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

Abstract

This study tests the hypothesis that an ultrasound generated dynamic mechanical signal can attenuate bone loss in an estrogen deficient model of osteopenia. Eighty-four, sixteen week old Sprague-Dawley rats were divided into six groups: baseline control, age-matched control, ovariectomy (OVX) OVX control, OVX + 5 mW/cm 2 ultrasound (US), OVX + 30 mW/cm 2 US and OVX + 100 mW/cm 2 US. Low intensity pulsed ultrasound (LIPUS) was delivered transdermally at the L4/L5 vertebrae, using gelcoupled plane wave US transducers. The signal, characterized by 200μs pulses of 1.5 MHz sine waves repeating at 1 kHz with spatial-averaged temporal-averaged (SATA) intensities of 5, 30 or 100mW/cm 2 , was applied 20 min/day, 5 days/ week for 4 weeks. OVX treatment reduced bone volume fraction 40% and compromised microstructure at 4 weeks. LIPUS treatment, however, significantly increased BV/TV 33% compared to OVX controls for the 100mW/cm 2 treated group. SMI, and Tb.N showed significant improvements compared with OVX for the 100mW/cm 2 treated group and Tb.Th was significantly improved in the 30 and 100mW/cm 2 treated groups. Improvements in bone's microstructural characteristics with 100mW/cm 2 US treatment translated into improved load bearing characteristics, including a significant, 42% increase in apparent level Elastic Modulus compared to OVX controls. Significant improvement of trabecular mechanical strength is also observed in the treated animals, e.g., principal compressive stress (represent bone's ability to resist loads) was significantly higher compared to OVX controls. Histomorphometric analysis also showed that treatment with 100mW/cm 2 US resulted in a 76% improvement in MS/BS. In addition, measures of bone quantity and quality at the femoral metaphysis suggest that LIPUS is site specific. This study indicates that ultrasound, delivered at specific intensities, has beneficial effects on intact bone and may represent a novel intervention for bone loss.

Gastrodin: An ancient Chinese herbal medicine as a source for anti-osteoporosis agents via reducing reactive oxygen species

“…Thus, we examined the trabecular micro-architecture using micro-CT scanning after the administration of gastrodin. Previous micro-CT analysis has shown that normal trabecular bone micro-architecture dramatically deteriorates after ovariectomy [59], which is consistent with the results obtained in our research. In addition, ovariectomy could induce osteoclast formation by TRAP staining in vivo.…”

Pulsed focused ultrasound treatment of muscle mitigates paralysis-induced bone loss in the adjacent bone: A study in a mouse model

“…The overall lack of trabecular bone alteration led to significant preservation of specific bone surface (BS/BV) in the Low20 group compared with the Obtx sham group. Interestingly, the Low20 average intensity was the lowest among all the treatment groups (see Table 1) and closely approached the average intensity used by Ferreri et al (2011) in the LIPUS treatment of osteopenic rat vertebrae (0.1 mW/cm 2 ). The LIPUS transducer used in that study was flat, with the aperture much larger than rat vertebrae, so that the surrounding muscle was likely affected as well.…”

“…LIPUS intensity of 100 mW/cm 2 was found to be the minimum intensity that mitigated bone loss in osteopenic animals (Ferreri et al 2011).…”

“…Ultrasound has also been used in animal models in an attempt to mitigate bone loss induced by spinal cord injury, ovariectomy and neurectomy, yet the results remain controversial (Carvalho and Cliquet Junior 2004;Cook et al 2001;Ferreri et al 2011;Gollwitzer et al 2013;van der Jagt et al 2013;Warden et al 2001a;Yang et al 2005). In particular, Ferreri et al (2011) applied LIPUS to the L4 and L5 vertebrae in ovariectomized rats for 20 min daily, 5 d a wk, for 4 wk, and observed partial mitigation of trabecular bone loss compared with the control group.…”

“…In particular, Ferreri et al (2011) applied LIPUS to the L4 and L5 vertebrae in ovariectomized rats for 20 min daily, 5 d a wk, for 4 wk, and observed partial mitigation of trabecular bone loss compared with the control group. The hypothesized mechanisms for this effect include ultrasoundinduced microstreaming caused by local pressure gradients within the bone microstructure, or the generation of an electric field caused by mechanical movement of ionic fluids within the bone.…”