中老年女性骨转换指标与骨密度和骨质疏松风险的关系

目的了解中老年女性骨转换指标变化对骨密度(BMD)和骨质疏松患病风险的影响。方法 632名健康中老年女性(年龄40~89岁),测定空腹血清骨特异性碱性磷酸酶(BAP)、骨钙素(OC)、骨I型胶原C-末端肽(s CTX)和N-末端肽(s NTX),以及腰椎和近端股骨骨密度(BMD),并分析这些骨转换指标与BMD和骨质疏松患病风险的关系。结果本研究检测的各种骨转换指标与腰椎、股骨颈和髋部BMD呈显著负相关(r=-0.238~-0.528,P均=0.000)。调整年龄、身高、体重和体重指数后,血清BAP、OC和s CTX与腰椎和股骨颈BMD的偏相关系数仍然有显著性意义。多元线性回归分析显示,这些骨转换指标对腰椎BMD是一个有意义的负性决定因素,大约可以解释腰椎BMD 7.6%~27.9%的变异性。各种骨转换指标水平最高的四分位组(Q4)与最低的组(Q1)比较,腰椎、股骨颈和髋部的骨质疏松患病风险,分别显著增加4.6~15倍(OR=4.6~15,95%CI:2.6~30),3.2~13倍(OR=3.2~13,95%CI:1.5~36)和3.0~13倍(OR=3.0~13,95%CI:1.3~44)。结论本研究揭示了中老年女性骨转换指标与BMD和骨质疏松患病风险的关系,提示骨转换指标水平变化是中老年女性BMD的重要决定因素,骨形成指标和/或骨吸收指标水平增加者骨质疏松患病率和患病风险大大增加。     

骨质疏松椎体变形与骨密度和骨代谢水平的相关性研究

目的探讨骨质疏松患者椎体变形与骨密度(BMD)和骨代谢水平的相关性。方法以GENANT半定量法为标准,按照胸腰椎椎体不同变形程度将883例骨质疏松患者分为GENANT 0级、0.5级、1级、2级、3级共5组,测量各组的BMD、体质量指数以及Ⅰ型前胶原氨基端前肽(PINP)、β胶原降解产物β-crosslaps、N端中分子片段骨钙素(N-MID)等骨代谢指标,分析骨质疏松椎体变形程度与上述指标的相关关系,统计骨质疏松患者年龄、性别以及上述指标与骨折风险的相关性。结果椎体变形等级与BMD、体质量指数呈负相关(P0.05),与骨代谢指标呈正相关(P0.05);椎体变形GENANT 3级骨质疏松患者BMD、体质量指数低于其他GENANT等级,GENANT 1~3级患者骨代谢水平高于GENANT 0级、0.5级,GENANT 0级患者骨代谢水平最低(P0.05)。骨质疏松性椎体骨折女性患者多于男性,其发生随年龄增加而呈现增大趋势;80岁以上人群BMD、体质量指数和骨代谢水平均低于其他年龄组,且存在椎体变形的比例最高(P0.05)。结论骨质疏松患者的椎体变形与BMD、体质量指数以及PINP、β-crosslaps、N-MID等骨代谢指标有一定的相关关系;综合运用性别、年龄、BMD、体质量指数和骨代谢指标能提高骨质疏松椎体变形的诊断准确率,对预测骨质疏松患者椎体变形程度和骨折风险具有重要的指导意义。     

老年人骨质疏松性骨折的风险预测

目的了解老年人骨质疏松性骨折的风险与骨矿密度(BMD)的关系,为预测发生骨质疏松性骨折的风险提供科学的指标。方法对1020例年龄≥60岁的老年人骨质疏松症患者进行定量超声骨密度仪(QUS)测定跟骨的BMD值,将数据输入计算机进行统计学处理分析。结果骨折发生例数随BMD的T值降低呈负相关,骨质疏松性骨折患者百分比分别在Ⅰ区间和Ⅱ区间均与Ⅲ区有非常显著性差异,当BMD的T值≤-3SD骨折发生例数呈显著增加(r=-0.973,P<0.01)。结论老年人BMD的T值为-3.0SD时,骨折发生率呈明显上升,临床上可将老年人的BMD的T值低于正常1个标准差(-3.0SD)作为预测骨质疏松性骨折的风险指标。     

