Bone Morphogenic Proteins: Their Role in Fracture Management

Abstract

Delayed fracture healing and non-union remain problems in fracture management. Over the last two decades improvement with fixation has assisted with the management of these problems. Bone morphogenic proteins represent a novel approach to biologically stimulate fractures to accelerate bone healing. This article overviews some of the experimental and clinical studies to support the use of this technique.

Bone morphogenic protein - delayed bone healing - fracture management

References

• 1 Bassett C A, Mitchell S N, Gaston S R. Treatment of ununited tibial diaphyseal fractures with pulsing electromagnetic fields.  J Bone Joint Surg [Am]. 1981;  63 511-523
• 2 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
• 3 Boden S D, Martin G J, Morone M A, Ugbo J L, Moskovitz P A. Posterolateral lumbar intertransverse process spine arthrodesis with recombinant human bone morphogenitic protein 2/hydroxyapatite-tricalcium phosphate after laminectomy in the nonhuman primate.  Spine. 1999;  24 1179-1185
• 4 Boden S D, Zdeblick T A, Sandhu H S, Helm S E. The use of rhBMP-2 in inter-body fusion cages. Definitive evidence of osteoinduction in humans; a preliminary report.  Spine. 2000;  25 376-381
• 5 Bogoch E R, Moran E L. Bone abnormalities in the surgical treatment of patients with rheumatoid arthritis.  Clin Orthop. 1999;  8 21
• 6 Bonatus T, Olson S A, Lee S, Chapman M W. Nonreamed locking intramedullary nailing for open fractures of the tibia.  Clin Orthop. 1997;  339 58-64
• 7 Boyd H B, Lipinski S W, Wiley J H. Observations on non-union of the shafts of the long bones, with a statistical analysis of 842 patients.  J Bone Joint Surg [Am]. 1961;  43 159-168
• 8 Boyne P J, Marx R E, Nevins M, Triplett G, Lazaro E, Lilly L C, Alder M, Nummikoski P. A feasibility study evaluating rhBMP-2/absorbable collagen sponge for maxillary sinus floor augmentation.  Int J Periodontics Restorative Dent. 1997;  17 11-25
• 9 Brighton C T, Shaman P, Heppenstall R B, Esterhai J L, Pollack S R, Friedenberg Z B. Tibial non-union treated with direct current, capacitive coupling or bone graft.  Clin Orthop. 1995;  321 223-234
• 10 Carter D R, Blenman P R, Beaupre G S. Correlations between mechanical stress history and tissue differentiation in initial fracture healing.  J Orthop Res. 1988;  6 736-748
• 11 Caudle R J, Stern P J. Severe open fractures of the tibia.  J Bone Joint Surg [Am]. 1987;  69 801-807
• 12 Chen X, Kidder L S, Lew W D. Osteogenic protein-1 induced bone formation in an infected segmental defect in the rat femur.  J Orthop Res. 2002;  20 142-150
• 13 Cook S D, Baffes G C, Wolfe M W, Sampath T K, Rueger D C. Recombinant human bone morphogenic proten-7 induces healing in a canine long bone segmental defect model.  Clin Orthop. 1994;  30 302-312
• 14 Cook S D, Baffes G C, Wolfe M W, Sampath T K, Rueger D C, Whitecloud T S. Effect of recombinant human osteogenic protein-l on healing of large segmental bone defects.  J Bone Joint Surg [Am]. 1994;  76 827-838
• 15 Cook S D, Salkeld S L, Brinker M R, Wolfe M W, Rueger D C. Use of an osteoinductive biomaterial (rhOP-1) in healing large segmental bone defects.  J Orthop Trauma. 1998;  12 407-412
