Abstract: PTH Therapy Reverses Radiation-Induced Non-Union and Normalizes Radiomorphometrics In a Murine Mandibular Model of Distraction Osteogenesis (Plastic Surgery 2011 (September 23-27, 2011))

Saturday, September 24, 2011: 7:55 AM

Colorado Convention Center

Kelly Gallagher, MD , Otolaryngology Head and Neck Surgery, University of Michigan, Ann Arbor, MI

Sagar Deshpande, BS , Plastic Surgery, University of Michigan, Ann Arbor, MI

Catherine Tchanque-Fossuo, MD, MS , Plastic Surgery, University of Michigan, Ann Arbor, MI

Alexis Donneys, MD, MS , Plastic Surgery, University of Michigan, Ann Arbor, MI

Deniz Sarhaddi, BA , Plastic Surgery, University of Michigan, Ann Arbor, MI

Noah Nelson, BS , Plastic Surgery, University of Michigan, Ann Arbor, MI

Hongli Sun, PhD , Biologic & Materials Science, School of Dentistry, University of Michigan, Ann Arbor

Paul Krebsbach, DDS, PhD , Biologic & Materials Science, School of Dentistry, University of Michigan, Ann Arbor

Douglas Chepeha, MD, MPH , Otolaryngology Head and Neck Surgery, University of Michigan, Ann Arbor, MI

Steven Buchman, MD , F7859 Mott Children's Hospital, Ann Arbor, MI

Presentation PDF file

Purpose: The authors have investigated therapies to circumvent the ravaging effects of radiation in the setting of mandibular distraction osteogenesis (MDO). Our global hypothesis is that radiation induced bone damage is partly driven by the pathologic depletion of both the number and function of osteogenic cells. Parathyroid Hormone (PTH) is an FDA-approved anabolic hormonal therapy that has demonstrated efficacy for increasing bone mineral density for the treatment of osteoporosis. We posit that intermittent systemic administration of PTH will serve as a stimulant to cellular function which will act to reverse radiation induced damage and enhance bone regeneration in a murine mandibular model of DO.

Methods: 20 isogenic male Lewis rats were randomly assigned into 3 groups: group 1 (XRT/DO, n=7) and group 2 (PTH, n=5) received a human bioequivalent dose of 70Gy fractionated over 5 days. All groups including group 3 (DO, n=8) underwent a left unilateral mandibular osteotomy with bilateral external fixator placement. Four days later, MDO was performed at a rate of 0.3 mm every 12 hours to reach a maximum gap of 5.1mm. Group 2 was injected PTH (60mg/kg) subcutaneously daily for 3 weeks following the start of MDO. On post-operative day 40, all left hemimandibles were harvested. mCT at 45 mm voxel size was performed and radiomorphometrics parameters of bone mineralization were generated. Union quality was evaluated on a 4-point Likert scale. All data was analyzed using one-way ANOVA, with statistical significance at p £ 0.05.

Results: Groups 1 and 2 appropriately demonstrated clinical signs of radiation induced-stress ranging from alopecia to mucositis. Union quality was statistically significantly higher in PTH-treated groups, compared to XRT-DO group (p=0.02). Mineralization metrics, including Bone Volume Fraction (BVF), Bone Mineral Density (BMD) also showed statistical significant improvement (Fig.1&2). The groups that were treated with PTH showed no statistical differences in union nor radiomorphometrics when compared to DO in non-radiated animals.

Conclusion: We have successfully demonstrated the therapeutic efficacy of PTH to stimulate and enhance bone regeneration in our irradiated murine mandibular model of DO. Our investigation effectively resulted in statistically significant increase in BMD, BVF, and clinical unions in PTH-treated mandibles. PTH demonstrates immense potential to be taken from the bench to the bedside to treat clinical pathologies where remediation of bone regeneration is essential.

19674 PTH Therapy Reverses Radiation-Induced Non-Union and Normalizes Radiomorphometrics In a Murine Mandibular Model of Distraction Osteogenesis