Osteonecrosis of the Jaws (ONJ) in Mice after Extraction of Teeth with Periradicular Disease
Identifieur interne : 006811 ( Ncbi/Merge ); précédent : 006810; suivant : 006812Osteonecrosis of the Jaws (ONJ) in Mice after Extraction of Teeth with Periradicular Disease
Auteurs : Akrivoula Soundia [États-Unis] ; Danny Hadaya [États-Unis] ; Navid Esfandi [États-Unis] ; Rafael Scaf De Molon [États-Unis, Brésil] ; Olga Bezouglaia [États-Unis] ; Sarah M. Dry [États-Unis] ; Flavia Q. Pirih [États-Unis] ; Tara Aghaloo [États-Unis] ; Sotirios Tetradis [États-Unis]Source :
- Bone [ 8756-3282 ] ; 2016.
Abstract
Osteonecrosis of the jaws (ONJ) is a complication of antiresorptive medications, such as denosumab or bisphosphonates, prescribed to patients with bone malignancy or osteoporosis. The most common instigating local factor in ONJ pathogenesis is tooth extraction. However, in adults the great majority of teeth are extracted due to dental disease. Here, we have investigated alveolar bone healing after extraction of healthy teeth or teeth with naturally occurring periradicular disease in mice treated with high dose zoledronic acid (ZA), a potent bisphosphonate, or OPG-Fc, a RANKL inhibitor. C57BL/6 mice were treated for eight weeks and
Url:
DOI: 10.1016/j.bone.2016.06.011
PubMed: 27327410
PubMed Central: 5471352
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<front><div type="abstract" xml:lang="en"><p id="P1">Osteonecrosis of the jaws (ONJ) is a complication of antiresorptive medications, such as denosumab or bisphosphonates, prescribed to patients with bone malignancy or osteoporosis. The most common instigating local factor in ONJ pathogenesis is tooth extraction. However, in adults the great majority of teeth are extracted due to dental disease. Here, we have investigated alveolar bone healing after extraction of healthy teeth or teeth with naturally occurring periradicular disease in mice treated with high dose zoledronic acid (ZA), a potent bisphosphonate, or OPG-Fc, a RANKL inhibitor. C57BL/6 mice were treated for eight weeks and <italic>in vivo</italic>
micro-CT was performed to identify spontaneously occurring periradicular lesions around the roots of maxillary molars. Then, extractions of molars with and without dental disease were performed in all groups. Four weeks later, animals were euthanized and maxillae were dissected and analyzed. Clinically, all vehicle animals with extraction of healthy or diseased teeth, and most OPG-Fc or ZA animals with extraction of healthy teeth showed normal mucosal healing. On the contrary, most animals with OPG-Fc or ZA treatment and extraction of diseased teeth demonstrated impaired healing with visible mucosal defects. Radiographically, bone socket healing was significantly compromised in OPG-Fc and ZA-treated mice with periradicular disease in comparison to other groups. Histologically, all vehicle animals showed normal mucosal healing and socket remodeling. OPG-Fc and ZA animals with extraction of healthy teeth showed normal mucosal healing, woven bone formation in the socket, and decreased remodeling of the original socket confines. OPG-Fc and ZA animals with extraction of diseased teeth showed mucosal defects, persistent prominent inflammatory infiltrate, bone exposure and areas of osteonecrosis. These findings support that dental disease is critical in the pathogenesis of ONJ, not only as the instigating cause for tooth extraction, but also as a compounding factor in ONJ development and pathophysiology.</p>
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<title-group><article-title>Osteonecrosis of the Jaws (ONJ) in Mice after Extraction of Teeth with Periradicular Disease</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Soundia</surname>
<given-names>Akrivoula</given-names>
</name>
<xref rid="FN2" ref-type="author-notes">#</xref>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hadaya</surname>
<given-names>Danny</given-names>
</name>
<xref rid="FN2" ref-type="author-notes">#</xref>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Esfandi</surname>
<given-names>Navid</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>de Molon</surname>
<given-names>Rafael Scaf</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bezouglaia</surname>
<given-names>Olga</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Dry</surname>
<given-names>Sarah M.</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pirih</surname>
<given-names>Flavia Q.</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Aghaloo</surname>
<given-names>Tara</given-names>
</name>
<xref rid="FN1" ref-type="author-notes">*</xref>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tetradis</surname>
<given-names>Sotirios</given-names>
</name>
<xref rid="FN1" ref-type="author-notes">*</xref>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A5">6</xref>
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<aff id="A1"><label>1</label>
Division of Diagnostic and Surgical Sciences, UCLA School of Dentistry, Los Angeles, CA 90095, USA</aff>
<aff id="A2"><label>2</label>
