Is GERD a Factor in Osteonecrosis of the Jaw? Evidence of Pathology Linked to G6PD Deficiency and Sulfomucins
Identifieur interne : 000F31 ( Main/Exploration ); précédent : 000F30; suivant : 000F32Is GERD a Factor in Osteonecrosis of the Jaw? Evidence of Pathology Linked to G6PD Deficiency and Sulfomucins
Auteurs : Stephanie Seneff [États-Unis] ; Nancy L. Swanson [États-Unis] ; Gerald Koenig [États-Unis] ; Chen Li [États-Unis]Source :
- Disease Markers [ 0278-0240 ] ; 2016.
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
Url:
DOI: 10.1155/2016/8376979
PubMed: 27773962
PubMed Central: 5059643
Affiliations:
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Swanson</name><affiliation wicri:level="1"><nlm:aff id="I2">Abacus Enterprises, Lummi Island, WA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Abacus Enterprises, Lummi Island, WA</wicri:regionArea><wicri:noRegion>WA</wicri:noRegion></affiliation></author><author><name sortKey="Koenig, Gerald" sort="Koenig, Gerald" uniqKey="Koenig G" first="Gerald" last="Koenig">Gerald Koenig</name><affiliation wicri:level="1"><nlm:aff id="I3">Health-e-Iron, LLC, 2800 Waymaker Way, No. 12, Austin, TX 78746, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Health-e-Iron, LLC, 2800 Waymaker Way, No. 12, Austin, TX 78746</wicri:regionArea><wicri:noRegion>TX 78746</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="I4">Iron Disorders Institute, Greenville, SC 29615, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Iron Disorders Institute, Greenville, SC 29615</wicri:regionArea><wicri:noRegion>SC 29615</wicri:noRegion></affiliation></author><author><name sortKey="Li, Chen" sort="Li, Chen" uniqKey="Li C" first="Chen" last="Li">Chen Li</name><affiliation wicri:level="1"><nlm:aff id="I1">Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139</wicri:regionArea><wicri:noRegion>MA 02139</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27773962</idno><idno type="pmc">5059643</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5059643</idno><idno type="RBID">PMC:5059643</idno><idno type="doi">10.1155/2016/8376979</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">003D85</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">003D85</idno><idno type="wicri:Area/Pmc/Curation">003D84</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">003D84</idno><idno type="wicri:Area/Pmc/Checkpoint">000860</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000860</idno><idno type="wicri:Area/Ncbi/Merge">008940</idno><idno type="wicri:Area/Ncbi/Curation">008940</idno><idno type="wicri:Area/Ncbi/Checkpoint">008940</idno><idno type="wicri:doubleKey">0278-0240:2016:Seneff S:is:gerd:a</idno><idno type="wicri:Area/Main/Merge">000F33</idno><idno type="wicri:Area/Main/Curation">000F31</idno><idno type="wicri:Area/Main/Exploration">000F31</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Is GERD a Factor in Osteonecrosis of the Jaw? Evidence of Pathology Linked to G6PD Deficiency and Sulfomucins</title><author><name sortKey="Seneff, Stephanie" sort="Seneff, Stephanie" uniqKey="Seneff S" first="Stephanie" last="Seneff">Stephanie Seneff</name><affiliation wicri:level="1"><nlm:aff id="I1">Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139</wicri:regionArea><wicri:noRegion>MA 02139</wicri:noRegion></affiliation></author><author><name sortKey="Swanson, Nancy L" sort="Swanson, Nancy L" uniqKey="Swanson N" first="Nancy L." last="Swanson">Nancy L. Swanson</name><affiliation wicri:level="1"><nlm:aff id="I2">Abacus Enterprises, Lummi Island, WA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Abacus Enterprises, Lummi Island, WA</wicri:regionArea><wicri:noRegion>WA</wicri:noRegion></affiliation></author><author><name sortKey="Koenig, Gerald" sort="Koenig, Gerald" uniqKey="Koenig G" first="Gerald" last="Koenig">Gerald Koenig</name><affiliation wicri:level="1"><nlm:aff id="I3">Health-e-Iron, LLC, 2800 Waymaker Way, No. 12, Austin, TX 78746, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Health-e-Iron, LLC, 2800 Waymaker Way, No. 12, Austin, TX 78746</wicri:regionArea><wicri:noRegion>TX 78746</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="I4">Iron Disorders Institute, Greenville, SC 29615, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Iron Disorders Institute, Greenville, SC 29615</wicri:regionArea><wicri:noRegion>SC 29615</wicri:noRegion></affiliation></author><author><name sortKey="Li, Chen" sort="Li, Chen" uniqKey="Li C" first="Chen" last="Li">Chen Li</name><affiliation wicri:level="1"><nlm:aff id="I1">Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139</wicri:regionArea><wicri:noRegion>MA 02139</wicri:noRegion></affiliation></author></analytic><series><title level="j">Disease Markers</title><idno type="ISSN">0278-0240</idno><idno type="eISSN">1875-8630</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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<italic> Streptococcus mutans</italic>, 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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Hoff, A O" uniqKey="Hoff A">A. O. Hoff</name></author><author><name sortKey="Toth, B B" uniqKey="Toth B">B. B. Toth</name></author><author><name sortKey="Altundag, K" uniqKey="Altundag K">K. Altundag</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nancollas, G H" uniqKey="Nancollas G">G. H. Nancollas</name></author><author><name sortKey="Tang, R" uniqKey="Tang R">R. 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Erler</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Seneff, Stephanie" sort="Seneff, Stephanie" uniqKey="Seneff S" first="Stephanie" last="Seneff">Stephanie Seneff</name></noRegion><name sortKey="Koenig, Gerald" sort="Koenig, Gerald" uniqKey="Koenig G" first="Gerald" last="Koenig">Gerald Koenig</name><name sortKey="Koenig, Gerald" sort="Koenig, Gerald" uniqKey="Koenig G" first="Gerald" last="Koenig">Gerald Koenig</name><name sortKey="Li, Chen" sort="Li, Chen" uniqKey="Li C" first="Chen" last="Li">Chen Li</name><name sortKey="Swanson, Nancy L" sort="Swanson, Nancy L" uniqKey="Swanson N" first="Nancy L." last="Swanson">Nancy L. Swanson</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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