Type I collagen and procollagen fragments in patients with metabolic bone diseases

The purpose of the present study was to evaluate the serum levels of two new markers, and to compare their clinical usefulness with two conventional markers. Healthy women and patients with aberrant bone metabolism were evaluated for serum or urine levels of different bone markers. We measured serum levels of the pyridinoline cross-linked telopeptide domain of type I collagen (S-ICTP) and carboxy-terminal propeptide of type I procollagen (S-PICP) as markers of bone resorption and formation, respectively. These levels were compared to the concentrations of serum bone gamma-carboxyglutamic acid protein (S-BGP) and total urinary pyridinium cross-links (U-PYD). The control group included 222 premenopausal and postmenopausal women, and the disease groups consisted of 61 individuals with malignancy-associated hypercalcemia, Graves' thyrotoxicosis or primary hyperparathyroidism. Both S-PICP and S-BGP reflected higher bone turnover in postmenopausal than premenopausal women. All patient groups had significantly higher S-ICTP and U-PYD than the controls. Increased S-PICP was seen in malignancy-associated hypercalcemia and Graves' thyrotoxicosis, but not in primary hyperparathyroidism, while higher S-BGP was seen in Graves' thyrotoxicosis and primary hyperparathyroidism, but not in malignancy-associated hypercalcemia. Discrepancy between S-PICP and S-BGP in malignancy-associated hypercalcemia and primary hyperparathyroidism was noted. S-ICTP and U-PYD had higher sensitivity and specificity in discriminating patients from controls. We conclude that S-ICTP is superior to U-PYD as an index of bone resorption in aberrant bone metabolism. S-PICP may also be a useful bone turnover marker but discrepancies between it and S-BGP in malignancy-associated hypercalcemia and primary hyperparathyroidism need further investigation.