Bone Geometry, Quality, and Bone Markers in Children with Type 1 Diabetes Mellitus
- 253 Downloads
Adults with Type 1 diabetes mellitus show a high risk of bone fracture, probably as a consequence of a decreased bone mass and microarchitectural bone alterations. The aim of the study was to investigate the potential negative effects of type 1 diabetes on bone geometry, quality, and bone markers in a group of children and adolescents. 96 children, mean age 10.5 ± 3.1 years, agreed to participate to the study. Bone geometry was evaluated on digitalized X-rays at the level of the 2nd metacarpal bone. The following parameters were investigated and expressed as SDS: outer diameter (D), inner diameter (d), cortical area (CA), and medullary area (MA). Bone strength was evaluated as Bending Breaking Resistance Index (BBRI) from the geometric data. Bone turnover markers (PINP, CTX-I, and BAP), sclerostin, Dkk-1, PTH, and 25OH-Vitamin D were also assessed. A group of healthy 40 subjects of normal body weight and height served as controls for the bone markers. D (− 0.99 ± 0.98), d (− 0.41 ± 0.88), CA (− 0.85 ± 0.78), and MA (− 0.46 ± 0.78) were all significantly smaller than in controls (p < 0.01). BBRI was significantly lower (− 2.61 ± 2.18; p < 0.0001). PTH, PINP, and BAP were higher in the diabetic children. Multiple regression analysis showed that CA and D were influenced by insulin/Kg/day and by BMI, while d was influenced by PINP only. Type 1 diabetic children show smaller and weaker bones. The increased bone turnover could play a key role since it might amplify the deficit in bone strength associated with the inadequate osteoblastic activity caused by the disease itself.
KeywordsBone geometry Bone quality Bone markers Children Sclerostin Dkk-1
The authors would like to thank Caterina Fraccarollo for ELISA assays and the LURM (Laboratorio Universitario di Ricerca Medica) Research Centre of University of Verona, where this study was partially performed.
Compliance with Ethical Standards
Conflict of interest
(Roberto Franceschi, Silvia Longhi, Vittoria Cauvin, Angelo Fassio, Giuseppe Gallo, Fiorenzo Lupi, Petra Reinstadler, Antonio Fanolla, Davide Gatti, and Giorgio Radetti) have no financial conflicts of interest. The authors have full control of all primary data and they agree to allow the journal to review their data if requested.
Human and Animal Rights and Informed Consent
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.
- 14.Fowlkes JL, Bunn RC, Thrailkill KM (2011) Contributions of the insulin/insulin-like growth factor-1 axis to diabetic osteopathy. J Diabetes Metab 25:S1-S3Google Scholar
- 17.Neumann T, Lodes S, Kästner B, Franke S, Kiehntopf M, Lehmann T, Müller UA, Wolf G, Sämann A (2014) High serum pentosidine but not esRAGE is associated with prevalent fractures in type 1 diabetes independent of bone mineral density and glycaemic control. Osteoporos Int 25:1527–1533CrossRefPubMedGoogle Scholar
- 18.Baroncelli GI, Federico G, Bertelloni S, Sodini F, De Terlizzi F, Cadossi R, Saggese G (2003) Assessment of bone quality by quantitative ultrasound of proximal phalanges of the hand and fracture rate in children and adolescents with bone and mineral disorders. Pediatr Res 54:125–136CrossRefPubMedGoogle Scholar
- 26.Gennari L, Merlotti D, Valenti R, Ceccarelli E, Ruvio M, Pietrini MG, Capodarca C, Franci MB, Campagna MS, Calabrò A, Cataldo D, Stolakis K, Dotta F, Nuti R (2012) Circulating sclerostin levels and bone turnover in type 1 and type 2 diabetes. J Clin Endocrinol Metab 97:1737–1744CrossRefPubMedGoogle Scholar
- 27.Tsentidis C, Gourgiotis D, Kossiva L, Marmarinos A, Doulgeraki A, Karavanaki K (2017) 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. Osteoporos Int 28:945–953CrossRefPubMedGoogle Scholar
- 29.McCarthy HD, Jarrett KV, Crawley HF (2001) The development of waist circumference percentiles in British children aged 5.0–16.9 y. 55:902–907Google Scholar
- 30.Tanner JM (1962) Growth at adolescence, 2nd edn. Blackwell, OxfordGoogle Scholar
- 31.Greulich WW, Pyle SI (1959) Radiographic atlas of skeletal development of the hand and wrist, 2nd edn. Stanford University Press, StanfordGoogle Scholar
- 43.Fassio A, Rossini M, Viapiana O, Idolazzi L, Benini C, Vantaggiato E, Gatti D (2017) New strategies for the prevention and treatment of systemic and local bone loss; from pathophysiology to clinical application. Curr Pharm Des. https://doi.org/10.2174/1381612823666170713104431 PubMedCrossRefGoogle Scholar