Pharmacogenetics of Bisphosphonate-associated Osteonecrosis of the Jaw

Abstract

Osteonecrosis of the jaws (ONJ) is a potentially severe disorder that develops in a subgroup of individuals who have used bisphosphonate (BP) medications. Several clinical risk factors have been associated with the risk of ONJ development, but evidence is limited and in most instances ONJ remains an unpredictable adverse drug reaction. Interindividual genetic variability can contribute to explaining ONJ development in a subset of BP users and the discovery of relevant associated gene variants could lead to the identification of individuals at higher risk. No genetic variant has been found to be robustly associated with susceptibility to ONJ.

Paradoxical side effects of bisphosphonates on the skeleton: What do we know and what can we do?

“…Genotype profiling has been considered a tool for identifying individuals with a risk of developing BRONJ (Fung et al, ; Khan et al, ). A genetic predisposition has been proposed (Fung et al, ; Khan et al, ) based on the identification of patients with similar comorbidities in BRONJ (Fung et al, ; Khan et al, ). Polymorphisms in the farnesyl pyrophosphate synthase and/or several genes such as cytochrome P450 CYP2C8 have been suggested as predisposing for BRONJ (Fung et al, ; Khan et al, ).…”

“…A genetic predisposition has been proposed (Fung et al, ; Khan et al, ) based on the identification of patients with similar comorbidities in BRONJ (Fung et al, ; Khan et al, ). Polymorphisms in the farnesyl pyrophosphate synthase and/or several genes such as cytochrome P450 CYP2C8 have been suggested as predisposing for BRONJ (Fung et al, ; Khan et al, ). However, there is little evidence for a pharmacogenetic susceptibility to the development of BRONJ (Fung et al, ; Khan et al, ).…”

“…Polymorphisms in the farnesyl pyrophosphate synthase and/or several genes such as cytochrome P450 CYP2C8 have been suggested as predisposing for BRONJ (Fung et al, ; Khan et al, ). However, there is little evidence for a pharmacogenetic susceptibility to the development of BRONJ (Fung et al, ; Khan et al, ).…”

“…CYP2C8, among others, have been suggested as predisposing certain individuals to BRONJ (Fung et al, 2015;Khan et al, 2015).…”

“…Genotype profiling has been considered a tool for identifying individuals with a risk of developing BRONJ (Fung et al, 2015;Khan et al, 2015). A genetic predisposition has been proposed (Fung et al, 2015;Khan et al, 2015) based on the identification of patients with similar comorbidities in BRONJ (Fung et al, 2015;Khan et al, 2015).…”