Endocrine Abstracts

Introduction: T1DM is a risk factor for reduced bone mass, disrupting several bone metabolic pathways. Dickkopf-1 is an inhibitor of the Wnt/b-catenin bone metabolic pathway. Increased fracture risk and elevated Dickkopf-1 levels have been documented in adult patients with T2DM. No relevant data exist on childhood T1DM. Our aim was to study plasma Dickkopf-1 concentration in children and adolescents with T1DM and controls and to correlate Dickkopf-1 levels with metabolic bone markers and bone mineral density (BMD).

Methods: Forty children and adolescents with T1DM were evaluated (mean±S.D. age: 13.04±3.53 years, T1DM duration: 5.15±3.33 years), along with 40 healthy matched controls (mean±S.D. age 12.99±3.3 years). Dickkopf-1, Sclerostin, osteocalcin, C-telopeptide crosslinks-CTX, electrolytes, PTH, total 25(OH) D were measured, while lumbar spine and total body BMD were evaluated.

Results: BMD was significantly lower in T1DM patients than controls. Dickkopf-1 levels demonstrated a Gaussian distribution, with higher levels in T1DM patients (13.56±5.34 vs 11.35±3.76 pmol/l, P=0.0194). A trend for lower values was found in girls (13.36±4.04 vs 11.72±5.14 pmol/l, P=0.06) and in pubertal children (13.61±4.87 vs 11.83±4.56 pmol/l, P=0.054). Dickkopf-1 correlated with Sclerostin and L1-L4 BMD z-score only in controls and with Osteoprotegerin and i-Phosphorus only in patients, while in both groups a significant correlation with log(CTX) and √ALP was documented. A significant correlation of Dickkopf-1 with IGF-1 and insulin dose was also shown in patients.

Conclusion: T1DM children and adolescents had higher levels of Dickkopf-1 than controls, indicating a downregulated Wnt signalling system and possible lower osteoblast activation that could be associated with T1DM osteopathy.