Transosseous application of low-intensity ultrasound for the enhancement and monitoring of fracture healing process in a sheep osteotomy model

• Published in: Bone (New York, N.Y.) N.Y.), 2006-04, Vol.38 (4), p.530-539
• Main Authors: Malizos, Konstantinos N., Papachristos, Athanasios A., Protopappas, Vasilios C., Fotiadis, Dimitrios I.
• Format: Article
• Language: English
• Subjects: Acceleration of fracture healing; Animal fracture model; Animals; Biological and medical sciences; Biomechanical Phenomena; Bone Density; Fracture Healing; Fundamental and applied biological sciences. Psychology; Injuries of the limb. Injuries of the spine; Low-intensity pulsed ultrasound; Medical sciences; Models, Animal; Monitoring of fracture healing; Orthopedic surgery; Osteotomy; Sheep; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Telemedicine; Traumas. Diseases due to physical agents; Ultrasonics; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Wearable medical devices
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2005.10.012

The purpose of this study is twofold: (a) to investigate the application of transosseous low-intensity pulsed ultrasound (LiUS) on the enhancement of fracture healing and (b) to demonstrate the ability of transosseous ultrasound propagation to monitor the healing process. A midshaft tibial osteotomy model was used on 40 skeletally mature sheep, and an external fixator was applied to maintain the reduction and stabilization of the osteotomy. Two ultrasound transducers were implanted into the fracture site in contact with the bone. For investigating the efficacy of LiUS, the animals were randomly divided in two equal groups: the treatment group and the control group. The LiUS-treated animals received 200-μs bursts of 1-MHz sine waves with a pulse repetition rate of 1 kHz and average intensity of 30 mW/cm 2, for 20 min daily. For monitoring purposes, an ultrasound dataset was constructed consisting of serial ultrasound measurements obtained from healing bones. Animals' sacrifice took place on the 100th post-operative day. The effect of LiUS on fracture healing was evaluated using radiographs, destructive three-point bending testing and quantitative CT-based bone mineral density (BMD) measurements. Survival analysis using Kaplan–Meier curves showed significantly higher probability of radiographic healing for the animals in the treatment group ( P = 0.009). Statistical significance was also observed for callus BMD ( P = 0.003, Wilcoxon nonparametric test), the breaking load ( P = 0.001), extrinsic stiffness ( P = 0.019), Young's modulus ( P = 0.043) and ultimate strength ( P = 0.051) in favor of the LiUS-treated limbs. Analysis of the obtained ultrasonic measurements showed that the propagation velocity across healing bones constitutes a significant feature able to early distinguish between healed and nonhealed bones (area under ROC curve was 0.810 and 0.841 on the 80th and 100th post-operative days, respectively). Both the LiUS application and the ultrasonic measurements are supported by an integrated telemedicine system which also incorporates an ultrasound wearable device and a patient management system.