老年骨质疏松患者骨代谢标志物的检测与应用

骨代谢的过程能反映成骨细胞和破骨细胞活动及骨基质和骨矿化的变化。骨密度的测量为骨质疏松的诊断、治疗提供了可靠的依据，但骨密度的高低并不能反映骨转换。对于抗骨吸收和促进骨形成药物的评价有一定的局限性。而无创伤性、灵敏和特异的骨代谢标志物检查对于骨质疏松分型、鉴别诊断和骨折危险性的预测和治疗评价也是不可缺少的。在诊断骨强度和骨折危险性方面，骨密度和骨代谢标志物是两个各自独立的指标，而联合使用将提高骨质疏松和骨折风险的检出率.     

骨小梁分数在风湿病并发骨质疏松管理中的应用价值

骨质疏松症是以骨强度下降、骨折风险增加为特征的骨骼疾病。风湿病是继发性骨质疏松症的常见原因之一,可显著增加患者罹患骨质疏松、脆性骨折的风险,导致疾病致残及致死率升高。风湿病患者并发骨质疏松的风险预测、早期诊断、早期干预和治疗监测均具有重要意义。目前诊断骨质疏松的金标准是骨密度值(BMD),但BMD仅反映骨量变化,不能显示骨微结构等骨质量信息。骨小梁分数(TBS)是一种基于双能X线吸收测定法(DXA)图像的新型骨微结构无创评估手段。研究表明,TBS可用于原发性及各种继发性骨质疏松症的骨质量评估,并能作为BMD和骨折风险预测工具FRAX的辅助指标,提高骨折风险预测能力。本文就TBS在风湿病并发骨质疏松领域的相关研究进行综述,提示TBS在骨质疏松识别、骨折风险评估、药物疗效监测等方面的潜在应用价值。     

骨质疏松骨折基础和临床研究方法进展

骨质疏松是一种常见的代谢性骨病,其最严重的危害在于发生骨折.骨质疏松骨折与骨量减少和骨组织微结构退行性改变有关.对骨微结构、微损伤的基础研究有助于揭示骨折机制,而临床运用影像学手段可检测骨结构变化,结合有限元分析可预测骨折危险性.独立于骨结构的代谢途径标志物及骨折风险评估工具对骨折的早期防治也起了积极作用,关注已骨折患者的生命质量可降低再骨折风险.这些研究方法将为骨质疏松骨折危险性分析、药效检测等提供新的研究方向和思路.     

跟骨定量超声骨强度在骨质疏松筛查和诊断中的价值

目的 在社区人群中进行跟骨定量超声法(QUS)骨强度(STI)与双能X线吸收法(DXA)腰椎和髋部骨密度(BMD)测量的临床对比,探讨QUS在骨质疏松筛查和诊断中的临床应用价值.方法 在上海长风社区对6 105例45岁以上常住户籍居民,采用DXA测定腰椎1～4、双侧髋部BMD值,同时采用QUS测定右侧跟骨STI值,分析两者的相关性,以DXA为金标准评价QUS测定STI在骨质疏松筛查和诊断中的灵敏度、特异度和诊断一致率.结果 DXA和QUS诊断的骨量减少、骨质疏松的患病率分别为38.82％、10.29％和64.50％、4.49％.STI与腰椎、左侧和右侧髋部BMD相关系数分别为0.536、0.574和0.570(P值均＜0.001).与DXA相比,QUS筛查骨量异常(骨量减少和骨质疏松)的灵敏度为86.16％、特异度为47.57％,诊断骨质疏松的灵敏度为23.57％、特异度为97.70％.结论 QUS测定STI与DXA测定BMD有较好的相关性和一致性,QUS筛查骨量异常的高灵敏度和诊断骨质疏松的高特异度使之成为值得在基层医疗机构推广使用的骨质疏松筛查和诊断工具.     

