Effects of combined therapy of alendronate and low-intensity pulsed ultrasound on metaphyseal bone repair after osteotomy in the proximal tibia of aged rats

Bisphosphonates and low-intensity pulsed ultrasound (LIPUS) are both known to maintain or promote callus formation during diaphyseal fracture healing. However, the effect of these treatments on the repair of metaphyseal fractures has not been elucidated. To evaluate the effects of bisphosphonates and/or LIPUS on cancellous bone healing, an osteotomy was performed on the proximal tibial metaphysis of 9-month-old Sprague–Dawley rats (n = 64). Treatment with alendronate (1 μg/kg/day), LIPUS (20 min/day), or a combination of both was administered for 2 or 4 weeks, after which changes in bone mineral density (BMD), bone histomorphometric parameters, and the rate of cancellous bony bonding were measured. Alendronate suppressed bone resorption parameters at 2 weeks (p = 0.019) and increased bone volume and BMD at 4 weeks (p = 0.034 and p = 0.008, respectively), without affecting bony bonding. LIPUS had no significant effect on any of the histomorphometric parameters at 2 or 4 weeks, but significantly increased in BMD at 4 weeks (p = 0.026) as well as the percentage of bony bonding at both 2 and 4 weeks (p < 0.01). The combined therapy also showed significantly increased BMD compared with the control group at 4 weeks (p = 0.010) and showed a trend toward increased bony bonding. In conclusion, alendronate and LIPUS cause an additive increase in BMD at the affected metaphysis: alendronate increases the bone volume at the osteotomy site without interrupting metaphyseal repair, whereas LIPUS promotes metaphyseal bone repair, without affecting bone histomorphometric parameters.