中医药从脾论治骨质疏松症

摘要：中医药防治骨质疏松症是医学领域研究的热点，临床从脾、肾论治多获良效，其机制研究也逐渐开展。脾虚是骨质疏松症发病的基础，益气健脾法以“资四肢形骸、丰肌肉筋骨”为旨，在缓解临床症状、改善骨密度、调节骨代谢平衡等方面具有显著作用。愈来愈多的基础研究表明，益气健脾法可通过调节内分泌、神经、运动、消化、循环等系统发挥抗骨质疏松作用。为进一步挖掘从脾论治骨质疏松症的临床价值与科学内涵，笔者从中医经典理论、临床研究与基础实验方面综述益气健脾法抗骨质疏松的疗效及可能机制，以期拓宽中医药防治骨质疏松症的研究思路。     

从肝论治甲亢性骨质疏松的相关性探讨

甲亢性骨质疏松是因甲状腺激素过多引起机体骨代谢及骨矿化紊乱而导致的继发性疾病,随着社会的节奏不断加快,其发病率也逐年升高。因其沉默性发病,临床上常常出现漏诊、误诊,耽误了治疗的最佳时机,使病情加重,病程延长,故早诊断、早治疗是治疗此病的关键。对于其治疗,现代医学尚无明确治疗方案和早期干预手段,中医药治疗甲亢性骨质疏松具有充分优势,《黄帝内经》认为"肝藏血主疏泄,调畅气机,以强筋骨",提示气血的运行、筋骨的生长与肝的疏泄功能密切相关。但目前临床治疗多集中在"肾为先天主骨生髓"方面,忽视了"从肝论治"在甲亢性骨质疏松防治中的重要性。本文旨在从中西医角度探讨"从肝论治"甲亢性骨质疏松临床研究的相关性,为甲亢性骨质疏松的防治诊疗提供新思路。     

糖尿病骨质疏松症相关问题探讨

糖尿病性骨质疏松是由于糖尿病患者胰岛素绝对或相对缺乏引起机体糖、蛋白质、脂肪代谢紊乱，钙、磷、镁等微量元素代谢障碍导致的骨矿物质含量减少，甚至出现病理性骨折的代谢性骨病。研究认为，胰岛素缺乏或组织对胰岛素敏感性降低是糖尿病性骨质疏松的基本原因。1948年Albright首先报告了长期控制不良的糖尿病病人可以发生骨质     

1型糖尿病骨质疏松大鼠模型的建立及评价

目的建立I型糖尿病性骨质疏松大鼠模型,通过骨形态计量学观察该模型的改变。方法选取3月龄雄性SD大鼠60只,随机分为正常对照组(30只)和造模组(30只),造模组腹腔注射STZ60 mg/kg,诱导建立I型糖尿病性骨质疏松大鼠模型。结果从血糖、体重、骨密度、骨组织形态计量学证实该方法可以成功制备1型糖尿病性大鼠模型。结论该方法制备的I型糖尿病性骨质疏松大鼠模型,成模率高,模型稳定。     

糖尿病大鼠骨质疏松发病过程中骨桥蛋白变化的实验研究

目的 研究糖尿病大鼠骨质疏松发病过程中骨桥蛋白的表达。方法 24只雄性Wistar大鼠随机分成2组，糖尿病大鼠组12只，空白对照组12只，饲养4月后处死动物，检查骨桥蛋白mRNA水平表达。 结果 糖尿病组骨桥蛋白总RNA提取及RT-PCR、琼脂糖凝胶电泳显示，糖尿病组大鼠在骨质疏松发病过程中，骨桥蛋白在骨组织中高表达，与空白对照组相比，差异具有显著性。 结论 骨桥蛋白在糖尿病大鼠骨组织有显著性改变，推测骨桥蛋白参与调节骨质疏松发病过程。     

2型糖尿病性骨质疏松降糖药物的选择

近年来,随着对糖尿病性骨质疏松研究的深入,2型糖尿病性骨质疏松降糖药物的选择也越来越引起人们的重视。肠促胰素、二甲双胍、胰岛素促泌剂等在抑制骨吸收、促进骨合成及诱导骨髓间充质细胞分化等多个层面上对2型糖尿病性骨质疏松可能有正面影响。胰岛素对骨质疏松的影响虽然有争议,但早期持续胰岛素治疗对糖尿病性骨质疏松的发生和发展可能具有控制和延缓作用,噻唑烷二酮类药物可显著增加2型糖尿病女性患者骨折发生率。     

糖尿病性骨质疏松

随着我国改革开放,经济的发展,人民生活水平的提高,人口寿命的增长和老龄人口的增多,目前我国己步入老龄化社会,许多与老年有关的疾病如2型糖尿病、骨质疏松等呈逐年增多,已成为当今世界广泛关注的严重社会问题之一。糖尿病性骨质疏松属于继发性骨质疏松,其在糖尿病患者并发症中发病率较高,关注糖尿病性骨质疏松对于提高老年人的健康水平和生活质量具有重要的意义。1严重后果不容忽视糖尿病性骨质疏松在国内外得到了广泛的研究,在骨质疏松的一些专著[1,2]和大量医学论文都对其进行过报道,尽管如此,但是人们对其的危害性认识还是不够的。骨质…     

糖尿病性骨质疏松症药物治疗研究

糖尿病性骨质疏松症药物治疗研究李兰，白纪香，雷琨，杨平安，陈素芳，周倜，张效春随着糖尿病治疗药物的应用，糖尿病的合并症骨质疏松也逐渐增多，我们对１９８８年～１９９４年门诊及住院患者进行了前瞻性研究。诊断标准：１６６例糖尿病患者按１９８０年ＷＨＯ标准均...     

间充质干细胞源性外泌体在糖尿病性骨质疏松中的研究进展

糖尿病性骨质疏松是糖尿病常见的并发症之一,是在糖尿病基础上继发的以骨量减少、骨脆性增加、骨折风险增加为主要特征的代谢性骨病.常规的抗骨质疏松药物对糖尿病性骨质疏松的疗效有限,存在增加非典型骨折的风险,因此亟待寻找新的积极高效的治疗手段.外泌体是一类包含蛋白质、脂质、核酸等物质的胞外囊泡,介导细胞间通讯发挥对靶细胞的生物...     

女性2型糖尿病骨质疏松的影响因素

糖尿病与骨质疏松是多发病及老年常见病,糖尿病性骨质疏松是一种继发性骨质疏松,是糖尿病在人体骨骼系统出现的严重并发症,对患者、家庭、社会带来沉重负担,目前对女性2型糖尿病患者的骨密度水平及骨质疏松的风险认识仍有争论,研究显示其骨密度值较对照组降低[1]、相似[2]或增高[3,5].下面结合国外文献,就影响女性2型糖尿病骨质疏松的相关因素作一简介.     

Osteoporosis in diabetes mellitus: Possible cellular and molecular mechanisms

Osteoporosis,a global age-related health problem in both male and female elderly,insidiously deteriorates the microstructure of bone,particularly at trabecular sites,such as vertebrae,ribs and hips,culminating in fragility fractures,pain and disability.Although osteoporosis is normally associated with senescence and estrogen deficiency,diabetes mellitus(DM),especially type 1 DM,also contributes to and/or aggravates bone loss in osteoporotic patients.This topic highlight article focuses on DM-induced osteoporosis and DM/ osteoporosis comorbidity,covering alterations in bone metabolism as well as factors regulating bone growth under diabetic conditions including,insulin,insulin-like growth factor-1 and angiogenesis.Cellular and molecular mechanisms of DM-related bone loss are also discussed.This information provides a foundation for the better understanding of diabetic complications and for development of early screening and prevention of osteoporosis in diabetic patients.     

