs act by inhibiting the production of PGs, results in an understanding of the likely mechanism through which NSAIDs impart their deleterious effects on bone healing. By inhibiting the COX enzymes and the subsequent production of PGs, NSAIDs not only achieve their desired anti-inflammatory effects but also inhibit the increased production of PGs that is necessary for bone healing to occur. Despite this understanding of the potential mechanism through which NSAIDs inhibit bone healing in a laboratory setting, few studies exist that show whether these inhibitory effects are also evident clinically. Thus, further studies will need to decipher whether similar inhibitory effects occur in a clinical setting.
authors.affiliation: Orthopaedic Research Laboratories, Medical University of South Carolina, 96 Jonathan Lucas Street, CSB708, Charleston, SC 29425, USA.
authors.forename: Adam T
authors.initials: AT
authors.lastname: Harder
authors.forename: Yuehuei H
authors.initials: YH
authors.lastname: An
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001842:Bone and Bones / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D006801:Humans; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors