变频振动对尾吊大鼠失重性骨质疏松防治作用的研究

目的探讨变频振动对尾吊大鼠失重性骨质疏松模型的防治作用。方法采用目前世界上广泛应用且技术已经成熟的鼠尾悬吊动物模型模拟失重环境,应用电磁振动台将振动强度为0.5 g(g为加速度)在不同频率45 Hz、90 Hz、变频(5~90Hz)振动应力作用于3月龄SD雄性大鼠40只,随机分成5组,每组8只:对照组(非鼠尾悬吊组);45 Hz组、90 Hz组、变频(5~90 Hz)组,鼠尾悬吊非振动组,每次振动10 min,每天1次,每周5次,休息间隔为2天,共4周。所有对照组不进行振动治疗,但置于与振动治疗组相同噪音环境下。实验后用Micro-CT测量股骨远端骨量、自动化分析仪测定血生化指标以及Elisa试剂盒测定骨钙素。结果振动刺激对失重性骨质疏松骨微结构的恢复及骨密度有明显的改善作用,变频振动对骨微结构的恢复及增加骨密度一定程度上要好于固定频率振动。结论对尾吊大鼠28天的不同频率振动刺激使松质骨骨矿物质以及空间上的结构进行了重构,导致尾吊大鼠骨质疏松模型中骨量的增加,骨密度的提高,对失重性骨质疏松有一定的防治作用,为临床上防治微重力环境下骨丢失提供了实验依据。     

失重与骨代谢调节失衡

在失重飞行引起的所有人体生理系统变化中，其骨代谢的调节失衡为最严重的危害。其他生理系统的变化在航天飞行中会达到一种新的平衡状态，返回地面后，经过一段时间可以很快得到恢复。但骨钙的丢失却持续发展，且在返回地面后需要很长时间恢复。今后载人航天的重点在于长期飞行，太空失重导致航天员骨质疏松引起的危害就更大，因此失重状态下骨质丢失的研究已成为目前航天医学研究的重点。     

失重骨丢失与防治措施研究进展

笔者综述了部分干预措施在稳定钙平衡和骨代谢以及防治骨量丢失方面的作用。空间飞行中提高钙的摄入量和补充维生素D,通过增加骨化三醇水平,能防止血清钙水平升高,维生素K能抵抗骨形成的减少。然而,目前还没有防止空间飞行航天员发生骨质疏松的有效药剂。在尾吊成年大鼠模拟失重动物模型中,应用双膦酸盐能够防护胫骨的松质骨量丢失,睾酮和维生素K2通过防止骨吸收增加和骨形成减少,能够对抗后肢的BMD下降。然而,这些药剂是否能够防止尾吊模拟失重大鼠引起的皮质骨骨量丢失尚不清楚。因此,除了补充钙、维生素D、维生素K,有待寻找有效的兼具抑制吸收和促合成代谢的药物来维持空间飞行中航天员的钙平衡和骨代谢,从而防护骨量丢失。     

太空环境下血管重塑引起骨量丢失的研究进展

在太空环境下,由于重力缺失导致的力学刺激减少等原因,宇航员的骨量会发生明显丢失。既往微重力模型下骨量丢失机制的研究表明,宇航员在太空环境下骨量丢失与骨内血管重塑密切相关。微重力环境下,下肢的血流量明显减少,血压降低,导致骨内血管发生重塑,血管数量减少、直径缩窄,进而导致骨内灌注压的降低。以上机制影响骨陷窝-骨小管内间质液的流动和物质转移,改变骨细胞周围微环境。骨细胞作为骨组织的力学感受器,受到间质液剪切应力的调节后,进一步调节成骨细胞和破骨细胞的活性,导致骨稳态破坏,最终造成废用性骨质疏松。本文通过查阅近年来微重力下血管重塑与骨量丢失的相关研究,理清二者之间的关系,以为太空环境下防治骨质疏松提供帮助。     