骨定量超声测量及OSTA指数与绝经后妇女非椎骨骨折的关系

目的横断面社区研究分析绝经后妇女OSTA指数及多部位定量骨超声（quantitative ultasound,QUS）[超声速率（speed of sound,SOS）],探讨该两个指标预测非椎骨骨折的价值。方法采用以色列Sunlisht Omnisense7000P型QUS仪测量513例女性受试者非优势侧桡骨远端1／3、中指近节指骨及胫骨中段SOS。测量受检者身高、体重,计算OSTA指数,上门问卷形式询问骨折史。结果（1）271例绝经后妇女桡骨、指骨、胫骨SOS显著低于242例绝经前妇女,P〈0．001。（2）绝经后妇女非椎骨骨折组桡骨SOS低于无骨折组（P=0．044）,发生于绝经后的非椎骨骨折妇女,指骨SOS低于无骨折组（P=0．003）。（3）以OSTA〈-4、-4- -1、〉-1将绝经后妇女分为骨质疏松高、中、低风险3组。随骨质疏松风险增加,发生于绝经后的非椎骨骨折率明显升高（χ^2=6．370,P=0．041）,且桡骨、指骨、胫骨SOS显著下降。（4）OSTA取-1及指骨SOSt值取-1．95反映绝经后非椎骨骨折的敏感性分别为75％和81％,特异性分别为48％和40％,受试者工作特征曲线下面积（AUC）分别为0．64和0．66。两者结合敏感性为83％,特异性提高至84％,AUC为0．64。结论OSTA和QUS尤其是指骨SOS具有反映绝经后妇女非椎骨骨折的能力。这两种非常简单、廉价、无创伤性的检查方法有助于筛查高危骨折风险的绝经后妇女。     

老年人骨折与骨密度及骨代谢生化测定探讨

目的　了解老年人骨折时骨骼的状态。方法　选取 60岁以上老年人 1 78例 ,询问病史及进行骨密度、骨代谢生化指标测定。结果　 (1 )骨密度下降与骨折发生密切相关 ,骨折发生的机会依次为骨质疏松组 >骨量丢失组 >骨量正常组。 (2 )骨折部位与此部位骨密度下降有关 ,髋部之股骨颈及大转子骨密度的下降对髋骨折的发生意义较大。 (3)骨生化测定仅骨钙素与骨密度呈正相关。结论　骨质疏松是老年人骨折的重要危险因素 ,骨密度下降提示骨折可能性增高 ,要防止老年人骨折必须减少骨量丢失。骨钙素测定可一定程度反映骨密度的量值 ,对骨质疏松的存在可做一初步的预测     

骨转换生化标志物预测骨质疏松性骨折的研究进展

骨质疏松症是一种全身疾病,多见于老年人,尤其是绝经后女性,其最严重的并发症为骨折,但目前对骨折发生风险的预测方法有限且准确性不足。骨转换生化标志物为骨重塑时骨组织自身代谢产物,较骨密度可更敏感地反映体内骨代谢情况。血清Ⅰ型前胶原氨基端前肽（P1NP）在骨质疏松性骨折的发生、评价骨量、监测治疗疗效等方面都有较高的应用价值;β-胶原降解产物（β-CTx）作为骨吸收的标志物对于骨质疏松性骨折有着显著的预测作用;血清N-端骨钙素（N-MID）可作为预测骨质疏松性骨折的生物学标志物,但其单一预测价值有限,与P1NP和β-CTx等联合检测,临床预测效能更为明显。     

老年人骨质疏松的遗传学研究

骨质疏松是一种常见的具有遗传倾向的年龄相关性疾病，其特点表现为骨量的减少、骨组织的超微结构破坏、骨强度减弱及骨折的风险增加。在美国，90%的白种老年女性和70%的白种老年男性所发生的髋骨和脊柱骨折与骨质疏松有关.随着人口预期寿命的延长,骨质疏松已成为老年人群发病率和病死率明显增高的主要公共卫生问题。目前大多数研究表明,骨量的获得和维持虽然受多种因素如遗传、激素、营养、生活方式等的影响，但70%左右的骨密度可以用遗传变异来解释.而且,骨丢失程度及骨转换率的变异也证实与遗传相关.因此,通过对骨质疏松遗传机制的深入研究,有望发现具有预测骨质疏松风险的易感基因,并可作为骨质疏松的遗传标记,使骨质疏松得到早期防治和诊断。     

慢性阻塞性肺疾病患者骨代谢研究进展

COPD是一种以气流持续受限为特征的慢性呼吸系统疾病,其患病率、致残率、病死率高.骨质疏松是以骨量减少、骨结构退化和骨折风险增加的骨代谢性疾病,是COPD的重要合并症之一,但在临床中常被忽视.当COPD合并骨折时,可引起患者肺功能下降、急性加重频率及病死率增加,因此及早诊治COPD合并的骨质疏松能有效预防骨折的发生,改善患者预后.因此,早期发现、早期诊治骨质疏松,预防骨质疏松相关的骨折对于COPD患者具有重要意义.     