Immunodeficiency as primary phenotype of diabetes mutation db. Studies with coxsackievirus B4

Restriction of food intake (R) in the C57BL/KsJ db/db diabetic mutant mouse prevents phenotypic expression of diabetes, whereas ad libitum feeding (AL) results in spontaneous diabetes. Previous results showed that coxsackievirus B4 (CB4)-infected genetically identical db/db mice with and without diabetes could be distinguished by the levels of CB4-neutralizing antibody and virus-specific antibodies as determined by enzyme-linked immunosorbent assay and the numbers of splenic antibody-forming cells. Our results show that the diabetic genotype db/db R was deficient in total spleen lymphocytes and lymphocyte subsets and was unable to produce agglutinating antibody to sheep erythrocytes (SRBCs) or specific antibody to noninfectious CB4. The db/db AL mutant expressing the diabetic phenotype was not as deficient in spleen cell parameters. The response to noninfectious CB4 was delayed but substantial. The db/db AL mouse was also unique with its higher agglutinating antibody levels after virus infection than its uninfected control or the infected or uninfected db/db R mouse. In vitro SRBC immunization of spleen lymphocytes determined that this enhanced response was largely dependent on the diabetic milieu and was not a property of the cells. Genetic predisposition to diabetes is characterized by immunodeficiency as evident from inadequate levels of antibodies to infectious or noninfectious antigens and absolute and relative deficiency in spleen lymphocyte subsets and total numbers of spleen cells. Phenotypic expression of diabetes results in partial amelioration of the immunodeficiency evident in diabetic genotype db/db R without disease.     

原发性骨质疏松症的中医证素辨证法

目的原发性骨质疏松症包括绝经后骨质疏松症(Ⅰ型)、老年骨质疏松症(Ⅱ型)以及特发性骨质疏松症,以Ⅰ、Ⅱ型为高发。探讨Ⅰ、Ⅱ型骨质疏松症与证素辨证法的相关性,推动中医辨证法的返本与开新。方法按照中西医结合诊断标准,将随机选取的100例Ⅰ、Ⅱ型骨质疏松症患者进行证素辨证法的临床观察,探索病位、病性证素与Ⅰ、Ⅱ型骨质疏松症,以及患者疼痛程度与证素之间的相关性。结果Ⅰ型骨质疏松症患者的病位在肾者人数最多,占Ⅰ型中总人数的59%;其次是脾,占50%;再次是肝,占41%。Ⅱ型骨质疏松症中病位在肾者最多,占Ⅱ型总人数的75%;其次是肝,占46%;再次是脾,占32%。Ⅰ型骨质疏松症中的病性证素例数分级:阴虚阳虚寒或痰或湿血瘀气滞。Ⅱ型骨质疏松症中的病性证素例数分级:阳虚气滞阴虚血瘀寒或痰或湿。疼痛程度是在肝、血瘀上痛势最重,在脾、阴虚中痛势较缓。在阳虚、寒痰湿中痛势尚可。结论根据证素辨证排列组合,Ⅰ型骨质疏松症以肾阴虚、脾肾阳虚更常见。Ⅱ型骨质疏松症患者以肾阴阳两虚、肝气郁滞等为多发。骨质疏松症疼痛程度在肝、血瘀上痛势最重,在脾、阴虚中痛势较缓。说明了Ⅰ、Ⅱ型骨质疏松症与证素辨证法有很强的相关性,将二者结合为疾病诊疗提供新的思路方法,为部分揭示证素辨证法的科学内涵提供理论基础。     

原发性骨质疏松症的中医辨证诊治进展

近年来骨质疏松症的中医辨证施治的规范化研究取得了长足的进步,中医认为骨质疏松症的发生与肾虚、脾虚、肝虚、血瘀密切相关,目前学界普遍比较接受的骨质疏松症的中医辨证分型是：肾阳虚证、肝肾阴虚证、脾肾阳虚证和血瘀气滞证,并按该分型进行辨证施治取得了良好的临床疗效。笔者就原发性骨质疏松症的中医辨证分型与治疗方面的规范化研究进展作一综述。     

