Faculty Collaboration Database

Transient Local Bone Remodeling Effects of rhBMP-2 in an Ovine Interbody Spine Fusion Model. J Bone Joint Surg Am 2016 Dec 21;98(24):2061-2070

Date

12/22/2016

Pubmed ID

28002369

DOI

10.2106/JBJS.16.00345

Scopus ID

2-s2.0-85015945754 (requires institutional sign-in at Scopus site)   20 Citations

Abstract

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.

Author List

Bae HW, Patel VV, Sardar ZM, Badura JM, Pradhan BB, Seim HB 3rd, Turner AS, Toth JM

Author

Jeffrey M. Toth PhD Associate Dean for Research in the School of Dentistry department at Marquette University

MESH terms used to index this publication - Major topics in bold

Animals
Bone Morphogenetic Protein 2
Bone Remodeling
Diskectomy
Dose-Response Relationship, Drug
Female
Lumbar Vertebrae
Models, Animal
Osteogenesis
Recombinant Proteins
Sheep
Spinal Fusion
Transforming Growth Factor beta
Treatment Outcome