Meddah B, Brazier M, Kamel S, Maamer M, Samson L, Desmet G, Sebert J L
Laboratoire de pharmacie clinique, faculté de pharmacie, Amiens, France.
Ann Biol Clin (Paris). 1996;54(10-11):353-8.
The measurement of urinary deoxypyridinoline (DPD) constitutes a specific and sensitive marker of bone resorption. Total and free forms of DPD are determined by chromatographic method (HPLC) after or without hydrolysis of urine, respectively. Pyrilinks-D, a new immunoassay, allows to assess directly the free forms and needs an appropriate hydrolysis step for measuring the total form. We have compared the values of free (F), total (T) and conjugated (NF) forms of DPD determined by HPLC and Pyrilinks-D, in elderly women (n = 21, mean age: 83.5 +/- 1.5 years) with vitamin D insufficiency (25 OH D < 6 ng/mL) and Ca insufficiency responsible for a secondary hyperparathyroidism (iPTH = 45.3 +/- 22.7 pg/mL) and in healthy elderly women (n = 25, mean age: 76.6 +/- 3.1 years) with a normal vit D status (25 OH D > 10 ng/mL) as control group. We have also measured DPD during the course of vit D and Ca supplementation. At baseline, the HPLC and Pyrilinks-D values of DPD/Cr are highly correlated (DPD-T: r = 0.92, p < 0.001 and DPD-F: r = 0.76, p < 0.001), DPD-F and -NF values are correlated with those of DPD-T, while DPD-F and -NF are not correlated between themselves. In elderly with vit D insufficiency, the values obtained with Pyrilinks-D as compared to control subjects, show a significant increase of urinary excretion of DPD-F (8.5 +/- 3.1 vs 5.7 +/- 1.9 nmol/mmol, Cr, p < 0.0001), DPD-T (16.8 +/- 10.2 vs 9.9 +/- 3.5 nmol/mmol, Cr; p < 0.001) and DPD-NF (8.3 +/- 9.0 vs 4.5 +/- 3.3 nmol/mmol, Cr, p < 0.05). The administration of 800 IU of vit D and 1 g of elemental Ca during a course of 6 months normalize the iPTH values (24.4 +/- 11.8 and 30.9 +/- 14.6 pg/mL at 3 and 6 months). Simultaneously, the urinary excretion at 3 and 6 months of DPD-T (12.9 +/- 6.0 and 13.6 +/- 6.5 nmol/mmol, Cr) and of DPD-NF (4.5 +/- 3.3 and 5.5 +/- 4.8 nmol/mmol Cr) assessed by Pyrilinks-D as well as by HPLC decreased significantly, while no change was seen with DPD-F assessed by both methods. The decreases expressed as percent of baseline values were about 20% for DPD-T and more than 30% for DPD-NF, while DPD-F levels remain unchanged. We conclude that the Pyrilinks-D immunoassay presents reliable characteristics and allows to assess either free or total forms of DPD, like the HPLC technique. It constitutes an excellent reflection of bone resorption in elderly with vit D insufficiency. However its application to monitor therapy like vit D and Ca supplementation, needs a hydrolysis step to determine DPD-T which appears in this study more sensitive to the treatment than DPD-F.
尿脱氧吡啶啉(DPD)的测定是骨吸收的一种特异性和敏感性标志物。分别在尿液水解或未水解后,通过色谱法(HPLC)测定DPD的总形式和游离形式。一种新的免疫测定法Pyrilinks-D可直接评估游离形式,测量总形式则需要适当的水解步骤。我们比较了通过HPLC和Pyrilinks-D测定的老年女性(n = 21,平均年龄:83.5±1.5岁)中DPD的游离(F)、总(T)和结合(NF)形式的值,这些老年女性维生素D不足(25 OH D < 6 ng/mL)且钙不足导致继发性甲状旁腺功能亢进(iPTH = 45.3±22.7 pg/mL),并与维生素D状态正常(25 OH D > 10 ng/mL)的健康老年女性(n = 25,平均年龄:76.6±3.1岁)作为对照组进行比较。我们还在维生素D和钙补充过程中测量了DPD。基线时,HPLC和Pyrilinks-D测定的DPD/Cr值高度相关(DPD-T:r = 0.92,p < 0.001;DPD-F:r = 0.76,p < 0.001),DPD-F和-NF值与DPD-T值相关,而DPD-F和-NF之间不相关。在维生素D不足的老年人中,与对照组相比,Pyrilinks-D获得的值显示DPD-F的尿排泄量显著增加(8.5±3.1对5.7±1.9 nmol/mmol Cr,p < 0.0001),DPD-T(16.8±10.2对9.9±3.5 nmol/mmol Cr;p < 0.001)和DPD-NF(8.3±9.0对4.5±3.3 nmol/mmol Cr,p < 0.05)。在6个月的疗程中给予800 IU维生素D和1 g元素钙可使iPTH值正常化(3个月和6个月时分别为24.4±11.8和30.9±14.6 pg/mL)。同时,通过Pyrilinks-D以及HPLC评估的3个月和6个月时DPD-T(12.9±6.0和13.6±6.5 nmol/mmol Cr)和DPD-NF(4.5±3.3和5.5±4.8 nmol/mmol Cr)的尿排泄量显著下降,而两种方法评估的DPD-F均未见变化。以基线值的百分比表示的下降,DPD-T约为20%,DPD-NF超过30%,而DPD-F水平保持不变。我们得出结论,Pyrilinks-D免疫测定法具有可靠的特性,并且与HPLC技术一样,能够评估DPD的游离形式或总形式。它是维生素D不足老年人骨吸收的良好反映。然而,其应用于监测维生素D和钙补充等治疗时,需要一个水解步骤来测定DPD-T,在本研究中DPD-T似乎比DPD-F对治疗更敏感。