Matthew R Allen1, David B Burr. 1. Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. matallen@iupui.edu
Abstract
PURPOSE: An increasing number of reports have implicated bisphosphonates as contributing to osteonecrosis of the jaw. The goal of this study was to evaluate mandible necrosis in beagle dogs treated for 3 years with oral alendronate (ALN). MATERIALS AND METHODS: Skeletally mature female beagles were treated daily for 3 years with oral doses of vehicle (VEH) or ALN (0.20 or 1.0 mg/kg/day). These doses approximate, on a mg/kg basis, those used for postmenopausal osteoporosis and Paget's disease, respectively. At necropsy, the second molar region of the mandible was excised, stained en bloc with basic fuchsin, and assessed for matrix necrosis and intracortical bone turnover rate using histology. Matrix necrosis was defined as a region greater than 500 microm(2) that was void of basic fuchsin stain, assessed using both bright-field and confocal microscopy. RESULTS: No animals developed exposed bone lesions in the oral cavity during the 3-year study. Matrix necrosis was observed in 25% of ALN0.2 animals, 33% of ALN1.0 animals, and was noticeably absent from all vehicle animals (P < .05 pooled ALN doses vs VEH). These necrotic regions occurred predominately in the alveolar bone and were clearly void of patent canaliculi. Intracortical bone turnover rate of the alveolar mandible bone region was significantly lower (-75%, P < .05) in ALN-treated animals compared with VEH. CONCLUSIONS: Three years of daily oral bisphosphonate treatment reduces bone turnover significantly and increases the incidence of matrix necrosis within the mandible of dogs.
PURPOSE: An increasing number of reports have implicated bisphosphonates as contributing to osteonecrosis of the jaw. The goal of this study was to evaluate mandible necrosis in beagle dogs treated for 3 years with oral alendronate (ALN). MATERIALS AND METHODS: Skeletally mature female beagles were treated daily for 3 years with oral doses of vehicle (VEH) or ALN (0.20 or 1.0 mg/kg/day). These doses approximate, on a mg/kg basis, those used for postmenopausal osteoporosis and Paget's disease, respectively. At necropsy, the second molar region of the mandible was excised, stained en bloc with basic fuchsin, and assessed for matrix necrosis and intracortical bone turnover rate using histology. Matrix necrosis was defined as a region greater than 500 microm(2) that was void of basic fuchsin stain, assessed using both bright-field and confocal microscopy. RESULTS: No animals developed exposed bone lesions in the oral cavity during the 3-year study. Matrix necrosis was observed in 25% of ALN0.2 animals, 33% of ALN1.0 animals, and was noticeably absent from all vehicle animals (P < .05 pooled ALN doses vs VEH). These necrotic regions occurred predominately in the alveolar bone and were clearly void of patent canaliculi. Intracortical bone turnover rate of the alveolar mandible bone region was significantly lower (-75%, P < .05) in ALN-treated animals compared with VEH. CONCLUSIONS: Three years of daily oral bisphosphonate treatment reduces bone turnover significantly and increases the incidence of matrix necrosis within the mandible of dogs.
Authors: Elizabeth Shane; Steve Goldring; Sylvia Christakos; Marc Drezner; John Eisman; Stuart Silverman; David Pendrys Journal: J Bone Miner Res Date: 2006-10 Impact factor: 6.741
Authors: Martha Q Lacy; Angela Dispenzieri; Morie A Gertz; Philip R Greipp; Kimberly L Gollbach; Suzanne R Hayman; Shaji Kumar; John A Lust; S Vincent Rajkumar; Stephen J Russell; Thomas E Witzig; Steven R Zeldenrust; David Dingli; P Lief Bergsagel; Rafael Fonseca; Craig B Reeder; A Keith Stewart; Vivek Roy; Robert J Dalton; Alan B Carr; Deepak Kademani; Eugene E Keller; Christopher F Viozzi; Robert A Kyle Journal: Mayo Clin Proc Date: 2006-08 Impact factor: 7.616
Authors: Rafael Scaf de Molon; Simon Cheong; Olga Bezouglaia; Sarah M Dry; Flavia Pirih; Joni Augusto Cirelli; Tara L Aghaloo; Sotirios Tetradis Journal: Bone Date: 2014-08-02 Impact factor: 4.398