Low‐intensity ultrasound stimulation prevents osteoporotic bone loss in young adult ovariectomized mice

Abstract

Osteoporosis is a disease characterized by low bone mass, increased bone fragility, and a greater risk for bone fracture. Currently, pharmacological intervention can generally aid in the prevention and treatment of osteoporosis, but these therapies are often accompanied by undesirable side effects. Therefore, alternative therapies that minimize side effects are necessary. Biophysical stimuli, especially low-intensity ultrasound stimulation (LIUS), may be potential alternatives to drug-based therapies for osteoporosis. Hence, we sought to address whether LIUS therapy can effectively prevent or treat osteoporotic bone loss induced by estrogen deficiency. LIUS (1.5 MHz frequency, 1.0 kHz pulse repetition on frequency, 30 mW/cm 2 intensity, 200 s pulse length) was applied to right tibiae of eight 14-week-old ovariectomized virgin ICR female mice for 20 min per day, 5 days per week, over a 6-week period. Changes in 3D structural bone characteristics were detected using in vivo micro-computed tomography. Left tibiae served as controls. Structural characteristics including bone volume/tissue volume, trabecular number, trabecular bone pattern factor, and mean polar moment inertia were significantly enhanced 6 weeks after LIUS compared to the control, nonstimulated group (p < 0.05). In particular, the bone volume/tissue volume in the region exposed directly to LIUS was significantly higher in the treated group (p < 0.05). These findings indicate that new bone formation may be activated or that bone structure may be maintained by LIUS, and that LIUS may be effective for preventing estrogen deficiency-induced bone loss.

Effects of ultrasound on estradiol level, bone mineral density, bone biomechanics and matrix metalloproteinase-13 expression in ovariectomized rabbits

“…A number of studies have reported an increase in BMD and mechanical strength and stiffness within the initial 7-38 days of US treatment of rabbit tibia (18,42-44). Furthermore, low-intensity ultrasound stimulation in OVX mice is able to activate new bone formation and maintain bone structure, preventing estrogen deficiency-induced bone loss (45). The data presented in the present study suggest that 2 weeks of US and ERT treatment increased the BMD and maximum bone load in OVX rabbits, which is consistent with the results of previous studies.…”

Mitigation of bone loss with ultrasound induced dynamic mechanical signals in an OVX induced rat model of osteopenia

“…While our study did not find significant improvements in BV/TV with 30mW/cm 2 US intervention, we observed a significant improvement with 100mW/cm 2 . Our study also supports the findings of Lim et al, who showed that low-intensity US stimulation was capable of preventing bone loss in your adult OVC mice [38]. …”

“…Histological analysis using mason tricrome staining showed qualitative improvements in ultrasound treated animals not observed in control groups [29]. In a more recent study, LIPUS (1.5 MHz, 1.0 kHz pulse repetition, 30 mW/cm 2 , with intensity of 200μs pulse length) was applied to 14-week-old OVX mice for 6-week; and indicated that bone volume of treated limb was significantly enhanced compared to the contralateral control [38]. In light of the differences among US stimulation protocols used in these studies, it is remained unclear what role ultrasound signal parameters, in particular signal intensity, play in bone’s response.…”

Changes in NO, iNOS and eNOS Expression in MLO-Y4 Cells After Low-intensity Pulsed Ultrasound Treatment With or Without Shear Stress Exposure

“…Low intensity pulsed US have been used for diagnostic purposes for a long time and been shown to have a positive effect on bone regeneration and fracture healing. 5,12,37 Bone remodeling is a dynamic and continuous process. It has already been shown in different studies that NO modulates fracture healing.…”