MECHANISMS IN ENDOCRINOLOGY: The endocrine role of the skeleton: background and clinical evidence

Abstract

Based on the observation that diabetes, obesity, and hypogonadism influence bone metabolism, the existence of a feedback loop and a common regulation was postulated and an endocrine role ascribed to the skeleton. In the first part of this review, two pathways are described whereby adipose tissue acts on bone mass. In the first, leptin activates the sympathetic nervous system via serotonin and diminishes bone mass accrual. The second pathway functions via the activation of CART (CARTPT) and inhibits bone resorption. The first pathway leads to a decrease in bioactivity of the osteoblast-produced hormone osteocalcin (OC) (part 2). In its undercarboxylated form, OC acts on the three targets pancreas, adipose tissue, and gonads (part 3) and thereby causes an increase in insulin secretion and sensitivity, b-cell proliferation, and male fertility. Insulin (part 4) is part of a recently discovered regulatory feedback loop between pancreas and osteoblasts. It is a strong counterplayer of leptin as it causes a decrease in OPG expression and enhances bone resorption and OC decarboxylation. Numerous clinical studies (part 5) have shown associations of total and undercarboxylated OC and markers of energy metabolism. Interventional studies, to date only performed in murine models, have shown positive effects of OC administration on energy metabolism. Whether bone tissue has an even further-reaching endocrine role remains to be elucidated. European Journal of Endocrinology 166 959-967

Associations Between Liver Function, Bone Turnover Biomarkers and Adipokines in Older Patients With Hip Fracture

“…2) Osteopenia/ osteoporosis (hepatic osteodystrophy) is present in 20-50% of patients with chronic liver disease [6][7][8][9][10]. 3) Osteocalcin (OC), an osteoblast-derived hormone, is recognized as a critical determinant of energy and glucose homeostasis [11][12][13][14][15][16]. 4) Dysregulation and dysfunction of adipokines, adipose tissue-derived hormones, in particular, adiponectin, leptin and resistin, which have receptors expressed in both hepatocytes and bone cells and control a vast diversity of physiological functions, are involved in initiation and progression of many diseases including liver and bone (osteoporosis) disorders [17][18][19][20][21][22][23].…”

Bone mineral density in male adolescents with autism spectrum disorders and disruptive behavior disorder with or without antipsychotic treatment

“…Despite their efficacy (5), there are concerns about metabolic (such as obesity, hyperglycemia, and dyslipidemia) and endocrine (such as hyperprolactinemia) side effects (6,7,8). AP such as olanzapine, clozapine, and risperidone can reduce hepatic insulin sensitivity (9), possibly by reducing serotonin levels in the brain, which causes a reduction in osteocalcin and adiponectin levels and ultimately diminished insulin sensitivity (10). AP-linked obesity and type 2 diabetes mellitus are more prevalent in children and adolescents than in adults (7), possibly because of differences in their body composition, e.g.…”

“…Disturbances in this process during puberty may increase the risk of osteoporosis later in life. The AP-induced change in energy metabolism and insulin signaling could lead to a lower bone mineral density (BMD) (10), which in turn could increase the risk of osteoporosis later in life.…”

Gene expression profile in bone of diabetes-prone BB/OK rats fed a high-fat diet

“…Now it is well-accepted that the skeleton is an endocrine organ that, through the secreted molecule osteocalcin (Bgla), favors insulin secretion by insulin-producing b cells and insulin sensitivity in liver, muscle, and adipocytes (Ferron et al 2008;Fukumoto and Martin 2009;Hinoi et al 2008;Lee et al 2007;Lee 2010;Lieben et al 2009;Schwetz et al 2012). The protein osteocalcin is produced by osteoblasts and odontoblasts and has been known as a marker of bone turnover (Brown et al 1984;Ducy 2011).…”