ESPE Abstracts (2018) 89 RFC11.5

The Determinants of Skeletal Fragility in Children with Type 1 Diabetes Mellitus

Suet Ching Chena,b, Sheila Shepherda, Martin McMillana, Jane McNeillyc, Christie McCombd, John Fosterd, Kenneth J Robertsonb, Sze Choong Wonga & S Faisal Ahmeda

aDevelopmental Endocrinology Research Group, School of Medicine, University of Glasgow, Royal Hospital for Children, Glasgow, UK; bPaediatric Diabetes Service, NHS Greater Glasgow & Clyde, Glasgow, UK; cDepartment of Clinical Biochemistry, Royal Hospital for Children, NHS Greater Glasgow and Clyde, Glasgow, UK; dDepartment of Clinical Physics and Bioengineering, NHS Greater Glasgow & Clyde and University of Glasgow, Glasgow, UK

Background: The pathophysiology of the increased fracture risk in Type 1 Diabetes Mellitus (T1DM) remains unclear.

Objectives: Perform multimodality assessment to determine the effects of T1DM on bone health and fractures.

Methods: Thirty-two children with T1DM at a median (range) age of 13.7 years (10.4, 16.7), and median HbA1c 65mmol/mol (27,100) were recruited. Serum bone alkaline phosphatase (BAP) and c-terminal telopeptide type 1 collagen (CTX) as well as DXA total body (TB) and lumbar spine (LS) bone mineral content (BMC) adjusted for bone area were converted to SDS. 3T MRI of the proximal tibia was performed to assess bone microarchitecture, by measuring bone volume/total volume (appBV/TV), trabecular number (appTbN), trabecular separation (appTbSp) and trabecular thickness (appTbTh). MR spectroscopy at lumbar spine was performed to assess bone marrow adiposity, by measuring marrow fat fraction (%). MRI data were compared to 26 age- and sex-matched healthy controls, with median age of 13.8 (10.2, 17.8).

Results: Fractures were encountered in 10/32 cases after diagnosis of T1DM and 5/26 controls. In T1DM, median BAP SDS and CTX SDS were −0.6 (−2.5,+2.1) and −1.1 (−2.5,+0.5), respectively whilst median TB and LS BMC SDS were −0.1 (−1.1,+0.9) and −0.3 (−1.0,+1.8), respectively. Children with T1DM had lower appBV/TV with a median of 0.55 (0.47, 0.63) (vs controls 0.59 (0.47, 0.63); P=0.024), lower appTbN 1.67 (1.56, 1.93) (vs controls 1.82 (1.56, 1.99); P=0.004), and higher appTbSp 0.27 (0.21, 0.32) (vs controls 0.24 (0.2, 0.33); P=0.001). The median bone marrow fat fraction in cases and controls were 23% (11, 66) and 20% (8, 61), respectively (P=0.25). Median BAP SDS was lower in poorly controlled T1DM (HbA1c>75 mmol/mol) at −0.79 (−2.5,−0.54) compared to 0.5 (−0.64,+2.10) in those with good glycaemic control HbA1c<58 mmol/mol) (P=0.009). Serum CTX was inversely related to the age at diagnosis (r, −0.4, P=0.012). The median HbA1c of T1DM with fracture was 72 mmol/mol (49,100) compared to 62 mmol/mol (27,87) in those without fracture (P=0.007). Median TB BMC SDS of T1DM with fracture was −0.5 (−1.1, 0.0) compared to 0.0 (−0.5,+0.9) in the non-fracture group (P<0.0001). There was no significant difference in bone microarchitecture findings between the fracture and non-fracture group.

Conclusion: Children with T1D display a low bone turnover state associated with reduced bone mineralisation and poorer bone microarchitecture. Fractures were more likely in those with poorer glycaemic control and bone mineral status.

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