骨代谢标志物在慢性肾病患者中的表达

目的分析慢性肾病(CKD)1～5期患者的骨钙素、Ⅰ型胶原N端前肽(PⅠNP)、β-胶原特殊序列(CTX)、25羟维生素D3[25(OH)D3]、血钙、血磷、血甲状旁腺激素(iPTH)之间的相关性。方法 157例CKD患者作为研究对象,收集临床资料,检测骨钙素、PⅠNP、β-CTX、25(OH)D3、血钙、血磷、血iPTH、血肌酐(Scr),使用流行病学合作(EPI)公式计算肾小球滤过率(eGFR)后将其分成CKD1～5期共5组,同时进行相关性分析,再将CKD5期的腹透患者根据iPTH水平及是否行腹膜透析分成iPTH正常+腹透组、iPTH正常+非腹透组、iPTH升高+腹透组、iPTH升高+非腹透组4组。结果男性CKD患者25(OH)D3水平显著高于女性(P0.05),骨钙素、PⅠNP、β-CTX、血磷、血钙、血iPTH水平无性别差异(P0.05)。CKD1～4期患者PⅠNP、β-CTX、骨钙素、血磷、血iPTH水平差异无统计学意义(P0.05),CKD5期患者以上各指标显著高于其他4期(P0.05);同时血钙及25(OH)D3在5组间差异无统计学意义(P0.05),其中25(OH)D3水平在各组间均呈现缺乏或不足状态。EPI-eGFR与骨钙素、PⅠNP、β-CTX、血磷、血iPTH呈明显负相关(P0.01),而与血钙及25(OH)D3无相关性(P0.05);CKD5期患者中iPTH升高+腹透组患者与iPTH正常+腹透组患者比较,血磷、骨钙素、PⅠNP、β-CTX、iPTH水平均明显升高(P0.05)。结论 CKD患者普遍存在25(OH)D3的缺乏,且在CKD早期即存在,女性较男性更容易出现25(OH)D3缺乏。不同CKD分期患者中,CKD5期患者表现出较前4期患者更活跃的骨代谢状态,骨形成加快,骨降解活跃,这种骨代谢状态和eGFR的变化呈显著负相关。在腹膜透析患者中高iPTH水平及低eGFR水平更容易导致骨代谢的异常。     

血清25羟维生素D、TRACP-5b、PINP、β-CTX在绝经期骨质疏松病人中的检测意义

目的 分析25羟维生素D[25(OH)D]、血清抗酒石酸酸性磷酸酶5b(TRACP-5b)、Ⅰ型前胶原氨基端原肽(PINP)、β胶原降解产物(β-CTX)诊断绝经后骨质疏松(osteoporosis, OP)的临床价值。方法 选取2019年3月至2021年7月在我院骨质疏松专病门诊诊疗的150例OP病人为绝经后OP组,另选取同时期体检骨量正常的150名绝经女性纳入对照组。所有受试者均进行骨密度(BMD)、25(OH)D、TRACP-5b、PINP、β-CTX检测,采用Logistic回归分析以上指标与OP的相关性,采用ROC曲线分析25(OH)D及骨代谢指标对OP的诊断效能。结果 OP组血清BMD及25(OH)D水平低于对照组,TRACP-5b、PINP、β-CTX水平高于对照组。Pearson相关分析得出,绝经后OP病人血清25(OH)D含量与BMD呈正相关,TRACP-5b、PINP、β-CTX水平与BMD呈负相关。Logistic回归分析显示,血清25(OH)D含量降低及TRACP5b、PINP、β-CTX水平升高可能是造成绝经后OP发生的影响因素。ROC曲线分析显示,上述四个指...     

