低强度复合振动联合阿仑膦酸钠预防卵巢切除大鼠骨质疏松的实验研究
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摘要
研究背景
骨质疏松(Osteoporosis, OP)是以骨量减少,骨组织微观结构退化,致使骨强度下降,骨脆性增加以及骨折风险增大为特征的一种全身性骨骼系统疾病。骨重建是一个骨组织自我更新的过程：破骨细胞不断吸收旧骨,而成骨细胞则不断形成新骨补充骨吸收部分。当机体骨骼发育成熟后,破骨细胞在骨重建过程中发挥重要作用。若破骨细胞活性增强或量增多,可以导致骨吸收增加,骨重建失衡,导致很多骨骼系统疾病的发生,如：OP。目前OP在世界常见病、多发病中居第7位。骨质疏松最常见的并发症是骨折,常见部位是髋部,椎体和桡骨远端。妇女在进入绝经期后骨量丢失明显,如无适当预防和治疗,骨质疏松将不可避免地造成桡骨、脊柱和髋部等处的骨折。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。目前关于骨质疏松症的治疗目的一是解除全身性疼痛,二是预防病理性骨折的发生。临床上关于骨质疏松症的治疗方案包括药物治疗、物理治疗及外科手术治疗等,其中以药物治疗为主要手段。临床上常使用的药物主要有骨吸收抑制剂、骨形成促进剂、解偶联剂、骨矿化剂以及中医药等五大类。目前临床上越来越多的患者服用骨吸收抑制剂二膦酸盐类药物来预防骨质疏松或者作为抗骨质疏松的主要药物。二膦酸盐类药物主要机制是通过抑制破骨细胞活性减少骨吸收,从而增加骨密度和抑制骨转换,可以减低椎体和非椎体骨折的发生率,并且已为临床研究所证实。阿伦膦酸钠是第三代二膦酸盐类药物的代表药物,也是临床上使用最为广泛的抗骨质疏松药物。阿仑膦酸钠(Alendronate ALE)是治疗OP的传统药物之一,以抑制骨吸收为主,改善骨的质量,同时也可以减轻腰背部疼痛和改善骨质疏松老年的生活质量。但是该药物治疗存在一定副作用,特别是胃肠道反应,限制一部分骨质疏松患者使用该药物。随着社会经济的发展和医疗模式的转变,在关注药物治疗的同时,越来越多的关注已转向了非药物的手段和措施。
近年来物理疗法(力学、电磁学)防治OP的研究成为热点。Wolff定律认为,骨的结构特点是适应功能需要而塑造的,并随着功能需要的改变而进行重建；骨的功能是承受活动期间骨组织的机械应变,并随着功能需要所产生的应力的变化而进行功能适应性重建。振动是一种力学刺激,它需要一定的强度和频率才能将有效刺激能量传递至成骨效应细胞,从而诱发成骨反应,过低的强度和频率难以到达有效部位或不能成为诱发成骨的阈上刺激,而过高的振动强度对人体是有危害的。众多研究已经证实,高频(≥30Hz)、低强度(<1g,1g=9.8m/s)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。所以说,低于引起骨组织损伤的机械振动信号具有很强的成骨效应,是一种新型、无创、副作用小治疗OP的模式,在防治老年性骨质疏松中有广阔的应用前景。但是目前关于低强度的全身复合振动联合阿仑膦酸钠预防骨质疏松症的研究仍未有报道。
实验目的：
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.评估阿仑膦酸钠预防卵巢切除大鼠骨质疏松的作用；
3.比较传统药物阿仑膦酸钠与新型的低强度全身复合振动在预防骨质疏松的效果；
4.观察低强度的全身复合振动联合阿仑膦酸钠预防骨质疏松的效果；
5.观察低强度全身复合振动是否增强阿仑膦酸钠预防骨质疏松的效果。
实验方法：
1.讨论高频率低强度复合振动对去势大鼠骨质疏松的预防作用
1.1实验材料与方法：
80只8周龄SD雌性未育大鼠随机分为对照组(sham)、治疗1组(OVX+VEH)、治疗2组(OVX+WBV),对照组32只大鼠,其余2个治疗组每组24只。对照组未切除卵巢,而治疗1组、治疗2组中大鼠切除双侧卵巢,制备骨质疏松大鼠模型；待卵巢切除切口愈合后开始干预,其中治疗1组是单纯卵巢切除后给予生理盐水(1mg/Kg,每周灌胃一次)；治疗2组是切除卵巢后给予全身复合振动(振动强度为0.3g,频率为45-55Hz,每次振动20min,每天1次,每周5次,休息间隔不大于2d,共12周)。
1.2检测指标：
在实验过程中每四周检测实验大鼠的体重。在实验4周、8周和12周分别处死8只大鼠,收集其血标本、子宫和双侧胫骨,并用酶法检测血标本中的骨钙素(osteocalcin OC)和工型胶原C末端肽(C-terminal cross-linked telopeptides of type I collagen, CTX),左侧胫骨标本接受micro-CT检查分析和右侧胫骨标本接受三点弯曲生物力学检测。
2.讨论阿仑膦酸钠对去势大鼠骨质疏松的预防作用
2.1实验材料与方法：
80只8周龄SD雌性未育大鼠随机分为对照组(sham)、治疗1组(OVX+VEH)、治疗2组(OVX+ALE),对照组32只大鼠,其余2个治疗组每组24只。对照组未切除卵巢,而治疗1组、治疗2组中大鼠切除双侧卵巢,制备骨质疏松大鼠模型；待卵巢切除切口愈合后开始干预,其中治疗1组是单纯卵巢切除后给予生理盐水(1mg/Kg,每周灌胃一次)；治疗2组是切除卵巢后给予阿仑膦酸钠(1mg/Kg,每周灌胃一次)。
2.2检测指标：
在实验过程中每四周检测实验大鼠的体重。在实验4周、8周和12周分别处死8只大鼠,收集其血标本、子宫和双侧胫骨,并用酶法检测血标本中的骨钙素(osteocalcin OC)和Ⅰ型胶原C末端肽(C-terminal cross-linked telopeptides of type I collagen, CTX),左侧胫骨标本接受micro-CT检查分析和右侧胫骨标本接受三点弯曲生物力学检测。
