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Michael D. McKee, M.D., FRCSC, Associate Professor,
Division of Orthopaedics, Department of Surgery
St. Michael’s Hospital, University of Toronto
Toronto, ON Osteogenic Protein 1 (OP-1) is recombinant human bone morphogenic protein (BMP) 7 imbedded in a bovine collagen matrix carrier. Low viscosity, carboxylmethycellulose has been added as an agent to improve the cohesiveness and viscosity of the product, allowing it to be used as a type of putty. Essentially bone morphogenic proteins are proteins which induce primitive mesenchymal stem cells to differentiate into cartilage and bone forming cells. This family of proteins (one of the TGF-beta superfamily) can be considered to be the “active ingredient” in iliac crest bone graft in terms of inducing further bone formation from locally responding cells. Thus OP-1 is not used in a structural fashion, but is osteo-inductive. Experimentally they have been dramatically successful in promoting the rapid healing of bony defects and critical size defects in a variety of animals including rabbit, canine, and monkey models1,2.
 | | Figure 1: Anteroposterior radiograph following intramedullary nailing of open proximal tibial fracture in an elderly female paedestrian. Following the nailing procedure, OP-1 was added to the fracture site. | In human studies, they have also been shown to promote healing of fibular defects following high tibial osteotomies. In a randomized clinical trial of 122 patients, OP-1 was as effective as autogenous bone grafting in promoting the healing of tibial nonunions treated with open intramedullary nailing3. In our own unpublished study of recalcitrant human long bone nonunion, OP-1 produced union in 8 of 9 patients who had previously failed conventional treatment including iliac crest bone grafting. Thus its promising biological potential seen in animal models appears to be borne out in human and clinical studies.
 | | Figure 2: Radiograph revealing solid bony union only six months postoperatively. Notice the abundant medial callus formation. |
On the strength of these studies and others, OP-1 has been approved by the FDA in the United States for the clinical treatment of long bone nonunion. The role of OP-1, and other osteo-inductive BMP’s in fracture care remains undefined at the present point. Our main experience with OP-1 comes from our participation in a multicentre randomized clinical trial conducted by Canadian Orthopaedic Trauma Society (COTS). Choosing a fracture model in which delayed and nonunion is a significant clinical concern, we randomized 136 patients with open tibial shaft fractures to conventional treatment (irrigation, debridement and intramedullary nailing) to conventional treatment plus the addition of OP-1 to the fracture site. At the present time, we are still evaluating the results of the trial and it is too early to make definitive statement regarding the applicability of this material to fresh fracture treatment.
It is clear that OP-1 and other recombinant BMP’s, pack a significant biological “punch” in inducing local bone formation. It is reasonable to postulate that in the future they, alone or in combination with other materials, may eliminate the requirements for autogenous iliac crest bone grafting. Certainly there is sufficient high quality clinical evidence to state that, in the absence of a requirement for a structural role, BMP’s are as efficacious as autogenous grafting in inducing healing of long bone nonunion in humans. As mentioned, their role in fracture care remains undefined4.
OP-1 and other BMP’s are not without their drawbacks. The complicated production technique means that they are very expensive and thus may never be realistic (at least in the Canadian medical system) for routine use in uncomplicated fractures. In a similar vein, they cannot act in isolation. BMP’s need a stable mechanical environment, reasonable soft tissue coverage, a population of responder cells, and the absence of any infection to be effective. They can be a useful and integral part of fundamentally sound orthopaedic and fracture care.
References
- Cook S.D., Baffes G.C., Wolfe M.W., Sampath T.K., Rueger D.C. Recombinant human bone morphogenetic protein-7 induces healing in a canine long-bone segmental defect model. Clin Ortho and Rel Res., 301: 302-12, 1994.
- Cook S.D., Baffes G.C., Wolfe M.W., Sampath T.K., Rueger D.C., Whitecloud T.S. The effect of recombinant human osteogenic protein-1 on healing of large segmental bone defects. J Bone Joint Surg., 76-A(6): 827-38, 1994.
- Muschler G.F., Perry C., Cole J.D., Cook S.D., Lisecki L.T.C., Wilkins R., Cierny G., Diana K., Yin S., Friedlaender G. Treatment of established tibial non-unions using human recombinant osteogenic protein-1 (OP-1). J Bone Joint Surg., 81-B, Supp 1, 30, 1999.
- Shimmin A.J. The use of osteogenic protein-1 (BMP-7) in the treatment of recalcitrant fractures. J Bone Joint Surg., 83-B, Supp II, 255, 2001.
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