Long-term pretreatment with alendronate inhibits calvarial defect healing in an osteoporotic rat model
Introduction This study aimed to observe the effects of long-term alendronate pretreatment on the healing of osteoporotic calvarial defects, and further investigate the effect of alendronate combined with once-weekly parathyroid hormone following 12 weeks of alendronate treatment in ovariectomized r...
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Veröffentlicht in: | Journal of bone and mineral metabolism 2021-11, Vol.39 (6), p.925-933 |
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creator | Zhang, Chenggui Zhu, Junxiong Jia, Jialin Guan, Zhiyuan Sun, Tiantong Zhang, Wang Yuan, Wanqiong Wang, Hong Song, Chunli |
description | Introduction
This study aimed to observe the effects of long-term alendronate pretreatment on the healing of osteoporotic calvarial defects, and further investigate the effect of alendronate combined with once-weekly parathyroid hormone following 12 weeks of alendronate treatment in ovariectomized rats.
Materials and methods
Thirty 3-month-old female rats were ovariectomized, and 24 rats received alendronate for 12 weeks. Then, a critical defect was created in the calvaria of all animals. Immediately after osteotomy, the animals received one of five treatments for 8 weeks: (1) continuation of vehicle (group E), (2) alendronate followed by vehicle (group A), (3) continuation of alendronate (group B), (4) alendronate followed by once-weekly parathyroid hormone alone (group C), or (5) continuation of alendronate combined with once-weekly parathyroid hormone (group D). Calvarial defect healing was assessed using dual-energy X-ray absorptiometry, micro-computed tomography, histology, and sequential fluorescence labeling.
Results
Group E showed a significantly higher volume of newly formed bone than groups A, B, C, and D. Evidence of new dense bone formation in group E was observed histologically. In addition, the immunohistochemical expression of runt-related transcription factor 2 was increased in group E but inhibited in groups A, B, C, and D. Sequential immunofluorescence also showed inhibited mineral apposition in groups A, B, C, and D compared with group E.
Conclusion
The present study shows that long-term pretreatment with alendronate inhibited calvarial defect healing in osteoporotic rats, and this effect could not be reversed by stopping alendronate, switching to parathyroid hormone, or combining with once-weekly parathyroid hormone. |
doi_str_mv | 10.1007/s00774-021-01235-0 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2538044690</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2538044690</sourcerecordid><originalsourceid>FETCH-LOGICAL-c376t-a557078833bd32098b55e141d15141019176246f3f487189a173fdd64e580dc3</originalsourceid><addsrcrecordid>eNp9kDFrHDEQhUWIIZdz_kAqgRs3a8-spJW2DMaxAwdu3Avd7uydzK50lnQx_veRfYZAijRvpvje4_EY-45whQD6OlfRsoEWG8BWqAY-sRXK-qgO5Ge2gh5lY7Tuv7CvOT8BoFYaV2zaxLBrCqWFHxKVRK4sFAp_8WXP3UxhTDG4QtyHvd_6kvng5t8ueTfzkSYaCt-Tm33YVYK7wGMuFA8xxeIHnlzhSxxpPmdnk5szffu4a_b48_bx5r7ZPNz9uvmxaQahu9I4pTRoY4TYjqKF3myVIpQ4oqoK2KPuWtlNYpJGo-kdajGNYydJGRgHsWaXp9hDis9HysUuPg80zy5QPGbbKmFAyq6Hil78gz7FYwq1XKX6zmDX1hpr1p6oIcWcE032kPzi0qtFsG_L29Pyti5v35e3b9HiZMoVDjtKf6P_4_oDLAeFng</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2596816283</pqid></control><display><type>article</type><title>Long-term pretreatment with alendronate inhibits calvarial defect healing in an osteoporotic rat model</title><source>SpringerLink Journals - AutoHoldings</source><creator>Zhang, Chenggui ; Zhu, Junxiong ; Jia, Jialin ; Guan, Zhiyuan ; Sun, Tiantong ; Zhang, Wang ; Yuan, Wanqiong ; Wang, Hong ; Song, Chunli</creator><creatorcontrib>Zhang, Chenggui ; Zhu, Junxiong ; Jia, Jialin ; Guan, Zhiyuan ; Sun, Tiantong ; Zhang, Wang ; Yuan, Wanqiong ; Wang, Hong ; Song, Chunli</creatorcontrib><description>Introduction
This study aimed to observe the effects of long-term alendronate pretreatment on the healing of osteoporotic calvarial defects, and further investigate the effect of alendronate combined with once-weekly parathyroid hormone following 12 weeks of alendronate treatment in ovariectomized rats.
