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

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Background/Objectives: Atopic dermatitis (AD) has been associated with osteoporosis and fractures, but the magnitude, mechanisms, therapeutic implications, and clinical relevance of this relationship remain uncertain. This review critically evaluates the epidemiological and osteoimmunological evidence linking AD to skeletal fragility and proposes a lifespan-based, risk-adapted screening framework. Methods: A structured search of PubMed/MEDLINE and supplementary sources identified peer-reviewed publications from January 2020 through July 2026. Seventy-five studies, reviews, meta-analyses, guidelines, and consensus documents addressing AD, bone mineral density (BMD), osteoporosis, fractures, immune–bone pathways, treatment exposure, and skeletal assessment were included in a critical narrative synthesis. Results: A recent cohort-based meta-analysis associated AD with osteoporosis (odds ratio [OR], 1.56) and any fracture (OR, 1.08), although heterogeneity was substantial. Risk appeared greater in severe or long-standing disease and reflected the interaction among inflammatory, therapeutic, nutritional, behavioral, and age-related determinants. Systemic glucocorticoids constituted the clearest modifiable treatment-related risk, but did not fully explain the association. The RANK–RANKL–osteoprotegerin system and IL-4, IL-13, IL-31, and IL-33 provide biological plausibility, although their skeletal effects are context-dependent and predominantly supported by indirect or preclinical evidence. Available data do not demonstrate that dupilumab causes osteoporosis; emerging pediatric findings suggest improvements in growth and bone-related biomarkers, but do not demonstrate fracture prevention. Conclusions: AD alone does not justify universal DXA screening. Assessment should be individualized according to age, fragility-fracture history, 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 required.

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