Garnero P, Delmas P D
INSERM Unit 234, Hôpital E. Herriot, Lyon, France.
J Clin Endocrinol Metab. 1993 Oct;77(4):1046-53. doi: 10.1210/jcem.77.4.8104954.
We measured serum bone alkaline phosphatase (B-ALP) with a new immunoradiometric assay (IRMA) in a large sample of healthy controls comprising 173 women and 180 men, 20-88 yr of age, and in patients with metabolic bone disease. Using serum samples from patients with liver disease and patients with Paget's disease with elevated total alkaline phosphatase (T-ALP) as a source of, respectively, liver and bone isoenzymes, we determined a liver cross-reactivity of the IRMA of 16% that was confirmed by electrophoresis of the circulating alkaline phosphatase isoenzymes. The IRMA was linear for serial sample dilutions, the recovery ranged from 89-110%, and the intra- and interassay variations were below 7% and 9%, respectively. B-ALP increased linearly with age in both sexes, and the mean B-ALP serum levels were not significantly different for women and men (11.3 +/- 4.8 ng/mL for women; 11.0 +/- 4.0 ng/mL for men). The increase in B-ALP after the menopause was significantly higher than that in T-ALP (+77% vs. +24%; P < 0.001). When the values of postmenopausal women were expressed as the SD from the mean of premenopausal women, the mean Z scores were 2.2 +/- 1.8 for B-ALP and 0.9 +/- 1.3 for T-ALP (P < 0.001 between the two). Serum B-ALP was increased from control values in patients with Paget's disease (n = 57; mean, 171.8 +/- 135.6 ng/mL; P < 0.001), in patients with primary hyperparathyroidism (n = 18; mean, 17.2 +/- 5.9 ng/mL; P < 0.001), and in patients with chronic renal failure on hemodialysis (n = 83; mean, 36.6 +/- 35.7 ng/mL; P < 0.001). In patients with Paget's disease, B-ALP was highly correlated with T-ALP (r2 = 0.94; P < 0.001), and the decrease in its serum level was larger than that in T-ALP after treatment with the bisphosphonate pamidronate (-58% vs. -43%; P < 0.03). In patients with various liver diseases, B-ALP was slightly increased, but stayed within the normal range (mean +/- 2 SD) until T-ALP did not exceed 4.5 mu katal/L. We conclude that this new IRMA for B-ALP is reliable, has a low cross-reactivity with the liver isoenzyme, and appears to be more sensitive than T-ALP for the clinical investigation of patients with osteoporosis and other metabolic bone diseases.
我们采用一种新的免疫放射分析（IRMA）法，对173名女性和180名年龄在20 - 88岁的男性健康对照者以及代谢性骨病患者的血清骨碱性磷酸酶（B - ALP）进行了检测。分别以肝病患者和总碱性磷酸酶（T - ALP）升高的佩吉特病患者的血清样本作为肝同工酶和骨同工酶的来源，我们测定出该IRMA法对肝的交叉反应率为16%，这一结果通过循环碱性磷酸酶同工酶的电泳得以证实。该IRMA法对系列样本稀释呈线性关系，回收率在89% - 110%之间，批内和批间变异分别低于7%和9%。男女两性的B - ALP均随年龄呈线性增加，且女性和男性的B - ALP血清平均水平无显著差异（女性为11.3±4.8 ng/mL；男性为11.0±4.0 ng/mL）。绝经后B - ALP的升高显著高于T - ALP（分别为+77%对+24%；P < 0.001）。当将绝经后女性的值表示为相对于绝经前女性均值的标准差时，B - ALP的平均Z评分为2.2±1.8，T - ALP为0.9±1.3（两者之间P < 0.001）。佩吉特病患者（n = 57；均值为171.8±135.6 ng/mL；P < 0.001）、原发性甲状旁腺功能亢进患者（n = 18；均值为17.2±5.9 ng/mL；P < 0.001）以及接受血液透析的慢性肾衰竭患者（n = 83；均值为36.6±35.7 ng/mL；P < 0.001）的血清B - ALP均高于对照值。在佩吉特病患者中，B - ALP与T - ALP高度相关（r2 = 0.94；P < 0.001），在用双膦酸盐帕米膦酸治疗后，其血清水平的下降幅度大于T - ALP（分别为-58%对-43%；P < 0.03）。在各种肝病患者中，B - ALP略有升高，但在T - ALP不超过4.5微 katal/L之前，其值仍处于正常范围（均值±2标准差）。我们得出结论，这种用于检测B - ALP的新型IRMA法可靠，与肝同工酶的交叉反应率低，并且在骨质疏松症和其他代谢性骨病患者的临床研究中似乎比T - ALP更敏感。
