Pediatric reference intervals for bone markers

Bone markers are specific bone-derived molecules that reflect bone remodeling activity and can be classified into two categories: bone formation and bone resorption markers. Children have significantly elevated bone marker levels due to high skeletal growth velocity and rapid bone turnover during childhood growth. Many physiological and pathological processes may influence bone metabolism and bone marker concentrations during childhood growth. Measurements of bone markers may be useful in investigating skeletal diseases in children and monitoring the response to treatment. This review documents recent advances in analytical methods, preanalytical considerations related to each marker and particularly highlights the most valuable bone formation markers, bone alkaline phosphatase and osteocalcin, and bone resorption markers, pyridinium cross-links and cross-linked telopeptides. Age- and sex-specific pediatric reference intervals and their limitations in clinical application are also discussed.