Biochemical markers of bone turnover: potential use in the investigation and management of postmenopausal osteoporosis

Introduction  The aim was to analyse data on the use of biochemical bone turnover markers (BTM) in postmenopausal osteoporosis. Methods  We carried out a comparative analysis of the most important papers concerning BTM in postmenopausal osteoporosis that have been published recently. Results  The BTM levels are influenced by several factors. They are moderately correlated with BMD and subsequent bone loss. Increased levels of bone resorption markers are associated with a higher risk of fracture. Changes in the BTM during the anti-osteoporotic treatment (including combination therapy) reflect the mechanisms of action of the drugs and help to establish their effective doses. Changes in the BTM during the anti-resorptive treatment are correlated with their anti-fracture efficacy. Conclusion  Biological samples should be obtained in a standardised way. BTM cannot be used for prediction of the accelerated bone loss at the level of the individual. BTM help to detect postmenopausal women who are at high risk of fracture; however, adequate practical guidelines are lacking. BTM measurements taken during the anti-resorptive therapy help to identify non-compliers. They may improve adherence to the anti-resorptive therapy and the fall in the BTM levels that exceeds the predefined threshold improves patients’ persistence with the treatment. There are no guidelines concerning the use of BTM in monitoring anti-osteoporotic therapy in postmenopausal women.     

New biochemical markers of bone resorption derived from collagen breakdown in the study of postmenopausal osteoporosis

The aim of this work was to perform a comparative study between three recently developed biochemical markers of bone resorption derived from collagen metabolism — (1) total urinary free pyridinolines (Pyr), (2) serum pyridinoline cross-linked carboxy-terminal telopeptides of type I collagen (ICTP) and (3) a urinary-specific sequence for a part of the C-telopeptide of the ₁ chain of type I collagen (CTX) — in the diagnosis and follow-up of postmenopausal osteoporosis. Results were also evaluated relative to the classical biochemical marker urinary hydroxyproline (Hyp). The study included 20 untreated osteoporotic postmenopausal women (OSP), age 60 ±6 years, range 46–69 years; 27 osteoporotic postmenopausal women treated (OSP-T) by cyclic therapy with disodium etidronate, 25-hydroxyvitamin D and calcium for a period between 3 months and 4 years (25±15 months), age 59±7 years, range 41–67 years; 17 osteopenic postmenopausal women, age 57±6 years, range 46±68 years; and 29 healthy control postmenopausal women, age 56±7 years, range 41–70 years. The diagnostic criterion for postmenopausal osteoporosis was a bone mineral density (BMD) (Hologic QDR-1000) in lumbar spine and/or femoral neck more than 2 SD below the mean value corresponding to an age- and sex-matched healthy control group. For inclusion in the osteopenic group BMD values had to be between 1 and 2 SD below the mean BMD value corresponding to the control group. We found a significant increase (p<0.01) in the levels of Pyr/Cr and CTX/Cr (Cr=creatinine) in OSP patients with respect to the control group and we did not obeserve any significant difference between control and OSP-T or osteopenic women. It is interesting to note that there was a mean increase in CTX/Cr in OSP patients of 101% of the control values, while the mean increase found in Pyr/Cr concentration was only 33%. However, we did not find significant differences in the concentrations of ICTP and Hyp/Cr between groups. In a comparison of Pyr/Cr and CTX/Cr, urinary CTX showed the higher diagnostic accuracy, as can be deduced from the receiver operating characteristic (ROC) curves. CTX sensitivity was 40% with a specificity of 100%, whereas the sensitivity was 25% for urinary Pyr/Cr. In conclusion, the results of the present work suggest that in osteoporotic women CTX has the highest diagnostic accuracy among the markers of bone resporption studied.     

广场舞对绝经期后骨质疏松患者的骨密度和骨转换指标影响的研究

目的观察广场舞对绝经后骨质疏松患者的骨密度、骨转换指标的影响。方法研究组:口服钙尔奇D600 mg每日1次的同时,联合广场舞运动方法干预,每周5次,每次平均0.5~1.0小时;对照组:单纯采用口服钙尔奇D600 mg每日1次,观察两组实验前及实验干预6个月后受试者骨密度、骨转换指标变化、骨痛。结果 (1)骨密度变化:研究组治疗6个月后,腰椎L2-4、股骨颈部的骨密度较治疗前明显升高(P0.05),Ward’s区骨密度无显著性改变。而对照组各部位骨密度较前无明显改变(P0.05)。(2)血生化中血钙、血磷及碱性磷酸酶指标值:两组生化指标在治疗前后无统计学差异(P0.05);治疗6个月后P1NP的水平明显升高(P0.05),β-CTX水平未有明显改变(P0.05)。(3)疼痛程度改善情况:两组治疗前后疼痛分级比较,研究组疼痛明显改善。结论广场舞运动能部分改善绝经后妇女骨密度,并且可以缓解骨质疏松引起的疼痛,是一种切实可行的预防和治疗骨质疏松症的临床方案。     

