Local administration of alendronate reduced peri-tunnel bone loss and promoted graft-bone tunnel healing with minimal systemic effect on bone in contralateral knee.

Continued systemic administration of alendronate was reported to reduce peri-tunnel bone resorption and promoted graft-bone tunnel healing at the early stage post-anterior cruciate ligament (ACL) reconstruction. However, systemic increase in bone mineral density (BMD) in the contralateral intact knee was observed. We tested if single local administration of alendronate into the bone tunnel during ACL reconstruction could achieve similar benefits yet without the systemic effect on bone. Seventy-two rats with unilateral ACL reconstruction were divided into three groups: saline, low-dose (6 μg/kg) and mid-dose (60 μg/kg) alendronate. For local administration, alendronate was applied to the bone tunnels for 2 min before graft insertion and repair. At weeks 2 and 6, the reconstructed complex was harvested for high-resolution computed tomography (vivaCT) imaging followed by biomechanical test or histology. Our results showed that local administration of low-dose alendronate showed comparable benefits on the reduction of peri-tunnel bone loss, enhancement of bone tunnel mineralization, tunnel graft integrity, graft osteointegration and mechanical strength of the reconstructed complex at early stage post-reconstruction, yet with minimal systemic effect on mineralized tissue at the contralateral intact knee. A single local administration of alendronate at the low-dose therefore might be used to promote early tunnel graft healing post-reconstruction.