Editor's choice| Volume 41, ISSUE 5, P602-608, May 2016

Download started.


Complications With the Use of BMP-2 in Scaphoid Nonunion Surgery

Published:March 22, 2016DOI:https://doi.org/10.1016/j.jhsa.2016.01.013


      In an effort to improve fracture healing and decrease the need for autologous bone graft, products such as recombinant human bone morphogenetic protein (rhBMP-2) have been developed and used in both spine and nonspine surgery. There is a paucity of literature regarding the use of rhBMP-2 in scaphoid nonunion surgery with very little reporting on the complications associated with its use. The objective of this study was to retrospectively review the complications documented for a case series of patients treated with revision fixation, bone graft, and rhBMP-2 in revision scaphoid nonunion surgery.


      We retrospectively reviewed 6 cases of scaphoid nonunion revision surgery comprising open reduction and internal fixation (ORIF). All cases were performed for persistent nonunion after a previous scaphoid ORIF. All patients were treated with revision screw fixation, bone graft, and rhBMP-2. Union was determined by computed tomography in all cases. Complications of nonunion, heterotopic bone formation, delayed wound healing, functional loss of motion, and need for revision surgery are reported.


      Between 2011 and 2014, 6 cases in which rhBMP-2 was used in revision scaphoid nonunion surgery were identified. All patients had failed an initial attempt at ORIF after delayed union or nonunion. The time from injury to index ORIF ranged from 3 months to 4 years (mean, 24 months). Revision surgery with rhBMP-2 was performed at an average of 6 months from the index ORIF. Of the 6 cases, 2 had resultant persistent nonunion. Both underwent scaphoid excision and midcarpal arthrodesis. Four cases developed notable heterotopic ossification (one of which required revision surgery). One patient had a loss of functional motion after the revision surgery. There were no cases of delayed wound healing. Only one of the 6 patients healed without complications.


      In this case series, the use of rhBMP-2 in scaphoid nonunions was associated with a higher complication rate than reported in previous studies. Surgeons performing off-label use of rhBMP-2 should be aware of the potential for complications including heterotopic ossification.

