Alendronate prevents collapse in mechanically loaded osteochondral grafts: a bone chamber study in rats

Abstract

Background: Subchondral bone necrosis is important in osteonecrosis, Mb Kienboeck, intraarticular fractures or osteochondral grafting. As revascularization follows, bone resorption may lead to collapse in load bearing areas during the remodeling. Bisphosphonates are potent osteoclast inhibitors. Our hypothesis was that local bisphosphonate treatment of an osteochondral graft, in a high load environment, would protect the subchondral bone from collapse and maintain the joint architecture during remodeling. To investigate this, we used a rat bone chamber model to subject a necrotic osteochondral graft to a large mechanical load during remodeling.

Method: Cylindrical osteochondral grafts were taken from the patellar groove of rats, one end of the cylinder being the joint surface. The grafts were frozen, thawed and treated with alendronate. The length of the cylinder was measured and the grafts were placed in the chambers, which were inserted into the proximal tibia of rats. The chambers were left to heal in for two weeks to allow establishment of a vascular supply, and then the transplanted osteochondral plugs were mechanically loaded for 4 weeks, once a day with 10 cycles of 2 MPa pressure at 0.16 Hz.

Results: At harvest, the graft length had decreased during remodeling in 5 of the 6 untreated controls, but only in 2 out of 8 alendronate-treated rats (p = 0.05). Histologically, the bone graft in the non-treated controls was resorbed in the remodeled part of the graft, whereas in the alendronate-treated rats a dense trabecular bone was found consisting of both new bone and graft.

Interpretation: Local treatment of the graft with bisphosphonate diminishes the risk of collapse during revascularization and bone remodeling in a mechanically loaded osteochondral graft. This could be useful in a variety of situations when bone remodeling occurs after a necrosis close to a joint, either spontaneously after osteonecrosis or a fracture, or after surgical procedures such as mosaic-plasty or other osteochondral grafting.