gms | German Medical Science

Objectives: Hypertension represents one of the major challenges for the public health care system, as it continues to be a critical contributor to the global burden of disease and mortality. Calcium channel blockers (CCBs) are widely used in the treatment of hypertension. Interestingly, CCBs have been shown to influence bone metabolism. However, there is little information on whether CCBs also influence the process of fracture healing. Therefore, we studied the effect of the CCB amlodipine on bone healing in a stable closed fracture model in mice using intramedullary screw fixation.

Methods: CD-1 mice with an age of 12-16 weeks were used. Under aseptic conditions a tungsten guidewire (diameter of 0.2 mm) was inserted through the intramedullary canal of the femur. Afterwards the femur wer fractured by a 3-point bending device and an intramedullary medical stainless steel screw (18 mm length, 0.5 mm diameter) was implanted over the guidewire to stabilize the fracture. Animals were treated daily with amlodipine low dose (1 mg/kg body weight), amlodipine high dose (3 mg/kg body weight) or vehicle (NaCl) per os. Bone healing was analyzed by radiology, biomechanics, histomorphometry and Western blot at 2 and 5 weeks after fracture healing.

Results and Conclusion: At 2 and 5 weeks after fracture healing, the histomorphometric analysis revealed a significantly higher ratio of bone tissue within the callus of amlodipine low dose- and high dose-treated animals, when compared to controls. This was associated with a lower amount of cartilaginous and fibrous tissue. Moreover, Western blot analysis revealed a significantly increased expression of bone morphogenetic protein (BMP)-2 and vascular endothelial growth factor (VEGF). In addition, the analysis showed a 5-fold higher expression of osteoprotegerin (OPG) and a 10-fold elevated expression of the receptor activator of NF-kappaB ligand (RANKL), indicating an increased bone turnover. These findings demonstrate that amlodipine accelerates fracture healing by stimulation of bone formation, callus remodeling and osteoclast activity.