The Journal of Physiological Sciences

, Volume 67, Issue 1, pp 71–81 | Cite as

Derangement of calcium metabolism in diabetes mellitus: negative outcome from the synergy between impaired bone turnover and intestinal calcium absorption

  • Kannikar Wongdee
  • Nateetip Krishnamra
  • Narattaphol CharoenphandhuEmail author


Both types 1 and 2 diabetes mellitus (T1DM and T2DM) are associated with profound deterioration of calcium and bone metabolism, partly from impaired intestinal calcium absorption, leading to a reduction in calcium uptake into the body. T1DM is associated with low bone mineral density (BMD) and osteoporosis, whereas the skeletal changes in T2DM are variable, ranging from normal to increased and to decreased BMD. However, both types of DM eventually compromise bone quality through production of advanced glycation end products and misalignment of collagen fibrils (so-called matrix failure), thereby culminating in a reduction of bone strength. The underlying cellular mechanisms (cellular failure) are related to suppression of osteoblast-induced bone formation and bone calcium accretion, as well as to enhancement of osteoclast-induced bone resorption. Several other T2DM-related pathophysiological changes, e.g., osteoblast insulin resistance, impaired productions of osteogenic growth factors (particularly insulin-like growth factor 1 and bone morphogenetic proteins), overproduction of pro-inflammatory cytokines, hyperglycemia, and dyslipidemia, also aggravate diabetic osteopathy. In the kidney, DM and the resultant hyperglycemia lead to calciuresis and hypercalciuria in both humans and rodents. Furthermore, DM causes deranged functions of endocrine factors related to mineral metabolism, e.g., parathyroid hormone, 1,25-dihydroxyvitamin D3, and fibroblast growth factor-23. Despite the wealth of information regarding impaired bone remodeling in DM, the long-lasting effects of DM on calcium metabolism in young growing individuals, pregnant women, and neonates born to women with gestational DM have received scant attention, and their underlying mechanisms are almost unknown and worth exploring.


Bone loss Calcium wasting Growth plate T1DM T2DM Osteoporosis 



Our research was supported by grants from the Cluster and Program Management Office (CPMO), National Science and Technology Development Agency (P-11-00639 to NK and P-13-00100 to NC), the Thailand Research Fund (TRF)–Mahidol University through the TRF Senior Research Scholar Grant (RTA5780001 to NC), the Faculty of Allied Health Sciences, Burapha University and TRF through TRF Research Scholar Award Grant (RSA5780041 to KW), the Higher Education Research Promotion and National Research University Project of Thailand, Office of the Higher Education Commission (6/2559 to KW).

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest.


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Copyright information

© The Physiological Society of Japan and Springer Japan 2016

Authors and Affiliations

  • Kannikar Wongdee
    • 1
    • 3
  • Nateetip Krishnamra
    • 1
    • 2
  • Narattaphol Charoenphandhu
    • 1
    • 2
    Email author
  1. 1.Center of Calcium and Bone Research (COCAB), Faculty of ScienceMahidol UniversityBangkokThailand
  2. 2.Department of Physiology, Faculty of ScienceMahidol UniversityBangkokThailand
  3. 3.Faculty of Allied Health SciencesBurapha UniversityChonburiThailand

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