Evaluation of maxillary bones and apical periodontitis induced in ovariectomized rats subjected or not to treatment with bisphosphonate or cathepsin K inhibitor

Author(s)

Priscilla Coutinho Romualdo

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Odontologia de Ribeirão Preto (PCARP/BC)
• Defense date: 2017-06-28

Examining board members

Paulo Nelson Filho; Gisele Faria; Lucianne Cople Maia de Faria; Alexandra Mussolino de Queiroz; Yara Teresinha Corrêa Silva Sousa

• Advisor: Paulo Nelson Filho; Raquel Assed Bezerra Segato

Abstract

The aim of this study was to evaluate maxillary bones and apical periodontitis induced in ovariectomized rats treated or not with bisphosphonate (Alendronate - ALD) or cathepsin K inhibitor (Odanacatib - ODN). Forty-five female rats were divided into 6 groups: I sham surgery; II - sham and apical periodontitis (AP); III - ovariectomy (OVX) without AP; IV - OVX and AP; V - OVX, AP and ALD; and Group VI - OVX, AP and ODN. One day after OVX or sham surgery, the animals in groups V and VI started receiving ALD or ODN, by gavage. After 9 weeks, the first molars of the rats in groups II, IV, V and VI were subjected to induction of AP for 3 weeks. Microbiological root canal sampling was collected for quantification of microorganisms and the animals were euthanized. Bone mineral density (BMD) of the femurs was analyzed by bone densitometry. The maxillas were analyzed by microcomputed tomography (micro-CT) to determine the microarchitecture and BMD of the interradicular bone while the mandibles were analyzed to determined AP volume. The mandibular first molars were subjected to histotechnical processing and hematoxylin and eosin-stained histological sections were examined with conventional microscopy. In addition, a morphometric analysis of AP area was performed using fluorescence microscopy and tartrate-resistant acid phosphatase (TRAP) histoenzymology. The maxillary first molars were used to evaluate the gene expression of cytokines, osteoclastogenesis markers and matrix metalloproteinases (MMP) using RT-PCR. The results were subjected to appropriate statistical analysis with 5% significance level. OVX affected femoral and maxillary BMD and femoral microarchitecture. ALD recovered the BMD of both types of bones. OVX was not able to influence the microbial levels of the root canal. In group IV, AP showed increased expression of RANK, RANKL, IL-1β, IL-6, TNF-α, MMP-8 and MMP-13, while ALD treatment (group V) reduced IL-6 and MMP-8 expression to the same level as the AP in group II. In group IV, AP area and volume were larger than in groups II and V. ODN, in the dosage and frequency of administration applied, was not able to promote significant changes. OVX and antiresorptive treatments did not influence the number of osteoclasts around the AP region. In conclusion, the hypoestrogenic condition induced by OVX was able to decrease the BMD of femur and maxilla and only the microarchitecture of the femur. ALD was able to recover the BMD phenotype, i.e., return to the levels observed in healthy animals. Furthermore, OVX exacerbated resorption, inflammation and MMP expression, inducing larger lesions. Treatment with ALD and ODN resulted in an improvement of the periapical response. However, only ALD recovered the phenotype, with AP similar to that of healthy animals. (AU)

• FAPESP's process: 13/18231-9 - Evaluation of induced apical periodontitis in osteoporotic mice submitted or not to treatment with alendronate
• Grantee: Priscilla Coutinho Romualdo
• Support Opportunities: Scholarships in Brazil - Doctorate