Role of Osteoclasts in Primary Bone Resorption and Marrow Recovery

Objectives: Primary bone is the first bone tissue that appears during fracture repair. It is meant to rapidly fill in the fracture gap and is typically replaced by secondary Haversian bone. Healing after a fracture or implant placement depends upon the interplay of osteoclast and osteoblast activity, and can be studied by modeling primary bone repair via bone marrow ablation. The aim of this study was to determine the role of osteoclasts in remodeling primary bone during recovery from bone marrow ablation.



Methods: Femoral marrow cavities of 3-month old male CD Sprague Dawley rats were accessed bilaterally by dental burr, and flushed with 20ml sterile saline to ablate the marrow. Femurs were recovered immediately after ablation (n=4), 7d post-operatively for sham-operated and ablated (n=4/group), and at 14d post-operatively (n=4/group). A pump was placed subcutaneously 7d post-ablation, which released 1mg/kg/day of the following (n = 8/treatment): PBS, IgG antibody, RANKL antibody, the cathepsin K inhibitor Odanacatib (ODN), or the bisphosphonate ibandronate (Bis). Animals were euthanized 28d post-surgery, and bone marrow recovery was assessed using microCT.

Results: Immediately after ablation of the bone marrow, no primary bone was observed. 7d post-ablation the marrow cavity was filled with primary bone in the ablated femurs compared to sham-operated controls. 14d post-ablation the primary bone had begun to be remodeled and resorbed. 28d post-operatively, Bis had significantly more primary bone remaining in the marrow space compared to all other groups. Treatment with ibandronate prevented resorption of the primary bone as indicated by the increased bone volume present in the marrow space, while treatment with either ODN or RANKL antibody did not significantly increase bone volume.

Conclusions: These data support they hypothesis that the signaling pathways occurring between osteoclasts and other bone cells play a critical role in bone healing.