      Type of study/level of evidence

      Therapeutic IV.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Hand Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Urist M.R.
        Bone: formation by autoinduction.
        Science. 1965; 150: 893-899
        • Govender S.
        • Csimma C.
        • Genant H.K.
        • et al.
        Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients.
        J Bone Joint Surg Am. 2002; 84: 2123-2134
        • Swiontkowski M.F.
        • Aro H.T.
        • Donell S.
        • et al.
        Recombinant human bone morphogenetic protein-2 in open tibia fractures: a subgroup analysis of data combined from two prospective randomized studies.
        J Bone Joint Surg Am. 2006; 88: 1258-1265
        • McKay W.
        • Peckham S.
        • Badura J.
        A comprehensive review of recombinant human bone morphogenic protein-2 (Infuse Bone Graft).
        Int Orthop. 2007; 31: 729-734
        • White A.
        • Vaccaro A.
        • Hall J.
        • Whang P.
        • Friel B.
        • McKee M.
        Clinical applications of BMP-7/OP-1 in fractures, nonunions, and spinal fusion.
        Int Orthop. 2007; 31: 735-741
        • Carragee E.J.
        • Mitsunaga K.A.
        • Hurwitz E.L.
        • Scuderi G.J.
        Retrograde ejaculation after anterior lumbar interbody fusion using rhBMP-2: a cohort controlled study.
        Spine J. 2011; 11: 511-516
        • Vaccaro A.
        • Patel T.
        • Fischgrund J.
        • et al.
        A pilot study evaluating the safety and efficacy of OP-1 putty (rhBMP-7) as a replacement for iliac crest autograft in posterolateral lumbar arthrodesis for degenerative spondylolisthesis.
        Spine. 2004; 29: 1885-1892
        • Vaccaro A.
        • Patel T.
        • Fischgrund J.
        • et al.
        A 2-year follow-up pilot study evaluating the safety and efficacy of OP-1 putty (rhBMP-7) as an adjunct for iliac crest autograft in posterolateral lumbar fusions.
        Eur Spine J. 2005; 14: 623-628
        • Perri B.
        • Cooper M.
        • Luaryssen C.
        • Anand N.
        Adverse swelling associated with use of rh-BMP-2 in anterior cervical discectomy and fusion: a case study.
        Spine J. 2007; 7: 235-239
        • Singh K.
        • Ahmadinia K.
        • Park D.
        • et al.
        Complications of spinal fusion with utilization of bone morphogenetic protein.
        Spine. 2013; 39: 91-101
        • Chen C.J.
        • Saulle D.
        • Fu K.M.
        • Smith J.S.
        • Shaffrey C.I.
        Dysphagia following combined anterior-posterior cervical spine surgeries.
        J Neurosurg Spine. 2013; 19: 279-287
        • Pountros I.
        • Panteli M.
        • Giannoudis P.
        • Giannoudis G.
        Neoplasia following use of BMPs: is there an increased risk?.
        Expert Opin Drug Saf. 2014; 13: 1525-1534
        • Tannourney C.
        • An H.
        Complications with the use of bone morphogenetic protein 2 (BMP-2) in spine surgery.
        Spine J. 2014; 14: 552-559
        • Boraiah S.
        • Omesh P.
        • Hawkes D.
        • Wickham M.
        • Lorich D.
        Complications of recombinant human BMP-2 for treating complex tibial plateau fractures: a preliminary report.
        Clin Orthop Relat Res. 2009; 467: 3257-3262
        • Chan D.
        • Garland J.
        • Infante A.
        • Sanders R.
        • Sagi H.
        Wound complications associated with bone morphogenetic protein-2 in orthopaedic trauma surgery.
        J Orthop Trauma. 2014; 28: 599-604
        • Woo E.J.
        Adverse effects after recombinant human BMP-2 in nonspinal orthopaedic procedures.
        Clin Orthop Relat Res. 2013; 471: 1707-1711
        • Rice I.
        • Lubahn J.
        Use of bone morphogenetic protein-2 (rh-BMP-2) in treatment of wrist and hand nonunion with comparison to historical control groups.
        J Surg Orthop Adv. 2013; 22: 256-262
        • Ablove R.H.
        • Abrams S.S.
        The use of BMP-2 and screw exchange in the treatment of scaphoid fracture non-union.
        Hand Surg. 2015; 20: 167-171
        • Ryu J.Y.
        • Cooney III, W.P.
        • Askew L.J.
        • An K.N.
        • Chao E.Y.
        Functional ranges of motion of the wrist joint.
        J Hand Surg Am. 1991; 16: 409-419
        • Kuschner S.H.
        • Lane C.S.
        • Brien W.W.
        • Gellman H.
        Scaphoid fractures and scaphoid nonunion: diagnosis and treatment.
        Orthop Rev. 1994; 23: 861-871
        • Daly K.
        • Gill P.
        • Magnussen P.A.
        • Simonis R.B.
        Established nonunion of the scaphoid treated by volar wedge grafting and Herbert screw fixation.
        J Bone Joint Surg Br. 1996; 78: 530-534
        • Inoue G.
        • Kuwahata Y.
        Repeat screw stabilization with bone grafting after a failed Herbert screw fixation for acute scaphoid fractures and nonunions.
        J Hand Surg Am. 1997; 22: 413-418
        • Robbins R.R.