失重性骨质疏松的发生机制及中药对其防治作用的研究进展

太空中由于重力消失,体液分布紊乱,会导致承重骨的肌肉发生进行性萎缩,骨骼所受到的应力刺激减少或消失,成骨细胞增殖障碍,从而导致了失重骨质疏松的发生。与其他骨质疏松不同的是该类型的骨质疏松的发生和发展具有一定的部位选择性,且返回地面后恢复比较困难。常规干预措施如药物、体育锻炼、机械刺激等虽然对缓解骨丢失起到一定的疗效,但也存在着一定弊端。中医认为"肾主骨生髓",主张从肾论治,收到了满意的疗效。在地面实验中,研究人员也发现采用补肾中药可以有效促进成骨细胞增殖,从而对抗模拟失重所造成的骨量丢失。因此本文拟对失重骨质疏松的发生机制及中医药在对抗失重骨质疏中的应用进行概述。     

五禽戏与原发性骨质疏松症相关研究概述

原发性骨质疏松症的主要特征是骨量减少、骨组织微结构破坏、骨脆性增高和骨折危险性增加.而科学合理的运动可有效地增加骨量,延缓骨量丢失,从而起到防治骨质疏松的目的.为更深刻地认识和探讨运动与原发性骨质疏松的关系,笔者从运动防治原发性骨质疏松的机制方面就五禽戏与原发性骨质疏松症相关研究进行综述.     

资阳地区定量超声跟骨骨量测定的流调分析

目的调查四川资阳地区健康人群骨密度值及骨质疏松患病率,为骨质疏松的诊断和防治提供科学依据。方法对资阳地区人群亚群抽样1976例,应用日本FURUNO公司生产的超声骨量测定仪CM100测试受试者的右跟骨的超声速度(SOS)值。结果男女骨量峰值(PBM)均出现在20～39岁组,随年龄增加骨量逐渐下降。女性50岁以后骨量丢失明显加快,60～69岁年龄组骨量丢失最快;男性70岁以后骨量丢失明显加快。80岁以前各年龄组女性骨量丢失明显高于男性,80岁以后男性骨量丢失高于女性,但累计骨量丢失女性仍明显高于男性。结论骨量随年龄增长而下降,骨质疏松发病率也随之增加。女性骨量丢失明显高于男性,女性骨质疏松发病率也明显高于男性。     

航天员中长期飞行骨骼健康管理研究现状

骨质疏松是航天员太空飞行后面临的主要健康威胁之一。中长期飞行会对航天员骨骼健康带来明显影响。1个月的太空飞行骨丢失量相当于绝经后妇女1年的丢失量。目前对失重后骨质疏松的研究和评估方法主要是骨密度、定量CT、有限元分析和生物力学测定。骨丢失的对抗性措施和治疗老年性骨质疏松症类似,主要包括运动锻炼、营养补充和药物治疗等。本文概述了国内外这一领域的研究现状、骨骼健康评估方法、常用对抗骨丢失应对措施,尝试提出对我国航天员中长期飞行骨骼健康管理的初步建议。     

微重力状态下骨量丢失对抗措施的研究进展

微重力状态下骨量丢失不同于老年性骨质疏松,是一种局部力学信号转导起主导作用、并受多层次调节的复杂变化过程,是一种特殊的废用性骨质疏松和继发性骨质疏松。长期的微重力环境,骨矿盐的持续丢失是航天飞行中人类所面临的严重生理反应之一,也是妨碍人类长期太空停留和探索外星球的主要障碍之一。目前微重力环境下骨量丢失的对抗措施主要有:物理对抗、营养、药物、细胞因子与基因治疗。航天飞行中,阻力锻炼、振动、人工重力等物理对抗措施的研究较为成熟;营养措施中着重阐述维生素、矿物质、蛋白质、Ω-3脂肪酸对骨代谢的作用,各种营养物质的具体摄入量仍有待规范;药物措施中双膦酸盐的使用基本得到广泛认可,其他药物的应用仍需要继续人体探索;细胞因子与基因的研究目前仍限于应用细胞进行研究。高级阻力训练系统(ARED)联合营养(部分联合双膦酸盐)是目前公认有效的对抗航天飞行中骨量丢失的措施。本文将详细阐述以上各个方面国内外的进展及争议,以及探讨未来微重力状态下骨量丢失的对抗措施的发展方向。     

