In dogs does the use of bone morphogenetic proteins with internal fixation accelerates fracture healing?

Published:

2025-10-16

Share
Open Access Logo

DOI

https://doi.org/10.18849/ve.v10i4.722

Abstract

Question

In dogs undergoing internal fracture fixation does the use of internal fixation and bone morphogenetic proteins (BMPs) accelerate healing compared to internal fixation alone?

 

Clinical bottom line

The category of research question was:

Treatment.

The number and type of study designs that were critically appraised were:

Zero.

Critical appraisal of the selected papers meeting the inclusion criteria collectively provide zero/weak/moderate/strong evidence in terms of their experimental design and implementation:

Zero.

The outcomes reported are summarised as follows…

There is no evidence showing that dogs undergoing fracture fixation with any internal fixation method (e.g. locking plates, dynamic compression plates) and BMPs present accelerated healing compared to internal fixation alone. In view of the absence of this evidence, it is recommended that veterinarians should base their treatment choice on their experience in internal fixation methods and BMPs usage, their available materials for the methods, the cost, the potential adverse effects, and the case-specific factors. Therefore, veterinarians should acknowledge that both methods have potential risks and complications.

In view of the strength of evidence and the outcomes from the studies the following conclusion is made…

In dogs undergoing fracture fixation, there is no statistical evidence to support fracture fixation with internal fixation and BMPs as a method that accelerates healing compared to internal fixation alone.

References

Anatolitou, A.A., Sideri, K.I. & Prassinos, N.N. (2021). Current research and application of stem cells in the dog and cat. Journal of the Hellenic Veterinary Medical Society. 72(2), 2791–2802.

Castilla, A., Filliquist, B., Spriet, M., Garcia, T.C., Arzi, B., Chou, P-Y. & Kapatkin, A.S. (2023). Long-Term Assessment of Bone Regeneration in Nonunion Fractures Treated with Compression-Resistant Matrix and Recombinant Human Bone Morphogenetic Protein-2 in Dogs. Veterinary and Comparative Orthopaedics and Traumatology. 36(1), 29–38. DOI: https://doi.org/10.1055/s-0042-1749451

Dvořák, M., NeÄas, A. & Zatloukal, J. (2000). Complications of long Bone Fracture Healing in Dogs: Functional and Radiological Criteria for their Assessment. Acta Veterinaria Brno. 69, 107–114. DOI: https://doi.org/10.2754/avb200069020107

Ferrigno, C.R.A., Nina,M.I.D., & Fantoni, D.T. (2007). A comparative study of osteosynthesis with plates and plates associated with grafts of bone morphogenetic proteins (Gen-Tech®) in distal radio-ulnar fractures of dogs of less than 6 kilograms. Pesquisa Veterinária Brasileira. 27(2), 65–69. DOI: https://doi.org/10.1590/S0100-736X2007000200002

Harasen, G. (2011). Stimulating bone growth in the small animal patient: Grafts and beyond! Canadian Veterinary Journal. 52(2), 199–200.

Lee, S. & Kang, B.J. (2024). Surgical Reconstruction of Canine Nonunion Fractures Using Bone Morphogenetic Protein-2-loaded Alginate Microbeads and Bone Allografts. In Vivo. 38(2), 6117–619. DOI: https://doi.org/10.21873/invivo.13480

López, S., Vilar, J.M., Sopena, J.J., Damià, E., Chicharro, D., Carrillo, J.M., Cuervo, B. & Rubio, M. (2019). Assessment of the Efficacy of Platelet-Rich Plasma in the Treatment of Traumatic Canine Fractures. International Journal of Molecular Sciences. 20(5), 1075. DOI: https://doi.org/10.3390/ijms20051075

Marsell, R. & Einhorn, T.A. (2011). The biology of fracture healing. Injury. 42(6), 551–555. DOI: https://doi.org/10.1016/j.injury.2011.03.031