Department of Diagnosis and Surgery, School of Dentistry at Araraquara, Sao Paulo State University, Araraquara 14801–903, Brazil</aff>
<aff id="A3"><label>3</label>
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA</aff>
<aff id="A4"><label>4</label>
Division of Constitutive & Regenerative Sciences, UCLA School of Dentistry, Los Angeles, CA 90095, USA</aff>
<aff id="A5"><label>6</label>
Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA</aff>
<author-notes><corresp id="FN1"><label>*</label>
Corresponding Authors: Sotirios Tetradis DDS, PhD, UCLA School of Dentistry, 10833 Le Conte Ave. CHS Rm. 53-068, Los Angeles, CA 90095-1668, Tel: (310) 825-5712, Fax: (310) 825-7232, <email>stetradis@dentistry.ucla.edu</email>
; Tara L. Aghaloo DDS, MD, PhD, UCLA School of Dentistry, 10833 Le Conte Ave. CHS Rm. 53-009, Los Angeles, CA 90095-1668, Tel: (310) 794-7070, Fax: (310) 825-7232, <email>taghaloo@dentistry.ucla.edu</email>
</corresp>
<fn id="FN2" fn-type="equal"><label>#</label>
<p>These authors contributed equally to the manuscript</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>13</day>
<month>4</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="epub"><day>18</day>
<month>6</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="ppub"><month>9</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>01</day>
<month>9</month>
<year>2017</year>
</pub-date>
<volume>90</volume>
<fpage>133</fpage>
<lpage>141</lpage>
<pmc-comment>elocation-id from pubmed: 10.1016/j.bone.2016.06.011</pmc-comment>
<abstract><p id="P1">Osteonecrosis of the jaws (ONJ) is a complication of antiresorptive medications, such as denosumab or bisphosphonates, prescribed to patients with bone malignancy or osteoporosis. The most common instigating local factor in ONJ pathogenesis is tooth extraction. However, in adults the great majority of teeth are extracted due to dental disease. Here, we have investigated alveolar bone healing after extraction of healthy teeth or teeth with naturally occurring periradicular disease in mice treated with high dose zoledronic acid (ZA), a potent bisphosphonate, or OPG-Fc, a RANKL inhibitor. C57BL/6 mice were treated for eight weeks and <italic>in vivo</italic>
micro-CT was performed to identify spontaneously occurring periradicular lesions around the roots of maxillary molars. Then, extractions of molars with and without dental disease were performed in all groups. Four weeks later, animals were euthanized and maxillae were dissected and analyzed. Clinically, all vehicle animals with extraction of healthy or diseased teeth, and most OPG-Fc or ZA animals with extraction of healthy teeth showed normal mucosal healing. On the contrary, most animals with OPG-Fc or ZA treatment and extraction of diseased teeth demonstrated impaired healing with visible mucosal defects. Radiographically, bone socket healing was significantly compromised in OPG-Fc and ZA-treated mice with periradicular disease in comparison to other groups. Histologically, all vehicle animals showed normal mucosal healing and socket remodeling. OPG-Fc and ZA animals with extraction of healthy teeth showed normal mucosal healing, woven bone formation in the socket, and decreased remodeling of the original socket confines. OPG-Fc and ZA animals with extraction of diseased teeth showed mucosal defects, persistent prominent inflammatory infiltrate, bone exposure and areas of osteonecrosis. These findings support that dental disease is critical in the pathogenesis of ONJ, not only as the instigating cause for tooth extraction, but also as a compounding factor in ONJ development and pathophysiology.</p>
</abstract>
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<name sortKey="Aghaloo, Tara" sort="Aghaloo, Tara" uniqKey="Aghaloo T" first="Tara" last="Aghaloo">Tara Aghaloo</name>
<name sortKey="Bezouglaia, Olga" sort="Bezouglaia, Olga" uniqKey="Bezouglaia O" first="Olga" last="Bezouglaia">Olga Bezouglaia</name>
<name sortKey="De Molon, Rafael Scaf" sort="De Molon, Rafael Scaf" uniqKey="De Molon R" first="Rafael Scaf" last="De Molon">Rafael Scaf De Molon</name>
<name sortKey="Dry, Sarah M" sort="Dry, Sarah M" uniqKey="Dry S" first="Sarah M." last="Dry">Sarah M. Dry</name>
<name sortKey="Esfandi, Navid" sort="Esfandi, Navid" uniqKey="Esfandi N" first="Navid" last="Esfandi">Navid Esfandi</name>
<name sortKey="Hadaya, Danny" sort="Hadaya, Danny" uniqKey="Hadaya D" first="Danny" last="Hadaya">Danny Hadaya</name>
<name sortKey="Pirih, Flavia Q" sort="Pirih, Flavia Q" uniqKey="Pirih F" first="Flavia Q." last="Pirih">Flavia Q. Pirih</name>
<name sortKey="Tetradis, Sotirios" sort="Tetradis, Sotirios" uniqKey="Tetradis S" first="Sotirios" last="Tetradis">Sotirios Tetradis</name>
<name sortKey="Tetradis, Sotirios" sort="Tetradis, Sotirios" uniqKey="Tetradis S" first="Sotirios" last="Tetradis">Sotirios Tetradis</name>
</country>
<country name="Brésil"><noRegion><name sortKey="De Molon, Rafael Scaf" sort="De Molon, Rafael Scaf" uniqKey="De Molon R" first="Rafael Scaf" last="De Molon">Rafael Scaf De Molon</name>
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</country>
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