Comparison of Biochemical Markers of Bone Resorption in Patients with Metabolic and Malignant Bone Diseases

Abstract

The clinical usefulness of the urinary excretion of three bone resorption markers is compared in patients after renal transplantation and in tumour patients with and without bone metastases. The markers were the 3-hydroxypyridinium derivatives pyridinoline and deoxypyridinoline (pyridinium cross-links; measured by a polyclonal enzyme immunoassay), the cross-linked N-telopeptid-to-helix domain of type I collagen and the destruction products of type I collagen metabolism cross-reacting with a peptide sequence of the α₁-chain of the C-terminal telopeptide region of type I collagen (CrossLaps™). In patients receiving renal transplantation the discriminating power of N-telopeptides was superior to that of pyridinium cross-links and CrossLaps™, with Z scores (number of SDs from apparently healthy controls) of 6·61, 2·17 and 1·35, respectively. However, the pyridinium cross-links were the only markers for bone resorption which showed a significant increase with time ( P < 0·001). Receiver operating-characteristic analysis for discriminating patients with bone metastases from those without revealed that the accuracy was 0·81 for pyridinium cross-links, 0·76 for the N-telopeptides and 0·61 for CrossLaps™. The discriminating power for patients with bone metastases was higher for pyridinium cross-links and N-telopeptides than for CrossLaps™, with Z scores (number of SDs from patients without bone metastases) of 4·38, 3·00 and 1·24, respectively. Linear correlation coefficients for the different markers were between + 0·35 and + 0·65 in patients receiving renal transplants, and between + 0·58 and + 0·84 in patients with bone metastases. In conclusion, in patients with metabolic and malignant bone diseases there are marked differences in the diagnostic performance of different biochemical markers of bone resorption. It is suggested that this may reflect the different facets of bone resorption or the different metabolic fates of the marker substances examined.