3.探讨低强度高频率复合振动联合阿仑膦酸钠对去势大鼠骨质疏松的预防效果
3.1实验材料与方法：
128只8周龄SD雌性未育大鼠随机分为对照组(sham)、治疗1组(OVX+VEH)、治疗2组(OVX+WBV)、治疗3组(OVX+ALE)和治疗4组(VOX+WBV+ALE),对照组32只大鼠,其余四个治疗组每组24只。对照组未切除卵巢,而治疗1组、治疗2组、治疗3组和治疗4组中大鼠切除双侧卵巢,制备骨质疏松大鼠模型；待卵巢切除切口愈合后开始干预,其中治疗1组是单纯卵巢切除后给予生理盐水(1mg/Kg,每周灌胃一次)；治疗2组是切除卵巢后给予全身复合振动(振动强度为0.3g,频率为45-55Hz,每次振动20min,每天1次,每周5次,休息间隔不大于2d,共12周)；治疗3组是切除卵巢后给予阿仑膦酸钠(1mg/Kg,每周灌胃一次);治疗4组是切除卵巢后给予全身复合振动及阿仑膦酸钠干预。
3.2检测指标：
在实验过程中每四周检测实验大鼠的体重。在实验4周、8周和12周分别处死8只大鼠,收集其血标本、子宫和双侧胫骨,并用酶法检测血标本中的骨钙素(osteocalcin OC)和Ⅰ型胶原C末端肽(C-terminal cross-linked telopeptides of type I collagen, CTX),左侧胫骨标本接受micro-CT检查分析和右侧胫骨标本接受三点弯曲生物力学检测。
实验结果
1.讨论高频率低强度复合振动对去势大鼠骨质疏松的预防作用
1.1实验大鼠体重和子宫指数的变化：大鼠切除卵巢后体重呈显著性增加(P<0.001),但子宫重量减轻显著(P<0.001)。
1.2血清骨转化标志物检测结果：血清OC和CTX在卵巢切除后均增加显著(P<0.001),说明卵巢切除后大鼠的骨代谢属于高转化状态。总体来说WBV对血清内OC和CTX两种骨代谢标志物影响不大。
1.3Micro-CT扫描胫骨近端骨微结构结果：在实验12周时,与sham组对比,OVX+VEH对照组Tb.N, Tb.Th, Tb. Sp, BV/TV, Conn. D均显著性减低,而SMI显著性增高。在实验12周时,相对于对照治疗组(OVX+VEH组),WBV治疗组能够显著提高胫骨近端松质骨的骨微结构参数[BV/TV (+38.1%, P<0.001), Tb. N (+12.3%, P=0.015)和Tb. T h(+33.7%, P=0.001)].
1.4胫骨的三点弯曲实验检测结果：与OVX+VEH组比较,OVX+WBV组在各个实验时间点的所有生物力学参数无统计学意义。在实验4周时,与sham组比较,OVX+VEH组所有生物力学参数同样无统计学意义,但在实验8周和12周时,OVX+VEH组所有生物力学参数均有显著性降低。
2.讨论阿仑膦酸钠对去势大鼠骨质疏松的预防作用
2.1血清骨转化标志物检测结果：血清OC和CTX在卵巢切除后均增加显著(P<0.001)。实验过程中发现ALE对OC影响不大,但ALE能够显著抑制血清CTX的增加。
2.2Micro-CT扫描胫骨近端骨微结构结果：在实验12周时,与sham组对比,OVX+VEH对照组Tb.N, Tb.Th, Tb. Sp, BV/TV, Conn. D均显著性减低,而SMI显著性增高。在实验12周时,相对于对照治疗组(OVX+VEH组),ALE治疗能够显著提高胫骨近端松质骨的骨微结构参数[BV/TV (+73%, P<0.001), TV apparent (+89.9%, P<0.001), Tb. N (+29.9%, P<0.001)和Tb. T h (+56.3%, P0.001)].
2.3胫骨的三点弯曲实验检测结果：在实验4周时,与sham组比较,OVX+VEH组所有生物力学参数同样无统计学意义,但在实验8周和12周时,所有生物力学参数均有显著性差异。在实验12周时,相对于对照治疗组(OVX+VEH组),ALE治疗组能够显著提高胫骨近端生物力学参数Fmax(+27.6%, P=0.009)和bone energy absorption (+27.4%, P=0.040),但对胫骨近端的stiffness没有任何影响。
3.探讨低强度高频率复合振动联合阿仑膦酸钠对去势大鼠骨质疏松的预防效果
3.1血清骨转化标志物检测结果：血清OC和CTX在卵巢切除后均增加显著(P<0.001)。WBV+ALE治疗组对OC影响不大,但WBV+ALE能够显著抑制血清CTX的增加。
3.2Micro-CT扫描胫骨近端骨微结构结果：在实验12周时,与sham组对比,OVX+VEH对照组Tb. N, Tb. Th, Tb. Sp, BV/TV, Conn. D均显著性减低,而SMI显著性增高。在实验12周时,相对于WBV治疗组来说,ALE治疗组更能够显著提高胫骨近端松质骨的骨微结构参数[BV/TV(+25.3%,p=0.004),TVapparent (+60.3%, P<0.001), BV material (+28.4%, P=0.044), Tb. N (+15.6%, P=0.001), and Tb. T h (+16.9%, p=0.037)].同样在实验12周时,相对于ALE治疗组来说,WBV+ALE治疗组更能够显著提高胫骨近端的骨微结构参数[BV/TV (+25%, p=0.001), TV apparent (+30.4%, P=0.032), Tb. N (+10%, P=0.015), and Conn. D (+44.5%, p=0.042)].