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世界卫生组织(WHO)推荐使用双能X线BMD测量仪(DXA)测定的骨密度诊断骨质疏松,以T≤-2.5为骨质疏松。对没有发生过骨折又有低骨量的人群(T>-2.5),采用骨折风险评估模型(FRAX)工具可以计算出每位个体发生骨折的绝对风险。面对每位"骨质疏松"患者,医师都应该做到低骨量的鉴别诊断、原发性或继发性骨质疏松的鉴别诊断、未来骨折风险的评估。     

The use of ultrasound in the assessment of bone status

The assessment of skeletal status has wide clinical applications, especially in the management of osteoporosis. Osteoporosis, once thought of as an unpreventable and untreatable aging process, has revealed many of its secrets over the last decade, and the advent of successful drug therapy has changed our perception of the disease. Non-invasive techniques play a fundamental role in the diagnosis of osteoporosis and in the assessment of the efficacy of drug treatments. The primary technique used in osteoporosis is dual X-ray absorptiometry (DXA), that has been established as a reliable means of measuring bone density. Quantitative ultrasound (QUS), because of the relative portability of the equipment, ease of use, lack of ionizing radiation and low cost, has great potential for widespread use. Five devices for QUS assessment have recently been approved by the Food and Drug Administration and many more applications are in progress. QUS is a relatively new technology, at least in its application to bone fragility. Nevertheless, QUS has demonstrated that it is able to detect bone fragility as well as DXA. However, diagnosis of osteoporosis by QUS remains contentious, but the problems are due more to the limitations of the present T-scores rather than to the technique. A better option for QUS would be to report results in terms of remaining lifetime fracture risk, keeping in mind that a risk estimate needs not only the QUS or DXA measurement, but also the specific data, such as age, weight, gender, hormonal status and fracture history of the patient.     

What is the role of DXA, QUS and bone markers in fracture prediction, treatment allocation and monitoring?

There is evidence that treatment can decrease the risk of fractures in osteoporotic patients, and screening of these patients is therefore relevant. Diagnosis of osteoporosis is based on the T-score calculated from bone mineral density (BMD) measurements. BMD measurements have been widely used for the management of osteoporosis, and a low BMD is a strong risk factor for fractures. But BMD measurement has several limitations in both diagnosis, prediction of fracture risk, and treatment follow-up. Quantitative ultrasound (QUS) parameters, an alternative to BMD in the assessment of bone, are independent risk factors for osteoporotic fracture. However, the use of QUS cannot be recommended for both allocation and monitoring of treatment. Biochemical markers of bone remodelling can be useful for both prediction of fracture risk and monitoring of treatment if sources of variability are controlled.     

原发性骨质疏松症的诊断和防治

骨质疏松症是以骨强度降低、骨折危险性增加为主要表现的骨骼疾病，骨强度反映了骨密度和骨质量的完整性。本文简要介绍现今对原发性骨质疏松症的诊断和防治。诊断基于双能X线吸收法测定的、由世界卫生组织制定标准的骨密度值。预防应置于首位，重视对医师和群众的宣教，针对认识上存在的误区。干预的阈值还存在不同的意见，尚须进一步探讨。药物治疗已有不少进展，选择用药应根据本病的特点、循证医学的证据、降低骨折发生和成本及效益分析而进行全面衡量，作出决策。     

The role of quantitative ultrasound in predicting osteoporosis defined by dual X-ray absorptiometry

The aim of this study was to establish whether quantitative ultrasound (QUS) parameters could identify patients classified as osteoporotic and osteopenic on the basis of dual energy X-ray absorptiometry (DEXA). One hundred and twenty-three patients (39 male, 84 female) with osteoporosis and suspected of having osteoporosis were included in this study. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured and bone mineral densities (BMD) of the lumbar spine and left hip was measured by DEXA. Subjects were classified into three groups (normal, osteopenic and osteoporotic) on the basis of BMD T-scores measured by DEXA. QUS parameters of the osteoporotic group were significantly lower than those of osteopenic and normal groups; there was no difference in QUS parameters between the normal and osteopenic groups. Correlations of both right and left SOS and BUA with the spine and femoral neck BMD were moderate (r = 0.343-0.539, P < 0.001). There was also reasonable correlation between DEXA and QUS T-scores (r = 0.364-0.510, P < 0.001). QUS had a sensitivity of 21% and a specificity of 95% for diagnosing osteoporosis. We concluded that, although DEXA and QUS parameters were significantly correlated, QUS parameters can not predict osteopenia as defined by DEXA, and sensitivities and specificities of QUS parameters were not sufficiently high for QUS to be used as an alternative to DEXA.     

