Ⅰ型胶原蛋白对骨矿化机制的影响

骨质疏松(OP)是以低骨量和骨组织显微结构退变为特征的一种全身性骨骼疾病,伴有骨脆性增加,易于发生骨折.骨强度的问题是引起OP骨折危险性增加重要因素之一,骨强度反映骨骼的两个主要方面是骨矿密度和骨质量.骨的"质"和"量"共同决定着骨的强度,恢复骨质量,改善骨生物力学性能是当前研究骨损伤修复的热点问题.骨的胶原成分是骨质量的重要决定因素之一,本文探讨骨基质内Ⅰ型胶原蛋白结构、含量及稳定性的异常对骨微结构的退变和生物力学特性异常的影响,旨在阐述Ⅰ型胶原蛋白与OP的相关性.     

血清骨碱性磷酸酶、尿吡啶啉测定的临床应用

目的：观察中老年人骨代谢生化指标的水平，研究变化规律，探讨与骨量变化的关系，并观察骨质疏松抗吸收治疗后的变化。方法：应用酶联免疫吸附法（ELISA）测定血清骨碱性磷酸酶（B－ALP）、尿吡啶啉（PYD），其中健康组488例，骨量减少组32例，骨质疏松组68例，骨质疏松治疗6个月后再次测定其含量。结果：女性血清骨碱性磷酸酶高于男性，女性50岁后各组明显高于40岁组。尿吡啶啉女性明显高于男性，男性随着增龄，有上升趋势。骨质疏松组B－ALP和PYD明显升高，阿伦膦酸钠治疗6个月后明显下降。结论：原发性骨质疏松的骨吸收指标明显升高，骨形成指标也升高，中老年人大多为高转换的骨质疏松。B－ALP和PYD是骨质疏松研究中有价值的生化指标。     

骨质量与骨质疏松性骨折

骨质疏松症是一种以骨量低下和骨微结构破坏导致骨脆性增加,易发骨折为特征的疾病。骨质疏松的主要合并症——骨折是骨强度降低的结果。骨强度取决于骨骼的矿物质含量和质量。双能X线骨密度测量仪(DXA)测出的骨密度(BMD)是骨质疏松症的诊断标准,可反映骨矿物质含量。其他一些影响骨强度的特性被称为骨质量。骨质量包括骨重建(骨转换)、骨几何学、骨微结构、骨基质、骨矿化、骨胶原、骨微损伤及其修复等。骨质量从以上各个方面影响骨质疏松性骨折。本综述旨在更新骨质量的相关内容,包括骨质量与生物力学的关系及其如何影响骨质疏松性骨折。     

糖尿病性骨质疏松的评价与对策

Pommer在1885年首先提出骨质疏松（osteoporosis，OP），但直到1990年在丹麦举行的第三届国际骨质疏松研讨会，以及1993年在香港举行的第四届国际骨质疏松研讨会上，OP才有了明确的定义，并得到世界的公认：是一种以骨量减少、骨的微观结构退化为特征的，致使骨的脆性增加以及易于发生骨折的一种全身性骨胳疾病。     

糖尿病性骨质疏松的评价与对策

Pommer在1885年首先提出骨质疏松（osteoporosis，OP），但直到1990年在丹麦举行的第三届国际骨质疏松研讨会，以及1993年在香港举行的第四届国际骨质疏松研讨会上，OP才有了明确的定义，并得到世界的公认：是一种以骨量减少、骨的微观结构退化为特征的，致使骨的脆性增加以及易于发生骨折的一种全身性骨胳疾病。     

骨质疏松及骨矿盐疾病诊疗指南(讨论稿)

原发性骨质疏松症诊治指南一、概述骨质疏松症(Osteoporosis,OP)是一种以骨量低下,骨微结构破坏,导致骨脆性增加,易发生骨折为特征的全身性骨病(世界卫生组织,WHO)。2001年美国国立卫生研究院(NIH)提出骨质疏松症是以骨强度下降、骨折风险性增加为特征的骨骼系统疾病,骨强度反映了骨骼的两个主要方面,即骨密度和骨质量。该病可发生于不同性别和任何年龄,但多见于绝经后妇女和老年男性。骨质疏松症分为原发性和继发性两大类。原发性骨质疏松症又分为绝经后骨质疏松症(Ⅰ型)、老年性骨质疏松症(Ⅱ型)和特发性骨质疏松(包括青少年型)3种。…     

炎症在骨质疏松发生中的作用与机制研究新进展

骨质疏松症（osteoporosis,OP）是最常见的骨代谢疾病,以骨量低下、骨微结构破坏为特征,容易导致骨折。据2008年IOF（国际骨质疏松基金会）统计,全球约有2亿骨质疏松患者,     

乙型肝炎肝硬化骨代谢异常的临床研究

目的探讨乙型肝炎肝硬化患者骨代谢异常的发病机制。方法用NM-300单光子骨密度测量系统检测61例乙型肝炎肝硬化患者的骨密度，空腹抽血检测血清钙调节激素：1，25二羟维生素D3[1，25（OH）2D3]、甲状旁腺素（PTH）、降钙素（CT）、骨钙素（BGP），白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子α（TNF α）、尿骨胶原交联（Corsslaps），并与30名健康者对照。结果肝硬化组尺骨密度、桡骨密度、尺桡密度均较对照组明显降低。肝硬化组血清1，25（OH）2D3、BGP水平较对照组明显降低，其中骨质疏松（OP）组较无骨质疏松（NOP）组降低更明显，尿Crosslaps水平肝硬化组较对照组明显升高，其中OP组较NOP升高更明显。血清1，25（OH）2D3、BGP水平与尺桡密度呈正相关。OP组尿Crosslaps水平与尺桡密度呈负相关，而NOP组尿Crosslaps水平与尺桡密度无相关关系。肝硬化组血清IL-1β、IL-6、TNF α水平较对照组明显升高。血清IL-1β、IL-6、TNF α水平肝硬化OP组较NOP组显著升高。肝硬化组IL-1β、IL-6、TNF α水平与尺桡密度呈负相关，其中OP组较NOP组相关性更明显。结论乙型肝炎肝硬化患者存在着骨形成减少和骨破坏过多两种因素，从而引起肝性骨病，在骨形成减弱的过程中1，25（OH）2D3起了主要作用，在骨吸收增强的过程中IL-1β、IL-6、TNF α起到了重要的作用。     

老年性骨质疏松临床常用钙制剂的研究进展

<正>骨质疏松(OP)是一类以骨量低、骨组织微结构恶化导致骨脆弱性增强、易发生骨折风险为特征的疾病^[1]。该疾病分为原发性OP和继发性OP两大类。其中，原发性OP包括绝经后OP(Ⅰ型)、老年OP(Ⅱ型)和特发性OP(包括青少年型)。继发性OP是指任何影响骨代谢疾病和(或)药物及其他明确病因导致的骨质疏松。该病发病隐蔽性强，早期通常无明显症状，发生骨折后经X线检查或骨密度检查等后方被确诊。     

