The Animal Research Of High-frequency And Low-magnitude Mechanical Vibration With Intermittent Intervals In Treating Osteoporosis And Short Clinical Trials

Osteoporosis is a systematic skeletal disorder, which is characterized by obvious bone loss and deterioration of bone microstructure leading to decreased strength, increased fragile and fracture risk. Until now, present regimes only can release symptoms without any resolution substantially. Although diphosphate could decrease the incidence of bone loss or fracture, many patients is unable to accept the medical treatment due to its severe side effects. Some investigations have already shown that low-magnitude is an effectious therapy in preventing bone loss induced by microgravity. However, mechanosensitivity fatigue was proved by recent studies, that bone cells would show a weak response to the mechanical signal if they were loaded for a long period. This mechanism could wane the osteogenesis significantly. Therefore, we designed the animal experiments and clinical trials to solve the problems respectively. The osteoporotic model was established by rat’s tail suspension. The studied animals were subjected to high-frequency and low-magnitude whole body vibration or mechanical stimulus with various intermittent intervals for comparison of the loading regimes in treating OP. Meanwhile, the clinical trials were carried out for the potential in treating osteoporotic postmenopausal women.First section: Animal research of high-frequency and low-magnitude mechanical vibration(HFLMMV) with intermittent intervals in treating osteoporosis. In this part, animal test was performed to discuss the efficacy of HFLMMV in treating osteoporosis, which may provide a theoretical basis for clinical applications. Twenty Wistar rats’ tails were suspended for 4 weeks in order to establish the osteoporosis model caused by mechanical disuse. Three-point bending test and Micro-CT scanning were used to assess the result of this method. After the rat model was built successfully, 70 rats were selected and tail suspended models were established. HFLMMV(35Hz,0.25g) with different intermittent intervals(1-day, 3-day, 5-day, 7-day) and constant vibrational loading(per day) were then started. All rats were killed eight weeks later. Three-point bending test and Micro-CT scanning were conducted to evaluate the mechanical properties(failure load and elastic modulus) and microarchitecture(cortical thickness of femoral neck and microstructural parameters of distal femoral trabecular). Mechanical distributions of femoral shaft cortical bone and distal femoral trabecular were also studied to confirm the vibration mechanisms on bone formation. The results of this study showed that, mechanical properties and microarchitectures of bone degenerated seriously 4 weeks after tail suspension. It demonstrated the osteoporosis model was built successfully. Then, the osteoporosis rats were loaded by HFLMMV for 8 weeks. It is showed that failure load and elastic modulus of cortical bone increased significantly in the groups of HFLMMV with 7 days interval(V7) and constant vibrational loading(VC); significant higher values were also found in cortical thickness of femoral neck and microstructural parameters of distal femoral trabecular(BMD, bone volume fraction, and trabecular thickness) in V7. Mechanical distribution of femoral shaft cortical bone and distal femoral trabecular were compared. Peak values of mechanical properties of cortical bone were presented twice on elastic modulus 14 GPa and 16 GPa respectively, on which points V7 showed significantly higher element proportions than tail suspension group(X). Only one peak value of mechanical properties of trabecular were observed on elastic modulus 10 GPa, on which all the vibrational groups showed significantly higher values than X. The results of this study showed that HFLMM with different intermittent intervals can treat osteoporosis caused by mechanical disuse and promoted bone macro biomechanical properties, microarchitecture and mechanical distribution effectively. Compared with other vibrational groups, V7 was more efficacious in improving bone loss caused by mechanical disuse, which may have a great potential in clinical applications.The second section: Shor-term clinical trials of high-frequency and low-magnitude mechanical vibration with intermittent intervals in treating osteoporotic distal radius. In the animal experiments, the efficacy of high-frequency and low-magnitude mechanical vibration with intermittent intervals, especially 7 days, was confirmed in treatment of osteoporotic rats. A hypothesis was presented that this mechanical vibration may also treat osteoporotic distal radius in human beings. One hundred and forty-nine females, older than 65 years, were recruited in the present clinical trials. They were divided into the following five groups according to the BMD of radius, a) baseline group; b) test group, osteoporotic women did not undergone any treatment; c) daily loading group, osteoporotic women were exposed to mechanical whole body vibration each day; d) intermittent loading group with 1-day intervals, mechanical signal were loaded on osteoporotic women every two days, and e) intermittent loading group with 7-day interval, women accepted mechanical stimulus in continuous 7 days followed by 7-day rest. The mechanical vibration, 30 Hz & 0.3g, last for 15 min each during the 8-week protocol. At the threshold and end of the experiment, the BMD, T score of radius were recorded after radiological scanning, while the blood routine test, renal function, hepatic function, serum ion, blood pressure and electrocardiograph were collected. T-test analysis was carried out to determine the statistical difference. It was shown that daily or various intermittent whole body mechanical loading could increase the BMD and T score of radius in osteoporotic women, while the stimulus with 7-day interval presented a more effectious improvement. The high-frequency and low-magnitude mechanical signal showed no harm to body fitness.