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

Autor(es)

de Molon, Rafael Scaf ^[1] ; Fiori, Leslie Cristine ^[1] ; Arruda Verzola, Mario Henrique ^[1] ; Belluci, Marina Montosa ^[1] ; de Souza Faloni, Ana Paula ^[2] ; Rodrigues Pereira, Rosa Maria ^[3] ; Tetradis, Sotirios ^{[4, 5]} ; Perez Orrico, Silvana Regina ^{[1, 6]}

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Sch Dent, Dept Diag & Surg, Araraquara, SP - Brazil

^[2] Univ Ctr Araraquara UNIARA, Dept Hlth Sci, Implantol Post Grad Course, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Med, Dept Rheumatol, BR-05508900 Sao Paulo - Brazil

^[4] Univ Calif Los Angeles, Mol Biol Inst, Los Angeles, CA 10833 - USA

^[5] Univ Calif Los Angeles, Sch Dent, Div Diagnost & Surg Sci, Los Angeles, CA 10833 - USA

^[6] Union Coll Great Lakes UNILAGO, Adv Res Ctr Med, Sao Jose Do Rio Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ARCHIVES OF ORAL BIOLOGY; v. 117, SEP 2020.
• Citações Web of Science: 0

Resumo

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 amino-terminal 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, runtrelated 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. (AU)

• Processo FAPESP: 15/21697-5 - Uma potencial nova classe de droga para inibir a reabsorção óssea, fitocistatina Csin-CPI-2 derivada da laranja, como possível candidato terapêutico para tratamento de doenças ósseas.
• Beneficiário: Rafael Scaf de Molon
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado