The vitamin D receptor Fok1 polymorphism and bone mineral density in Chinese children

BACKGROUND: To evaluate the relationship between vitamin D receptor (VDR) gene polymorphism and bone mineral density (BMD) in 213 healthy children aged 6-10 year in China. METHODS: A questionnaire survey of dietary pattern, outdoor activity was conducted among 213 children (boys 126, girls 86) randomly selected in Xishui county of Hubei province. The BMD was determined by dual energy X-ray absorptiometry at the distal forearm, calcium, phosphorus, and alkaline phosphatase in serum were immediately analyzed. The FokI polymorphism was detected by using PCR-RFLP. RESULTS: BMD was significantly higher in boys than in girls in 8/9 year group. (2) the frequencies of FF, Ff, and ff genotype were 25.8%, 62.0% and 12.2%, respectively; no difference was found between boys and girls. (3) BMD of children carrying FF genotype was higher (0.256+/-0.03) than those of carrying Ff genotype (0.241+/-0.03), P<0.01; the Ff genotype was associated with lowest forearm BMD in both boys and girls. Outdoor activity also positively affected peak bone mass. CONCLUSION: The Fok1 polymorphism of the VDR receptor seems to directly affect bone mineral mass in Chinese children.     

甲状旁腺素、维生素D受体、雌激素受体基因多态对糖尿病患者骨密度的影响

目的探讨甲状旁腺素(PTH)基因多态与中国北方汉族人糖尿病患者骨密度的关系。分析维生素D受体(VDR)、雌激素受体(ER)基因多态性对PTH基因多态性与骨密度、骨量减少及骨质疏松关系的影响。方法运用PCR-RFLP技术检测1型糖尿病(T1DM)组54例、2型糖尿病(T2DM)组104例、健康对照(CON)组102例的中国北方汉族人PTH基因多态性。结果甲状旁腺素基因型和等位基因分布频率在T1DM组、T2DM组与CON组间差异无统计学意义(P0.05);DM患者Bb/bb基因型者发生骨量减少/骨质疏松的相对危险度增加(OR=2.8684)。联合VDR基因多态分析,Bbaa基因型组糖尿病患者并发骨量减少/骨质疏松的相对危险度增高(OR=4.3125);联合ER基因多态分析,bPxx基因型骨量减少/骨质疏松的相对危险度也增高(OR=4.0);联合分析PTH、VDR、ER基因型,同时存在3个或4个易感基因型者伴有骨量减少或骨质疏松,相对危险度增加(OR=5.5385)。结论糖尿病患者PTH基因多态性(BST B1位点)可能是预测骨量减少、骨质疏松易感性的遗传标志。联合VDR、ER基因多态有助于识别DM患者发生骨质疏松的高危人群。     

Bone mineral density,body height,and vitamin D receptor gene polymorphism in middle‐aged men

BACKGROUND. Polymorphisms of the vitamin D receptor (VDR) gene have been suggested to account for some of the genetic variation in bone mass. However, the relationship has been controversial. It has been suggested that environmental factors such as physical activity may be one of the many reasons for this controversy.

AIM. We investigated the possible interactions of VDR gene polymorphisms and low to moderate intensity exercise on bone mineral density (BMD) in a four‐year controlled, randomized intervention trial in 140 middle‐aged Finnish men.

METHOD. The TaqI, FokI, and ApaI restriction fragment length polymorphism (RFLP)‐markers of the VDR gene were evaluated. BMDs of the lumbar spine (L2–L4), femoral neck, and total proximal femur were measured with dual‐energy X‐ray absorptiometry (DXA). In addition, the relations of the VDR gene polymorphism with bone turnover markers (serum tartrate‐resistant acid phosphatase (TRAP) 5b activity and serum osteocalcin concentration) were evaluated.

RESULTS. At the randomization, the subjects with the VDR TaqI Tt or tt genotype had a greater body height than the subjects with TT genotype (P = 0.001). In addition, the association of VDR TaqI polymorphism with femoral BMD was found. The Tt or tt genotype associated with higher femoral neck values than the TT genotype (P = 0.003) at randomization. After adjusting the femoral neck for body height, the association remained (P = 0.021). We did not find any association between VDR gene polymorphism and bone turnover markers or any interactions of VDR gene polymorphisms and exercise on BMD.

