Ne-Osteo Bone Growth Factor for Posterolateral Lumbar Spine Fusion: Results From a Nonhuman Primate Study and a Prospective Human Clinical Pilot Study

Abstract

Study Design. Prospective animal and human clinical pilot trial.Objectives. The purpose of this study was to determine and test the dose of Ne-Osteo growth factor extract and carrier required for consistent radiographic bone induction in humans.Summary of Background Data. Preclinical studies have demonstrated that Ne-Osteo, an extract-containing bone morphogenetic proteins, was successful at generating spine fusion in rabbits and rhesus monkeys. Consistent fusions have yet to be achieved in nonhuman primates and humans.Methods. Adult rhesus monkeys underwent singlelevel posterolateral intertransverse lumbar arthrodesis with either 3.0 mg (N ϭ 4), 5.0 mg (N ϭ 4), 12.5 mg (N ϭ 4), or 25 mg (N ϭ 4) of Ne-Osteo per side. Animals were killed after 24 weeks. In the human clinical trial, 22 patients (18 females, 4 males) had lumbar spinal stenosis and/or spondylolisthesis requiring spine arthrodesis. To minimize patient risk of nonunion, patients received autogenous bone graft from the posterior iliac crest on one side and Ne-Osteo growth factor on the other. The dose was 12.5 mg, 25 or 50 mg, or 25 mg Ne-Osteo per side performed in the three phases, respectively.Results. Three of four monkeys that received 12.5 mg Ne-Osteo per side and four of four that received 25 mg per side achieved solid fusions. In phase I of the human clinical trial, two of six patients showed radiographic bone induction (plain radiograph, CT scans-blindly evaluated) on the Ne-Osteo side (12.5-mg dose). In phase II, both sides were graded as fused in five of six patients. Although graded as fused, the 6-month scans demonstrated a ring of new bone with the center filling in slower (12-24 mo) than was predicted by nonhuman primate studies. As a result, phase III carrier was designed to have a more porous/open early fusion mass than with the dense DBM paste (used in phase I and II) by mixing in local bone or cancellous allograft chips. Results using the 25-and 50-mg doses were the same, so 25 mg was used in phase III. In phase III, 9 of 10 autograft were fused by 12 months. Five of five patients with Ne-Osteo plus local bone and four of five with allograft chips were fused by 6 months. The one patient in this group that did not heal on either the autograft or the Ne-Osteo side was a smoker.Conclusions. A graft composite of Ne-Osteo bone growth factor with human DBM with or without cancellous allograft or local bone autograft was capable of achieving a contiguous spine fusion mass in 15 of 16 patients at a dose of at least 25 mg per side. This result was comparable with the results using iliac crest autograft (94%) in this side-by-side model. These results warrant confirmation in a definitive trial using Ne-Osteo on both sides of the spine and thus avoiding the need for iliac crest bone graft harvest. [

Influence of decortication of the recipient graft bed on graft integration and tissue neoformation in the graft-recipient bed interface

“…They are considered to be the first choice of bone graft due to their osteoconductive, osteoinducing and osteogenic properties, with their integration with the recipient bed occurring through a cascade of cellular and molecular events [11]. Bone graft integration in vertebral arthrodesis is related to local and systemic factors and the recipient graft bed acts as an important local factor for graft integration [2]. Decortication of the recipient graft bed exposes the elements of bone marrow and accelerates bone integration [6].…”

The Clinical Use of Allografts, Demineralized Bone Matrices, Synthetic Bone Graft Substitutes and Osteoinductive Growth Factors: A Survey Study

“…Despite their potential limitations such as cost, possible adverse effects, and lack of osteoconductive properties, these growth factors are highly osteogenic [5,6]. Therefore, it is recommended to use such products when host bone is biologically compromised to aid in the incorporation of additional bone graft material.…”

Influência da decorticação vertebral na neoformação dos tecidos da interface do enxerto ósseo

“…12 Decortication of the receptor bone bed of the graft accelerates bone integration. 4 The biological factors involved in this phenomenon are not yet fully known, 13 having been the motivation for the preparation of the experimental model, in which a small animal like the rat was used to quantify the phenomenon of osteogenesis between the decorticated or non-decorticated receptor bed and the bone graft.…”