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

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 μg, 50 μg, 200 μg, and 500 μg 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 μg) 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 μg of rhBMP-2 and 100% for 500 μg. The improved fusion rates of the 50 μg or higher groups compared with those of control were statistically significant. The fusion rates of the 6-week group were 75% for 10 μg of rhBMP-2 and 100% for 50 μg or higher. Similarly, the improved fusion rates of the 10 μg or higher groups compared with those of control were statistically significant. Significantly higher percent volumes were observed in the 3-week 200 μg of rhBMP-2 group and 6-week 200 μg 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 μg of rhBMP-2 group than the 3-week HA group. Histologic analysis of the 10 μg group showed bone tissues within the pores from 3 weeks, and this was observed more vividly in the 50, 200, and 500 μg groups. The 6-week 10 μg and 50 μg 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 μg 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.