Serum CrossLaps compared with other markers of bone turnover in severely malnourished children before and after refeeding.

Abstract

In growing children, bone turnover is generally high. There are several biochemical markers of bone formation and resorption that have been validated in adults by bone histomorphometry and calcium kinetics. Markers of bone formation are all measured in plasma and include bone-specific alkaline phosphatase (ALP), osteocalcin, and the C-terminal propeptide of type I collagen (PICP). Their use as markers of growth and bone formation in children is now well established (1)(2). However, most markers of bone resorption are measured in urine, including total pyridinoline (Pyd) and the more bone-specific deoxypyridinoline (Dpd). The main problems associated with the urinary markers in pediatric practice are high within-individual biological variation and the need for either timed collections (frequently impossible in children) or, for random urine samples, expressing results as a ratio to creatinine. Creatinine is itself subject to biological variation and changes with muscle mass. Dpd:creatinine excretion in children is highly variable (3) and hence relatively insensitive to therapeutic interventions. Until recently, only one commercially available marker of bone resorption could be measured in plasma, the cross-linked telopeptide of type I collagen (ICTP). Plasma ICTP appears to be less sensitive than some of the other markers to changes in bone resorption in certain clinical situations (e.g., bisphosphonate treatment), perhaps because of metabolism by osteoclastic cathepsin K (4). There is now a new marker for bone resorption that can be measured in serum or plasma, serum CrossLapsTM (5), for which we have recently reported pediatric reference data (6). The CrossLaps assay is specific for the amino acid sequence EKAHD-β-GGR where the aspartic acid residue (D) is β-isomerized. It detects only cross-linked degradation products of C-terminal telopeptides of type I collagen and is therefore specific for bone resorption. It has been clinically evaluated in adults in whom changes in CrossLaps were inversely …