Authors:
Qing Zhang, Jodi Carlson, Hua-Zhu Ke, Jiliang Li, Michael Kim, Kieran Murphy, MB, BCH FRCPC FSIR, Nozer Mehta, James Gilligan, & Agnès Vignery
Summary:
We previously reported that following mechanical ablation of the marrow from the mid-shaft of rat femurs, there is a rapid and abundant, but transient growth of bone, and this growth is enhanced and maintained over a three-week period by the bone anabolic hormone PTH. Here we ask whether further treatment with PTH or bisphosphonates can extend the half-life of the new bone formed in lieu of marrow. We subjected the left femur of rats to mechanical marrow ablation and treated the animals five days a week with PTH for three weeks to replace the marrow by bone, or with vehicle as a control. Some rats were sacrificed and used as positive controls or treated with vehicle, PTH or the bisphosphonate alendronate for a further nine weeks. We subjected both femurs from each rat to soft X-ray, pQCT, microCT, dynamic histomorphometry analysis and biomechanical testing. We also determined the concentrations of serum osteocalcin to confirm the efficacy of PTH. Treatment with PTH for three months dramatically enhanced endosteal and periosteal bone formation leading to a 30% increase in cortical thickness. In contrast, alendronate protected the bone that had formed in the femoral marrow cavity after marrow ablation and three weeks treatment with PTH, but failed to promote endosteal bone growth and to improve the biomechanical properties of ablated femurs. We further asked whether calcium-phosphate cements could potentiate the formation of bone after marrow ablation. Marrow cavities from ablated femurs were filled with one of two calcium-phosphate cements and rats were treated with PTH or PBS for 84 days. Both cements helped to protect the new bone formed after ablation. To some extent, they promoted the formation of bone after ablation even in the absence of any anabolic hormone. Our data therefore expand the role of PTH in bone engineering and open new avenues of investigations to the field of regenerative medicine and tissue engineering. Local bone marrow removal in conjunction with an anabolic agent, a bisphosphonate or a calcium-phosphate cement might provide a new platform for rapid preferential site-directed bone growth in areas of high bone loss.
Source:
Journal of Bone & Mineral Research; (02/02/10)