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Bone. 2016 Jan;82:69-78. doi: 10.1016/j.bone.2015.02.019. Epub 2015 Feb 24.

Biochemical bone turnover markers in diabetes mellitus - A systematic review.

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Department of Endocrinology and Internal Medicine, Aarhus University Hospital THG, Aarhus, Denmark; Department of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark. Electronic address:
Department of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark; Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark.



Diabetes mellitus is associated with an increased risk of fractures, which is not explained by bone mineral density. Other markers as bone turnover markers (BTMs) may be useful.


To assess the relationship between BTMs, diabetes, and fractures.


A systematic literature search was conducted in August 2014. The databases searched were Medline at Pubmed and Embase. Medline at Pubmed was searched by "Diabetes Mellitus" (MESH) and "bone turnover markers" and Embase was searched using the Emtree by "Diabetes Mellitus" and "bone turnover", resulting in 611 studies. The eligibility criteria for the studies were to assess BTM in either type 1 diabetes (T1D) or type 2 diabetes (T2D) patients.


Of the 611 eligible studies, removal of duplicates and screening by title and abstract lead to 114 potential studies for full-text review. All these studies were full-text screened for eligibility and 45 studies were included. Two additional studies were added from other sources. Among the 47 studies included there were 1 meta-analysis, 29 cross-sectional studies, 13 randomized controlled trials, and 4 longitudinal studies. Both T1D and T2D were studied. Most studies reported fasting BTM and excluded renal disease.


Markers of bone resorption and formation seem to be lower in diabetes patients. Bone specific alkaline phosphatase is normal or increased, which suggests that the matrix becomes hypermineralized in diabetes patients. The BTMs: C-terminal cross-link of collagen, insulin-like growth factor-1, and sclerostin may potentially predict fractures, but longitudinal trials are needed. This article is part of a Special Issue entitled Bone and diabetes.


Bone; Bone turnover; Bone turnover markers; Diabetes mellitus; Diabetes treatment; Fracture

[Indexed for MEDLINE]

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