骨密度拟合参考曲线在骨质疏松诊断中的作用

骨质疏松(OP)是一种以骨量减少和骨组织微结构破坏为特征,继而导致骨脆性增加和骨强度下降及骨折危险性增加的全身性骨骼疾病。测量骨密度(BMD)诊断OP和评价各种疾病状态下的骨量变化及预测发生骨折的风险,已在临床多种学科领域得到广泛应用。BMD是一个非常特殊的定量指标,它不但具有年龄、性别和种族特异性,而且还具有骨骼部位特异性。因此,判别其正常与否,必须采用种族、性别和骨骼部位相匹配的及年龄范围尽可能广泛的BMD拟合参考曲线(也称参考数据库)进行比较和评价。鉴于BMD拟合参考曲线在OP诊断和骨量评价中的重要作用,笔者就…     

骨代谢指标在老年骨质疏松性骨折后变化的临床应用

目的 通过测定老年骨质疏松患者骨折后骨代谢生化指标,揭示骨代谢指标在老年骨折患者中的变化规律,提供早期控制老年骨质疏松性骨折后骨吸收的依据,有利于加强骨形成的能力,缩短骨折愈合时间,防止再次骨折及并发症的发生.方法 对82例(男33例,女49例)60岁以上髋部骨折及椎体压缩骨折患者和61例(男29例,女32例)老年健康对照组进行血清骨特异性碱性磷酸酶(Serum Bone Alkaline Phosphates,BALP)、骨钙素(bone gla-containing protein BGP)和血清抗洒石酸酸性磷酸酶5b(tart rate-resistant acid phosphates isoform-5b)测定.结果 (1)老年骨质疏松性骨折患者中TRACP-5b水平明显高于对照组(P<0.001),且女性骨转换高于男性;老年骨质疏松骨折患者BALP水平高于正常组(P<0.01).(2)骨折后骨转换指标(BAP,TRACP-5b)与骨密度呈负相关.结论 骨折后患者骨吸收增加,女性骨转换高于男性,女件骨折后更加重骨质疏松,不利于骨折后愈合,而骨折后监测骨代谢指标,提供早期控制骨吸收的依据,女性更应长期监测骨代谢并抗骨吸收治疗,利于加强骨形成的能力,缩短患者卧床时间,防止再次骨折及并发症.     

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。     

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。     

绝经后女性骨折风险与肌源性因子及骨代谢指标的相关性研究

目的 探讨绝经后女性肌源性因子及骨代谢指标与骨质疏松性骨折风险的相关性。方法 研究南京中医药大学无锡附院2021年6月至2022年6月门诊绝经后女性患者215例，根据纳排标准筛选出184例，其中绝经后骨质疏松88例，骨量减少65例，正常骨量31例。收集基线资料、肌骨代谢指标（碱性磷酸酶（ALP）、I型原胶原氨基端前肽（PINP）、鸢尾素（irisin）及肌肉抑制素（MSTN）等）及BMD，应用FRAX评估软件来评估骨折风险。控制年龄、骨量、FRAX风险等级比较肌骨代谢指标、体质指数（BMI）及体表面积（BS）的差异，并对绝经后女性骨折风险和各指标进行相关性分析；多重线性回归分析骨折风险概率与相关变量间的关系。结果 不同年龄组间BMD、PMOF及PHF差异存在统计学意义（P<0.05）；不同骨量组间BMI、BS、ALP、PMOF及PHF差异存在统计学意义（P<0.05）；FRAX不同风险组年龄、BS、BMD、Ca、ALP、PINP、irisin及MSTN之间差异存在统计学意义（P<0.05）；相关性分析显示FRAX骨折概率与年龄、PINP、MSTN成正相关（P<0.05）,与BMI、BS、BMD及irisin成负相关（P<0.05），二元Logistic回归分析显示年龄、PINP与irisin是骨折风险的重要相关因素。结论 基于适合亚洲人群的FRAX干预阈值研究，绝经后女性年龄、PINP与irisin是骨折风险评估的敏感因素，这对优化骨质疏松骨折风险模型有重要意义。     

用骨强度概念探索骨密度测量的诊断指标

30多年来，医学上一直用骨矿密度（BMD,g/cm^2）诊断骨质疏松，骨质疏松引起骨折，骨折由骨强度减低引起，体重是骨强度的重要决定因素。 本引入体重评价BMC（g）和BMD两个指标。结果，体重与BMC的相关明显强于与BMD的相关，证明男女之间的BMC差由体重引起，男女间相同体重配对的BMC没有差异，所以在评价骨的 力学强度上体重标准化后BMC优于BMC指标。     

