维生素K对幼鼠骨量及骨强度影响的实验研究

目的从骨计量学及骨生物力学等方面评价维生素Ｋ对幼鼠骨发育的影响。结果股骨及腰椎骨计量学各参数值（骨湿重、干重、骨体积、骨密度、骨小梁面积等）随维生素Ｋ摄入水平增加而增加;腰椎各计量学参数值在饲料维生素Ｋ水平超过３００μｇ／ｋｇ时,无显著变化;维生素Ｋ可提高股骨的结构力学性能（最大载荷与结构硬度）,而对其材料力学性能无显著影响。结论维生素Ｋ能促进幼鼠骨发育;从骨健康角度考虑,目前根据凝血功能需求建议的大鼠饲料维生素Ｋ需要量（即本实验低剂量组：５０μｇ／ｋｇ饲料）不能满足幼鼠骨发育需求     

维生素K2促进BM-MSCs成骨分化及其机制研究

目的探讨维生素K2对骨髓来源间充质干细胞(BM-MSCs)成骨分化能力的影响和机制。方法通过CCK-8活细胞计数法检测维生素K2不同浓度(1 nmol/L,10 nmol/L,100 nmol/L,1μmol/L,10μmol/L)在不同时间(24、48、72 h)对BMMSCs生长增殖的影响,运用Q-PCR检测不同浓度维生素K2对BM-MSCs成骨分化相关基因BMP-2表达水平的影响,进一步探讨维生素K2是否通过成骨信号通路Smad1/5/8、Runx2及Osterix调控BM-MSCs成骨分化。结果与对照组比较,低浓度(1 nmol/L)的维生素K2不影响BM-MSCs的生长活性,中浓度(10 nmol/L,100 nmol/L,1μmol/L)明显促进BM-MSCs的生长,高浓度(10μmol/L)明显抑制细胞的生长(P0.05)。中浓度范围的维生素K2呈剂量依赖性地促进BM-MSCs成骨过程中BMP-2 mRNA表达及钙结节的形成,且1μmol/L的维生素K2明显促进BM-MSCs的Smad1/5/8、Runx2及Osterix蛋白水平。结论维生素K2能够促进BM-MSCs的成骨分化,并且可能通过成骨信号轴BMP-2/Smad/Runx2/Osterix来调控BM-MSCs的成骨分化过程。     

维生素D缺乏对骨和骨外作用研究进展

维生素D缺乏作为一种在人群中发病率较高的疾病,日益受到人们的广泛关注。维生素D缺乏的主要诊断指标是血清25-羟维生素D水平。大量研究表明,维生素D缺乏不仅可以引起体内钙磷代谢障碍、佝偻病、软骨病和骨质疏松性骨折等骨骼系统疾病,而且还可能引起癌症、免疫系统疾病、心血管疾病、代谢性疾病(2型糖尿病和肥胖症)、肌肉功能障碍和跌倒等其他骨外系统疾病。维生素D缺乏对骨骼系统的作用,目前学术界已形成共识,然而维生素D缺乏对骨外系统的作用,目前学术界存在较大争议。笔者就维生素D缺乏对骨和骨外作用的研究进展进行全面介绍,探讨维生素D具有广泛作用的可能机理。初步阐述维生素D缺乏对骨和骨外系统的作用,不仅为研究维生素D缺乏对骨和骨外作用及可能机理提供新的研究思路,而且为防治维生素D缺乏的相关疾病提供新的临床思路。尽管目前对维生素D缺乏的骨外作用观点不一,但有充分证据表明补充适量的维生素D有助于身体健康。     

维生素K2调节骨代谢的生物学研究回顾

维生素K(vitamin K,VK)是一类2-甲基-1,4-萘醌衍生物,维生素K2是一种人体必需的天然营养素,主要分布在肾、骨、生殖器及血管壁等组织,维生素K2除参与体内凝血功能外,还与人体的许多生理功能有关,在骨代谢的多个环节中具有重要作用,其调节骨代谢的机制错综复杂。本文回顾性综述了维生素K2对骨代谢调节的生理作用、动物实验及临床试验研究,以及维生素K2在防治骨质疏松中的重要作用。     