CONCLUSIONS. The TaqI polymorphism may be associated with body height and femoral neck BMD values. The present findings also suggest that the VDR polymorphisms do not modify the effect of regular aerobic exercise on BMD. However, more randomized controlled exercise trials are needed to investigate the role of exercise intensity on VDR gene polymorphisms, and the role of VDR gene polymorphisms on BMD.     

Association between increased serum osteoprotegerin levels and improvement in bone mineral density after parathyroidectomy in hemodialysis patients

Secondary hyperparathyroidism (SHPT) is a common complication in chronic renal disease. Osteoprotegerin (OPG), an extracellular cytokine receptor secreted by osteoblasts, can promote bone formation by inhibiting the function of osteoclasts. Hemodialysis (HD) patients have elevated serum OPG levels. OPG secretion can be suppressed with high parathyroid hormone (PTH) levels. HD patients with refractory SHPT can benefit from parathyroidectomy (PTX) treatment, but the changes of serum OPG, bone turnover markers and bone mineral density (BMD) following PTX in HD patients remain unclear. In this study, patients on maintenance HD who received PTX for refractory SHPT (n = 28) were prospectively followed for 1 year. Serum intact PTH (iPTH), alkaline phosphatase (Alk-P), and OPG were measured serially; BMD was measured pre-PTX and at 1 year after PTX. After PTX, serum iPTH levels reduced profoundly. Serum Alk-P levels increased rapidly, peaking at 2 weeks post-PTX, while serum OPG levels gradually increased at 2 weeks after PTX and peaked at 2 months. BMD improved in both femoral neck (FN; cancellous and cortical bone) and lumbar spine (LS; cancellous bone). Higher baseline iPTH levels were associated with greater FN and LS BMD improvements at one year after PTX. The increment of serum OPG was correlated with the increase in LS BMD, implying that inhibition of osteoclastic bone resorption may improve BMD within the first year after PTX. These findings suggest that PTX removes the suppressive effects of high PTH on OPG secretion, resulting in the increased serum OPG levels that may contribute to BMD improvement.     

ACE gene polymorphism and long-term renal graft function

OBJECTIVES: The long-term outcome of transplanted kidneys has not changed substantially and only a minority of grafts survives more than 15 yr. The aim of this study was to determine the influence of ACE gene polymorphism on long-term outcome after renal transplantation. DESIGN AND METHODS: Using PCR, we evaluated ACE I/D gene polymorphism in a group of patients with long-term graft function (LTF) over 15 yr and compared it with control groups of transplant recipients and population sample. RESULTS: The distribution of genotypes in the LTF group differed from transplant controls (p < 0.05). Moreover, DD homozygotes in the LTF group had better creatinine clearance (DD: 1.1 +/- 0.3, ID: 0.96 +/- 0.3, II: 0.76 +/- 0.3 mL/s; p < 0.05). There were no differences in genotype distribution between transplant and population samples. CONCLUSIONS: Results of our study have demonstrated a possible connection between the DD variant of ACE I/D gene polymorphism and excellent long-term graft function.     

Biochemical markers of bone formation in hemodialysis and after allotransplantation of cadaveric kidney

AIM: To ascertain informative value of estimation of bone forming markers in patients on chronic hemodyalisis (CHD) and recipients of cadaveric kidney (CK). MATERIAL AND METHODS: Parathyroid hormone (PTH), beta-crosslaps (CTX), osteocalcin (OC), amino-terminal procollagen propeptide 1 (PINP), bone alkaline phosphatase (BAP), bone mineral density (BMD) were determined in 152 patients on CHD (89 males and 63 females aged 49 +/- 13 years) and 195 CK recipients (106 males and 89 females aged 42 +/- 12 years) 30 +/- 38 months after kidney transplantation. RESULTS: PTH, CTX and BAP determination specifies skeletal disease (secondary hyperparathyroidism or adynamic bone disease) in CHD patients. In patients with CK recipients osteoporosis differed from osteopenia by higher levels of PTH, CTX, OC in the absence of any differences in BAP, PINP. All bone forming markers were lower than CTX showing suppression of bone forming. Bone fractures in CK recipients' anamnesis were associated with OC and BAP decrease in men and low border of normal OC in women. Determination of bone formation and resorption markers in patients on CHD and CK recipients is of great clinical importance.     