合并不同疾病的男性骨量异常患者骨代谢、骨密度及骨折情况研究

目的了解合并不同疾病的男性骨量异常患者骨代谢指标、骨密度(bone mineral density,BMD)及骨折的情况。方法对2006年1月至2017年12月在上海市第一人民医院内分泌科骨质疏松亚专科就诊的928例男性骨量异常患者进行回顾性研究。根据研究目的不同,将患者分为有或无糖尿病组、有或无慢性肝病组、有或无慢性肾病组、有或无慢性胃病组、有或无心血管疾病组及骨量减低组和骨质疏松组。分别观察各组各项指标的差异。结果单因素回归分析提示受试者年龄、体重、L1~4BMD、股骨颈BMD、全髋BMD、β-CTX、慢性胃病、骨质疏松症是骨折史的影响因素,差异具有统计学意义(P<0.05);骨折史与受试者年龄、β-CTX、慢性胃病、骨质疏松症因素成正相关,与体重、L1~4BMD、股骨颈BMD、全髋BMD成负相关;多因素回归分析提示年龄、BALP、2型糖尿病、骨质疏松是骨折的危险因素,而25OHD水平是骨折的保护性因素。结论对于男性骨量异常患者,需要重点关注年龄较大、β-CTX和BALP水平较高、合并慢性胃病以及2型糖尿病的患者,对这类患者应积极进行抗骨质疏松干预及治疗,以减少此类患者骨折的发生率。     

Bone turnover markers: understanding their value in clinical trials and clinical practice

While bone mineral density (BMD) by dual-energy X-ray absorptiometry is the primary method of determining fracture risk, assessing bone turnover may add valuable information for the management of patients with low bone mass. Bone turnover markers (BTMs) are used in clinical trials where they can provide essential information on the biological efficacy of osteoporosis treatments. In such population-based studies, BTMs can predict fracture risk independent of BMD. When combined with BMD, they improve the fracture risk estimate above and beyond BMD alone in postmenopausal osteoporotic women. Since changes in bone turnover after the initiation of therapy with bone resorption inhibitors occur much more rapidly than changes in BMD, treatment efficacy could, in theory, be determined within weeks of using BTMs. However, such predictive value is limited by the large biological variability of these biochemical markers, even though newer automated methods have reduced their analytical variability. Consequently, widespread adoption as a means of predicting treatment efficacy in fracture prevention for individual patients cannot yet be recommended. BTMs may be useful for monitoring adherence to antiresorptive therapy and may aid in identifying patients for whom antiresorptive therapy is most appropriate. Thus, although BTMs are currently confined to clinical research applications, further improvement in assay precision may extend their diagnostic value in clinical settings.     

Clinical Use of Biochemical Markers of Bone Remodeling: Current Status and Future Directions

Biochemical markers of bone turnover provide a means of evaluating skeletal dynamics that complements static measurements of bone mineral density (BMD). This review evaluates the use of commercially available bone turnover markers as aids in diagnosis and monitoring response to treatment in patients with osteoporosis. High within-person variability complicates but does not preclude their use. Elevated bone resorption markers appear to be associated with increased fracture risk in elderly women, but there is less evidence of a relationship between bone formation markers and fracture risk. The critical question of predicting fracture efficacy with treatment has not been answered. Changes in bone markers as currently determined do not predict BMD response to either bisphosphonates or hormone replacement therapy. Single measurements of markers do not predict BMD cross-sectionally (except possibly in the very elderly), or change in BMD in individual patients, either treated or untreated. On the other hand, research applications of bone turnover markers are of value in investigating the pathogenesis and treatment of bone diseases. Markers have potential in the clinical management of osteoporosis, but their use in this regard is not established. Additional studies with fracture endpoints and information on negative and positive predictive value are needed to evaluate fully the utility of bone turnover markers in individual patients.     

Monitoring strontium ranelate therapy in patients with osteoporosis

Purpose  The purpose of this study was to review the monitoring of strontium ranelate osteoporosis therapy. Methods  The method used in this study was comprehensive literature review with clinical perspectives. Results  Changes in bone turnover markers (BTM) or bone mineral density (BMD) have been documented in osteoporosis clinical trials. However, neither BMD nor BTM changes fully explain the observed fracture risk reduction in treated patients. If changes in BMD or BTM on therapy would be easily discernable in individual patients, and were strongly associated with fracture risk reduction, monitoring individuals would be more useful. BMD changes in patients on strontium ranelate are of a greater magnitude and hence can be easily determined in an individual patient. In addition, there exists a better correlation between fracture risk reduction and increases in BMD. Conclusions  The strong correlation between measured BMD increases and fracture risk reduction in patients on strontium ranelate therapy will be of clinical benefit to physicians wishing to evaluate both treatment persistence and fracture risk reduction.     