Increased bone resorption and decreased bone formation in Chinese patients with hip fracture

Biochemical markers of bone formation (bone-specific alkaline phosphatase and osteocalcin) and bone resorption (hydroxyproline excretion and bone isoenzyme of acid phosphatase) were measured in 30 patients (15 M and 15 F) with hip fracture and 30 healthy subjects matched for age and sex. Bone isoenzyme of tartrate-resistant acid phosphatase (TRACP) was measured by a recently developed specific immunoassay. Serum osteocalcin concentration and bone-specific alkaline phosphatase activity were significantly lower and serum TRACP concentration and urinary hydroxyproline excretion were elevated in patients compared with healthy subjects. We suggest that there is reduced bone formation and increased bone resorption in patients with hip fracture.     

原发性甲状旁腺机能亢进症手术治疗后骨量和骨代谢指标的变化

目的 了解甲状旁腺切除术对原发性甲状旁腺机能亢进症病人的骨矿密度及骨代谢指标变化的影响。方法 ４０例病人,其中３０例未治疗组（男：女＝３：２７）;１０例已手术治疗组（男：女＝３：７）,手术后时间１～２４月（平均５．３±７．９月）。用ＤＥＸＡ测量腰椎及股骨颈的骨矿密度,同时,测定血清中的甲状旁腺素（ＰＴＨ）,骨钙素（ＯＣ）,及骨唾液酸蛋白（ＢＳＰ）。结果 在已手术组病人其腰椎及股骨颈骨矿密度再没有明     

依替膦酸二钠抑制绝经后骨质疏松症患者骨吸收的临床研究

目的　评价依替膦酸二钠对绝经后骨质疏松症患者骨吸收的抑制作用。方法　绝经后骨质疏松症患者 32例 ,测定其腰椎、股骨颈骨密度和尿中脱氧吡啶啉的浓度。口服依替膦酸二钠2 0 0mg ,2次 d ,2周后改服钙尔奇D片 (钙 6 0 0mg及维生素D 12 5IU d) 11周 ,共 13周为一疗程 ,治疗两个疗程后复查骨密度和尿脱氧吡啶啉的浓度。结果　治疗两个疗程后 ,患者腰椎骨密度显著增高 (治疗前为 0 6 94± 0 12 4g cm2 ,治疗后为 0 72 1± 0 10 8g cm2 ,P <0 0 5 ) ,股骨颈骨密度无显著变化 (治疗前为 0 5 91± 0 117g cm2 ,治疗后为 0 6 0 2± 0 0 98g cm2 ,P >0 0 5 ) ;尿脱氧吡啶啉浓度显著降低 (治疗前为 6 6 7± 2 0 4nmol mmolCr,治疗后为 4 2 2± 1 6 3nmol mmolCr,P <0 0 1)。结论　依替膦酸二钠能有效抑制绝经后骨质疏松症患者的骨吸收。     

细胞因子在绝经后骨质疏松症发病机制中的作用

雌激素、免疫细胞因子及骨代谢三者相互作用,绝经后骨质疏松症主要与雌激素缺乏导致细胞因子激活破骨细胞的活性密切相关。雌激素缺乏导致巨噬细胞和T细胞分泌IL-1和TNFα,抑制调节性T细胞增殖和成熟,促进NFκB、IL-15和IL-17的产生,从而诱导破骨细胞发展;抑制成骨细胞和骨系细胞产生OPG,促进RANK-RANKL相互作用,导致破骨细胞活性增强;抑制成骨细胞和骨细胞的TGFβ,减少破骨细胞凋亡。     

