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PARATHYROID HORMONE REVERSES RADIATION INDUCED HYPOVASCULARITY IN A MURINE MODEL OF DISTRACTION OSTEOGENESIS
Presenter: Stephen Y Kang, MD
Co-Authors: Deshpande SS; Donneys A; Nelson NS; Rodriguez J; Felice PA; Chepeha DB; Buchman SR
University of Michigan

Background: Radiation therapy (XRT) diminishes vascularity and impairs regeneration during mandibular distraction osteogenesis (DO). Parathyroid hormone (PTH) has demonstrated efficacy for increasing bone mineral density in the treatment of osteoporosis and has also shown the ability to enhance union quality in an irradiated murine model of mandibular distraction osteogenesis. We hypothesize that intermittent delivery of PTH reverses radiation-induced hypovascularity during mandibular distraction osteogenesis.

Experimental Design: Three groups of Lewis rats underwent distraction osteogenesis of the left mandible. The experimental group (xPTH) underwent preoperative XRT followed by daily subcutaneous PTH injections during mandibular distraction. The radiation control group (xDO) underwent preoperative XRT followed by mandibular distraction. The normal control group (DO) underwent mandibular distraction alone. After consolidation, the rats were perfused and imaged with micro-computed tomography angiography. The following quantitative metrics were calculated: vessel volume fraction, vessel number, vessel diameter, and vessel separation. Statistical analysis was performed using SPSS Statistics software (SPSS, Chicago, IL).

Results: The xPTH and DO groups had significantly increased vessel number, vessel volume fraction, and vessel diameter compared to the xDO group (p < 0.05). The xPTH and DO groups had significantly decreased vessel separation compared to the xDO group (p < 0.05). No significant differences found in vessel number, vessel volume fraction, vessel diameter, or vessel separation between the xPTH and the DO groups.

Conclusion: PTH reverses radiation-induced hypovascularity in the murine model of distraction osteogenesis. Quantitative vascular analysis revealed no significant differences between the xPTH and DO groups. PTH may become a useful therapeutic agent to ameliorate the adverse effects of XRT on bone regeneration and bone healing.


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