Alexis Donneys1, Catherine N Tchanque-Fossuo1, Jordan T Blough2, Noah S Nelson1, Sagar S Deshpande1, Steven R Buchman3. 1. Research Fellow, Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI. 2. Research Assistant, Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI. 3. M. Haskell Newman Collegiate Professor of Plastic Surgery, Professor of Surgery, and Professor of Neurosurgery, Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI. Electronic address: sbuchman@med.umich.edu.
Abstract
PURPOSE: Radiation is known to decrease osteocyte count and function, leading to bone weakening. A treatment strategy to mitigate these consequences could have immense therapeutic ramifications. The authors previously reported significantly decreased osteocyte count and mineralization capacity in a rat model of fracture healing after radiotherapy. They hypothesized that amifostine (AMF) would preserve osteocyte number and function in this model. MATERIALS AND METHODS: Thirty-six rats were divided into 3 groups: fracture, radiated fracture, and radiated fracture with AMF. Radiated groups underwent human-equivalent radiotherapy to the mandible before fixator placement and mandibular osteotomy. The AMF group received a subcutaneous injection before each dose of radiotherapy. After 40 days, mandibles were harvested for histologic processing. Quantification of osteocyte count (Oc), empty lacunae (EL), and osteoid ratio (osteoid volume [OV] to tissue volume [TV]) was performed and the results were compared using analysis of variance (P < .05). RESULTS: Radiated fractures showed significantly decreased Oc, increased EL, and a decreased capacity to produce new osteoid at the fracture site as measured with OV/TV compared with nonradiated fractures. In mandibles treated with AMF, these metrics were not statistically different than the control, indicating a preservation of osteocyte number and function. CONCLUSIONS: These results support the hypothesis that AMF preserves osteocyte number and function, thereby preventing the pernicious effects of radiotherapy on the cellular environment of fracture healing. Based on these findings, the authors encourage future investigation of this promising therapy for use in the prevention of pathologic fractures and osteoradionecrosis. Published by Elsevier Inc.
PURPOSE: Radiation is known to decrease osteocyte count and function, leading to bone weakening. A treatment strategy to mitigate these consequences could have immense therapeutic ramifications. The authors previously reported significantly decreased osteocyte count and mineralization capacity in a rat model of fracture healing after radiotherapy. They hypothesized that amifostine (AMF) would preserve osteocyte number and function in this model. MATERIALS AND METHODS: Thirty-six rats were divided into 3 groups: fracture, radiated fracture, and radiated fracture with AMF. Radiated groups underwent human-equivalent radiotherapy to the mandible before fixator placement and mandibular osteotomy. The AMF group received a subcutaneous injection before each dose of radiotherapy. After 40 days, mandibles were harvested for histologic processing. Quantification of osteocyte count (Oc), empty lacunae (EL), and osteoid ratio (osteoid volume [OV] to tissue volume [TV]) was performed and the results were compared using analysis of variance (P < .05). RESULTS:Radiated fractures showed significantly decreased Oc, increased EL, and a decreased capacity to produce new osteoid at the fracture site as measured with OV/TV compared with nonradiated fractures. In mandibles treated with AMF, these metrics were not statistically different than the control, indicating a preservation of osteocyte number and function. CONCLUSIONS: These results support the hypothesis that AMF preserves osteocyte number and function, thereby preventing the pernicious effects of radiotherapy on the cellular environment of fracture healing. Based on these findings, the authors encourage future investigation of this promising therapy for use in the prevention of pathologic fractures and osteoradionecrosis. Published by Elsevier Inc.
Authors: Giorgio C La Scala; David A O'Donovan; Ivan Yeung; Johnson Darko; Patrick D Addison; Peter C Neligan; Cho Y Pang; Christopher R Forrest Journal: Plast Reconstr Surg Date: 2005-06 Impact factor: 4.730
Authors: Martee L Hensley; Karen L Hagerty; Tarun Kewalramani; Daniel M Green; Neal J Meropol; Todd H Wasserman; Gary I Cohen; Bahman Emami; William J Gradishar; R Brian Mitchell; J Tate Thigpen; Andy Trotti; Daniel von Hoff; Lynn M Schuchter Journal: J Clin Oncol Date: 2008-11-17 Impact factor: 44.544
Authors: Alexis Donneys; Noah S Nelson; Joseph E Perosky; Yekaterina Polyatskaya; Jose J Rodriguez; Christian Figueredo; Cheyenne A Vasseli; Hannah C Ratliff; Sagar S Deshpande; Kenneth M Kozloff; Steven R Buchman Journal: Bone Date: 2015-12-23 Impact factor: 4.398
Authors: Kevin M Urlaub; Russell E Ettinger; Noah S Nelson; Jessie M Hoxie; Alicia E Snider; Joseph E Perosky; Yekaterina Polyatskaya; Alexis Donneys; Steven R Buchman Journal: J Craniofac Surg Date: 2019 Mar/Apr Impact factor: 1.046
Authors: Peter A Felice; Bo Gong; Salman Ahsan; Sagar S Deshpande; Noah S Nelson; Alexis Donneys; Catherine Tchanque-Fossuo; Michael D Morris; Steven R Buchman Journal: J Bone Miner Metab Date: 2014-10-16 Impact factor: 2.626
Authors: Kavitha Ranganathan; Eric Simon; Jeremy Lynn; Alicia Snider; Yu Zhang; Noah Nelson; Alexis Donneys; Jose Rodriguez; Lauren Buchman; Dawn Reyna; Elke Lipka; Steven R Buchman Journal: Pharm Res Date: 2018-03-19 Impact factor: 4.200
Authors: Kevin M Urlaub; Kavitha Ranganathan; Jeremy V Lynn; Alexandra O Luby; Lauren N Patrick; Noah S Nelson; Alexis Donneys; Steven R Buchman Journal: Plast Reconstr Surg Date: 2021-04-01 Impact factor: 4.730
Authors: Meredith K Bartelstein; Divya Yerramilli; Alexander B Christ; Shachar Kenan; Koichi Ogura; Tomohiro Fujiwara; Nicola Fabbri; John H Healey Journal: Sarcoma Date: 2021-03-15
Authors: Man Huen Victoria Choy; Ronald Man Yeung Wong; Simon Kwoon Ho Chow; Meng Chen Li; Yu Ning Chim; Tsz Kiu Li; Wing Tung Ho; Jack Chun Yiu Cheng; Wing Ho Cheung Journal: J Orthop Translat Date: 2019-08-08 Impact factor: 5.191