Effect of anti-angiogenesis induced by chemotherapeutic monotherapy, chemotherapeutic/bisphosphonate combination therapy and anti-VEGFA mAb therapy on tooth extraction socket healing in mice
Osteonecrosis of the jaw (ONJ), which is a rare but severe adverse effect, mainly occurs in oncology patients receiving chemotherapeutic agents and bisphosphonates. However, the combined impact of chemotherapy and bisphosphonates on wound healing after tooth extraction remains unknown. The aim of th...
Gespeichert in:
| Veröffentlicht in: | Journal of bone and mineral metabolism 2018-09, Vol.36 (5), p.547-559 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 559 |
|---|---|
| container_issue | 5 |
| container_start_page | 547 |
| container_title | Journal of bone and mineral metabolism |
| container_volume | 36 |
| creator | Akita, Yuri Kuroshima, Shinichiro Nakajima, Kazunori Hayano, Hiroki Kanai, Riho Sasaki, Muneteru Sawase, Takashi |
| description | Osteonecrosis of the jaw (ONJ), which is a rare but severe adverse effect, mainly occurs in oncology patients receiving chemotherapeutic agents and bisphosphonates. However, the combined impact of chemotherapy and bisphosphonates on wound healing after tooth extraction remains unknown. The aim of this study was to determine the precise etiology of ONJ induced by chemotherapy and bisphosphonate combination therapy. Mice received zoledronate (ZA) monotherapy, cyclophosphamide (CY) monotherapy or CY/ZA combination therapy. The maxillary first molars were extracted 3 weeks after the initiation of drug treatment. Moreover, antivascular endothelial growth factor A (VEGFA) monoclonal antibody (mAb) was administered once every 2 days just after tooth extraction for 2 weeks. Soft and hard tissue wound healing was evaluated 2 and 4 weeks post-extraction using histomorphometry, microcomputed tomography and immunohistochemistry. ZA monotherapy did not induce impaired oral wound healing and ONJ-like lesions 2 and 4 weeks post-extraction, respectively. Tooth extraction socket healing worsened with severe anti-angiogenesis by CY monotherapy and CY/ZA combination therapy 2 weeks post-extraction. However, CY monotherapy rarely induced ONJ-like lesions with severe angiogenesis suppression, whereas CY/ZA combination therapy frequently induced ONJ-like lesions with severe angiogenesis inhibition 4 weeks post-extraction. Interestingly, anti-VEGFA mAb therapy delayed osseous wound healing with normal soft tissue wound healing of tooth extraction sockets, although this therapy significantly suppressed blood vessel formation. Our findings suggest that anti-angiogenesis alone is not the main cause of ONJ-like lesions induced by CY/ZA combination therapy. The combination of suppressed osteoclasts and anti-angiogenesis, in addition to other risk factors such as chemotherapy, may contribute to the development of ONJ. |
| doi_str_mv | 10.1007/s00774-017-0872-1 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1952530191</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2094098492</sourcerecordid><originalsourceid>FETCH-LOGICAL-c517t-d46c204c10731b0b2975de3680d7ca74d8e4138e059c06eb0f7f9a7a713594863</originalsourceid><addsrcrecordid>eNp1kcFu1DAQhi0EokvhAbggS1w4EDpOnDg-rqptQarEhfZqOc5k12VjL7YjsS_Hs-GQpUhFPdgea77_n5F-Qt4y-MQAxEXMl-AFMFFAK8qCPSMrxqu6qBvgz8kKJONFK4Q8I69ivIcM1oK9JGelBF7xhq3Ir80woEnUD1S7ZAvtttZv0WG0kVrXTwZ72h2p2eHo0w6DPuCUrKGjd6f_8eN_3YvOxsPOz8fphNT4sbO5st7RkyiP65eRd5vrqzUd191Da6Z89qP4MwVt_siiN98x0R3qvXXbvBodrcHX5MWg9xHfnN5zcnu1-Xb5ubj5ev3lcn1TmJqJVPS8MSVww0BUrIOulKLusWpa6IXRgvctcla1CLU00GAHgxikFlqwqpa8bapz8mHxPQT_Y8KY1Gijwf1eO_RTVEzWZV0Bkyyj7x-h934KLm-nSpAcZMtlmSm2UCb4GAMO6hDsqMNRMVBzuGoJV-XM1Byump3fnZynbsT-QfE3zQyUCxBzy20x_Bv9tOtvhmey-w</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2094098492</pqid></control><display><type>article</type><title>Effect of anti-angiogenesis induced by chemotherapeutic monotherapy, chemotherapeutic/bisphosphonate combination therapy and anti-VEGFA mAb therapy on tooth extraction socket healing in mice</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Akita, Yuri ; Kuroshima, Shinichiro ; Nakajima, Kazunori ; Hayano, Hiroki ; Kanai, Riho ; Sasaki, Muneteru ; Sawase, Takashi</creator><creatorcontrib>Akita, Yuri ; Kuroshima, Shinichiro ; Nakajima, Kazunori ; Hayano, Hiroki ; Kanai, Riho ; Sasaki, Muneteru ; Sawase, Takashi</creatorcontrib><description>Osteonecrosis of the jaw (ONJ), which is a rare but severe adverse effect, mainly occurs in oncology patients receiving chemotherapeutic agents and bisphosphonates. However, the combined impact of chemotherapy and bisphosphonates on wound healing after tooth extraction remains unknown. The aim of this study was to determine the precise etiology of ONJ induced by chemotherapy and bisphosphonate combination therapy. Mice received zoledronate (ZA) monotherapy, cyclophosphamide (CY) monotherapy or CY/ZA combination therapy. The maxillary first molars were extracted 3 weeks after the initiation of drug treatment. Moreover, antivascular endothelial growth factor A (VEGFA) monoclonal antibody (mAb) was administered once every 2 days just after tooth extraction for 2 weeks. Soft and hard tissue wound healing was evaluated 2 and 4 weeks post-extraction using histomorphometry, microcomputed tomography and immunohistochemistry. ZA monotherapy did not induce impaired oral wound healing and ONJ-like lesions 2 and 4 weeks post-extraction, respectively. Tooth extraction socket healing worsened with severe anti-angiogenesis by CY monotherapy and CY/ZA combination therapy 2 weeks post-extraction. However, CY monotherapy rarely induced ONJ-like lesions with severe angiogenesis suppression, whereas CY/ZA combination therapy frequently induced ONJ-like lesions with severe angiogenesis inhibition 4 weeks post-extraction. Interestingly, anti-VEGFA mAb therapy delayed osseous wound healing with normal soft tissue wound healing of tooth extraction sockets, although this therapy significantly suppressed blood vessel formation. Our findings suggest that anti-angiogenesis alone is not the main cause of ONJ-like lesions induced by CY/ZA combination therapy. The combination of suppressed osteoclasts and anti-angiogenesis, in addition to other risk factors such as chemotherapy, may contribute to the development of ONJ.</description><identifier>ISSN: 0914-8779</identifier><identifier>EISSN: 1435-5604</identifier><identifier>DOI: 10.1007/s00774-017-0872-1</identifier><identifier>PMID: 29043461</identifier><language>eng</language><publisher>Tokyo: Springer Japan</publisher><subject><![CDATA[Angiogenesis ; Angiogenesis Inhibitors - administration & dosage ; Angiogenesis Inhibitors - pharmacology ; Animals ; Antibodies, Monoclonal - administration & dosage ; Antibodies, Monoclonal - pharmacology ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Bisphosphonates ; Blood Vessels - drug effects ; Bone Density Conservation Agents - therapeutic use ; Chemotherapy ; Combination therapy ; Computed tomography ; Cyclophosphamide ; Diphosphonates - administration & dosage ; Diphosphonates - pharmacology ; Drug Therapy, Combination ; Etiology ; Histomorphometry ; Imidazoles - administration & dosage ; Imidazoles - pharmacology ; Immunohistochemistry ; Jaw ; Male ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Mice, Inbred C57BL ; Molars ; Monoclonal antibodies ; Original Article ; Orthopedics ; Osteoclasts ; Osteonecrosis ; Risk factors ; Teeth ; Tooth Extraction ; Tooth Socket - drug effects ; Tooth Socket - pathology ; Vascular Endothelial Growth Factor A - antagonists & inhibitors ; Vascular Endothelial Growth Factor A - pharmacology ; Wound healing ; Wound Healing - drug effects ; X-Ray Microtomography ; Zoledronic Acid]]></subject><ispartof>Journal of bone and mineral metabolism, 2018-09, Vol.36 (5), p.547-559</ispartof><rights>The Japanese Society for Bone and Mineral Research and Springer Japan KK 2017</rights><rights>Journal of Bone and Mineral Metabolism is a copyright of Springer, (2017). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c517t-d46c204c10731b0b2975de3680d7ca74d8e4138e059c06eb0f7f9a7a713594863</citedby><cites>FETCH-LOGICAL-c517t-d46c204c10731b0b2975de3680d7ca74d8e4138e059c06eb0f7f9a7a713594863</cites><orcidid>0000-0001-9891-9987</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00774-017-0872-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00774-017-0872-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,781,785,27929,27930,41493,42562,51324</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29043461$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Akita, Yuri</creatorcontrib><creatorcontrib>Kuroshima, Shinichiro</creatorcontrib><creatorcontrib>Nakajima, Kazunori</creatorcontrib><creatorcontrib>Hayano, Hiroki</creatorcontrib><creatorcontrib>Kanai, Riho</creatorcontrib><creatorcontrib>Sasaki, Muneteru</creatorcontrib><creatorcontrib>Sawase, Takashi</creatorcontrib><title>Effect of anti-angiogenesis induced by chemotherapeutic monotherapy, chemotherapeutic/bisphosphonate combination therapy and anti-VEGFA mAb therapy on tooth extraction socket healing in mice</title><title>Journal of bone and mineral metabolism</title><addtitle>J Bone Miner Metab</addtitle><addtitle>J Bone Miner Metab</addtitle><description>Osteonecrosis of the jaw (ONJ), which is a rare but severe adverse effect, mainly occurs in oncology patients receiving chemotherapeutic agents and bisphosphonates. However, the combined impact of chemotherapy and bisphosphonates on wound healing after tooth extraction remains unknown. The aim of this study was to determine the precise etiology of ONJ induced by chemotherapy and bisphosphonate combination therapy. Mice received zoledronate (ZA) monotherapy, cyclophosphamide (CY) monotherapy or CY/ZA combination therapy. The maxillary first molars were extracted 3 weeks after the initiation of drug treatment. Moreover, antivascular endothelial growth factor A (VEGFA) monoclonal antibody (mAb) was administered once every 2 days just after tooth extraction for 2 weeks. Soft and hard tissue wound healing was evaluated 2 and 4 weeks post-extraction using histomorphometry, microcomputed tomography and immunohistochemistry. ZA monotherapy did not induce impaired oral wound healing and ONJ-like lesions 2 and 4 weeks post-extraction, respectively. Tooth extraction socket healing worsened with severe anti-angiogenesis by CY monotherapy and CY/ZA combination therapy 2 weeks post-extraction. However, CY monotherapy rarely induced ONJ-like lesions with severe angiogenesis suppression, whereas CY/ZA combination therapy frequently induced ONJ-like lesions with severe angiogenesis inhibition 4 weeks post-extraction. Interestingly, anti-VEGFA mAb therapy delayed osseous wound healing with normal soft tissue wound healing of tooth extraction sockets, although this therapy significantly suppressed blood vessel formation. Our findings suggest that anti-angiogenesis alone is not the main cause of ONJ-like lesions induced by CY/ZA combination therapy. The combination of suppressed osteoclasts and anti-angiogenesis, in addition to other risk factors such as chemotherapy, may contribute to the development of ONJ.</description><subject>Angiogenesis</subject><subject>Angiogenesis Inhibitors - administration & dosage</subject><subject>Angiogenesis Inhibitors - pharmacology</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - administration & dosage</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Bisphosphonates</subject><subject>Blood Vessels - drug effects</subject><subject>Bone Density Conservation Agents - therapeutic use</subject><subject>Chemotherapy</subject><subject>Combination therapy</subject><subject>Computed tomography</subject><subject>Cyclophosphamide</subject><subject>Diphosphonates - administration & dosage</subject><subject>Diphosphonates - pharmacology</subject><subject>Drug Therapy, Combination</subject><subject>Etiology</subject><subject>Histomorphometry</subject><subject>Imidazoles - administration & dosage</subject><subject>Imidazoles - pharmacology</subject><subject>Immunohistochemistry</subject><subject>Jaw</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Mice, Inbred C57BL</subject><subject>Molars</subject><subject>Monoclonal antibodies</subject><subject>Original Article</subject><subject>Orthopedics</subject><subject>Osteoclasts</subject><subject>Osteonecrosis</subject><subject>Risk factors</subject><subject>Teeth</subject><subject>Tooth Extraction</subject><subject>Tooth Socket - drug effects</subject><subject>Tooth Socket - pathology</subject><subject>Vascular Endothelial Growth Factor A - antagonists & inhibitors</subject><subject>Vascular Endothelial Growth Factor A - pharmacology</subject><subject>Wound healing</subject><subject>Wound Healing - drug effects</subject><subject>X-Ray Microtomography</subject><subject>Zoledronic