中西医结合治疗慢性肾脏病-矿物质和骨代谢异常的Meta分析

目的评价以补肾为主的中药结合西医治疗慢性肾脏病一矿物质和骨代谢异常（chronic kidney disease-mineral and bone disorder,CKD-MBD）的疗效及安全性。方法电子检索PubMed、中国知网（CNKI）、万方数据库、维普中文科技期刊数据库。收集以西医治疗为基础,加用以补肾为主要功效的中药治疗CKD-MBD的随机对照试验（RCT）,评价纳入的临床研究质量,用Review Manager．2进行统计分析。结果共纳入10个RCT,496例患者。各纳入研究的质量总体较差。系统评价的结果显示,在西医治疗的基础上,加用以补肾为主要功效的中药治疗CKD-MBD,能更有效地降低甲状旁腺激素（PTH）[均数差值（MD）=-36．44,95％可信区间（cI）为（-60．31,-12．56）],而对钙[MD=0．07,95％CI（-0．03,0．17）]和磷[MD=0．2,95％CI（-0．41,0．02）]无显著作用。不良反应不清楚。结论在西医治疗的基础上,加用以补肾为主要功效的中药治疗CKI）-MBD,能更有效地改善CKD-MBD。但由于纳入的RCT研究方法学质量和证据强度普遍较低,其确切的临床疗效及安全性需要严格设计的大样本、多中心的随机双盲对照实验和系统评价来进一步证实。     

滁州市维持性血液透析患者矿物质和骨异常现状调查

目的了解滁州地区维持性血液透析(maintenance hemodialysis,MHD)患者的矿物质和骨异常(mineral and bone disorder,MBD)现状。方法调查2014年4~6月滁州地区7家医院血液透析中心的MHD患者情况。调查内容包括患者一般人口学特征、实验室检查、临床表现及用药情况等。分别以肾脏疾病患者生存质量指导(Kidney Disease Outcomes Quality Initiative,KDOQI)和改善全球肾脏病预后组织(Kidney Disease:Improving Global Outcomes,KDIGO)指南为标准,观察血校正钙、血磷、全段甲状旁腺素(immunoreactive parathyroid hormone,iPTH)达标情况,将其达标率与透析预后和实践模式研究(the dialysis outcomes and practice patterns study,DOPPS)4比较;并比较三级医院与二级医院MHD者血校正钙、血磷、iPTH达标率。结果①入选病例1 021例,平均透析时间(46.6±37.3)月。原发病前3位是慢性肾小球肾炎(512例,占50.1%)、糖尿病肾脏疾病(206例,占20.2%)、高血压肾病(144例,占14.1%)。②以KDOQI指南为标准,滁州市MHD者血校正钙、磷、iPTH达标率分别为40.5%、37.4%、21.3%,低于DOPPS4的56.7%、52.6%、29.6%(均P0.01)。③以KDIGO指南为标准,上述指标达标率分别为51.5%、19.8%、46.2%。④以KDOQI指南为标准,三级医院患者血磷、血iPTH达标率高于二级医院(P0.05),而血校正钙达标率两者差异无统计学意义。⑤MBD治疗状况:以KDIGO指南为标准,低钙、高磷和继发性甲状旁腺功能亢进的不当治疗分别占47.5%、47.6%、32.5%。结论滁州地区MHD者血钙、血磷及iPTH达标率低。三级医院MHD患者MBD控制情况较二级医院好,加强检测和管理有望提高相关指标的达标率。     

安徽省维持性血液透析患者矿物质和骨异常现状调查

目的 了解安徽省维持性血液透析(MHD)患者矿物质和骨异常(MBD)现状;探讨高磷血症相关危险因素.方法 调查2014年1月1日至2014年3月31日在安徽省皖南、皖中、皖北26家医院(其中三级医院19家,二级医院7家)血液透析中心的MHD患者情况.调查内容包括患者一般人口学特征、实验室检查、临床表现及用药情况等.分别以肾脏疾病患者生存质量指导(KDOQI)和改善全球肾脏病预后组织(KDIGO)指南为标准,观察血校正钙、血磷、全段甲状旁腺激素(iPTH)达标情况,将其达标率与透析预后和实践模式研究(DOPPS)3和DOPPS 4比较;并对不同等级医院MHD患者血校正钙、血磷、iPTH达标率进行比较.结果 (1)入选病例2774例,其中男性1662例,女性1112例,平均年龄(52.4±14.4)岁.平均透析龄(45.4±39.1)个月.原发病位于前3位的是慢性肾小球肾炎(49.8％)、高血压肾硬化症(18.7％)、糖尿病肾病(15.4％).(2)以KDOQI指南为标准,安徽省MHD患者校正钙、血磷、iPTH达标率分别为40.1％、36.9％、23.0％,低于DOPPS 3(50.4％、49.8％、31.4％)及DOPPS 4(56.7％、52.6％、29.6％)(均P＜ 0.01);与我国发达地区相比,iPTH达标率偏低(P＜0.05),而血校正钙、血磷达标率差异无统计学意义.(3)以KDIGO指南为标准,上述各指标达标率分别为52.0％、21.6％、47.8％.(4)不同等级医院进行比较:三级医院患者血磷、血iPTH达标率明显高于二级医院(均P＜ 0.05),而血校正钙达标率差异无统计学意义.(5)MBD治疗状况:以KDIGO指南为标准,低钙、高磷和继发性甲状旁腺功能亢进(SHPT)的不当治疗分别占46.4％、47.0％、31.8％.(6)性别、透析龄、血红蛋白、地区分布、经济收入水平与高磷血症发病率无关;超重、血清白蛋白升高为高磷血症的独立危险因素;入住三级医院、年龄增加是高磷血症的保护因素.结论 安徽省MHD患者血钙、血磷以及iPTH达标率不容乐观.三级医院MHD患者MBD控制情况较基层医院更为理想,提示加强监测与管理有望提高达标率.超重、血清白蛋白升高为高磷血症的独立危险因素;入住三级医院、年龄增加是高磷血症的保护因素.     

