Comparative Efficacy of Commonly Available Human Bone Graft Substitutes as Tested for Posterolateral Fusion in an Athymic Rat Model

Neil Bhamb; Linda E A Kanim; Susan Drapeau; Suneeth Mohan; Erick Vasquez; Dan Shimko; William McKAY; Hyun W Bae

doi:10.14444/6059

Comparative Efficacy of Commonly Available Human Bone Graft Substitutes as Tested for Posterolateral Fusion in an Athymic Rat Model

Int J Spine Surg. 2019 Oct 31;13(5):437-458. doi: 10.14444/6059. eCollection 2019 Oct.

Authors

Neil Bhamb¹, Linda E A Kanim², Susan Drapeau³, Suneeth Mohan³, Erick Vasquez³, Dan Shimko³, William McKAY³, Hyun W Bae¹

Affiliations

¹ Cedars-Sinai Medical Center, Los Angeles, California.
² Translational and Clinical Research, Spine Center, Cedars-Sinai Medical Center, Los Angeles, California.
³ Medtronic, Inc, Memphis, Tennessee.

PMID: 31745449
PMCID: PMC6836878
DOI: 10.14444/6059

Abstract

Background: Insufficient data exist on bone graft substitute materials efficacy; two thirds lack any clinical data.1,2 This prospective animal study identified efficacy differences among commercially available materials of several classes.

Methods: Historically validated muscle pouch osteoinduction study (OIS) and posterolateral fusion (PLF) were performed in an athymic rat model. Grafting material products implanted were demineralized bone matrix (DBM)-based allografts (Accell EVO3, DBX Mix, DBX Strip, Grafton Crunch, Grafton Flex, Grafton Matrix, Grafton Putty, Magnifuse, and Progenix Plus), allografts (OsteoSponge, MinerOss), cellular allograft (Osteocel Plus), ceramics (Mozaik Strip), or activated ceramics (Actifuse ABX Putty, Vitoss BA). After 4 weeks, OIS specimens were evaluated ex vivo by histologic osteoinductivity. After 8 weeks, PLF ex vivo specimens were evaluated for fusion by manual palpation (F_MP), radiography (F_XR), and histology (F_HISTO).

Results: OIS: No materials exhibited a rejection reaction on histology. All DBM-based materials exhibited osteoinductive potential as new bone formation at > 88% of implanted sites. One plain allograft (OsteoSponge) formed bone at 25% of sites. No bone formed for one ceramic (Mozaik Strip), three activated ceramics (Actifuse ABX Putty), or one cellular allograft, regardless of human bone marrow aspirate (hBMA) when added. PLF: Among the 10 DBMs, 6 had F_MP of 100% (Accell EVO3, DBX Mix, DBX Strip, Grafton Flex, Grafton Putty, Magnifuse), 2 had F_MP of 94% (Grafton Crunch, Grafton Matrix), and 2 conditions had F_MP of 0% (Progenix Plus, Progenix Plus + athymic rat iliac crest bone graft [arICBG]). Ceramics (Mozaik Strip), activated ceramics (Actifuse ABX Putty, Vitoss BA), plain allograft (OsteoSponge, MinerOss (PLF study), and cellular allograft (Osteocel Plus) demonstrated 0% F_MP. ArICBG demonstrated 13% F_MP.

Conclusions: Eight DBM-based materials (Accell EVO3, DBX Mix, DBX Strip, Grafton Crunch, Grafton Flex, Grafton Matrix, Grafton Putty, Magnifuse) demonstrated excellent (> 90% F_MP) efficacy in promoting fusion via bone healing. Two DBM conditions (Progenix Plus, Progenix Plus + arICBG) showed no manual palpation fusion (F_MP). Systematically, over the 2 studies (OIS and PLF), cellular (Osteocel Plus), plain allografts (OsteoSponge, MinerOss; PLF study), ceramic (Mozaik Strip), and activated ceramics (Actifuse ABX Putty, Vitoss BA) demonstrated poor F_MP efficacy (< 10%).

Clinical relevance: When selecting DBMs, clinicians must be cognizant of variability in DBM efficacy by product and lot. While theoretically osteoinductive, cellular allograft and activated ceramics yielded poor in vivo efficacy. Whole allograft and ceramics may provide osteoconductive scaffolding for mixed-material grafting; however, surgeons should be cautious in using them alone. Direct clinical data are needed to establish efficacy for any bone graft substitute.

Keywords: activated ceramic; allografts; athymic rats; autograft; bone; bone grafts; bone morphogenetic protein; cellular allografts; ceramic; demineralized bone matrix (DBM); demineralized bone matrix-based products (DBM-based products); differentiation factor; expander; muscle pouch; peptide; posterolateral fusion; rat model; rats; recombinant human bone morphogenetic protein; rhBMP; rhBMP-2; substitute.