姜黄素治疗骨质疏松的研究进展

姜黄素在骨质疏松的防治中具有显著的作用,可通过抑制骨髓间充质干细胞的凋亡与成脂分化,促进骨髓间充质干细胞增殖与成骨分化,促进成骨细胞增殖与分化,增强成骨细胞活力,减少成骨细胞凋亡,降低破骨细胞活性,诱导破骨细胞凋亡,抑制破骨细胞的生成、分化与骨吸收,改善骨代谢与骨小梁微观结构,减少骨量的丢失,增加骨骼的强度。但目前有关姜黄素治疗骨质疏松基本处于实验室研究阶段,姜黄素投入抗骨质疏松的临床使用仍需进一步以及更多的基础实验研究证实。综述姜黄素治疗骨质疏松的相关机制与进展,以期为姜黄素治疗骨质疏松在基础医学研究、药物临床应用以及新药物的开发等提供参考。     

Physiological Effects of Microgravity on Bone Cells

Life on Earth developed under the influence of normal gravity (1g). With evidence from previous studies, scientists have suggested that normal physiological processes, such as the functional integrity of muscles and bone mass, can be affected by microgravity during spaceflight. During the life span, bone not only develops as a structure designed specifically for mechanical tasks but also adapts for efficiency. The lack of weight-bearing forces makes microgravity an ideal physical stimulus to evaluate bone cell responses. One of the most serious problems induced by long-term weightlessness is bone mineral loss. Results from in vitro studies that entailed the use of bone cells in spaceflights showed modification in cell attachment structures and cytoskeletal reorganization, which may be involved in bone loss. Humans exposed to microgravity conditions experience various physiological changes, including loss of bone mass, muscle deterioration, and immunodeficiency. In vitro models can be used to extract valuable information about changes in mechanical stress to ultimately identify the different pathways of mechanotransduction in bone cells. Despite many in vivo and in vitro studies under both real microgravity and simulated conditions, the mechanism of bone loss is still not well defined. The objective of this review is to summarize the recent research on bone cells under microgravity conditions based on advances in the field.     

运动疗法防治骨质疏松症机制的研究进展

骨质疏松症是一类全身性、代谢性骨病，表现为持续骨量减少、骨组织微结构退变，骨的强度降低，继发骨脆性增加，引起疼痛和驼背等症状，并能极易出现病理性骨折的疾病。合理适当的运动有助于改善骨质流失而防治骨质疏松症。为更加清晰地认知运动疗法防治骨质疏松的理论基础，以帮助指导临床制定更为合理的运动治疗处方，更好发挥其防治骨质疏松症的优势，本文详细介绍了中西运动疗法在防治骨质疏松症的作用机制。例如西医注重运动机械应力对骨骼的效应作用、运动对钙的调节效应作用、运动诱导细胞调节因子、激素的变化对骨代谢的作用、运动对骨代谢信号通路的调节作用以及其他新陈代谢作用；中医则认为其病因病机主要是与肾、脾、肝三脏的关系，传统中医导引运动疗法防治骨质疏松的作用机制正是通过功法由外到内的调理三脏。中医运动疗法-导引功法与西医运动疗法比较更适合在我国的推广，临床应用中更具有独特的优势，以发挥其“简、便、廉、效”的目的。     

中药调控Notch信号通路治疗骨质疏松症的研究

骨质疏松症（osteoporosis,OP）作为临床骨科方面常见的骨代谢性疾病，其发病原因主要是由于成骨细胞与破骨细胞共同介导的骨形成与骨吸收失去动态平衡关系所致，造成机体单位体积内的骨量减少、骨密度下降以及骨微结构改变，从而导致OP的发生和发展。机体内的骨代谢过程受多条信号传导通路的调控，神经源性位点缺口同源蛋白（Notch）信号通路作为重要的骨重建通路在调控与维持骨代谢稳定方面发挥着至关重要的作用，通过影响其通路蛋白的表达量，可以直接或间接地调控相关骨细胞的增殖、分化和凋亡，从而维持“骨平衡”的动态关系。近年来，运用中医药手段防治OP在临床上取得了良好的疗效，海内外学者对中药调控Notch信号通路防治OP的作用机制进行了多层次、多维度的探究，发现中药、Notch信号通路和OP三者之间存在明显的相关性。基于此，本文通过对中药单体及复方调控Notch信号通路防治OP的相关研究文献进行收集，整理、分析并总结目前的研究现状，以期为中药防治OP提供参考，为新药的研发和中医药特色诊疗方法的应用提供新的思路。     

