Dynamic Effects of the Third Generation Bisphosphonate of Risedronate on Rat Osteoporotic Fractures for Clinical Usage Guidance

Objective To better understand the risks of bisphosphonates in order to develop guidance for appropriate clinical usage, to compared femoral fracture healing at different time points and to explore the effects of Residronate on fracture healing. Methods Osteoporosis model was achieved by ovariectomy...

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Main Authors: Cheng‐hui Ke, Hong‐yun Li, Dan Yang, Hao Ying, Jun Xu, Jian Wang, Hong‐wen Zhu, Lin Wang
Format: Article
Language:English
Published: Wiley 2021-12-01
Series:Orthopaedic Surgery
Subjects:
Online Access:https://doi.org/10.1111/os.13158
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author Cheng‐hui Ke
Hong‐yun Li
Dan Yang
Hao Ying
Jun Xu
Jian Wang
Hong‐wen Zhu
Lin Wang
author_facet Cheng‐hui Ke
Hong‐yun Li
Dan Yang
Hao Ying
Jun Xu
Jian Wang
Hong‐wen Zhu
Lin Wang
author_sort Cheng‐hui Ke
collection DOAJ
description Objective To better understand the risks of bisphosphonates in order to develop guidance for appropriate clinical usage, to compared femoral fracture healing at different time points and to explore the effects of Residronate on fracture healing. Methods Osteoporosis model was achieved by ovariectomy surgery, followed by surgical incision of left femoral shaft 4 weeks after ovariectomy surgery. Three days after fracture surgery, risedronateor saline was fed by intragastric administration. X ray examination was used to check the callus formation, Bone Mineral Density (BMD), Bone Mineral Content (BMC), biomechanical, imaging and micromorphological of bone tissue as well as the trabecular bone parameters were all examined. The femoral pathology tissue of each rat was used to analyze trabecular bone parameters, including trabecular bone volume/tissue volume (Tb. BV/TV), bone surface to tissue volume ratio (BS/TV), trabecular bone mineral density (Tb. BMD), trabecular bone number (Tb. N), trabecular bone thickness (Tb. Th) and small bone Trabecular bone space (Tb. Sp). Results Via X‐ray and pathologically, risedronate treatment promoted the callus forming at the fracture site during the following 6 weeks after osteoporotic fracture by X‐ray (P < 0.01), increased the local bone mineral density (P < 0.01), and accelerated the fracture healing during the first 3 weeks (P <0.01), but delayed facture healing in the later 3 weeks (P < 0.01). Risedronate increased the bone continuity of fracture at 7th week, but this phenomenon was not found at the 10th week (P < 0.01). Delayed fracture healing occurred locally at the fracture site. At 7th week, Risedronate may promote cartilage cells proliferating at fracture site, increase the dense of bone trabeculae and the connection of bone trabeculae, thicken the bone cortex showing better fracture healing than OPF‐Saline groups (P < 0.01). However, these parameter did not continue during the 7th and 10th weeks. Comparing the first and the later 3 weeks, the rats in group Osteoporotic Fracture‐Risedronate (OPF‐RD) accelerated the local fracture healing in the first 3 weeks but not in the last 3 weeks, which is consistent for the BMD and BMC among each group (P < 0.05). Through evaluation of bone mineral density and bone mineral content, risedronate dramatically increased the BMD at the fracture site and resulted in reduction of BMC by risedronate at the fracture site (P < 0.05) among each group still exist, indicating dramatic (P < 0.05). Through load testing, Risedronate increased the structural strength and mechanical indexes of the new callus (P < 0.01). Conclusion Risedronate can improve the structural strength and mechanical index of newborn callus. Longer than 7 weeks usage of third generation bisphosphonate of risedronate does not contribute to osteoporotic fracture.