Bone Mineral Density and Biochemical Markers of Bone Turnover in Peri- and Postmenopausal Women

Bone mineral density (BMD) measured by densitometry is the elective parameter for the diagnosis of osteopenia and osteoporosis. Biochemical markers have been proposed as sensitive indicators of high bone turnover and for monitoring response to antiresorptive treatment. We conducted a retrospective study to investigate the values of biochemical markers of bone metabolism with a view to early diagnosis of osteoporosis and monitoring of hormone replacement and calcitonin therapy. The subjects were 415 women, mean age 51 ± 8 years (43–62 years) in peri- and postmenopause, recruited at the Menopause Center of Obstetrics and Gynecology Department of Siena University and divided in five groups. Bone densitometry was performed in all subjects and blood samples were taken for assayed biochemical markers, that is, [osteocalcin (OC), parathyroid hormone (PTH), type 1 procollagen (PICP), and calcitonin (CT)]. Three groups of women were divided into two subgroups: those with normal and those with low BMD (<1 SD). Basal concentrations of PCP1, OC, PTH, and CT were compared in the various groups. Two groups of postmenopausal women with BMD below the normal were treated with estrogen replacement therapy and unmodified eel calcitonin. We evaluated whether some of these biochemical markers of bone turnover could help identify women with low BMD and whether they could be useful for monitoring the results of antiresorptive therapies. Markers of bone formation (PICP and OC) make it possible to distinguish women with high turnover who are at risk for osteoporosis from women with low turnover in menopause. A good correlation was also found between changes in levels of these markers and changes in BMD during treatments, which suggests that the PICP and OC would be useful for monitoring response to antiresorptive therapy. Received: 29 March 1998 / Accepted: 2 November 1999     

骨转换标志物在骨质疏松诊治中的分析评价及临床应用前景

骨代谢的生化标志物是成骨细胞和破骨细胞活动而释放至血和尿中的骨基质成分,可以反映整体骨转换率,对诊断骨质疏松症及其分型、预测骨量丢失情况、评估完全骨折的危险性、监测药物治疗疗效等均有重要的意义。目前BALP、TRACP、PINP、β-CTX等骨转换标志物已被大量应用于临床,但每种骨转换标志物均有其特殊性及变异性,综合分析才能对骨质疏松的演变及治疗进展有一个较好的评判。本文主要探讨了临床常用的骨转换标志物的应用现状及应用前景。     

骨转换标志物在糖尿病中的研究进展

随着糖尿病和骨质疏松症在我国的广泛流行,糖尿病性骨质疏松症已成为糖尿病患者致死、致残的重要原因,严重影响患者的生活质量,并给个人、社会带来沉重负担。1型糖尿病患者骨密度降低,骨折风险增加;2型糖尿病患者骨密度常增高或正常,但骨折风险也是增加的,这不能仅靠双能X线骨密度来解释。骨转换标志物具有灵敏度高、特异性强、稳定性好等优点,近年来在糖尿病中得到广泛研究,如骨碱性磷酸酶、1型原胶原N-端前肽、1型胶原交联C-末端肽、骨钙素、骨保护素、脱氧吡啶啉等。骨转换标志物反映骨吸收和骨形成的具体变化情况,反映骨强度,较骨密度更早的反映骨量变化,大量临床研究发现,它为临床早期发现和诊断糖尿病性骨质疏松症,评估糖尿病患者骨折风险提供了新思路。联合检测骨转换标志物和骨密度,更全面、合理的评估骨转换,及时发现高危人群,更有利于糖尿病性骨质疏松症患者的早期诊断及治疗,预防骨折的发生。本文将对骨转换标志物在糖尿病中的研究进展作一综述。     

Daily and intermittent oral ibandronate normalize bone turnover and provide significant reduction in vertebral fracture risk: results from the BONE study

