Arachidonic acid, eicosanoids, and fracture repair

Not all fractures heal well or rapidly in the adult skeleton, and basic scientists and clinicians continue to search for ways to make fractures heal more predictably. It is a fundamental tenet of orthopaedics that skeletal injury is followed by inflammation and that this inflammatory response is the first stage in a sequence of events that culminate in skeletal repair. Modulating this response can affect the inflammatory stage and in turn subsequent stages that are required for healing. Literally dozens of studies in animals dating back to the 1970s have investigated the effects of commonly used anti-inflammatory medications on prostaglandin synthesis and fracture repair with strikingly uniform results. More recently, investigators have begun examining other means of modulating the early inflammatory stages after fracture in an effort to enhance fracture healing. This article reviews recent investigations into the potential role of leukotrienes as negative regulators of fracture healing and potential pharmacologic use of medications that block this effect.