特发性高钙尿与骨质疏松的研究进展

特发性高钙尿症(idiopathic hypercalciuria,IH)主要有两大危害,一则影响骨代谢,容易引起骨量减少、骨质疏松,增加骨折风险;二则影响泌尿系统,主要表现为增加患肾结石风险。高钙尿引起骨质疏松及肾结石的具体机制尚不明确。现有的研究表明核因子κB受体活化因子配体(RANKL)/核因子κB受体活化因子(RANK)/护骨素(OPG)通路激活可能是IH患者引起骨质疏松的主要机制之一。雌激素缺乏会引起尿钙升高、骨量减少,是高钙尿及骨质疏松的重要病因。高钙尿症还可能通过单核细胞趋化因子-1(MCP-1)等细胞因子的增加从而引起骨量减少。对遗传因素的研究中发现了许多与高钙尿及骨量减少相关联的基因,主要包括降钙素受体基因、瞬时感受器电位阳离子通道香草精受体5基因、维生素D受体基因。但对上述一些基因型与骨质疏松的研究存在不同的结论,而雌激素缺乏还可通过影响瞬时感受器电位阳离子通道香草精受体5基因的表达起作用,因此遗传因素可能成为未来研究的热点。     

24h尿枸橼酸定量分析在尿石症患者诊治中的意义

目的对30例含钙尿石症患者24h尿枸橼酸排泄进行了病例对照研究,旨在从病因学角度对尿石症的影响因素进行探讨,为临床诊治提供依据。方珐测定30例尿石症患者和30例正常人的24h尿枸橼酸和钙的含量,比较两组的差异;并比较低枸橼酸尿症与高钙尿症与尿石症发病的相关性。结果24h尿枸橼酸的排泄量在结石患者为（224．26±147．63）mg,显著低于正常人（434．58土280．89）mg,且性别差异具有显著性意义,男性低于女性（P〈0．05）。结石患者24h尿液中的枸橼酸／钙比值明显高于正常人（P〈0．05）。低枸橼酸尿症与尿石症发病的相关性高于高钙尿症（P〈0．05）。结论女性24h尿枸橼酸排泄量约为男性的1．4～1．6倍,建议对尿石症患者的代谢评估应考虑性别差异。在结石的代谢评估中,按照性别分类的24h尿枸橼酸／钙比值的降低可能比单纯尿枸橼酸降低更有意义。低枸橼酸尿症在尿石症的代谢评估中可能是比高钙尿症更加重要的指标。     

骨关节炎与骨质疏松的相关性研究

关于骨关节炎与骨质疏松的相关性研究已有半个世纪,两者的相关性存在很大争议,骨关节炎与骨质疏松作为两种与骨代谢相关的疾病,雌激素、NO、基因遗传、甲状旁腺激素等多种因素对其存在影响。两者均属于与人体衰老密切联系且发病机制并不相同的退行性疾病。有的研究认为两者是对立的,OA患者的BMD是普遍增高的,系列的纵向研究也发现OA患者伴BMD升高其骨折发生率反而增加。有的研究认为BMD增高可以阻止OA的疾病进展。也有一部分学者认为两者并不关联。本文通过查阅国内外近10年的文献,探讨两者的确切关系,应用于临床,使患者受益。     

护骨素基因多态性与原发性骨质疏松的研究进展

骨质疏松是一种以低骨量和骨组织微结构破坏为特征、导致骨骼脆性增加和易发生骨折的全身性疾病。在原发性骨质疏松的众多发病因素中，遗传是重要的因素。自1994年澳大利亚Morrison等首先提出维生素D受体基因多态性与骨质疏松的相关性后，近年来各国学者对骨质疏松候选基因进行了许多研究，证实了维生素D受体基因、雌激素受体基因等候选基因的多态性与骨密度、骨峰值量、骨折风险等相关，证明了基因多态性在原发性骨质疏松病因中起重要作用。     

骨质疏松与腰椎间盘退变相关性的研究进展

骨质疏松和腰椎间盘退变是骨科临床常见的退行性疾病,两者存在相似的发病机制,骨密度值反映了骨质疏松的严重程度,其与椎间盘退变程度的相关性一直是研究热点。一种观点认为骨密度值与腰椎间盘退变的严重程度呈正相关,有观点则认为是负相关,也有学者认为没有关联。本文将对近年来骨密度与腰椎间盘退变的相关性作一综述,并探讨两者之间相关联的发病机制。     