Klotho蛋白在甲状旁腺细胞弥漫性增生与结节性增生中的不同表达探讨

目的 探讨Klotho蛋白在慢性肾衰竭继发性甲状旁腺功能亢进症（secondary hyperparathyroidism,SHPT）甲状旁腺细胞不同增生类型中表达的意义.方法 选取在武警总医院肾内科住院行甲状旁腺全切术的SHPT患者50例为SHPT组,尸体甲状旁腺组织供体8例为健康对照组,收集其血清及甲状旁腺组织标本,SHPT组甲状旁腺组织按病理表现分为结节性增生组和弥漫性增生组,检测血成纤维细胞生长因子-23（fibroblast growth factor-23,FGF-23）及甲状旁腺激素（parathyroid hormone,PTH）水平,免疫组化检测甲状旁腺组织中Klotho蛋白及增殖指标Ki67的表达.结果 ①SHPT患者血FGF-23[（1316.80±375.15）pg/ml]与PTH[（2106.00±806.78） pg/ml]呈正相关（r=0.438,P=0.001）.②SHPT患者血FGF-23与甲状旁腺组织中Klotho的表达呈负相关（r=-0.379,P=0.007）,血PTH与Klotho蛋白呈负相关（r=0.361,P=0.01）.③SHPT组甲状旁腺细胞中Ki67的表达显著高于对照组（F=54.417,P=0.000）,Klotho蛋白的表达显著低于对照组（F49.243,P=0.000）;SHPT组结节性增生甲状旁腺组织中Ki67的表达显著高于弥漫性增生组（t=3.760,P=0.001）,Klotho蛋白的表达显著低于弥漫性增生组（t=6.039,P=0.000）.结论 结节性增生甲状旁腺组织中Klotho蛋白表达低于弥漫性增生组织可能是导致SHPT患者甲状旁腺呈不同增生方式的重要原因.     

Bone mineral density, body height, and vitamin D receptor gene polymorphism in middle-aged men

BACKGROUND: Polymorphisms of the vitamin D receptor (VDR) gene have been suggested to account for some of the genetic variation in bone mass. However, the relationship has been controversial. It has been suggested that environmental factors such as physical activity may be one of the many reasons for this controversy.AIM. We investigated the possible interactions of VDR gene polymorphisms and low to moderate intensity exercise on bone mineral density (BMD) in a four-year controlled, randomized intervention trial in 140 middle-aged Finnish men. METHOD: The TaqI, FokI, and ApaI restriction fragment length polymorphism (RFLP)-markers of the VDR gene were evaluated. BMDs of the lumbar spine (L2-L4), femoral neck, and total proximal femur were measured with dual-energy X-ray absorptiometry (DXA). In addition, the relations of the VDR gene polymorphism with bone turnover markers (serum tartrate-resistant acid phosphatase (TRAP) 5b activity and serum osteocalcin concentration) were evaluated. RESULTS: At the randomization, the subjects with the VDR TaqI Tt or tt genotype had a greater body height than the subjects with TT genotype (P=0.001). In addition, the association of VDR TaqI polymorphism with femoral BMD was found. The Tt or tt genotype associated with higher femoral neck values than the TT genotype (P=0.003) at randomization. After adjusting the femoral neck for body height, the association remained (P=0.021). We did not find any association between VDR gene polymorphism and bone turnover markers or any interactions of VDR gene polymorphisms and exercise on BMD. CONCLUSIONS: The TaqI polymorphism may be associated with body height and femoral neck BMD values. The present findings also suggest that the VDR polymorphisms do not modify the effect of regular aerobic exercise on BMD. However, more randomized controlled exercise trials are needed to investigate the role of exercise intensity on VDR gene polymorphisms, and the role of VDR gene polymorphisms on BMD.     

