Osteocalcin is a peptide hormone found in bone with various functions. It is significantly involved in bone metabolism and serves as a marker for various bone diseases in the blood. However, it also plays a major role in carbohydrate or fat metabolism.
What is osteocalcin?
Osteocalcin is a peptide hormone produced in the osteoblasts of bone or the odontoblasts of teeth. As part of the extracellular bone matrix, it binds to the mineral hydroxyapatite. There it is present in approximately one to two percent. Due to its binding to the calcium of the mineral, osteocalcin inhibits the uninhibited mineralization of bone. It is encoded by a gene on chromosome 1q25q31. In studies on mice, mutations of this gene led to increased mineralization of bone and thus to the development of marble bone disease. This resulted in increased bone formation with concomitant increased brittleness. Synthesis of the hormone is dependent on the vitamin D metabolite calcitriol (1,25(OH)2D3). Binding to calcium is in turn catalyzed with the aid of the enzyme glutamyl carboxylase. Vitamin K acts as a cofactor in this process. Osteocalcin acts as a marker of bone formation. It has already been isolated from preserved Neanderthal bones. For diagnostic purposes, it is measured in blood.
Function, effects, and roles
Osteocalcin fulfills several functions in the organism. It is a hormone that is synthesized only in the osteoblasts of bones or the odontoblasts of teeth. There it is significantly involved in bone metabolism. Within the skeletal system, bone-building and bone-degrading processes are constantly taking place. When bone resorption processes predominate, osteoporosis occurs. Although the hormone does not prevent osteoporosis, it functions as an important marker for certain bone diseases. Within the bone, it has the task of limiting the mineralization of the bones. In doing so, it binds to the hydroxyapatite of the extracellular non-collagenous bone matrix. The bones form normally and obtain the necessary strength against fractures. It is present in the matrix up to two percent. However, in order to bind to the calcium atoms of the mineral, the glutamyl residues contained in osteocalcin must first be removed with the help of an enzyme. This enzyme is glutamyl carboxylase, which in turn is activated by the cofactor vitamin K. The enzyme is also known as osteocalcin. According to the latest findings, osteocalcin also has a blood sugar-lowering and fat-reducing effect. The lowering of blood sugar occurs in two ways. Osteocalcin stimulates the synthesis of the hormone insulin directly by stimulating the “islets of Langerhans” of the pancreas. Furthermore, it also increases insulin efficacy indirectly by stimulating the hormone adiponectin. In recent years, it has been found that [[insulin resistance is caused by decreased production of adiponectin. The more fat is stored in the adipocytes, the lower the adiponectin synthesis. This in turn decreases the effectiveness of insulin. In addition, it has also been found in animal studies that osteocalcin boosts fat burning. Mice with high osteocalcin levels did not develop obesity or diabetes. Based on this research, future approaches may emerge to more effectively combat obesity and type II diabetes with the help of osteocalcin.
Formation, occurrence, properties, and optimal values
As mentioned above, osteocalcin is synthesized in the osteoblasts of bones and in the odontoblasts of teeth. Its production rate is dependent on vitamin K and is stimulated by vitamin D. After its formation, it is then incorporated mainly as a component in the extracellular bone matrix. Only there it is stable. In free form, it has only a short half-life. In blood plasma, for example, it is broken down by half within four minutes by the proteases contained there. It is released during bone turnover and enters the blood in the process. The measured concentrations in blood and urine provide information about the metabolic activity of the bones and are therefore a good marker for certain bone diseases.
Diseases and disorders
The levels of osteocalcin in blood and urine depend on many factors. In very general terms, they characterize the rate of bone turnover. During bone turnover, bone is constantly being broken down and rebuilt.If bone resorption processes predominate, bone density decreases in the long term and brittleness increases. Naturally, this also results in the increased release of substances that are involved in bone formation. This also includes osteocalcin. High levels in the blood always mean increased degradation processes. Osteocalcin levels in the blood that are too high are found in osteoporosis with a high metabolic rate, hyperparathyroidism, bone metastases in malignancies, Paget’s disease, osteomalacia, hyperthyroidism or renal insufficiency. Osteocalcin levels that are too low occur with prolonged cortisone therapy, osteoporosis with low bone turnover, rheumatoid arthritis, or hypoparathyroidism. Osteoporosis in particular can be caused by many different things. Therefore, bone turnover can be high or low. Common to all forms of osteoporosis is that bone resorption outweighs bone formation. Hormone disorders based on an overactivity of the parathormone cause osteocalcin levels in the blood to rise sharply. Parathyroid hormone regulates blood calcium levels by breaking down bone. Conversely, too low parathyroid hormone concentrations also lead to low osteocalcin levels in the blood. In Paget’s disease, irregular remodeling processes occur in the skeletal system, which also leads to increased osteocalcin concentrations. Of course, with generally increased metabolic rates in the context of hyperthyroidism, bone turnover also increases with increased osteocalcin levels. Cortisone therapy slows bone turnover. The blood values are typical for certain diseases. However, osteocalcin determination provides only one finding as part of the overall diagnosis.
