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

Ital J Pediatr. 2019 Dec 10;45(1):161. doi: 10.1186/s13052-019-0748-1.

Abstract

Background: Type 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.

Methods: Serum 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.

Results: Plasma 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.

Conclusions: Our 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.

Keywords: Osteoprotegerin; Receptor activator of nuclear factor kappa-B; Receptor activator of nuclear factor kappa-B ligand; Type 1 diabetes mellitus.

MeSH terms

  • Adolescent
  • Biomarkers / blood
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / diagnosis
  • Disease Progression
  • Female
  • Humans
  • Male
  • Osteoprotegerin / blood*
  • Parathyroid Hormone / blood*
  • Prognosis
  • RANK Ligand / blood*
  • Receptor Activator of Nuclear Factor-kappa B / blood*
  • Reference Values
  • Vitamin D / blood*

Substances

  • Biomarkers
  • Osteoprotegerin
  • Parathyroid Hormone
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • TNFRSF11A protein, human
  • TNFRSF11B protein, human
  • TNFSF11 protein, human
  • Vitamin D