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. PROSPERO (CRD42020200819). • First meta-analysis of BMC and micro-architectural deficits in children with T1D • Meta-regressions indicated greater deficits in total body BMC and aBMD with age. • Deficits in trabecular bone thickness and density were pronounced in T1D. • Prospective, advanced imaging data of bone development in children with T1D needed