3.3胫骨的三点弯曲实验检测结果：在实验4周时,与sham组比较,OVX+VEH组所有生物力学参数同样无统计学意义,但在实验8周和12周时,所有生物力学参数均有显著性差异。在实验12周时,相对于对照治疗组(OVX+VEH组),WBV+ALE治疗组均能够显著提高胫骨近端生物力学参数Fmax(+28.7%,P=0.008)和bone energy absorption (+47.6%, P=0.003),但对胫骨近端的stiffness没有任何影响。在实验12周时,虽然ALE治疗组和WBV+ALE治疗组生理力学参数均无统计学意义,但对比ALE治疗组,WBV+ALE治疗组能够提高胫骨近端的最大应力、骨的刚度参数和胫骨近端破坏的吸收能量。
实验结论
1.低强度高频率的复合振动可以一定程度上增加骨的形成,改善骨的微结构。
2.阿仑膦酸钠能够通过抑制破骨细胞活性,减少骨吸收,抑制骨转换,从而减缓了骨质疏松的进行；阿仑膦酸钠还能够改善松质骨的微结构,提高骨的生物力学性能。
3.相对于低强度全身复合振动,阿仑膦酸钠能够更好的预防去除卵巢大鼠骨质疏松和改善骨的微结构；全身复合振动联合阿仑膦酸钠能够很好的预防去势大鼠骨质疏松,而且低强度复合振动能够增强阿仑膦酸钠预防骨质疏松的效果。
Backgrounds
As a systemic skeletal disease, osteoporosis (OP) is characterized by bone loss, degradation of bone tissue microstructure, and the resulting in increasing of bone brittleness and easy fracture. Bone remodeling is a self-renewal process, including absorbing bone by osteoclasts and forming new bone constantly by osteoblasts on the resorption bone. Osteoclasts play an important role in maintaining stable bone mass in the remodeling process after bones mature. More or osteoclast activity increased results in increased bone resorption and bone remodeling imbalance, and even leads to the occurrence of many bone diseases such as:OP. There had been more than90millions patients in China. Its incidence has leapt to the7th of common diseases. One of OP'S major complication is OP fractures, a common disease which is harmful to the health of the elderly, Especially in the postmenopausai women. 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 by1%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. At present, there are two aim of the treatment for osteoporosis. One is to relieve ache, the other is to prevent the happening of the pathological fracture. The clinical treatments of
osteoporosis include drug therapy, physical therapy and surgical treatment, etc. The drug treatment has been become as the main method. Clinical commonly used drugs for preventing osteoporosis include five categories, such as bone formation actived agent, bone resorption inhibited agent, uncoupler, bone mineralization agent and traditional Chinese medicine. Now more and more patients take bone resorption inhibited drug to prevent osteoporosis, such as bisphostates that is the main anti-osteoporosis drug. Bisphostates which can inhibit osteoclast activity to reduce bone resorption, to increase bone mineral density and bone turnover, can reduce the incidence of vertebral body and the vertebral fracture which has been confirmed in clinical researches. Alendronate, which is the third generation representative drug of bisphostates, is a drug widely used for preventing osteoporosis in the clinical. Alendronate (ALE) is one of the traditional medicines for the treatment of OP. ALE can inhibit bone absorption, improve the quality of the bone. At the same time, ALE also can relieve lower back pain and improve the quality of life of senile osteoporosis. But there are some side effects, especially the gastrointestinal tract reaction, limiting some osteoporosis patients using this drug. With the development of social economy and the transformation of medical model, more and more attention has turned to non-drug methods and measures.
In recent years, the studies of prevention OP using physical therapy (mechanics, electromagnetism) have become hotspot. Wolff law shows that the bone remodels to adapt to the needs of function and the changes of the mechanical stress. So the mechanical stress loading on osteocytes within the bone is the original power for bone reconstruction. A certain frequency and intensity are required for vibration inducing osteoblastic bone formation. Two low intensity or frequency is hard to reach the stimulation for bone formation. While too high-intensity, vibration is harmful to human. Many researches confirmed that high frequency(>30Hz), low level( Objectives
1. To evaluate the preventive effects of high frequency and low level compound vibration on ovariectomized rats;
2. To evaluate the preventive effects of alendronate on ovariectomized rats;
3. To differentiate the effect in ovariectomized rats between conventionally alendronate drug and low-magnitude whole-body vibration.
4. To investigate the effect of low-magnitude WBV combined with ALE in ovariectomized rats
5. To determine whether low-magnitude WBV could enhance the effect of ALE on bone turnover and bone properties in ovariectomized rats.
Methods
1. To evaluate the preventive effects of high frequency and low level compound vibration on ovariectomized rats
1.1Materials and methods:
A total of80Sprague-Dawley rats were randomly divided into three groups (SHAM, OVX+VEH, OVX+WBV). The sham group not received ovariectomy and the other two treat groups received ovariectomy. The level of WBV was applied0.3g at45-55Hz for20min/day,5day/week, for12weeks. VEH was administered in dose of1mg/Kg, once a week.
1.2Measurements:
During the experimental period, the body weight of the rats in all groups was measured using electronic scale and was recorded every four weeks during the experimental period. The rats were sacrificed at four predetermined time points for the Sham group (0,4,8and12weeks) and three time points for the remaining four groups (4,8and12weeks). Every four weeks, eight rats from each group were sacrificed and their blood and both tibiae were harvested. At sacrifice, whole blood was collected with a cardiac puncture to determine the serum osteocalcin (OC) and CTX (C-terminal cross-linked telopeptides of type I collagen, CTX) using standard laboratory techniques. The bilateral tibiae were collected, with the soft tissues being thoroughly removed and wrapped in normal saline-soaked gauze and stored at-20℃until further use for biomechanical testing and micro-CT scanning.
2. To investigate the effect of ALE on ovariectomized rats
2.1Materials and methods:
A total of80Sprague-Dawley rats were randomly divided into three groups (SHAM, OVX+VEH, OVX+ALE). The sham group not received ovariectomy and the other two treat groups received ovariectomy. VEH and ALE were administered in dose of1mg/Kg, once a week.
2.2Measurements:
During the experimental period, the body weight of the rats in all groups was measured using electronic scale and was recorded every four weeks during the experimental period. The rats were sacrificed at four predetermined time points for the Sham group (0,4,8and12weeks) and three time points for the remaining four groups (4,8and12weeks). Every four weeks, eight rats from each group were sacrificed and their blood and both tibiae were harvested. At sacrifice, whole blood was collected with a cardiac puncture to determine the serum osteocalcin (OC) and CTX (C-terminal cross-linked telopeptides of type I collagen, CTX) using standard laboratory techniques. The bilateral tibiae were collected, with the soft tissues being thoroughly removed and wrapped in normal saline-soaked gauze and stored at-20℃ until further use for biomechanical testing and micro-CT scanning.