Increasing evidence suggests that a high rate of bone turnover is associated with low bone mineral density (BMD) and is strongly linked to fracture risk. Measurement of biochemical markers of bone turnover is therefore becoming a more widely used endpoint in clinical trials in postmenopausal osteoporosis. This multinational double-blind, fracture-prevention study enrolled 2946 postmenopausal women with osteoporosis. Patients were randomized to receive placebo or oral ibandronate administered daily (2.5 mg/day) or intermittently (20 mg every other day for 12 doses every 3 months). The primary endpoint was the incidence of new vertebral fractures after 3 years. Secondary outcome measures included changes in the rate of bone turnover as assessed by biochemical markers and increases in spinal and hip BMD. Daily and intermittent oral ibandronate significantly reduced the risk of vertebral fractures by 62% and 50%, respectively, and produced significant and sustained reductions in all the measured biochemical markers of bone turnover. By 3 months, the rate of bone turnover was reduced by approximately 50–60%, and this level of suppression was sustained throughout the remainder of the study. In summary, oral ibandronate, given daily or with a between-dose interval of >2 months, normalizes the rate of bone turnover, provides significant increases in BMD and a marked reduction in the incidence of vertebral fractures. Thus, intermittent ibandronate has potential to become an important alternative to currently licensed bisphosphonates in postmenopausal osteoporosis.     

激素替代联合二磷酸盐预防和治疗绝经后骨质疏松症疗效的系统评价

目的 评价联合与单一用激素替代和二磷酸盐预防和治疗绝经后骨质疏松的疗效性和安全性.方法 计算机检索MEDLINE(1966～2008.10)、Embase(1984～2005)、PubMed(1966～2008.10)、Cocharane图书馆(CENTRAL 2008年第三期)、中国生物医学文献光盘数据库(1978～2006年)和中国期刊全文数据(1979～2008.10),并手工检索相关领域其他杂志.对纳入文献进行质量评价.数据分析采用RevMan 5.0,对于异质性小的研究合并效应量.结果 共纳入13 个随机对照试验,包括3341 例患者.Meta 分析结果显示:①联合治疗组与二磷酸盐单一用药组比较,在增加腰椎骨密度和减少骨折风险方面无明显差别,在降低骨转化标志物及药物副作用方面无优势.②联合治疗组与激素替代单一治疗组比较,在增加腰椎骨密度、药物副作用方面具有明显优势,在减少骨折风险、降低骨转化标志物方面无明显差别.结论 激素替代联合二磷酸盐预防和治疗绝经后骨质疏松症疗效优于激素替代单一治疗,但与二磷酸盐单一治疗比较并没有优势,且副作用明显增加.     

Hormonal profiles and biochemical indices of bone turnover in Indian women

Summary The study establishes Indian referent database for bone turnover markers. The levels of markers decreased across the four quartiles of BMD showing a negative correlation with BMD. The study depicts that levels of hormones and bone turnover makers can aid in identifying women at risk for osteoporosis. Introduction Biochemical markers of bone turnover reflect changes in bone metabolism earlier and aid in the management of osteoporosis. Since a referent database for Indian women is lacking, the study was initiated to establish the same and suggest that hormonal profiles and markers of bone turnover can aid in identifying women at risk for osteoporosis. Methods Osteocalcin (OC), bone specific alkaline phosphatase ((BSAP), C-terminal crosslinking telopeptide of type-I collagen (CTX-I), deoxypyridinoline (DPD), follicle-stimulating hormone (FSH) and estrone glucuronide (E₁G) were measured in 365 Indian women (20–70 years) and correlated with BMD measurements by dual energy absorptiometry (DXA) using one way analysis of variance (ANOVA). Results The mean levels of bone resorption markers; CTX-I and DPD increased significantly across the age showing a negative correlation with BMD. The increase in levels of CTX-I and DPD was significantly higher (p < 0.0001) as compared to the femoral and spinal BMD, which dropped only 30–36%. The levels of bone turnover markers and FSH decreased across the four quartiles of spinal and femoral BMD showing a negative correlation whereas E₁G levels increased across the four quartiles. Conclusion The bone turnover markers were comparatively low in cohort of Indian women studied.     

Bone density and markers of bone turnover in predicting fracture risk and how changes in these measures predict fracture risk reduction

Surrogate markers in clinical medicine provide a useful means to assess therapeutic response to pharmacologic therapy in a wide range of chronic disease states. In the area of osteoporosis, the surrogate markers of change in bone mineral density (BMD) and bone turnover markers (BTM) provide the clinician with a means of assessing the biologic response to osteoporosis-specific pharmacologic agents. Increases in BMD and/or reductions in BTM can independently be correlated to reductions in vertebral and nonvertebral fracture risk. In managing osteoporosis patients, the BTM change at an earlier point of time after initiation of therapy and a change in BTM can provide earlier feed-back to the patient and clinician regarding issues such as compliance and a bone biologic response. An increase in BMD at 12 or 24 months after initiation of therapy is also evidence of an improvement in bone strength though with antiresorptive agents no change in BMD may also be associated with risk reduction within clinical trial sets. In this regard, changes in BMD and BTM are complimentary in their application to patient management.