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Review
. 2021 Jul 15;12(7):997-1009.
doi: 10.4239/wjd.v12.i7.997.

Mechanisms of altered bone remodeling in children with type 1 diabetes

Giacomina Brunetti  1 , Gabriele D'Amato  2 , Stefania De Santis  3 , Maria Grano  4 , Maria Felicia Faienza  5
Affiliations
Review

Mechanisms of altered bone remodeling in children with type 1 diabetes

Giacomina Brunetti et al. World J Diabetes. .

Abstract

Bone loss associated with type 1 diabetes mellitus (T1DM) begins at the onset of the disease, already in childhood, determining a lower bone mass peak and hence a greater risk of osteoporosis and fractures later in life. The mechanisms underlying diabetic bone fragility are not yet completely understood. Hyperglycemia and insulin deficiency can affect the bone cells functions, as well as the bone marrow fat, thus impairing the bone strength, geometry, and microarchitecture. Several factors, like insulin and growth hormone/insulin-like growth factor 1, can control bone marrow mesenchymal stem cell commitment, and the receptor activator of nuclear factor-κB ligand/osteoprotegerin and Wnt-b catenin pathways can impair bone turnover. Some myokines may have a key role in regulating metabolic control and improving bone mass in T1DM subjects. The aim of this review is to provide an overview of the current knowledge of the mechanisms underlying altered bone remodeling in children affected by T1DM.

Keywords: Bone remodeling; Children; Osteoblasts; Osteoclasts; Type 1 diabetes.

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Conflict of interest statement

Conflict-of-interest statement: No potential conflicts of interest to declare.

Figures

Figure 1
Figure 1
Mechanisms underlying altered bone remodeling in type-1-diabetes. APC: Adenomatous polyposis coli; BMP6: Bone morphogenetic protein-6; BMSCs: Bone marrow-derived mesenchymal stem cells; CK1: Casein kinase I; CTX: C-terminal cross-link of collagen; DKK-1: Dickkopf-1; DVL: Disheveled; GH: Growth hormone; GSIS: Glucose-stimulated insulin secretion; GSK3: Glycogen synthase kinase 3 beta; IR: Insulin receptor; IGF1: Insulin-like growth factor-1; IGF1R: Insulin-like growth factor-1 receptor; IGFBPs: IGF-1 binding proteins; IL-6: Interleukin-6; IL-8: Interleukin-8; LPR5/6: LDL receptor related protein 5; OCN: Osteocalcin; OPG: Osteoprotegerin; PPAR: Peroxisome proliferator-activated receptors; RANK: Receptor activator of nuclear factor-kappa B; RANKL: Receptor activator of nuclear factor-kappa B ligand; RUNX2: Related transcription factor 2; SOST: Sclerostin; TCF/LEF: T-cell factor/lymphoid enhancer factor.
See this image and copyright information in PMC

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