Demineralized bone matrix, bone morphogenetic proteins, and animal models of spine fusion: an overview

Abstract

IntroductionThe last few decades have seen the remarkable development of spinal fixation devices. In current clinical use, devices are used to attach nearly every component of the spinal anatomy, including lamina, pedicles, spinous processes, facet joints, pars interarticuli and vertebral bodies. Unstable motion segments are often fused using constructs composed of plates, rods, wires and cages. Metals used include stainless steel, titanium and tantalum alloys. Ultimately, however, the success of any spinal fusion is dictated by biologic principles. Only a biologic environment conducive to bone formation and consolidation will allow successful osseous arthrodesis to occur.Research efforts in the last decade have focused on morphogenetic proteins, opening exciting new avenues in spinal fusion surgery. Several osteoinductive growth factors, referred to as the bone morphogenetic proteins (BMP), have been shown to induce the transformation of undifferentiated mesenchymal cells into chondroblasts and osteoblasts, resulting in the formation of de novo bone [2, 18, 19, 22, 36, 42, 43, 47, 55,72,73]. Numerous preclinical animal studies have demonstrated the superiority of BMP implants over traditional autogenous bone grafts for a variety of orthopedic applications [17, 25, 29, 32, 37, 49,66]. Considerable attention has been focused towards spinal applications for these innovative biologic tools, particularly for augmenting spinal fusion. Indeed, with the advances in molecular biology techniques, these proteins have been used in conjunction with gene therapy principles to deliver the protein at the desired fusion site in rats, leading to speculation as to "percutaneous" fusion in humans! The following sections thus summarize the key preclinical studies involving the BMPs and spinal fusion.Abstract Preclinical investigations on the use of bone morphogenetic proteins (BMP) in the spine have yielded promising results. This has led to the preliminary introduction of these growth factors in controlled clinical trials. Initial data made available suggest that these differentiating factors will play a major role in the treatment of spinal disorders in the future. This article reviews key preclinical studies and their results that formed the basis for introduction into clinical trials. Non-primate and nonhuman primate models of spine fusion with BMP are reviewed objectively, and important issues regarding carrier, dose, and site of implantation are discussed. Finally, exciting new gene therapy research is discussed, with comments made on its applicability for the future.

Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery

“…The identification of BMPs has generated great interest due to their potential use in bone regeneration. 3 Several recombinant forms of BMPs, mostly rhBMP-2 and rhBMP-7 (a.k.a., OP-1), have been shown to induce bone formation in vivo, [13][14][15][16][17][18][19][20][21][22][23][24] and both rhBMP-2 and rhBMP-7 have been tested in clinical trials. [25][26][27] In addition to the direct application of recombinant BMP proteins, numerous reports have confirmed the ability of adenoviral or retroviral vector-mediated gene transfer of several BMPs to induce bone formation in animal models.…”

Comparing ectopic bone growth induced by rhBMP‐2 on an absorbable collagen sponge in rat and rabbit models

“…23 It is clear, however, that ossicles can be induced in rabbit tissue. This would suggest that differences between the rat and rabbit results in this investigation may be due to the different site of implantation: SC versus IM.…”

Risk of graft fracture after dorso-ventral thoraco-lumbar spondylodesis: is there a correlation with graft size?

“…In USA, 200,000 surgeries for spinal fusion with bone grafting are performed every year [2]. This high number of spine surgeries confirms the recommendation that a surgical rather than a non-surgical approach should be preferred in the cases of spinal instability since the outcomes after surgical treatment are significantly superior to non-surgical treatment [3].…”