从肝脾肾探讨原发性骨质疏松症与老年衰弱综合征

骨质疏松症(osteoporosis, OP)是一种全身代谢性骨病，随着我国人口老龄化进程的发展，原发性OP和老年衰弱综合征成为目前常见的两种老年疾病。在中医理论方面，原发性OP以肾虚为本，脾虚为源，肝虚为关键，衰弱多由于老年人五脏俱虚，脾肾尤甚，二者有部分相同的病机。从分子生物学角度，二者在钙磷调节激素、外泌体、营养物质、炎症因子等方面均有联系。通过对相关文献的梳理和总结，从肝脾肾和分子生物学角度寻找原发性OP和衰弱之间的相同点，为后续两种疾病的预防和治疗提供理论依据。     

Investigation of the Relationship between Type 2 Diabetes and Osteoporosis Using Bayesian Inference

This study aims to determine the prevalence of Type 2 diabetes in women with osteoporosis and estimate the odds ratio (OR) of osteoporosis in women with Type 2 diabetes using Bayesian inference. This is a case-control study design that looked into prevalence of diabetes among 582 female patients who had normal bone mineral density (BMD) and 598 female patients with osteoporosis. The subjects included women at least 30 yr of age who had their BMD measured in the lumbar spine and femoral neck using dual-energy X-ray absorptiometry at a tertiary referral center in Manila, Philippines. Prevalence of Type 2 diabetes in subjects with osteoporosis is 22.41%, whereas 19.07% of the subjects with normal BMD had diabetes. The odds of developing osteoporosis is 22.54% higher for Type 2 diabetic subjects. Patients with osteoporosis were older than subjects with normal BMD by almost 10 yr. Of the diabetic osteoporotic patients, 44.78% were physically active compared with 20.72% diabetics with normal BMD. Most of the diabetics (60.36%) with normal BMD were obese, whereas majority of diabetic osteoporotics (64.93%) have normal body mass index (BMI). Less than 10% of both diabetic osteoporotics and diabetics with normal BMD have ever undergone hormone replacement therapy. Of the 598 subjects with osteoporosis, 124 (20.74%) had suffered from fragility fractures. When controlling for physical activity and BMI, the odds of developing osteoporosis was 21.73% and 53.89% higher for Type 2 diabetics, respectively. In considering all possible confounders and effect modifiers (age, physical activity, BMI, and hormone replacement therapy) in the model which made use of a diffuse normal prior distribution, the estimate for OR (Model 1) is 0.67. A separate analysis excluding modifiable confounders (Model 2) gave the measure of association an equal likelihood of diabetes being a protective factor or a risk factor. The crude OR indicated that Type 2 diabetes is a risk factor for osteoporosis. However, when identified confounders were included in the model, the direction of the relationship changed. Considering the credible intervals (95% credible interval in both models), the study concluded that diabetes is indeed a protective factor for osteoporosis. Results of the study may have potential limitations. There are sources of bias that have been identified—selection bias where patients included in the study were referred by primary care givers for a specified reason as well as misclassification and recall biases on certain information such as type and duration of physical activity. Diabetes is a protective factor for osteoporosis in this referred population of women. However, with the well-known diabetes-related factors, that is, microvascular complications, visual acuity, and risk for fall, one should still strongly consider assessing and screening for osteoporosis and fracture risk reduction in diabetic patients.     

绝经后骨质疏松症中医证型与握力的研究

目的 探讨绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)患者中医证型与握力的关系.方法 选取2017年11月至2018年10月在济南各社区及山东中医药大学附属医院骨质疏松门诊纳入的绝经后骨质疏松症女性142例(骨质疏松组)、绝经后非骨质疏松症女性39例(非骨质疏松组).依照中医辨证...     

