Is GERD a Factor in Osteonecrosis of the Jaw? Evidence of Pathology Linked to G6PD Deficiency and Sulfomucins

Stephanie Seneff,Nancy L Swanson,Gerald Koenig,Chen Li

doi:10.1155/2016/8376979

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, 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 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.

Highlights

Osteonecrosis of the jaw (ONJ) is a debilitating disorder that was originally linked to radiation therapy to treat cancers of the head and neck [1]
Our research into Food and Drug administration (FDA)’s Adverse Event Reporting System (FAERS) data subsets has led to the observation that ONJ is associated with adrenal insufficiency and symptoms of vitamin C insufficiency
We propose that Glucose 6 phosphate dehydrogenase (G6PD) deficiency may be an important high-level factor in the disease process

Summary

Introduction

Osteonecrosis of the jaw (ONJ) is a debilitating disorder that was originally linked to radiation therapy to treat cancers of the head and neck [1]. It later became apparent that ONJ was a risk factor in cancers not involving radiation of the head/neck region, mainly multiple myeloma and breast cancer. ONJ has been established as a potential side effect of bisphosphonate (BP) therapy, the nitrogencontaining intravenous BPs (N-IBPs) frequently given to cancer patients. The evidence is strong in support of a link to ONJ, the mechanism by which this occurs remains unclear, despite much research. The fact that the jaw is so susceptible to osteonecrosis compared to other bones in the body remains a mystery

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