Sex- and pubertal stage–specific bone microarchitecture and strength in adolescents with type 1 diabetes

CONTEXT: Adults with type 1 diabetes (T1D) have elevated fracture risk, but the effects of T1D on bone accrual during adolescence remain unclear. OBJECTIVE: To assess group differences in bone microarchitecture and strength between adolescents with type 1 diabetes and controls during sex-specific stages of pubertal bone accrual. DESIGN: Cross-sectional. SETTING: Tertiary medical center. PARTICIPANTS: Forty youth with T1D and 40 matched controls; early pubertal girls (Tanner 2-3) and mid-pubertal boys (Tanner 3-4). MAIN OUTCOME MEASURES: Assessments included dual-energy X-ray absorptiometry, high-resolution peripheral quantitative computed tomography (HR-pQCT) with individual trabecula segmentation, and micro-finite element analysis, as well as HbA1c, continuous glucose monitoring (CGM), advanced glycation end-products (AGEs: skin autofluorescence [SAF], pentosidine), IGF-1, and bone turnover markers. RESULTS: Compared with control boys, boys with T1D had lower trabecular bone volume fraction (-14%; p=0.033), plate-like trabeculae (-23%; p=0.007), and failure load (-12%; p=0.008) at the distal tibia, and lower cortical area (-8%; p=0.026) at the proximal tibia, with similar deficits at the radius. In contrast, compared with control girls, girls with T1D in early puberty showed no deficits. In boys, higher HbA1c was linked to fewer plate-like trabeculae (β = -0.31, p=0.038) and reduced strength, while lower IGF-1 predicted decreased trabecular volume and strength. Across the T1D cohort, CGM hyperglycemia and higher SAF correlated with suppressed bone turnover. CONCLUSIONS: T1D exerts sex- and pubertal stage-specific skeletal effects. Mid-pubertal boys show trabecular and cortical deficits with reduced strength, whereas early-pubertal girls show no deficits. Mid-puberty in boys represents a critical window for skeletal vulnerability and potential intervention.