【作者】 邓轩赓；

【导师】 陈建庭； 金大地；

【作者基本信息】 南方医科大学 ， 骨外科， 2008， 博士

【摘要】 1研究背景骨质疏松症是中老年人群的常见病,以骨量减少,骨微结构破坏,骨强度下降,骨脆性增加,骨折风险增大为特点。据估计目前全球骨质疏松症患者总人数超过2亿人,仅我国罹患人口就高达8400万以上。骨质疏松症最主要的风险来自骨质疏松性骨折,其中以髋部骨折危害最大,不仅髋部活动功能损伤明显,而且死亡率高。随着人口老龄化和人均寿命的延长,骨质疏松性骨折发生率全球每年平均以大于1%的速度递增,因此更多有效、简便的非药物的辅助手段以满足不同人群对骨质疏松预防和治疗的需要是目前研究的重点内容之一。降低骨质疏松性骨折发生率是骨质疏松症预防和治疗的核心任务。骨质疏松性骨折发生率取决于骨质量和非暴力跌倒几率。振动作为一种特殊的力学刺激近年来在骨质疏松防治领域内被广泛研究。众多研究已经证实,高频(≥30Hz)、低强度(＜1g,1g=9.8m/s~2)和短时(＜30分钟)的振动可以调节骨代谢,抑制骨吸收和促进骨形成。同时一定的振动刺激还可以增加肌量,预防或改善肌萎缩,增强肌力,改善机体平衡能力。但目前研究大多仍处于实验阶段,而且许多研究所使用的频率及强度并不适合人体长期使用。存在的主要问题是振动强度大多相对较大,人体的不适感较强,一定程度上影响了振动的临床应用。复合振动仪防治骨质疏松相关研究由广东省自然科学基金资助,课题组拥有复合振动和复合振动仪知识产权。复合振动是在全身垂直振动的基础上复合一定平衡干扰振动而成,希翼在保留垂直振动成骨作用的同时,强化肌肉功能和平衡控制能力,通过对骨质量和平衡能力的改善以达到预防和治疗骨质疏松的作用。2目的2.1评估高频低强度复合振动预防卵巢切除大鼠骨质疏松的作用;2.2评估高频低强度复合振动治疗不同年龄卵巢切除骨质疏松大鼠的作用;2.3综合评价复合振动仪对骨质疏松预防和治疗的作用,为后期研究提供一定的基础。3方法3.1骨质疏松预防实验:48只4月龄雌性未育大鼠随机分为正常对照组(NC)、预防对照组(PC)以及4振动干预组(VP1、VP2、VP3、VP4)。NC组为假手术组,其余组均切除双侧卵巢。切口愈合后开始振动干预,两对照组不振动。4个振动组分别接受相应4种不同振动(振动Ⅰ:频率35Hz-45Hz,加速度0.05g-0.1g;振动Ⅱ:频率35Hz-45Hz,加速度0.12g-0.21g;振动Ⅲ:频率45Hz-55Hz,加速度0.05g-0.1g;振动Ⅳ:频率45Hz-55Hz,加速度0.12g-0.21g),干预时间13周。比较骨密度(bonemineral density,BMD)、血清骨转换标志物、骨生物力学性能、骨微结构、强制游泳时间以及腓肠肌相对重量、各型肌纤维比例、肌纤维横截面积、运动终板光密度(optical density,OD)及积分光密度(integrated optical densit5 IOD)等。3.2骨质疏松治疗实验:24只4.5月龄雌性未育大鼠随机分为青年对照组(YC)和两振动组(YT1、YT2);16只13月龄经产大鼠随机分成老年对照组(OC)和老年振动组(OT),所有组大鼠均切除双侧卵巢骨质疏松造模。术后3月骨密度检测证实骨质疏松造模成功后开始振动干预。YT1、YT2两组选用预防实验中效果较好的两组振动,OT组选用预防实验中效果最好的一组振动,干预方法和测试比较内容同前。4结果4.1骨质疏松预防实验大鼠切除卵巢后体重增加显著(P=0.000),腰椎BMD显著下降(P=0.000),骨微结构破坏,腰椎骨强度极限显著下降(P=0.008)。腓肠肌肌重比(肌重/体重)显著下降(P=0.000),Ⅰ型肌纤维比例显著下降(P=0.000)且横截面积显著减小(P=0.001),Ⅱa型(P=0.033)和Ⅱb型(P=0.000)肌纤维比例显著上升以及Ⅱb型纤维横截面积显著减小(P=0.001),游泳时间显著缩短(P=0.047),运动终板OD值(P=0.001)及IOD值(P=0.014)显著下降。经不同复合振动干预后与PC组对比,VP4组体重显著增加(P=0.017),骨结构有一定程度改善;VP3、VP4两组腰椎BMD显著增加(P=0.012,0.002),腰椎垂直压缩强度极限显著增加(P=0.032,0.008);VP2、VP3、VP4组腓肠肌肌重比显著增加(P=0.024,0.014,0.000),VP3、VP4组Ⅰ型肌纤维比例显著改善(P=0.022,0.002);所有振动组Ⅰ型纤维横截面积显著增加(P=0.025,0.002,0.000,0000),VP2、VP3、VP4组Ⅱb型纤维横截面积显著增加(P=0.030,0.004,0.000)且这3组强制游泳时间(P=0.042,0.000,0.007)和运动终板OD值(P=0.037,0.014,0.000)也显著增加。4.2骨质疏松治疗实验青年组振动分别选用振动Ⅲ和振动Ⅳ,老年组选用振动Ⅳ。青年组大鼠腰椎骨质疏松造模成功,老年组大鼠腰椎、股骨造模均成功。振动干预3月后与对照组比较,青年组中两振动组腰椎BMD显著增加(P=0.022,0.001);YT2组股骨BMD增加显著(P=0.007),骨结构一定程度改善,腰椎、股骨强度极限显著增强(P=0.020,0.023)。两振动组均可显著增加Ⅰ型纤维比例(P=0.015,0.000)和Ⅱa型肌纤维横截面积(P=0.030,0.001),运动终板染色OD值(P=0.014,0.003)及IOD值(P=0.003,0.001)均有显著增加;但仅YT2组腓肠肌肌重比显著上升(P=0.021),Ⅱa(P=0.013)和Ⅱb(P=0.048)型肌纤维比例显著下降,显著增大了Ⅰ型纤维横截面积(P=0.003),显著延长了强制游泳时间(P=0.025);OT组体重也有显著增加(P=0.039),腰椎、股骨BMD显著增加(P=0.000,0.004),相应腰椎、股骨强度极限也显著增加(P=0.038,0.014),骨结构略有改善;肌重比显著增加(P=0.036),Ⅰ、Ⅱa型肌纤维比例显著改善(P=0.001,0.012)及横截面积显著增加(P=0.047,0.033),强制游泳时间显著增加(P=0.000),运动终板染色OD值显著增加(P=0.012)。预防试验中腰椎、股骨BMD与腓肠肌肌纤维比例存在紧密相关,腰椎BMD还和Ⅱa型纤维横截面积紧密相关。治疗试验中腰椎BMD以及腰椎、股骨强度极限与腓肠肌肌重比、Ⅱb型纤维横截面积、运动终板OD值存在紧密相关,股骨强度极限还与肌纤维比例存在紧密相关。5结论一定的复合振动可以在更低强度下增加不同阶段卵巢切除大鼠BMD、改善骨微结构、提高骨强度。在改善骨质量的同时还可在一定程度上预防或改善肌萎缩,维持或增强肌力,减轻或改善外周末梢神经神经功能退变,可能有助于改善或增强平衡能力。对骨骼肌的有益刺激也可能有助于骨质量的改善或提高。复合振动仪可提高卵巢切除大鼠骨质量、增强肌力以及可能增强平衡能力,如临床也能证实上述作用,则将具有预防和治疗骨质疏松的较好前景,值得进一步研究。更多还原

【Abstract】 1 BackgroundsOsteoporosis is a common disease in middle- aged and old people,characterized by low bone mass and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture.It was estimated that the people with osteoporosis had been more than 200 millions in the world,and there had been more than 84 millions patients in China.The major consequence of osteoporosis is osteoporotic fracture.Fracture of hip,which had obviously decreased activity and a high mortality,was thought as the most dangerous consequence in osteoporosis. With ageing and prolonging