Bisphosphonate-related osteonecrosis: genetic and acquired risk factors.
The objectives of this study were to review epidemiological, clinical and biological aspects associated with the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in multiple myeloma (MM) patients, with special emphasis on the genetic aspects. A detailed review of previously described risk factors as well as recent genetic findings mostly comprises this work. The most recent meeting abstracts and relevant articles published in journals covered by the Science Citation Index and Medline are also examined. The review pays special attention to the genetic component of BRONJ. A total of 15 series and 14 guidelines or revisions were selected to fit the aims of the review. Gene variability was reviewed in depth to give a clinical illustration on the genetic aspects of BRONJ. Crude prevalence and 5-year cumulative incidence were considered as the most important end points for predictive purposes. Several acquired factors were recognized as predictors for BRONJ in MM, especially intravenous bisphosphonates, dental trauma and advanced age. Among genetic factors, polymorphisms on CYP2C8 gene arise as a promising risk factor. Bisphosphonate-related osteonecrosis of the jaw can be predicted with a conjunction of genetic and environmental risk factors.
Molecular Biology and HLA Unit, Department of Haematology, University Hospital of Salamanca, Salamanca, Spain.
M E
ME
Sarasquete
M
M
González
J F
JF
San Miguel
R
R
García-Sanz
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D065727:Cytochrome P-450 CYP2C8; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D020022:Genetic Predisposition to Disease; D006801:Humans; D007262:Infusions, Intravenous; D007571:Jaw Diseases / Q000139:chemically induced* / Q000150:complications / Q000235:genetics / Q000473:pathology; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D010020:Osteonecrosis / Q000139:chemically induced* / Q000150:complications / Q000235:genetics / Q000473:pathology; D012307:Risk Factors
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8