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Osteoporosis International

, Volume 28, Issue 3, pp 945–953 | Cite as

Increased levels of Dickkopf-1 are indicative of Wnt/β-catenin downregulation and lower osteoblast signaling in children and adolescents with type 1 diabetes mellitus, contributing to lower bone mineral density

  • C. Tsentidis
  • D. Gourgiotis
  • L. Kossiva
  • A. Marmarinos
  • A. Doulgeraki
  • K. Karavanaki
Original Article

Abstract

Summary

Higher levels of Dickkopf-1, which is an inhibitor of Wnt/β-catenin bone metabolic pathway, could be indicative of downregulated Wnt system, with possible lower osteoblast activation and higher osteoclast signaling in type 1 diabetes mellitus children and adolescents. Dickkopf-1 could significantly contribute to diabetes osteopathy.

Introduction

Increased fracture risk and elevated Dickkopf-1 levels, which is an inhibitor of Wnt/β-catenin bone metabolic pathway, have been documented in adult patients with type 2 diabetes mellitus (T2D), while no relevant data exist on childhood type 1 diabetes (T1D). Our aim was to study plasma Dickkopf-1 distribution in children and adolescents with T1D and to correlate Dickkopf-1 with metabolic bone markers and bone mineral density (BMD).

Methods

We evaluated 40 children and adolescents with T1D (mean ± SD age 13.04 ± 3.53 years, T1D duration 5.15 ± 3.33 years) and 40 healthy age-matched and gender-matched controls (age 12.99 ± 3.3 years). Dickkopf-1 and bone metabolic markers were measured, while total body and lumbar spine BMD were evaluated with dual-energy X-ray absorptiometry (DXA).

Results

Dickkopf-1 demonstrated a Gaussian distribution, with higher levels in T1D patients (13.56 ± 5.34 vs 11.35 ± 3.76 pmol/L, p = 0.024). Higher values were found in boys and in prepubertal children. Dickkopf-1 correlated positively with osteoprotegerin and fasting glucose in patients, while positive correlation with sclerostin and total soluble receptor activator of nuclear factor-kappaB ligand (s-RANKL) was found in controls. Positive correlations with C-telopeptide cross-links (CTX), osteocalcin, alkaline phosphatase, phosphate, and insulin-like growth factor 1 (IGF1) were documented in both groups. Lumbar spine Z-score was positively associated with Dickkopf-1 in controls, while a negative trend was found in patients.

Conclusions

Higher levels of Dickkopf-1 could indicate a downregulated Wnt/β-catenin system with possible lower osteoblast activation and higher osteoclast signaling in T1D children and adolescents. Dickkopf-1 could possibly be a significant contributor of T1D osteopathy. Future therapies could focus on Wnt/β-catenin metabolic pathway.

Keywords

Adolescents Bone metabolism Children Dickkopf-1 Osteoporosis Type 1 diabetes 

Notes

Compliance with ethical standards

Conflicts of interest

None.

Funding

This research did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.

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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2016

Authors and Affiliations

  1. 1.Diabetes Clinic, 2nd Department of PediatricsAthens University Medical School, “P&A Kyriakou” Children’s HospitalAthensGreece
  2. 2.Laboratory of Clinical Biochemistry-Molecular Diagnostics, 2nd Department of PediatricsAthens University Medical School, “P & A Kyriakou” Children’s HospitalAthensGreece
  3. 3.Department of Bone and Mineral MetabolismInstitute of Child Health, “Aghia Sophia” Children’s HospitalAthensGreece

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