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Transient Local Bone Remodeling Effects of rhBMP-2 in an Ovine Interbody Spine Fusion Model

Bae, Hyun W. MD; Patel, Vikas V. MD; Sardar, Zeeshan M. MD CM, MSc, FRCSC; Badura, Jeffrey M. MS; Pradhan, Ben B. MD, MSE; Seim, Howard B. III DVM, Dipl ACVS; Turner, A. Simon BVSc, MS, Dipl ACVS, DVSc(h-c); Toth, Jeffrey M. PhD

Journal of Bone & Joint Surgery - American Volume: 21 December 2016 - Volume 98 - Issue 24 - p 2061–2070
doi: 10.2106/JBJS.16.00345
Scientific Articles

Background: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a powerful osteoinductive morphogen capable of stimulating the migration of mesenchymal stem cells (MSCs) to the site of implantation and inducing the proliferation and differentiation of these MSCs into osteoblasts. Vertebral end-plate and vertebral body resorption has been reported after interbody fusion with high doses of rhBMP-2. In this study, we investigated the effects of 2 rhBMP-2 doses on peri-implant bone resorption and bone remodeling at 7 time points in an end-plate-sparing ovine interbody fusion model.

Methods: Twenty-one female sheep underwent an end-plate-sparing discectomy followed by interbody fusion at L2-L3 and L4-L5 using a custom polyetheretherketone (PEEK) interbody fusion device. The PEEK interbody device was filled with 1 of 2 different doses of rhBMP-2 on an absorbable collagen sponge (ACS): 0.13 mg (1×) or 0.90 mg (7×). Bone remodeling and interbody fusion were assessed via high-resolution radiography and histological analyses at 1, 2, 3, 4, 8, 12, and 20 weeks postoperatively.

Results: Peri-implant bone resorption peaked between 3 and 8 weeks in both the 1× and the 7× rhBMP-2/ACS-dose group. Osteoclastic activity and corresponding peri-implant bone resorption was dose-dependent, with moderate-to-marked resorption at the 7×-dose level and less resorption at the 1×-dose level. Both dose (p < 0.0007) and time (p < 0.0025) affected bone resorption significantly. Transient bone-resorption areas were fully healed by 12 weeks. Osseous bridging was seen at all but 1 spinal level at 12 and at 20 weeks.

Conclusions: In the ovine end-plate-sparing interbody fusion model, rhBMP-2 dose-dependent osteoclastic resorption is a transient phenomenon that peaks at 4 weeks postoperatively.

Clinical Relevance: Using the U.S. Food and Drug Administration (FDA)-approved rhBMP-2 concentration and matching the volume of rhBMP-2/ACS with the volume of desired bone formation within the interbody construct may limit the occurrence of transient bone resorption.

1Spine Center, Department of Surgery (H.W.B.), Cedars-Sinai Medical Center (Z.M.S.), Los Angeles, California

2Department of Orthopaedic and Spine Surgery, University of Colorado Health Sciences Center, Aurora, Colorado

3Medtronic Sofamor Danek, Inc., Memphis, Tennessee

4Risser Orthopaedic Group, Pasadena, California

5Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado

6Department of Orthopaedic Surgery, The Medical College of Wisconsin, Milwaukee, Wisconsin

E-mail address for H.W. Bae: baemd@me.com

Copyright 2016 by The Journal of Bone and Joint Surgery, Incorporated
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