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Osteoporosis International

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01-03-2017 | Original Article

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

Authors: C. Tsentidis, D. Gourgiotis, L. Kossiva, A. Marmarinos, A. Doulgeraki, K. Karavanaki

Published in: Osteoporosis International | Issue 3/2017

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.

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Title: 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
Authors: C. Tsentidis
D. Gourgiotis
L. Kossiva
A. Marmarinos
A. Doulgeraki
K. Karavanaki
Publication date: 01-03-2017
Publisher: Springer London
Published in: Osteoporosis International / Issue 3/2017
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-016-3802-5

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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

Abstract

Summary

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusions

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