title: Experimental development of bisphosphonate-related osteonecrosis of the jaws in rodents.
abstract: Osteonecrosis of the jaw (ONJ) following the use of bisphosphonates has become of increased interest in the scientific community, due in particular to its as-yet-unsolved pathogenesis. An experimental model of ONJ was induced in normal male rats [alendronate (ALN); 1 mg/Kg/day; n = 10] and matched controls (saline solution; n = 10). After 60 days of drug treatment, all animals were subjected to extractions of the left first lower molars and were euthanized at 3 and 28 days postsurgery. The following analyses were performed: (i) descriptive and quantitative (scores) histological evaluation, (ii) stereometry of distal sockets and (iii) biochemical measurement of C-telopeptide cross-linked collagen type I (CTX) and bone-specific alkaline phosphatase (BALP). The results showed that 28 days postsurgery the animals treated with ALN had areas of exposed and necrotic bone, associated with significant infection, especially in the interalveolar septum area and crestal regions, compared with controls. The levels of CTX, BALP and bone volume, as well as the degrees of inflammation and vascularization, were significantly reduced in these animals. Therefore, analysis of the data presented suggests that ALN therapy is associated with the development of osteonecrosis in the jaws of rodents after tooth extraction.
authors: Division of Periodontology, Department of Diagnosis and Surgery, School of Dentistry, UNESP- Univ. Estadual Paulista, Araraquara, SP, Brazil.
authors: Nicolau
authors: N
authors: Conte Neto
authors: Luis C
authors: LC
authors: Spolidorio
authors: Cleverton R
authors: CR
authors: Andrade
authors: Alliny
authors: A
authors: S Bastos
authors: Morgana
authors: M
authors: Guimarães
authors: Elcio
authors: E
authors: Marcantonio
mesh_terms: D019386:Alendronate; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D016723:Bone Remodeling; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D007568:Jaw / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008963:Molar / Q000601:surgery; D056948:Orthognathic Surgical Procedures; D010455:Peptides / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014081:Tooth Extraction / Q000009:adverse effects; D015430:Weight Gain
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D000469:Alkaline Phosphatase; D019386:Alendronate