Chenggui Zhang1,2, Junxiong Zhu1,2, Jialin Jia1,2, Zhiyuan Guan1,2, Tiantong Sun1,2, Wang Zhang1,2, Wanqiong Yuan1,2, Hong Wang1,2, Chunli Song3,4. 1. Department of Orthopedics, Peking University Third Hospital, No. 49, Huayuan North Road, Haidian District, Beijing, 100191, China. 2. Beijing Key Laboratory of Spinal Diseases, Beijing, China. 3. Department of Orthopedics, Peking University Third Hospital, No. 49, Huayuan North Road, Haidian District, Beijing, 100191, China. schl@bjmu.edu.cn. 4. Beijing Key Laboratory of Spinal Diseases, Beijing, China. schl@bjmu.edu.cn.
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.
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 osteoporoticrats, and this effect could not be reversed by stopping alendronate, switching to parathyroid hormone, or combining with once-weekly parathyroid hormone.
Authors: Zhaoyang Chen; Bowen Zhang; Jun Shu; Haiyang Wang; Yudi Han; Quan Zeng; Youbai Chen; Jiafei Xi; Ran Tao; Xuetao Pei; Wen Yue; Yan Han Journal: J Biomed Mater Res A Date: 2020-12-09 Impact factor: 4.396