Relations between VDR3 and COL1A1 genes and markers of bone tissue metabolism in patients with chronic obstructive pulmonary disease

AIM: To study correlation between polymorphism of the genes of vitamin D3 (VDR3), collagen of type 1 alpha-1 (COL1A1) and markers of bone tissue metabolism in chronic obstructive pulmonary disease MATERIAL AND METHODS: A total of 56 COPD patients were examined. Bone metabolism was evaluated by osteocalcin (OC) level and betaCL in the blood; BsmI polymorphism of gene VDR3 (genotypes BB, Bb, bb) and Sp1 polymorphism of gene COL1A1 (genotypes SS, Ss, ss)--by polymerase chain reaction. The control group consisted of 50 healthy persons of matched gender and age. RESULTS: OC and S allele were not the same in genotypes BB, Bb and bb. Ss and ss genotypes carriers had higher beta CL level than SS-carriers. SS and ss genotypes carriers did not differ with betaCL concentrations (p > 0.05). CONCLUSION: Testing of VDR3 and COL1A1 genes gives grounds for detection of predisposition to development of pulmonogenic osteopenic syndrome.     

FGF 23, PTH and vitamin D status in end stage renal disease patients affected by VDR FokI and BsmI variants

ObjectivesThe aim of this study was to evaluate the association between two VDR SNPs FokI and BsmI and mineral status in ESRD patients.Design and methodsOur case-control study included 100 patients with chronic renal failure in ESRD and 149 healthy subjects. We measured the serum Vitamin D levels and the serum intact PTH level by Electrochemiluminescence Technology (cobas E411 analyzer). We evaluated the serum FGF23 levels by indirect ELISA method. The genotyping of two VDR gene variants FokI and BsmI was carried out by PCR-RFLP technique.ResultsIn our study, the FokI TT genotype was associated with lower risk of ESRD development (OR = 0.176, Padj = 0.039). The difference in PTH and FGF23 levels between cases and controls was statistically significant. The expression of FokI CT genotype in subjects with diabetic nephropathy was associated with a negative correlation between VD and PTH levels (r = −0.620, P = 0.032) and a positive correlation between VD and FGF23 levels (r = 0.967, P = 0.012). A significant differences in VD levels between patients and controls was observed in the presence of FokI TT (P = 0.044) and CT (P = 0.036) genotypes. The expression of FGF23 serum level was significantly elevated in patients than in controls in the presence of the FokI CC and BsmI AG genotypes.ConclusionsIn conclusion, our study shows the existence of an association between VDR FokI, BsmI polymorphisms and mineral status in ESRD patients. The presence of VDR variants affect the protein expression of VD, phosphorus, FGF23 and PTH.     

Biochemical markers of bone metabolism and bone tissue losses after allotransplantation of the cadaveric kidney: a cross-sectional

The biochemical markers of bone metabolism (osteocalcin (OC), C- and N-terminal procollagen I propeptides (PICP) and PINP), bone alkaline phosphatase (BALP), deoxypyridinoline (DPD), beta-crosslaps (beta-CL), bone acid phosphatase (BAP), osteoprotegerin (OPG), insulin-like growth factor I (IGF-I), and parathyroid hormone (PTH)), daily urinary calcium excretion (DUCE) (intestinal calcium absorption), and lumbar and hip bone mineral density (BMD) were determined in 195 patients (78 females and 74 males with normal function of the grafted kidney and 11 females and 31 males with chronic renal failure (CRF) 40 +/- 33 months after renal transplantation (RT). All RT recipients received triple immunosuppressive therapy (cyclosporin, prednisolone, and azathioprine). All groups showed a significant increase in resorption markers and a moderate increase in bone formation markers (except BALP), which suggested bone remodeling dissociation, as well as elevated levels of PTH and OPG and decreased DUCE and BMD in the vertebral column and hip. Increased bone metabolism and decreased intestinal calcium absorption were largely pronounced in CRF. In the majority of recipients, the BMD reduction in the vertebral column and hip was moderate (osteopenia) and only in male recipients with CRF, axial osteopenia was concurrent with peripheral osteoporosis. The main predictor of accelerated bone metabolism and BMD losses following RT was hyperparathyroidism mainly caused by decreased renal graft function. Decreased IGF-I may be a cause of bone remodeling dissociation after RT/ and the increase in OPG seems to be compensatory, which suppresses bone resorption and reduces bone losses.     

Homocysteine and B-group vitamins in renal transplant patients.

