title: Is GERD a Factor in Osteonecrosis of the Jaw? Evidence of Pathology Linked to G6PD Deficiency and Sulfomucins.
abstract: 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, particularlyStreptococcus 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 Sjögren'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.
authors: Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139, USA.
authors: Stephanie
authors: 0000-0001-8191-1049
authors: S
authors: Seneff
authors: Abacus Enterprises, Lummi Island, WA, USA.
authors: Nancy L
authors: NL
authors: Swanson
authors: Health-e-Iron, LLC, 2800 Waymaker Way, No. 12, Austin, TX 78746, USA; Iron Disorders Institute, Greenville, SC 29615, USA.
authors: Gerald
authors: 0000-0002-6405-9410
authors: G
authors: Koenig
authors: Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139, USA.
authors: Chen
authors: C
authors: Li
mesh_terms: D000465:Algorithms; D001206:Ascorbic Acid Deficiency / Q000150:complications; D004164:Diphosphonates / Q000009:adverse effects; D005764:Gastroesophageal Reflux / Q000503:physiopathology*; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000150:complications*; D006801:Humans; D007571:Jaw Diseases / Q000139:chemically induced / Q000453:epidemiology / Q000473:pathology*; D009077:Mucins / Q000009:adverse effects*; D010020:Osteonecrosis / Q000139:chemically induced / Q000453:epidemiology / Q000473:pathology*; D011379:Prognosis
chemical_list: D004164:Diphosphonates; D009077:Mucins; C012564:sulfomucin