Acid</subject><issn>0914-8779</issn><issn>1435-5604</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kcFu1DAQhi0EokvhAbggS1w4EDpOnDg-rqptQarEhfZqOc5k12VjL7YjsS_Hs-GQpUhFPdgea77_n5F-Qt4y-MQAxEXMl-AFMFFAK8qCPSMrxqu6qBvgz8kKJONFK4Q8I69ivIcM1oK9JGelBF7xhq3Ir80woEnUD1S7ZAvtttZv0WG0kVrXTwZ72h2p2eHo0w6DPuCUrKGjd6f_8eN_3YvOxsPOz8fphNT4sbO5st7RkyiP65eRd5vrqzUd191Da6Z89qP4MwVt_siiN98x0R3qvXXbvBodrcHX5MWg9xHfnN5zcnu1-Xb5ubj5ev3lcn1TmJqJVPS8MSVww0BUrIOulKLusWpa6IXRgvctcla1CLU00GAHgxikFlqwqpa8bapz8mHxPQT_Y8KY1Gijwf1eO_RTVEzWZV0Bkyyj7x-h934KLm-nSpAcZMtlmSm2UCb4GAMO6hDsqMNRMVBzuGoJV-XM1Byump3fnZynbsT-QfE3zQyUCxBzy20x_Bv9tOtvhmey-w</recordid><startdate>20180901</startdate><enddate>20180901</enddate><creator>Akita, Yuri</creator><creator>Kuroshima, Shinichiro</creator><creator>Nakajima, Kazunori</creator><creator>Hayano, Hiroki</creator><creator>Kanai, Riho</creator><creator>Sasaki, Muneteru</creator><creator>Sawase, Takashi</creator><general>Springer Japan</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9891-9987</orcidid></search><sort><creationdate>20180901</creationdate><title>Effect of anti-angiogenesis induced by chemotherapeutic monotherapy, chemotherapeutic/bisphosphonate combination therapy and anti-VEGFA mAb therapy on tooth extraction socket healing in mice</title><author>Akita, Yuri ; Kuroshima, Shinichiro ; Nakajima, Kazunori ; Hayano, Hiroki ; Kanai, Riho ; Sasaki, Muneteru ; Sawase, Takashi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c517t-d46c204c10731b0b2975de3680d7ca74d8e4138e059c06eb0f7f9a7a713594863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Angiogenesis</topic><topic>Angiogenesis Inhibitors - administration & dosage</topic><topic>Angiogenesis Inhibitors - pharmacology</topic><topic>Animals</topic><topic>Antibodies, Monoclonal - administration & dosage</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Bisphosphonates</topic><topic>Blood Vessels - drug effects</topic><topic>Bone Density Conservation Agents - therapeutic use</topic><topic>Chemotherapy</topic><topic>Combination therapy</topic><topic>Computed tomography</topic><topic>Cyclophosphamide</topic><topic>Diphosphonates - administration & dosage</topic><topic>Diphosphonates - pharmacology</topic><topic>Drug Therapy, Combination</topic><topic>Etiology</topic><topic>Histomorphometry</topic><topic>Imidazoles - administration & dosage</topic><topic>Imidazoles - pharmacology</topic><topic>Immunohistochemistry</topic><topic>Jaw</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Mice, Inbred C57BL</topic><topic>Molars</topic><topic>Monoclonal antibodies</topic><topic>Original Article</topic><topic>Orthopedics</topic><topic>Osteoclasts</topic><topic>Osteonecrosis</topic><topic>Risk factors</topic><topic>Teeth</topic><topic>Tooth Extraction</topic><topic>Tooth Socket - drug effects</topic><topic>Tooth Socket - pathology</topic><topic>Vascular Endothelial Growth Factor A - antagonists & inhibitors</topic><topic>Vascular Endothelial Growth Factor A - pharmacology</topic><topic>Wound healing</topic><topic>Wound Healing - drug effects</topic><topic>X-Ray Microtomography</topic><topic>Zoledronic Acid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Akita, Yuri</creatorcontrib><creatorcontrib>Kuroshima, Shinichiro</creatorcontrib><creatorcontrib>Nakajima, Kazunori</creatorcontrib><creatorcontrib>Hayano, Hiroki</creatorcontrib><creatorcontrib>Kanai, Riho</creatorcontrib><creatorcontrib>Sasaki, Muneteru</creatorcontrib><creatorcontrib>Sawase, Takashi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of bone and mineral metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Akita, Yuri</au><au>Kuroshima, Shinichiro</au><au>Nakajima, Kazunori</au><au>Hayano, Hiroki</au><au>Kanai, Riho</au><au>Sasaki, Muneteru</au><au>Sawase, Takashi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of anti-angiogenesis induced by chemotherapeutic monotherapy, chemotherapeutic/bisphosphonate combination therapy and anti-VEGFA mAb therapy on tooth extraction socket healing in mice</atitle><jtitle>Journal of bone and mineral metabolism</jtitle><stitle>J Bone Miner Metab</stitle><addtitle>J Bone Miner Metab</addtitle><date>2018-09-01</date><risdate>2018</risdate><volume>36</volume><issue>5</issue><spage>547</spage><epage>559</epage><pages>547-559</pages><issn>0914-8779</issn><eissn>1435-5604</eissn><abstract>Osteonecrosis of the jaw (ONJ), which is a rare but severe