| アブストラクト | Osteonecrosis of the jaw (ONJ), a rare side effect of bisphosphonate therapy, is a debilitating disorder with a poorly understood etiology. FDA's Adverse Event Reporting System (FAERS) provides the opportunity to investigate this disease. Our goals were to analyze FAERS data to discover possible relationships between ONJ and specific conditions and drugs and then to consult the scientific literature to deduce biological explanations. Our methodology revealed a very strong association between gastroesophageal reflux and bisphosphonate-induced ONJ, suggesting acidosis as a key factor. Overgrowth of acidophilic species, particularly Streptococcus mutans, in the oral microbiome in the context of insufficient acid buffering due to impaired salivary glands maintains the low pH that sustains damage to the mucosa. Significant associations between ONJ and adrenal insufficiency, vitamin C deficiency, and Sjogren's syndrome were found. Glucose 6 phosphate dehydrogenase (G6PD) deficiency can explain much of the pathology. An inability to maintain vitamin C and other antioxidants in the reduced form leads to vascular oxidative damage and impaired adrenal function. Thus, pathogen-induced acidosis, hypoxia, and insufficient antioxidant defenses together induce ONJ. G6PD deficiency and adrenal insufficiency are underlying factors. Impaired supply of adrenal-derived sulfated sterols such as DHEA sulfate may drive the disease process. |
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| ジャーナル名 | Disease markers |
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| 投稿日 | 2016/10/25 |
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| 投稿者 | Seneff, Stephanie; Swanson, Nancy L; Koenig, Gerald; Li, Chen |
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| 組織名 | Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA;02139, USA.;Abacus Enterprises, Lummi Island, WA, USA.;Health-e-Iron, LLC, 2800 Waymaker Way, No. 12, Austin, TX 78746, USA; Iron;Disorders Institute, Greenville, SC 29615, USA. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/27773962/ |
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