Bone deficits in children and youth with type 1 diabetes: A systematic review and meta-analysis

Deficits in bone mineral and weaker bone structure in children with type 1 diabetes (T1D) may contribute to a lifelong risk of fracture. However, there is no meta-analysis comparing bone properties beyond density between children with T1D and typically developing children (TDC). This meta-analysis aimed to assess differences and related factors in bone mineral content (BMC), density, area, micro-architecture and estimated strength between children with T1D and TDC. We systematically searched MEDLINE, Embase, CINAHL, Web of Science, Scopus, Cochrane Library databases, and included 36 in the meta-analysis (2222 children and youth with T1D, 2316 TDC; mean age <= 18 yrs., range 1-24). We estimated standardized mean differences (SMD) using random-effects models and explored the role of age, body size, sex ratio, disease duration, hemoglobin A1c in relation to BMC and areal density (aBMD) SMD using meta-regressions. Children and youth with T1D had lower total body BMC (SMD: -0.21, 95% CI: -0.37 to -0.05), aBMD (-0.30, -0.50 to -0.11); lumbar spine BMC (-0.17, -0.28 to -0.06), aBMD (-0.20, -0.32 to -0.08), bone mineral apparent density (-0.30, -0.48 to -0.13); femoral neck aBMD (-0.21, -0.33 to -0.09); distal radius and tibia trabecular density (-0.38, -0.64 to -0.12 and -0.35, -0.51 to -0.18, respectively) and bone volume fraction (-0.33, -0.56 to -0.09 and -0.37, -0.60 to -0.14, respectively); distal tibia trabecular thickness (-0.41, -0.67 to -0.16); and tibia shaft cortical content (-0.33, -0.56 to -0.10). Advanced age was associated with larger SMD in total body BMC (-0.13, -0.21 to -0.04) and aBMD (-0.09; -0.17 to -0.01) and longer disease duration with larger SMD in total body aBMD (-0.14; -0.24 to -0.04). Children and youth with T1D have lower BMC, aBMD and deficits in trabecular density and microarchitecture. Deficits in BMC and aBMD appeared to increase with age and disease duration. Bone deficits may contribute to fracture risk and require attention in diabetes research and care.