IMR Press / FBE / Volume 3 / Issue 1 / DOI: 10.2741/E251

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Pharmacogenetics of bisphosphonate-associated osteonecrosis of the jaw
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1 Department of Internal Medicine, University of Florence, Medical School, Viale Pieraccini 6, 50139 Florence, Italy
2 Department of Odontostomatology, University of Florence, Medical School, Viale Morgagni 85, 50139, Florence, Italy

*Author to whom correspondence should be addressed.

Academic Editor: Reina Armamento-Villareal

Front. Biosci. (Elite Ed) 2011, 3(1), 364–370; https://doi.org/10.2741/E251
Published: 1 January 2011
(This article belongs to the Special Issue Skeletal biology)
Abstract

An undesirable effect associated with bisphosphonates is osteonecrosis of the jaw (ONJ). Case reports discussed ONJ development in patients with multiple myeloma or metastatic cancers receiving bisphosphonates as palliation for malignant bone disease. No causative relationship has been unequivocally demonstrated between ONJ and bisphosphonate therapy. To determine if a higher sensitivity to bisphosphonates could in part explain the development of ONJ, the segregation of A/C rs2297480 polymorphism of gene encoding for the farnesyl pyrophosphate synthase (FDPS) with ONJ was evaluated in a cohort of 68 Caucasian patients treated with zoledronic acid for multiple myeloma and metastatic mammary and prostate cancer. The AA and CC genotypes were highly differently distributed among ONJ patients and controls, matched for sex and type of malignant disease, with a positive correlation between AA carrier status and occurrence of ONJ (p=0.03) after 18-24 months of treatment. Because FDPS gene variants have been associated with bone morbidity, these pharmacogenetic association likely reflect the interaction of amino-bisphosphonates with germline sensitivity to drug actions, and might identify patients at highest risk to develop ONJ.

Keywords
Bisphosphonates
Osteonecrosis
Metastases
Mevalonate Pathway
Gene Polymorphisms
Pharmacogenetics
Review
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