Increased plasma homocysteine is an independent risk factor for cardiovascular disease. We have investigated homocysteine and B-group vitamin levels in renal transplant patients. Fasting blood was collected from 55 renal transplant recipients with good renal function and 32 age/sex matched control subjects. Total homocysteine was increased in transplant recipients in comparison to controls (10.9+/-1.5 vs. 6.7+/-1.3 micromol/l, P < 0.001). There was no difference in homocysteine between patients receiving cyclosporin (n = 39, homocysteine 11.0+/-1.5 micromol/l) and patients receiving prednisolone + azathioprine (n = 16, 10.8+/-1.6 micromol/l, mean+/-S.D.), although there was a significant correlation between homocysteine and serum cyclosporin concentration in the sub-group of patients receiving that immunosuppressive regimen (r = 0.42, P < 0.05). Levels of B-group vitamins were similar in patients and controls. Plasma homocysteine is increased in renal transplant recipients even in the presence of minor degrees of renal impairment and normal levels of B-group vitamins.     

肾移植删艮用他克莫司的药物基因组学因素分析

目的探讨CYP3A5基因多态性对服用他克莫司的肾移植患者的药代动力学参数的影响。方法选择24例肾移植患者,治疗方案为他克莫司＋霉酚酸酯＋强的松联合用药;CYP3A5基因分型采用PCR法和Pyrosequencing测序法;药代动力学模型采用LR法和GLM法。分析肾移植患者性别、CYP3A5×1等位基因、肾移植时年龄、肝肾功能对他克莫司药代动力学的影响。结果基因型CYP3A5×3／×317例,CYP3A5×1／×36例,CYP3A5×1／×11例。肾移植后14d及1、3、6、12个月时,CYP3A5＊1等位基因与较低的他克莫司剂量调整浓度相关（P值为0．000）;移植术后3个月,肝肾功能与他克莫司的剂量调整浓度相关（P值为0．028）。性别因素对他克莫司药代动力学无明显影响。结论在达到相同目标浓度的情况下,与携带CYP3A5×1基因型的个体相比,CYP3A5×3基因型需要更低的用药剂量。     

70例肾移植术后受者血清生化指标水平的调查

目的 调查肾移植术后患者血清生化指标水平,探讨肾移植手术的临床应用效果、意义。方法 用全自动OLYMPUS AU600生化分析仪分别对肾移植术后患者及正常对照组的血清生化指标进行分析比较。结果 肾移植组血清中ALT、AST、URIC基本正常（P〉0.05）,TP、ALB、GLOB水平明显低于对照组（P〈0.01）,BUN、CR的水平虽在正常参考范围内,但与对照组比存在显著性差异（P〈0.01）。心肌酶谱中的CK、CK-MB水平也在正常参考范围内,但与对照组相比存有差异（P〈0.05）。LDH、HBDH水平明显高于对照组（P〈0.01）。血脂中的CHOL、TG、HDL-C、AproA的水平两组无显著性差异（P〉0.05）,移植组中LDL-C、AproB水平升高,（P〈0.05）,Lp（a）水平明显升高（P〈0.01）。结论 肾移植术后受者肾功能有明显改善,但不能恢复到与正常对照组完全一致,其血清中蛋白水平低于对照组,肝功能基本正常,血脂代谢部分紊乱。     

Gene polymorphisms of the renin-angiotensin-aldosterone system and angiotensin II type 1-receptor activating antibodies in renal rejection

Steroid refractory acute rejection (SRAR) is a major vital factor in renal transplantation recipients. The pathogenesis of SRAR may involve both immune and non-immune mechanisms. A decreased renal allograft function has also been associated with increased activity of renin-angiotensin-aldosterone system (RAS), which may be genetically determined. A total 206 renal transplant recipients, 116 males and 90 females, were included. The effects of gene polymorphisms of the four components of RAS including angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin type 1 receptor (AT1R), and aldosterone synthase (CYP11B2) were investigated in 19 cases of renal transplant patients with SRAR. The association between SRAR and the activating antibodies targeting the AT1R were also investigated. Genotyping was performed for the M235T-AGT, the I/D-ACE, the A1166C-AT1R, and the -344T/C-CYP11B2 gene polymorphisms using polymerase chain reaction. Our results showed that renal allograft recipients with SRAR had significantly higher occurrences of the DD genotype of ACE and CC genotype of AT1R than recipients without SRAR. The other genetic polymorphisms of the RAS were not associated with SRAR. Activating antibodies targeting the AT1R were detected in the sera from 14 SRAR victims with malignant hypertension and without anti-HLA antibodies. This study provides evidence that determination before transplantation of the polymorphism of the gene encoding components of RAS may help identify patients who are at risk for SRAR. The detection of the antibodies of AT1R may contribute to the prevention of SRAR.     

