THE EFFECT OF SYSTEMIC ADMINISTRATION OF SIMVASTATIN TO FRACTURE HEALING: AN EXPERIMENTAL STUDY

Abstract

Introduction: Approximately 15% of fractures account for delayed or impaired healing. The popularity of new

Methods: that enhance fracture healing along with conventional ones is growing. The purpose of this study was to determine the effects, the safety and the efficacy of systemic simvastatin administration to bone healing.

Materials and Methods: Unilateral mid-ulnar osteotomies (approximately 2.0 mm wide) were performed to 56 skeletally mature male rabbits. The limbs were assigned to one of three groups: those treated with 30 mg/kg/day of simvastatin per os, those administered with 10 mg/kg/day of simvastatin orally and the control group. The rabbits were killed at two or four weeks postoperatively after taking blood samples for biochemical analysis to detect drug-induced side effects. After the rabbits were killed, the limbs were scanned with peripheral quantitative computed tomography to assess the area and mineral content of the mineralized callus. The bones were subjected to mechanical bending testing and histomorphometry.

Results: At 2 weeks the total density for the mineralized callus was on average 531.7±32.7 for the control group, 466.05±10.6 for the first group (p< .01) and at 4 weeks the total density was 617.5±12.42 for the control group, 551.26±27.61 for the first group, and 553.72±20.66 for the second group respectively (p< .001). Biomechanical properties were similar to all groups at 2 and 4 weeks. The% cartilage portion area was 17.28±2.61 for the control group, 11.89±1.84 for the first group (p< .001) and 14.06±2.17 for the second group (p< .05).

Discussion: The data show that daily systemic administration of simvastatin in 30 mg/kg/day or 10 mg/kg/day do not seem to produce a clear anabolic effect in fracture healing through the remodeling phase.

Conclusion: The use of simvastatin to promote fracture healing is still under study. The limitations from its use are the side effects from its systematic administration over 30 mg/kg/day. Most likely, alternative ways of administration should be considered for future studies.