绝经后骨质疏松妇女血清相关激素水平的改变

目的　通过分析绝经后骨质疏松妇女某些骨代谢相关激素的血清水平的改变 ,探讨其与绝经后骨质疏松的关系。方法　 6 2名绝经 2年以上妇女 ,测量腰椎骨密度 ,分为骨质疏松组 (30名 )和对照组 (32名 )。隔夜空腹取血测定血清LH、FSH、E1、E2 、DHEA、DHEA S、SHBG、GH、CT、PTH、2 5 (OH)D3 。结果　绝经后妇女骨质疏松组和对照组在年龄上无差异 (5 9 5 6± 6 6 5vs 5 9 35± 7 6 3,P>0 0 5 )。骨质疏松组体重指数BMI (2 4 2 7± 2 4 6 )低于对照组 (2 6 83± 4 16 ,P <0 0 5 )。绝经后妇女血清E1(r= 0 6 0 0 ,P <0 0 0 1)、DHEA(r= 0 70 8,P <0 0 0 1)、DHEAS(r = 0 5 82 ,P <0 0 0 1)与年龄负相关。骨密度与LH负相关 (r= 0 4 39,P <0 0 5 )。骨质疏松组与对照组相比 ,LH、SHBG显著增高 (P<0 0 5 ) ,DHEA、DHEAS显著降低 (P <0 0 5 )。FSH、CT、PTH、2 5 (OH)D3 、GH、E1、E2 差异无显著性。结论　绝经后妇女骨代谢相关激素血清水平的改变参与了绝经后骨质疏松的发病     

绝经后骨质疏松及骨量减少患者治疗前后骨密度变化的研究

目的 观察利塞膦酸钠防治绝经后骨质疏松症的疗效。方法 绝经后骨质疏松症48例,对照组24例,服安慰剂,实验组24例,服利塞膦酸钠5 mg/d,两组每日均服凯思立D 1片,2组共观察6月。结果 利塞膦酸钠组腰椎、股骨颈及大粗隆的骨密度均明显升高(P<0.05),实验组总有效率为80.95％,明显高于对照组的45.45％(P<0.01)。结论 利塞膦酸钠能明显提高绝经后骨质疏松症患者的骨密度,副作用轻。     

Serum levels of 25-hydroxyvitamin D in postmenopausal osteoporosis

Summary Serum concentrations of 25-hydroxyvitamin D were measured in a group of women with symptomatic postmenopausal osteoporosis, assessed by bone biopsy. A competitive protein binding assay was used, which included a chromatographic step. Accurate surveys of dietary or therapeutic vitamin D intake and light environment were obtained in each patient. Women with severe postmenopausal osteoporosis were found to have significantly (P<0.001) higher serum levels of 25-hydroxyvitamin D than age-matched normal women, the mean values being 27.5 ng/ml (±13.6 SD) and 8.2 ng/ml (±5.7), respectively. The authors hypothesize that the reduction in 1,25-dihydroxyvitamin D, recently reported in postmenopausal osteoporotic women, might be responsible for the increased serum levels of 25-hydroxyvitamin D through an inadequate product inhibition of liver vitamin D 25-hydroxylase.     

Effects of salmon calcitonin in postmenopausal osteoporosis: A controlled double-blind clinical study

Summary In this paper we present the results of a 12-month double-blind clinical multicenter study assessing the effects of synthetic salmon cacitonin (CT) administration in a group of white postmenopausal osteoporotic women. Treated patients were given 100 MRC units of synthetic salmon CT injected i.m. in the morning every other day. Control patients received a placebo injection. All patients received 500 mg of elementary calcium p.o., b.i.d. Bone mineral content (BMC) was measured at the extreme distal radius of the nondominant arm by a dual photon bone densitometer which utilizes two radionuclides,²⁴¹Am and¹²⁵I, with energies of about 60 keV and 30 keV respectively. Biochemical parameters of calcium-phosphorus metabolism were also measured. After 12 months of treatment a significant mean increment of BMC and nondialyzable OHPr/creatinine values and a significant decrease of total OHPr/creatinine values were observed in the treated group, while controls showed a significant decrease in BMC values. These results, together with the observation that in some patients the decrease in total OHPr/creatinine values was not accompanied by an increment of BMC, show that long-term salmon CT treatment may be of benefit in postmenopausal osteoporosis and that the effects of CT on bone mass may be due not only to the inhibition of bone resorption but also to the stimulation of bone formation. The results of this study were partially reported in an abstract presented at the International Symposium “Calcitonin '84”, held in Milan on 2–4 October 1984.     

