骨代谢生化指标临床应用专家共识（2019）

骨代谢生化指标包括钙磷代谢调节指标、骨形成标志物、骨吸收标志物、激素与细胞因子。骨代谢生化指标分别来源于骨、软骨、软组织、皮肤、肝、肾、小肠、血液及内分泌腺体等,是由成骨细胞或破骨细胞分泌的酶和激素,以及骨基质的胶原蛋白代谢产物或非胶原蛋白。骨代谢生化指标可及时反映骨转换状态,灵敏度高、特异性强,用于骨质疏松诊断分型、预测骨折风险、抗骨质疏松治疗疗效评价,以及代谢性骨病的鉴别诊断。并且在骨质疏松流行病学、发病机制、骨质疏松药物的研究方面具有重要的临床意义。     

骨转换生化标志物的研究进展

骨转换生化标志物具有灵敏性高、特异性强、稳定性好等优点,较骨密度更早反映出骨量变化,联合检测骨转换生化标志物,对评估骨形成和骨吸收的平衡状态、骨代谢疾病的鉴别诊断、抗骨质疏松疗效等方面有重要意义。骨转换生化标志物在骨质疏松症的诊断及骨代谢相关疾病的鉴别诊断以及抗骨质疏松治疗疗效判断方面均有重要意义,目前BALP、P1NP、TRAP、CTX作为相对研究较广泛的骨转化标志物已被应用于临床,一些较新的骨转换标志物(如OPG、LP、Cat K等)是否能作为预测骨折风险、监测治疗疗效的指标仍需临床医师进一步研究,以使其发挥最大的价值。本文对骨形成生化标志物、骨吸收生化标志物的研究进展及其在临床中的应用进行了简单综述。     

中国老年学学会骨质疏松委员会骨代谢生化指标临床应用专家共识

骨代谢生化指标包括：钙磷代谢调节指标、骨吸收标志物、骨形成标志物。骨代谢生化指标分别来源于骨、软骨、软组织、皮肤、肝、肾、小肠、血液及内分泌腺体等,是由成骨细胞或破骨细胞分泌的酶和激素,以及骨基质的胶原蛋白代谢产物或非胶原蛋白。骨代谢生化指标可及时反映骨转换状态,灵敏度高、特异性强,用于骨质疏松诊断分型、预测骨折风险、抗骨质疏松治疗疗效评价,以及代谢性骨病的鉴别诊断。并且在骨质疏松发病机制、骨质疏松药物的研究及流行病学研究方面具有重要临床意义。随着骨代谢生化指标检测技术逐渐成熟,临床应用日趋广泛,但不同来源的标本、不同方法、不同设备、不同试剂、人的不同年龄段、不同种族和不同性别等,检测结果存在差异。至今,骨代谢生化指标测定国内外尚无统一检测标准;为此,将骨代谢生化指标的生物学作用及临床意义、技术应用与质量控制,分别整理、凝炼成一篇为各位同仁可读、可用、可参考的文字材料。期待通过＂共识＂为推动临床骨代谢生化指标检测技术的提高,规范检测流程,建立科学的参考范围,使骨代谢生化指标在骨质疏松规范诊断、规范治疗、抗骨质疏松药物疗效评价及科研工作中发挥重要作用。     

骨代谢标志物在乳腺癌骨质疏松中的评估价值

目的探究骨代谢标志物在乳腺癌骨质疏松中的诊断价值。方法选取2014年6月至2017年6月在我院住院接受治疗的182例乳腺癌骨质疏松患者为本次研究的研究对象,对本研究对象的骨代谢标志物BALP以及uNTx水平进行检测,统计并对比治疗前后乳腺癌骨质疏松患者骨代谢标志物的变化情况,采用单因素分析方法及多元线性回归分析方法分析影响乳腺癌骨质疏松患者骨代谢标志物水平的因素。结果乳腺癌骨质疏松患者骨代谢标志物BALP以及uNTx水平明显高于正常水平(P0.05),治疗后两者水平均明显低于治疗前(P0.05);单因素分析显示,骨代谢标志物BALP以及uNTx水平与患者骨转移数目呈正相关(P0.05),与骨痛程度无明显联系(P0.05);多元线性回归分析,骨代谢标记物和骨转移数目是影响患者近期疗效的相关因素。结论骨代谢标志物水平与骨质疏松有着密切联系,可作为乳腺癌骨质疏松的理想诊断指标,且该指标相对于影像学检查反应敏感性更强。     

