骨转换指标和骨密度预测骨折危险性的可行性

背景:骨密度虽然可以诊断骨质疏松,但不能及时反映受试者正在发生的骨代谢情况:骨转换指标虽然不能诊断骨质疏松,但它可以及时反映受试个体正在发生的骨转换速率.目的:概述骨转换指标和骨密度预测骨质疏松症的骨折危险性,从理论上分析,骨折术后愈合与否的预测方法的可行性.方法:以bone tunrnover,biochemical marker,osteoporosis为检索词,检索Pubmed数据库(1999-01/2009-01);以骨转换,骨代谢,生化标志物,骨密度,骨质疏松,骨折为检索词,检索CNKI数据库(1999-01/2009-01).文献检索语种限制为英文和中文.纳入与骨转换指标和骨密度预测骨折危险性的研究紧密相关的文章;排除重复文献.结果与结论:计算机初检得到631篇文献,根据纳入排除标准,对其中31篇文献进行分析.骨质疏松症是老年人发病及死亡的主要原因之一,早期预测骨质疏松症的骨折危险性意义重大.文章介绍了长期制动后的骨代谢机制、骨生化标志物种类、骨密度测量、多细胞基本单位和OPG-RANKL-RANK系统在骨重建中的作用;重点介绍了国内外学者运用骨转换指标和骨密度预测骨质疏松症和长期制动后的骨折危险性,从理论上分析骨折术后愈合与否的预测方法的可行性.     

Relationship between bone mineral density and biochemical markers of bone turnover in hemodialysis patients

End-stage renal disease is closely associated with changes in bone and mineral metabolism. In recent times, osteoporosis has become important among hemodialysis (HD) patients. In this study, the investigators sought to evaluate the relationship between bone mineral density (BMD) and biochemical markers of bone turnover among HD patients. A total of 70 uremic patients on a maintenance HD program for at least 1 y were enrolled in the study. All patients were treated with conventional bicarbonated HD for 5 h through the use of low-flux hollow-fiber dialyzers. Bone densitometry was measured by dual energy x-ray absorptiometry in the lumbar spine (LS) and the femoral neck (FN). BMD was classified according to World Health Organization criteria on the basis of BMD T scores. Biochemical bone turnover markers such as calcium, phosphorus, ionized calcium, intact parathyroid hormone, alkaline phosphatase, plasma bicarbonate, blood pH, serum albumin, and hematocrit levels were measured before the HD session in the morning. Male patients (n=37; 52.9%; mean age, 46.2+/-17.0 y) were assigned to a single study group, and female patients (n=33; 47.1%; mean age, 44.0+/-13.1 y) to another. Mean duration of HD treatment was 33.7+/-28.5 mo in females and 33.0+/-26.0 mo in males. Among all patients, BMD T scores in the osteopenia/osteoporosis range were observed at the LS in 58 patients (82.8%) and at the FN in 45 patients (64.3%). According to BMD measurements in FN T score, 10% of patients (n=7) were osteoporotic, 54.3% (n=38), osteopenic, and 35.7% (n=25), normal. On the other hand, in LS T score, the results were 47.1% (n=33) osteoporotic, 35.7% (n=25), osteopenic, and 17.1% (n=12), normal. No statistically significant association was found in osteopenia/osteoporosis between sexes according to FN and LS T score (P=.542, P=.267, respectively). No significant relationship was noted between BMD and biochemical markers of bone turnover. A positive correlation was found between FN T scores of BMD and age (r=.413, P=.000). BMD T scores within the range of scores for osteopenia/osteoporosis were observed in 78.5% of patients at the LS and in 58.5% of patients at the FN. The investigators concluded that no correlation could be found between markers of bone turnover and bone mass measurements in both skeletal regions. LS T score results were worse than FN T score results. Elevated alkaline phosphastase levels combined with high intact parathyroid hormone levels are predictive of renal osteodystrophy but not of adynamic bone disease/osteoporosis.     