Risk assessment for osteoporosis by quantitative ultrasound of the heel in ankylosing spondylitis

OBJECTIVE: The aim of this cross-sectional cohort study is to assess the potential of quantitative ultrasound (QUS) of the calcaneus in pre-screening for vertebral/non-vertebral fractures, and in discriminating osteoporotic from normal bone density in patients with ankylosing spondylitis (AS); a second objective is to determine the prevalence of osteoporosis using dual-energy X-ray absorptiometry (DEXA) in this patient group. RESULTS: Included are 50 consecutive AS patients with no history of osteoporosis: mean (SD) age 52 (12) yrs, range 26-75 yr; female/male ratio 15/35. The mean (SD) DEXA T score in the lumbar spine (AP view) was -0.82 (1.73), mean (SD) DEXA T score in femoral neck -1.46 (1.12). The mean (SD) calcaneal QUS T score was -0.73 (0.95). In our population of AS patients the prevalence of femoral neck osteoporosis according to the WHO definition (DEXA T < -2.5) was 20%. Osteoporosis criteria were met at the femoral neck in 10 (20%) patients, and 7 of them (70%) were correctly diagnosed using QUS, with T < -1.0 as cut-off value; normal bone density at the femoral neck was found in 15 AS patients (30%), yet in 2 of them the calcaneal QUS T was < -1.0. In AS the 20% pretest probability of having femoral neck osteoporosis increased using calcaneal QUS, with a cut-off level T < -1.0 (70% sensitivity, 68% specificity), and then rose to 35% as the predictive value of a positive test, yielding a net result of QUS testing of +15%. The predictive value of a negative QUS test result was 90%, which makes QUS applicable to exclude severe osteoporosis. Vertebral and/or non-vertebral fractures occurred in 12 out of 50 AS patients (24%); 5 of them (10%) were associated with osteoporosis as defined by WHO criteria measured via DEXA. CONCLUSION: The performance of QUS is similar to DEXA in finding patients with osteoporosis-associated fractures: the sensitivity of QUS T < -1.0 in finding the fracture is 80%, and the sensitivity of femoral neck DEXA T < -2.5 in finding fractured patients is 60%. We conclude that both osteoporosis and fractures are common sequelae in AS. Calcaneal QUS offers a promising approach to screen for osteoporosis, and may be applied to exclude osteoporosis-associated high fracture risk in AS.     

Recommendations based on the evidence for secondary prevention of fractures/osteoporosis

For Japanese women aged 65 years and older and men aged 75 years and older, osteoporosis screening through the use of DXA is recommended. For those with risk factors of osteoporosis and bone fracture among postmenopausal women younger than 65 years of age and men younger than 75, osteoporosis screening is considered to be beneficial. Regarding effectiveness of the screening among perimenopausal women, there is simply no evidence to recommend the screening. Further investigation is necessary into the effectiveness of using QUS for osteoporosis screening, as accuracy tends to suffer depending on the type of QUS device used and the level of values measured.     

骨质疏松诊断中的几个关键问题

本文对骨质疏松临床诊断中的一些关键问题作了论述,首先阐明了骨质疏松和骨折风险评价相关的概念,以及如何避免临床实践中经常会遭遇的误区,进而对骨代谢检验指标和骨量(bone mass)测定的常用方法作了系统的分析,分析了各项指标的适用范围和局限性,以使临床医生在临床实践中能够合理选用这些指标.

Abstract：

Several key issues in the diagnosis of osteoporosis were discussed. The definition of osteoporosis and some concepts in bone fracture risk evaluation were explained, so as the methods to avoid the common misunderstandings in clinical practice. Finally, the parameters used in determination of bone metabolism and bone mass were listed, and their application and limitation were analyzed. It may help the clinicians to make correct choice of these parameters.     

