OPG/RANK/RANKL signaling axis in patients with type I diabetes: Associations with parathormone and vitamin D

Paraskevi Karalazou,Maria Taousani,Dimitrios Ntelios,Konstantina Mouzaki,Fani Chatzopoulou,Georgios Tzimagiorgis,Aikaterini Fragou,Assimina Galli-Tsinopoulou,Sofia Kouidou

doi:10.1186/s13052-019-0748-1

Abstract

BackgroundType 1 diabetes (T1D) has been associated with a higher fracture risk due to alterations in bone structure and metabolism. On the other hand, the important role of the RANKL/OPG/RANK signaling axis in bone physiology is well established. The aim of this study was to evaluate the levels of receptor activator of nuclear factor kappa-B ligand (RANKL), receptor activator of nuclear factor kappa-B (RANK) and plasma osteoprotegerin (OPG) levels, in T1D youngsters and to investigate factors that could influence the OPG/RANK/RANKL signaling axis such as 25-hydroxy vitamin D [25(OH) D], parathormone (PTH) and age.MethodsSerum RANKL, RANK, 25(OH) D, PTH levels and plasma OPG levels, were measured in 71 youngsters with T1D and 50 healthy controls matched for age and gender.ResultsPlasma OPG levels were significantly lower (p = 0.025) in T1D patients compared to controls. Serum RANKL levels were significantly higher (p = 0.037), while no differences were observed in serum RANK levels (p = 0.946) between the two groups. Serum 25(OH) D levels found significantly decreased (p < 0.001) while serum PTH levels were significantly elevated (p < 0.001) in T1D patients than in controls.ConclusionsOur results demonstrated that OPG and RANKL may be promising biomarkers for T1D patients. However, their circulating levels were associated with several factors including PTH, 25(OH) D and therefore, may represent an integrative biomarker for a variety of endocrine signaling disturbances observed in T1D.

Highlights

Type 1 diabetes (T1D) has been associated with a higher fracture risk due to alterations in bone structure and metabolism
Circulating levels of OPG, receptor activator of nuclear factor kappa-B ligand (RANKL), receptor activator of nuclear factor kappa-B (RANK) in patients with Τ1D compared to controls OPG plasma levels were significantly lower in patients with T1D than controls (p = 0.025) (Fig. 1a)
Serum RANKL were significantly higher in the patients group (p = 0.037) (Fig. 1b)

Summary

Introduction

Type 1 diabetes (T1D) has been associated with a higher fracture risk due to alterations in bone structure and metabolism. There is evidence for poor bone mineralization, abnormal glycosylation and cross-linking of skeletal collagen [5,6,7] This reduced bone strength and quality can lead to fractures at any site, predominantly at femoral neck [7, 8]. There is a great need to improve our understanding of the mechanisms behind the development of bone complications in diabetic patients and to develop new biomarkers that better stratify high-risk patient groups in a preclinical stage. To this extent, the study of OPG/ RANKL/RANK signaling axis in diabetes has been proposed as a promising new research direction. Karalazou et al Italian Journal of Pediatrics (2019) 45:161

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