Can we acceleratefr acture healing? A critical analysis of the liter ature P eter Giannoudis 1 , Spyridon Psarakis 1 , George Kontakis 2 1 Department of Trauma & Orthopaedics, School of Medicine, University of Leeds, UK 2 Department of Trauma & Orthopaedics, School of Medicine, University of Crete, Greece KEYWORDS: Fracture healing, acceleration,growth factors, BMPs Summary 1 Thecharacterization of the molecular mediators regulating thefrac- ture healing response over the past decade has vastly expanded our knowledge in this area at the molecular level. It is clear todaythatthe physiological mecha- nisms governing thebiology ofbone repair and turnover arecomplex andfar from being well understood. Severalof the molecules implicated in the healing process have become availablefor use in theclinicalsetting thanks to advancesmade in recombinant technology . Current evidence of their effect in acceleratingfracture healing in both experimental andclinical studies is promising. However , despite thesefindings, several factors requirefurther investigation, including the ideal timing to administer these molecules, which is the most effectivedose, and the factors affecting the lackofconsistency in theexperimental designsand animal modelsthat have been used. In addition, the availableevidence lacks phase III, level I studies. Until such studies become available, the results should be inter- preted with caution. Introduction Fracture healing involves the interaction of mo- lecularmediators and cells [8]. A local inflammatory reaction is initiated in the immediate aftermath of a fracture leading to chemotaxis of cellsand activation of several intracellular signal molecules, cytokines, adhesion molecules, and other autocoids [21, 23, 25]. Fracture healing is a well-orchestrated physiologicalprocess that leadstoproliferation and differentiation of osteoprogenitor cellstoosteob- lasts, osteoclasts,chondroblasts,fibroblasts, and endothelial cells [26]. Depending on its personality , every fracture requires special consideration bythe treating phy- sicianpriorto deciding whether it can be treated surgically or nonsurgically . Either way , thefracture is usually expected toprogress tohealing within an defined period of time. Different modalities have been used to stabilizefractures, with excellent results in most cases. However ,complications such as nonunion or delayed union can still occur , albeit rarely [31]. It is estimated that of the six million fracturesthat occur annually in the United States, between 5% and 10% end up in nonunion or delayed union [10]. Autogenous cancellous bonegrafting remainsthegold standard method used topromote union by stimulating the local biology atthe nonun- ion site[2]. However ,due to the limited quantity of such bonegrafting, other biologically based strate- gies have been developed overthe years, including electrical, ultrasound, and shockwave stimulation, a variety ofbonegraft substituteswith either os- teoconductive or bothosteoconductive and oste- oinductive properties, andgrowth factors that are 1 Abstracts in German, French, Spanish, Japanese, and Russian are printed attheend of this supplement. Injury, Int. J. Care Injured (2007) 38S1, S81—S89 www.elsevier.com/locate/injury 0020–1383/$ — see front matter # 2007 Published by Elsevier Ltd. doi:10.1016/j.injury.2007.02.013