        • Ridge O.
        • Carter P.R.
        Iliac crest bone grafting and Herbert screw fixation of nonunions of the scaphoid with avascular proximal poles.
        J Hand Surg Am. 1995; 20: 818-831
        • Carrozzella J.C.
        • Stern P.J.
        • Murdock P.A.
        The fate of failed bone graft surgery for scaphoid nonunions.
        J Hand Surg Am. 1989; 14: 800-806
        • Smith B.S.
        • Cooney W.P.
        Revision of failed bone grafting for nonunion of the scaphoid: treatment options and results.
        Clin Orthop Relat Res. 1996; : 98-109
        • Chen A.C.
        • Chao E.K.
        • Tu Y.K.
        • Ueng S.W.
        Scaphoid nonunion treated with vascular bone grafts pedicled on the dorsal supra-retinacular artery of the distal radius.
        J Trauma. 2006; 61: 1192-1197
        • Tambe A.D.
        • Cutler L.
        • Stilwell J.
        • Murali S.R.
        • Trail I.A.
        • Stanley J.K.
        Scaphoid non-union: the role of vascularized grafting in recalcitrant non-unions of the scaphoid.
        J Hand Surg Br. 2006; 31: 185-190
        • Gras M.
        • Mathoulin C.
        Vascularized bone graft pedicled on the volar carpal artery from the volar distal radius as primary procedure for scaphoid non-union.
        Orthop Traumatol Surg Res. 2011; 97: 800-806
        • Sawaizumi T.
        • Nanno M.
        • Nanbu A.
        • Ito H.
        Vascularised bone graft from the base of the second metacarpal for refractory nonunion of the scaphoid.
        J Bone Joint Surg Br. 2004; 86: 1007-1012
        • Jones Jr., D.B.
        • Moran S.L.
        • Bishop A.T.
        • Shin A.Y.
        Free-vascularized medial femoral condyle bone transfer in the treatment of scaphoid nonunions.
        Plast Reconstr Surg. 2010; 125: 1176-1184
        • Guimberteau J.C.
        • Panconi B.
        Recalcitrant non-union of the scaphoid treated with a vascularized bone graft based on the ulnar artery.
        J Bone Joint Surg Am. 1990; 72: 88-97
        • Fernandez D.L.
        • Eggli S.
        Non-union of the scaphoid: revascularization of the proximal pole with implantation of a vascular bundle and bone-grafting.
        J Bone Joint Surg Am. 1995; 77: 883-893
        • Sotereanos D.G.
        • Darlis N.A.
        • Dailiana Z.H.
        • Sarris I.K.
        • Malizos K.N.
        A capsular-based vascularized distal radius graft for proximal pole scaphoid pseudarthrosis.
        J Hand Surg Am. 2006; 31: 580-587
        • Mathoulin C.
        • Haerle M.
        Vascularized bone graft from the palmar carpal artery for treatment of scaphoid nonunion.
        J Hand Surg Br. 1998; 23: 318-323
        • Chang M.A.
        • Bishop A.T.
        • Moran S.L.
        • Shin A.Y.
        The outcomes and complications of 1,2-intercompartmental supraretinacular artery pedicled vascularized bone grafting of scaphoid nonunions.
        J Hand Surg Am. 2006; 31: 387-396
        • Waitayawinyu T.
        • McCallister W.V.
        • Katolik L.I.
        • Schlenker J.D.
        • Trumble T.E.
        Outcome after vascularized bone grafting of scaphoid nonunions with avascular necrosis.
        J Hand Surg Am. 2009; 34: 387-394
        • Lindström F.
        • Nyström Å.
        Natural history of scaphoid nonunion, with special reference to “asymptomatic” cases.
        J Hand Surg Br. 1992; 17: 697-700
        • Düppe H.
        • Johnell O.
        • Lundborg G.
        • Karlsson M.
        • Redlund-Johnell I.
        Long-term results of fracture of the scaphoid: a follow-up study of more than thirty years.
        J Bone Joint Surg Am. 1994; 76: 249-252
        • Kozin S.H.
        Incidence, mechanism, and natural history of scaphoid fractures.
        Hand Clin. 2001; 17: 515-524
        • Merrell G.A.
        • Wolfe S.W.
        • Slade J.F.
        Treatment of scaphoid nonunions: quantitative meta-analysis of the literature.
        J Hand Surg Am. 2002; 27: 685-691
        • Reigstad O.
        • Thorkildsen R.
        • Grimsgaard C.
        • Reigstad A.
        • Rokkum M.
        Is revision bone grafting worthwhile after failed surgery for scaphoid nonunion? Minimum 8 year follow-up of 18 patients.
        J Hand Surd Eur Vol. 2009; 34: 772-777
        • Jones N.
        • Brown E.
        • Mostofi A.
        • Vogelin E.
        • Urist M.
        Healing of a scaphoid nonunion using human bone morphogenic protein.
        J Hand Sur Am. 2005; 30: 528-533
        • Bilic R.
        • Simic P.
        • Jelic M.
        • et al.
        Osteogenic protein-1 (BMP-7) accelerates healing of scaphoid non-union with proximal pole sclerosis.
        Int Orthop. 2006; 30: 128-134
        • Kujala S.
        • Raatikainen J.
        • Ryhanen O.
        • Jalovaara P.
        Composite implant of native bovine bone morphogenic protein (BMP) and biocoral in the treatment of scaphoid nonunions: a preliminary study.
        Arch Orthop Trauma Surg. 2004; 124: 26-30

      Linked Article