绝经后2型糖尿病患者骨质疏松影响因素及骨转换特点

目的 探讨绝经后2型糖尿病(T2DM)人群骨质疏松影响因素及骨转换特点及其防治策略.方法 150例绝经后T2DM住院患者测定骨密度(BMD)后分为骨量正常(NP)、骨量减低(DP)和骨质疏松(OP)组.登记年龄(Age),绝经年限(LOP),糖尿病病程(YSM),计算体重指数(BMI),测定空腹血糖(FPG)、餐后2 h血糖(PPG),空腹胰岛素(FIns)、餐后2 h胰岛素(2 h Ins),血Ⅰ型胶原C端肽(CTX-Ⅰ)、抗酒石酸酸性磷酸酶5b(TRACP5b)、骨特异性碱性磷酸酶(BALP)、雌激素(E2).结果 ①绝经后T2DM人群OP发病率54%;②绝经后T2DM并发OP患者与骨量减少和骨量正常组比较绝经年限、糖尿病病程及血糖水平明显增高,胰岛素和E2水平明显降低(P<0.05);③OP组患者与骨量减少和骨量正常组比较CTX-Ⅰ、TRACP5b、BALP等骨转换指标明显升高(P<0.05);④CTX-Ⅰ与腰椎2～4、股骨颈BMD呈明显负相关(P<0.05),与大转子、粗隆间BMD无明显相关性;TRACP5b、BALP与腰椎2～4、股骨颈、大转子、粗隆间BMD呈明显负相关(P<0.05).结论 LOP、血糖、YSM、FIns和E2水平可影响绝经后T2DM患者骨量;该人群骨重建特点为高转换型,骨吸收标记物TRACP5b可作为早期预测绝经后T2DM骨量减少及OP的敏感指标.     

Adolescence: the period of dramatic bone growth

Adolescence is a period of rapid skeletal growth during which nearly half of the adult skeletal mass is accrued. This life stage is a window of opportunity for influencing peak bone mass and reducing the risk of osteoporosis later in life. Endocrine factors that may influence peak bone mass include insulin-like growth factor-1, which regulates skeletal growth, and gonadotropic hormones, which stimulate epiphyseal maturation. Estrogen deficiency and amenorrhea can reduce skeletal mass. Weight-bearing exercise can increase bone mass. Appropriate mineralization of the skeleton requires adequate dietary intakes of minerals involved in the formation of hydroxyapatite; the most likely to be deficient is calcium.     

Low bone mass in children and adolescents

Osteoporosis is a disease characterized by low bone mass and micro architectural alterations of bone tissue leading to enhanced bone fragility and increased fracture risk. Although research in osteoporosis has focused mainly on the role of bone loss in the elderly population, it is becoming increasingly clear that the amount of bone that is gained during growth is also an important determinant of future resistance to fractures. Thus, considerable interest is being placed on defining preventive strategies that optimize the gain of bone mass during childhood and adolescence. Knowledge of the determinants accounting for the physiologic and genetic variations in bone accumulation in children will provide the best means toward the early diagnosis and treatment of osteoporosis. This article reviews the techniques available for bone mass measurements in children and the major determinants and diseases influencing bone accretion during childhood and adolescence.     

Metabolic bone disease and bone quality

On the progress of study concerned with pathology of metabolic bone disease such as osteoporosis, it has been known that most of bone strength can be explained by bone volume. As bone volume can be determine by bone mineral density (BMD) with dual-energy X-ray absorptiometry (DXA), it has been widely used for diagnosis of osteoporosis or efficacy of treatment. However, with the advance of bone morphometry, decrease of bone strength or existence of insufficiency fracture is influenced by not only loss of BMD but also deterioration of bone quality especially bone microstructure. In this chapter, we will give an outline of change of bone quality in metabolic bone disease.     

Osteoporosis and bone quality referred in NIH consensus 2000

National Institute of Health Consensus Development Conference Statement 2000 included four main items. They were;definition of osteoporosis and fracture risk, different fracture risks among different segments of the population, factors for building and maintaining skeletal health throughout life, and evaluation and treatment of osteoporosis. It is clearly documented in the statement that bone strength reflects the integration of bone density and bone quality, and that evaluation of fracture in osteoporosis should depend on risk-based assessment rather than solely on the assessment of a BMD T-score. These issues indicate a new direction in the management of osteoporosis in near future.     

Calcium and peak bone mass.

