title: The effects of bisphosphonate on the remodeling of different irregular bones in mice.
abstract: BACKGROUND
  We aimed to compare the effects of bisphosphonate on the remodeling of irregular bones (the jaw and ilium) in mice after trauma.
  
  
  METHODS
  To verify the feasibility of modeling osteonecrosis, 20 mice were injected intraperitoneally with zoledronate and dexamethasone (ZOL&DEX group), dexamethasone (DEX group), or phosphate-buffered saline (PBS) [control (CTR) group]. Mice then underwent extraction of the right maxillary first molar and creation of an artificial bony cavity in the ilium. Bone sections were stained with H&E for morphological studies. To further compare differences between the maxilla and the ilium caused by similar traumas, 80 mice were injected intraperitoneally with ZOL&DEX or PBS. Pathological progression at the injury sites was assessed at 1 day and at 1, 3, and 8 weeks after trauma using micro-computed tomography (CT), H&E and immunohistochemistry analyses, high-performance liquid chromatography-mass spectrometry, and enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Only the ZOL&DEX model group effectively developed osteonecrosis. Bony sequestra, osseous sclerosis, unhealed mucosa, and radiopaque alveolar bone were found in the maxilla. In the ilium, there was a lower frequency of osteonecrotic disease and osseous sclerosis, and less suppression of bone remodeling than in the maxilla following long-term bisphosphonate administration. Zoledronate levels were higher in the maxilla. ZOL&DEX treatment suppressed the levels of RANKL and IL-17, but induced an upregulation of osteoprotegerin and FAM20C in both bones.
  
  
  CONCLUSIONS
  Accumulation of bisphosphonate may increase the incidence of osteonecrosis. The RANKL/OPG pathway and IL-17 and FAM20C cytokines play key roles in the progression of pathologically abnormal bone remodeling.
authors.affiliation: Laboratory of Oral Biomedical Science and Translational Medicine, School of Stomatology, Tongji University, Shanghai, China.
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Su
authors.affiliation: Laboratory of Oral Biomedical Science and Translational Medicine, School of Stomatology, Tongji University, Shanghai, China.
authors.forename: Mu
authors.initials: M
authors.lastname: Feng
authors.affiliation: Laboratory of Oral Biomedical Science and Translational Medicine, School of Stomatology, Tongji University, Shanghai, China.
authors.forename: Wenfei
authors.initials: W
authors.lastname: Han
authors.affiliation: Laboratory of Oral Biomedical Science and Translational Medicine, School of Stomatology, Tongji University, Shanghai, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Zhao
mesh_terms: D000818:Animals; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D016723:Bone Remodeling / Q000187:drug effects*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004164:Diphosphonates / Q000494:pharmacology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D007085:Ilium / Q000187:drug effects / Q000473:pathology; D007093:Imidazoles / Q000494:pharmacology*; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000378:metabolism; D007568:Jaw / Q000187:drug effects / Q000473:pathology; D008437:Maxilla / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D053245:RANK Ligand / Q000378:metabolism; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D002135:Calcium-Binding Proteins; D004164:Diphosphonates; D016326:Extracellular Matrix Proteins; C509696:FAM20C protein, mouse; D007093:Imidazoles; D020381:Interleukin-17; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D000077211:Zoledronic Acid; D003907:Dexamethasone
keywords: bisphosphonate-related osteonecrosis of the jaw; bisphosphonates; bone remodeling; osteonecrosis; pathogenesis