title: Parathyroid hormone reverses radiation induced hypovascularity in a murine model of distraction osteogenesis.
abstract: BACKGROUND
  Radiation treatment results in a severe diminution of osseous vascularity. Intermittent parathyroid hormone (PTH) has been shown to have an anabolic effect on osteogenesis, though its impact on angiogenesis remains unknown. In this murine model of distraction osteogenesis, we hypothesize that radiation treatment will result in a diminution of vascularity in the distracted regenerate and that delivery of intermittent systemic PTH will promote angiogenesis and reverse radiation induced hypovascularity.
  
  
  METHODS
  Nineteen Lewis rats were divided into three groups. All groups underwent distraction of the left mandible. Two groups received radiation treatment to the left mandible prior to distraction, and one of these groups was treated with intermittent subcutaneous PTH (60 μg/kg, once daily) beginning on the first day of distraction for a total duration of 21 days. One group underwent mandibular distraction alone, without radiation. After consolidation, the rats were perfused and imaged with micro-CT angiography and quantitative vascular analysis was performed.
  
  
  RESULTS
  Radiation treatment resulted in a severe diminution of osseous vascularity in the distracted regenerate. In irradiated mandibles undergoing distraction osteogenesis, treatment with intermittent PTH resulted in significant increases in vessel volume fraction, vessel thickness, vessel number, degree of anisotropy, and a significant decrease in vessel separation (p < 0.05). No significant difference in quantitative vascularity existed between the group that was irradiated, distracted and treated with PTH and the group that underwent distraction osteogenesis without radiation treatment.
  
  
  CONCLUSIONS
  We quantitatively demonstrate that radiation treatment results in a significant depletion of osseous vascularity, and that intermittent administration of PTH reverses radiation induced hypovascularity in the murine mandible undergoing distraction osteogenesis. While the precise mechanism of PTH-induced angiogenesis remains to be elucidated, this report adds a key component to the pleotropic effect of intermittent PTH on bone formation and further supports the potential use of PTH to enhance osseous regeneration in the irradiated mandible.
authors: Craniofacial Research Laboratory, University of Michigan Medical School, Ann Arbor, MI, USA. steveyk@med.umich.edu
authors: Stephen Y
authors: SY
authors: Kang
authors: Sagar S
authors: SS
authors: Deshpande
authors: Alexis
authors: A
authors: Donneys
authors: Jose J
authors: JJ
authors: Rodriguez
authors: Noah S
authors: NS
authors: Nelson
authors: Peter A
authors: PA
authors: Felice
authors: Douglas B
authors: DB
authors: Chepeha
authors: Steven R
authors: SR
authors: Buchman
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D008334:Mandible / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000187:drug effects; D019857:Osteogenesis, Distraction; D010027:Osteotomy; D011832:Radiation Injuries / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew; D019379:Teriparatide / Q000494:pharmacology* / Q000627:therapeutic use*; D055114:X-Ray Microtomography
chemical_list: D019379:Teriparatide
keywords: Angiogenesis; CT; DA; DO; Distraction osteogenesis; Gy; HIFα; Mandible; POD; PTH; Parathyroid hormone; ROI; Radiation; VEGF; VN; VS; VT; VVF; XRT; computed tomography; degree of anisotropy; distraction osteogenesis; gray; hypoxia-inducible factor-1 alpha; parathyroid hormone; postoperative day; radiation treatment; region of interest; vascular endothelial growth factor; vessel number; vessel separation; vessel thickness; vessel volume fraction
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