A new assay method that detects only intact osteocalcin. Two-step non-invasive diagnosis to predict adynamic bone disease in haemodialysed patients

Background. We studied the usefulness of a new assay method that detects on ly the intact human osteocalcin molecule in haemodialysed patients. Methods. Iliac bone biopsy specimens obtained from 62 haemodialysed patient s were analysed. Results. Bone formation rates (BFR/BS) correlated positively with serum int act osteocalcin concentrations (n = 62), osteocalcin concentrations assayed by a conventional method (n = 31), parathyroid hormone (PTH) concentration s (n = 62), and total alkaline phosphatase concentrations (r = 0.602, 0.588 , 0.650, and 0.401 respectively). Based on ROC curve and Youden index analy sis, the optimal cut-off value to distinguish adynamic bone disease from a mild lesion was 195 pg/ml of serum PTH concentration (Youden index = 0.233) or 30 ng/ml of serum intact osteocalcin concentration (Youden index = 0.62 8). The optimal cut-off Value to distinguish between hyperparathyroid bone and a mild lesion was 455 pg/ml of serum PTH level (Youden index = 0.63) or 50 ng/ml of serum intact osteocalcin concentration (Youden index = 0.634). Since both ROC curve and Youden index suggested that the serum PTH concent ration was not a good marker to distinguish adynamic bone from a mild lesio n or hyperparathyroid bone, we designed a two-step procedure. The first ste p was the diagnosis of adynamic bone (cut-off: 65 pg/ml) or hyperparathyroi d bone (cut-off: 455 pg/ml) according to serum PTH concentration. In a seco nd step, we assessed serum intact osteocalcin concentration in patients wit h serum PTH concentrations between 65 and 455 pg/ml. The cut-off values for adynamic and hyperparathyroid bone in this diagnostic approach were 30 and 70 ng/ml respectively. As a result, 49 out of 62 patients were diagnosed p roperly. The Youden index of this two-step diagnosis was 0.527 and 0.661 fo r adynamic bone and hyperparathyroid bone respectively. Sensitivity markedl y improved to 94.4% and 96.2% for adynamic bone and hyperparathyroid bone r espectively, without sacrificing specificity (84.0 and 88.8% respectively). Conclusion. Measurement of serum intact osteocalcin concentration is useful for the diagnosis of adynamic bone in haemodialysed patients. A two-step p rocedure involving also simultaneous measurement of serum PTH concentration further improved the sensitivity of each individual marker while maintaini ng specificity.