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 only the intact human osteocalcin molecule in haemodialysed patients.


METHODS
Iliac bone biopsy specimens obtained from 62 haemodialysed patients were analysed.


RESULTS
Bone formation rates (BFR/BS) correlated positively with serum intact osteocalcin concentrations (n=62), osteocalcin concentrations assayed by a conventional method (n=31), parathyroid hormone (PTH) concentrations (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 analysis, 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=0.628). 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 concentration was not a good marker to distinguish adynamic bone from a mild lesion or hyperparathyroid bone, we designed a two-step procedure. The first step was the diagnosis of adynamic bone (cut-off: 65 pg/ml) or hyperparathyroid bone (cut-off: 455 pg/ml) according to serum PTH concentration. In a second step, we assessed serum intact osteocalcin concentration in patients with 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 properly. The Youden index of this two-step diagnosis was 0.527 and 0.661 for adynamic bone and hyperparathyroid bone respectively. Sensitivity markedly improved to 94.4% and 96.2% for adynamic bone and hyperparathyroid bone respectively, without sacrificing specificity (84.0 and 88.8% respectively).


CONCLUSIONS
Measurement of serum intact osteocalcin concentration is useful for the diagnosis of adynamic bone in haemodialysed patients. A two-step procedure involving also simultaneous measurement of serum PTH concentration further improved the sensitivity of each individual marker while maintaining specificity.
Morishita
T
T
Division of Nephrology, Fourth Department of Medicine, Kitasato University School of Medicine, Kanagawa, Japan.
Nomura
M
M
Hanaoka
M
M
Saruta
T
T
Matsuo
T
T
Tsukamoto
Y
Y
D000328:Adult; D000368:Aged; D001706:Biopsy; D001847:Bone Diseases / Q000097:blood / Q000209:etiology* / Q000473:pathology; D005260:Female; D005544:Forecasting; D006801:Humans; D006961:Hyperparathyroidism / Q000097:blood / Q000473:pathology; D007085:Ilium / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009398:Nephrology / Q000379:methods*; D015675:Osteocalcin / Q000097:blood* / Q000737:chemistry; D010018:Osteomalacia / Q000097:blood / Q000473:pathology; D012372:ROC Curve; D006435:Renal Dialysis / Q000009:adverse effects*
D015675:Osteocalcin