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Long-term evaluation of alendronate treatment on the healing of calvaria bone defects in rats. Biochemical, histological and immunohistochemical analyses

Author(s): de Molon, Rafael Scaf [UNESP] ; Fiori, Leslie Cristine [UNESP] ; Verzola, Mario Henrique Arruda [UNESP] ; Belluci, Marina Montosa [UNESP] ; de Souza Faloni, Ana Paula ; Pereira, Rosa Maria Rodrigues ; Tetradis, Sotirios ; Orrico, Silvana Regina Perez [UNESP]

Date: 2020

Persistent ID: http://hdl.handle.net/11449/201871

Origin: Oasisbr

Subject(s): Alendronate; Bisphosphonate; Bone; Calvaria; Immunohistochemistry; Osteoclast; Rats; Alendronate; Alendronate; Bisphosphonate; Bisphosphonate; Bone; Bone; Calvaria; Calvaria; Immunohistochemistry; Immunohistochemistry; Osteoclast; Osteoclast; Rats; Rats


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Objective: The aim of this study was to investigate the effects of the long-term alendronate administration on bone healing in defects created in rat calvarias. Materials and methods: Female Wistar rats were randomly distributed into 2 groups: Control (CTL): animals received saline solution once a week; and Alendronate (ALD): rats underwent alendronate treatment (1 mg/kg/weekly). After 120 days from the commencement of treatment, a critical size defect was created in all animals, and 10 animals from each group were sacrificed at 5, 10, 15, 20, 25, 30, 45 and 60-days after the defect creation. On the day of sacrifice, urine and blood samples were collected for determination of the serum levels of bone resorption and formation markers by enzyme linked immunosorbent assay, and the urinary concentration of deoxypyridinoline. Bone mineral density (BMD) in the femurs, descriptive histology, tartrate-resistant acid-phosphatase staining and immunohistochemical analyzes were assessed in the calvaria. Results: Alendronate group showed increased BMD compared to the test group. The concentration of C-terminal telopeptide of type I collagen and deoxypyridinoline decreased significantly, and the concentration of aminoterminal propeptide of procollagen type 1 and osteocalcin were significant lower in the alendronate group. Immunohistochemical analysis showed significant downregulation in the inducible nitric oxide synthase, runt-related transcription factor-2, cathepsin-K and receptor activator of nuclear factor kappa-B ligand expression in the alendronate group. Vascular endothelial growth factor and osteopontin were upregulated in the later periods of alendronate group. Conclusions: Our results suggest that long-term treatment with alendronate did not compromise the repair processing of critical size defects in rat.

Department of Diagnosis and Surgery São Paulo State University (UNESP) School of Dentistry

Department of Health Sciences Implantology Post Graduation Course University Centre of Araraquara – UNIARA

Department of Rheumatology School of Medicine University of São Paulo

Division of Diagnostic and Surgical Sciences UCLA School of Dentistry

Molecular Biology Institute UCLA

Advanced Research Center in Medicine Union of the Colleges of the Great Lakes (UNILAGO)

Department of Diagnosis and Surgery São Paulo State University (UNESP) School of Dentistry

Document Type Journal article
Language English
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