Healos/recombinant human growth and differentiation factor-5 induces posterolateral lumbar fusion in a New Zealand white rabbit model.

STUDY DESIGN: Posterolateral lumbar spine fusions in New Zealand white rabbits. OBJECTIVE: To evaluate the efficacy of recombinant human growth and differentiation factor-5 (rhGDF-5) lyophilized to a Healos carrier (cross-linked type I collagen with hydroxyapatite coating; DePuy Spine, Inc., Raynham, MA) in inducing fusion. SUMMARY OF BACKGROUND DATA: Bone graft substitutes have become an area of considerable interest. rhGDF-5 is one such product. Limited lumbar preclinical studies have been performed with this product. METHODS: Single-level, intertransverse process fusions were performed in 67 rabbits using iliac crest autograft (n = 13), Healos alone (n = 13), or 0.5, 1.0, or 1.5 mg/cc rhGDF-5 lyophilized to Healos (n = 13 per group). At 8 weeks, the rabbits were euthanized. Fusion masses were assessed. RESULTS: There were 2 animals (3%) lost to complication. Manual palpation revealed fusion rates for autograft of 38% (5/13), Healos alone of 0% (0/13), and each of the Healos/rhGDF-5 groups of 100% (13/13). Histologic analyses were 95% sensitive and 95% specific for confirming fusion. Histologic differences were found among the treatment groups. CONCLUSIONS: In this rabbit fusion model, Healos/rhGDF-5 induced fusion in 100% of the rabbits studied. This rate was significantly higher than the fusion rate induced by autograft (38%). Overall, these results support continued research of Healos/rhGDF-5 as a potential bone graft alternative.

Effect of daily parathyroid hormone (1-34) on lumbar fusion in a rat model.

BACKGROUND CONTEXT: Despite numerous studies evaluating the anabolic effects of intermittent administration of parathyroid hormone (PTH) on bone, there are no published studies examining its effect on spinal fusion outcomes. PURPOSE: To determine the effect of daily injection of human recombinant PTH(1-34) on posterolateral lumbar fusions in a rat model. STUDY DESIGN: Prospective, case-controlled, preclinical animal study. OUTCOME MEASURES: Manual palpation and serum osteocalcin. METHODS: Single-level, intertransverse process spinal fusions were performed with iliac crest autograft in 56 Sprague-Dawley rats. Animals received daily injections of placebo or PTH(1-34). At 6 weeks, fusion masses were assessed by manual palpation. Serum osteocalcin levels were assessed in a subset of the animals. RESULTS: Manual palpation revealed the control group to have a fusion rate of 37% (10/27) and the PTH(1-34)-treated group to have a fusion rate of 52% (15/29). Mean serum osteocalcin levels were 59.8 and 88.6 ng/L for the control and PTH(1-34) groups, respectively. CONCLUSIONS: There was a trend towards greater fusion rate in the PTH(1-34) group as compared with the placebo group. Further, PTH(1-34) administration was associated with a significant increase in osteocalcin levels. Certainly, further investigations are warranted, as an injectable agent capable of increasing fusion rates would be of great clinical value.

Animal models for spinal fusion.

Animal models for spinal fusion are essential for preclinical testing of new fusion methods and adjuncts. They allow for control of individual variables and quantification of outcome measures. Model characteristics are considered. Preclinical experiments to evaluate proof of concept, feasibility, and efficacy are generally studied in an orderly progression from smaller to larger animal models with an evolving cascade of evidence which has become known as the "burden of proof". Methods of fusion analysis include manual palpation, radiographs, computed tomography, histology, biomechanical testing, and molecular analysis. Models which have been developed in specific species are reviewed. This sets the stage for the interpretation of studies evaluating bone graft materials such as allograft, demineralized bone matrices, bone morphogenetic proteins, ceramics, and others with consideration of the variables affecting their success. As evidence accumulates, clinical trials and applications are defined.