Comparative study of fusion rate induced by different dosages of Escherichia coli-derived recombinant human bone morphogenetic protein-2 using hydroxyapatite carrier

Abstract

BACKGROUND CONTEXT: Hydroxyapatite (HA) is considered to be useful because of its high affinity for recombinant human bone morphogenetic protein (rhBMP), mechanical resistance to compressive force, and possible reduction of rhBMP dose. PURPOSE: To evaluate the osteoinductivity of Escherichia coli-derived rhBMP-2 and the suitability of porous HA as an rhBMP-2 carrier. STUDY DESIGN: In vivo study using microcomputerized tomography (micro-CT) scanning. PATIENT SAMPLE: Seventy-six New Zealand white male rabbits were randomized into a single control group (n=14) without rhBMP-2 and four experimental groups (10 mu g, 50 mu g, 200 mu g, and 500 mu g of rhBMP-2; n=14 in each group). The subjects were divided into 3- and 6-week groups. OUTCOME MEASURES: Outcome was evaluated by radiography, bending test, three-dimensional micro-CT, and histologic examinations. METHODS: Bilateral posterolateral fusion was carried out, and rhBMP-2 (0, 10, 50, 200, 500, 1,000, and 2,000 mu g) was implanted into the bilateral transverse processes using HA as a carrier. RESULTS: The fusion rates of the 3-week group were 83.3% for 50 and 200 mu g of rhBMP-2 and 100% for 500 mu g. The improved fusion rates of the 50 mu g or higher groups compared with those of control were statistically significant. The fusion rates of the 6-week group were 75% for 10 mu g of rhBMP-2 and 100% for 50 mu g or higher. Similarly, the improved fusion rates of the 10 mu g or higher groups compared with those of control were statistically significant. Significantly higher percent volumes were observed in the 3-week 200 mu g of rhBMP-2 group and 6-week 200 mu g of rhBMP-2 group than the 3-week HA group and 6-week HA group, respectively. Trabecular thickness was significantly higher in the 3-week 200 mu g of rhBMP-2 group than the 3-week HA group. Histologic analysis of the 10 mu g group showed bone tissues within the pores from 3 weeks, and this was observed more vividly in the 50, 200, and 500 mu g groups. The 6-week 10 mu g and 50 mu g of rhBMP-2 groups had lower amounts of new tissue but higher portions of complete bone tissue within the HA specimen, along with higher formation of completely reconstituted bone tissues outside HA. CONCLUSIONS: Injection of 50 mu g or more of E. coli-derived rhBMP-2 into a HA carrier induced earlier bone fusion in the intertransverse process of rabbits, which confirms the excellent bone forming ability of E. coli-derived rhBMP-2 and the suitability of HA as a carrier of rhBMP-2. (C) 2012 Elsevier Inc. All rights reserved.