慢性肾脏病一矿物质和骨代谢异常诊疗进展

慢性。肾脏病一矿物质和骨代谢异常（CKD-mineraland bone disorders,CKD-MBD）是由于慢性肾脏病肾功能进行性下降,引起矿物质和骨代谢紊乱,所表现的全身性临床综合征。这些表现包括三个特点：1．钙、磷、甲状旁腺激素（PTH）、维生素D代谢的实验室异常;2．骨转运,骨矿化,骨容量,骨线性生长或骨强度变化的骨异常;3．血管或其他组织（如皮肤、关节、软骨、肺）钙化等异常。     

碳酸镧联合不同血液净化方式对慢性肾脏病-矿物质和骨代谢异常患者钙磷代谢的影响

目的探讨碳酸镧联合不同血液净化方式对慢性肾脏病-矿物质和骨代谢异常(chronic kidney disease mineral and bone disorder,CKD-MBD)患者钙磷代谢的影响,为CKD-MBD患者选择最佳治疗方案,改善患者的生存质量。方法选择陕西省人民医院2014年1月至2015年5月行维持性血液透析的CKD-MBD患者76例,给予口服碳酸镧并按透析方式分为3组,血液透析(hemodialysis,HD)组24例、血液透析联合血液透析滤过(HD and hemodialysis filtration,HD+HDF)组27例,血液透析联合血液灌流(HD and blood perfusion,HD+HP)组25例,比较各组治疗前和治疗3个月后血钙、血磷、钙磷乘积及甲状旁腺素(parathyroid hormone,PTH)的变化。观察3组治疗中不良反应的发生率并进行比较。结果治疗3个月后,3组血钙较治疗前均升高,3组间血钙变化无统计学差异(P0.05);3组血磷及钙磷乘积较治疗前明显下降(P0.05),但HD+HDF组、HD+HP组较HD组下降更为明显(P0.05)。HD组门H在治疗前、后变化不大(P0.05),HD+HDF组和HD+HP组治疗3个月后PTH较前明显下降(P0.05)。HD组、HD+HDF组及HD+HP组患者并发症发生率分别为75.0%、18.5%、32.0%,HD组并发症明显高于HD+HDF组和HD+HP组,差异有统计学意义(P0.05),HD+HDF组并发症发生率最低。结论碳酸镧联合不同血液净化方式对血钙、血磷及PTH的清除效果不同,联合HDF和HP方式能明显清除血磷、PTH,改善钙磷代谢紊乱,不良反应小,适合临床应用治疗CKD-MBD。     

Management of chronic kidney disease-mineral bone disorder

Chronic kidney disease mineral-bone disorder (CKD-MBD) is a systemic disorder of abnormal serum levels of mineral-related biochemistries, abnormal bone, and extraskeletal calcification. Although we have gained understanding on how these components are interrelated, our therapeutic tools remain focused on only one aspect of CKD-MBD at a time. However, the management of these disorders is also interrelated; treatments may help one aspect of the disorder but cause or accelerate another. As such, management remains a major challenge to nephrologists and requires balancing risk and benefit of the various available therapies. Our challenge for the decade ahead is to determine which combinations of therapy can be used safely together to prevent morbidity and mortality in CKD. Furthermore, the pathophysiology that sets these events into motion begins well before the onset of ESRD. Future therapies and guidelines should, therefore, also emphasize the need for earlier detection and management of CKD, shaped by the results of valid clinical trials.     