Effect of a long-term treatment with 1,25-dihydroxyvitamin D3 on osteocalcin in postmenopausal osteoporosis

Summary Serum bone Gla-protein (BGP or osteocalcin) was measured in 25 women with histologically confirmed postmenopausal osteoporosis before and during long-term treatment with 1 μg/day of 1,25-dihydroxyvitamin D₃(1,25(OH)₂D₃). Basal serum BGP was significantly lower in osteoporotic women (3.8±1.4 ng/ml) than in agematched controls (6.8±2.0 ng/ml). During 1,25(OH)₂D₃ therapy serum BGP increased so that the mean of the values observed on treatment (4.8±1.5) was significantly higher than the mean basal value. It is known that BGP synthesis is stimulated by 1,25 (OH)₂D₃ and that serum BGP is a specific marker of bone formation; therefore, it is possible that the low basal levels of osteocalcin we observed were related to the low serum 1,25(OH)₂D concentrations reported in osteoporotic women and that the increase in BGP levels observed under 1,25(OH)₂D₃ treatment was a consequence of osteoblast stimulation.     

细胞因子与绝经后骨质疏松症关系的研究进展

雌激素、免疫细胞因子和骨组织的代谢三者之间具有密切而又复杂的联系。雌激素除了可直接与成骨细胞和破骨细胞上的雌激素受体结合产生生物学效应外,另一方面还可以影响骨细胞和成纤维细胞等对某些细胞因子的表达,如激活OPG/RANK/RANKL系统、增加TGF-β、IGF-1等的分泌;减少IL-1、IL-6、TNF-α等抑制性细胞因子的表达等。各种细胞因子之间相互作用、联系,组成复杂的调控网络,与细胞外基质一起形成骨组织发育所特需的骨微环境,它们作用于成骨细胞和破骨细胞,介导骨细胞的分化及成熟,参与正常的骨组织的代谢。因此绝经后由于雌激素的丢失,使细胞因子的表达发生改变,其在骨组织的代谢及代谢性骨病的发病中起到重要作用。     

Intestinal hyperabsorption of calcium and low bone turnover in hypercalciuric postmenopausal osteoporosis

Hypercalciuria of intestinal origin has been linked with bone loss in calcium nephrolithiasis and idiopathic osteoporosis. This retrospective data analysis was performed to explore potential pathogenetic link between intestinal hyperabsorption of calcium and postmenopausal osteoporosis. Data were retrieved from postmenopausal women who were evaluated for osteoporosis or osteopenia at the Mineral Metabolism Clinic of UT Southwestern Medical Center. A total of 319 patients underwent the test of calciuric response to oral calcium load to obtain an indirect measure of intestinal calcium absorption. Serum and urinary biochemistry and L2–L4 bone mineral density (BMD) were compared between five quintiles of calciuric response. There was a statistically significant trend toward a rise in 24-h urinary calcium and a decrease in urinary deoxypyridinoline (DPD) and BMD, with increasing order of quintiles. The presentation of those in the 1st quintile was consistent with vitamin D insufficiency or deficiency, with impaired calcium absorption, secondary hyperparathyroidism, and stimulated bone turnover (high normal urinary DPD). In contrast, patients in the 5th quintile displayed a picture of absorptive hypercalciuria of stone disease, with intestinal hyperabsorption of calcium, high or high normal urinary calcium and suppressed bone turnover (low or low normal urinary DPD). Thus, the assessment of intestinal calcium absorption in a seemingly homogeneous group of postmenopausal women with osteoporosis or osteopenia revealed a spectrum of calciuric response whose extremes may represent two physiologically distinct subtypes that have important diagnostic and therapeutic implications.     

绝经后骨质疏松症影响因素的Meta分析

目的 系统评价绝经后骨质疏松症的危险因素及保护因素.方法 以电子检索结合手工检索及索引检索的方式检索所有绝经后骨质疏松症影响因素的病例对照研究、队列研究的中英文研究文献,对纳入的文献进行质量评价后提取数据信息,采用专用软件RevMan 5.0完成系统评价过程.结果 共纳入13篇临床研究.家族骨折史、个人骨折史、绝经年限(≥5年)、经常吸烟、文化程度低、体重指数(≥25)、激素替代疗法、补充钙剂、少量饮酒、经常运动等与绝经后骨质疏松症的发生有关.结论 初步得出家族骨折史、个人骨折史、绝经年限(≥5年)、经常吸烟、文化程度低能够促进绝经后骨质疏松症的发生,而体重指数(≥25)、激素替代疗法、补充钙剂、少量饮酒、经常运动等有助于预防绝经后骨质疏松症的发生.     