阿法骨化醇对慢性阻塞性肺疾病患者骨代谢的影响

目的探讨阿法骨化醇对慢性阻塞性肺疾病患者骨代谢的影响。方法以240例骨量减少的C级、D级COPD患者为研究对象,随机分为对照组(A组)、阿法骨化醇组(B组)、阿法骨化醇联合碳酸钙组(C组)。随访1年,测定入组时、第6月及第12月患者骨密度、血清[25(OH)D]、Ca、P、PINP、β-CTX、PTH指标,比较3组患者不同时间点指标的差异,计算有关指标之间的相关性。结果 3组患者入院时上述指标之间的差异均无统计学意义(P均0.05)。3组患者在随访第6及第12月时,B组、C组患者骨密度、血清25(OH)D、Ca均明显高于A组,其余指标均低于A组(P均0.05)。组内间比较,A组患者随访第12月骨密度、血清25(OH)D及Ca均低于入院时,其余指标均高于入院时(P均0.05)。B、C两组患者随访第12月骨密度、血清25(OH)D及Ca均高于入院时及第6月,其余指标均低于入院时及第6月(P均0.05)。三组患者入院时、第6月及第12月骨密度均与血清25(OH)D、Ca呈正相关(P均0.05),而与血清P、PINP、β-CTX、PTH呈负相关(P均0.05)。结论阿法骨化醇通过升高血清25(OH)D、Ca浓度增加慢性阻塞性肺疾病患者的骨密度。     

老年骨质疏松患者骨代谢指标、骨密度与骨质疏松性骨折的相关性

目的研究老年骨质疏松(OP)患者骨代谢指标、骨密度(BMD)与OP性骨折的关系。方法 OP患者432例中发生OP性骨折194例为骨折组,非骨折238例为非骨折组,检测髋及腰椎BMD,抽血清检测25羟维生素D3[25-(OH)D3]、总Ⅰ型原胶原氨基端延长肽(PINP)、β胶原降解产物(β-CTX),采用Logistic回归分析OP性骨折的危险因素。结果骨折组BMD明显低于非骨折组,PINP、β-CTX均显著高于非骨折组,而25-(OH)D3显著低于非骨折组(P<0.01)。年龄与体质指数(BMI)、BMD(股骨颈、股骨大转子、股骨转子间、总髋部、Ward三角区、腰椎等部位)及25-(OH)D3水平呈负相关(P<0.01);与其他骨代谢指标无明显相关性。股骨颈、股骨大转子、股骨转子间、总髋部BMD与β-CTX呈负相关、与25-(OH)D3呈正相关(P<0.05),与PINP无相关性;各部位BMD与女性、年龄呈负相关,与BMI呈正相关(P<0.01)。β-CTX的升高、女性是骨折的危险因素,而25-(OH)D3是骨折的保护性因素。结论骨代谢指标和BMD及OP性骨折关系密切,β-CTX升高可用于骨折危险的预测,25-(OH)D3的升高可减少骨折的风险。     

25-羟维生素D与糖尿病慢性肾脏疾病患者血糖控制的相关性研究

目的探讨25-羟维生素D[25(OH)D]与糖尿病慢性肾脏疾病(CKD)患者血糖控制的相关性。方法收集CKD患者130例和健康体检(NC)者45名,根据eGFR分为CKD1期、CKD2期和CKD3~5期组,测定各组血清25(OH)D和HbA1c。结果 CKD各组25(OH)D水平低于NC组(P0.05);CKD1期、CKD2期和CKD3~5期组25(OH)D水平依次降低(P0.05),HbA1c依次升高(P0.05)。25(OH)D与HbA1c呈负相关(r=-0.511,P=0.002)。多元线性回归分析结果显示,HbA1c、年龄、病程和BMI是25(OH)D的影响因素。结论 CKD患者血糖控制情况与25(OH)D水平密切相关。     

