• Record: found
  • Abstract: found
  • Article: found
Is Open Access

Relationships between Bone Turnover and Energy Metabolism

Read this article at

      There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


      It is well established that diabetes can be detrimental to bone health, and its chronic complications have been associated with an increased risk of osteoporotic fracture. However, there is growing evidence that the skeleton plays a key role in a whole-organism approach to physiology. The hypothesis that bone may be involved in the regulation of physiological functions, such as insulin sensitivity and energy metabolism, has been suggested. Given the roles of insulin, adipokines, and osteocalcin in these pathways, the need for a more integrative conceptual approach to physiology is emphasized. Recent findings suggest that bone plays an important role in regulating intermediary metabolism, being possibly both a target of diabetic complications and a potential pathophysiologic factor in the disease itself. Understanding the relationships between bone turnover and glucose metabolism is important in order to develop treatments that might reestablish energy metabolism and bone health. This review describes new insights relating bone turnover and energy metabolism that have been reported in the literature.

      Related collections

      Most cited references 107

      • Record: found
      • Abstract: found
      • Article: not found

      Endocrine regulation of energy metabolism by the skeleton.

      The regulation of bone remodeling by an adipocyte-derived hormone implies that bone may exert a feedback control of energy homeostasis. To test this hypothesis we looked for genes expressed in osteoblasts, encoding signaling molecules and affecting energy metabolism. We show here that mice lacking the protein tyrosine phosphatase OST-PTP are hypoglycemic and are protected from obesity and glucose intolerance because of an increase in beta-cell proliferation, insulin secretion, and insulin sensitivity. In contrast, mice lacking the osteoblast-secreted molecule osteocalcin display decreased beta-cell proliferation, glucose intolerance, and insulin resistance. Removing one Osteocalcin allele from OST-PTP-deficient mice corrects their metabolic phenotype. Ex vivo, osteocalcin can stimulate CyclinD1 and Insulin expression in beta-cells and Adiponectin, an insulin-sensitizing adipokine, in adipocytes; in vivo osteocalcin can improve glucose tolerance. By revealing that the skeleton exerts an endocrine regulation of sugar homeostasis this study expands the biological importance of this organ and our understanding of energy metabolism.
        • Record: found
        • Abstract: found
        • Article: not found

        A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance.

        Skeletal muscle insulin resistance is among the earliest detectable defects in humans with type 2 diabetes mellitus. To determine the contribution of muscle insulin resistance to the metabolic phenotype of diabetes, we used the Cre-loxP system to disrupt the insulin receptor gene in mouse skeletal muscle. The muscle-specific insulin receptor knockout mice exhibit a muscle-specific > 95% reduction in receptor content and early signaling events. These mice display elevated fat mass, serum triglycerides, and free fatty acids, but blood glucose, serum insulin, and glucose tolerance are normal. Thus, insulin resistance in muscle contributes to the altered fat metabolism associated with type 2 diabetes, but tissues other than muscle appear to be more involved in insulin-regulated glucose disposal than previously recognized.
          • Record: found
          • Abstract: found
          • Article: not found

          Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism.

          The broad expression of the insulin receptor suggests that the spectrum of insulin function has not been fully described. A cell type expressing this receptor is the osteoblast, a bone-specific cell favoring glucose metabolism through a hormone, osteocalcin, that becomes active once uncarboxylated. We show here that insulin signaling in osteoblasts is necessary for whole-body glucose homeostasis because it increases osteocalcin activity. To achieve this function insulin signaling in osteoblasts takes advantage of the regulation of osteoclastic bone resorption exerted by osteoblasts. Indeed, since bone resorption occurs at a pH acidic enough to decarboxylate proteins, osteoclasts determine the carboxylation status and function of osteocalcin. Accordingly, increasing or decreasing insulin signaling in osteoblasts promotes or hampers glucose metabolism in a bone resorption-dependent manner in mice and humans. Hence, in a feed-forward loop, insulin signals in osteoblasts activate a hormone, osteocalcin, that promotes glucose metabolism. Copyright 2010 Elsevier Inc. All rights reserved.

            Author and article information

            1Instituto Superior de Ciências da Saúde Egas Moniz (ISCSEM), Campus Universitário-Quinta da Granja, 2829-511 Monte de Caparica, Portugal
            2Centro de Investigação Interdisciplinar Egas Moniz (CiiEM), Campus Universitário-Quinta da Granja, 2829-511 Monte de Caparica, Portugal
            3Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal
            Author notes
            *Tânia A. P. Fernandes: tania.apf@

            Academic Editor: Toshiyasu Sasaoka

            J Diabetes Res
            J Diabetes Res
            Journal of Diabetes Research
            11 June 2017
            : 2017
            Copyright © 2017 Tânia A. P. Fernandes et al.

            This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

            Funded by: Egas Moniz-Cooperativa de Ensino Superior
            Funded by: CRL
            Review Article


            Comment on this article