网络药理学在中医药防治骨质疏松症中的应用进展

随着人口老龄化程度的加剧,骨质疏松症已成为全球所面临的重要公共卫生难题。西医针对骨质疏松症的治疗,主要围绕骨吸收与骨形成之间的失衡状态展开,以抑制骨吸收、促进骨形成两大类药物为主,同时配合骨矿化物,具有一定的局限性。立足于整体观念与辨证论治,中医药在骨质疏松症的防治中更具优势,无论是中药复方还是单味药均具有多靶点、多系统的调节作用,但具体的分子学机制尚未明确。随着大数据信息化的快速发展,将网络药理学与生物信息学相结合并运用于中药及复方的研究领域,是分析其潜在活性成分和作用靶点的有效策略。本文就近年来网络药理学应用技术在中医药防治骨质疏松领域取得的研究进展作出综述,阐明中医药防治该病的具体分子机制,以期为后续的实验研究和临床应用提供新的思路和方法。     

Mechanical Stimulation in the Form of Vibration Prevents Postmenopausal Bone Loss in Ovariectomized Rats

Physical exercise is recommended for the prevention and treatment of osteoporosis. However, its exact role and effectiveness in adulthood is unclear. While vigorous exercise of long duration enhances bone density, few adult individuals comply with such training programs. The present study evaluates the influence of nonphysiological mechanical stimulation, in the form of low intensity vibration (frequency: 50 Hz, acceleration: 2 g, 30 min/day for 5 days/week), on the prevention of bone loss in an animal model of postmenopausal osteoporosis. In the ovariectomised groups of rats a statistically significant (p < 0.05) decrease of bone density (femur and tibia) was recorded at 5 weeks postovariectomy. This effect was maintained for the 12 week duration of the study. Vibration prevented early bone loss after ovariectomy. Vibrated ovariectomised rats showed statistically significantly higher (p < 0.05) BMD values compared to those of their ovariectomised controls at 5 weeks. Vibration did not influence the bone density of the SHAM-operated rats. Although vibration increased ultimate strength (fracture load of the rat femur) in the ovariectomised rats, this finding was not statistically significant. Our data indicate that this method of safe and easily applicable vibration, in the form of a vibrating platform, is effective in preventing early postovariectomy bone loss in an animal model. Received: 16 April 1997 / Accepted: 8 April 1998     

Whole body vibration therapy in fracture prevention among adults with chronic disease

Due to various physical impairments, individuals with chronic diseases often live a sedentary lifestyle, which leads to physical de-conditioning. The associated muscle weakness, functional decline and bone loss also render these individuals highly susceptible to falls and fragility fractures. There is an urgent need to search for safe and effective intervention strategies to prevent fragility fractures by modifying the fall-related risk factors and enhancing bone health. Whole body vibration (WBV) therapy has gained popularity in rehabilitation in recent years. In this type of treatment, mechanical vibration is delivered to the body while the individual is standing on an oscillating platform. As mechanical loading is one of the most powerful stimuli to induce osteogenesis, it is proposed that the mechanical stress applied to the human skeleton in WBV therapy might be beneficial for enhancing bone mass. Additionally, the vibratory signals also constitute a form of sensory stimulation and can induce reflex muscle activation, which could potentially induce therapeutic effects on muscle strength and important sensorimotor functions such as postural control. Increasing research evidence suggests that WBV is effective in enhancing hip bone mineral density, muscle strength and balance ability in elderly patients, and could have potential for individuals with chronic diseases, who often cannot tolerate vigorous impact or resistance exercise training. This article aims to discuss the potential role of WBV therapy in the prevention of fragility fractures among people with chronic diseases.     