Pathophysiology of chronic kidney disease-mineral and bone disorder

Chronic kidney disease (CKD) alters the metabolism of several minerals, thereby inducing bone lesions and vessel-wall calcifications that can cause functional impairments and excess mortality. The histological bone abnormalities seen in CKD, known as renal osteodystrophy, consist of alterations in the bone turnover rate, which may be increased (osteitis fibrosa [OF]) or severely decreased (adynamic bone disease [AD]); abnormal mineralization (osteomalacia [OM]), and bone loss. Secondary hyperparathyroidism is related to early phosphate accumulation (responsible for FGF23 overproduction by bone tissue), decreased calcitriol production by the kidneys, and hypocalcemia. Secondary hyperparathyroidism is associated with OF. Other factors that affect bone include acidosis, chronic inflammation, nutritional deficiencies, and iatrogenic complications.     

慢性肾脏病-矿物质和骨代谢异常的研究进展

慢性肾脏病-矿物质和骨代谢异常(CKD-MBD)不仅提高心血管疾病的发生率,也是致死、骨折、生活质量下降及骨外组织钙化的重要原因。本文综述了CKD-MBD的发生机制、临床诊断、治疗措施三个方面的最新研究进展。     

Optimal targets of chronic kidney disease-mineral and bone disorder markers for Chinese patients with maintenance peritoneal dialysis: a single-center retrospective cohort study

BackgroundThe chronic kidney disease-mineral and bone disorder（CKD-MBD) is known to be associated with increased mortality in dialysis patients, but whether current global guidelines for CKD-MBD, which were primarily developed from hemodialysis, are suitable for peritoneal dialysis (PD) patients practice require further investigation.MethodsThis is a single-center retrospective cohort study. In total 491 prevalent PD patients (median follow-ups: 34 months) from Peking Union Medical College Hospital (PUMCH) from January 2004 to December 2017 were included and followed until 30 June 2018. In the first dialysis year, the average levels of serum calcium, albumin-corrected calcium (CorCa), phosphorus, and parathyroid hormone (PTH) levels were the interested predictors in Cox proportional regression model.ResultsOf these PD patients (age 58 ± 17 years), 52% were male and 36% had diabetic nephropathy. In Cox regression over first-year mean parameters, PTH <100 pg/mL (HR = 1.97, 95% CI 1.32 to 2.94, p < 0.001) and ≥300 pg/mL (HR = 2.24, 95% CI 1.32 to 3.81, p = 0.003) were associated with increased all-cause mortality than that of PTH 100–200 pg/mL. Patients with albumin-corrected serum calcium level < 2.13 mmol/L also had higher risk of death than patients with level of 2.13 to 2.38 mmol/L (HR = 2.06, 95% CI 1.06 to 4.01, p = 0.02). Serum phosphorus ≥1.45 mmol/L were associated with increased all-cause mortality. However, lacking of data on 25-hydroxy vitamin D, alkaline phosphatase, and activated vitamin-D are limitations of our analysis.ConclusionsAs one of the largest PD cohort study focusing on CKD-MBD, we demonstrated that the level of CKD-MBD markers in the first PD year are independent predictors of all-cause mortality. PTH 100–300 pg/mL might be the best target for Chinese PD patients.     

A rat model of chronic kidney disease-mineral bone disorder

Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) is a newly defined syndrome encompassing patients with chronic kidney disease that have a triad of biochemical alterations in calcium, phosphorus and parathyroid hormone, vascular calcification, and bone abnormalities. Here we describe a novel Cy/+ rat model of slowly progressive kidney disease spontaneously developing the three components of CKD-MBD when fed a normal phosphorus diet. Since the renal disorder progressed 'naturally' we studied the effect of dietary manipulation during the course of the disease. Animals with early, but established, chronic kidney disease were fed a casein-based or a grain-based protein diet both of which had equivalent total phosphorus contents. The two different sources of dietary protein had profound effects on the progression of CKD-MBD, likely due to differences in intestinal bioavailability of phosphorus. Although both dietary treatments resulted in the same serum phosphorous levels, the casein-fed animals had increased urinary phosphorus excretion and elevated serum FGF23 compared to the grain-fed rats. This model should help identify early changes in the course of chronic kidney disease that may lead to CKD-MBD.     