Biochemical markers of bone turnover and bone mineral density in patients with beta-thalassaemia major

In this study, bone formation markers (bone-specific alkaline phosphatase and osteocalcin) and bone resorption markers (pyridinoline and deoxypyridinoline) were analysed. Bone formation, as evidenced by the levels of serum alkaline phosphatase and osteocalcin, did not appear to be impaired, while bone resorption was grossly increased in all patient groups. The decrease of bone mineral density values was more prominent in the lumbar spine, thus making this site particularly interesting for such studies. The patients had significantly lower femoral neck and lumbar spine bone mineral density when compared with control (all p <0.001). Our conclusion is that, in spite of the severe bone destruction that occurs in thalassaemia major, the fact that bone formation remains intact calls for a more intensive treatment.     

Utility of biochemical markers of bone turnover and bone mineral density in management of osteoporosis

Biochemical markers of bone turnover (bone-turnover markers) are released during bone formation or resorption and can be measured in blood and/or urine. The concentration of bone-turnover markers in serum or urine reflect bone remodeling activity and can potentially be used as surrogate markers of the rate of bone formation or bone resorption. While the diagnosis of osteoporosis is based on bone mineral density (BMD), the absolute fracture risk for a particular BMD measurement varies several fold depending on age and is also influenced by other clinical risk factors. The measurement of bone-turnover markers may be of additional value to BMD and clinical risk factors in fracture risk assessment by improving the sensitivity and specificity of prediction of future fractures. In clinical practice, bone-turnover markers may help make cost-effective treatment decisions in patients with borderline absolute risk. BMD changes following treatment cannot be detected with confidence for 12-24 months due to measurement imprecision. Bone-turnover markers, which show an early response following treatment, may be useful for monitoring therapy, identifying non-compliance and non-responders, and predicting early response to therapy. This review concludes by identifying the need for internationally agreed-upon standards for bone resorption and formation.     

老年男性代谢综合征患者血睾酮水平与骨密度及骨转换指标的相关性研究

目的分析老年男性代谢综合征(MS)患者血睾酮(T)水平与骨密度(BMD)及骨转换指标之间的相互关系。方法收集60～90岁老年男性111例,分为MS组(61例)和非MS组(50例)。测定T、N-MID骨钙素(N-MID-OC)、总I型胶原氨基端延长肽(PINP)、血清β-胶原特殊系列(β-CTX)水平,同时使用双能X线骨密度测量仪测量左前臂、左髋部及腰椎的BMD,分析血清T水平与BMD及骨转换指标的相关性。结果 MS组的T、N-MID-OC、PINP、腰椎、髋骨及桡骨BMD水平均低于非MS组(P<0.05),β-CTX高于非MS组(P<0.05),且随着MS组分的增加,血T、N-MID-OC、PINP水平及腰椎、髋部、桡骨BMD平逐渐下降,β-CTX逐渐增高,差异有统计学意义(P<0.05)。相关性分析表明:血清T与N-MID-OC、PINP及腰椎、髋部、桡骨BMD呈正相关,与β-CTX水平呈负相关(P<0.05)。结论老年男性MS患者中血T水平与BMD及骨转换指标密切相关,低T水平可作为老年男性骨质疏松(OP)的预测因子。     

Bone mineral density and bone turnover in postmenopausal women treated for breast cancer

Chemotherapy and endocrine treatments for breast cancer are believed to increase risk of osteoporosis by causing early menopause in premenopausal women and by further depleting estrogen levels in postmenopausal women. Multivariate analyses were used to evaluate the contributions of 7 predictors (age, body mass index [BMI], family history of osteoporosis, months since menopause, past use of chemotherapy, and current use of tamoxifen or aromatase inhibitors) in explaining variability in bone mineral density (BMD) at the hip and the spine and bone turnover in 249 postmenopausal women who are breast cancer survivors. This report was an analysis of baseline data from a federally funded (1 R01 NR07743-01A1) intervention study on osteoporosis prevention. Mean age of the women was 58.5 years, and average BMI was 26.7 kg/m; 98% were white. All had measurable bone loss, 167 had chemotherapy, 76 were on tamoxifen, and 21 were on aromatase inhibitors. Women with higher BMI had higher BMD at the hip (P < .001) and the spine (P = .004). Women on tamoxifen had lower measures of bone formation (Alkphase B) (P < .001), suggesting less bone turnover, and higher BMD at the hip (P = .035). There was a trend for women who had received chemotherapy to have lower BMD at the spine (P = .06). The implications of these findings are discussed in the article.     