阿德福韦酯致骨痛、Fanconi综合征1例报告

Fanconi综合征(fanconi’s syndrome,FS)是由于先天或后天性因素导致近曲小管转运功能障碍,造成糖、磷酸盐、钙、尿酸、氨基酸、碳酸氢盐等从肾脏丢失,出现肾性糖尿、氨基酸尿、磷酸盐尿、尿酸盐尿、碳酸氢盐尿及肾小管酸中毒,由此引起低磷血症和低钙血症性骨病(骨质疏松、骨畸形)的一组综合征。本症的病因分为二大类,第一类是遗传性或特发性,第二类是非遗传性。现将1例服用阿德福韦酯5年多导致骨痛为首发     

泌尿系结石

本次大会共收到有关泌尿系结石论文 1 49篇 ,其中专题发言 65篇。河南作者对泌尿系结石相关因素对人肾小管细胞表达骨桥蛋白 (ＯＰＮ)及其ｍＲＮＡ的影响进行了研究 ,发现草酸钙、人甲状旁腺素、维生素Ｄ3、睾酮及雌二醇均可增加正常肾小管细胞分泌ＯＰＮ。武汉作者比较了几种实验性大鼠肾草酸钙结石模型 ,对维生素Ｄ受体基因多态性与草酸钙结石及高钙尿症的关系进行了研究 ,研究提示草酸钙结石及高钙尿症与维生素Ｄ受体基因启动子Ｆｏｋｌ基因多态性可作为鉴别尿石症病因的基因标记物。泌尿系结石临床方面 ,多篇论文从不同角度总结了ＥＳＷ…     

鹿茸生长素对维甲酸所致大鼠骨质疏松影响的实验研究

目的探讨鹿茸生长素对维甲酸所致大鼠骨质疏松的疗效作用机制.方法 Wistar大鼠60只,随机分为正常对照组、模量组、密钙息组及鹿茸生长素高、中、低剂量组各10只,用维甲酸诱导大鼠骨质疏松模型为对象,测24 h尿中总尿钙、磷、肌酐和羟脯氨酸和血浆中磷、碱性磷酸酶.并测定股骨的骨密度、骨重、骨长、骨直径、抗弯强度和骨钙含量,并对结果进行统计分析.结果经鹿茸生长素治疗后,维甲酸所致骨质疏松大鼠骨密度、骨重、骨长均有不同程度的升高,抗弯强度和骨钙含量也明显升高,与密钙息组比较差异无显著(P＜0.01),有一定量效关系,但对骨直径影响不明显.高剂量治疗组和药物对照组均能明显提高维甲酸所致骨质疏松大鼠组织的相对骨体积和平均骨小梁宽度,二者之间差异无显著性(P＜0.01).结论鹿茸生长素对维甲酸所致大鼠骨质疏有明显治疗作用.     

低钙日粮诱导蛋鸡骨质疏松模型的研究

目的建立蛋鸡骨质疏松模型,研究蛋鸡骨质疏松,为人类骨质疏松的研究提供参考。方法用低钙日粮(钙含量1.5%),连续60d诱发笼养蛋鸡骨质疏松症,并设立对照组(钙含量3.7%),分光光度法检测血清中钙、磷、碱性磷酸酶和抗酒石酸酸性磷酸酶的含量;称量蛋鸡股骨和胫骨的重量;游标卡尺测量骨骼的长度、宽度;万能材料试验机进行三点弯曲实验检测骨骼的强度;并制作观察骨组织切片进行HE染色,分析骨切片上成骨细胞、破骨细胞和骨细胞的变化。结果研究发现与对照组相比,低钙日粮导致了血清中碱性磷酸酶含量显著性增加,血清钙含量显著性下降,蛋鸡股骨和胫骨重量显著性变轻,宽度显著性变窄,骨强度显著性降低。病理切片结果显示,与对照组相比,低钙组蛋鸡股骨远端骨切片中成骨细胞和破骨细胞含量均增加,但骨细胞含量减少。结论连续60d给蛋鸡饲喂低钙日粮可成功建立蛋鸡骨质疏松模型,且该模型为高转化型骨质疏松。     