3. To investigate the effect of low-magnitude WBV combined with ALE in ovariectomized rats
3.1Materials and methods:
A total of128Sprague-Dawley rats were randomly divided into five groups (SHAM, OVX+VEH, OVX+WBV, OVX+ALE, OVX+WBV+ALE). The sham group not received ovariectomy and the other four treat groups received ovariectomy. The level of WBV was applied0.3g at45-55Hz for20min/day,5day/week, for12weeks. VEH and ALE were administered in dose of1mg/Kg, once a week.
3.2Measurements:
During the experimental period, the body weight of the rats in all groups was measured using electronic scale and was recorded every four weeks during the experimental period. The rats were sacrificed at four predetermined time points for the Sham group (0,4,8and12weeks) and three time points for the remaining four groups (4,8and12weeks). Every four weeks, eight rats from each group were sacrificed and their blood and both tibiae were harvested. At sacrifice, whole blood was collected with a cardiac puncture to determine the serum osteocalcin (OC) and CTX (C-terminal cross-linked telopeptides of type I collagen, CTX) using standard laboratory techniques. The bilateral tibiae were collected, with the soft tissues being thoroughly removed and wrapped in normal saline-soaked gauze and stored at-20℃until further use for biomechanical testing and micro-CT scanning.
Results
1. To evaluate the preventive effects of high frequency and low level compound vibration on ovariectomized rats
1.1The change of experimental rats weight and uterus index:
The rat weight increased significantly after the ovary removed (P<0.001), but the uterus weight reduced significantly (P<0.001).
1.2The results of serum markers:
Osteocalcin (OC) and CTX rose with ovariectomy. They were not appreciably changed by WBV.
1.3The bone microstructure results of the tibia measured by Micro-CT:
Compared with the Sham group, nearly all tested indices were lower in the OVX+VEH group at week12, such as the BV/TV, Tb. N, Tb. T h, Tb. Sp and Conn. D. Moreover, compared with the OVX+VEH group, the BV/TV (+38.1%, P<0.001), Tb. N (+12.3%, P=0.015), Tb. Th (+33.7%, P=0.001), and Conn. D (+47.5%, P=0.029) were higher, and the SMI (-17.9%, P=0.003) was lower in the OVX+WBV group.
1.4Three point bending experiment result of tibiae:
All biomechanical parameters in various time points showed no significant difference between the OVX+VEH and OVX+WBV groups. All biomechanical parameters at week4also showed no significant difference between the OVX+VEH and Sham group. However, compared with the Sham group, all biomechanical parameters were lower in the OVX+VEH group at week8and week12.
2. To investigate the effect of ALE in ovariectomized rats
2.1The results of serum markers:
Osteocalcin (OC) and CTX rose with ovariectomy. The level of OC was not appreciably changed by alendronate alone. Alendronate treatment significantly prevented an increase in this CTX serum marker.
2.2The bone microstructure results of the tibia measured by Micro-CT:
Compared with the Sham group, nearly all tested indices were lower in the OVX+VEH group at week12, such as the BV/TV, Tb. N, Tb. T h, Tb. Sp and Conn. D. Moreover, compared with the OVX+VEH group, nearly all tested indices were higher in the OVX+ALE group at week12, such as the BV/TV (+73%, P<0.001), TV apparent (+89.9%, P<0.001), Tb. N (+29.9%, P<0.001), Tb. T h (+56.3%, P<0.001), and Conn. D (+53.6%, P=0.012), and the SMI (-31.3%, P<0.001) and Tb. Sp (-38.7%, P=0.027) were lower in the OVX+ALE group.
2.3Three point bending experiment result of tibiae:
All biomechanical parameters at week4also showed no significant difference between the OVX+VEH and Sham group. However, compared with the Sham group, all biomechanical parameters were lower in the OVX+VEH group at week8and week12. Compared with the OVX+VEH (69.80±9.23N) group, the F max were higher in the OVX+ALE group (+27.6%, P=0.009) at week12. At week12, compared with the OVX+VEH group (52.03±1.58N), bone energy absorption were higher in the OVX+ALE group (66.27±2.64N,+27.4%, P=0.040). However, there were no significant differences for stiffness at any point in the two study groups examined.
3. To investigate the effect of low-magnitude WBV combined with ALE in ovariectomized rats
3.1The results of serum markers:
Osteocalcin (OC) and CTX rose with ovariectomy. The level of OC was not appreciably changed by WBV combined ALE. WBV+ALE treatment significantly prevented an increase in this CTX serum marker.
3.2The bone microstructure results of the tibia measured by Micro-CT:
Compared with the Sham group, nearly all tested indices were lower in the OVX+VEH group at week12, such as the BV/TV, Tb. N, Tb. T h, Tb. Sp and Conn. D. Compared with the OVX+WBV group, the BV/TV (+25.3%, p=0.004), TV apparent (+60.3%, P<0.001), BV material (+28.4%, P=0.044), Tb. N (+15.6%, P=0.001), and Tb. T h (+16.9%, p=0.037) were higher, and the SMI (-16.4%, p=0.013) was lower in the OVX+ALE group at week12. At week12, significant differences were found for some tested indices between the OVX+ALE and OVX+WBV+ALE groups. Compared with the OVX+ALE group, the BV/TV (+25%, p=0.001), TV apparent (+30.4%, P=0.032), Tb. N (+10%, P=0.015), and Con. D (+44.5%, p=0.042) were higher, and the SMI (-18.4%, p=0.042) was lower in the OVX+WBV+ALE group.
3.3Three point bending experiment result of tibiae:
All biomechanical parameters at week4also showed no significant difference between the OVX+VEH and Sham group. However, compared with the Sham group, all biomechanical parameters were lower in the OVX+VEH group at week8and week12. Compared with the OVX+VEH (69.80+-9.23N) group, the F M were higher in the OVX+WBV+ALE group (89.86±6.21N,+28.7%, P=0.008) at week12. At week12, compared with the OVX+VEH group (52.03±1.58N), bone energy absorption were higher in the OVX+WBV+ALE group (76.81±3.23N,+47.6%, P=0.003). However, there were no significant differences for stiffness at any point in the four study groups examined.
Conclusions
1. Low-magnitude, high-frequency whole body vibration can increase bone formation and improve bone microstructure.
2. Alendronate can inhibit osteoclaste activity, reduce bone resorption, inhibit bone transformation. Alendronate also can improve the microstructure and biomechanical properties of cancellous bone.
3. Compared with the WBV, ALE was more effective at preventing bone loss and improved the trabecular architecture. Moreover, WBV enhance the effect of alendronate in ovariectomized rats by inducing further improvements in trabecular architecture.