• 16 Cook S D, Wolfe M W, Salkeld S L, Rueger D C. Recombinant human osteogenic protein-1 (rhOP-1) heals segmental defects in nonhuman primates.  J Bone Joint Surg [Am]. 1995;  77 734-750
• 17 Day S M, Ostrum R F, Chao E YS, Rubin C T, Aro H T, Einhorn T A. Bone injury, regeneration and repair. In: Buckwalter JA, Einhorn TA, Simon SR (eds). Orthopaedic basis science - biology and biomechanical of the musculoskeletal system. American Academy of Orthopaedic Surgeons, Rosemont, IL 2000; 371
• 18 Einhorn T A, Levine B, Michel P. Nutrition and bone.  Orthop Clin North Am. 1990;  21 4350
• 19 Fischgrund J S, James S B, Chabot M C, Hankin R, Herkowitz H N, Wozney J M, Shirkhoda A. Augmentation of autograft using rhBMP-2 and different carrier media in the canine spinal fusion model.  J Spinal Disord. 1997;  10 467-472
• 20 Friedlaender G E, Perry C R, Cole D, Cook S D, Ciemy G, Muschler G F, Zych G A, Calhoun J H, LaForte, Yin S. Osteogenic protein-1 (bone morphogenic protein-7) in the treatment of tibial non-unions.  J Bone Joint Surg [Am]. 2001;  83 (suppl I, part 2) 151-158
• 21 Geesink R GT, Hoefnagels N HM, Bulstra S K. Osteogenic activity of OP-1 bone morphogenic protein (BMP-7) in a human fibular defect.  J Bone Joint Surg [Br]. 1999;  81 710-718
• 22 Heppenstall R B, Brighton C T, Esterhai J R, Muller G. Prognosis factors in non-unions of the tibia; an evaluation of 185 cases treated with constant direct current.  J Trauma. 1984;  24 790-795
• 23 Kwiatowski T C, Hanley E N, Ramp W K. Cigarette smoking and its orthopaedic consequences.  Am J Orthop. 1996;  25 590-597
• 24 Kyro A, Usenius J P, Aamio M, Kunnamo I, Avikainen V. Are smokers a risk group for delayed healing of tibial shaft fractures?.  Ann Chir Gynaecol. 1993;  82 254-262
• 25 Mayr E, Frankel V, Ruter A. Ultrasound - an alternative healing method for nonunions?.  Arch Orthop Trauma Surg. 2000;  120 1-8
• 26 Patel T C, Erulkar J S, Grauer I N, Troiano N W, Panjabi M M, Friedlaender G E. Osteogenic protein-1 overcomes the inhibitory effect of nicotine on posterolateral lumbar fusion.  Spine. 2001;  25 1656-1661
• 27 Perren S M. Physical and biological aspects of fracture healing with special reference to internal fixation.  Clin Orthop. 1979;  138 175-196
• 28 Praemer A, Furner S, Rice D P. Musculoskeletal conditions in the United States. The American Academy of Orthopaedic Surgeons, Park Ridge, IL, 1992; 83
• 29 Riemer B L, DiChristina D G, Cooper A, Sagiv S, Butterfield S L, Burke C J, Lucke J F, Schlosser J D. Nonreamed nailing of tibial diaphyseal fractures in blunt polytrauma patients.  J Orthop Trauma. 1995;  9 66-75
• 30 Ryaby J T. Clinical effects of electromagnetic and electric fields on fracture healing.  Clin Orthop. 1998;  355 (Suppl) 205-215
• 31 Sampath T K, Ozkaynak E, Jones E, Sasa H, Tucker R, Tucker M. et al . Recombinant human osteogenic protein-1 (hOP-1) induces new bone formation in vivo with a specific activity comparable with natural bovine osteogenic protein and stimulates osteoblast proliferation and differentiation in vitro.  J Biol Chem. 1992;  267 352-362
• 32 Sanders R, Jersinovich I, Anglen J, DiPasquale T, Herscovici D. The treatment of open tibial shaft fractures using an interlocked intramedullary nail without reaming.  J Orthop Trauma. 1994;  8 501-510
• 33 Shimmin A, Ruff S. Clinical use of recombinant human osteogenic protein-1 (rhOP-1).  Bone. 1999;  24 409-431