骨重建中的骨代谢指标

骨重建是破骨细胞和成骨细胞共同完成的旧骨退化,等量新骨取代的骨组织更新过程,在骨重建过程中,许多激素和细胞、体液因子以及细胞代谢产物影响骨的重建.目前国内外通过生物化学检测技术获得的骨代谢指标分为骨代谢调节激素、细胞与体液因子、骨吸收、骨形成标志物.笔者将影响骨重建生物化学指标的生理作用、临床意义进行综述.骨代谢指标虽不能作为骨质疏松诊断的金标准,但已广泛应用于临床,评价骨代谢状态、骨质疏松诊断分型、预测骨折风险、观察药物治疗的疗效,以及代谢性骨病的鉴别诊断.并且在抗骨质疏松药物的研究及流行病学研究方面具有重要应用价值.     

绝经后女性骨代谢生化指标与骨质疏松性腰椎骨折之间的相关性

目的探讨骨代谢标志物对预测绝经后骨质疏松患者合并腰椎骨折风险的诊断价值。方法采用双能X线骨密度仪、酶联免疫检测法(ELISA)和速率法对70例绝经后骨质疏松症腰椎无骨折患者和70例绝经后骨质疏松症腰椎骨折患者的髋部及腰椎骨密度、各项骨代谢生化指标进行检测,并分析骨代谢生化指标的变化与骨质疏松症、骨质疏松性腰椎骨折之间的相关性。结果绝经后骨质疏松性腰椎骨折的发生风险与年龄、体重、身高、体重指数、骨密度等一般指标和骨钙素N端中分子片段(N-MID osteocalcin,N-MID)、骨碱性磷酸酶(bone alkaline phospha,BAP)、钙离子(calcium ionic,Ca~(2+))、骨吸收标志物β-Ⅰ型胶原羧基端肽(β-C-terminal telopeptide of type I collagen,β-CTx)等生化指标之间无关联,而与血清I型原胶原氨基端延长肽(propeptide of type I procollagen,PINP)、抗酒石酸酸性磷酸酶5b(TRAP-5b)和25-羟维生素D(25-hydroxy vitamin,25-(OH)D)之间存在显著相关性(P=0.002、0.007、0.001),其中与PINP、TRAP-5b呈正相关,与25-(OH)D呈负相关。结论绝经后女性血清PINP、TRAP-5b和25-(OH)D与骨质疏松性骨折的发生存在显著的相关性,骨代谢标志物与骨密度的联合检测对预测绝经后骨质疏松腰椎骨折具有一定的临床意义。     

骨转换标志物在骨质疏松症诊断与治疗中的应用进展

骨转换标志物为骨重塑期间骨组织的自身代谢产物,可分为骨吸收标志物和骨形成标志物。与骨密度相比,骨转换标志物能更敏感地反映体内骨代谢情况,其早期检测有助于及时发现骨质流失患者。在评估骨质疏松性骨折风险和抗骨质疏松症治疗效果监测上,骨转换标志物也有重要临床价值。近年来,骨转换标志物与骨质疏松症的相关研究逐渐增多,学者们对其认识进一步加强。该文从骨转换标志物及其临床应用两方面进行综述,以期为骨质疏松症的诊断和治疗提供参考。     

骨代谢生化指标临床应用专家共识(2020)

骨代谢生化指标包括钙磷代谢调节指标、骨形成标志物、骨吸收标志物、激素与细胞因子。骨代谢生化指标分别来源于骨、软骨、软组织、皮肤、肝、肾、小肠、血液及内分泌腺体等,是由成骨细胞或破骨细胞分泌的酶和激素,以及骨基质的胶原蛋白或非胶原蛋白代谢产物。骨代谢生化指标可及时反映骨转换状态,灵敏度高、特异性强,用于骨质疏松诊断分型、预测骨折风险、抗骨质疏松治疗疗效评价,以及代谢性骨病的诊断与鉴别诊断。并且在骨质疏松流行病学、发病机制、骨质疏松药物的研究方面具有重要的临床意义。本文对《骨代谢生化指标临床应用专家共识(2019)》进行了修订,共有41处修改,保留了经典文献,删减了部分内容,增加了近三年的文献,收集整理了骨代谢指标实验检测参考范围。     