骨质疏松(Osteoporosis, OP)是以骨量减少,骨组织微观结构退化,致使骨强度下降,骨脆性增加以及骨折风险增大为特征的一种全身性骨骼系统疾病。骨重建是一个骨组织自我更新的过程：破骨细胞不断吸收旧骨,而成骨细胞则不断形成新骨补充骨吸收部分。当机体骨骼发育成熟后,破骨细胞在骨重建过程中发挥重要作用。若破骨细胞活性增强或量增多,可以导致骨吸收增加,骨重建失衡,导致很多骨骼系统疾病的发生,如：OP。目前OP在世界常见病、多发病中居第7位。骨质疏松最常见的并发症是骨折,常见部位是髋部,椎体和桡骨远端。妇女在进入绝经期后骨量丢失明显,如无适当预防和治疗,骨质疏松将不可避免地造成桡骨、脊柱和髋部等处的骨折。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。目前关于骨质疏松症的治疗目的一是解除全身性疼痛,二是预防病理性骨折的发生。临床上关于骨质疏松症的治疗方案包括药物治疗、物理治疗及外科手术治疗等,其中以药物治疗为主要手段。临床上常使用的药物主要有骨吸收抑制剂、骨形成促进剂、解偶联剂、骨矿化剂以及中医药等五大类。目前临床上越来越多的患者服用骨吸收抑制剂二膦酸盐类药物来预防骨质疏松或者作为抗骨质疏松的主要药物。二膦酸盐类药物主要机制是通过抑制破骨细胞活性减少骨吸收,从而增加骨密度和抑制骨转换,可以减低椎体和非椎体骨折的发生率,并且已为临床研究所证实。阿伦膦酸钠是第三代二膦酸盐类药物的代表药物,也是临床上使用最为广泛的抗骨质疏松药物。阿仑膦酸钠(Alendronate ALE)是治疗OP的传统药物之一,以抑制骨吸收为主,改善骨的质量,同时也可以减轻腰背部疼痛和改善骨质疏松老年的生活质量。但是该药物治疗存在一定副作用,特别是胃肠道反应,限制一部分骨质疏松患者使用该药物。随着社会经济的发展和医疗模式的转变,在关注药物治疗的同时,越来越多的关注已转向了非药物的手段和措施。
近年来物理疗法(力学、电磁学)防治OP的研究成为热点。Wolff定律认为,骨的结构特点是适应功能需要而塑造的,并随着功能需要的改变而进行重建；骨的功能是承受活动期间骨组织的机械应变,并随着功能需要所产生的应力的变化而进行功能适应性重建。振动是一种力学刺激,它需要一定的强度和频率才能将有效刺激能量传递至成骨效应细胞,从而诱发成骨反应,过低的强度和频率难以到达有效部位或不能成为诱发成骨的阈上刺激,而过高的振动强度对人体是有危害的。众多研究已经证实,高频(≥30Hz)、低强度(<1g,1g=9.8m/s)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。所以说,低于引起骨组织损伤的机械振动信号具有很强的成骨效应,是一种新型、无创、副作用小治疗OP的模式,在防治老年性骨质疏松中有广阔的应用前景。但是目前关于低强度的全身复合振动联合阿仑膦酸钠预防骨质疏松症的研究仍未有报道。
实验目的：
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.评估阿仑膦酸钠预防卵巢切除大鼠骨质疏松的作用；
3.比较传统药物阿仑膦酸钠与新型的低强度全身复合振动在预防骨质疏松的效果；
4.观察低强度的全身复合振动联合阿仑膦酸钠预防骨质疏松的效果；
5.观察低强度全身复合振动是否增强阿仑膦酸钠预防骨质疏松的效果。
实验方法：
1.讨论高频率低强度复合振动对去势大鼠骨质疏松的预防作用
1.1实验材料与方法：
80只8周龄SD雌性未育大鼠随机分为对照组(sham)、治疗1组(OVX+VEH)、治疗2组(OVX+WBV),对照组32只大鼠,其余2个治疗组每组24只。对照组未切除卵巢,而治疗1组、治疗2组中大鼠切除双侧卵巢,制备骨质疏松大鼠模型；待卵巢切除切口愈合后开始干预,其中治疗1组是单纯卵巢切除后给予生理盐水(1mg/Kg,每周灌胃一次)；治疗2组是切除卵巢后给予全身复合振动(振动强度为0.3g,频率为45-55Hz,每次振动20min,每天1次,每周5次,休息间隔不大于2d,共12周)。
1.2检测指标：
在实验过程中每四周检测实验大鼠的体重。在实验4周、8周和12周分别处死8只大鼠,收集其血标本、子宫和双侧胫骨,并用酶法检测血标本中的骨钙素(osteocalcin OC)和工型胶原C末端肽(C-terminal cross-linked telopeptides of type I collagen, CTX),左侧胫骨标本接受micro-CT检查分析和右侧胫骨标本接受三点弯曲生物力学检测。
2.讨论阿仑膦酸钠对去势大鼠骨质疏松的预防作用
2.1实验材料与方法：
80只8周龄SD雌性未育大鼠随机分为对照组(sham)、治疗1组(OVX+VEH)、治疗2组(OVX+ALE),对照组32只大鼠,其余2个治疗组每组24只。对照组未切除卵巢,而治疗1组、治疗2组中大鼠切除双侧卵巢,制备骨质疏松大鼠模型；待卵巢切除切口愈合后开始干预,其中治疗1组是单纯卵巢切除后给予生理盐水(1mg/Kg,每周灌胃一次)；治疗2组是切除卵巢后给予阿仑膦酸钠(1mg/Kg,每周灌胃一次)。
2.2检测指标：
在实验过程中每四周检测实验大鼠的体重。在实验4周、8周和12周分别处死8只大鼠,收集其血标本、子宫和双侧胫骨,并用酶法检测血标本中的骨钙素(osteocalcin OC)和Ⅰ型胶原C末端肽(C-terminal cross-linked telopeptides of type I collagen, CTX),左侧胫骨标本接受micro-CT检查分析和右侧胫骨标本接受三点弯曲生物力学检测。
