基于“肾痰”认识骨-脂代谢异常失衡在绝经后骨质疏松症发病中的作用

绝经后骨质疏松症（PMOP）是绝经后妇女常发生的一种全身性代谢疾病,主要表现为骨量低下、骨微结构退行性改变、骨脆性增加且极易发生脆性骨折,严重威胁着绝经后妇女的健康。现代研究表明绝经后骨代谢紊乱与脂代谢失衡常常并见,中医学则认为PMOP的发病多从肾论治。课题组长期从事PMOP的临床与基础研究工作,认为骨-脂代谢失衡是PMOP的重要发病机制,“肾痰”亦是PMOP发病的关键所在,临床论治除了补肾,还应化痰,并通过一系列实验研究证实了从“肾痰”论治PMOP的可能性。因此,本文拟基于“肾痰”探讨骨-脂代谢失衡在绝经后骨质疏松症发病中的作用,丰富中医药论治PMOP的科学内涵。     

补钙与骨质疏松症防治研究的进展

骨质疏松症的发生是一个渐进的过程,其临床表现为疼痛、驼背和骨折等。不管是原发性还是继发性骨质疏松症,均有一个共同的防治原则:延缓骨量丢失或增加骨量,对症处理和预防骨折发生。这就需要补充钙制剂。补钙与骨质疏松症防治研究主要进展包括:(1)青少年期摄入钙对其骨矿化的作用。(2)妊娠、哺乳期钙需要量与骨矿含量的关系。(3)老年人的维生素D和钙摄入。(4)缺钙与异位钙化(Cetopiccal-cification)。(5)口服钙补充剂。(6)补钙新问题。现综述如下。一、青少年时期摄入钙对其骨矿化的作用体内99.9%的钙在骨骼中,青少年骨骼生长迅速,是骨量…     

基质GLA蛋白与绝经后骨质疏松症

基质GLA蛋白（matrix gla protein MGP）是体内软骨内骨形成和血管内钙化的重要调节因子，是矿盐沉积的重要抑制物。近年来发现绝经后妇女在发生骨质疏松症的同时还常伴有血管的钙化，认为两者可能存在着密切的联系。MGP抑制血管钙化同时与骨代谢密切相关。笔者对MGP与绝经后骨质疏松症的关系进行了简要的综述。     

慢性肾脏病高磷血症所致并发症的机制及防治进展

以往认为,慢性肾脏病(CKD)患者血管钙化是由于体内钙磷代谢失衡、钙磷过饱和所致的钙盐被动沉积于细胞和细胞外基质的一个非细胞介导的过程.近年来,血管钙化的分子机制研究结果表明,细胞介导的主动调节过程在血管钙化的发生过程中占重要地位,其形成过程与骨骼的矿化相似,是一个受多因素调控的、与骨发生类似的主动的可调节过程,其中心环节是血管平滑肌向成骨细胞分化,分泌成骨细胞样基质,最终形成钙化.     

基于肠道菌群探讨中医实脾防治骨质疏松症的机制

骨质疏松的发病机制较为复杂,研究发现肠道菌群与骨代谢关系密切,影响着骨质疏松症的发病及预后。中医学认为,骨质疏松症是脾肾亏虚所致。脾为气血生化、生痰之源,脾肾先后天相互资生。脾之功能与肠道菌群的作用极为相似,两者均能资先天脏腑,益骨生髓。近年来,随着中医学的不断创新和发展,实脾类药物调节肠道菌群防治骨质疏松症的相关研究成为热点。总结肠道菌群对骨代谢的影响及实脾类药物对肠道菌群的影响,以期为中医学从脾论治骨质疏松症提供科学依据,为中医药防治骨质疏松症提供新思路。     

降钙素治疗慢性肾脏病-矿物质和骨异常的研究进展

正肾性骨病是由慢性肾脏病(CKD)导致的钙磷代谢异常、继发性甲状旁腺功能亢进、骨骼成分与结构的改变和血管及软组织钙化,是CKD的常见并发症之一。目前,学术界称之为慢性肾脏病-矿物质和骨异常(CKD-MBD),定义为由于CKD导致的矿物质及骨代谢异常综合征,临床上出现以下一项或多项表现:(1)钙、磷、甲状旁腺素或维生素D代谢异常;(2)骨转化、矿化、骨量、骨线性或骨强度异常;(3)血管或其     