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spelling doaj.art-f478ecb0233f4892acf8f0fe2fdfcd222022-12-21T21:43:23ZengWileyOrthopaedic Surgery1757-78531757-78612021-12-011382433244110.1111/os.13158Dynamic Effects of the Third Generation Bisphosphonate of Risedronate on Rat Osteoporotic Fractures for Clinical Usage GuidanceCheng‐hui Ke0Hong‐yun Li1Dan Yang2Hao Ying3Jun Xu4Jian Wang5Hong‐wen Zhu6Lin Wang7Department of Orthopaedics Children's Hospital of Shanghai Shanghai ChinaDepartment of Anesthesiology Children's Hospital of Shanghai Shanghai ChinaDepartment of Orthopaedics Children's Hospital of Shanghai Shanghai ChinaDepartment of Orthopaedics Children's Hospital of Shanghai Shanghai ChinaTongji University School of Medicine Shanghai ChinaTongji University School of Medicine Shanghai ChinaTianjin Hospital, Tianjin Academy of Integrative Medicine Tianjin ChinaDepartment of Orthopaedics Children's Hospital of Shanghai Shanghai ChinaObjective To better understand the risks of bisphosphonates in order to develop guidance for appropriate clinical usage, to compared femoral fracture healing at different time points and to explore the effects of Residronate on fracture healing. Methods Osteoporosis model was achieved by ovariectomy surgery, followed by surgical incision of left femoral shaft 4 weeks after ovariectomy surgery. Three days after fracture surgery, risedronateor saline was fed by intragastric administration. X ray examination was used to check the callus formation, Bone Mineral Density (BMD), Bone Mineral Content (BMC), biomechanical, imaging and micromorphological of bone tissue as well as the trabecular bone parameters were all examined. The femoral pathology tissue of each rat was used to analyze trabecular bone parameters, including trabecular bone volume/tissue volume (Tb. BV/TV), bone surface to tissue volume ratio (BS/TV), trabecular bone mineral density (Tb. BMD), trabecular bone number (Tb. N), trabecular bone thickness (Tb. Th) and small bone Trabecular bone space (Tb. Sp). Results Via X‐ray and pathologically, risedronate treatment promoted the callus forming at the fracture site during the following 6 weeks after osteoporotic fracture by X‐ray (P < 0.01), increased the local bone mineral density (P < 0.01), and accelerated the fracture healing during the first 3 weeks (P <0.01), but delayed facture healing in the later 3 weeks (P < 0.01). Risedronate increased the bone continuity of fracture at 7th week, but this phenomenon was not found at the 10th week (P < 0.01). Delayed fracture healing occurred locally at the fracture site. At 7th week, Risedronate may promote cartilage cells proliferating at fracture site, increase the dense of bone trabeculae and the connection of bone trabeculae, thicken the bone cortex showing better fracture healing than OPF‐Saline groups (P < 0.01). However, these parameter did not continue during the 7th and 10th weeks. Comparing the first and the later 3 weeks, the rats in group Osteoporotic Fracture‐Risedronate (OPF‐RD) accelerated the local fracture healing in the first 3 weeks but not in the last 3 weeks, which is consistent for the BMD and BMC among each group (P < 0.05). Through evaluation of bone mineral density and bone mineral content, risedronate dramatically increased the BMD at the fracture site and resulted in reduction of BMC by risedronate at the fracture site (P < 0.05) among each group still exist, indicating dramatic (P < 0.05). Through load testing, Risedronate increased the structural strength and mechanical indexes of the new callus (P < 0.01). Conclusion Risedronate can improve the structural strength and mechanical index of newborn callus. Longer than 7 weeks usage of third generation bisphosphonate of risedronate does not contribute to osteoporotic fracture.https://doi.org/10.1111/os.13158BiomechanicsBone mineral content (BMC)Bone mineral density (BMD)Primary osteoporotic fracture (p‐OPF)Risedronate (RD)
spellingShingle Cheng‐hui Ke
Hong‐yun Li
Dan Yang
Hao Ying
Jun Xu
Jian Wang
Hong‐wen Zhu
Lin Wang
Dynamic Effects of the Third Generation Bisphosphonate of Risedronate on Rat Osteoporotic Fractures for Clinical Usage Guidance
Orthopaedic Surgery
Biomechanics
Bone mineral content (BMC)
Bone mineral density (BMD)
Primary osteoporotic fracture (p‐OPF)
Risedronate (RD)
title Dynamic Effects of the Third Generation Bisphosphonate of Risedronate on Rat Osteoporotic Fractures for Clinical Usage Guidance
title_full Dynamic Effects of the Third Generation Bisphosphonate of Risedronate on Rat Osteoporotic Fractures for Clinical Usage Guidance
title_fullStr Dynamic Effects of the Third Generation Bisphosphonate of Risedronate on Rat Osteoporotic Fractures for Clinical Usage Guidance
title_full_unstemmed Dynamic Effects of the Third Generation Bisphosphonate of Risedronate on Rat Osteoporotic Fractures for Clinical Usage Guidance
title_short Dynamic Effects of the Third Generation Bisphosphonate of Risedronate on Rat Osteoporotic Fractures for Clinical Usage Guidance
title_sort dynamic effects of the third generation bisphosphonate of risedronate on rat osteoporotic fractures for clinical usage guidance
topic Biomechanics
Bone mineral content (BMC)
Bone mineral density (BMD)
Primary osteoporotic fracture (p‐OPF)
Risedronate (RD)
url https://doi.org/10.1111/os.13158
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