镁与女性绝经后骨质疏松的关系研究进展

女性绝经后体内雌激素水平下降可导致骨质疏松。近年来有学者发现,除了雌激素通过调节钙离子水平在骨代谢过程中发挥重要作用外,镁离子也有可能会影响骨质的形成与吸收。血清镁及雌激素相互作用改变了骨质的钙含量,即二者与女性绝经后骨质疏松存在一定关联,但两者之间的具体关系却并不十分明确。众多试验结果表明,相对于单独一种镁离子或钙离子含量对骨质疏松发生率的影响,在女性绝经后体内雌激素水平低下的情况下,镁/钙离子的含量比显得更为重要。研究显示,血清镁离子含量过高或者过低都可能会引起钙离子代谢异常,可能导致两种离子的浓度比失衡,进而对骨代谢产生不利影响,增加女性绝经后患骨质疏松的风险。因此维持绝经后体内镁/钙平衡有利于维持骨组织代谢的稳定,同时为治疗骨质疏松提供线索。即不能单纯的强调补充镁离子或者钙离子,而是应该根据患者血清中钙镁离子的具体浓度和比例来制定治疗方案。     

The Relationship Among Hypertension, Antihypertensive Medications, and Osteoporosis: A Narrative Review

Osteoporosis and hypertension are two frequent diseases among the aging population that share a similar etiopathology and often coexist. Moreover, treatment of hypertension affects bone mineral density and, therefore, can worsen osteoporosis. This narrative review considers the influence of the main etiologic factors that contribute to the development of hypertension and osteoporosis and examines the effect of the most often used antihypertensives on bones. A computerized literature search of relevant English publications regarding the etiology of hypertension and osteoporosis as well as the impact of antihypertensives on osteoporosis from 1996 to 2011 was completed in October 2011. The latest update in the search was performed from May to June 2012. The most relevant nongenetic factors in the etiology of osteoporosis and hypertension are low calcium intake, vitamin D and vitamin K deficiency, high consumption of sodium salt, and the effects of different forms of nitric oxide. Thiazide diuretics are the only antihypertensives that have a positive influence on bone mineral density. For other antihypertensive drugs, the data are conflicting, indicating that they may have a potentially negative or positive influence on bone mineral density and fracture risk reduction. Some studies did not find a correlation between the use of antihypertensives and bone mineral density. Due to the frequent coexistence of hypertension and osteoporosis, when selecting long-term antihypertensive therapy the potential effects of antihypertensive drugs on development, worsening, or improvement of osteoporosis should also be considered.     

基于钙沉积异常探讨原发性骨质疏松症“痰邪”的理论研究

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。与骨骼强度相关的因素主要包括骨矿密度和骨质量,骨矿化是骨代谢的重要过程,而钙的异常沉积是骨矿化异常的表现,是骨质疏松症发病及加重的因素之一。多种骨基质蛋白参与血管钙化等异位钙化的过程,研究发现治疗骨质疏松症的药物也能同时改善血管钙化,因此骨质疏松症的治疗可以从调节钙的沉积入手,通过对骨钙相关蛋白的调节,促进正常的骨矿化而抑制异位钙化,从而达到治疗骨质疏松症的目的。向楠教授领导的课题组在前期的研究中,基于对脂代谢紊乱与骨质疏松症的相关性的认识及痰浊在骨质疏松症发病中作用的认识,提出了"脂代谢异常可能与骨质疏松症痰浊有关"的假说,并制定了补肾化痰的新治则,进行了一系列的实验研究,表明了从"痰"论治骨质疏松症的可行性。现在,根据正常的钙代谢在人体内环境的调节作用及钙的异常沉积引起的病理表现,认为钙的异常沉积亦属于中医"痰邪"的范畴,因此从"痰"论治骨质疏松症还可从调节钙沉积的角度入手,运用补肾化痰法调节钙的沉积,从而达到治疗骨质疏松症的目的,这还有待进一步的研究与证实。     

Total Joint Arthroplasty and Osteoporosis: Looking Beyond the Joint to Bone Health