Materials and methods
Thirty 3-month-old female rats were ovariectomized, and 24 rats received alendronate for 12 weeks. Then, a critical defect was created in the calvaria of all animals. Immediately after osteotomy, the animals received one of five treatments for 8 weeks: (1) continuation of vehicle (group E), (2) alendronate followed by vehicle (group A), (3) continuation of alendronate (group B), (4) alendronate followed by once-weekly parathyroid hormone alone (group C), or (5) continuation of alendronate combined with once-weekly parathyroid hormone (group D). Calvarial defect healing was assessed using dual-energy X-ray absorptiometry, micro-computed tomography, histology, and sequential fluorescence labeling.
Results
Group E showed a significantly higher volume of newly formed bone than groups A, B, C, and D. Evidence of new dense bone formation in group E was observed histologically. In addition, the immunohistochemical expression of runt-related transcription factor 2 was increased in group E but inhibited in groups A, B, C, and D. Sequential immunofluorescence also showed inhibited mineral apposition in groups A, B, C, and D compared with group E.
Conclusion
The present study shows that long-term pretreatment with alendronate inhibited calvarial defect healing in osteoporotic rats, and this effect could not be reversed by stopping alendronate, switching to parathyroid hormone, or combining with once-weekly parathyroid hormone.</description><identifier>ISSN: 0914-8779</identifier><identifier>EISSN: 1435-5604</identifier><identifier>DOI: 10.1007/s00774-021-01235-0</identifier><language>eng</language><publisher>Singapore: Springer Singapore</publisher><subject>Alendronic acid ; Apposition ; Bisphosphonates ; Bone density ; Bone growth ; Calvaria ; Computed tomography ; Defects ; Dual energy X-ray absorptiometry ; Fractures ; Histology ; Immunofluorescence ; Laboratory animals ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Metabolism ; Oophorectomy ; Original Article ; Orthopedics ; Osteogenesis ; Osteoporosis ; Osteotomy ; Ovariectomy ; Parathyroid ; Parathyroid hormone ; Rodents ; Surgery</subject><ispartof>Journal of bone and mineral metabolism, 2021-11, Vol.39 (6), p.925-933</ispartof><rights>The Japanese Society Bone and Mineral Research 2021</rights><rights>The Japanese Society Bone and Mineral Research 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c376t-a557078833bd32098b55e141d15141019176246f3f487189a173fdd64e580dc3</citedby><cites>FETCH-LOGICAL-c376t-a557078833bd32098b55e141d15141019176246f3f487189a173fdd64e580dc3</cites><orcidid>0000-0002-3690-9457</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/s00774-021-01235-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00774-021-01235-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids></links><search><creatorcontrib>Zhang, Chenggui</creatorcontrib><creatorcontrib>Zhu, Junxiong</creatorcontrib><creatorcontrib>Jia, Jialin</creatorcontrib><creatorcontrib>Guan, Zhiyuan</creatorcontrib><creatorcontrib>Sun, Tiantong</creatorcontrib><creatorcontrib>Zhang, Wang</creatorcontrib><creatorcontrib>Yuan, Wanqiong</creatorcontrib><creatorcontrib>Wang, Hong</creatorcontrib><creatorcontrib>Song, Chunli</creatorcontrib><title>Long-term pretreatment with alendronate inhibits calvarial defect healing in an osteoporotic rat model</title><title>Journal of bone and mineral metabolism</title><addtitle>J Bone Miner Metab</addtitle><description>Introduction
This study aimed to observe the effects of long-term alendronate pretreatment on the healing of osteoporotic calvarial defects, and further investigate the effect of alendronate combined with once-weekly parathyroid hormone following 12 weeks of alendronate treatment in ovariectomized rats.