3.探讨低强度高频率复合振动联合阿仑膦酸钠对去势大鼠骨质疏松的预防效果
3.1实验材料与方法：
128只8周龄SD雌性未育大鼠随机分为对照组(sham)、治疗1组(OVX+VEH)、治疗2组(OVX+WBV)、治疗3组(OVX+ALE)和治疗4组(VOX+WBV+ALE),对照组32只大鼠,其余四个治疗组每组24只。对照组未切除卵巢,而治疗1组、治疗2组、治疗3组和治疗4组中大鼠切除双侧卵巢,制备骨质疏松大鼠模型；待卵巢切除切口愈合后开始干预,其中治疗1组是单纯卵巢切除后给予生理盐水(1mg/Kg,每周灌胃一次)；治疗2组是切除卵巢后给予全身复合振动(振动强度为0.3g,频率为45-55Hz,每次振动20min,每天1次,每周5次,休息间隔不大于2d,共12周)；治疗3组是切除卵巢后给予阿仑膦酸钠(1mg/Kg,每周灌胃一次);治疗4组是切除卵巢后给予全身复合振动及阿仑膦酸钠干预。
3.2检测指标：
在实验过程中每四周检测实验大鼠的体重。在实验4周、8周和12周分别处死8只大鼠,收集其血标本、子宫和双侧胫骨,并用酶法检测血标本中的骨钙素(osteocalcin OC)和Ⅰ型胶原C末端肽(C-terminal cross-linked telopeptides of type I collagen, CTX),左侧胫骨标本接受micro-CT检查分析和右侧胫骨标本接受三点弯曲生物力学检测。
实验结果
1.讨论高频率低强度复合振动对去势大鼠骨质疏松的预防作用
1.1实验大鼠体重和子宫指数的变化：大鼠切除卵巢后体重呈显著性增加(P<0.001),但子宫重量减轻显著(P<0.001)。
1.2血清骨转化标志物检测结果：血清OC和CTX在卵巢切除后均增加显著(P<0.001),说明卵巢切除后大鼠的骨代谢属于高转化状态。总体来说WBV对血清内OC和CTX两种骨代谢标志物影响不大。
1.3Micro-CT扫描胫骨近端骨微结构结果：在实验12周时,与sham组对比,OVX+VEH对照组Tb.N, Tb.Th, Tb. Sp, BV/TV, Conn. D均显著性减低,而SMI显著性增高。在实验12周时,相对于对照治疗组(OVX+VEH组),WBV治疗组能够显著提高胫骨近端松质骨的骨微结构参数[BV/TV (+38.1%, P<0.001), Tb. N (+12.3%, P=0.015)和Tb. T h(+33.7%, P=0.001)].
1.4胫骨的三点弯曲实验检测结果：与OVX+VEH组比较,OVX+WBV组在各个实验时间点的所有生物力学参数无统计学意义。在实验4周时,与sham组比较,OVX+VEH组所有生物力学参数同样无统计学意义,但在实验8周和12周时,OVX+VEH组所有生物力学参数均有显著性降低。
2.讨论阿仑膦酸钠对去势大鼠骨质疏松的预防作用
2.1血清骨转化标志物检测结果：血清OC和CTX在卵巢切除后均增加显著(P<0.001)。实验过程中发现ALE对OC影响不大,但ALE能够显著抑制血清CTX的增加。
2.2Micro-CT扫描胫骨近端骨微结构结果：在实验12周时,与sham组对比,OVX+VEH对照组Tb.N, Tb.Th, Tb. Sp, BV/TV, Conn. D均显著性减低,而SMI显著性增高。在实验12周时,相对于对照治疗组(OVX+VEH组),ALE治疗能够显著提高胫骨近端松质骨的骨微结构参数[BV/TV (+73%, P<0.001), TV apparent (+89.9%, P<0.001), Tb. N (+29.9%, P<0.001)和Tb. T h (+56.3%, P0.001)].
2.3胫骨的三点弯曲实验检测结果：在实验4周时,与sham组比较,OVX+VEH组所有生物力学参数同样无统计学意义,但在实验8周和12周时,所有生物力学参数均有显著性差异。在实验12周时,相对于对照治疗组(OVX+VEH组),ALE治疗组能够显著提高胫骨近端生物力学参数Fmax(+27.6%, P=0.009)和bone energy absorption (+27.4%, P=0.040),但对胫骨近端的stiffness没有任何影响。
3.探讨低强度高频率复合振动联合阿仑膦酸钠对去势大鼠骨质疏松的预防效果
3.1血清骨转化标志物检测结果：血清OC和CTX在卵巢切除后均增加显著(P<0.001)。WBV+ALE治疗组对OC影响不大,但WBV+ALE能够显著抑制血清CTX的增加。
3.2Micro-CT扫描胫骨近端骨微结构结果：在实验12周时,与sham组对比,OVX+VEH对照组Tb. N, Tb. Th, Tb. Sp, BV/TV, Conn. D均显著性减低,而SMI显著性增高。在实验12周时,相对于WBV治疗组来说,ALE治疗组更能够显著提高胫骨近端松质骨的骨微结构参数[BV/TV(+25.3%,p=0.004),TVapparent (+60.3%, P<0.001), BV material (+28.4%, P=0.044), Tb. N (+15.6%, P=0.001), and Tb. T h (+16.9%, p=0.037)].同样在实验12周时,相对于ALE治疗组来说,WBV+ALE治疗组更能够显著提高胫骨近端的骨微结构参数[BV/TV (+25%, p=0.001), TV apparent (+30.4%, P=0.032), Tb. N (+10%, P=0.015), and Conn. D (+44.5%, p=0.042)].
