Serum N-terminal midfragment vs. intact osteocalcin immunoradiometric assay as markers for bone turnover and bone loss in hemodialysis patients.

Although labile, assay of intact osteocalcin (iOC) is established as the standard assay for evaluating osteoblastic function. The present study examines the clinical usefulness of the newly developed immunoradiometric assay for osteocalcin (OC), which identifies the stable N-terminal midfragment of OC (N-MID OC assay), in hemodialysis (HD) patients. The performance of N-MID OC assay was compared to that of iOC assay in the sera obtained from 137 male HD patients, by comparing these assays with those of other bone metabolic markers and bone loss during a 1-year period before determination of serum markers. Serum N-MID OC values did not decrease significantly during 24 h incubation at room temperature, whereas serum iOC decreased significantly after 1 h incubation. Serum N-MID and iOC in the 137 male HD patients were 197.3 +/- 57.8 and 34.6 +/- 30.0 ng/ml, respectively, or 3.9 +/- 3.1 and 2.8 +/- 2.4 times above the respective reported normal upper limits. Serum N-MID OC correlated significantly in a positive manner with serum iOC (r = 0.934, P < 0.0001). Serum N-MID OC correlated no less significantly in a positive manner with serum levels of bone alkaline phosphatase, deoxypyridinoline, and intact parathyroid hormone compared to serum iOC. Of interest was the fact that serum N-MID OC, but not iOC, correlated significantly with both the amount and the rate of bone loss at the distal radius 1/3. In summary, the findings suggest that N-MID OC immunoreactivity is much more stable than iOC immunoreactivity and that N-MID OC assay may be less susceptible to the OC fragments reported to accumulate in uremic serum. It may, therefore, prove more reliable than iOC assay for evaluating bone turnover, and thus for reflecting bone loss, in HD patients.