Materials and methods
Thirty 3-month-old female rats were ovariectomized, and 24 rats received alendronate for 12 weeks. Then, a critical defect was created in the calvaria of all animals. Immediately after osteotomy, the animals received one of five treatments for 8 weeks: (1) continuation of vehicle (group E), (2) alendronate followed by vehicle (group A), (3) continuation of alendronate (group B), (4) alendronate followed by once-weekly parathyroid hormone alone (group C), or (5) continuation of alendronate combined with once-weekly parathyroid hormone (group D). Calvarial defect healing was assessed using dual-energy X-ray absorptiometry, micro-computed tomography, histology, and sequential fluorescence labeling.
Results
Group E showed a significantly higher volume of newly formed bone than groups A, B, C, and D. Evidence of new dense bone formation in group E was observed histologically. In addition, the immunohistochemical expression of runt-related transcription factor 2 was increased in group E but inhibited in groups A, B, C, and D. Sequential immunofluorescence also showed inhibited mineral apposition in groups A, B, C, and D compared with group E.
Conclusion
The present study shows that long-term pretreatment with alendronate inhibited calvarial defect healing in osteoporotic rats, and this effect could not be reversed by stopping alendronate, switching to parathyroid hormone, or combining with once-weekly parathyroid hormone.</description><subject>Alendronic acid</subject><subject>Apposition</subject><subject>Bisphosphonates</subject><subject>Bone density</subject><subject>Bone growth</subject><subject>Calvaria</subject><subject>Computed tomography</subject><subject>Defects</subject><subject>Dual energy X-ray absorptiometry</subject><subject>Fractures</subject><subject>Histology</subject><subject>Immunofluorescence</subject><subject>Laboratory animals</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Metabolism</subject><subject>Oophorectomy</subject><subject>Original Article</subject><subject>Orthopedics</subject><subject>Osteogenesis</subject><subject>Osteoporosis</subject><subject>Osteotomy</subject><subject>Ovariectomy</subject><subject>Parathyroid</subject><subject>Parathyroid hormone</subject><subject>Rodents</subject><subject>Surgery</subject><issn>0914-8779</issn><issn>1435-5604</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kDFrHDEQhUWIIZdz_kAqgRs3a8-spJW2DMaxAwdu3Avd7uydzK50lnQx_veRfYZAijRvpvje4_EY-45whQD6OlfRsoEWG8BWqAY-sRXK-qgO5Ge2gh5lY7Tuv7CvOT8BoFYaV2zaxLBrCqWFHxKVRK4sFAp_8WXP3UxhTDG4QtyHvd_6kvng5t8ueTfzkSYaCt-Tm33YVYK7wGMuFA8xxeIHnlzhSxxpPmdnk5szffu4a_b48_bx5r7ZPNz9uvmxaQahu9I4pTRoY4TYjqKF3myVIpQ4oqoK2KPuWtlNYpJGo-kdajGNYydJGRgHsWaXp9hDis9HysUuPg80zy5QPGbbKmFAyq6Hil78gz7FYwq1XKX6zmDX1hpr1p6oIcWcE032kPzi0qtFsG_L29Pyti5v35e3b9HiZMoVDjtKf6P_4_oDLAeFng</recordid><startdate>20211101</startdate><enddate>20211101</enddate><creator>Zhang, Chenggui</creator><creator>Zhu, Junxiong</creator><creator>Jia, Jialin</creator><creator>Guan, Zhiyuan</creator><creator>Sun, Tiantong</creator><creator>Zhang, Wang</creator><creator>Yuan, Wanqiong</creator><creator>Wang, Hong</creator><creator>Song, Chunli</creator><general>Springer Singapore</general><general>Springer Nature B.V</general><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/0000-0002-3690-9457</orcidid></search><sort><creationdate>20211101</creationdate><title>Long-term pretreatment with alendronate inhibits calvarial defect healing in an osteoporotic rat model</title><author>Zhang, Chenggui ; Zhu, Junxiong ; Jia, Jialin ; Guan, Zhiyuan ; Sun, Tiantong ; Zhang, Wang ; Yuan, Wanqiong ; Wang, Hong ; Song, Chunli</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c376t-a557078833bd32098b55e141d15141019176246f3f487189a173fdd64e580dc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Alendronic acid</topic><topic>Apposition</topic><topic>Bisphosphonates</topic><topic>Bone density</topic><topic>Bone growth</topic><topic>Calvaria</topic><topic>Computed tomography</topic><topic>Defects</topic><topic>Dual energy X-ray absorptiometry</topic><topic>Fractures</topic><topic>Histology</topic><topic>Immunofluorescence</topic><topic>Laboratory