类风湿关节炎合并骨质疏松的骨转换标志物研究进展

骨质疏松是类风湿关节炎常见的合并症,类风湿关节炎患者继发骨质疏松的概率是正常人的2倍,骨重塑失衡导致骨吸收增加而骨形成减少,早期表现为局部或区域性骨丢失,随着病情进展骨量进行性降低,晚期可出现全身性骨质疏松.骨转换标志物包括骨形成标志物和骨吸收标志物,在骨代谢过程中被释放至骨微环境,最终可从血液或尿液中检出,反映体内骨...     

骨转换生化标志物的研究进展

骨转换生化标志物是反映骨骼细胞活性与骨基质代谢水平的生化产物,是在骨骼重建过程中释放于血液或尿液中的生化标志物,包括骨形成生化标志物、骨吸收生化标志物和骨转换调节剂,能较骨密度更早反映全身骨组织的动态变化。其具有敏感性好、特异度高、重复性好、非侵入性、经济适用等特点,是成为代谢性骨病的鉴别诊断、评估疗效、预测骨折风险的重要指标。目前,BALP、P1NP、CTX等指标已广泛应用于临床,一些新的标志物如CXC、GSN、ANXA2等在国外已经有一定研究,但国内临床相关研究较少,其能否作为有效指标反映全身骨组织的动态变化仍需进一步研究,笔者对一些新的骨转换生化标志物研究进展作一简单综述。     

甲状旁腺素联合雌二醇对大鼠骨质疏松的影响

目的探讨甲状旁腺素联合雌二醇对骨质疏松的影响及其作用机制,为临床用药提供理论依据。方法选取100只雌性SD大鼠随机分为5组:假手术组、去势组、甲状旁腺素组、雌二醇组、联合用药组,每组20只。首先构建去卵巢大鼠骨质疏松性动物模型,然后分别进行骨组织骨密度(bone mineral density,BMD)测定、骨代谢相关生化指标检测、骨代谢标志物检测、骨形态结构变化观察。结果去势组腰椎和股骨BMD、股骨最大载荷和刚度及血清Ca、P水平均较假手术组显著降低(P0. 05),而联合用药组上述指标均较去势组显著增高(P0. 05)。去势组血清ALP、COL-I、OC、OPG水平均较假手术组显著增高(P0. 05),而联合用药组上述指标均较去势组显著降低(P0. 05)。去势组骨小梁少见,细小稀疏,小梁间断裂分离,排列疏松紊乱;而联合用药组骨组织结构较完整,骨小梁形态结构较规整,数量多,致密均匀,连续性好呈网状。结论甲状旁腺素联合雌二醇可调节维持骨质疏松性骨代谢,增加骨密度,改善生物力学性能和骨组织病理形态学,促进骨形成,抑制骨吸收,具有骨保护作用。     

骨代谢昼夜节律研究进展

大量研究表明骨代谢具有昼夜节律性,大部分骨代谢相关细胞因子均呈现昼夜振荡,进一步分析显示大都呈现夜晚高峰而日间低谷的节律性。骨代谢与昼夜节律之间具有双向交互作用,骨代谢异常可扰乱昼夜节律,导致钟基因的表达紊乱,其中Bmal1的变化最为明显;紊乱的昼夜节律又进一步抑制骨形成、加速骨吸收,导致骨骼的内稳态失衡,从而损害骨骼健康。骨代谢标志物昼夜节律形成的机制及其与钟基因之间的生理、病理联系是未来的研究重点,可为时间药物治疗提供有力的循证医学证据。     