3.3胫骨的三点弯曲实验检测结果：在实验4周时,与sham组比较,OVX+VEH组所有生物力学参数同样无统计学意义,但在实验8周和12周时,所有生物力学参数均有显著性差异。在实验12周时,相对于对照治疗组(OVX+VEH组),WBV+ALE治疗组均能够显著提高胫骨近端生物力学参数Fmax(+28.7%,P=0.008)和bone energy absorption (+47.6%, P=0.003),但对胫骨近端的stiffness没有任何影响。在实验12周时,虽然ALE治疗组和WBV+ALE治疗组生理力学参数均无统计学意义,但对比ALE治疗组,WBV+ALE治疗组能够提高胫骨近端的最大应力、骨的刚度参数和胫骨近端破坏的吸收能量。
实验结论
1.低强度高频率的复合振动可以一定程度上增加骨的形成,改善骨的微结构。
2.阿仑膦酸钠能够通过抑制破骨细胞活性,减少骨吸收,抑制骨转换,从而减缓了骨质疏松的进行；阿仑膦酸钠还能够改善松质骨的微结构,提高骨的生物力学性能。
3.相对于低强度全身复合振动,阿仑膦酸钠能够更好的预防去除卵巢大鼠骨质疏松和改善骨的微结构；全身复合振动联合阿仑膦酸钠能够很好的预防去势大鼠骨质疏松,而且低强度复合振动能够增强阿仑膦酸钠预防骨质疏松的效果。
Backgrounds
As a systemic skeletal disease, osteoporosis (OP) is characterized by bone loss, degradation of bone tissue microstructure, and the resulting in increasing of bone brittleness and easy fracture. Bone remodeling is a self-renewal process, including absorbing bone by osteoclasts and forming new bone constantly by osteoblasts on the resorption bone. Osteoclasts play an important role in maintaining stable bone mass in the remodeling process after bones mature. More or osteoclast activity increased results in increased bone resorption and bone remodeling imbalance, and even leads to the occurrence of many bone diseases such as:OP. There had been more than90millions patients in China. Its incidence has leapt to the7th of common diseases. One of OP'S major complication is OP fractures, a common disease which is harmful to the health of the elderly, Especially in the postmenopausai women. 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 by1%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. At present, there are two aim of the treatment for osteoporosis. One is to relieve ache, the other is to prevent the happening of the pathological fracture. The clinical treatments of
osteoporosis include drug therapy, physical therapy and surgical treatment, etc. The drug treatment has been become as the main method. Clinical commonly used drugs for preventing osteoporosis include five categories, such as bone formation actived agent, bone resorption inhibited agent, uncoupler, bone mineralization agent and traditional Chinese medicine. Now more and more patients take bone resorption inhibited drug to prevent osteoporosis, such as bisphostates that is the main anti-osteoporosis drug. Bisphostates which can inhibit osteoclast activity to reduce bone resorption, to increase bone mineral density and bone turnover, can reduce the incidence of vertebral body and the vertebral fracture which has been confirmed in clinical researches. Alendronate, which is the third generation representative drug of bisphostates, is a drug widely used for preventing osteoporosis in the clinical. Alendronate (ALE) is one of the traditional medicines for the treatment of OP. ALE can inhibit bone absorption, improve the quality of the bone. At the same time, ALE also can relieve lower back pain and improve the quality of life of senile osteoporosis. But there are some side effects, especially the gastrointestinal tract reaction, limiting some osteoporosis patients using this drug. With the development of social economy and the transformation of medical model, more and more attention has turned to non-drug methods and measures.
In recent years, the studies of prevention OP using physical therapy (mechanics, electromagnetism) have become hotspot. Wolff law shows that the bone remodels to adapt to the needs of function and the changes of the mechanical stress. So the mechanical stress loading on osteocytes within the bone is the original power for bone reconstruction. A certain frequency and intensity are required for vibration inducing osteoblastic bone formation. Two low intensity or frequency is hard to reach the stimulation for bone formation. While too high-intensity, vibration is harmful to human. Many researches confirmed that high frequency(>30Hz), low level(
1. To evaluate the preventive effects of high frequency and low level compound vibration on ovariectomized rats;
2. To evaluate the preventive effects of alendronate on ovariectomized rats;
3. To differentiate the effect in ovariectomized rats between conventionally alendronate drug and low-magnitude whole-body vibration.
4. To investigate the effect of low-magnitude WBV combined with ALE in ovariectomized rats
5. To determine whether low-magnitude WBV could enhance the effect of ALE on bone turnover and bone properties in ovariectomized rats.
Methods
1. To evaluate the preventive effects of high frequency and low level compound vibration on ovariectomized rats
1.1Materials and methods:
A total of80Sprague-Dawley rats were randomly divided into three groups (SHAM, OVX+VEH, OVX+WBV). The sham group not received ovariectomy and the other two treat groups received ovariectomy. The level of WBV was applied0.3g at45-55Hz for20min/day,5day/week, for12weeks. VEH was administered in dose of1mg/Kg, once a week.
1.2Measurements:
During the experimental period, the body weight of the rats in all groups was measured using electronic scale and was recorded every four weeks during the experimental period. The rats were sacrificed at four predetermined time points for the Sham group (0,4,8and12weeks) and three time points for the remaining four groups (4,8and12weeks). Every four weeks, eight rats from each group were sacrificed and their blood and both tibiae were harvested. At sacrifice, whole blood was collected with a cardiac puncture to determine the serum osteocalcin (OC) and CTX (C-terminal cross-linked telopeptides of type I collagen, CTX) using standard laboratory techniques. The bilateral tibiae were collected, with the soft tissues being thoroughly removed and wrapped in normal saline-soaked gauze and stored at-20℃until further use for biomechanical testing and micro-CT scanning.
2. To investigate the effect of ALE on ovariectomized rats
2.1Materials and methods:
A total of80Sprague-Dawley rats were randomly divided into three groups (SHAM, OVX+VEH, OVX+ALE). The sham group not received ovariectomy and the other two treat groups received ovariectomy. VEH and ALE were administered in dose of1mg/Kg, once a week.
2.2Measurements:
During the experimental period, the body weight of the rats in all groups was measured using electronic scale and was recorded every four weeks during the experimental period. The rats were sacrificed at four predetermined time points for the Sham group (0,4,8and12weeks) and three time points for the remaining four groups (4,8and12weeks). Every four weeks, eight rats from each group were sacrificed and their blood and both tibiae were harvested. At sacrifice, whole blood was collected with a cardiac puncture to determine the serum osteocalcin (OC) and CTX (C-terminal cross-linked telopeptides of type I collagen, CTX) using standard laboratory techniques. The bilateral tibiae were collected, with the soft tissues being thoroughly removed and wrapped in normal saline-soaked gauze and stored at-20℃ until further use for biomechanical testing and micro-CT scanning.
3. To investigate the effect of low-magnitude WBV combined with ALE in ovariectomized rats
3.1Materials and methods:
A total of128Sprague-Dawley rats were randomly divided into five groups (SHAM, OVX+VEH, OVX+WBV, OVX+ALE, OVX+WBV+ALE). The sham group not received ovariectomy and the other four treat groups received ovariectomy. The level of WBV was applied0.3g at45-55Hz for20min/day,5day/week, for12weeks. VEH and ALE were administered in dose of1mg/Kg, once a week.