骨血管内皮细胞：治疗骨质疏松症的新靶点

近期的许多研究结果显示, 骨组织血管内皮细胞对骨代谢发挥重要调节作用。骨质疏松症作为最常见的骨代谢疾病, 其发生发展过程中伴随着骨组织血管的功能异常和结构紊乱;而恢复骨血管及血管内皮细胞的正常结构和功能后, 骨质疏松症也在一定程度上得到缓解。因此, 骨血管内皮细胞有望成为防治骨质疏松症的重要靶点, 本文将介绍正常骨组织的血管内皮细胞类型、骨血管对骨代谢的调节作用以及骨质疏松病理状态下的血管结构功能异常, 重点评述近年来基于骨血管内皮细胞治疗骨质疏松症的研究进展, 以求为骨质疏松症和其他骨代谢疾病的治疗提供新思路。     

TNF-α介导绝经后骨质疏松症发病机制的研究进展

肿瘤坏死因子-α(tumor necrosis factorα,TNF-α)作为免疫系统和骨骼系统共有的细胞因子,可刺激免疫细胞活化,促进炎性因子分泌,加剧炎症反应的作用,直接或间接促进骨吸收的作用,通过多环节多途径调节绝经后骨质疏松症的发生发展,可作为监测绝经后骨质疏松症的指标,也有望成为有效治疗绝经后骨质疏松症的药物靶点。本文从免疫反应、炎症反应、氧化应激反应等三个方面分析TNF-α对骨代谢细胞、细胞因子、骨代谢环境的影响,分析TNF-α介导绝经后骨质疏松症发病的机制,为绝经后骨质疏松症的诊断与治疗及其机制研究提供一定的研究思路。     

维生素K对CKD-MBD骨代谢异常以及血管钙化的治疗及作用机制

慢性肾脏疾病矿物质和骨异常(chronic kidney disease mineral and bone disorder ,CKD-MBD)是慢性肾脏病（chronic kidney disease,CKD）的主要并发症之一,是一种全身性的矿物质和骨代谢障碍,包括钙、磷、甲状旁腺素（PTH）或维生素D代谢异常,骨转换、矿化、骨量、骨的线性生长或强度异常以及血管或其他软组织钙化,增加了CKD患者的心血管风险、骨折风险以及死亡率[1]。临床治疗上以控制钙磷平衡、降低甲状旁腺素、抑制血管钙化为主,包括使用含钙/非含钙磷结合剂、活性维生素D及其类似物、西那卡塞等。维生素K是一组脂溶性维生素,可作为γ-谷氨酰羧化酶（γ-glutamyl carboxylase ,GGCX）的辅助因子,该酶通过激活维生素K依赖蛋白（vitamin K-dependent proteins,VKDP）参与凝血因子的活化、凋亡,以及抑制血管钙化、调节骨矿化[2]。越来越多的证据表明,CKD患者患有亚临床维生素K缺乏症,补充维生素K尤其是维生素K2,可增加CKD患者骨强度、抑制血管钙化。本文将从维生素K的缺乏和补充对CKD相关矿物质和骨疾病（CKD-MBD）的影响及其作用机制、临床应用等方面进行阐述。     

肌肉、骨骼与骨质疏松专家共识

骨质疏松症已成为全球性的公共健康问题和前沿研究难题。老年人骨骼肌肉系统的衰退会造成肌肉萎缩、骨质减少,进而引起肌力减退、运动能力、平衡能力下降、步行缓慢、骨脆性增大、易骨折,最终导致老年人生活质量下降。如何从肌肉、骨骼方面研究其与骨质疏松的关系非常迫切和重要。为此,中国老年学学会骨质疏松委员会成立了肌肉、骨骼与骨质疏松学科组,组织专家编写《肌肉、骨骼与骨质疏松专家共识》,为骨质疏松症的临床诊疗和科学研究提供参考。共识认为:骨质疏松与肌肉、骨骼密切相关。骨质疏松症和肌少症存在着很多共同的风险因素。肌骨代谢生化指标可反映肌骨代谢状态,对代谢性肌肉骨骼疾病的诊断和疗效评价有指导作用。推荐使用DXA测量肌肉质量和骨密度。肌力和平衡能力评定有助于判断跌倒风险。肌肉、骨骼存在潜在的药物作用共同靶点。肌肉骨骼运动可以增加峰值骨量,调节骨代谢信号通路,促进骨形成。骨质疏松人群应注重个体化运动锻炼。中医学认为肌肉、骨骼与脾、肝、肾关系密切,骨质疏松症的病位主要在肾、脾、经络,主要与肾虚、脾虚和血瘀有关,强调骨筋肉并重,动静结合,治疗原则宜补肾、健脾、活血。     

