Osteocalcin is the major non-collagen calcium binding protein and it is excreted by osteoblasts in the bone. The serum concentrations are an indication of bone formation. The synthesis of osteocalcin is vitamin D independent. Elevated results are usually associated with increased bone turnover such as what is seen in osteoporosis. Bisphosphonated drugs used to treat osteoporosis can be monitored for effectiveness by measuring osteocalcin levels. Levels are normally high in childhood and then peak in early puberty. During menopause a second peak usually occurs in females.
Although results are not strictly diagnostic of osteoporosis, a decrease in the value can be interpreted as evidence of a favorable response to treatment. Patients that are on vitamin K antagonist medication can have unreliable results. Therefore, ELISA methodology is the best choice to test for undercarboxylated osteocalcin. This assay should be used in conjunction with other bone markers for best interpretation. Bone mineral densitometry and imaging studies are the gold standard for the evaluation of osteoporosis. Bone formation/ resorption may be accurately reflected in patients taking 1,25-dihydroxyvitamin D or if there is an abnormality with it.
Of note, bone formation and serum Osteocalcin level follows a diurnal rhythm and is also subject to the menstrual cycle. Variation by as much as 50% can be seen from a nocturnal peak to a morning low, with a 10% day to day variation, and as large as a 60% increase can be seen following a fracture.