Osteocalcin (OC) is an osteoblast-derived protein implicated in the regulation of glucose tolerance and energy metabolism. This endocrine function has been suggested to be exerted via its undercarboxylated form, which has been shown to induce expression of adiponectin, insulin, and islet cell proliferation in mice. Furthermore, insulin has recently been shown to regulate the biological activity of OC in bone. Our aim was to explore the association between glucose and bone metabolism by evaluating the effect of a standard 75g oral glucose tolerance test (OGTT) on serum OC, carboxylated OC (cOC) and bone-turnover markers (BTMs) C terminal telopeptide (βCTX-I) and N terminal propeptide (PINP) of type I collagen and tartrate-resistant acid phosphatase 5b (TRACP5b). Serum samples collected at 0 and at 120min were analyzed in a cohort of normoglycemic young adults (n=23, mean age 23.6years). During OGTT a significant decrease was observed in all BTMs (P<0.001 for all variables). The median decreases from 0 to 120min for OC, cOC, βCTX-I, PINP, and TRACP5b were -32.1% (-37.9 to -19.6), -34.4% (-39.8 to -22.2), -61.4% (-68.5 to -53.0), -26.8% (-33.2 to -19.2), and -44.5% (-48.3 to -40.2), respectively. A strong association between the changes in OC and cOC was observed (r=0.83, P<0.001). The decrease in PINP was associated with changes in OC, whereas the changes in βCTX-I and TRACP5b were not associated with decreases in OC or cOC. The observed OGTT-induced changes in bone-derived proteins were partially independent of each other and potentially mediated by different mechanisms.