BackgroundMetabolic bone diseases in the total joint arthroplasty (TJA) population are undertested and undertreated, leading to increased risk of adverse outcomes such as periprosthetic fractures. This study aims to better characterize the current state of bone care in TJA patients using Fracture Risk Assessment Tool (FRAX) score risk stratifications.MethodsIn total, 505 consecutive TJA patients who meet the Endocrine Society guidelines for osteoporosis screening were included for review. They were divided into a high risk or low risk group depending on FRAX scores and were compared based on screening, diagnosis, and treatment of metabolic bone disease. Logistic regression models were used to analyze factors influencing screening and treatment. A population analysis involving 2,000 TJA patients, and a complication analysis involving 40 periprosthetic fracture patients were conducted.ResultsAmong high risk patients undergoing TJA, 90% did not receive any pharmacological treatment for osteoporosis, 45% were not treated with vitamin D or calcium, and 88% did not receive bone density testing in the routine care period. Among patients with pre-existing osteoporosis undergoing TJA, 80% were not treated with any osteoporosis medications and 33% of these patients were not taking vitamin D or calcium. Female gender and past fracture history contributed to whether patients received screening and treatment. Patients with periprosthetic hip fractures have significantly higher FRAX scores compared to control THA patients.ConclusionThere are significant gaps in metabolic bone care of the geriatric TJA population regarding both screening and treatment. Metabolic bone care and risk identification with FRAX should be highly considered for TJA patients.     

Osteoporosis among Ethiopian immigrant women: a risk analysis

Summary The objective was to evaluate the prevalence of osteoporosis among Ethiopian immigrant and Israeli-born women and to determine the risk factors. The study revealed extreme prevalence of osteoporosis among Ethiopian immigrants (38.7). A strong association between calcium intake during adolescence, BMI, lactation duration, physical activity, oral contraceptive and osteoporosis is suggested. Introduction Osteoporosis is a chronic disease characterized by low bone mass and deterioration in the micro-architecture of bone that increases its susceptibility to fractures. We set out to evaluate the prevalence of osteoporosis among Ethiopian immigrant and Israeli-born women and to determine the risk factors. Methods A cross-sectional study among 181 Ethiopians immigrants and 98 Israeli-born women. Hip, forearm and spinal bone mineral density (BMD) were measured. Risk factor information was obtained from an interview. BMD and osteoporosis rates were compared between the groups. Step-wise regression models were constructed for osteoporosis as the dependent variable controlling for potential confounders. Results We defined 38.7% Ethiopian and 5.2% Israeli-born women as having osteoporosis. Rates of low BMI, prolonged lactation, age at first giving birth and sunlight exposure were higher in Ethiopian women compared to the Israeli-born. Multivariate analysis revealed a strong association between calcium intake during adolescence, BMI, lactation duration, physical activity, oral contraceptive use and osteoporosis. Conclusions The prevalence of osteoporosis among Ethiopian immigrant women living in Israel is extremely high compared to national and international rates. Therefore, we suggest that an immediate prevention program among Ethiopian women be started and guidelines for care-givers be developed, in order to raise their awareness for osteoporosis. Drs. Peled and Dahan contributed equally to this article.     

HDL cholesterol and bone mineral density: is there a genetic link?

Overwhelming evidence has linked cardiovascular disease and osteoporosis, but the shared root cause of these two diseases of the elderly remains unknown. Low levels of high density lipoprotein cholesterol (HDL) and bone mineral density (BMD) are risk factors for cardiovascular disease and osteoporosis respectively. A number of correlation studies have attempted to determine if there is a relationship between serum HDL and BMD but these studies are confounded by a number of variables including age, diet, genetic background, gender and hormonal status. Collectively, these data suggest that there is a relationship between these two phenotypes, but that the nature of this relationship is context specific. Studies in mice plainly demonstrate that genetic loci for BMD and HDL co-map and transgenic mouse models have been used to show that a single gene can affect both serum HDL and BMD. Work completed to date has demonstrated that HDL can interact directly with both osteoblasts and osteoclasts, but no direct evidence links bone back to the regulation of HDL levels. Understanding the genetic relationship between BMD and HDL has huge implications for understanding the clinical relationship between CVD and osteoporosis and for the development of safe treatment options for both diseases.     

