Dynamic acoustic radiation force retains bone structural and mechanical integrity in a functional disuse osteopenia model

• Published in: Bone (New York, N.Y.) Vol. 75; pp. 8 - 17
• Main Authors: Uddin, Sardar M.Z, Qin, Yi-Xian
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2015
• Subjects: Animals; Bone and Bones; Bone Density - physiology; Bone Diseases, Metabolic - diagnostic imaging; Bone Diseases, Metabolic - etiology; Disease Models, Animal; Disuse osteopenia; Hindlimb Suspension - adverse effects; LIPUS; Low Intensity Pulsed Ultrasound; Mice; Mice, Inbred C57BL; Microgravity; Nonunion fracture; Orthopedics; Osteoporosis; Ultrasonic Therapy - methods; Ultrasonic Waves; Ultrasonography; X-Ray Microtomography; LIPUS; Osteoporosis; Nonunion fracture; Low Intensity Pulsed Ultrasound; Microgravity; Disuse osteopenia
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2015.01.020

Abstract Disuse osteopenia and bone loss have been extensively reported in long duration space mission and long term bed rest. The pathology of the bone loss is similar to osteoporosis but highly confined to weight bearing bones. The current anabolic and/or anti-resorptive drugs have systemic effects and are costly over extended time, with concerns of long term fracture risk. This study use Low Intensity Pulsed Ultrasound (LIPUS) as a non-invasive acoustic force and anabolic stimulus to countermeasure disuse induced bone loss. Four-month old C57BL/6 mice were randomized into five groups, 1) age-matched (AM), 2) non-suspended sham (NS), 3) non-suspended-LIPUS (NU), 4) suspended sham (SS), and 5) suspended-LIPUS (SU) groups. After four weeks of suspension, μCT analyses showed significant decreases in trabecular bone volume fraction (BV/TV) (− 36%, p < 0.005), bone tissue mineral density (TMD) (− 3%, p < 0.05), trabecular thickness (Tb.Th) (− 12.5%, p < 0.005), and increase in bone surface/bone volume (+ BS/BV) (+ 16%, p < 0.005), relative to age-matched (AM). The application of LIPUS for 20 min/day for 5 days/week, significantly increased TMD (+ 3%, p < 0.05), Tb.Th (+ 6%, p < 0.05), and decreased BS/BV (− 10%, p < 0.005), relative to suspension alone (SS) mice. Histomorphometry analyses showed a breakdown of bone microstructure under disuse conditions consist with μCT results. In comparison to SS mice, LIPUS treated bone showed increased structural integrity with increased bone formation rates at metaphysical endosteal and trabecular surfaces (+ 0.104 ± 0.07 vs 0.031 ± 0.30 μm3 /μm2 /day) relative to SS. Four-point bending mechanical tests of disused SS femurs showed reduced elastic modulus (− 53%, p < 0.05), yield (− 33%, p < 0.05) and ultimate strength (− 45%, p < 0.05) at the femoral diaphysis relative to AM bone. LIPUS stimulation mitigated the adverse effects of disuse on bone elastic modulus (+ 42%, p < 0.05), yield strength (+ 29%, p < 0.05), and ultimate strength (+ 39%, p < 0.05) relative to SS femurs. LIPUS provides the essential mechanical stimulus to retain bone morphological and mechanical integrity in disuse conditions. This study demonstrates LIPUS potential as regional therapeutic agent to countermeasure disuse induced bone loss while maintaining bone's integrity.