Relation between homocysteine and biochemical bone turnover markers and bone mineral density in peri- and post-menopausal women.

Background: Recently, increased plasma homocysteine (Hcy) has been suggested as an independent risk factor for osteoporotic fractures. Therefore, it is tempting to speculate that Hcy adversely affects bone metabolism. This study aimed to analyze the relation between Hcy and biochemical markers of bone metabolism and bone mineral density (BMD). Materials and methods: We investigated 143 peri- and post-menopausal women [median age (25th-75th percentile), 67 (57-75) years]. All subjects underwent a detailed medical examination, measurement of bone mineral density at lumbar spine (BMD-LS) and total hip (BMD-HIP), and fasting venous blood and urine sampling. Osteocalcin (OC), serum calcium (Ca), urinary desoxypyridinoline cross-links (DPD), osteoprotegerin (OPG) and soluble receptor activator of NF-kappaB ligand (sRANKL) were studied. Results: According to BMD subjects were classified as normal (n=24), osteopenic (n=51) or osteoporotic (n=68). Median Hcy did not differ between normal, osteopenic and osteoporotic subjects (p=0.647). Partial correlation analysis, controlling for the major confounders, age, creatinine, menopause and previous fractures, revealed significant correlations between Hcy and DPD (r=0.193, p=0.022), as well as between Hcy and Ca (r=0.170, p=0.045). After adjustment for the same confounders, subsequent regression analysis confirmed significant associations of Hcy with DPD and Ca. No significant relations could be observed between Hcy and BMD-LS, BMD-HIP, OC, OPG or sRANKL. Conclusion: Our results demonstrate weak, but significant, relations between Hcy and markers of organic and inorganic bone resorption, suggesting a mechanistic role of Hcy in bone metabolism. The relation between Hcy and bone resorption was not dependent on OPG or sRANKL.     

转化生长因子β1与骨生化指标和骨密度的关系

背景：转化生长因子β1是一种重要的调节骨构塑的细胞因子,其是否能作为反应骨转换的敏感因子尚不清楚。目的：探讨转化生长因子β1与骨形成、骨吸收指标,以及腰椎正位骨密度间的关系。方法：实验共纳入来自长沙的健康妇女663名,年龄20～80岁。采用ELISA法测定空腹血清转化生长因子β1、骨特异性碱性磷酸酶和Ⅰ型胶原羧基末端肽的水平,同时应用双能X射线骨密度仪测定腰椎正位的骨密度。并分析转化生长因子β1与其他各指标的相关性。结果与结论：检测结果显示30～39岁,40～49岁年龄段妇女的血清转化生长因子β1水平最高,转化生长因子β1水平与年龄呈负相关,与体质量指数无相关。校正体质量指数后发现,转化生长因子β1与骨特异性碱性磷酸酶和Ⅰ型胶原羧基末端肽负相关,校正体质量指数和年龄后血清转化生长因子β1水平与腰椎正位骨密度正相关。说明转化生长因子β1能动态地反映骨转换情况。     

转化生长因子β1与骨生化指标和骨密度的关系

背景:转化生长因子β1 是一种重要的调节骨构塑的细胞因子,其是否能作为反应骨转换的敏感因子尚不清楚.目的:探讨转化生长因子β1 与骨形成、骨吸收指标,以及腰椎正位骨密度间的关系.方法:实验共纳入来自长沙的健康妇女663 名,年龄20～80 岁.采用ELISA 法测定空腹血清转化生长因子β1、骨特异性碱性磷酸酶和Ⅰ型胶原羧基末端肽的水平,同时应用双能X 射线骨密度仪测定腰椎正位的骨密度.并分析转化生长因子β1 与其他各指标的相关性.结果与结论:检测结果显示30～39 岁,40～49 岁年龄段妇女的血清转化生长因子β1 水平最高,转化生长因子β1 水平与年龄呈负相关,与体质量指数无相关.校正体质量指数后发现,转化生长因子β1 与骨特异性碱性磷酸酶和Ⅰ型胶原羧基末端肽负相关,校正体质量指数和年龄后血清转化生长因子β1 水平与腰椎正位骨密度正相关.说明转化生长因子β1 能动态地反映骨转换情况.     

