Abstract
Introduction: The potential of Bone Morphogenic Protein (BMP) to improve fracture healing is of great interest to orthopaedic surgeons. Although the complex mechanisms leading from the presence of local BMP to the fracture scenario has yet to be elucidated. The purpose of this study was to investigate whether introducing rhBMP-2 to the fracture arena, some days after fixation could be more beneficial to fracture repair.
Methods: 40 animals were randomised into 4 groups; namely control treatment at day 0 or rhBMP-2 treatment at days 0, 4 or 8 post-surgery. All animals underwent a previously validated surgical procedure involving creation of an open femoral fracture fixed using a 4-pin external fixator. 30 μl of bovine serum albumin (BSA) alone (control) or mixed with 2.5 μg of rhBMP-2 (treatments) was injected via a lateral approach directly into the fracture gap, either following closure of the wounds (day 0) or at 4 or 8 days postoperatively. Animals were assessed as to the outcome of surgery by digital sequential x-ray at days 0, 8, 16 and 22 using a Faxitron MX-20 camera; and y either biomechanical testing under a 3-point bending technique (Lloyd Instruments Ltd, UK) or histological examination following sacrifice at day 22. Data were analysed using Mann-Whitney U and Wilcoxon Tests for statistical differences (SPSS, Version 9). Differences were considered significant when p< 0.05.
Results: X-ray analysis indicated that healing of fractures treated with rhBMP-2 at day 0 or day 4 was significantly greater than the two other groups at days 16 and 22. BMP given at day 4 tended to a greater effect than when given at day 0, though the range was too great to show a statistical difference. There were no differences between the BMP-8 and the BSA control groups. Mechanical testing showed that only animals that had received rhBMP-2 at day 4 had attained similar peak loads to failure to those of their contralateral unoperated leg. Bones from animals receiving rhBMP-2 at day 0 had attained the next greatest strength, which was followed by rhBMP-2 administration at day 8 animals, whereas the animals receiving BSA attaining the least strength. There was a statistical difference (p< 0.05) between both rhBMP-2 day 4 and day 0 groups compared to the BSA control group. Qualitative histology suggested that the rhBMP-2 day 0 and day 4 groups had almost fully healed with new bone whereas the BSA and rhBMP-2 day 8 groups still had considerable mounts of fibrous tissue and cartilage at the fracture gap 22 days following surgery.
Conclusions: The study demonstrates that a single percutaneous injection of rhBMP-2 has a positive effect on fracture healing, when prescribed at the time of injury or during the early period of fracture repair. Data suggests that the most effective timing of delivery of BMP may not be at the time of surgery but in the early healing phase. The day 4 time point in the mouse model is likely to equate to that of 7–10 days in larger animals or humans. Further investigation as to the most appropriate time for intervention using these proteins is warranted and may negate the current requirement for carried products and large doses of these expensive drugs.
The abstracts were prepared by Emer Agnew. Correspondence should be addressed to Irish Orthopaedic Association, Secretariat, c/o Cappagh National Orthopaedic Hospital, Finglas, Dublin 11, Ireland.
