Circulating bone Gla protein in end-stage renal disease determined by newly developed two-site immunoradiometric assay.

As a marker for bone formation, bone Gla protein (BGP) levels in the circulation have been measured in clinical research and management for metabolic bone diseases. We evaluated the clinical availability of a newly developed two-site immunoradiometric assay (IRMA) for human BGP and determined the serum BGP concentrations using this methodology in patients with abnormal calcium metabolism including those with end-stage renal disease undergoing maintenance dialysis. A cross-reactivity test revealed that this assay system specifically recognizes intact molecules (1-49) of BGP and excludes fragments of the molecules (1-19, 12-33, 23-33). Serum BGP levels in dialysis patients were positively correlated with those by conventional radioimmunoassay (RIA) (r = 0.918, p less than 0.00001, n = 37) as well as normal individuals (r = 0.935, p less than 0.0001, n = 16). However, the levels of BGP determined by IRMA were estimated to be significantly lower than those by RIA (23.6 +/- 9.8 vs. 29.6 +/- 9.1 ng/ml, p less than 0.00001). These results suggest that this IRMA system, with a rapid and easy procedure, excludes fragment forms of BGP in the circulation, which are found in uremic sera and probably attributed to increased bone resorption. Further studies are needed to ensure that serum intact BGP levels mainly reflect BGP production in osteoblasts, particularly in end-stage renal disease.