Influence of systemic bisphosphonate treatment on mechanical properties of BMP-induced calluses in a rat fracture model: comparison of three-point bending and twisting test.

Abstract

The combination of autograft, BMP and bisphosphonate has been shown to produce strong calluses. In this study, without autograft we investigate the effect of bisphosphonate treatment on BMP-induced calluses, both in bending and in rotation. Sprague-Dawley rats (n = 42) underwent femoral osteotomy and BMP-7 treatment. At 2 weeks an injection of saline or bisphosphonate was administered. The animals were sacrificed after 6 weeks. Both femurs were tested in either three-point bending or twisting. All femurs healed. BMP + bisphosphonate-treatment led to larger calluses (p < 0.05) and in three-point bending, higher ultimate force (p < 0.01) and greater stiffness (p < 0.05) than BMP alone. The BMP + bisphosphonate group was nearly 60% stronger than controls, while the BMP group did not reach the strength (p < 0.05) nor stiffness (p < 0.01) of the controls. In the twisting test, similar trends were found but less pronounced. Three-point bending produced transverse callus associated fractures, whereas the twisting test produced spiral fractures, located in the structurally weaker distal femur. BMP + bisphosphonate-treatment produces calluses that are mechanically superior to calluses induced by BMP alone, when tested both in three-point bending and in twisting. For the mechanical evaluation of pharmacologically enhanced calluses with breaking strengths exceeding the native bone, the bending test is recommended.