年龄和雌激素对绝经后妇女骨转换生化指标的影响

目的调查骨转换生化指标的差异,并评估激素和年龄相关因素与绝经前和绝经后妇女生化指标的关系。方法选取在2016年1月至2018年1月期间在我院就诊的女性患者作为研究对象。根据问卷调查,共选出496名健康女性,其中绝经前244例,绝经后女性252例。根据试剂制造商提供的指南评估不同的骨标志物,并且采用化学发光免疫测定法进行激素测定,特别是雌二醇水平评估。结果与绝经前妇女相比,绝经后妇女血清钙水平和雌二醇水平显著降低,而绝经后妇女血清磷和碱性磷酸酶(ALP)水平显著升高(P0.05)。年龄与绝经后骨标志物(ALP和钙)显著相关(P 0.05),而绝经前组无显著相关性。绝经后妇女钙与雌二醇之间呈显著正相关,而ALP与雌二醇之间呈显著负相关。此外,在体质指数和年龄校正偏相关分析中,绝经后妇女雌二醇和骨标志物之间没有显著相关性。结论绝经后女性雌激素水平和骨代谢异常对骨质疏松症的预测有积极的意义。     

Age-related changes in bone biochemical markers and their relationship with bone mineral density in normal Chinese women

Measurements of bone biochemical markers are increasingly being used to evaluate the state of bone turnover in the management of bone metabolic diseases, especially osteoporosis. However, changes in the bone turnover rate vary with age. The aim of this study was to establish the laboratory reference range of serum bone-specific alkaline phosphatase (sBAP), serum type I collagen cross-linked C-terminal telopeptide (sCTx), and urine CTx (uCTx), based on values from 665 healthy Chinese women aged 20–80 years. We measured the levels of sBAP, sCTx, serum alkaline phosphatase (sALP), and uCTx and evaluated the age-related changes and their relationship with bone mineral density (BMD) in the anteroposterior (AP) lumbar spine, hip, and left forearm. We found significant correlations between biochemical markers and age, with coefficients of determination (R ²) of 0.358 for sBAP, 0.126 for sCTx, 0.125 for uCTx, and 0.336 for sALP. The net changes in different biochemical markers were inversely correlated with the rates of BMD loss in the AP lumbar spine. After correction for age, body weight, and height, the levels of the markers had significant negative correlations with the BMD of the AP lumbar spine, femoral neck, and ultradistal forearm. All four biochemical markers had the highest negative correlation with BMD of the AP lumbar spine (partial correlation coefficients of −0.366, −0.296, −0.290, and −0.258 for sBAP, sCTx, uCTx, and sALP, respectively). The mean and SD values of these markers in premenopausal and postmenopausal women with normal BMD values were used as the normal reference ranges. The reference ranges of sBAP, sCTx, and uCTx for pre- vs postmenopausal women were 17.3 ± 6.23 vs 18.9 ± 7.52 U/l, 3.18 ± 1.49 vs 3.23 ± 1.57 nmol/l, and 15.5 ± 11.4 vs 16.2 ± 12.4 nM bone collagen equivalents/mM urinary creatinine, respectively. Levels of the bone formation marker (sBAP) and bone resorption markers (sCTx, uCTx) increased rapidly in women with osteopenia or osteoporosis, indicating that they may be sensitive markers to determine the bone turnover rate in healthy Chinese women.     

Basic principles and clinical applications of biochemical markers of bone metabolism: biochemical and technical aspects.

The interest in and the need for effective measures to be used in the screening, diagnosis, and follow-up of disorders of connective tissue, bone, and mineral metabolism has markedly grown. Next to clinical and imaging techniques, indices of bone turnover have come to play an important role in the assessment of metabolic bone disease. In osteoporosis, recent research has shown that bone markers may also be used to predict future bone loss and hip fractures (in larger cohorts of older patients), identify individuals at risk for osteoporosis, select therapy, and predict and monitor the therapeutic response in individual patients. The development of new markers of bone metabolism has greatly enriched the spectrum of serum and urine analytes used in the assessment of skeletal pathologies. Besides total alkaline phosphatase, other markers such as bone-specific alkaline phosphatase, osteocalcin, or the collagen propeptides are being used to measure bone formation. Bone resorption, previously assessed only by the measurement of urinary calcium and hydroxyproline, may now be detected more precisely by a number of new serum and urine markers. Among these, the pyridinium crosslinks and the telopeptides of collagen type I are presently considered the most specific markers of bone resorption. More recently, bone sialoprotein has also been suggested as a marker of bone resorption in serum. Tartrate-resistant acid phosphatase is now measurable by immunoassay. This article surveys the biochemistry and relevant technical aspects of the currently available markers of bone metabolism.     

Evaluation of bone loss and the serum markers of bone metabolism in patients with hyperparathyroidism

Bone loss and the serum markers of bone metabolism were studied in 22 patients with primary hyperparathyroidism and 108 patients with renal hyperparathyroidism. The parameters of bone loss were bone mineral density in the distal radius and lumbar vertebrae, measured by dual energy X-ray absorptiometry, and bone mass index (GS/D) and the metacarpal index, in the second metacarpal bone, measured by the digital image processing method. Alkaline phosphatase (AIP), intact osteocalcin (OC), and the carboxyterminal propeptide of type I procollagen (PICP) were measured as serum markers of bone formation, while tartrate-resistant acid phsophatase (TRACP) and the carboxyterminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) were measured as serum markers of bone resorption. Bone loss and elevated markers of bone metabolism were observed both in patients with skeletal symptoms and in those without. Furthermore, the decrease in the cortical bone mass was more predominant than that of the trabecular bone. As markers of bone formation, AIP and OC seemed to be more sensitive than PICP, and as markers of bone resorption, ICTP appeared to be more sensitive than TRACP. Thus, a close correlation was observed between bone loss and the markers of bone formation and resorption.     

阿仑膦酸钠对2型糖尿病合并骨质疏松患者骨代谢标志物的影响

目的 观察阿仑膦酸钠对2型糖尿病合并骨质疏松症患者骨代谢标志物的影响,以评价该药的治疗效果。方法 收集2011年1月至2012年6月门诊及住院患者共103例。对所有患者均早晨空腹采血。测量空腹血糖(FPG)、血钙、血磷、碱性磷酸酶(ALP)、糖化血红蛋白(HbA1c)、血清抗酒石酸酸性磷酸酶-5b（TRACP-5b）、血清Ⅰ型胶原C末端肽（s-CTX）、血清骨源性碱性磷酸酶（BAP）和血清骨钙素（OC）。利用双能X线吸收法进行腰椎和髋骨的骨密度检测。使用阿仑膦酸钠治疗6个月后复查上述各项生化指标和骨密度。将每例样本治疗前后的检测结果进行对比分析,统计学方法为配对t检验。结果 治疗前后血钙、血磷、碱性磷酸酶的差异无统计学意义;TRACP-5b、s-CTX治疗后较治疗前升高, BAP与OC较治疗前降低。治疗后腰椎和髋部的骨密度较治疗前均有不同程度升高。结论 阿仑膦酸钠对2型糖尿病合并骨质疏松症的治疗效果明显,其机制可能与抑制骨吸收,促进骨形成有关。     

Synthetic human calcitonin in postmenopausal osteoporosis: A placebo-controlled,double-blind study

Summary A placebo-controlled, double-blind study was carried out over 4 months to evaluate two doses of synthetic human calcitonin (0.25 and 0.125 mg) given s.c. three times per week. Enrolled were 60 women, aged 56–82 years, who had experienced a vertebral fracture due to low-energy trauma within the preceding year. During active treatment there was within the first month a dose-dependent decrease of the indices of bone resorption (fasting urinary calcium and hydroxyproline excretions), whereas only the higher dose and a treatment period of 4 months produced a reduction of bone formation (serum osteocalcin). The bone mineral content (BMC) of the nondominant forearm was unchanged. Treatment with calcitonin also had significant, dosedependent, analgetic effects. The amelioration of pain was, in multivariate analyses, related to a reduction in parameters felt to be markers for bone resorption. In the placebo group there was a significant reduction of the BMC of the forearm but no changes of any of the biochemical markers for bone turnover and no improvement of pain. In conclusion, treatment with two low doses of calcitonin induced changes of the biochemical markers of bone turnover in a dosedependent manner. The analgetic properties of calcitonin were also of salient clinical importance. The knowledge derived from this study could be adapted to the dosage schedule in long-term trials in osteoporosis.