Graves病患者骨质疏松的相关影响因素分析

目的研究Graves病(GD)继发骨质疏松患者的生化指标的变化,为寻找Graves病继发骨质疏松的预测因子提供信息支持。方法收集141例GD患者,其中29例患者伴有骨量降低,归为低骨量组; 112例患者骨密度(BMD)正常,归为对照组。检测所有患者游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)、25-羟维生素D(25-OHD)、甲状腺受体抗体(TRAb)、血清碱性磷酸酶(ALP)、血清总Ⅰ型前胶原N末端肽(PINP)、血清β-胶原C末端肽(β-CTX)水平以及腰椎(L1-L4)、股骨颈(FN)、桡骨远端(DR)的BMD。结果低骨量组患者TSH、TRAb、25-OHD、BMD水平较对照组显著降低(P0.01),FT3、FT4、ALP、PINP、β-CTX水平显著高于对照组(P0.05)。GD患者骨代谢标志物PINP、β-CTX与LS、FN、DR的BMD均呈负相关(P0.05)。结论 GD患者BMD的降低与血清骨代谢标志物升高相关。监测骨代谢标志物水平可预测骨量的变化,有助于早期发现GD继发性骨质疏松患者。     

老年慢性肾脏病患者铁调素与骨形态发生蛋白-2关系

目的老年慢性肾脏病(CKD)患者铁调素(hepcidin)与骨代谢指标骨形态发生蛋白-2(BMP-2)关系探讨。方法随机选择在本科门诊随访的30例非透析CKD 1~3A期患者,30例非透析CKD 4~5期患者及健康体检者30例作为对照。检测参试者血红细胞计数(RBC)、血红蛋白(Hb)、红细胞比容(Hct)、血清铁调素、血钙(Ca)、血磷(P)、全段甲状旁腺激素(i PTH)、超敏C反应蛋白(hs-CRP)、血清铁蛋白(SF)、BMP-2水平,并比较组间差异。采用多元回归分析铁调素的影响因素。结果 CKD患者血清铁调素水平显著高于健康对照组(P0.01)。与CKD 1~3A期相比,CKD患者CKD 4~5期血清铁调素水平升高(P0.05)。Pearson相关分析显示CKD患者血清铁调素水平与估算肾小球滤过率(e GFR)呈负相关(r=-0.484,P0.05),血清铁调素水平与尿素氮(BUN)、血肌酐(Scr)、Ca、P、BMP-2呈正相关(r=0.45、0.377、0.582、0.514、0.947,P均0.05)。多元逐步回归分析显示,CKD患者血清Scr、SF、BMP-2与铁调素水平密切相关。结论铁调素与e GFR相关,随e GFR下降,CKD进展、BUN、Scr水平上升,铁调素水平逐渐上升。铁调素与BMP-2水平密切相关,铁调素可能通过调节BMP-2,参与CKD患者骨代谢调节。     

绝经后妇女25羟基维生素D浓度及其与甲状旁腺素和骨转换指标关系548例研究

目的探讨健康绝经后妇女25羟基维生素D[25(OH)D]缺乏状况及与甲状旁腺素(PTH)和骨转换指标值的关系。方法筛选2010年2—3月上海市徐汇区548例绝经后健康妇女,平均年龄为(63.6±6.5)岁。受试者按照25(OH)D浓度分为维生素D严重缺乏组(<24 nmol/L)、维生素D缺乏组(24～<48 nmol/L)、维生素D不足组(48～<72 nmol/L)和维生素D充足组(≥72 nmol/L)。检测空腹血25(OH)D、PTH和各骨转换指标包括1型胶原羧基末端肽β降解产物(β-CTX)、全端骨钙素(OC)和1型原胶原氨基端前肽(P1NP)。结果 184例(33.6%)为严重缺乏,251例(45.9%)为缺乏,30例(5.5%)为不足和82例(15.0%)为充足。进一步分析各组间年龄、体重指数(BMI)、PTH和各骨转换指标水平的差异,发现各组年龄和BMI差异无统计学意义,但随着25(OH)D浓度下降,PTH、β-CTX、OC和P1NP水平逐步增加,与≥72 nmol/L组比较,其他3组上述各指标水平差异有统计学意义。25(OH)D浓度与PTH及各转换指标呈显著的负相关(P均<0.01)。结论在冬季上海市健康绝经后妇女维生素D缺乏非常普遍,随之引起血PTH水平和骨转换指标的明显增加,临床必须加以重视。     