of life,the rate of osteoporotic fracture increased by 1% each year in the world.To deal with the problem,we had to seek more effective and convenient non-pharmacal ways for osteoporosis prevention and treatment.Bone quality and probability of non-trauma fall were the key factors of oseoporotic fracture.So the most effective way to prevention and treatment of osteoporosis was to improve bone quality or/and balance control.Many researches confirmed that high frequency(=30Hz),low level(＜1g) and short time(＜30minutes) mechanical vibration could regulate bone metabolism,inhibit bone absorption and promote bone formation.On the other hand,it also could increase muscle mass,and improve muscle force and be helpful in balance control.But the current researches still stayed in laboratory,because most of the vibration level in current researches was too large to accept by people for long time using.Our research was supported by natural science found of Guangdong province. And we had the intellectual property rights of compound vibration and compound vibration machine.The compound vibration was compound by special balance interruption and vertical whole-body-vibration(WBV).We hoped it could enhance the muscle function and balance control based on the bone formation situation of WBV, and gain the improvement of both bone quality and balance control.2 Objectives1.To evaluate the preventive effects of high frequency and low level compound vibration on ovariectomized SD rats;2.To evaluate the therapeutic effects of compound vibration on different months old SD rats with osteoporosis;3.To evaluate the effects of compound vibration machine for osteoporosis prevention and treatment,and provide evidences for the further research.3 Methods3.1 Osteoporosis prevention experimentSix groups of 4-months old SD female rats,of which 5 groups received ovariectomy (OVX) and one was sham OVX,were arranged randomly(n=8),including normal control group(NC,sham-OVX group),prevented control group(PC),vibration prevented group(VP) 1-4.The VP groups corresponded with four different vibrations respectively as following:vibration 135Hz-45Hz,0.05g-0.1g;vibrationⅡ35Hz-45Hz, 0.12g-0.21g;vibrationⅢ45Hz-55Hz,0.05g-0.1g;vibrationⅣ45Hz-55Hz, 0.12g-0.21g.The intervention lasted 13 weeks with 20minutes/d and 5days/week from wound healing.There were some parameters to be compared bet-ween groups, such as BMD,time of forced swimming,bone microarchitecture,bone biomechanical character,serum bone turnover marker,the ratio and cross section area(CSA) of gast-rocnemius fibra types,area,OD and IOD values of myoceptor,et al.3.2 Osteoporosis treatment experiment24 SD female rats of 4.5-months old were divided into three groups randomly: young control group(YC),young treated group(YT) 1 and 2.And two random groups of 8 SD multiparous rats with 13-months named as old control group(OC) and old treated group(OT).The intervention began when osteoporosis occurred in these rats.The better two vibrations in the former would be used in young groups,and the best one used in old group.The experiment time and the comparisons between groups were as same as prevention experiment.4 Results4.1 Osteoporosis prevention experimentCompared with NC,The rats of PC changed a lot resulted from ovariectomy. Something increased significantly including weight(P=0.000),the ratio of gastroc-nemius fibra typeⅡa(P=0.033) andⅡb(P=0.000).The other things decreased or dete-riorated significantly,including lumbar BMD(P=0.000),bone microarchitecture, lumbar ultimate