ESPE Abstracts (2014) 82 P-D-1-3-55

Increased Osteoclast Activity in Children and Adolescents with Type 1 Diabetes Mellitus Indicated by Higher Levels of Osteoprotegerin and s-RANKL may Predispose to Lower Bone Mass

Charalampos Tsentidisa, Dimitrios Gourgiotisb, Lydia Kossivaa, Artemis Doulgerakic, Antonios Marmarinosb, Triantafillia Sdogoua & Kyriaki Karavanakia

aDiabetic Clinic, Second Pediatric Department, University of Athens, ‘P&A Kyriakou’ Children’s Hospital, Athens, Attica, Greece; bBiochemistry Laboratory, Second Pediatric Department, University of Athens, ‘P&A Kyriakou’ Children’s Hospital, Athens, Attica, Greece; cDepartment of Bone and Mineral Metabolism, Institute of Child Health, ‘Aghia Sophia’ Children’s Hospital, Athens, Attica, Greece

Background: Several bone metabolic pathways seem to be disrupted in patients with type 1 diabetes mellitus (T1DM), leading to reduced bone mass.

Objective and hypotheses: Our aim was to study bone metabolism markers in children and adolescents with T1DM and their correlation with bone mineral density (BMD).

Method: We evaluated 40 patients (mean±S.D. age 13.04±3.53 years, mean±S.D. T1DM duration 5.15±3.33 years) and 40 healthy age- and gender-matched controls (mean±S.D. age 12.99±3.3 years). Osteoprotegerin (OPG), receptor activator of nuclear factor-KappaB ligand (s-RANKL), osteocalcin, C-telopeptide crosslinks-CTX, electrolytes, PTH, total 25(OH)D were measured. Total body (TB) and lumbar spine (LS) BMD were evaluated with dual energy X-ray absorptiometry (DXA).

Results: Patients had significantly higher levels of OPG than controls (6.15±1.56 vs 5.01±1.5 pmol/l, P<0.001) and s-RANKL (logS-RANKL 5.97±0.63 vs 5.51±0.84, P=0.004). Patients also had lower levels of PTH (logPTH 3.25±0.52 vs 3.43±0.33, P=0.036) and magnesium (1.88±0.12 vs 2.03±0.12 mg/dl, P<0.001) and higher ALP levels (√ALP 14.07±4.13 vs 12.6±3.24, P=0.05). Patients and controls had comparable 25(OH)vitD levels, while one third of both groups had low 25(OH)vitD levels (<20 ng/ml). Osteocalcin was highly correlated with CTX in both groups (r=0.75, P<0.001), indicating coupling of bone resorption and formation. OPG and s-RANKL were significantly associated in controls (R2=0.15, P=0.021), but not in patients (R2=0.006, P=0.64), possibly indicating an osteoclastic disorder. Bone formation was not significantly affected. Although BMD was not significantly different between patients and controls, it had greater variance in patients. Longer T1DM duration was associated with lower BMD Z-scores (TB-BMD r=−0.41, P=0.009, LS-BMD r=−0.34, P=0.043).

Conclusion: RANKL/OPG axis seems to be significantly activated in children and adolescents with T1DM. These changes could indicate abnormal osteoclast function and could be associated with the lower bone mass, found in patients with longer disease duration.