成纤维细胞生长因子23与慢性肾脏病钙磷代谢相关性研究

目的研究血清钙(Ca)、磷(P)、甲状旁腺激素(iPTH)、1,25(OH)2D3以及肾功能与成纤维细胞生长因子23(FGF23)的关系。方法将2009年9月至2010年2月中国医科大学附属第一医院住院的慢性肾脏病(CKD)患者58例分为3组,另设对照组20例。采用免疫酶联吸附(ELISA)法测定FGF23及1,25(OH)2D3浓度。全自动生化分析仪测定血清Ca、P、肌酐(Scr)、尿素氮(BUN)浓度,化学免疫发光法测定全段iPTH。结果 FGF23在CKD血清中的质量浓度均高于健康对照组,且随肾小球滤过率(GFR)的降低逐渐升高,在CKD 4,5期FGF23升高明显,与CKD 3期比较差异有统计学意义(P<0.05),1,25(OH)2D3显著下降,与对照组差异有统计学意义(P<0.01)。随着GFR的降低,血清Scr、P、iPTH逐渐升高。Pearson相关分析显示,CKD 3～5期logFGF23与logiPTH、Scr、P呈正相关(r=0.516,P<0.01;r=0.397,P<0.01;r=0.344,P<0.01),与GFR,1,25(OH)2D3呈负相关(r=-0.491,P<0.01;r=-0.413,P<0.01)。结论血清FGF23、iPTH、P随着GFR降低逐渐升高,1,25(OH)2D3逐渐降低,尤以CKD 4～5期明显。当GFR<30时FGF23质量浓度与GFR、血清iPTH、P、1,25(OH)2D3等因素有关。     

常规血液透析和血液透析滤过对骨代谢标记物的影响

目的:分析不同透析方式[常规血液透析(HD)与血液透析滤过(HDF) ]对HD患者骨代谢的影响探讨可能的原因.方法:入选30例维持性血液透析患者,随机分为HD组((n=15)和HDF组(n=15),15例健康体检者作为正常对照组.比较入组时、透析10个月后及单次两组患者透析前后血骨钙素(BGP),β-Ⅰ型胶原C-末端肽(β-CTX),I型前胶原氨基端前肤肽PINP),甲状旁腺素(PTH)的变化,并比较各组间是否存在差别.结果:入组时两组BGP,β-CTX,PINP及PTH水平差异无统计学意义(P＞0.05),10个月后HD组患者透析前BGIβ-CTX,PINP及PTH均高于HDF组(P＜0.05),同时两组均显著高于对照组(P＜0.01).透析后HD组患者β-CTX明显下降(P＜0.05),但PTH无明显变化.HDF组患者透析后BGP,β-CTX,PTH均有显著下降,其下降幅度大于HD组.两组患者透析前后PINP均无变化.结论:采用HDF可降低透析患者的骨转运指标,尤其对高PTH患者代谢指标改善效更佳.     

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.     

Metabolic bone markers and bone cell biology

Various metabolic bone markers have been developed in order to analyze each process of bone resorption and bone formation. By evaluating the two processes using bone markers, an imbalance between bone resorption and formation can be estimated. Metabolic bone markers have already been in clinical use for the early diagnosis and the assessment of treatment efficacy in osteoporotic patients and for the diagnosis of cancer-induced bone diseases. Further elucidation of the mechanisms of formation and secretion, metabolic clearance, diurnal rhythm as well as their changes in various disorders should enable us to evaluate bone turnover at a real-time scale and to utilize for the diagnosis of a variety of metabolic bone diseases.     