Comparison of quantitative ultrasound parameters with dual energy X-ray absorptiometry in pre- and postmenopausal women

BACKGROUND: Quantitative ultrasound (QUS) has been claimed as an alternative technique for risk assessment of hip fractures associated with osteoporosis. However, reports concerning modest correlations between QUS parameters and dual energy X-ray absorptiometry (DXA) in women raise questions about the reliability of QUS technology to predict bone mineral density (BMD). Partially, the lack of stronger correlations may be due to heterogeneity in bone architecture deterioration which may be more pronounced in older than in younger women. Therefore, it was thought important to study QUS/DXA interrelationships in subgroups of pre- and postmenopausal women. METHODS: We studied 217 pre- and postmenopausal women between the ages of 25 and 75 years, who were referred for a BMD measurement because of osteoporosis in at least one family member either in the first or in the second degree. All women had a calcaneal QUS and a DXA measurement at the lumbar spine, total hip and femoral neck. RESULTS: The linear regression coefficients between the QUS parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) and DXA at the various sites in the group as a whole were 0.53 to 0.54 (P<0.0001). Significantly lower regression coefficients between BUA and DXA at the total hip and the femoral neck were found in premenopausal women (r=0.31 and 0.38, P<0.0001) compared to postmenopausal women (r=0.56 and 0.53, P<0.0001). For SOS there was no significant difference between the regression coefficients in the pre- and postmenopausal group. The overall prevalence of osteoporosis as assessed by DXA in the total group was 25% (6% in the pre- and 36% in the postmenopausal group). BUA failed to detect osteoporosis in all five premenopausal women but also in 20 out of 50 postmenopausal women with osteoporosis according to DXA measurements. SOS measurements were even worse in this respect. CONCLUSIONS: Linear regression coefficients between calcaneal QUS parameters and DXA are only modest considering a group of 25--75-year-old Dutch women. In the subgroup of premenopausal women correlations between BUA and BMD at the hip and femoral neck are worse compared to those in postmenopausal women. The predictive value of QUS parameters for BMD is limited, therefore it is not appropriate to use QUS as a surrogate for DXA.     

Quantitative ultrasound of the proximal phalanges and dual-energy X-ray absorptiometry in Crohn's disease patients with osteopenia

Background: Osteopenia and osteoporosis are frequent complications in Crohn's disease, and these features are associated with an increased risk of vertebral and appendicular fractures. Bone mineral density (BMD) measurements are widely accepted to assess the fracture risk in postmenopausal osteoporosis. In recent years, quantitative ultrasound (QUS) has become attractive for the diagnosis of osteopenia as a nonionizing method. The aim of the present study was to investigate QUS and BMD measurements in osteopenic patients with Crohn's disease. Methods: BMD of the lumbar spine and femoral neck and QUS of proximal phalanges II-V (DBM Sonic 1200; IGEA) were performed prospectively in 171 patients with Crohn's disease. The amplitude-dependent sound-of-speed (AD-SoS) and the ultrasound bone profile score (UBPS) were calculated using the WinSonic PRO 1.1 software program. X-ray examination of the spine was performed in 131 patients. Vertebral deformity was morphometrically defined according to the published methods of McCloskey and Eastell. Results: BMD of the lumbar spine and femoral neck correlated significantly (r = 0.62), but no correlation between BMD and QUS could be demonstrated. Vertebral deformities (VD) were detected in 28/131 (21.4%) patients. Two patients had a history of femoral fracture (FF). Lumbar BMD was lower in patients with either VD or FF than in those patients with no preexisting fractures (T-score: −2.46 vs −2.04; P = 0.0233). QUS parameters correlated negatively to patients' age but could not be used to discriminate between patients with and without VD/FF. Conclusions: Osteoporosis-related fractures are associated with a low lumbar bone density in Crohn's disease patients. QUS of the proximal phalanges cannot detect manifest osteoporosis in Crohn's disease patients and is therefore not valuable as a screening tool for these patients. Received: January 10, 2002 / Accepted: August 30, 2002 Acknowledgments. Morphometry of vertebral radiographs was supported by the Osteoporosis Study Group of the Clinic for Radiology and Nuclear Medicine, Klinikum Benjamin Franklin, Berlin, Germany. Reprint requests to: C. von Tirpitz