Effects of Glucose on Bone Markers: Overview of Current Knowledge with Focus on Diabetes, Glucose, and Bone Markers

  • Jakob Starup-LindeEmail author
  • Sidse Westberg-RasmussenEmail author
  • Simon LykkeboeEmail author
  • Peter VestergaardEmail author
Reference work entry
Part of the Biomarkers in Disease: Methods, Discoveries and Applications book series (BDMDA)


Diabetes mellitus is associated with an increased risk of fracture. However, in patients with diabetes the bone mineral density does not explain this. Bone turnover markers give information on bone formation and bone resorption and may explain the decreased bone material competence in patients with diabetes. Diabetes mellitus is characterized by the lack of a fasting condition, which also may affect the general bone turnover and be reflected in the bone turnover markers. This chapter focuses on the relation between bone turnover markers and plasma glucose, and bone turnover markers in diabetes subjects. In clinical trials, an oral glucose tolerance test (OGTT) decreased bone resorption markers in both patients with type 2 diabetes and healthy individuals. During an OGTT, bone formation markers were decreased in healthy individuals, but the markers were not investigated in patients with diabetes. An intravenous glucose tolerance test decreases the bone resorption marker C-terminal cross-linked telopeptide of type-I collagen (CTX) but not as much as the OGTT. Therefore a gastrointestinal interaction may affect the relation between glucose and bone turnover markers. In patients with diabetes, both CTX and the bone formation marker osteocalcin were decreased compared to controls. However, heterogeneity was present in the markers, which may be due to differences in glycemic status. In vitro studies show direct effects of glucose on the bone cells: osteoblasts, osteoclasts, and osteocytes. Hyperglycemia had detrimental effects on osteoblasts and osteoclasts and increased the sclerostin production in osteocytes; thus both bone resorption and formation seemed to decrease during hyperglycemia. However, in the mild hyperglycemia with a glucose level of 11–15 mmol/l, the osteoblasts increased the mineralization. Thus, hyperglycemia may hypermineralize the bone, so the bone mineral density is increased relatively to the bone material competence due to a relative decrease in non-mineralized matrix, e.g., collagen.

Further, investigations are needed to determine if the glucose bone turnover marker interaction may be a prognostic marker of fracture in patients with diabetes.


Glucose Hyperglycemia Bone turnover markers Bone turnover Diabetes mellitus Osteoblasts Osteoclasts Osteocytes Hypermineralization 

List of Abbreviations


Bone-specific alkaline phosphatase


Bone mineral density


Bone sialoprotein




C-terminal cross-linked telopeptide of type-I collagen


Fibroblast growth factor-23


The fracture risk assessment tool


Gastric inhibitory peptide


Glucagon-like peptide-1


Glucagon-like peptide-2


Glycated hemoglobin A1c


Human mesenchymal stem cells


Human mesenchymal stem cells telomerase-immortalized


Insulin-like growth factor-1


Intravenous glucose tolerance test


N-terminal cross-linked telopeptide of type-I collagen


Oral glucose tolerance test




Procollagen type 1 N-terminal propeptide


Parathyroid hormone


Receptor activator of nuclear factor kappa-B


Receptor Activator of Nuclear factor Kappa beta Ligand


Runt-related protein 2


Tartrate resistant acid phosphatase


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Copyright information

© Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  1. 1.Department of Endocrinology and Internal MedicineAarhus University HospitalAarhus CDenmark
  2. 2.Department of Clinical BiochemistryAalborg University HospitalAalborgDenmark
  3. 3.Department of EndocrinologyAalborg University HospitalAalborgDenmark

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