骨折患者长期固定治疗尿脱氧吡啶啉变化的临床研究

目的　探讨骨折长期固定治疗患者尿脱氧吡啶啉的变化及其临床意义。方法　测定 3 7例 (男 2 2例 ,女 15例 )骨折长期固定治疗患者及 3 0例 (男 15例 ,女 15例 )健康对照者的血清钙 (Ca)、磷 (P)、总碱性磷酸酶 (AKP)、尿钙 /肌酐 (Ca/Cr)、尿脱氧吡啶啉 (DPD)的水平。结果　骨折长期固定治疗患者血清钙、磷水平较正常对照组显著降低 (P <0 0 5 ) ;AKP、Ca/Cr、DPD水平较正常对照组有不同程度的增高 (P <0 0 5 ,P <0 0 5和P <0 0 1)。其中以尿DPD的活性增高更为显著 (增高 5 98倍 )。而且 ,骨折长期固定治疗患者尿DPD的变化还与病程呈正相关。结论　尿DPD是反映骨吸收的一项敏感而特异的指标 ,尿DPD的监测对骨折长期固定治疗患者的临床治疗和预防发生新的骨折具有重要的参考价值。     

Osteodystrophy in patients with chronic hepatitis and liver cirrhosis

Bone mineral density (BMD) of the lumber vertebrae and factors related to bone metabolism were determined in patients with chronic viral hepatitis and patients with liver cirrhosis to clarify correlations between hepatic dysfunction, considered to be one of the causes of hepatic osteodystrophy, and decrease in bone mass. BMD of the second to fourth lumbar vertebrae was determined with a Lunar (Madison, WI, USA) DPX, a dual-energy X-ray absorptiometry diagnostic system. BMD was significantly lowest in patients with liver cirrhosis, followed by patients with chronic hepatitis, and healthy subjects, in this order. There was a significantly positive but weak correlation between albumin and BMD. Levels of 25(OH)D and 1,25(OH)₂D were significantly lower in patients with liver cirrhosis than in those with chronic hepatitis. BMD and vitamin D were decreased in all patients whose cholinesterase (ChE) was below 0.3ΔpH. Urinary pyridinoline(Upyr) was significantly higher in the patients with liver cirrhosis, in whom bone mass was decreased, than in the patients with chronic hepatitis, whereas serum osteocalcin levels were distributed in the upper normal range in patients with chronic hepatitis and those with liver cirrhosis. There was a positive correlation between 25(OH)D and serum osteocalcin levels in patients with liver cirrhosis. These results indicate that osteogenesis is decreased and suggest that the decrease in BMD which occurs in viral liver cirrhosis, probably related to decreased, bone formation and slight promotion of bone resorption, reflects deranged hepatic function. This is the first report of Upyr and urinary deoxypyridinoline (UDpyr) determination in patients with liver cirrhosis and patients with chronic hepatitis. The negative correlation of Upyr and UDpyr with ChE is a novel finding.     

甲亢患者骨密度及骨代谢生化指标的临床观察

测定甲亢患者的骨密度及骨代谢生化指标,探讨甲亢患者骨质疏松发生的机理.应用双能X线骨密度仪(DEXA),检查149例甲亢患者骨密度(BMD)变化,同时测定其中81例患者血清FT3、FT4、碱性磷酸酶(ALP)、骨钙素(BGP)、尿游离脱氧吡啶啉(D-pyd)的水平.结果显示甲亢时骨密度减低发生率30.2%,骨质疏松发生率24.1%.与对照组比较,甲亢患者各项骨代谢指标均明显升高.结论:甲亢时各项骨代谢指标均明显升高,呈高转换性骨质疏松.在治疗甲亢时应注意检测患者的骨密度,以便尽早发现骨质疏松.     

骨质疏松骨折血清骨钙素和尿脱氧吡啶酚变化的研究

目的了解骨质疏松骨折患者在骨折愈合过程中骨代谢的变化,更好地指导临床有效的治疗。方法对80例骨折患者愈合过程中血清骨钙素和尿脱氧吡啶酚变化进行观察。结果骨质疏松性骨折后骨钙素呈增高趋势,可超出正常值范围。第3周达到最高峰,第6周逐渐下降到正常值范围;骨质疏松性骨折后尿脱氧吡啶酚亦呈增高趋势,完全超出正常值范围。第6周达到最高峰,第9周逐渐下降但未完全回复正常范围。结论骨质疏松骨折患者早期骨转换都很活跃,血清骨钙素和尿脱氧吡啶酚均增高,尿脱氧吡啶酚的增高较血清骨钙素的增高显著,骨吸收持续影响较大,骨代谢处于失偶联的状态。若早期能有效地控制骨吸收将有利于加强骨形成的能力,最终有利于缩短骨折愈合时间。     

A clinical assessment of the relationship between bone scintigraphy and serum biochemical markers in hemodialysis patients

