Pharmacogenetics of medication-related osteonecrosis of the jaw: a systematic review and meta-analysis

Guo, Ziheng; Cui, Weicheng; Que, Lijuan; Li, C.; Tang, Xi; Liu, J.

doi:10.1016/j.ijom.2019.07.016

Cited by 18 publications

(20 citation statements)

References 53 publications

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“…In the pharmacogenetic review and meta‐analysis of GWAS data, the functional alleles of CYP2C8 ( CYP2C8*2 and *3 ) have not been considered because they are not detected in the genome‐wide SNP arrays 1 . The variants occurring in the GWAS studies were in the non‐coding regions, therefore, could not be studied in functional enzyme assays.…”

Section: Discussionmentioning

confidence: 99%

Role of cytochrome P450 2C8 genetic polymorphism and epoxygenase uncoupling in periodontal remodelling affecting orthodontic treatment

Yamoune

Wintz

Niederau

et al. 2021

Basic Clin Pharma Tox

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In genome‐wide association studies, the CYP2C8 gene locus has been reported to be associated with bisphosphonate‐related osteonecrosis of the jaw, a severe devastating side effect of antiresorptive bone treatment. The aim of this study was to elucidate the putative pathomechanism explaining the association between the genetic polymorphism with the alleles CYP2C8*2 and *3 causing low CYP2C8 activity, and disturbed periodontal remodelling in periodontal fibroblasts cultured from patients undergoing orthodontic treatment. CYP2C8 activity, enzyme expression and substrate metabolism were detected in human periodontal fibroblast cultures. Zoledronic acid caused enhanced reactive oxygen species (ROS) production in periodontal fibroblasts, which was enhanced by arachidonic acid as inflammatory signal. Enhanced bisphosphonate‐induced uncoupling of the CYP2C8 enzyme was detected in the variant allele (CYP2C8*3) with the result of increased H2O2 production and lowered substrate oxidation. Conversely, substrate (amodiaquine) addition led to decreased H2O2 production in isolated CYP2C8 enzymes, but in CYP2C8*3 enzyme, increased H2O2 was still detected, especially in presence of arachidonic acid. CYP2C8 variants leading to decreased enzyme activity in substrate oxidation may enhance ROS production by reaction uncoupling, and thus, contribute to difficulties in orthodontic treatment and the risk of side effects of antiresorptive drugs.

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Section: Discussionmentioning

confidence: 99%

Role of cytochrome P450 2C8 genetic polymorphism and epoxygenase uncoupling in periodontal remodelling affecting orthodontic treatment

Yamoune

Wintz

Niederau

et al. 2021

Basic Clin Pharma Tox

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“…Bisphosphonate-related osteonecrosis of the jaw is defined by the American Society for Bone and Mineral Research (ASBMR) as an area of necrotic bone [11] exposed in the maxillofacial region that does not heal within 8 weeks after identification by a health care provider, in a patient who was receiving or had been exposed to a bisphosphonate and has not received radiation therapy to the craniofacial region [12,13] . Bisphosphonates are antiresorptive, osteoclastic bone resorption blocking drugs that inhibit mineral dissolution [7,14,15,16] . It is characterized by refractory bone exposure [17] .…”

Section: Etiologymentioning

confidence: 99%

Osteonecrosis of the jaw: An update

Guerrero¹,

Garza²,

Silva³

et al. 2021

Int. J. Appl. Dent. Sci.

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Introduction: Osteonecrosis of the jaw (ONJ) is a well-known pathological condition in oncology arising from bisphosphonate use. In recent years, the number of cases of drug-related osteonecrosis of the jaw has steadily increased due to the introduction of new immunological drugs. Objective: To analyze the literature on osteonecrosis of the jaw and its relation to drugs. Methodology: The search was performed in PubMed, SCOPUS and Google Scholar databases. The quality of the articles was assessed using PRISMA guidelines. The terms "osteonecrosis jaw", "etiology", "epidemiology", "diagnostic methods", "oral manifestations", "treatment", in conjunction with logical Boolean operators AND, OR and NOT were used. Results: Although the pathogenesis of ONJ is still unclear, genetic factors have shown an important role in this disease. It is more frequent in patients who ingest bisphosphonates, whether orally or intravenously, with a frequency of 65% in the mandible. Necrotic bone exposure is one of the most frequent oral manifestations that occur. The most characteristic diagnostic methods include orthopantomography, magnetic resonance imaging and computed tomography. One of the treatments to consider is the education and instruction in oral hygiene that the patient should perform/take, as well as the use of oral antibacterial rinses. Conclusion: Every patient treated with bisphosphonates is susceptible to present mandibular osteonecrosis when undergoing invasive dental procedures, therefore, it is necessary to consider which are the most significant clinical characteristics, as well as the diagnostic methods by which we can identify it in the patient; the treatments are very varied depending on the situation in which each case is found.

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“…Los bifosfonatos (BP) son una familia de medicamentos comúnmente usados para tratamiento de la osteoporosis, neoplasias malignas y mieloma múltiple 1 , se consideran análogos sintéticos de los pirofosfatos inorgánicos, con gran afinidad por el calcio presente en la matriz ósea extracelular 2,3 .…”

Section: Introductionunclassified

“…A pesar de que han transcurrido más de 15 años de la descripción de esta patología y de miles de investigaciones sobre el tema todavía falta claridad sobre su patogénesis 15,16 , llegándose incluso a proponer la posibilidad de un factor genético asociado a un polimorfismo 3 .…”

Section: Introductionunclassified

Osteonecrosis of the jaw associated to biphosponates in Cali-Colombia

Arcila¹,

Llano²

2020

Rev Estomatol

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Background: After more than 15 years of the first report of osteonecrosis associated with bisphosphonate (BP), still cases related to BP and other medications continue to be reported and there is an alert about the increase in the number of prescriptions. The need for both patients and students and health professionals to be familiar with medications, pathology, prevention and treatment measures has been highlighted. Aim: To characterize patients with osteonecrosis in the maxilla associated to bisphosphonate (BRONJ), from Cali, Colombia. Materials and Methods: A structured survey was conducted of 32 maxillofacial surgeons from the city of Cali, Colombia, where different topics related to affected patients and the development of the pathology such as age and gender of patients, type of medication, time of study were asked. administration, exposed bone, etc. Results: Thirty-two maxillofacial surgeons answered the survey with a total of 8 cases, it was found that 6 corresponded to women and 2 to men and the age was over 44 years; 4 of the treatments were oral prescription and 4 intravenous; the majority of cases were presented in the jaw (88%) and 6 cases (75%) presented bone exposure. Conclusions: Osteonecrosis associated with bisphosphonates is a situation that still occurs and could increase its incidence due to the increase in the number of prescriptions for osteoporosis medications, it is necessary that the patient community and health staff know More about this situation.

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Pharmacogenetics of medication-related osteonecrosis of the jaw: a systematic review and meta-analysis

Cited by 18 publications

References 53 publications

Role of cytochrome P450 2C8 genetic polymorphism and epoxygenase uncoupling in periodontal remodelling affecting orthodontic treatment

Role of cytochrome P450 2C8 genetic polymorphism and epoxygenase uncoupling in periodontal remodelling affecting orthodontic treatment

Osteonecrosis of the jaw: An update

Osteonecrosis of the jaw associated to biphosponates in Cali-Colombia

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