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

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Biomarkers in Bone Disease

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Abstract

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.

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Abbreviations

BAP:

Bone-specific alkaline phosphatase

BMD:

Bone mineral density

BSP:

Bone sialoprotein

CA/P:

Calcium/phosphate

CTX:

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

FGF-23:

Fibroblast growth factor-23

FRAX:

The fracture risk assessment tool

GIP:

Gastric inhibitory peptide

GLP-1:

Glucagon-like peptide-1

GLP-2:

Glucagon-like peptide-2

HbA1c:

Glycated hemoglobin A1c

hMSC:

Human mesenchymal stem cells

hMSC-TERT:

Human mesenchymal stem cells telomerase-immortalized

IGF-1:

Insulin-like growth factor-1

IVGTT:

Intravenous glucose tolerance test

NTX:

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

OGTT:

Oral glucose tolerance test

OPG:

Osteoprotegerin

P1NP:

Procollagen type 1 N-terminal propeptide

PTH:

Parathyroid hormone

RANK:

Receptor activator of nuclear factor kappa-B

RANKL:

Receptor Activator of Nuclear factor Kappa beta Ligand

Runx2:

Runt-related protein 2

TRAP:

Tartrate resistant acid phosphatase

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Authors and Affiliations

  1. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Tage Hansens Gade 2, 8000, Aarhus C, Denmark

    Jakob Starup-Linde & Sidse Westberg-Rasmussen

  2. Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark

    Simon Lykkeboe

  3. Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark

    Peter Vestergaard

Authors
  1. Jakob Starup-Linde
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  2. Sidse Westberg-Rasmussen
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  3. Simon Lykkeboe
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  4. Peter Vestergaard
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Corresponding authors

Correspondence to Jakob Starup-Linde , Sidse Westberg-Rasmussen , Simon Lykkeboe or Peter Vestergaard .

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Editors and Affiliations

  1. Sciences Division, King's College, London, United Kingdom

    Victor R. Preedy

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Starup-Linde, J., Westberg-Rasmussen, S., Lykkeboe, S., Vestergaard, P. (2015). Effects of Glucose on Bone Markers: Overview of Current Knowledge with Focus on Diabetes, Glucose, and Bone Markers. In: Preedy, V. (eds) Biomarkers in Bone Disease. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7745-3_15-1

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  • DOI: https://doi.org/10.1007/978-94-007-7745-3_15-1

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