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Pathophysiology/Complications
Lower estimated bone strength and impaired bone microarchitecture in children with type 1 diabetes
  1. Gitte Fuusager1,2,3,4,
  2. Nikolaj Milandt1,5,
  3. Vikram Vinod Shanbhogue6,
  4. Anne Pernille Hermann6,
  5. Anders Jørgen Schou1,4,7,
  6. Henrik Thybo Christesen1,4
  1. 1Clinical Research, Syddansk Universitet, Odense, Syddanmark, Denmark
  2. 2Department of Internal Medicine, Hospitalsenheden Vest, Herning, Denmark
  3. 3OPEN - Odense Patient data Explorative Network, Odense Universitets Hospital, Odense, Denmark
  4. 4Hans Christian Andersen Children’s Hospital, Odense Universitetshospital, Odense, Denmark
  5. 5The Orthopedic Research Unit, Odense University Hospital, Odense, Denmark
  6. 6Department of Endocrinology, Odense Universitetshospital, Odense, Denmark
  7. 7Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark
  1. Correspondence to Dr Gitte Fuusager; gitte.bjerg.fuusager2{at}rsyd.dk

Abstract

Introduction Patients with type 1 diabetes has an increased risk of fracture. We wished to evaluate estimated bone strength in children and adolescents with type 1 diabetes and assess peripheral bone geometry, volumetric bone mineral density (vBMD) and microarchitecture.

Research design and methods In a cross-sectional study, high-resolution peripheral quantitative CT (HR-pQCT) was performed of the radius and tibia in 84 children with type 1 diabetes and 55 healthy sibling controls. Estimated bone strength was assessed using a microfinite element analysis solver. Multivariate regression analyses were performed adjusting for age, sex, height and body mass index.

Results The median age was 13.0 years in the diabetes group vs 11.5 years in healthy sibling controls. The median (range) diabetes duration was 4.2 (0.4−15.9) years; median (range) latest year Hb1Ac was 7.8 (5.9−11.8) % (61.8 (41−106) mmol/mol). In adjusted analyses, patients with type 1 diabetes had reduced estimated bone strength in both radius, β −390.6 (−621.2 to −159.9) N, p=0.001, and tibia, β −891.9 (−1321 to −462.9) N, p<0.001. In the radius and tibia, children with type 1 diabetes had reduced cortical area, trabecular vBMD, trabecular number and trabecular bone volume fraction and increased trabecular inhomogeneity, adjusted p<0.05 for all. Latest year HbA1c was negatively correlated with bone microarchitecture (radius and tibia), trabecular vBMD and estimated bone strength (tibia).

Conclusion Children with type 1 diabetes had reduced estimated bone strength. This reduced bone strength could partly be explained by reduced trabecular bone mineral density, adverse microarchitecture and reduced cortical area. We also found increasing latest year HbA1c to be associated with several adverse changes in bone parameters. HR-pQCT holds potential to identify early adverse bone changes and to explain the increased fracture risk in young patients with type 1 diabetes.

  • diabetes mellitus, type 1
  • diabetes complications
  • bone and bones
  • bone density
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjdrc-2020-001384

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    Footnotes

    • AJS and HTC contributed equally.

    • Contributors GF contributed to the study protocol, recruited the patients and control siblings, collected the hospital file data, performed the HR-pQCT scans and statistical analyses and wrote the manuscript. NM contributed to data management, statistical analysis and revised the manuscript. VVS and APH contributed to the study protocol, performed and supervised the HR-pQCT scans and approved the manuscript. AJS and HTC initiated and supervised the study and revised the manuscript. AJS and HTC are joint last authors.

    • Funding This study was supported financially by The Consultant’s Research Fund at Odense University Hospital (ID: A1869).

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethics approval Oral and written consents from parents of children younger than 15 years and adolescents older than 15 were acquired before the physical examination and scans were performed. HR-pQCT is associated with a maximum radiation dose of 0.015 mSv. The risk of this radiation dose is considered insignificant according the guidelines from the International Commission on Radiation Protection (ICRP). The study was approved by the Regional Ethical Committee of Southern Denmark (Project-ID: S-20160159) and the Data Protection Agency (Journal nr:18/44863).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data are available on reasonable request. The data generated and analyzed during the current study are available in Odense Patient Data Explorative Network (OPEN), project number 495, https://open.rsyd.dk/OpenProjects/openProject.jsp?openNo=495&lang=da.