The use of bone morphogenic protein-7 (OP-1) in the management of resistant non-unions in the upper and lower limb M.C. Papanna a,b, *, N. Al-Hadithy c , B.V. Somanchi a , M.D. Sewell c , P.M. Robinson a,d , S.A. Khan a , R.A. Wilkes a a Dept of Orthopaedics and Limb Reconstruction, Salford Royal Hospital, Salford, UK b Doncaster Royal Infirmary, Doncaster DN2 5LT, UK c Lister General Hospital, Stevenage, UK d Peterborough District General Hospital, Peterborough, UK Introduction Impaired bone healing and non-union affects between five and ten percent of all fractures. 1 Non-unions can be difficult to treat and may have devastating effects on patients, often requiring multiple operations, prolonged periods of recovery, causing significant psychosocial and functional disability. 2,3 Hypertrophic non-unions are associated with adequate vascularity and favour- able biological environment. They require mechanical stabilisation for callus progression to occur at the fracture site. Atrophic non- unions are associated with inadequate vascularity and generally require a biological stimulus in addition to mechanical stability for healing to occur. Autologous bone grafting (ABG) has osteogenic, osteoinductive and osteoconductive properties and is the gold standard biological treatment for diaphyseal non-union. 4,5 How- ever limited availability and complications related to its use such as further surgery, increased hospital stay, wound infections, discharging sinuses and chronic pain may limit its use. 6–10 When ABG has failed to stimulate healing in a non-union or where there is a contraindication to use, alternative biological enhancements have been sought to promote fracture healing. In 1965 Marshall Urist 11 first hypothesised that certain proteins were capable of inducing new bone formation and subsequently named them bone morphogenic proteins (BMPs). BMPs are members of the transforming growth factor-beta superfamily and stimulate bone healing by promoting chemotaxis and the proliferation and differentiation of mesenchymal stem cells into chondrogenic and osteogenic cell lines. Fifteen BMPs have been discovered in humans. 12 In May 2001 the US Food and Drug Administration approved BMP-7 for the treatment of tibial non- unions. BMP-7 has subsequently been shown to stimulate union in tibial non-unions and posterolateral spinal fusion, 13–16 however few studies have evaluated their effects at other sites. 17 The aim of the present study was to investigate the safety and efficacy of local implantation of BMP-7 for the treatment of resistant non-unions in the upper and lower limb. Methods and materials Between 2003 and 2009, fifty-two consecutive patients with persistent non-unions were treated with application of composite paste consisting of BMP-7 and bovine bone-derived collagen with or without revision of fixation. Indications for implantation included persistent non-union despite previous surgery that Injury, Int. J. Care Injured 43 (2012) 1135–1140 A R T I C L E I N F O Article history: Accepted 4 March 2012 Keywords: Fracture Nonunion Bone morphogenic protein-7 Healing A B S T R A C T The aim of the present study was to investigate the safety and efficacy of local implantation of BMP-7 for the treatment of resistant non-unions in the upper and lower limb. Fifty-two patients (30 males, mean age 52.8 years; range 20–81) were treated with local BMP-7 implantation in a bovine bone-derived collagen paste with or without revision of fixation. Thirty-six patients had closed injuries, ten had open injuries and six had infected non-unions. Patients had undergone a mean of 2 (1–5) operations prior to implantation of BMP-7. Clinical and radiological union was achieved in 94% at a mean time of 5.6 months (3–19). Two patients with subtrochanteric femoral fractures failed to achieve union secondary to inadequate fracture stabilisation, persistent unfavourable biological environment and systemic co- morbidities. One patient developed synostosis attributed to the BMP-7 application. This study demonstrates BMP-7 implanted in a bovine-derived collagen paste is an effective adjunctive treatment for resistant non-unions in the upper and lower limb. ß 2012 Elsevier Ltd. All rights reserved. * Corresponding author at: Department of Orthopaedics, Doncaster Royal Infirmary, Doncaster DN2 5LT, UK. Tel.: +44 07709493320. E-mail address: drmadhavan@hotmail.com (M.C. Papanna). Contents lists available at SciVerse ScienceDirect Injury jo ur n al ho m epag e: ww w.els evier .c om /lo cat e/inju r y 0020–1383/$ – see front matter ß 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.injury.2012.03.007