Clinical Efficacy of Bone Morphogenetic Proteins

Abstract

Fracture healing is a time-consuming process, concerning a relative young patient population. Five to 10 per cent of the fractures develop a complicated bone healing process resulting in either a delayed union or a non-union. The associated morbidity and costs related to fracture healing are considerable and treatment methods to accelerate the bone healing process have been studied intensively over the last decades. Several treatment methods for accelerating bone healing have been proposed, but one of the most promising techniques is the application of bone morphogenetic proteins (BMPs). The BMPs were first described in 1965 by Urist, and these growth factors are capable of inducing de novo bone formation when implanted at heterotopic sites. Their osteoinductive capacity has been well-established in animal experiments. Some of the members of the BMP family, BMP-2 (InductOs™) and BMP-7/OP-1 (Osigraft™), have demonstrated their effectiveness and safety in clinical applications such as accelerating fresh fracture healing, treatment of bone defects and non-unions, and promoting spinal fusion. So, BMPs will offer a great therapeutic potential for replacing or augmenting current surgical strategies for the enhancement of bone repair in the forthcoming years.

Key words

Clinical trials - BMPs - spinal fusion - fresh fracture healing - bone defects - non-unions

References

• 1 Burkus J K, Dorchak J D, Sanders D L. Radiographic assessment of interbody fusion using recombinant human bone morphogenetic protein type 2.  Spine. 2003;  28 372-377
• 2 Burkus J K, Gornet M F, Dickman C A, Zdeblick T A. Anterior lumbar interbody fusion using rhBMP-2 with tapered interbody cages.  J Spinal Disord Tech. 2002;  15 337-349
• 3 Cook S D, Wolfe M W, Salkeld S L, Rueger D C. Effect of recombinant human osteogenic protein-1 on healing of segmental defects in non-human primates.  J Bone Joint Surg [Am]. 1995;  77 734-750
• 4 Den Boer F C, Patka P, Bakker F C, Haarman H JTM. Current concepts of fracture healing, delayed unions, and non-unions.  Osteosynthesis and Trauma Care. 2002;  10 1-8
• 5 Friedlaender G E, Perry C R, Cole J D. et al . Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions.  J Bone Joint Surg [Am]. 2001;  83 (Suppl 1) S151-S158
• 6 Geesink R G, Hoefnagels N H, Bulstra S K. Osteogenic activity of OP-1 bone morphogenetic protein (BMP-7) in a human fibular defect.  J Bone Joint Surg [Br]. 1999;  81 710-718
• 7 Govender S, Csimma C, Genant H K. et al . Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomised study of four hundred and fifty patients.  J Bone Joint Surg [Am]. 2002;  84 2123-2134
• 8 Johnsson R, Stromqvist B, Aspenberg P. Randomized radiostereometric study comparing osteogenic protein-1 (BMP-7) and autograft bone in human noninstrumented posterolateral lumbar fusion: 2002 Volvo Award in clinical studies.  Spine. 2002;  27 2654-2661
• 9 Laursen M, Hoy K, Hansen E S, Gelineck J, Christensen F B, Bunger C E. Recombinant bone morphogenetic protein-7 as an intracorporal bone growth stimulator in unstable thoracolumbar burst fractures in humans: preliminary results.  Eur Spine J. 1999;  8 485-490
• 10 Lieberman J R, Daluiski A, Einhorn T A. The role of growth factors in the repair of bone. Biology and clinical applications.  J Bone Joint Surg [Am]. 2002;  84 1032-1044
• 11 McKee M, Schemitsch E, Waddel J. et al .The effect of human recombinant bone morphogenic protein (rhBMP-7) on the healing of open tibial shaft fractures: Results of a multi-center, prospective, randomised clinical trial. Orthopaedic Trauma Association: Annual Meeting, Toronto 2002
• 12 Patel T C, Vaccaro A R, Trumees E. Two-years follow-up on a safety and efficacy study of OP-1 (rhBMP-7) as an adjunct to posterolateral lumbar fusion. Proceedings of the North American Spine Society 16th Annual Meeting, 2001
• 13 Poynton A R, Lane J M. Safety profile for the clinical use of bone morphogenetic proteins in the spine.  Spine. 2002;  27 40-48
• 14 Riedel G E, Valentin-Opran A. Clinical evaluation of rhBMP-2/ACS in orthopedic trauma: a progress report.  Orthopedics. 1999;  22 663-665
• 15 Sciadini M F, Johnson K D. Evaluation of recombinant human bone morphogenetic protein-2 as a bone-graft substitute in a canine segmental defect model.  J Orthop Res. 2000;  18 289-302
• 16 Vaccaro A R, Anderson D G, Toth C A. Recombinant human osteogenic protein-1 (bone morphogenetic protein-7) as an osteoinductive agent in spinal fusion.  Spine. 2002;  27 S59-S65