Serum osteopontin levels in relation to bone mineral density and bone turnover markers in postmenopausal women

Osteopontin (OPN) is an extracellular matrix protein that is expressed in bone cells such as osteoblast and osteocytes and associated with bone turnover and bone mineral density (BMD) in postmenopausal women. Here, we aimed to investigate the relationship between circulating OPN levels and BMD in postmenopausal women in Southern China. A total of 362 postmenopausal women were consecutively recruited into this study from 2011–2013. Serum levels of OPN, receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL), and bone turnover markers were analyzed. BMD was measured by dual energy X-ray absorptiometry. Osteoporosis and osteopenia were diagnosed according to the World Health Organization criteria. Serum OPN levels were remarkably higher in the osteoporotic group than those in the osteopenic and normal groups (all p?r?=??0.25, p?=?0.004; r?=??0.66, p?r?=??0.28, p?=?0.001; respectively) and positively associated with type I procollagen amino-terminal propeptide (PINP), carboxy-terminal cross-linking telopeptide of type I collagen (CTX), and RANKL (r?=?0.20, p?=?0.020; r?=?0.17, p?=?0.036; r?=?0.19, p?=?0.028, respectively) in the osteoporotic group. In multiple regression analyses, lumbar spine BMD, PTH and RANKL were the predictors for serum OPN levels. In conclusion, OPN serum levels are negatively related to BMD and positively correlated with bone turnover levels in this group of Chinese postmenopausal women.     

Biomarkers of bone turnover and bone mineral density in hyperprolactinemic amenorrheic women.

We tested the hypothesis that biomarkers of bone resorption are increased in hyperprolactinemic amenorrheic patients with estrogen (E) deficiency, augmenting the possible risk of developing osteoporosis. Fifty hyperprolactinemic patients with amenorrhea of more than 12 months and with low serum E2, as well as 30 healthy fertile women (controls), matched for age and body mass index, participated in this study. Bromocriptine was administered orally to hyperprolactinemic patients and blood and urine samples were collected before and 12 weeks after treatment. Serum osteocalcin (OC) and bone-specific alkaline phosphatase (B-ALP), reflecting bone formation, and urinary deoxypridinoline (D-Pyr) and N-telopeptide of type 1 collagen (NTX) excretion, reflecting bone resorption, were measured using direct immunoassays. Hyperprolactinemic patients had higher (p < 0.0005) levels of all the biomarkers compared to control values: (OC, 22+/-1.2 [SE] vs. 14+/-.99 ng/ml (+57 %); B-ALP, 14.2+/-0.7 vs. 7.5+/-0.8 ng/ml (+89 %); D-Pyr, 8.8+/-0.6 vs. 3.2+/-0.3 nmol/mmol creatinine (+175%) and NTX, 65+/-5.1 vs. 25+/-3.2 nmol bone collagen equivalent (BCE)/mmol creatinine (+160%)). These results were associated with significantly decreased lumbar spine bone mineral density (LS-BMD), measured by dual energy X-ray absorptiometry (DEXA). Treatment of hyperprolactinemia with bromocriptine restored normal values of bone formation and resorption markers. In conclusion, hyperprolactinemia with estrogen deficiency exhibits a significant increase of bone resorption which is associated with a significant decrease of LS-BMD. These changes may subject the patient to the possible risk of developing osteoporosis.     

Effects of alendronate and risedronate on bone mineral density and bone turnover markers in late postmenopausal women with osteoporosis

This study was undertaken to compare the effects of alendronate and risedronate on bone mineral density (BMD) and bone turnover markers (BTMs) in late postmenopausal women with osteoporosis. Thirty women older than 60 y of age were randomly assigned to receive alendronate 10 mg (n=16) or risedronate 5 mg (n=14) on a daily basis. The patients were followed every 3 mo for 12 mo. BMD measurements were taken at baseline and at the end of the study, and BTMs were measured at 3-mo intervals. By the end of the study, there were statistically significant increases in BMD in both groups at all sites at which they were measured (P < .001). However, these differences were not statistically significant between groups. By the end of the study, all BTMs had decreased significantly and to a similar extent in both groups. The most significant change was observed in the third month of the study. A negative correlation was noted between percentage change in bonespecific alkaline phosphatase and femoral neck BMD (r=-0.467). This study reported no difference between the 2 drugs in their effects on BMD and BTMs.     