Secondary hyperparathyroidism: review of the disease and its treatment

BACKGROUND: Most patients with chronic kidney disease (CKD) stage 5 develop secondary hyperparathyroidism (SHPT). SHPT is an adaptive response to CKD and its associated disruptions in the homeostatic control of serum phosphorus, calcium, and vitamin D. The poor control of mineral and parathyroid hormone (PTH) levels characteristic of SHPT is associated with serious clinical consequences. OBJECTIVE: This review discusses the pathophysiology and consequences of SHPT, as well as the efficacy and limitations of current treatment modalities. METHODS: Literature searches were conducted using the MEDLINE, EMBASE, and BIOSIS databases. Additional information was obtained from Internet web sites, textbooks, and nephrology congress abstracts. RESULTS: Patients with uncontrolled SHPT are at higher risk for cardiovascular morbidity and mortality, hospitalization, bone disease, vascular and soft-tissue calcification, and vascular access failure than patients whose mineral and PTH levels are well managed. New National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) targets for calcium, phosphorus, calcium-phosphorus product, and PTH control have recently been published with the aim of improving the management of mineral metabolism in CKD patients. Data from observational studies suggest that the majority of patients currently have PTH and mineral levels outside these target ranges. CONCLUSIONS: Given the inadequacies of current therapies, novel agents are being developed that may help improve the management of SHPT.     

中国汉族、维吾尔族、哈萨克族、蒙古族健康绝经后妇女维生素D受体基因多态性的分布

背景:维生素D受体基因在内切酶BsmⅠ,ApaⅠ,TaqⅠ作用下,呈限制性内切酶片段长度多态性,并且与骨密度密切相关熏而骨密度的变化对骨质疏松起着重要作用,但维生素D受体基因多态性与骨密度、骨质疏松相关性尚无定论。目的:分析在中国汉族、维吾尔族、哈萨克族、蒙古族绝经后妇女中与骨密度密切相关的维生素D受体基因多态性分布规律。设计:对比观察。单位:解放军总医院老年医学研究所。对象:选择2002-01/2003-12在解放军总医院进行健康体检的汉族绝经后妇女179名,平均年龄穴59±3雪岁。选择2001-01/2003-12于解放军兰州军区乌鲁木齐总医院老年科进行健康体检的维吾尔族、哈萨克族、蒙古族绝经后妇女者122,63,112名,平均年龄分别为(56±4),(55±3),(57±3)岁。均对检测项目知情同意。方法:应用聚合酶链反应限制性片段长度多态性技术确定维生素D受体基因BsmⅠ基因型,分析汉族、维吾尔族、哈萨克族和蒙古族绝经后妇女维生素D受体基因BsmⅠ多态性分布频率,并与已知的美国、澳大利亚、法国和日本相应数据进行比较。计数资料差异比较采用χ2检验。主要观察指标:汉族、维吾尔族、哈萨克族和蒙古族绝经后妇女维生素D受体基因BsmⅠ多态性分布频率,以及该分布特点与美国、澳大利亚、法国和日本相应数据比较结果。结果:汉族、维吾尔族、哈萨克族和蒙古族绝经后妇女维生素D受体基因bb基因型频率分别为90.5%,69.67%,38.1%和50%,BB基因型频率分别为0,4.1%,6.35%和4.46%,汉族与维吾尔族、哈萨克族和蒙古族维生素D受体基因型频率分布比较,差异明显穴P<0.01雪。哈萨克族与欧美人种比较熏维生素D受体基因型差异不明显,与日本、韩国人种差异明显(P<0.01)。结论:中国汉族与维吾尔族、哈萨克族和蒙古族绝经后妇女维生素D受体基因型多态性具明显种族差异性;哈萨克族维生素D受体基因型频率分布接近欧美人种,与日本、韩国人种差异明显。     