Serum osteoprotegerin measurement for early diagnosis of chronic kidney disease-mineral and bone disorder

Aim: Chronic kidney disease‐mineral and bone disorder (CKD‐MBD) has been proposed to be the replacement of renal osteodystrophy by the Organization of Kidney Disease: Improving Global Outcomes since 2005 because the mineral disorder is not confined to the skeleton in CKD. Accordingly, laboratory and imaging tests have been emphasized for the clinical assessment of patients with CKD besides renal biopsy. The objective of the current study was to investigate whether osteoprotegerin (OPG) could be made a useful biomarker for early diagnosis of CKD‐MBD. Methods: Sixty pre‐dialysis patients with CKD 1–5 were enrolled in this study. The serum calcium, phosphorus, blood urea nitrogen, creatinine, alkaline phosphatase, Osteocalcin, Calcitonin, intact parathyroid hormone and OPG were measured. Bone mineral densities of the lumbar spine (L2–L4), femoral neck, Ward's triangle and trochanter were measured by dual‐energy X‐ray absorptiometry. Results: Among all measured serum bone metabolism indexes, the changing of serum OPG level happened at the earliest time (CKD 3) and its correlation coefficient with estimated glomerular filtration rate (eGFR) was also the highest (r = ?0.601, P = 0.001). In the multivariable analysis that included sex, age and eGFR as controlling factors, the serum OPG correlated with the bone mineral density (BMD) of Ward's triangle (r = ?0.390, P = 0.041). Conclusion: Serum OPG may be a useful biomarker for early diagnosis of CKD‐MBD.     

Risk factors of bone density disorder and vascular calcification in non-dialysis chronic kidney disease patients

Objective To explore the risk factors of bone density disorder and vascular calcification in non-dialysis chronic kidney disease (CKD) patients. Methods Clinical data of non-dialysis CKD patients who were admitted to the First Affiliated Hospital of Fujian Medical University between January 2013 and June 2014 were retrospectively analyzed. Using dual energy X-ray absorptiometry to evaluate their bone mineral density (BMD) and T value. Patients were divided into normal BMD group (T≥-1), osteopenia group (-2.5＜T＜-1) and osteoporosis group (T≤-2.5). The vascular calcification was evaluated by pectoral computed tomography. Multi-factor stepwise logistic regression analysis was used to assess the risk factors for low bone density and vascular calcification in non-dialysis CKD patients. Results A total of 337 non-dialysis CKD patients were enrolled. There were 110 (32.6%) patients with normal BMD, and 146(43.3%) patients with osteopenia, and 81(24.0%) patients with osteoporosis. Gender, history of hypertension, 25-hydroxy vitamin D and N-terminal osteocalcin shown statistical differences among three groups (all P＜0.05). The incidence rate of 25-hydroxy vitamin D deficiency shown statistical difference among three groups (P=0.012). Further, the rates were increased with the decreased bone mass (χ2=7.100, P=0.008). The other mineral bone disorders, such as hypocalcemia, hyperphosphatemia, low intact parathyroid hormone (iPTH) and high iPTH had no statistical difference among three groups (all P＞0.05). Multi-factor stepwise logistic regression analysis revealed that increased iPTH (OR=1.938), and low bone density (OR=1.724) were independent risk factors for CKD patients with vascular calcification (all P＜0.05), while women (OR=3.312) and vascular calcification (OR=1.742) were independent risk factors for CKD patients with low bone density (all P＜0.05). Conclusion Increased iPTH and low bone density are independent risk factors for non-dialysis CKD patients with vascular calcification, while women and vascular calcification are independent risk factors for non-dialysis CKD patients with low bone density.     

Bone health in chronic kidney disease-mineral and bone disease

Chronic kidney disease (CKD) is accompanied by disturbances in calcium, phosphate, vitamin D, and parathyroid hormone (PTH) homeostasis that play an important role in the pathophysiology of renal bone disease. The increased cardiovascular morbidity and mortality observed among patients with CKD has recently been recognized to be associated with these disturbances in mineral metabolism. Thus, disturbances in mineral metabolism observed in renal failure results in a multisystem disorder, making the development of a standardized definition of these disorders a top priority. Therefore, the Board of Directors of Kidney Disease: Improving Global Outcomes proposed to define the broader category of mineral disorders associated with CKD as CKD-mineral and bone disorder (CKD-MBD). This newly proposed definition will include the disorders of mineral metabolism, bone histology (renal osteodystrophy), and the extraskeletal manifestations such as vascular calcification. This new definition and stratification of disease should result in improvement not only in the clinical management of patients but also will facilitate the interpretation and translation of clinical research. Renal osteodystrophy is now considered as 1 component of this disorder and will be defined as a morphologic alteration only, based on unification of the histomorphometric definitions that will include parameters of turnover, mineralization, and volume. An internationally accepted classification system will enable the consensus for bone biopsy evaluation as well as for the role of biomarkers. This article will focus on the newly proposed definitions of bone disease as part of CKD-MBD, based on the complex pathophysiologic process underlying bone disease in CKD stages 2 to 5.