3.2Measurements:
During the experimental period, the body weight of the rats in all groups was measured using electronic scale and was recorded every four weeks during the experimental period. The rats were sacrificed at four predetermined time points for the Sham group (0,4,8and12weeks) and three time points for the remaining four groups (4,8and12weeks). Every four weeks, eight rats from each group were sacrificed and their blood and both tibiae were harvested. At sacrifice, whole blood was collected with a cardiac puncture to determine the serum osteocalcin (OC) and CTX (C-terminal cross-linked telopeptides of type I collagen, CTX) using standard laboratory techniques. The bilateral tibiae were collected, with the soft tissues being thoroughly removed and wrapped in normal saline-soaked gauze and stored at-20℃until further use for biomechanical testing and micro-CT scanning.
Results
1. To evaluate the preventive effects of high frequency and low level compound vibration on ovariectomized rats
1.1The change of experimental rats weight and uterus index:
The rat weight increased significantly after the ovary removed (P<0.001), but the uterus weight reduced significantly (P<0.001).
1.2The results of serum markers:
Osteocalcin (OC) and CTX rose with ovariectomy. They were not appreciably changed by WBV.
1.3The bone microstructure results of the tibia measured by Micro-CT:
Compared with the Sham group, nearly all tested indices were lower in the OVX+VEH group at week12, such as the BV/TV, Tb. N, Tb. T h, Tb. Sp and Conn. D. Moreover, compared with the OVX+VEH group, the BV/TV (+38.1%, P<0.001), Tb. N (+12.3%, P=0.015), Tb. Th (+33.7%, P=0.001), and Conn. D (+47.5%, P=0.029) were higher, and the SMI (-17.9%, P=0.003) was lower in the OVX+WBV group.
1.4Three point bending experiment result of tibiae:
All biomechanical parameters in various time points showed no significant difference between the OVX+VEH and OVX+WBV groups. All biomechanical parameters at week4also showed no significant difference between the OVX+VEH and Sham group. However, compared with the Sham group, all biomechanical parameters were lower in the OVX+VEH group at week8and week12.
2. To investigate the effect of ALE in ovariectomized rats
2.1The results of serum markers:
Osteocalcin (OC) and CTX rose with ovariectomy. The level of OC was not appreciably changed by alendronate alone. Alendronate treatment significantly prevented an increase in this CTX serum marker.
2.2The bone microstructure results of the tibia measured by Micro-CT:
Compared with the Sham group, nearly all tested indices were lower in the OVX+VEH group at week12, such as the BV/TV, Tb. N, Tb. T h, Tb. Sp and Conn. D. Moreover, compared with the OVX+VEH group, nearly all tested indices were higher in the OVX+ALE group at week12, such as the BV/TV (+73%, P<0.001), TV apparent (+89.9%, P<0.001), Tb. N (+29.9%, P<0.001), Tb. T h (+56.3%, P<0.001), and Conn. D (+53.6%, P=0.012), and the SMI (-31.3%, P<0.001) and Tb. Sp (-38.7%, P=0.027) were lower in the OVX+ALE group.
2.3Three point bending experiment result of tibiae:
All biomechanical parameters at week4also showed no significant difference between the OVX+VEH and Sham group. However, compared with the Sham group, all biomechanical parameters were lower in the OVX+VEH group at week8and week12. Compared with the OVX+VEH (69.80±9.23N) group, the F max were higher in the OVX+ALE group (+27.6%, P=0.009) at week12. At week12, compared with the OVX+VEH group (52.03±1.58N), bone energy absorption were higher in the OVX+ALE group (66.27±2.64N,+27.4%, P=0.040). However, there were no significant differences for stiffness at any point in the two study groups examined.
3. To investigate the effect of low-magnitude WBV combined with ALE in ovariectomized rats
3.1The results of serum markers:
Osteocalcin (OC) and CTX rose with ovariectomy. The level of OC was not appreciably changed by WBV combined ALE. WBV+ALE treatment significantly prevented an increase in this CTX serum marker.
3.2The bone microstructure results of the tibia measured by Micro-CT:
Compared with the Sham group, nearly all tested indices were lower in the OVX+VEH group at week12, such as the BV/TV, Tb. N, Tb. T h, Tb. Sp and Conn. D. Compared with the OVX+WBV group, the BV/TV (+25.3%, p=0.004), TV apparent (+60.3%, P<0.001), BV material (+28.4%, P=0.044), Tb. N (+15.6%, P=0.001), and Tb. T h (+16.9%, p=0.037) were higher, and the SMI (-16.4%, p=0.013) was lower in the OVX+ALE group at week12. At week12, significant differences were found for some tested indices between the OVX+ALE and OVX+WBV+ALE groups. Compared with the OVX+ALE group, the BV/TV (+25%, p=0.001), TV apparent (+30.4%, P=0.032), Tb. N (+10%, P=0.015), and Con. D (+44.5%, p=0.042) were higher, and the SMI (-18.4%, p=0.042) was lower in the OVX+WBV+ALE group.
3.3Three point bending experiment result of tibiae:
All biomechanical parameters at week4also showed no significant difference between the OVX+VEH and Sham group. However, compared with the Sham group, all biomechanical parameters were lower in the OVX+VEH group at week8and week12. Compared with the OVX+VEH (69.80+-9.23N) group, the F M were higher in the OVX+WBV+ALE group (89.86±6.21N,+28.7%, P=0.008) at week12. At week12, compared with the OVX+VEH group (52.03±1.58N), bone energy absorption were higher in the OVX+WBV+ALE group (76.81±3.23N,+47.6%, P=0.003). However, there were no significant differences for stiffness at any point in the four study groups examined.
Conclusions
1. Low-magnitude, high-frequency whole body vibration can increase bone formation and improve bone microstructure.
2. Alendronate can inhibit osteoclaste activity, reduce bone resorption, inhibit bone transformation. Alendronate also can improve the microstructure and biomechanical properties of cancellous bone.
3. Compared with the WBV, ALE was more effective at preventing bone loss and improved the trabecular architecture. Moreover, WBV enhance the effect of alendronate in ovariectomized rats by inducing further improvements in trabecular architecture.
引文
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