Alendronate reduced peri-tunnel bone loss and enhanced tendon graft to bone tunnel healing in anterior cruciate ligament reconstruction

Abstract

Peri-tunnel bone loss after anterior cruciate ligament (ACL) reconstruction is commonly observed, both clinically and experimentally. We aimed to study the effect and mechanisms of different doses of alendronate in the reduction of peritunnel bone loss and promotion of graft-bone tunnel healing in ACL reconstruction. Eighty-four ACL-reconstructed rats were divided into 4 groups. Alendronate at different dosages, or saline, were injected subcutaneously weekly, for 2 or 6 weeks post-reconstruction, for vivaCT (computed tomography) imaging, biomechanical tests, histology and immunohistochemistry. Alendronate significantly increased bone mass and density of tissue inside bone tunnels except at the epiphyseal region of tibial tunnel. The femoral tunnel diameter decreased significantly in the mid-dose and highdose alendronate groups compared to that in the saline group at week 6. Alendronate significantly increased the peri-tunnel bone mass and density along all tunnel regions at week 6. Better graft-bone tunnel integration and intra-tunnel graft integrity were observed in the alendronate groups. The ultimate load was significantly higher in the mid-dose and high-dose alendronate groups at week 2, but not at week 6. There was a reduction in matrix metalloprotein (MMP)1, MMP13 and CD68-positive cells at the peri-tunnel region and graft-bone interface in the alendronate-treated group compared to the saline group. Alendronate reduced peritunnel bone resorption, increased mineralised tissue inside bone tunnel as well as histologically and biomechanically promoted graft-bone tunnel healing, probably by reducing the expression of MMP1, MMP13 and CD68-positive cells. Alendronate might be used for reducing peri-tunnel bone loss and promoting graft-bone tunnel healing at early stage post-ACL reconstruction.

A comparative study of effect of autograft compared with allograft anterior cruciate ligament reconstruction on expressions of LOXs and MMPs

“…MMPs expression increased in the ACL itself after ACL injury [27]. Therefore, the graft bone tunnel healing could be improved by inhibiting MMPs expression [28]. The increase in MMP expression in the ligament is consistent with prior report that levels of MMP-1 and MMP-3 in the knee were significantly higher, suggesting that increased levels of both enzymes in the knee indicate enhanced severity of synovial inflammation and also accelerated activity of joint destruction [29].…”

Application of Tendon-Derived Stem Cell Sheet for the Promotion of Graft Healing in Anterior Cruciate Ligament Reconstruction

“…We managed this issue by having 2 experienced investigators performing all the surgical procedures according to the published standardized protocol. 14,15 The tendon graft was fixed to the femoral and tibial tunnel exits by suturing to the neighboring periosteum. However, the tendon graft is secured by interference screws, endobuttons, or staples in clinical settings.…”

Small-molecule based musculoskeletal regenerative engineering

“…investigated the effects of systematic administration of alendronate on the healing of tendon-bone interface in a rat ACL reconstruction model. Results showed that alendronate treatment reduced the expression of MMP1, MMP3 and CD68-positive cells (CD68: marker for the various cells of the macrophage lineage, including osteoclasts precursors and osteoclasts) at the region of peri-tunnel region as well as the interface of graft-bone tunnel (59). In addition, Lui et al .…”