Osteocalcin is an important protein that is critical to the formation and maintenance of bones. It also acts as a hormone to adjust insulin and glucose levels, increase testosterone, and improve muscle strength and cognitive function. Read on to learn more about osteocalcin and its complex role in health.
What is Osteocalcin?
As a hormone, osteocalcin is also released into the blood, where it:
- Increases the production of insulin by the pancreas [3, 1]
- Adjusts blood glucose levels [3, 1]
- Stimulates testosterone production [1, 4]
- Increases muscle strength [1, 5]
- Improves brain function 
Osteocalcin Function & Health Effects
1) Builds Strong Bones
Osteocalcin is responsible for binding calcium to bone tissue, which is what gives bones their strength and flexibility. For this process to occur, osteocalcin first needs to be activated by vitamin K2 .
Since it increases bone strength, osteocalcin increases during periods of rapid growth, such as in children during the first year of life and during puberty .
Mice with low levels of osteocalcin have weaker bones that are more likely to break .
However, more osteocalcin is not always a sign of bone strength. Osteocalcin levels can increase as a result of a widespread bone loss. In older people, high blood levels predict lower bone density (particularly in the hip and spine) and fracture risk, including hip fractures [8, 1, 9, 10, 11, 12].
2) Adjusts Insulin and Glucose Levels
Osteocalcin works as a hormone to control insulin and glucose (sugar) balance in the body .
Osteocalcin also acts on muscles and other tissues to help keep sugar levels in check. It works by increasing the production of adiponectin in fat cells (adipocytes). Adiponectin, in turn, increases the uptake of glucose into fat and muscle cells [15, 16].
3) Stimulates Testosterone Production
Osteocalcin is linked to reproductive health in men. From the blood, osteocalcin reaches cells in the testicles and increases the production of testosterone (through the GPRC6A receptor) [4, 19, 1, 20, 21, 4, 19].
Blood levels of osteocalcin normally rise during puberty in boys, while low levels are associated with slowed or delayed puberty. However, because osteocalcin levels can vary a lot from person to person, they are not necessarily a reliable marker of sexual development .
4) May Improve Muscle Strength
Osteocalcin may increase the strength of skeletal (limb) muscles. It helps your muscles adapt to exercise, which is particularly important for preventing a drop in exercise capacity and muscle loss in older people [23, 24, 5, 25, 26].
Higher levels were linked to muscle strength in women over the age of 70. Plus, osteocalcin may reduce the risk of falls and bone fractures by maintaining muscle mass. Indirectly, osteocalcin helps build muscles by increasing testosterone [23, 5].
5) May Improve Brain Function
Osteocalcin increased the production of monoamine neurotransmitters (dopamine, noradrenaline, and serotonin) in the brains of mice. These neurotransmitters play significant roles in motivation, learning, mood, and memory .
In 44 people, low osteocalcin levels were linked to negative changes in the microstructure of the brain (in the caudate, hypothalamus, thalamus, putamen, and subcortical white matter) and reduced cognitive performance .
In another study of 117 women between the ages of 71 and 78 years, higher osteocalcin levels improved cognitive function .
Health Risks of Low Osteocalcin
1) Insulin Resistance and Diabetes
In 98 healthy people, low osteocalcin levels were linked to the poor use of insulin by the body (insulin resistance), low production of insulin, and elevated glucose levels (high blood sugar) .
In turn, high osteocalcin was associated with better control of blood glucose levels in 128 people with type 1 diabetes. Osteocalcin also protected rat beta cells, which produce insulin, from damage caused by high glucose levels [39, 40, 41].
Sex differences may affect how osteocalcin affects insulin resistance. One study revealed that long-term osteocalcin administration actually increased insulin resistance in male mice on a high-fat diet .
However, some researchers dispute the existence of a causal link between osteocalcin and glucose levels. They argue that even if a link exists, it is not clear whether it is osteocalcin that affects glucose levels or the other way around .
2) Heart Disease Risk
Low levels of osteocalcin in the blood can indicate heart disease. The current evidence suggests that normal osteocalcin levels support the overall health of the heart and blood vessels. However, it’s not as simple. Many other factors–including age, sex, physical activity, and so on–play in [47, 48].
