Bone Turnover Markers: Basic Biology to Clinical Applications

Bone turnover markers (BTMs) are used widely, in both research and clinical practice. In the last 20 years, much experience has been gained in measurement and interpretation of these markers, which include commonly used bone formation markers (bone alkaline phosphatase, osteocalcin, and procollagen I N-propeptide); and commonly used resorption markers (serum C-telopeptides of type I collagen, urinary N-telopeptides of type I collagen, and tartrate-resistant acid phosphatase type 5b). BTMs are usually measured by enzyme-linked immunosorbent assay or automated immunoassay. Sources contributing to BTM variability include uncontrollable factors (eg, age, gender, ethnicity) and controllable factors, particularly relating to collection conditions (eg, fasting/feeding state, and timing relative to circadian rhythms, menstrual cycling, and exercise). Pregnancy, season, drugs, and recent fracture(s) can also affect BTMs. BTMs correlate with other methods of assessing bone turnover, such as bone biopsies and radiotracer kinetics, and can usefully contribute to diagnosis and management of several diseases such as osteoporosis, osteomalacia, Paget’s disease, fibrous dysplasia, hypophosphatasia, primary hyperparathyroidism, and chronic kidney disease–mineral bone disorder.