Reverse Dynamization Efficiently Heals Large Segmental Bone Defects Using a Reduced Dose of BMP-2

Introduction: Several treatments exist for the healing of large bone defects, including recombinant human bone morphogenetic protein-2 (BMP-2). In previous studies we demonstrated that the local mechanical environment influenced the healing of defects using 11μg dose of BMP-2. Improved results were obtained with Reverse Dynamization (RD), in which defects are initially stabilized with low axial stiffness followed with high. The goal of the study was to determine whether RD can reduce the dose of BMP-2 needed for bone union.

Methods: Rat, femoral, 5 mm defects were stabilized with 3 different stiffnesses, using the RD treatment with 5.5μg BMP-2. For RD, the defects were stabilized with low stiffness for 2 weeks followed by high stiffness for 6 weeks. Groups were healed under constant conditions of low (40%), medium (70%), high (100%; axial stiffness-254 N/mm²), and RD. Healing was monitored by X-rays, and at the end of treatment (8 wks) by μCT and histology.

Results: The results showed that the callus size was smaller at 8-weeks with the two highest fixation stiffnesses. This data confirms our previous findings that a lower stiffness fixator produced bigger callus formation compared to more rigid fixators, and showed an accelerated healing process with RD. These defects appeared to be smaller in diameter compared to the constant low stiffness (40%) group, having a more organized architecture with thicker distribution of new cortical bone and less trabecular bone.

Discussion: This data confirms the influence of modulating the mechanical environment on the healing of defects usinga reduced dose of 5.5 μg BMP-2. Healing of defects in the RD group was superior to all other groups, showing significantly improved and accelerated healing. The data confirms that the axial stiffness of the fixator can be modulated to maximise the regenerative capacity of bone healing with a reduced dose of BMP-2.