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Vet Comp Orthop Traumatol 2023; 36(01): 29-38
DOI: 10.1055/s-0042-1749451
Clinical Communication

Long-Term Assessment of Bone Regeneration in Nonunion Fractures Treated with Compression-Resistant Matrix and Recombinant Human Bone Morphogenetic Protein-2 in Dogs

Andrea Castilla
1   Veterinary Medical Teaching Hospital, Davis, University of California, California, United States
,
Barbro Filliquist 
2   Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, California, United States
,
Mathieu Spriet
2   Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, California, United States
,
Tanya C. Garcia
2   Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, California, United States
,
Boaz Arzi
2   Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, California, United States
3   Veterinary Institute for Regenerative Cures, School of Veterinary Medicine, University of California, Davis, California, United States
,
Po-Yen Chou 
2   Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, California, United States
,
Amy S. Kapatkin
2   Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, California, United States
› Author Affiliations Funding Funded by the Center for Companion Animal Health, School of Veterinary Medicine, University of California, Davis. 2019-55-R
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Abstract

Objective The aim of this study was to assess bone density, bone architecture and clinical function of canine nonunion distal appendicular long bone fractures with a defect treated with fixation, compression-resistant matrix and recombinant human bone morphogenetic protein-2 (rhBMP-2).

Study Design Prospective cohort study with dogs at least 1-year post treatment. Computed tomography was performed and quantitative measurements from previous fracture sites were compared with measurements from contralateral limbs. Subjective evaluation included gait assessment and palpation.

Results Six patients met the inclusion criteria. The rhBMP-2 treated bone exhibited higher density at the periphery and lower density in the centre, similar to the contralateral limb. All patients were weight bearing on the treated limb and all fractures were healed.

Conclusion The rhBMP-2-treated bone underwent restoration of normal architecture and density. Acceptable limb function was present in all patients. The results of this study can serve as a basis for long-term response in treating nonunion fractures in veterinary patients.

Keywords

Bone morphogenetic protein 2 - rhBMP-2 - nonunion fracture - compression-resistant matrix - bone regeneration

Authors' Contributions

All authors contributed to the development of study design. ASK performed the surgery on all of the patients. AC and ASK evaluated the clinical cases. MS, AC, BF, ASK and T.G contributed to the acquisition of data, data analysis and interpretation. AC and BF developed the main manuscript and all the authors contributed to the review and approval of the manuscript prior to submission.