animals</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Metabolism</topic><topic>Oophorectomy</topic><topic>Original Article</topic><topic>Orthopedics</topic><topic>Osteogenesis</topic><topic>Osteoporosis</topic><topic>Osteotomy</topic><topic>Ovariectomy</topic><topic>Parathyroid</topic><topic>Parathyroid hormone</topic><topic>Rodents</topic><topic>Surgery</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Chenggui</creatorcontrib><creatorcontrib>Zhu, Junxiong</creatorcontrib><creatorcontrib>Jia, Jialin</creatorcontrib><creatorcontrib>Guan, Zhiyuan</creatorcontrib><creatorcontrib>Sun, Tiantong</creatorcontrib><creatorcontrib>Zhang, Wang</creatorcontrib><creatorcontrib>Yuan, Wanqiong</creatorcontrib><creatorcontrib>Wang, Hong</creatorcontrib><creatorcontrib>Song, Chunli</creatorcontrib><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>Zhang, Chenggui</au><au>Zhu, Junxiong</au><au>Jia, Jialin</au><au>Guan, Zhiyuan</au><au>Sun, Tiantong</au><au>Zhang, Wang</au><au>Yuan, Wanqiong</au><au>Wang, Hong</au><au>Song, Chunli</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long-term pretreatment with alendronate inhibits calvarial defect healing in an osteoporotic rat model</atitle><jtitle>Journal of bone and mineral metabolism</jtitle><stitle>J Bone Miner Metab</stitle><date>2021-11-01</date><risdate>2021</risdate><volume>39</volume><issue>6</issue><spage>925</spage><epage>933</epage><pages>925-933</pages><issn>0914-8779</issn><eissn>1435-5604</eissn><abstract>Introduction
This study aimed to observe the effects of long-term alendronate pretreatment on the healing of osteoporotic calvarial defects, and further investigate the effect of alendronate combined with once-weekly parathyroid hormone following 12 weeks of alendronate treatment in ovariectomized rats.
Materials and methods
Thirty 3-month-old female rats were ovariectomized, and 24 rats received alendronate for 12 weeks. Then, a critical defect was created in the calvaria of all animals. Immediately after osteotomy, the animals received one of five treatments for 8 weeks: (1) continuation of vehicle (group E), (2) alendronate followed by vehicle (group A), (3) continuation of alendronate (group B), (4) alendronate followed by once-weekly parathyroid hormone alone (group C), or (5) continuation of alendronate combined with once-weekly parathyroid hormone (group D). Calvarial defect healing was assessed using dual-energy X-ray absorptiometry, micro-computed tomography, histology, and sequential fluorescence labeling.
Results
Group E showed a significantly higher volume of newly formed bone than groups A, B, C, and D. Evidence of new dense bone formation in group E was observed histologically. In addition, the immunohistochemical expression of runt-related transcription factor 2 was increased in group E but inhibited in groups A, B, C, and D. Sequential immunofluorescence also showed inhibited mineral apposition in groups A, B, C, and D compared with group E.
Conclusion
The present study shows that long-term pretreatment with alendronate inhibited calvarial defect healing in osteoporotic rats, and this effect could not be reversed by stopping alendronate, switching to parathyroid hormone, or combining with once-weekly parathyroid hormone.</abstract><cop>Singapore</cop><pub>Springer Singapore</pub><doi>10.1007/s00774-021-01235-0</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-3690-9457</orcidid></addata></record> |
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subjects | Alendronic acid Apposition Bisphosphonates Bone density Bone growth Calvaria Computed tomography Defects Dual energy X-ray absorptiometry Fractures Histology Immunofluorescence Laboratory animals Medicine Medicine & Public Health Metabolic Diseases Metabolism Oophorectomy Original Article Orthopedics Osteogenesis Osteoporosis Osteotomy Ovariectomy Parathyroid Parathyroid hormone Rodents Surgery |
title | Long-term pretreatment with alendronate inhibits calvarial defect healing in an osteoporotic rat model |
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