BACKGROUND: Renal osteodystrophy is a metabolic bone disease and a common complication of end-stage chronic renal failure and maintenance dialysis treatment. In this study, we examined the correlation between quantifying bone scintigraphy and serum biochemical markers in hemodialysis patients. METHODS: Bone scintigraphy with technetium-99m-hydroxy-methylene-diphosphonate (99mTc-HMDP) was performed on 28 patients on maintenance hemodialysis. Bone scintigraphy was performed using a standard protocol and was quantified by setting regions of interest (ROIs) over selected regions. The bone-to-soft-tissue ratio (B/ST ratio) at each region was calculated in all patients. The B/ST ratios were then compared with serum biochemical markers. RESULTS: The B/ST ratio for the skull correlated well with serum bone-specific alkaline phosphatase (BAP) (r = 0.735, p < 0.001), serum deoxypyridinoline (DPD) (r = 0.806, p < 0.001) and intact parathyroid hormone (intact PTH) (r = 0.701, p < 0.001). The B/ST ratio for the lumbar spine correlated with intact PTH (r = 0.387, p < 0.05) but not with serum BAP or serum DPD. The B/ST ratio for the femoral neck correlated with serum DPD (r = 0.431, p < 0.05) and intact PTH (r = 0.449, p < 0.05) but not with serum BAP. CONCLUSIONS: Our data suggest that quantitative bone scintigraphy is a sensitive and useful method for evaluating bone metabolism in hemodialysis patients. The B/ST ratio for the skull may reflect changes of bone metabolism in hemodialysis patients.     

Analytical and clinical evaluation of the Bio-Rad HPLC kit for measurement of type I collagen cross links

 The measurement of hydroxylysylpyridinoline (PYD) and lysylpyridinoline (DPD), the degradation products of type I collagen, by manual HPLC assay posed practical difficulties. The present study was undertaken to evaluate the first commercially available HPLC kit, which provides a convenient substitute for cumbersome classical HPLC methods. The HPLC procedure is based on an improved sample clean-up chromatography, convenient ready-to-use HPLC reagents, and quicker isocratic elution of PYR and DPD on reverse-phase analytical column. The analytical parameters assessed include sensitivity, within- and between-assay variation, method comparison, recoveries, and interference. Clinical evaluation included discriminatory power of PYD and DPD and response to treatment of osteoporosis patients with Alendronate. DPD and PYD concentrations showed linear (r ² > 0.99) response between 10–400 pmol/ml and 75–4000 pmol/ml, respectively. The average within-assay imprecision, over a range of clinically relevant cross-links concentrations, was CV < 7% (n = 30). The total imprecision (n = 35 days), by ANOVA, for PYD and DPD was CV < 7.5% and CV < 10%, respectively. Average spike recovery was 95.4% ± 6.5%. Comparison with the historical HPLC method exhibited a close correlation (r values between 0.87 and 0.91, P < 0.0001). Creatinine-corrected DPD in postmenopausal (Z score = 2.4, P < 0.05, n = 17) and osteoporotic (Z score = 3.0, P < 0.01, n = 29) women were 44% and 64% higher, respectively, compared to premenopausal samples (n = 15). Similarly, PYD concentration was 26% and 54% higher in postmenopausal and postmenopausal osteoporotic women, respectively. There was a 47% (P < 0.001) decrease in DPD concentration (n = 16), and a 30% decrease in PYD concentration after 90 days of treatment of osteoporotic patients with Alendronate. DPD concentration correlated with N-telopeptide with an r value of 0.69 (n = 67, P < 0.0001). The reported kit method is substantially simpler and precise than the manual method. DPD concentrations determined by the current method reaffirm the clinical value in identifying increased bone resorption in pathological conditions and monitoring response to antiresorptive therapy. Received: June 28, 2002 / Accepted: November 6, 2002 Offprint requests to: D.J. Baylink     

辛伐他汀对老年高脂血症伴骨量减少病人骨代谢的干预研究

目的：探讨辛伐他汀对老年高脂血症伴骨量减少病人骨代谢的影响。方法：收集86例确诊为高脂血症的病人，随机分为试验组（49例）和对照组（ST例）。两组病人均给予相似饮食以及等剂量阿法骨化醇和复方氨基酸螯合钙，试验组在此基础上加用辛伐他汀40mg／d，疗程3个月。于用药前、用药后3个月分别采集静脉血测定骨代谢指标及检查骨密度。结果：试验组和对照组病人用药后总碱性磷酸酶（TAP）及骨源性碱性磷酸酶（BAP）均有明显升高（P〈0．01或P〈0．05），试验组TAP及BAP比对照组用药后升高更显著（P〈0．05）。试验组和对照组用药后尿脱氧吡啶啉与肌酐的比值、骨宽频超声衰减值差异均无统计学意义。结论：辛伐他汀短期内对骨形成的生化指标有促进作用，因时间较短，对骨吸收的生化指标和骨密度的影响尚无统计学意义，有待进一步研究。     

Biochemical markers in oncology. Part I: molecular basis. Part II: clinical uses

The investigation of the molecular mechanisms involved in carcinogenesis and tumor progression has led to the development of numerous biochemical markers. Biochemical markers may serve for early prediction of tumor recurrence, progression and development of metastases including bone metastases and for prediction of response to therapy. Tumor antigens have been used for more than a decade and although they have shown promising clinical results, their sensitivity and specificity remain limited. A lot of knowledge on the key molecules which control cell cycle, apoptosis and angiogenesis has been acquired during recent years, but their clinical value remains uncertain. Molecular markers which are linked to malignant transformation may provide a non-surgical therapeutic approach by targeting these molecules through gene therapy or antisense molecules. Because of the complexity of the physiopathogical processes involved in tumorogenesis and metastases, we first provide a review on the molecular basis of the various tumor markers and then discuss their potential clinical utility for the major cancers. The review of the current literature indicates that at the exception of a few examples, such as the use of Her-2 to predict response of the targeted Herceptin therapy, no single marker is sensitive and specific enough to perform an accurate diagnosis, predict disease progression or response to treatment. A combination of different biochemical and imaging markers appears to be the most promising strategy to monitor patients with cancer.