Salivary Osteocalcin

Background

Osteocalcin (also known as OCN, OC, and Bone-Gla-Protein (BGP) or bone gamma-carboxyglutamic acid-containing protein (BGLAP)), is a bone-derived hormone protein released solely by osteoblasts during bone remodeling in vertebrates. Research interest in Osteocalcin has revealed endocrine-related properties related to several physiological pathways. Recent findings suggest that Osteocalcin may also be a key factor in the body’s acute response to stress. Osteocalcin has also been reported to serve several key biological functions including the regulation of insulin secretion, increased adaptation to exercise, improved brain development and cognitive functioning, and maintaining male fertility. In a high-profile, 2019 study published in Cell Metabolism, researchers measured significant increases in serum Osteocalcin levels in both humans and mice, in response to an acute stressor, with evidence to indicate Osteocalcin’s direct contribution to the body’s fight or flight response. This study demonstrated that the increased release of osteocalcin from bones in response to acute stress lead to receptor mediated downstream signaling of post-ganglionic parasympathetic neurons to inhibit their cholinergic activity (1). The study identified the bone as a stress organ and osteocalcin as a stress hormone capable of evolutionarily conferring a survival advantage to bony vertebrates. Increased Osteocalcin levels have been observed within minutes of the application of a stressor in both mice and humans in several studies prior to this one, and its role in stress is well documented (15-16). In conjunction with exercise, osteocalcin may be a vital catalyst for the increase of interleukin-6 which is important for muscle function while exercising. Results from a 2016 study in mice identified osteocalcin signaling in myofibers as a novel and powerful means to fight age-related decline in muscle function (2). Osteocalcin levels have also been reported to increase in response to exercise, by regulating glucose production in response to energy demands. Another study found that declining Osteocalcin levels due to aging may have had a direct effect on declining exercise capacity and may also correlate with muscle strength (3). In addition, research has shown that Osteocalcin may regulate proper brain development and cognitive function (2,4). Osteocalcin has also been implicated in male fertility through the regulation of the synthesis of testosterone in Leydig cells (4). In saliva osteocalcin has also been frequently studied in dentistry as a biomarker of bone loss, and more specifically targeted in studies of periodontitis and effects of smoking (6, 7). Many of these studies have confirmed that osteocalcin in saliva is readily available and may be a reliable measure of bone remodeling and identify the progression of periodontal disease (8-10).