Abstract
Microbubbles magnify the acoustic pressure of low-intensity pulsed ultrasound (LIPUS) and may enhance its bioeffect for diagnostic and therapeutic purposes. This study compared the effect of this novel microbubble-mediated ultrasound (MUS) with that of the traditional LIPUS on osteogenesis and neovascularization in a rabbit model of steroid-associated osteonecrosis. We hypothesized that MUS might outweigh LIPUS on promoting osteogenesis and neovascularization in steroid-associated osteonecrosis. The bilateral femoral head necrosis was induced by lipopolysaccharide and methylprednisolone in the rabbits. The indices of bone mineral density (BMD), trabecular number, maximal loading strength, and mineral apposition rate were analyzed, demonstrating that the animal model of steroid-associated osteonecrosis was successfully established. Both the MUS group (GM) and the LIPUS group (GL) were insonated 20 min daily for six weeks. GM received an extra intracapsular injection of microbubbles before insonation every other day. Fluorescence bone labeling, Micro-CT Analysis, biomechanical test, quantitative real-time PCR, Western blot analysis, and histological evaluation were performed for comparing GM with GL. The results demonstrated a 39% higher mineral apposition rate in GM compared with GL. The BMD and the maximal loading strength of femoral head of GM increased by 4.3% and 27.8% compared to those of GL, respectively. The mRNA and protein expression of BMP-2 and VEGF were also significantly higher in GM. The number of blood vessels of GM was 65% greater than that of GL. MUS is more potent than LIPUS in enhancing osteogenesis, neovascularization, and biomechanical strength of femoral head in the animal model of steroid-associated osteonecrosis. Without increasing the intensity of insonation or the risk of tissue damage, MUS is better for inhibiting the process of steroid-associated osteonecrosis.
Highlights
Steroid usage is the most common nontraumatic cause of osteonecrosis [1]
Our team for the first time reported the effect of Low intensity pulsed ultrasound (LIPUS) on steroid-associated osteonecrosis in a rabbit model of steroidassociated osteonecrosis [7]
This study aimed to explore the enhancive effect of mediated ultrasound (MUS) on bone microstructure, mechanical strength, and vascularization compared with LIPUS
Summary
Steroid usage is the most common nontraumatic cause of osteonecrosis [1]. To our knowledge there is no established preventative method for steroid-associated osteonecrosis. Low intensity pulsed ultrasound (LIPUS) is understood as a noninvasive, feasible, and economic modality for the delayed union and the nonunion of bone fractures. It is approved by the Food and Drug Administration in 1994. The therapeutic application of LIPUS is worldwide nowadays. Our team for the first time reported the effect of LIPUS on steroid-associated osteonecrosis in a rabbit model of steroidassociated osteonecrosis [7]. It provides us a new insight to preventing the progression of steroid-associated osteonecrosis
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