strength(P=0.008),weight ratio of gastrocnemius and body,proportion(P=0.000) and CSA(P=0.001) of gastrocnemius fibra typeⅠ,swimming time (P=0.047),OD(P=0.001) and IOD(P=0.014) of myoceptor.VP4 showed that body weight increased significantly(P=0.017) and bone micro-architecture improved significantly compared with PC.VP3 and VP4 got a significant gain in lumbar BMD(P=0.012,0.002) and lumbar ultimate strength(P=0.032, 0.008).Weight ratio of gatrocnemius and body increased significantly in VP2,VP3, VP4(P=0.024,0.014,0.000).There were significant improvements of fibra typeⅠproportion in VP3 and VP4(P=0.022,0.002),of fibra typeⅠCSA in all vibration groups (P=0.025,0.002,0.000,0000),and of fibraⅡb CSA in VP2,VP3,VP4(P=0.030,0.004, 0.000).The prolonged swimming times(P=0.042,0.000,0.007) and increased value of OD were found in VP2,VP3 and VP4.4.2 Osteoporosis treatment experimentVibrationⅢandⅣcontinued to be used in YT1 and YT2,and OT received vibra-tionⅣ.Osteoporotic modeling occurred in lumbar of young groups,and in both lumbar and femur of old groups 3 months after OVX.Compared with YC,the two vibration groups obtained increased BMD at lumbar (P=0.022,0.001).But only YT2 increased femur BMD(P=0.007) and improved bone microarchitecture and enhanced bone ultimate strength of lumbar and femur(P=0.020, 0.023) significantly.Two vibration groups were found that fibra typeⅠproportion (P=0.015,0.000),Ⅱa CSA(P=0.030,0.001),OD(P=0.014,0.003) and IOD(P=0.003, 0.001) increased significantly.But only YT2 increased significantly the weight ratio of gastroc-nemius and body(P=0.021),enlarged fibra typeⅠCSA(P=0.003),prolonged the swim-ming time(P=0.025) and decreased significantly proportion of fibra typeⅡa(P=0.013) andⅡb(P=0.048).Some parameters also increased significantly,such as weight(P=0.039),BMD of lumbar and femur(P=0.000,0.004),ultimate strength of lumbar and femur(P=0.038,0.014),weight ratio of gastrocnemius and body(P=0.036), swimming time(P=0.000) and OD value(P=0.012) of myoceptor in OT group.And OT also was found some significant improvements on bone microarchitecture,proportion (P=0.001,0.012) and CSA(P=0.047,0.033) of fibra typeⅠandⅡa. There were some close correlations between the muscle and bone quality.BMD of lumbar and femur correlated with ratio of gastrocnemius fibra significantly,and lumbar BMD also correlated with CSA of libra typeⅡa in the prevention experiment. In the treatment experiment,more tight correlations had be found between bone quailty including lumbar BMD,lumbar and femur ultimate strength,and muscle quality, such as ratio of gastrocnemius weight,CSA of fibra typeⅡb,OD value of myoceptor. The significant correlation between femur ultimate strength and propor-tion of fibra types also was found in the latter experiment.5 ConclusionsSpecial compound vibration with lower level could improve bone quality by enhanced BMD and bone strength,and improved bone microarchitecture of ovariectomized rats at different stages.And it could enhance muscle function by inhibited or improved amyotrophy,maintained or enhanced muscle force and improved some peripheral nerve function,which potentially resulted in an improvement of balance control.If these effects could be confirmed in clinics,the compound vibration machine would be helpful to increase the anti-fracture capability of bone and decrease the possibility of non-trauma falls.Based on that,a prospect in osteoporosis preven- tion and treatment of compound vibration machine would be on the way to reality.So it was worth to research more in future.更多还原