Publication History

Received: 27 August 2021

Accepted: 13 April 2022

Article published online:
27 June 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Brinker W, Piermattei DL, Flo G. Delayed union and nonunion. In: Handbook of Small Animal Orthopedics and Fracture Repair. 5th edition. Saunders;; 2016: 163-173
    Google Scholar
  • 2 Calori GM, Mazza E, Colombo M, Ripamonti C, Tagliabue L. Treatment of long bone non-unions with polytherapy: indications and clinical results. Injury 2011; 42 (06) 587-590
    CrossrefPubMedGoogle Scholar
  • 3 Welch JA, Boudrieau RJ, DeJardin LM, Spodnick GJ. The intraosseous blood supply of the canine radius: implications for healing of distal fractures in small dogs. Vet Surg 1997; 26 (01) 57-61
    CrossrefPubMedGoogle Scholar
  • 4 Munakata S, Nagahiro Y, Katori D. et al. Clinical efficacy of bone reconstruction surgery with frozen cortical bone allografts for nonunion of radial and ulnar fractures in toy breed dogs. Vet Comp Orthop Traumatol 2018; 31 (03) 159-169
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Wang RN, Green J, Wang Z. et al. Bone Morphogenetic Protein (BMP) signaling in development and human diseases. Genes Dis 2014; 1 (01) 87-105
    CrossrefPubMedGoogle Scholar
  • 6 Rosen V. BMP2 signaling in bone development and repair. Cytokine Growth Factor Rev 2009; 20 (5-6): 475-480
    CrossrefPubMedGoogle Scholar
  • 7 McKay WF, Peckham SM, Badura JM. A comprehensive clinical review of recombinant human bone morphogenetic protein-2 (INFUSE Bone Graft). Int Orthop 2007; 31 (06) 729-734
    CrossrefPubMedGoogle Scholar
  • 8 Lebl DR. Bone morphogenetic protein in complex cervical spine surgery: a safe biologic adjunct?. World J Orthop 2013; 4 (02) 53-57
    CrossrefPubMedGoogle Scholar
  • 9 James AW, LaChaud G, Shen J. et al. A review of the clinical side effects of bone morphogenetic protein-2. Tissue Eng Part B Rev 2016; 22 (04) 284-297
    CrossrefPubMedGoogle Scholar
  • 10 Song J, Kim Y, Kweon OK, Kang BJ. Use of stem-cell sheets expressing bone morphogenetic protein-7 in the management of a nonunion radial fracture in a Toy Poodle. J Vet Sci 2017; 18 (04) 555-558
    CrossrefPubMedGoogle Scholar
  • 11 Park J, Kwon S, Hwang NS, Kang BJ. 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 (03) 575-581
    PubMedGoogle Scholar
  • 12 Itoh T, Mochizuki M, Fuda K. et al. Femoral nonunion fracture treated with recombinant human bone morphogenetic protein-2 in a dog. J Vet Med Sci 1998; 60 (04) 535-538
    CrossrefPubMedGoogle Scholar
  • 13 Faria ML, Lu Y, Heaney K, Uthamanthil RK, Muir P, Markel MD. Recombinant human bone morphogenetic protein-2 in absorbable collagen sponge enhances bone healing of tibial osteotomies in dogs. Vet Surg 2007; 36 (02) 122-131
    CrossrefPubMedGoogle Scholar
  • 14 Minier K, Touré A, Fusellier M. et al. BMP-2 delivered from a self-crosslinkable CaP/hydrogel construct promotes bone regeneration in a critical-size segmental defect model of non-union in dogs. Vet Comp Orthop Traumatol 2014; 27 (06) 411-421
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Schmökel HG, Weber FE, Seiler G. et al. Treatment of nonunions with nonglycosylated recombinant human bone morphogenetic protein-2 delivered from a fibrin matrix. Vet Surg 2004; 33 (02) 112-118
    CrossrefPubMedGoogle Scholar
  • 16 Verstraete FJM, Arzi B, Huey DJ, Cissell DD, Athanasiou KA. Regenerating mandibular bone using rhBMP-2: Part 2–treatment of chronic, defect non-union fractures. Vet Surg 2015; 44 (04) 410-416
    CrossrefPubMedGoogle Scholar
  • 17 Boudrieau RJ. Initial experience with rhBMP-2 delivered in a compressive resistant matrix for mandibular reconstruction in 5 dogs. Vet Surg 2015; 44 (04) 443-458
    CrossrefPubMedGoogle Scholar
  • 18 Arzi B, Cissell DD, Pollard RE, Verstraete FJ. Regenerative approach to bilateral rostral mandibular reconstruction in a case series of dogs. Front Vet Sci 2015; 2: 4
    CrossrefPubMedGoogle Scholar
