Exposure to antiresorptive therapy with bisphosphonates does not induce histological changes in human alveolar jawbone

Alberto Bedogni,Stella Blandamura,Giorgia Saia,Giorgio Bedogni,Giordana Bettini,Nooshin Abbasi

doi:10.32388/191840

Abstract

Aim: The identification of specific alterations in the alveolar jawbone of patients treated with nitrogen-containing bisphosphonates (NBP) but without bisphosphonate-related osteonecrosis of the jaw (BRONJ) may help to identify the early steps of BRONJ and to select patients at risk for it. Materials and Methods: We performed a case-control study. Cases were 60 individuals treated with NBP without clinical and radiological signs of BRONJ and requiring surgical tooth extraction. Controls were 60 individuals never treated with NBP and requiring tooth extraction. Cases and controls were matched by sex (same) and age (within 5 years). 18 categorical (basophile reversal lines, osteoblasts, osteoblastic lines, osteocytes, empty osteocytic lacunae, osteoclasts, Howship’s lacunae, vessel dilatation, vascular congestion, arteriolar thickening, intravascular fat globules, calcific fat necrosis, fatty bone marrow, ruptured adipocytes, granular cytoplasm of adipocytes, oil cysts, perivascular fibrosis, diffuse fibrous metaplasia) and 2 ordinal histopathological variables (inflammation and bone maturation) were investigated. Exact univariable and multivariable (correction for gender and age) logistic regression was used to test the association between NBP use and the histopathological variables. Because of multiple comparisons, the critical p-value was set to 0.0025 (0.05/20). Results: Cases and controls did not differ for any study variable except for vascular congestion that was significantly associated with NBP use (multivariable OR = 0.24, exact 95% CI 0.10 to 0.57 for cases vs. controls, p = 0.0006). Conclusions: Use of NBP does not produce specific histological alveolar bone alterations in the absence of overt BRONJ disease.

Highlights

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the first and most studied[1] of a number of bone disorders that have been linked to the use of different classes of medications, including antiresorptive drugs
Aim: The identification of specific alterations in the alveolar jawbone of patients treated with nitrogen-containing bisphosphonates (NBP) but without bisphosphonate-related osteonecrosis of the jaw (BRONJ) may help to identify the early steps of BRONJ and to select patients at risk for it
Bacterial invasion through a discontinuation of the oral mucosa would subsequently lead to the exposure of infected necrotic bone.[14][15][16] In a recent study, we found that alveolar bone histology at the time of tooth extraction can predict BRONJ occurrence in patients treated with NBP

Summary

Introduction

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the first and most studied[1] of a number of bone disorders that have been linked to the use of different classes of medications, including antiresorptive drugs These osteonecrotic processes have been recently gathered under the term of Medication-related osteonecrosis of the jaw.[2] the pathogenesis of BRONJ is likely to be multifactorial,[3][4][5] prolonged therapy with antiresorptives and NBP in particular seems to influence jawbone remodeling and predispose to development of clinical signs of BRONJ.[6] Tooth extraction, oral surgery and use of corticosteroids are additional risk factors.[7][8][9] These antiresorptive agents are worldwide administered in malignant and benign disruptive bone diseases and, because interfering with osteoclasts functions, NBP effectively reduce bone resorption rate.[10] NBP are thought to accumulate in the jaws at higher concentration than in other bones owing to the high turnover of the dento-alveolar region.[11] An increase of bone remodeling at the sites of NBP accumulation promotes osteoclasts migration and activation of NBP that, in turn, interfere with bone healing ensuing the accumulation of non-viable bone.[11][12][13] According to this hypothesis, a mucosal breakdown caused by local precipitating factors such as tooth extraction and ill-fitting prostheses would expose the “non-viable” bone and promote its superinfection. The identification of specific histopathological alterations of the alveolar jawbone of patients treated with NBP but without BRONJ may help to better understand the effects of NBP on jawbone and identify the early steps of disease

Objectives

Methods

Results