Osteoporosis

Osteoporosis is a disorder of decreased bone mass, microarchitectural deterioration, and fragility fractures. Osteoporosis is widespread and can affect people of all ethnic backgrounds and many older women and men. An essential element in preventing osteoporosis is the achievement of normal peak bone mass. Adequate nutrition, appropriate calcium and vitamin D intake, regular menstrual cycles and a well balanced exercise program of exercise are essential elements in achieving peak bone mass. At menopause women undergo accelerated bone loss. Thereafter, women and men gradually lose bone mass. A loss of one standard deviation give rise to an enhanced twofold risk of spine fractures or a 2.5 risk of hip fracture. Bone mass is determined by dual energy x-ray absorptiometry, quantitative computed tomography scan, and a peripheral ultrasound. Dual energy x-ray absorptiometry has outstanding precision (within 1% to 2%), and has the ability to show the efficacy of drug intervention. Peripheral measurements may identify osteoporosis but only have a 70% correlation with hip and spine bone mass. Dual energy x-ray absorptiometry determines bone mass in a patient but the bone collagen breakdown products (N-telopeptide crosslinks) establish the current rate of bone loss. Major risk factors leading to fragility fracture include low body weight, history of fracture, family history of osteoporosis, and smoking. All individuals should ingest adequate calcium and vitamin D, exercise, and prevent falls. Women with low bone mass, high urinary bone collagen breakdown products, and/or major risk factors should consider hormone replacement therapy or a selective estrogen receptor modulator (Evista), calcitonin and bisphosphonates (alendronate). These agents successfully increase bone mass and limit fracture risk. Men at risk for fragility fractures respond similarly as women to alendronate and calcitonin. Although vertebral compression fractures can occur spontaneously, hip fractures are attributable to low bone mass coupled with a fall. Hence, fall prevention programs in addition to medical treatment are critical in the prevention of fragility fractures.     

Intestinal hyperabsorption of calcium and low bone turnover in hypercalciuric postmenopausal osteoporosis

Hypercalciuria of intestinal origin has been linked with bone loss in calcium nephrolithiasis and idiopathic osteoporosis. This retrospective data analysis was performed to explore potential pathogenetic link between intestinal hyperabsorption of calcium and postmenopausal osteoporosis. Data were retrieved from postmenopausal women who were evaluated for osteoporosis or osteopenia at the Mineral Metabolism Clinic of UT Southwestern Medical Center. A total of 319 patients underwent the test of calciuric response to oral calcium load to obtain an indirect measure of intestinal calcium absorption. Serum and urinary biochemistry and L2–L4 bone mineral density (BMD) were compared between five quintiles of calciuric response. There was a statistically significant trend toward a rise in 24-h urinary calcium and a decrease in urinary deoxypyridinoline (DPD) and BMD, with increasing order of quintiles. The presentation of those in the 1st quintile was consistent with vitamin D insufficiency or deficiency, with impaired calcium absorption, secondary hyperparathyroidism, and stimulated bone turnover (high normal urinary DPD). In contrast, patients in the 5th quintile displayed a picture of absorptive hypercalciuria of stone disease, with intestinal hyperabsorption of calcium, high or high normal urinary calcium and suppressed bone turnover (low or low normal urinary DPD). Thus, the assessment of intestinal calcium absorption in a seemingly homogeneous group of postmenopausal women with osteoporosis or osteopenia revealed a spectrum of calciuric response whose extremes may represent two physiologically distinct subtypes that have important diagnostic and therapeutic implications.     

The relationship of dietary calcium intake to radiographic bone density in normal and osteoporotic persons

Lifetime daily calcium intake was estimated through interview of 398 individuals from 15 to 90 years of age. The correlation of calcium intake with vertebral mineralization as determined by quantitative radiographic densitometry was low but persistently significant. In 53 persons with osteoporosis matched by age with 53 individuals from the control group, vertebral mineralization values were 60% lower than those of the control group, and the mean estimated total calcium intake in osteoporotics was 21% lower. In those persons reporting a single lifetime calcium intake, the control patients ingested almost twice as much calcium as those with osteoporosis. A mean decrease in calcium intake with advancing years has been shown. Evidence points to a decrease in calcium absorption with age, osteoporosis, or both, as well as a greater need for calcium intake in the elderly to maintain a positive calcium balance. Regardless of the intricacies of calcium homeostasis, a negative calcium balance leads eventually to greater bone resorption than formation, hence the rationality of insuring an adequate calcium intake with recognized nutritional needs. Evidence suggests that many factors are involved in the etiology and pathogenesis of osteoporosis; the data in this report support the likelihood that availability of calcium in the diet is one of them.