Alcohol-induced bone loss and deficient bone repair

BACKGROUND: Chronic consumption of excessive alcohol eventually results in an osteopenic skeleton and increased risk for osteoporosis. Alcoholics experience not only increased incidence of fractures from falls, but also delays in fracture healing compared with non-alcoholics. In this review the term "alcohol-induced bone disease" is used to refer to these skeletal abnormalities. Alcohol-induced osteopenia is distinct from osteoporoses such as postmenopausal osteoporosis and disuse osteoporosis. Gonadal insufficiency increases the rate of bone remodeling, whereas alcohol decreases this rate. Thus, histomorphometric studies show different characteristics for the bone loss that occurs in these two disease states. In particular, alcohol-induced osteopenia results mainly from decreased bone formation rather than increased bone resorption. Human, animal and cell culture studies of the effects of alcohol on bone strongly suggest alcohol has a dose-dependent toxic effect on osteoblast activity. The capacity of bone marrow stromal cells to differentiate into osteoblasts has a critical role in the cellular processes involved in the maintenance of the adult human skeleton by bone remodeling. Chronic alcohol consumption suppresses osteoblastic differentiation of bone marrow cells and promotes adipogenesis. In fracture healing, the effect of alcohol is to suppress synthesis of an ossifiable matrix, possibly due to inhibition of cell proliferation and maldifferentiation of mesenchymal cells in the repair tissue. This results in the deficient bone repair observed in animal studies, characterized by repair tissue of lower stiffness, strength and mineral content. Current knowledge of cellular effects and molecular mechanisms involved in alcohol-induced bone disease is insufficient to develop interventional strategies for its prevention and treatment. OBJECTIVES: The objectives of this review are 1) to identify the characteristics of alcohol-induced bone loss and deficient bone repair as revealed in human and animal studies, 2) to determine the current understanding of the cellular effects underlying both skeletal abnormalities, and 3) to suggest directions for future studies to resolve current ambiguities regarding the cellular basis of alcohol-induced bone disease.     

Measurements of bone mass and bone density

X-ray-based procedures are available to measure bone mineral density in vitro at almost any skeletal site. These bone density measurements are not useful in the diagnosis of the cause of bone loss but at present are the only tests available for assessing bone mass prior to the occurrence of irreversible changes such as fractures or vertebral compression, which are easily recognizable on x-rays. When fractures are present, the severity of the bone loss and the risk for future fractures can be assessed. Repeated measurements permit estimation of the rate of bone loss, which gives useful information for monitoring treatment effect or course of the disease. Measurement of total body calcium is of less clinical importance because of the predominantly trabecular bone loss that generally occurs in metabolic bone disease. Dual-energy x-ray absorptiometry (DEXA) and quantitative computed tomography (QCT) of the spine are of about equal clinical value in the first approach to the patient with metabolic bone disease, although DEXA allows greater variety in sampling sites. For repeated measurements, DEXA provides better precision at significantly lower radiation burden. For bone mineral measurements, the lumbar spine appears to be the most sensitive skeletal site.     

Histomorphometric analysis of bone in metabolic bone disease

Most of the tools necessary for a detailed study of bone remodeling are now available. These methods will enable us to substitute simple surface-based histomorphometry with pertinent derived variables that reveal more information about the processes going on. Because of the inherent variability of the methods, bone histomorphometry is less well suited for investigations in single individuals. However, in terms of basic investigations of cell and tissue activity in grouped materials of patients with metabolic bone disease and the evaluation of treatment regimens in these materials, bone histomorphometric investigations still yield the most detailed analyses.     

