Research Blog

April 15, 2022

Biomarkers of Bone Metabolism: Osteocalcin

Optimal Takeaways

Osteocalcin is a protein that is found in abundance in bone. It not only contributes to bone structure but also regulates the activity of osteoblasts and osteoclasts, influences the production of neurotransmitters and testosterone: and affects insulin production and function. Increased levels reflect bone turnover or growth, while low levels may be associated with cardiometabolic dysfunction.

Standard Range: 9 - 38 ng/mL

The ODX Range: 13.5 - 16 ng/mL

Low levels of osteocalcin are associated with vitamin K insufficiency, insulin resistance, metabolic syndrome, diabetes risk, cardiovascular disease, and impaired cognitive function. Both decreased and elevated osteocalcin were associated with arterial stiffness (Yun 2016).

High levels of osteocalcin are associated with increased loss of bone mineral density, risk of fracture, osteoporosis, menopause, chronic kidney disease, and vitamin D insufficiency (Gossiel 2014).


Osteocalcin reflects bone metabolism. It is produced exclusively by osteoblasts and is one of the most abundant proteins found in bone. It effectively binds calcium and hydroxyapatite, creating a strong matrix of bone tissue (Neve 2013). Osteocalcin regulates osteoblast and osteoclast activity, and elevated levels can be a sign of growth or increased bone turnover (Kanbur 2002). Osteocalcin also has broader effects on insulin production, secretion, and sensitivity; neurotransmitter production; and testosterone production (Zoch 2017).

Very low levels of osteocalcin, below 6.1 ng/mL, have been associated with an increased risk of diabetes (Urano 2017, Pittas 2009). However, a cut-off of 13.5 ng/mL and below had good sensitivity and specificity for diabetes risk in postmenopausal women. Further investigation is warranted at this level and intervention to prevent progression to diabetes may be prudent (Garcia-Martin 2011). Older women in an anti-resorptive, estrogen-replete state, maintained osteocalcin at an average level of 16.5 ng/mL (Gossiel 2014).

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Garcia-Martín, Antonia et al. “Osteocalcin as a marker of metabolic risk in healthy postmenopausal women.” Menopause (New York, N.Y.) vol. 18,5 (2011): 537-41. doi:10.1097/gme.0b013e3181f8565e

Gossiel, Fatma et al. “Establishing reference intervals for bone turnover markers in healthy postmenopausal women in a nonfasting state.” BoneKEy reports vol. 3 573. 3 Sep. 2014, doi:10.1038/bonekey.2014.68

Kanbur, Nuray O et al. “Osteocalcin. A biochemical marker of bone turnover during puberty.” International journal of adolescent medicine and health vol. 14,3 (2002): 235-44. doi:10.1515/ijamh.2002.14.3.235

Neve, Anna et al. “Osteocalcin: skeletal and extra-skeletal effects.” Journal of cellular physiology vol. 228,6 (2013): 1149-53. doi:10.1002/jcp.24278

Pagana, Kathleen Deska; Pagana, Timothy J.; Pagana, Theresa N. Mosby's Diagnostic and Laboratory Test Reference. Elsevier Health Sciences. 2019.

Pittas, Anastassios G et al. “Association between serum osteocalcin and markers of metabolic phenotype.” The Journal of clinical endocrinology and metabolism vol. 94,3 (2009): 827-32. doi:10.1210/jc.2008-1422

Shetty, Sahana et al. “Bone turnover markers: Emerging tool in the management of osteoporosis.” Indian journal of endocrinology and metabolism vol. 20,6 (2016): 846-852. doi:10.4103/2230-8210.192914

Tag(s): Biomarkers

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