Atopic Dermatitis and Bone Fragility: Osteoimmunological Pathways, Therapeutic Paradoxes, and Risk-Adapted Screening Across the Lifespan

Atopic dermatitis (AD) has been linked to osteoporosis and fractures, but the strength, mechanisms, treatment implications, and clinical significance of this relationship remain uncertain. This review critically assesses epidemiological and osteoimmunological evidence connecting AD with skeletal fragility and proposes a lifespan-based, risk-adapted screening framework. A recent cohort-based meta-analysis found associations between AD and osteoporosis (odds ratio [OR], 1.56) and any fracture (OR, 1.08), although heterogeneity was substantial. Risk appeared higher with severe or long-standing disease and reflected interactions among inflammatory, therapeutic, nutritional, behavioral, and age-related factors. Systemic glucocorticoids were the clearest modifiable treatment-related risk, but did not fully account for the association. The RANK–RANKL–osteoprotegerin system and IL-4, IL-13, IL-31, and IL-33 offer biological plausibility, although their skeletal effects are context-dependent and supported primarily by indirect or preclinical evidence. Available data do not show that dupilumab causes osteoporosis. Emerging pediatric findings suggest improvements in growth and bone-related biomarkers, but provide no evidence of fracture prevention. AD alone does not warrant universal DXA screening. Assessment should be individualized based on age, history of fragility fractures, disease severity and duration, cumulative systemic glucocorticoid exposure, nutritional status, physical activity, muscle function, and falls. Prospective studies combining standardized AD phenotyping with longitudinal imaging, biomarkers, and adjudicated fractures are needed.