Analytical and clinical evaluation of a method to quantify bone alkaline phosphatase, a marker of osteoblastic activity.

An immunoradiometric assay (IRMA), involving specific monoclonal antibodies (Ostase, Hybritech) and agarose electrophoresis (Isopal, Beckman), two methods for quantification of serum bone alkaline phosphatase (ALP), a marker for osteoblastic activity, were analytically and clinically compared in 293 patients: 79 with end-stage renal failure treated with hemodialysis and 214 with malignant disease. Acceptable within-assay precision was obtained for the IRMA method: 82.5% of the duplicate determinations had a coefficient of variation (CV) < 5%. Curve fitting characteristics were bad and the sensitivity was better than the one mentioned by the manufacturer. Overall correlation between the two methods was good (r = 0.92), except (a) for low values of bone ALP and (b) in some samples with high total liver ALP activity. Low bone ALP determined with the IRMA (< 5 micrograms/L) was confirmed by electrophoresis (< 22 U/L), but ALP activity determined by electrophoresis to be low (< 22 U/L) was not correlated with the IRMA results. After standardizing our results by computing z-values for bone ALP, delta z (= zostase - zelectrophoresis) was significant correlated with liver ALP activity (r = 0.73, P < 0.0001). We conclude that the IRMA for quantifying bone ALP is acceptable. However, when high values for bone ALP are found with the Ostase method, confirmation by electrophoresis remains mandatory to rule out cross-reactivity with high amounts of liver ALP.