PTH检测对长期血透患者继发甲旁亢临床应用价值的研究

目的 探讨甲状旁腺激素检测对长期血透患者继发甲状旁腺功能亢进早期诊断、预防和治疗中的应用价值。方法 选择84例长期血液透析患者,分为服钙剂组与不服钙剂组,另选择30例非肾功能减退的普通患者为正常对照组,分别检测患者血清甲状旁腺激素、钙、磷、尿素氮、肌酐等。结果 服钙剂组患者血清甲状旁腺激素、磷明显低于不服钙剂组,两者之间有显著性差异(P<0.05),而两组患者的血清钙没有明显差异(P>0.05);血透患者的血清甲状旁腺激素明显大于正常对照组,与尿素氮、肌酐和磷呈正相关。结论 甲状旁腺激素检测对长期血透患者继发甲状旁腺功能亢进的早期诊断、预防和治疗有重要的指导意义;服用钙剂能预防和治疗继发性甲状旁腺功能亢进,减少继发性甲状旁腺功能亢进的发生率。     

Serum osteoprotegerin levels in patients after liver transplantation and correlation to bone turnover,bone mineral density and fracture status

The aim of this cross sectional study was to evaluate the prevalence of osteoporosis, vertebral fracture status and possible risk factors of bone loss including serum osteoprotegerin, a novel key regulator of osteoclast proliferation and activity in the posttransplantation period. We investigated 15 patients (10 male, 5 female) 20 +/- 6 (SE) months after orthotopic liver transplantation (OLT). All patients received immunosuppressive therapy and non were on calcium and/or vitamin D supplements at the time of admission to our osteoporosis outpatient clinic. Examinations included a bone densitometry measurement at the femoral neck, a standardized spinal X-ray and a morning blood sample. According to WHO criteria, osteoporosis at the femoral neck was present in 67% (10/15) of the patients with a mean T-score of -2.55 +/- 0.35. Vertebral fractures were seen in 33% and the mean number of fractures was 2.4 per patient. Secondary hyperparathyroidism (33%), vitamin D deficiency (53%) as well as impaired renal function (47%) were frequent findings in the patients. Low serum calcium was associated with elevated PTH- (r = -0.75, p = 0.001), serum cross laps- (r = -0.61, p = 0.01), osteocalcin levels (r = -0.49, p = 0.05), was an independent predictor of femoral neck bone mass (r = 0.57, p = 0.02) and accounted for 36% of this variance. Similarly, serum magnesium levels were also independently correlated to femoral neck Z-scores (r = -0.68, p = 0.0005). Two-thirds of the patients had elevated serum cross-laps, osteocalcin and bone specific alkaline phosphatase levels reflecting increased bone turnover. Serum osteoprotegerin (OPG) in liver transplant recipients was not significantly different when compared to healthy, matched controls (84.7 +/- 6.6 vs. 97.3 +/- 9.4 pg/ml, p = 0.50) and similar when fractured/non-fractured or osteoporotic/non-osteoporotic patients were compared. Serum OPG was, however, significantly correlated to serum cross laps (r = 0.71, p = 0.003), osteocalcin (r = 0.63, p = 0.01), serum parathyroid hormone (r = 0.61, p = 0.01) and serum creatinine levels (r = 0.53, p = 0.04) and showed only a weak and non-significant correlation to femoral neck Z-scores (r = -0.38, p = 0.16). Multiple regression analysis revealed that serum OPG was correlated independently of PTH, serum calcium and creatinine to serum cross-laps concentrations (r = 0.63, p = 0.04). In summary, we found a high prevalence of osteoporosis and vertebral fractures in liver transplant recipients with many of the patients showing evidence of vitamin D deficiency, secondary hyperparathyroidism and accelerated bone turnover. We conclude that secondary hyperparathyroidism and possibly serum magnesium seems to contribute significantly to the changes in bone mass during the posttransplantation period. Serum OPG was not correlated to bone mass or fracture status in this cross sectional setting but was elevated together with other bone resorption and -formation markers.