On the basis of previous epidemiological, clinical and experimental studies, it was demonstrated that adequate calcium intake during growth may influence peak bone mass/density, and may be instrumental in preventing subsequent postmenopausal and senile osteoporosis. Calcium intake during adolescence appears to affect skeletal calcium retention directly, and a calcium intake of up to 1600 mg d-1 may be required. Therefore, adolescent females at the time of puberty probably represent the optimal population for early prevention of osteoporosis with calcium. Young individuals must be in positive calcium balance to provide the calcium necessary for skeletal modelling and consolidation, but the degree of positive balance required to achieve peak bone mass and density is unknown. To assess calcium requirements in young individuals, and also to evaluate the determinants of calcium metabolism during the period of acquisition of peak bone mass, 487 calcium balances from previously published reports have been collected and analysed according to developmental phase and calcium intake. The results of this analysis showed that calcium intake and skeletal modelling/turnover are the most important determinants of calcium balance during growth. The highest requirements for calcium are during infancy and adolescence, and then during childhood and young adulthood. Infants (adequate vitamin D supply) and adolescents have higher calcium absorption than children and young adults to meet their high calcium requirements. Calcium absorption during the periods of rapid bone modelling/turnover is probably mediated by Nicolaysen's endogenous factor. Urinary calcium increases with age, and reaches a maximum by the end of puberty. The results also show that calcium intake has little effect on urinary calcium excretion during the period of most rapid skeletal formation: a weak correlation is present in children and young adults. On the basis of the above studies it was suggested that the RDA for calcium should be higher than currently established for children, adolescents, and young adults, in order to ensure a level of skeletal retention of calcium sufficient for maximal peak bone mass. In addition to nutrition, heredity (both parents) and endocrine factors (sexual development) appear to have profound effects on peak bone mass formation. Most of the skeletal mass will be accumulated by late adolescence, indicating early timing of peak bone mass.     

Biochemical markers of bone turnover

Recent developments in biomarkers in many fields of medicine have expanded the array of tools health care providers can use today for disease management. Essentially, biomarkers assist clinicians today in four main ways: screening, diagnosis, assessment of severity or risk, and monitoring of, or deciding on, treatment (1). Surrogate markers known as biochemical markers of bone turnover have been used for decades in the management of diseases of the skeleton. Historically, bone biomarkers required 24-h urine collections, lacked accuracy and reliability, and were cumbersome to use. More recently, they have been shown to be effective surrogates for assessments of treatment response and efficacy in osteoporosis. Although used extensively in research and development and in metabolic bone disease clinics, they are still infrequently used tools for osteoporosis management in clinical practice. Today they have been incorporated into the assessment and management of a variety of diseases of bone including complex metabolic bone disorders, osteoporosis, Paget's disease of bone, and skeletal metastases. Developments in the last decade have greatly enhanced their performance characteristics. A variety of tests and assays are now widely available and significantly more accurate and reliable measures of bone metabolism have been developed. However, techniques and assays vary substantially. In order to maximize their clinical usefulness, an understanding of their strengths and weaknesses, factors that influence them, and knowledge of their unique intricacies is crucial for the ordering physician during the decision-making process. As the field continues to develop, more specific markers and standardization of measurement techniques will enhance reliability, which facilitate their use in practice. The aim of this review is to increase knowledge of the variety of tests available, their potential and limitations, and current best practice for practitioners and researchers, focusing primarily on their use in the management of osteoporosis.     

类风湿关节炎患者骨密度及骨矿物质含量的变化及意义

目的探讨类风湿关节炎(RA)患者骨密度(BMD)及骨矿物质(BMC)含量的变化及意义。方法选择71例RA患者(RA组)及20例正常人(对照组),采用双能X线骨密度仪检测各组前臂BMD、BMC含量,魏氏法检测血沉(ESR),免疫比浊法检测血清C反应蛋白(CRP),速率散射比浊法检测类风湿因子(RF),ELISA法检测抗环瓜氨酸肽抗体(ACCP);同时进行X线分期,计算患者疾病活动分数(DAS28)。结果 RA组前臂BMD、BMC均低于对照组(P均<0.01),ESR、CRP、RF、ACCP均高于对照组(P均<0.01)。Pearson’s相关分析显示,前臂BMD与DAS28、ESR、RF呈负相关(r分别为-0.357、-0.390、-0.255,P<0.05或<0.01),前臂BMC与DAS28、ESR呈负相关(r分别为-0.344、-0.401,P均<0.01)。多元线性回归分析显示,前臂BMD与RF、年龄呈负相关(T分别为-7.544、-3.254,P均<0.01);前臂BMC与DAS28呈负相关(T=-4.44,P<0.01)。RA组中X线分期为Ⅰ期的有15例,其中BMD示骨质疏松6例、骨量减少2例。结论 RA患者BMD、BMC含量明显减少,其含量减少与RA活动密切相关;RF可能是导致RA骨量丢失的危险因素;BMD检测能更早反映RA患者的骨量丢失情况。     

