Genetic Polymorphism in BRONJ Patients

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a complication seen in patients on bisphosphonates (BPs) for malignant diseases such as cancer and serious conditions including osteoporosis. Oral, periodontal, and endodontic treatment has been implicated as possible risk factors of BRONJ for those taking BPs. Studies indicate that patients taking BPs are at a higher risk of developing BRONJ. We hypothesize that genetic and environmental factors may contribute to the development of the disease given that several patients who have taken BPs have not developed BRONJ. A weakened microbicidal activity of the immune cells could be one of the factors attributable to the etiology of ONJ.  Inflammatory markers such as myeloperoxidase (MPO), catalase, and others have been analyzed for polymorphisms.  MPO is found in leukocytes and interact with H₂O₂ and halide to defend the human cells from bacteria, fungi, and viruses. Objective: To gather conclusive evidence linking polymorphisms in both ONJ patients who have and have not been administered BPs.  Additionally, from experimental studies published in recent articles and journals we hope to better explain the etiological role of genetic polymorphisms in ONJ patients. Methods: A literature search was conducted using sites such as PubMed to locate experimental studies published regarding this topic. After assessing the validity of the scientific methods used in these studies, we documented, compared, and analyzed the results.  Results: Genetic polymorphism of MPO gene is reported in cancer patients, which further suggest that these genetic mutations may have a possible role in BRONJ pathogenesis.  With a limited sample size of mucosal tissue from patients with BRONJ, we have identified genetic polymorphism in G-463A MPO gene. Conclusions: A mutation in MPO would suggest that genetic factors could be one etiological factor in increasing susceptibility to chronic infections associated with bone necrosis.