Role of alfacalcidiol on bone quality and immunomodulation in autoimmune disease and organ transplantation

In autoimmune diseases, as well as in organ transplantation, corticosteroids are often an obligatory part of the treatment regimen. The deleterious effect of corticosteroids on bone metabolism is well known, although still controversial [1–3]. It is easier to maintain bone mass than to restore it. Although the treatment of choice for prevention of bone loss is hormone replacement therapy, it cannot always be applied, and for many reasons compliance is low over the world. Alternative strategies to prevent bone loss are now tried out in many centers. Calcitonin and bisphosphonates are well-known antiresorbing drugs, but costs and long-term efficiency for calcitonin and fear for bone toxicity for the bisphosphonates limits their use for prevention. An attractive strategy to prevent osteoporosis is the treatment with alfacalcidiol because it is a natural product with important effects on bone metabolism in physiological and pharmacological dosages. Calcium absorption from the gut and mineralization of the bone matrix are optimalized by alfacalcidiol. The purpose of this paper is to report on our experience with alfacalcidiol concerning bone mass and quality in corticosteroid-induced osteoporosis in experimental animals and on long-term bone quality in autoimmune diseases and organ transplantation. We have studied the effects of alfacalcidiol on bone mass and quality in ovariectomized animals with and without corticosteroids. In these fundamental studies we have found that alfacalcidiol had a profound protective and curative effect not only on bone mass but also on bone quality as tested by mechanical testing, namely, impact torsional loading test of whole bones. The combination of alfacalcidiol with estrogens was less effective than alfacalcidiol, but more effective than estrogens alone [4–6] (Fig. 1).     

中药复方干预3周模拟失重大鼠骨丢失的初步研究

目的：研究中药复方对3周模拟失重大鼠骨骼改变的干预作用,初步观察模拟失重情况下,复方对钙剂（牡蛎醋酸水解物）的协同作用。方法：Wistar大鼠,雄性,30只,随机分为3组,空白组、模型组、中药组,每组10只。尾吊模拟失重3周,中药复方（含熟地黄、怀牛膝、黄芪、当归、牡蛎醋酸水解物等）水煎剂灌胃。观察中药对模拟失重大鼠血清钙与磷水平、后身骨密度、骨矿盐含量、力学强度的影响。结果：模拟失重3周后,与空白组比较,模型组血清钙磷均显著升高（P〈0.01）,后身骨密度、骨力学强度均显著降低（P〈0.01）;中药组血钙磷升高程度有减小趋势,骨密度显著提高（P〈0.01或0.05）,骨力学强度有较大改善趋势。结论：3周尾吊模拟失重可造成大鼠后身骨量显著丢失和强度下降,中药可较好地改善上述情况。单纯补充钙剂不足以对抗模拟失重所致骨丢失,复方中熟地黄、怀牛膝、黄芪、当归等可能对钙剂牡蛎起到了协同作用。     

Effects of calcitonin on animal and in vitro models of skeletal metabolism

During the 40 years since its discovery, calcitonin (CT) has been regarded primarily as an inhibitor of bone resorption and its therapeutic applications have been based on this property. A significant body of literature also indicates additional anabolic effects in animal and in vitro models. In a variety of bone loss histomorphometric models in the rat, CT, especially the salmon species, prevents or retards bone loss. In other species, similar results have been obtained, except in the beagle given human CT, in which a recent study reported increased bone resorption and bone loss. Consonant with the histomorphometric effects in several different species, bone mass (density) measured by a variety of methods increases, reversing the bone loss induced by the model. In related studies of mechanical properties, bone strength is increased by CT except in the beagle study which utilized human CT. In other species, experimentally induced fractures show either accelerated healing or heal normally, and there is no effect of CT to impair healing. Finally, studies of bone formation/mineralization strongly suggest an anabolic effect on cartilage formation, bone matrix synthetic activity, and bone growth. These animal effects are reflected by recent fracture prevention studies in humans. If its anabolic effects are ultimately found to be separable and additive to CT's basic action to inhibit bone resorption, new approaches to osteoporosis prevention, and possibly other treatment situations such as cartilage regeneration, may evolve using novel CT-like molecules.