Handgrip Strength is an Independent Predictor of Distal Radius Bone Mineral Density in Postmenopausal Women

Several cross-sectional studies have reported a positive correlation between muscle strength and local bone mineral density. However, very few studies have evaluated the possible role of confounding variables, which may be substantial as both bone mineral density and muscle strength are multifactorial variables. We studied 140 postmenopausal women who underwent their first osteodensitometry in our hospital. Of these, 102 women affected neither by bone diseases apart from primary osteoporosis nor treated with drugs affecting bone mass were selected. Distal radius bone mineral density of the non-dominant arm was assessed by dual photon absorptiometry. Handgrip strength was measured by a handheld dynamometer. The following factors influencing bone mass were also considered: age, years since menopause, years of cyclic ovarian activity, body weight, body height, body mass index, and both calcium and alcohol dietary intake. Statistical evaluation was performed by stepwise multiple regression analysis. This showed that only two variables were independently related to bone mineral density: handgrip strength (which was the best bone density predictor among the studied independent variables) and years since menopause. R² value was 0.43 (F=38.04, p<0.001). All the other variables studied were not significantly related to bone density when the effects of both strength and years since menopause were considered. In conclusion, the data showed that handgrip strength was a strong independent predictor of distal radius bone mineral density in postmenopausal women. Clinical assessment of osteoporosis risk factors, including muscle strength, is recommended: although it is not an adequate substitute for bone densitometry, it can help clinicians to identify the risk groups at which to direct bone density measurement. Received: 1 October 1999 / Accepted: 29 May 2000     

Differential effects of intermittent and continuous administration of parathyroid hormone on bone histomorphometry and gene expression

A mechanism explaining the differential skeletal effects of intermittent and continuous elevation of serum parathyroid hormone (PTH) remains elusive. Intermittent PTH increases bone formation and bone mass and is being investigated as a therapy for osteoporosis. By contrast, chronic hyperparathyroidism results in the metabolic bone disease osteitis fibrosa characterized by osteomalacia, focal bone resorption, and peritrabecular bone marrow fibrosis. Intermittent and continuous PTH have similar effects on the number of osteoblasts and bone-forming activity. Many of the beneficial as well as detrimental effects of the hormone appear to be mediated by osteoblast-derived growth factors. This hypothesis was tested using cDNA microgene arrays to compare gene expression in tibia of rats treated with continuous and pulsatile administration of PTH. These treatments result in differential expression of many genes, including growth factors. One of the genes whose steady-state mRNA levels was increased by continuous but not pulsatile administration was platelet-derived growth factor-A (PDGF-A). Administration of a PDGF-A antagonist greatly reduced bone resorption, osteomalacia, and bone marrow fibrosis in a rat model for hyperparathyroidism, suggesting that PDGF-A is a causative agent for this disease. These findings suggest that profiling changes in gene expression can help identify the metabolic pathways responsible for the skeletal responses to the hormone.     

Puberty and bone development

Puberty has a key role for bone development. Skeletal mass approximately doubles at the end of adolescence. The main determinants of pubertal gain of bone mass are the sex steroids, growth hormone and insulin-like growth factors (by their effects on bone and muscle mass), 1,25-dihydroxyvitamin D (by stimulating calcium absorption and retention) and muscle mass (by regulating modelling/remodelling thresholds). Calcium intake is an additional factor influencing bone formation. The interactions among these factors are undefined. The accrual of bone mass during puberty is a major determinant of peak bone mass and, thereby, of the risk of osteoporotic fractures during advanced age.