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Review
. 2018 Jan 24:9:6.
doi: 10.3389/fendo.2018.00006. eCollection 2018.

The Impact of Type 2 Diabetes on Bone Fracture Healing

Carlos Marin  1   2   3 , Frank P Luyten  1   2 , Bart Van der Schueren  4 , Greet Kerckhofs  1   2 , Katleen Vandamme  2   3
Affiliations
Review

The Impact of Type 2 Diabetes on Bone Fracture Healing

Carlos Marin et al. Front Endocrinol (Lausanne). .

Abstract

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease known by the presence of elevated blood glucose levels. Nowadays, it is perceived as a worldwide epidemic, with a very high socioeconomic impact on public health. Many are the complications caused by this chronic disorder, including a negative impact on the cardiovascular system, kidneys, eyes, muscle, blood vessels, and nervous system. Recently, there has been increasing evidence suggesting that T2DM also adversely affects the skeletal system, causing detrimental bone effects such as bone quality deterioration, loss of bone strength, increased fracture risk, and impaired bone healing. Nevertheless, the precise mechanisms by which T2DM causes detrimental effects on bone tissue are still elusive and remain poorly studied. The aim of this review was to synthesize current knowledge on the different factors influencing the impairment of bone fracture healing under T2DM conditions. Here, we discuss new approaches used in recent studies to unveil the mechanisms and fill the existing gaps in the scientific understanding of the relationship between T2DM, bone tissue, and bone fracture healing.

Keywords: bone regeneration; bone turnover; fracture healing; fracture risk; hyperglycemia; type 2 diabetes mellitus.

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Figures

Figure 1
Figure 1
Schematic representation of the selection procedure for the articles included.
Figure 2
Figure 2
(A) 3D representation generated after micro-computed tomography (microCT) scanning of the subcritical femoral defect model in control vs type 2 diabetes mellitus (T2DM) rats, 12 weeks post-surgery. (B) microCT-based quantification of the bone defect filling in control and T2DM femora, 12 weeks post-surgery. n = 7–10. ap < 0.01. Figure taken and adapted from Ref. (10).
Figure 3
Figure 3
Assessment of adipocyte presence in the fracture callus of control and type 2 diabetes mellitus (T2DM) mice tibiae through immunological staining for peripilin. Right panels show a magnified area of the sections, where stained adipocytes (red arrows) can be appreciated more clearly. Timepoint post-fracture surgery: 21 days. Black scale bar in left panel = 1 mm. Black scale bar in right panel = 100 µm. Figure taken and adapted from Ref. (5).
Figure 4
Figure 4
(A) Fluorescence immunohistochemistry staining for PECAM-1, to detect the presence of blood vessels and endothelial cells in control vs type 2 diabetes mellitus (T2DM) mice tibiae, 3 days post-surgery. (B) Magnification of the areas in (A) represented by white squares. White arrows signal blood vessels and endothelial cells, stained in red. White scale bar in (A): 200 µm. White scale bar in (B): 45 µm. Figure taken and adapted from Ref. (15).
Figure 5
Figure 5
Schematic representation of both the bone tissue state and the different factors involved in the impairment of the fracture healing process, under type 2 diabetes conditions. T2DM, type 2 diabetes mellitus; AGEs, advanced glycation end products; TZDs, thiazolidinediones; Scl, sclerostin; CTX, terminal cross-linked telopeptide of type-I collagen; OC, osteocalcin; TNF-α, tumoral necrosis factor alpha.
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