title: Short-term muscle atrophy caused by botulinum toxin-A local injection impairs fracture healing in the rat femur.
abstract: Damaged bone is sensitive to mechanical stimulation throughout the remodeling phase of bone healing. Muscle damage and muscular atrophy associated with open fractures and subsequent fixation are not beneficial to maintaining optimum conditions for mechanical stability. The aim of this study was to investigate whether local muscle atrophy and dysfunction affect fracture healing in a rat femur fracture model. We combined the rat model of a short period atrophy of the quadriceps with femur fracture. Forty-four-month-old male Wistar rats were adopted for this study. Two units of botulinum toxin-A (BXTA) were administered locally into the right side of the quadriceps of each rat, while the same dose of saline was injected into the contralateral quadriceps. After BXTA had been fully absorbed by the quadriceps, osteotomy was performed in both femurs with intramedullary fixation. Gross observation and weighing of muscle tissue, X-ray analysis, callus histology, and bone biomechanical testing were performed at different time points up to 8 weeks post-surgery. Local injection of BXTA led to a significant decrease in the volume and weight of the quadriceps compared to the control side. At the eighth week, the left side femurs of the saline-injected quadriceps almost reached bony union, and fibrous calluses were completely calcified into woven bone. However, a gap was still visible in the BXTA-treated side on X-ray images. As showed by bone histology, there were no mature osseous calluses or woven bone on the BXTA-treated side, but a resorption pattern was evident. Biomechanical testing indicated that the femurs of the BXTA-treated side exhibited inferior mechanical properties compared with the control side. The inferior outcome following BXTA injection, compared with saline injection, in terms of callus resistance may be the consequence of unexpected load and mechanical unsteadiness caused by muscle atrophy and dysfunction.
authors.affiliation: Shanghai Key Laboratory of Orthopeadic Implant, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, People's Republic of China. hao_yongqiang@hotmail.com
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Hao
authors.forename: Yongcheng
authors.initials: Y
authors.lastname: Ma
authors.forename: Xuepeng
authors.initials: X
authors.lastname: Wang
authors.forename: Fangchun
authors.initials: F
authors.lastname: Jin
authors.forename: Shengfang
authors.initials: S
authors.lastname: Ge
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects / Q000502:physiology; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005269:Femur / Q000000981:diagnostic imaging / Q000293:injuries / Q000502:physiology; D017102:Fracture Healing / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D009121:Muscle Denervation / Q000379:methods; D009133:Muscular Atrophy / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D009465:Neuromuscular Agents / Q000494:pharmacology; D009929:Organ Size; D010027:Osteotomy; D052097:Quadriceps Muscle / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D011859:Radiography; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical
chemical_list: D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A