Bone remodeling during alveolar repair is impaired by RANKL antagonist

Ana Cláudia Ervolino Da Silva,Fábio Roberto De Souza Batista,Juliana Zorzi Coléte,Roberta Okamoto,Fernando Chiba,Juliana De Moura,Pedro Henrique Silva Gomes-Ferreira

doi:10.33448/rsd-v10i1.11975

Ana Cláudia Ervolino Da Silva, Fábio Roberto De Souza Batista + Show 5 more

Open Access

https://doi.org/10.33448/rsd-v10i1.11975

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Abstract

Post-menopausal osteoporosis is detrimental to bone metabolism as well as alveolar repair. This osteometabolic disorder is an obstacle to the success of maxillofacial rehabilitations, since a large number of patients are carriers of the disease. Denosumab is widely used as a treatment for post menopausal osteoporosis. This drug exerts an antiabsorptive action by inhibiting RANKL, helping to reduce the bone loss caused by osteoporosis. This study aimed to evaluate the repair bone formed after the extraction of the upper incisor of estrogen-deficient rats treated with anti-RANKL monoclonal antibody. The rats (Rattus novergicus albinus, Wistar) were ovariectomized or SHAM operated (n=36). Half of the ovariectomized rats were treated with osteoprotegerin with an Fc fragment (OPG-Fc; 10mg/kg, twice a week), the other half received saline solution as control. After 30 days the rats had their right upper incisor extracted. After 60 days of extraction, the alveoli were evaluated by immunohistochemical, computerized microtomography and confocal microscopy. The OPG-Fc decreased the percentage of bone volume (BV/TV), thickness (Tb.Th) and number of alveolar trabecules (Tb.N) when compared to groups that received saline solution (p<0.005). The OPG-Fc increased the separation between the trabecules (Tb.Sp) and the porosity (Po.tot) of the reparative alveolar bone (p<0.005). The OPG-Fc decreased immunolabelling for RANKL and TRAP when compared to groups that received saline solution. Treatment with OPG-Fc decreased bone neoformation but preserved preexisting bone tissue. This data is supported by the mineral apposition rate, which showed higher values for OVX/OPG-Fc when compared to the OVX group.

Highlights

Osteoporosis is a worldwide public health problem, and its incidence is rising, in view of the increased life expectancy of the population
3.1 Immunohistochemical Analysis The immunohistochemical reaction was done to characterize the stage of bone tissue development in the different experimental groups through the expression of osteocalcin, as well as the balance of the bone remodeling process through the expression of RANKL, OPG and Tartarate Resistant Phosphatase (TRAP), related to osteoclastic activity and bone resorption
Moderate marking for RANKL was observed in the SHAM group (Figure 2D), showing balance in the bone remodeling process, since the OPG presented itself in a moderate manner

Summary

Introduction

Osteoporosis is a worldwide public health problem, and its incidence is rising, in view of the increased life expectancy of the population. Estrogen deficiency increases osteoclastic activity without a corresponding increase in osteoblastic activity, leading to osteopenia, which affects about two thirds of the female population When it is associated with age, estrogen deficiency causes osteoporoses (Gallagher, 2008). Denosumab is a fully human monoclonal antibody that acts by inhibiting RANKL, one of the main modulators of osteoclastogenesis, being the first RANKL molecule inhibitor approved by the FDA for use in postmenopausal women at risk of osteoporosis. In humans it is administered subcutaneously in doses of 60mg every six months. Antibodies against RANKL are powerful antiabsorbing agents (Kostenuik et al, 2009; Adami et al, 2012), they do not interact with murine

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