Plasminogen Activator Inhibitor-1 Is Involved in Streptozotocin-Induced Bone Loss in Female Mice

In diabetic patients, the risk of fracture is high because of impaired bone formation. However, the details of the mechanisms in the development of diabetic osteoporosis remain unclear. In the current study, we investigated the role of plasminogen activator inhibitor (PAI)-1 in the pathogenesis of type 1 diabetic osteoporosis by using PAI-1–deficient mice. Quantitative computed tomography analysis showed that PAI-1 deficiency protected against streptozotocin-induced bone loss in female mice but not in male mice. PAI-1 deficiency blunted the changes in the levels of Runx2, osterix, and alkaline phosphatase in tibia as well as serum osteocalcin levels suppressed by the diabetic state in female mice only. Furthermore, the osteoclast levels in tibia, suppressed in diabetes, were also blunted by PAI-1 deficiency in female mice. Streptozotocin markedly elevated the levels of PAI-1 mRNA in liver in female mice only. In vitro study demonstrated that treatment with active PAI-1 suppressed the levels of osteogenic genes and mineralization in primary osteoblasts from female mouse calvaria. In conclusion, the current study indicates that PAI-1 is involved in the pathogenesis of type 1 diabetic osteoporosis in females. The expression of PAI-1 in the liver and the sensitivity of bone cells to PAI-1 may be an underlying mechanism.Type 1 diabetes is a disease in which patients have little or no insulin secretion and hyperglycemia. A decrease in bone mineral density (BMD) and a marked increase in fracture risk have been described in patients with type 1 diabetes (1,2). The detrimental skeletal effects of glucose toxicity, insulin deficiency, and diabetes complications might partly explain the association between type 1 diabetes and osteoporosis (3–5). Previous findings suggest that a decrease in osteoblastic bone formation is a major contributor to diabetic osteoporosis (4,6). However, the pathogenesis of this skeletal fragility and markers for the evaluation of bone metabolism in type 1 diabetic patients remain to be fully clarified.Plasminogen activator inhibitor (PAI)-1 functions as the principal inhibitor of plasminogen activators and, hence, fibrinolysis. PAI-1 has been of particular focus in cardiovascular disease because of strong positive correlations between serum PAI-1 levels and cardiovascular risk (7). Several reports have shown that circulating PAI-1 levels are elevated in type 1 and type 2 diabetic patients and in animal models (8,9). Furthermore, Ma et al. (10) reported that PAI-1 contributes to the development of diabetes. PAI-1 has various functions, including regulating the degradation of the extracellular matrix, cell migration, and apoptosis (11), which may be related to osteoblast differentiation and function. Daci et al. (12) previously reported that PAI-1 deficiency partially protected against bone loss in estrogen-deficient mice. These findings suggest that PAI-1 may contribute to impairment of bone remodeling and the development of osteoporosis. However, the role of PAI-1 in the pathogenesis of diabetic osteoporosis has not yet been elucidated. In the current study, we examined the effects of PAI-1 deficiency on streptozotocin-induced diabetic bone loss by using wild-type and PAI-1–deficient mice.     

中医从脾论治原发性骨质疏松症的研究进展

骨质疏松症是一种以骨量低下,骨微结构损坏,导致骨脆性增加,易发生骨折为特征的全身性骨病。当前实验研究及临床观察对原发性骨质疏松症以肾虚为主要病机,补肾为主要治法形成普遍认识,而脾虚对本病的影响研究相对较少。根据中医学对骨质疏松症病因病机特点的认识,结合现代医学对中医药治疗骨质疏松症的研究,对骨质疏松症的防治要按照中医的理法方药进行辩证论治,因证施治,不能简单地治疗某一脏一腑,要看到骨质疏松症的复杂性和难治性。从传统医学中脾对骨质疏松症的认识到脾脏与骨质疏松症关系的实验研究再到健脾补肾的临床观察,无不表明脾虚在原发性骨质疏松症的重要地位。肾虚为骨质疏松症的主要病机,补肾滋肾的治疗总则固然重要,与此同时必须要重视补益脾胃。