A soluble bone morphogenetic protein type IA receptor increases bone mass and bone strength

Diseases such as osteoporosis are associated with reduced bone mass. Therapies to prevent bone loss exist, but there are few that stimulate bone formation and restore bone mass. Bone morphogenetic proteins (BMPs) are members of the TGFβ superfamily, which act as pleiotropic regulators of skeletal organogenesis and bone homeostasis. Ablation of the BMPR1A receptor in osteoblasts increases bone mass, suggesting that inhibition of BMPR1A signaling may have therapeutic benefit. The aim of this study was to determine the skeletal effects of systemic administration of a soluble BMPR1A fusion protein (mBMPR1A-mFc) in vivo. mBMPR1A-mFc was shown to bind BMP2/4 specifically and with high affinity and prevent downstream signaling. mBMPR1A-mFc treatment of immature and mature mice increased bone mineral density, cortical thickness, trabecular bone volume, thickness and number, and decreased trabecular separation. The increase in bone mass was due to an early increase in osteoblast number and bone formation rate, mediated by a suppression of Dickkopf-1 expression. This was followed by a decrease in osteoclast number and eroded surface, which was associated with a decrease in receptor activator of NF-κB ligand (RANKL) production, an increase in osteoprotegerin expression, and a decrease in serum tartrate-resistant acid phosphatase (TRAP5b) concentration. mBMPR1A treatment also increased bone mass and strength in mice with bone loss due to estrogen deficiency. In conclusion, mBMPR1A-mFc stimulates osteoblastic bone formation and decreases bone resorption, which leads to an increase in bone mass, and offers a promising unique alternative for the treatment of bone-related disorders.     

Aseptic bone/bone marrow necrosis in leukaemia

Aseptic (avascular) bone/bone marrow necrosis (ABN) was found in 21 leukaemic patients during a period of 14 yr, with a frequency of 6.5% in autopsied leukaemic patients, and with the highest frequency in ALL. 8 patients (38%) complained of bone pain. X-ray examination was carried out in 7 of these with a positive result in 3 (43%). Only 1 patient had elevated S-Alkaline phosphatase. Leucocytosis was found in 12 patients. Only 1 patient (ALL) received steroid in a rather high dose during 6 weeks. At autopsy ABN was found localized to the femur in all patients and 2 patients also had ABN in other bones. Post-mortem X-ray examination demonstrated changes in 8 of 15 cases (53%), with osteolysis in 6 and sclerosis in 2. 19 patients had had recent ABN with some fibroblast proliferation. In 4 of these, appositional bone formation had started. 2 patients had sclerosis as the only change. The pathogenesis of ABN is not known; an important factor, however, may be ischaemia due to vascular obstruction.     

Injectable bone

Tissue engineering applies the principles of biology and engineering to the development of functional substitutes,for example 1) cells, 2) scaffolds, 3) some cytokines, for lost tissues. The meaning of this bone regeneration is that it decreases the needed tissues and burden of patients. In this time, we applied to mesenchymal stem cells (MSCs) from the own bone marrow as cell sources. MSCs are thought to be multipotent cells that can replicate. And we also used a beta-tricalcium phosphate (beta-TCP) as a scaffold and fibrin glue as materials to regenerate a injectable bone and we injected into the subcutaneous space on the dorsum of the rat. After 8 weeks of implantation, it could be confirmed newly formed bone and fibrin glue functioned as a injectable materials without loosing the cell activity and the proliferation of MSCs. Next we applied Platelet Rich Plasma (PRP) to improve the ability of osteogenesis. PRP contains some cytokines and are expected to promote the increase of osteogenesis. The merit is not immunity rejection from autologous blood collected in the immediate preoperative period. The admixtures of PRP or fibrin glue have fluidity and gel-like consistency as the thrombin mixing. They can be injected with a syringe in tissues. We named this "Injectable Bone". According to the histological observations, the MSCs with PRP were well formed mature bone and neovascularization compared with control (defect only) after 8 weeks implantation. These results demonstrated that the mixture of MSCs and PRP were useful as injectable bone substitute and its ability of bone regeneration is almost equal to autogenous particulate cancellous bone and marrow (PCBM).