补肾化痰方对去势骨质疏松大鼠钙沉积的影响

目的观察补肾化痰方对去势骨质疏松大鼠钙沉积的影响。方法 6月龄SD大鼠40只,随机分为4组,每组10只,即假手术组、模型组、补肾化痰组和补肾组。采用micro CT检测大鼠的骨密度((bone mineral density,BMD),酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)检测血清胎球蛋白(fetuin-A)、基质gla蛋白(matrix gla protein,MGP)水平,蛋白质印迹法(Western blot,WB)检测骨组织Fetuin-A、MGP蛋白的表达,免疫组化(immunohistochemical,IHC)检测其定位。结果与假手术组相比,模型组、补肾化痰组及补肾组的BMD均降低,血清Fetuin-A、MGP水平及骨组织Fetuin-A水平均降低,骨组织MGP水平升高,差异有统计学意义(P0.001);与模型组相比,补肾化痰组及补肾组的BMD均升高,血清Fetuin-A、MGP水平及骨组织Fetuin-A水平均升高,而骨组织MGP水平降低,差异有统计学意义(P0.001);补肾化痰组与补肾组相比较,补肾化痰组血清Fetuin-A、MGP水平升高明显,差异有统计学意义(P0.001),而两组的BMD、骨组织Fetuin-A、MGP含量则没有明显的差异(P0.05)。结论补肾化痰方能够影响血清胎球蛋白-基质gla蛋白-钙磷矿化复合物的形成,从而改善钙沉积,促进骨矿化,起到防治骨质疏松的作用。     

Disorders of bone metabolism

Bone remodelling is critical to bone health. Alterations in the normal processes and regulation impact on bone mass and bone strength. Changes may be generalized or focal and underlie many of the common disorders of bone metabolism. This article focusses on the changes in bone remodelling which underlie both the development and treatment of osteoporosis. Osteomalacia, as an example of a mineralization disorder and Paget’s disease as an example of a focal disorder of bone remodelling, are also briefly reviewed.     

Disorders of bone metabolism

Bone remodelling is critical to bone health. Alterations in the normal processes and regulation of remodelling may impact on bone mass and bone strength. Changes may be generalized or focal and underlie many of the common disorders of bone metabolism. This article focuses on the changes in bone remodelling which underlie both the development and treatment of osteoporosis. Osteomalacia, as an example of a mineralization disorder and Paget's disease as an example of a focal disorder of bone remodelling, are also briefly reviewed.     

The connections between vascular calcification and bone health

Vascular calcification, bone loss and increased fracture risk are age-associated disorders. Several epidemiological studies have suggested a relationship between vascular calcification, impaired bone metabolism and increased mortality. So far, this relationship had been under-estimated as osteoporosis and vascular calcification have been considered non-modifiable disorders of aging. Recent data suggest that this association is not simply an artefact of age, stressing that the co-incidence of vascular calcification with low bone activity and osteoporosis could be biologically linked. During the development of vascular calcification, the transition of vascular smooth muscle cells towards an osteoblast-like phenotype promotes the release of the vesicular structures and mineralization within these structures is promoted by several players, including those related to mineral metabolism, like phosphorus, calcium or parathyroid hormone, which influence either the supersaturation within the structure or the expression of osteogenic factors. However, an intriguing question is whether the presence of vascular calcification impacts bone metabolism, thus demonstrating true crosstalk between these tissues. Evidence is now emerging, suggesting that some inhibitors of the Wnt pathway, such as secreted frizzled Proteins 2 and 4 and Dickkopf related protein-1 (DKK-1), may play a role linking vascular calcification and bone loss. An additional important question to answer, from the patient's perspective, is whether or not progression of vascular calcification can be prevented or restricted and whether altering this progression we can efficiently impact patients' outcomes. Much evidence suggests that the control of the chronic kidney disease-mineral and bone disorder components, particularly serum phosphorus, are the main targets to maintain normal bone turnover and protect against vascular calcification.     

