Low-intensity pulsed ultrasound accelerated callus formation, angiogenesis and callus remodeling in osteoporotic fracture healing

Abstract

Osteoporotic fracture is a critical medico-social challenge leading to burdens in health care costs and hospital bed stays. Low-intensity pulsed ultrasound (LIPUS) was reported to accelerate normal fracture; however, its effect on osteoporotic fracture has not been previously addressed. We hypothesize that LIPUS can accelerate osteoporotic fracture healing and up-regulate the expression in the osteogenesis-, remodeling- and angiogenesis-related genes. Ovariectomy-induced osteoporotic fracture rat model was used to investigate the effects of LIPUS. Fractured rats were assigned to LIPUS or control group and healing was assessed by gene expression quantification, radiographic callus morphometry and histomorphometry. In the LIPUS group, Col-1 and bone morphogenetic protein-2 were up-regulated at earlier time points of week 2 to week 4 post-fracture; vascular endothelial growth factor was found to be up-regulated at week 4 to week 8; osteoprotegerin was up-regulated at week 2 post-fracture, followed by the surge of RANKL expression. Callus width and area measurements showed higher callus formation at weeks 2-4 in the LIPUS group and more rapid drop at weeks 6-8. Histomorphometry showed enhanced endochondral ossification in the callus at weeks 2-4, and lower at week 8. We conclude that LIPUS can accelerate osteoporotic fracture healing by enhancing callus formation, angiogenesis and callus remodeling.