Novel biological markers of bone: from bone metabolism to bone physiology.

Biochemical markers of bone turnover have been used for decades in the management of bone diseases, to assess the prognosis of these conditions and to monitor treatments. The new markers, however, also reflect specific physiological mechanisms in the bone or other organs. Periostin may be more specific to the periosteum; cathepsin K is an osteoclastic enzyme that may be involved in the cardiovascular system and joints; Dickkopf-1 is involved in bone formation and vascular calcification; sclerostin is a major regulator of bone formation in response to mechanical loading and may also play a role in chronic kidney disease bone and mineral disorder; sphingosine-1-phosphate is a lipid mediator interacting with bone resorption. Some of the bone markers are in fact hormones produced by the bone that affect various physiological and pathological functions in other organs. Thus, osteocalcin is produced by osteoblasts and participates in the regulation of insulin sensitivity and fertility in men. Fibroblast growth factor 23 is produced by osteocytes to regulate phosphorus and 1,25(OH)2D3, but it also plays a major role in the adverse consequences of declining renal function, in particular with respect to the myocardium. Micro RNAs are single-stranded RNAs that regulate several pathways, including the development timing, organogenesis, cell apoptosis, proliferation and differentiation. Their serum concentration may reflect the links between bone physiology and certain conditions in other organs, for example, the cardiovascular system.