Marshall, W.G., Filliquist, B., Tzimtzimis, E., Fracka, A., Miquel, J., Garcia, J. & Fontana, M.D. (2022). Delayed union, non-union and mal-union in 442 dogs. Veterinary Surgery. 51(7), 1087–1095. DOI: https://doi.org/10.1111/vsu.13880

Massie, A.M, Kapatkin, A.S., Fuller, M.C., Verstraete, F.J.M. & Arzi, B. (2017). Outcome of nonunion fractures in dogs treated with fixation, compression resistant matrix, and recombinant human bone morphogenetic protein-2. Veterinary and Comparative Orthopaedics and Traumatology. 30(2), 153–159. DOI: https://doi.org/10.3415/VCOT-16-05-0082

May, R.D., Frauchiger, D.A., Albers, C.E., Tekari, A., Benneker, L.M., Klenke, F.M., Hofstetter, W. & Gantenbein, B. (2019). Application of Cytokines of the Bone Morphogenetic Protein (BMP) Family in Spinal Fusion - Effects on the Bone, Intervertebral Disc and Mesenchymal Stromal Cells. Current Stem Cell Research and Therapy. 14(8), 618–643. DOI: http://dx.doi.org/10.2174/1574888X14666190628103528

Medtronic Sofamor Danek. (2002). Summary of Safety and Effectiveness Data: InFUSE Bone Graft/LT-CAGE Lumbar Tapered Fusion Device. Food and Drug Administration. P000058. Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf/p000058b.pdf [Accessed: 01/10/2025]

Murakami, N., Saito, N., Takahashi, J., Ota, H., Horiuchi, H., Nawata, M., Okada, T., Nozaki, K. & Takaoka, K. (2003). Repair of a proximal femoral bone defect in dogs using a porous surfaced prosthesis in combination with recombinant BMP-2 and a synthetic polymer carrier. Biomaterials. 24(13), 2153–2159. DOI: https://doi.org/10.1016/S0142-9612(03)00041-3

Nina, M.I.D, Schmaedecke, A., Leandro, R., & Ferrigno, C.R.A. (2007). Comparison between bone plate osteosinthesis and bone plate associated to bone morphogenetic protein in a bilateral distal fracture of radius and ulna in a dog - case report. Brazilian Journal of Veterinary Research and Animal Science. 44(4), 297–303.

Park, J., Kwon, S., Hwang, N.S. & Kang, B.J. (2018). Clinical Application of Bone Morphogenetic Protein-2 Microcarriers Fabricated by the Cryopolymerization of Gelatin Methacrylate for the Treatment of Radial Fracture in Two Dogs. In Vivo. 2018 32(3), 575–581. DOI: https://10.21873/invivo.11278

Pinel, C.B. & Pluhar, G.E (2012). Clinical application of recombinant human bone morphogenetic protein in cats and dogs: a review of 13 cases. Canadian Veterinary Journal. 53(7), 767–774.

Ree, J.J., Baltzer, W.I. & Nemanic, S. (2018). Randomized, controlled, prospective clinical trial of autologous greater omentum free graft versus autogenous cancellous bone graft in radial and ulnar fractures in miniature breed dogs. Veterinary Surgery. 47(3), 392–405. DOI: https://doi.org/10.1111/vsu.12774

Riley, E.H., Lane, J.M., Urist, M.R., Lyons, K.M. & Lieberman, J.R. (1996). Bone morphogenetic protein-2: biology and applications. Clinical Orthopaedics and Related Research. (324), 39–46.

