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
Hauptverfasser: Zhang, Chenggui, Zhu, Junxiong, Jia, Jialin, Guan, Zhiyuan, Sun, Tiantong, Zhang, Wang, Yuan, Wanqiong, Wang, Hong, Song, Chunli
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container_end_page 933
container_issue 6
container_start_page 925
container_title Journal of bone and mineral metabolism
container_volume 39
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
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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 &amp; 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 &amp; 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 ; 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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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