Changes in serum RANKL and OPG with sexual development and their associations with bone turnover and bone mineral density in a cohort of girls

Objectives

To characterize the variations of serum osteoprotegerin (OPG) and RANK ligand (RANKL) with sexual development in adolescent girls, and to estimate their associations with bone turnover and bone mineral density (BMD).

Design and methods

We studied 300 girls evaluated at 13 and 17 years of age. Fasting blood samples were collected and the following substances were quantified: RANKL, OPG, C-terminal telopeptide of type I collagen (CTX), and procollagen type I N propeptide (PINP). BMD was measured at the distal forearm. Correlation coefficients were used to quantify associations between those variables at 13 and 17 years of age. Random-effects linear models were used to quantify associations between bone parameters and sexual development (years from menarche).

Results

RANKL was positively correlated with bone resorption (CTX) in early and late adolescence (r₁₃ = 0.15 and r₁₇ = 0.23) and the OPG/RANKL ratio correlated inversely with CTX at 17 (r₁₇ = − 0.24). No significant associations were found between RANKL and OPG and bone formation (PINP). In early adolescence, there was an inverse correlation of BMD with CTX (r₁₃ = − 0.52) but no significant correlations were found between osteoclast regulators and BMD. We observed a linear decrease in serum RANKL with increasing sexual development (− 0.09 pmol/L per year, 95% CI: − 0.10, − 0.07) alongside an increase in OPG (0.02 pmol/L, 95% CI: 0.01, 0.04).

Conclusions

Serum RANKL and OPG levels varied markedly with sexual development in adolescence. These cytokines were not predictive of bone turnover or BMD at 13, but serum RANKL bioactivity was associated with bone resorption in late adolescence.     

Association of immune function with bone mineral density and biochemical markers of bone turnover in patients with anklylosing spondylitis

The lymphocyte-osteoclast interaction has recently been described. The aim of this study was to investigate the possible relationship between ankylosing spondylitis (AS) and bone metabolism. Bone metabolism was evaluated in the blood of 49 patients with AS by means of biochemical markers and bone mineral density (BMD) with a Lunar device. Bone formation markers, bone specific alkaline phosphatase (BALP), osteocalcin (BGP), bone resorption markers, pyridinoline (Pyd), deoxypyridinoline (Dpyd) and lymphocyte surface markers (CD3, CD19, CD4, CD8, CD16+56) were analysed with ELISA and flow-cytometry methods. The patients had significantly lower femoral neck and trochanter BMD than the controls. Dpyd concentrations were negatively correlated to CD3+% and CD3-/CD16+56% cells. Neither mineral nor hormone levels were significantly correlated with absolute T scores of BMD of the hip sites. BALP and BGP were negatively correlated to BMD when expressed as T scores. We conclude that AS is related to accelerated osteoclastic activity. Many lymphokines and growth factors produced by lymphocytes can influence osteoclastogenesis and probably play a role in rheumatologic/inflammatory disorders.     

老年男性吸烟与骨转换标志物、骨密度和骨质疏松性骨折风险的关系

目的 调查老年男性吸烟与骨转换标志物、骨密度和骨质疏松性骨折风险的关系.方法 调查576例60～97岁老年男性吸烟等情况,按照是否吸烟分成吸烟组31例和非吸烟组545例.检测两组骨转换标志物[包括I型胶原羧基末端肽交联(CTX)、I型前胶原氨基端前肽(P1NP)和骨钙素(OC)]、骨密度[包括股骨颈骨密度(FNBMD)...     