Tooth dentin defects reflect genetic disorders affecting bone mineralization

Several genetic disorders affecting bone mineralization may manifest during dentin mineralization. Dentin and bone are similar in several aspects, especially pertaining to the composition of the extracellular matrix (ECM) which is secreted by well-differentiated odontoblasts and osteoblasts, respectively. However, unlike bone, dentin is not remodelled and is not involved in the regulation of calcium and phosphate metabolism. In contrast to bone, teeth are accessible tissues with the shedding of deciduous teeth and the extractions of premolars and third molars for orthodontic treatment. The feasibility of obtaining dentin makes this a good model to study biomineralization in physiological and pathological conditions. In this review, we focus on two genetic diseases that disrupt both bone and dentin mineralization. Hypophosphatemic rickets is related to abnormal secretory proteins involved in the ECM organization of both bone and dentin, as well as in the calcium and phosphate metabolism. Osteogenesis imperfecta affects proteins involved in the local organization of the ECM. In addition, dentin examination permits evaluation of the effects of the systemic treatment prescribed to hypophosphatemic patients during growth. In conclusion, dentin constitutes a valuable tool for better understanding of the pathological processes affecting biomineralization.     

高胆固醇对骨代谢影响的研究进展

近年来,以高脂血症为代表的脂代谢异常疾病及骨代谢疾病发病率日益增高,且脂代谢异常会引发骨代谢异常。高脂血症是引发骨质疏松等骨代谢疾病的危险因素之一,对骨代谢通常起负调控作用。胆固醇又是血脂的主要成分,因此对骨代谢调节有重要影响,这种影响在分子水平上涉及多种胆固醇与成骨/破骨细胞的关系及对骨髓间充质干细胞选择性分化的调控。胆固醇与骨代谢之间的相互调节机制复杂多样,至今仍未完全阐明。因此,该文主要综述胆固醇对成骨/破骨细胞的影响及探讨其对骨代谢影响的通路机制,以明确两者间相关性的靶点,为骨代谢疾病的防治提供新的方向。     

微量元素缺乏与骨病

骨病是一类发生在骨骼、关节、肌腱及筋膜等运动系统的疾病，包括骨质疏松、骨软骨病、骨质增生硬化、股骨头坏死及骨折等。骨病的发生发展受众多因素的影响，包括遗传、环境、内分泌和营养等。除了钙、磷等常量元素及维生素与骨病的发生发展相关，体内一些微量元素也参与骨的生长发育和新陈代谢，且各种微量在骨代谢调节和骨病发生发展中发挥的作用不同。因而，体内缺乏参与骨代谢和骨再生的微量元素，使骨生长、骨吸收及骨矿物质沉积等过程紊乱，引起不同类型的骨病。本文就与骨代谢相关的微量元素在骨组织中的分布及在骨代谢调节中的作用，微量元素缺乏所致的骨病及补充微量元素对骨病的防治作用作一综述，为临床诊治微量元素性骨病提供一定的理论依据。     

脂代谢与骨代谢相关机制的研究进展

脂代谢紊乱和骨质疏松症均是代谢性疾病。近年来发现脂代谢紊乱易合并骨质疏松,研究二者的相关性,对预防与治疗骨质疏松有一定临床指导意义。骨代谢包括骨生成和骨吸收,血脂则包含总胆固醇、甘油三酯、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇等几个方面,研究脂代谢与骨代谢之间的关系,涉及到多种血脂与成骨细胞及破骨细胞的关系,关于二者相互影响的分子机理目前有了一定的研究成果,本文就二者相关性的可能机制作一综述。     

Pyrophosphate and diphosphonates in skeletal metabolism. Physiological, clinical and therapeutic aspects.

Pyrophosphate and diphosphonates produce striking results on calcium metabolism in experimental animals and man. Compounds containing P-O-P- bonds (e.g. inorganic pyrophosphate [PP-ii1 or P-C-P bonds (diphosponates) inhibit both the formation and dissolution of calcium phosphate crystals in vitro. PP-i may have a physiological function in regulating calcification and bone turnover, and obnormalities in its metabolism may occur in some human diseases notably hypophosphatasia and pseudogout. Diphosphonates inhibit ectopic calcification, and slow down resorption and bone turnover in several experimental systems in vivo. They have helped in studies of various aspects of the regulation of calcium metabolism. The diphosphonate, disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) has been shown in clinical studies to be effective against ectopic calcification particularly in myositis ossificans progressiva and in disorders of increased bone resorption such as Paget's diseases and some types of osteoporosis. -99mTechnetium complexes of EHDP, PP-i and other polyphosphates have also recently been used successfully as bone scanning agents.