Bone turnover markers during the remission phase in children and adolescents with type 1 diabetes.

BACKGROUND AND AIM: In rodents, osteocalcin (OCN) stimulates insulin production and insulin sensitivity, both important factors during partial remission in humans with type 1 diabetes (T1D). However, decreased OCN has been reported in both adult and pediatric T1D. This study aims at investigating bone turnover and partial remission in children and adolescents with recent onset T1D. SUBJECTS AND METHODS: Ninety-nine individuals (33% girls) were recruited within 3 months of T1D onset and examined three times, 6 months apart. Outcome variables were bone formation markers OCN and procollagen type 1 amino-terminal propeptide (P1NP) and the bone resorption marker C-terminal crosslinked telopeptide of type 1 collagen (CTX). Dependent variables included IDAA1c (surrogate marker of partial remission), total body bone mineral density (BMD) and stimulated C-peptide as representative of endogenous insulin production. RESULTS: OCN- and P1NP Z-scores were significantly decreased throughout the study, whereas CTX Z-scores were increased. None of the bone turnover markers changed significantly between visits. Total body BMD Z-score did not change during the study but was significantly higher than the reference population at visit 2 (P = .035). There were no differences in the bone turnover markers for those in partial remission as defined by either C-peptide or IDAA1c at any visit. The individual change in CTX Z-score was negatively associated with the increase of IDAA1c (P = .030) independent of C-peptide decline (P = .034). CONCLUSION: Bone turnover markers indicate increased bone resorption and decreased bone formation during the first year of T1D. The negative association between bone resorption and IDAA1c might represent compensatory mechanisms affecting insulin sensitivity.

Bone turnover markers in children and adolescents with type 1 diabetes-A systematic review.

Type 1 diabetes (T1D) is associated with impaired bone health and both osteocalcin (OCN) and procollagen type 1 amino terminal propetide (P1NP) (markers of bone formation) and C-terminal cross-linked telopeptide (CTX) (marker of bone resorption) are decreased in adult patients with T1D. We review the existing literature characterizing these bone turnover markers in children and adolescents with T1D and by meta-analysis examine whether alterations in OCN, P1NP, and CTX are evident and if potential changes correlate to the metabolic control (hemoglobin A1c, HbA1c). Systematic searches at MEDLINE and EMBASE were conducted in January 2018 identifying all studies describing OCN, P1NP, or CTX in children and adolescents with T1D. A total of 26 studies were included, representing data from more than 1000 patients with T1D. Pooled analyses of standard mean difference and summary effects analysis were performed when sufficient data were available. Pooled analysis revealed mean OCN to be significantly lower in children and adolescents with T1D compared to healthy controls (standard mean difference: -1.87, 95% confidence interval, CI: -2.83; -0.91) whereas both P1NP and CTX did not differ from the controls. Only data on OCN was sufficient to make pooled correlation analysis revealing a negative correlation between OCN and HbA1c (-0.31 95% CI: -0.45; -0.16). In conclusion, OCN is decreased in children and adolescents with T1D, whether CTX and P1NP are affected as well is unclear, due to very limited data available. New and large studies including OCN, P1NP, and CTX (preferably as z-scores adjusting for age variability) is needed to further elucidate the status of bone turnover in children and adolescents with T1D.