In 247 older people with heart disease, those with lower osteocalcin levels had a higher risk of future cardiovascular health problems .
3) Hardening of the Arteries (Atherosclerosis)
The relationship between osteocalcin and hardening of the arteries is complex. A meta-analysis found 26 positive, 17 negative, and 29 neutral relationships .
In 774 men, higher osteocalcin levels indicates less artery hardening (calcification) and lower heart disease risk .
Also, researchers prevented hardening of the arteries in diabetic rats by increasing osteocalcin levels .
However, high blood osteocalcin levels were associated with heart artery hardening in 114 men, regardless of other cardiovascular risk factors and bone density .
Finally, one study of over 3,000 people found that osteocalcin levels and stiffness in the arteries were related in an “inverse J-shaped curve.” This means that both low and high levels of osteocalcin can increase the risk of hardening of the arteries, although low levels increase the risk to a greater degree .
4) Metabolic Syndrome
In a meta-analysis of 55 studies of 47k people, low osteocalcin blood levels were linked to a higher risk of metabolic syndrome. Similarly, in 798 older men, low levels pointed to metabolic syndrome [18, 57].
Additionally, in a study of over 2,000 people, lower osteocalcin levels were associated with higher levels of C-reactive protein (CRP), a marker of chronic inflammation in people with metabolic syndrome .
Finally, when obese female mice were given osteocalcin during pregnancy, their offspring were protected against metabolic disorders that are caused by maternal obesity .
According to a meta-analysis, people with low osteocalcin levels are more likely to have a higher body mass index (BMI). Other studies in children, adolescents, and pre- and post-menopausal women support this association [60, 61, 62, 63, 64, 65].
6) Fatty Liver
Osteocalcin blood tests can help predict the severity of fatty liver disease (NAFLD).
In a study of 120 children aged 7 to 13 years old (60 NAFLD patients and 60 controls), low osteocalcin blood levels predicted the severity of NAFLD. Low levels were also an indicator of NAFLD in 4 studies that included almost 9k adults [67, 68, 69, 70, 71].
Health Risks of High Osteocalcin
High levels point to bone loss and predict low bone density and fracture risk in older people.
Animal studies suggest that this is because bone re-absorption–the breakdown of bone tissue that releases minerals–frees osteocalcin from the bones, raising its blood levels .
Vitamin K, vitamin D, and calcium supplements reduced osteocalcin levels and increased bone density in a study of 78 postmenopausal women .
2) Diabetes in Pregnancy
From 130 pregnant women, those with high blood osteocalcin levels were more likely to experience insulin resistance during pregnancy, which can lead to a condition called gestational diabetes. Osteocalcin levels were higher throughout pregnancy in 48 women with gestational diabetes, compared to 48 healthy pregnant women [79, 80].
In another study of 134 pregnant women, gestational diabetes in the first trimester was linked with high blood osteocalcin .
3) Increased Breast Cancer Risk
Obese, postmenopausal women with high blood osteocalcin levels are more likely to have higher breast density, a significant risk factor for developing breast cancer. A study of 239 premenopausal and postmenopausal women aged between 40 and 60 identified this link .
Osteocalcin levels may affect the formation of red blood cells, which carry oxygen. In 939 elderly men aged 72 to 79 years, high levels were associated with having low numbers of red blood cells (anemia). However, how osteocalcin affects the formation of red blood cells is not yet known .
Read the next post in this series:
Irregular Osteocalcin Levels?
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Osteocalcin is a protein produced by the bones. It helps lock calcium into bones, increasing their strength and healing.
Osteocalcin also works as a hormone. Released into the blood, it increases muscle mass and exercise capacity. Plus, it helps the pancreas produce insulin, maintains normal blood sugar levels, and enhances cognition.
Low osteocalcin levels have been linked with numerous health problems–from diabetes to obesity to bone fractures to heart disease to chronic inflammation.
However, abnormally high levels are not good either. Too much osteocalcin in the blood may point to rapid bone loss and increase your risk of breast cancer, anemia, and diabetes in pregnancy.