骨密度与血脂及运动的相关性

学术背景:骨密度与血脂异常关系密切,运动对血脂及骨代谢均有显著影响,因而通过运动可以改善血脂,增加骨密度,达到预防骨质疏松的作用。目的:就骨密度与血脂的关联研究、骨代谢与脂代谢相互影响的可能机制,以及运动对骨密度与血脂作用的研究进展做一综述。检索策略:应用计算机检索Pubmed数据库1990-01/2006-12的相关文献,检索词"Exercise,Dyslipidemia,Osteoporosis,bone mineral density",限定文章语言种类为English。同时检索中国期刊全文数据库2000-01/2007-04期间的相关文章,检索词"运动,血脂异常,骨质疏松,骨密度",限定文章语言种类为中文。纳入标准:筛选针对性强、影响因子较大的论文。文献评价:选择骨密度与血脂及骨密度与运动密切相关的文献共43篇,其中综述9篇,34篇均为临床或基础实验研究。资料综合:①骨质疏松诱因较多,近年来研究证实,骨质疏松与脂代谢异常之间存在内在联系,脂代谢与骨代谢之间可能有潜在的病因学上的联系,而运动对绝经后妇女骨代谢和脂代谢影响的研究对揭示两者的关系可能会提供新的线索。②文章就骨密度与血脂的关联研究、骨代谢与脂代谢相互影响的可能机制以及骨密度与运动的作用进行了归纳总结。结论:尽管动物实验和体外实验均证实血脂异常与骨质疏松关系密切,而且运动可以改善血脂、提高骨密度,但如何将这些研究成果应用于实践任重而道远。     

Effect of alendronate on bone mineral density and biochemical markers of bone turnover in type 2 diabetic women: the fracture intervention trial

OBJECTIVE: Alendronate sodium (ALN) increases bone mineral density (BMD) in heterogeneous populations of postmenopausal women, but its effect is unknown in women with type 2 diabetes. The objective of this project was to compare changes in BMD during 3 years of ALN treatment versus placebo in diabetic women. RESEARCH DESIGN AND METHODS: We used data from the Fracture Intervention Trial, a randomized blinded placebo-controlled trial conducted at 11 centers in which 6458 women aged 54-81 years with a femoral neck BMD of or=200 mg/dl. RESULTS: In diabetic women, 3 years of ALN treatment was associated with increased BMD at all sites studied, including 6.6% at the lumbar spine and 2.4% at the hip, whereas women in the placebo group experienced a decrease in BMD at all sites except the lumbar spine. The safety/tolerability of ALN was similar to placebo, except for abdominal pain, which was more likely in the ALN group. CONCLUSIONS: ALN increased BMD relative to placebo in older women with type 2 diabetes and was generally well tolerated as a treatment for osteoporosis. Increases in BMD with ALN therapy compared with placebo were similar between women with and without diabetes.     

Biochemical markers of bone turnover and response of bone mineral density to intervention in early postmenopausal women: an experience in a clinical laboratory

BACKGROUND: Markers of bone formation and resorption may be useful as early indicators of response to therapy. Our aim in this study was to investigate the use of bone markers for monitoring of intervention for bone loss in early postmenopausal women and to assess the relationships between these markers and changes in bone mineral density (BMD). METHODS: Subjects were randomly assigned to the following groups: a control group; a group receiving calcium alone; groups receiving calcium plus low or conventional doses of conjugated equine estrogen; and groups receiving calcium plus low or conventional doses of calcitriol. At baseline and at 1 and 3 months after intervention, we measured serum intact osteocalcin, serum N-terminal midfragment osteocalcin, serum C-terminal telopeptide of type I collagen (CTx), urinary deoxypyridinoline cross-links, and urinary CTX: The BMD of the lumbar spine and the femoral neck was measured at baseline and after 1 and 2 years of intervention. RESULTS: No marker changed significantly in the control group except urinary CTx, which increased at 3 months. Serum CTx decreased in all regimens at 1 or 3 months of intervention. In addition, the changes of all markers at 3 months were inversely associated with the change in the BMD of the lumbar spine at 1 or 2 years (r = -0.144 to -0.314), whereas only the changes of bone resorption markers at 3 months were inversely correlated with the changes in femoral BMD at 1 or 2 years (r = -0.143 to -0.366). CONCLUSIONS: Biochemical markers of bone turnover appear to be of use in assessing early response to therapy. Bone resorption markers, especially serum CTx, are better indicators than bone formation markers for estimating the response to intervention in early postmenopausal women. However, the early changes in bone markers were weakly related to the later changes in BMD.