  • 19 Arzi B, Verstraete FJM, Huey DJ, Cissell DD, Athanasiou KA. Regenerating mandibular bone using rhBMP-2: Part 1–immediate reconstruction of segmental mandibulectomies. Vet Surg 2015; 44 (04) 403-409
    CrossrefPubMedGoogle Scholar
  • 20 Pinel CB, Pluhar GE. Clinical application of recombinant human bone morphogenetic protein in cats and dogs: a review of 13 cases. Can Vet J 2012; 53 (07) 767-774
    PubMedGoogle Scholar
  • 21 Milovancev M, Muir P, Manley PA, Seeherman HJ, Schaefer S. Clinical application of recombinant human bone morphogenetic protein-2 in 4 dogs. Vet Surg 2007; 36 (02) 132-140
    CrossrefPubMedGoogle Scholar
  • 22 Schmoekel HG, Weber FE, Hurter K. et al. Enhancement of bone healing using non-glycosylated rhBMP-2 released from a fibrin matrix in dogs and cats. J Small Anim Pract 2005; 46 (01) 17-21
    CrossrefPubMedGoogle Scholar
  • 23 Massie AM, Kapatkin AS, Fuller MC, Verstraete FJM, Arzi B. Outcome of nonunion fractures in dogs treated with fixation, compression resistant matrix, and recombinant human bone morphogenetic protein-2. Vet Comp Orthop Traumatol 2017; 30 (02) 153-159
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Seeherman H, Wozney J, Li R. Bone morphogenetic protein delivery systems. Spine 2002; 27 (16, Suppl 1): S16-S23
    CrossrefPubMedGoogle Scholar
  • 25 Lu SX, Fiorini T, Lee J. et al. Evaluation of a compression resistant matrix for recombinant human bone morphogenetic protein-2. J Clin Periodontol 2013; 40 (07) 688-697
    CrossrefPubMedGoogle Scholar
  • 26 Zaidi Q, Danisa OA, Cheng W. Measurement techniques and utility of Hounsfield unit values for assessment of bone quality prior to spinal instrumentation: a review of current literature. Spine 2019; 44 (04) E239-E244
    CrossrefPubMedGoogle Scholar
  • 27 Schreiber JJ, Anderson PA, Hsu WK. Use of computed tomography for assessing bone mineral density. Neurosurg Focus 2014; 37 (01) E4
    CrossrefPubMedGoogle Scholar
  • 28 Cook JL, Evans R, Conzemius MG. et al. Proposed definitions and criteria for reporting time frame, outcome, and complications for clinical orthopedic studies in veterinary medicine. Vet Surg 2010; 39 (08) 905-908
    CrossrefPubMedGoogle Scholar
  • 29 Moreno MR, Zambrano S, DeJardin LM, Saunders WB. Bone biomechanics and fracture biology. In: Veterinary Surgery: Small Animal. 2nd edition. St. Louis, MO: Elsevier; 2018: 613-649
    Google Scholar
  • 30 Franczuszki D, Chalman JA, Butler HC, DeBowes RM, Leipold H. Postoperative effects of experimental femoral shortening in the mature dog. J Am Anim Hosp Assoc 1987; 23: 429-437
    PubMedGoogle Scholar
  • 31 Andreoni AA, Rytz U, Vannini R, Voss K. Ground reaction force profiles after partial and pancarpal arthrodesis in dogs. Vet Comp Orthop Traumatol 2010; 23 (01) 1-6
    Article in Thieme ConnectPubMedGoogle Scholar
  • 32 Eward C, Gillette RL, Eward W. Effects of unilaterally restricted carpal range of motion on kinematic gait analysis of the dog. Vet Comp Orthop Traumatol 2003; 16 (03) 158-163
    Article in Thieme ConnectPubMedGoogle Scholar
  • 33 Schmoekel H, Schense JC, Weber FE. et al. Bone healing in the rat and dog with nonglycosylated BMP-2 demonstrating low solubility in fibrin matrices. J Orthop Res 2004; 22 (02) 376-381
    CrossrefPubMedGoogle Scholar
  • 34 Krestan CR, Noske H, Vasilevska V. et al. MDCT versus digital radiography in the evaluation of bone healing in orthopedic patients. AJR Am J Roentgenol 2006; 186 (06) 1754-1760
    CrossrefPubMedGoogle Scholar
  • 35 Fisher JS, Kazam JJ, Fufa D, Bartolotta RJ. Radiologic evaluation of fracture healing. Skeletal Radiol 2019; 48 (03) 349-361
    CrossrefPubMedGoogle Scholar
  • 36 Markel MD, Morin RL, Wikenheiser MA, Lewallen DG, Chao EYS. Quantitative CT for the evaluation of bone healing. Calcif Tissue Int 1991; 49 (06) 427-432
    CrossrefPubMedGoogle Scholar
  • 37 Do TD, Sutter R, Skornitzke S, Weber MA. CT and MRI techniques for imaging around orthopedic hardware. Röfo Fortschr Geb Röntgenstr Nuklearmed 2018; 190 (01) 31-41
    Article in Thieme ConnectPubMedGoogle Scholar