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 micro-architecture. 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. STUDY REGISTRATION: PROSPERO (CRD42020200819).