免疫系统在绝经后骨质疏松症中的作用

随着我国老龄人口的不断增加,绝经后骨质疏松症（postmenopausal osteoporosis,PMOP）的发病率在不断增加。雌激素的减少导致的骨量丢失是引起PMOP的主要原因。雌激素引起骨量丢失的机制十分复杂,而且与免疫系统密切联系。本文将对免疫系统在PMOP的作用进行简要综述,以期为本病的治疗提供一种新的思路。     

Histomorphometric evaluation of daily and intermittent oral ibandronate in women with postmenopausal osteoporosis: results from the BONE study

The bisphosphonate ibandronate, administered either daily or intermittently with an extended between-dose interval of >2 months, has been shown to reduce significantly the incidence of vertebral fractures, to increase bone mineral density and to reduce levels of biochemical markers of bone turnover in a phase III randomized study in women with postmenopausal osteoporosis (PMO). Bone histomorphometry was performed on a subgroup of women participating in this study in order to assess bone quality and architecture. The patients were randomized to receive one of the following: placebo, continuous oral daily ibandronate (2.5 mg/day) or intermittent oral ibandronate (20 mg every other day for 12 doses every 3 months). Out of the overall study population of 2,946 patients, 110 were randomly assigned to undergo transiliac bone biopsy at either month 22 or month 34 of treatment. The primary safety endpoint was osteoid thickness in trabecular bone, which was measured to exclude treatment-induced bone mineralization defects. Secondary safety endpoints assessed bone volume, bone turnover and micro-architecture. The primary efficacy endpoint was bone mineralizing surface. In all bone biopsy cores, newly formed trabecular bone retained its structure without any signs of woven bone. Marrow fibrosis and signs of cellular toxicity were not observed. Quantitative assessment demonstrated no impairment in mineralization of bone matrix: osteoid thickness tended to be similar or slightly lower in the ibandronate groups versus the placebo group. All secondary safety variables and the bone efficacy parameter were consistent with the production of normal-quality, newly formed bone and a modest reduction in bone turnover with both ibandronate regimens relative to placebo. Long-term treatment with oral ibandronate, even when administered with an extended between-dose interval of >2 months, produces normal-quality, newly formed bone in women with PMO.     

葛根素对绝经后骨质疏松大鼠不同部位骨骼的抗骨质疏松作用差异的研究

目的本文拟通过动物实验研究葛根素对大鼠骨密度的影响,探讨葛根素对不同部位骨骼抗骨质疏松作用的差异。 方法对24只雌性SD大鼠行双侧卵巢切除术,构建大鼠绝经后骨质疏松模型。采用葛根素处理大鼠后,分别于第2、4、8、12周采用双能X射线吸收法（DXA）检测其各部位骨骼骨密度随时间发生的变化,并对比不同部位骨骼骨密度、骨矿含量的差异,同时通过组织切片观察葛根素对骨组织微结构的影响。 结果葛根素应用后的第8周疗效最为显著,经葛根素处理后股骨远端、腰椎等松质骨的骨密度、骨矿含量显著提高,且骨小梁更粗、数量更多,而股骨中段等皮质骨的骨密度、骨矿含量变化则不大。 结论葛根素对绝经后骨质疏松大鼠松质骨的抗骨质疏松作用优于皮质骨。     

绝经后骨质疏松患者的骨特异性碱性磷酸酶变化及其临床意义

为了解骨形成的变化在绝经后骨质疏松发病中的作用，本文测定３７例绝经后骨质疏松患者和３１例健康绝经后妇女的骨特异性碱性磷酸酶，分析了这一变化与血总碱性磷酸酶及骨密度（用双能Ｘ线吸收仪测定）的相关性。结果发现绝经后骨质疏松患者骨特异性碱性磷酸酶和骨钙素较对照组明显降低，但这一变化与骨密度值无明显的相关性。提示骨形成减低并非绝经后骨质疏松的主要发病机理。     

绝经后骨质疏松症五种治疗方案临床疗效观察 (附389例资料分析）

为探讨绝经后骨质疏松症的有效治疗方案，本文对近年临床实施的五种方案３８９例疗效观察结果作了总结。发现益钙宁（鳗鱼降钙素，ＥｌｃａｔｏｎｉｎＥｌｃ），或其联合方案对止痛效果肯定、迅速；骨密度（ＢＭＤ）也有明显提高。尤其Ｅｌｃ加钙尔奇Ｄ方案效果最好。利维爱（ｌｉｖｉａｌ）加钙尔奇Ｄ有效但缓慢。而单纯钙尔奇Ｄ近期效果不肯定。并对方案与适用人群作出了建议。