adverse effect, mainly occurs in oncology patients receiving chemotherapeutic agents and bisphosphonates. However, the combined impact of chemotherapy and bisphosphonates on wound healing after tooth extraction remains unknown. The aim of this study was to determine the precise etiology of ONJ induced by chemotherapy and bisphosphonate combination therapy. Mice received zoledronate (ZA) monotherapy, cyclophosphamide (CY) monotherapy or CY/ZA combination therapy. The maxillary first molars were extracted 3 weeks after the initiation of drug treatment. Moreover, antivascular endothelial growth factor A (VEGFA) monoclonal antibody (mAb) was administered once every 2 days just after tooth extraction for 2 weeks. Soft and hard tissue wound healing was evaluated 2 and 4 weeks post-extraction using histomorphometry, microcomputed tomography and immunohistochemistry. ZA monotherapy did not induce impaired oral wound healing and ONJ-like lesions 2 and 4 weeks post-extraction, respectively. Tooth extraction socket healing worsened with severe anti-angiogenesis by CY monotherapy and CY/ZA combination therapy 2 weeks post-extraction. However, CY monotherapy rarely induced ONJ-like lesions with severe angiogenesis suppression, whereas CY/ZA combination therapy frequently induced ONJ-like lesions with severe angiogenesis inhibition 4 weeks post-extraction. Interestingly, anti-VEGFA mAb therapy delayed osseous wound healing with normal soft tissue wound healing of tooth extraction sockets, although this therapy significantly suppressed blood vessel formation. Our findings suggest that anti-angiogenesis alone is not the main cause of ONJ-like lesions induced by CY/ZA combination therapy. The combination of suppressed osteoclasts and anti-angiogenesis, in addition to other risk factors such as chemotherapy, may contribute to the development of ONJ.</abstract><cop>Tokyo</cop><pub>Springer Japan</pub><pmid>29043461</pmid><doi>10.1007/s00774-017-0872-1</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-9891-9987</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0914-8779 |
| ispartof | Journal of bone and mineral metabolism, 2018-09, Vol.36 (5), p.547-559 |
| issn | 0914-8779 1435-5604 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1952530191 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Angiogenesis Angiogenesis Inhibitors - administration & dosage Angiogenesis Inhibitors - pharmacology Animals Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal - pharmacology Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Bisphosphonates Blood Vessels - drug effects Bone Density Conservation Agents - therapeutic use Chemotherapy Combination therapy Computed tomography Cyclophosphamide Diphosphonates - administration & dosage Diphosphonates - pharmacology Drug Therapy, Combination Etiology Histomorphometry Imidazoles - administration & dosage Imidazoles - pharmacology Immunohistochemistry Jaw Male Medicine Medicine & Public Health Metabolic Diseases Mice, Inbred C57BL Molars Monoclonal antibodies Original Article Orthopedics Osteoclasts Osteonecrosis Risk factors Teeth Tooth Extraction Tooth Socket - drug effects Tooth Socket - pathology Vascular Endothelial Growth Factor A - antagonists & inhibitors Vascular Endothelial Growth Factor A - pharmacology Wound healing Wound Healing - drug effects X-Ray Microtomography Zoledronic Acid |
| title | Effect of anti-angiogenesis induced by chemotherapeutic monotherapy, chemotherapeutic/bisphosphonate combination therapy and anti-VEGFA mAb therapy on tooth extraction socket healing in mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-11T08%3A22%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Effect%20of%20anti-angiogenesis%20induced%20by%20chemotherapeutic%20monotherapy,%20chemotherapeutic/bisphosphonate%20combination%20therapy%20and%20anti-VEGFA%20mAb%20therapy%20on%20tooth%20extraction%20socket%20healing%20in%20mice&rft.jtitle=Journal%20of%20bone%20and%20mineral%20metabolism&rft.au=Akita,%20Yuri&rft.date=2018-09-01&rft.volume=36&rft.issue=5&rft.spage=547&rft.epage=559&rft.pages=547-559&rft.issn=0914-8779&rft.eissn=1435-5604&rft_id=info:doi/10.1007/s00774-017-0872-1&rft_dat=%3Cproquest_cross%3E2094098492%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2094098492&rft_id=info:pmid/29043461&rfr_iscdi=true |