Ristiniemi, J., Flinkkilä, T., Hyvönen, P., Lakovaara, M., Pakarinen, H. & Jalovaara, P. (2007). RhBMP-7 accelerates the healing in distal tibial fractures treated by external fixation. The Journal of Bone and Joint Surgery British Volume. 89(2), 265–272. DOI: https://doi.org/10.1302/0301-620X.89B2.18230

Sanchez-Duffhues, G., Williams, E., Goumans, M-J., Heldin, C.H. & ten, Dijke, P. (2020). Bone morphogenetic protein receptors: Structure, function and targeting by selective small molecule kinase inhibitors. Bone. 138, 115472. DOI: https://doi.org/10.1016/j.bone.2020.115472

Schmoekel, H., Schense, J.C., Weber, F.E., Grätz, K.W., Gnägi, D., Müller, R. & Hubbell, J.A. (2004). Bone healing in the rat and dog with nonglycosylated BMP-2 demonstrating low solubility in fibrin matrices. Journal of Orthopaedic Research. 22(2), 376–381. DOI: https://doi.org/10.1016/S0736-0266(03)00188-8

Schmoekel, H.G., Weber, F.E., Hurter, K., Schense, J.C., Seiler, G., Ryrz, U., Spreng, D., Schawalder, P. & Hubbell, J. (2005). Enhancement of bone healing using non-glycosylated rhBMP-2 released from a fibrin matrix in dogs and cats. Journal of Small Animal Practice. 46(1), 17–21. DOI: https://doi.org/10.1111/j.1748-5827.2005.tb00269.x

Stokovic, N., Ivanjko, N., Maticic, D., Luyten, F.P. & Vukicevic, S. (2021). Bone Morphogenetic Proteins, Carriers, and Animal Models in the Development of Novel Bone Regenerative Therapies. Materials. 14(13), 3513. DOI: https://doi.org/10.3390/ma14133513

Sykaras, N. & Opperman, L.A. (2003). Bone morphogenetic proteins (BMPs): how do they function and what can they offer the clinician? Journal of Oral Science. 45(2), 57–73. DOI: https://doi.org/10.2334/josnusd.45.57

Toriumi, D.M., Kotler, H.S., Luxenberg, D.P., Holtrop, M.E. & Wang, E.A. (1991). Mandibular Reconstruction With a Recombinant Bone-Inducing Factor: Functional, Histologic, and Biomechanical Evaluation. Archives of Otolaryngol Head & Neck Surgery. 117(10), 1101–1112. DOI: https://doi.org/10.1001/archotol.1991.01870220049009

Tuominen, T., Jämsä, T., Oksanen, J., Tuukkanen, J., Gao, T.J., Lindholm, TS. & Jalovaara, P. (2001). Composite implant composed of hydroxyapatite and bone morphogenetic protein in the healing of a canine ulnar defect. Annales Chirurgiae et Gynaecologiae. 90. 32–36.

Urist, M.R. (1965). Bone: Formation by Autoinduction. Science. 150 (3698), 893–899. DOI: https://doi.org/10.1126/science.150.3698.893

Verstraete, F.J., Arzi, B., Huey, D.J., Cissell, D.D. & Athanasiou, K.A. (2015). Regenerating Mandibular Bone Using rhBMP--2: Part 2-Treatment of Chronic, Defect Non-Union Fractures. Veterinary Surgery. 44(4), 410–416. DOI: https://doi.org/10.1111/j.1532-950X.2014.12122.x

Wu, M., Wu, S., Chen, W., Li, Y-P. (2024). The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease. Cell Research. 34(2), 101–123. DOI: https://doi.org/10.1038/s41422-023-00918-9

Zhu, L., Liu, Y., Wang, A., Zhu, Z., Li, Y., Zhu, C., Che, Z., Liu, T., Liu, H. & Huang, L. (2022). Application of BMP in Bone Tissue Engineering. Frontiers in Bioengineering and Biotechnology. 10:810880. DOI: https://doi.org/10.3389/fbioe.2022.810880

Zygmuntowicz, A., Burmańczuk, A. & Markiewicz, W. (2020). Selected Biological Medicinal Products and Their Veterinary Use. Animals. 10(12), 2343. DOI: https://doi.org/10.3390/ani10122343