More than a skin condition

Atopic dermatitis is a common chronic inflammatory disease characterized by itching, recurrent eczematous manifestations, and impaired skin barrier function. Treatment typically focuses on skin symptoms and inflammation control. However, accumulating evidence suggests that this condition may also warrant attention to extracutaneous risks, including potential effects on bone health.

There are several reasons to investigate this association. Chronic inflammation may affect bone remodeling. Systemic glucocorticoid use, reduced physical activity due to itching, sleep disturbances, dietary factors, and potentially limited calcium and vitamin D intake may also be relevant.

Earlier reviews included a limited number of studies and did not allow for a sufficiently detailed assessment of the association with fractures at different anatomical sites. Therefore, the authors of the new study pooled data specifically from cohort studies to clarify the risks of osteoporosis and fractures in patients with atopic dermatitis [1].

How the study was conducted

The authors performed a systematic review and meta-analysis in accordance with PRISMA 2020 guidelines. The protocol was registered prospectively in the PROSPERO database. Searches were conducted in PubMed, Embase, and the Cochrane Library from database inception through May 30, 2025.

The analysis included prospective and retrospective cohort studies comparing patients with atopic dermatitis with individuals without this diagnosis. Eligible studies had to report data on osteoporosis, fractures at all sites, or fractures in specific anatomical regions, as well as measures of association, including odds ratios (ORs), relative risks, or 95% confidence intervals.

Of 1,525 publications initially identified, 10 cohort studies from the United Kingdom, China, Korea, the United States, and Taiwan were included after multistage screening. The studies involved both children and adults; the number of patients with atopic dermatitis ranged from 368 to more than 2 million. In studies reporting this information, follow-up duration ranged from 4 to 9 years. Most studies received 7–8 out of 9 points on the Newcastle–Ottawa Scale.

A random-effects model was used to pool the results. The authors also conducted sensitivity analyses, assessed the risk of publication bias, and separately examined fracture risk according to atopic dermatitis severity and fracture location [1].

Osteoporosis and fracture risk: key findings

The pooled analysis showed a statistically significant association between atopic dermatitis and an increased risk of osteoporosis: the combined OR was 1.56. In other words, across the included cohorts, the risk of this outcome was 56% higher in patients with atopic dermatitis than in individuals without the disease. However, this finding was accompanied by extremely high heterogeneity across studies: the I² value was 99.9%. In meta-analysis, I² reflects the proportion of variation between study results that is due to real differences rather than chance. Such a high value indicates that the effect size varied substantially across individual studies, requiring caution when generalizing the findings [1].

The risk of fractures at all sites was also higher, with an OR of 1.08, or an 8% increase. Heterogeneity was also high in this analysis, with an I² of 82.1%. Sensitivity analyses showed that excluding individual studies did not change the overall direction of the results. The authors found no statistically significant evidence of publication bias according to Egger’s test, with p=0.316 [1].

The association with disease severity is of particular interest. The OR for fractures was 1.05 in mild atopic dermatitis, 1.08 in moderate disease, and 1.26 in severe disease. Among patients with moderate-to-severe disease, the OR reached 1.23. This pattern suggests that greater disease activity may be associated with a higher fracture risk, although the criteria used to define atopic dermatitis severity were not consistent across studies.

When fracture location was analyzed, increased risk was identified for vertebral fractures (OR 1.14) and lower-extremity fractures (OR 1.11). The association was less pronounced for upper-extremity fractures, with an OR of 1.06. No statistically significant association was found for rib and thoracic fractures [1].

Why might this association exist?

The meta-analysis does not establish a causal relationship, but the authors discuss several possible mechanisms.

Chronic inflammation in atopic dermatitis is associated with the activation of proinflammatory signaling pathways. Several cytokines, including IL-1, IL-6, IL-17, IL-31, IL-33, TNF-α, and RANKL, may contribute to osteoclast activation and increased bone resorption [2].

Glucocorticoids remain a separate consideration. Their systemic use can suppress bone formation and increase bone resorption, including through effects on calcium and vitamin D metabolism, muscle strength, and other mechanisms [3]. At the same time, in one large cohort study, the association between atopic dermatitis and fractures persisted after adjustment for oral corticosteroid use. Therefore, medication use alone cannot fully explain the observed association [4].

Other factors may also be relevant, including reduced physical activity due to persistent itching, sleep disturbances, stress, restrictive eating habits, and insufficient calcium or vitamin D intake. However, these factors were not equally accounted for across all included studies [1].

Considerations for clinical practice

The findings do not mean that every patient with atopic dermatitis requires routine osteoporosis screening. The study did not allow calculation of absolute risk differences, and all included studies were retrospective cohort studies. Differences in participant age, diagnostic criteria, comorbidities, treatment, and access to healthcare may influence the results.

Patients with atopic dermatitis may seek medical care more often, which can lead to more frequent detection of both the condition itself and coexisting bone disorders. In addition, the authors could not fully account for physical activity, diet, sun exposure, vitamin D and calcium intake, smoking, alcohol use, or the dose and duration of topical or systemic corticosteroid treatment.

Nevertheless, the study highlights the need for clinical awareness. According to the authors, particular attention may be warranted for patients with moderate-to-severe atopic dermatitis, older adults, and those receiving long-term systemic glucocorticoid therapy. In these cases, it may be appropriate to assess individual risk factors for osteoporosis and fractures, discuss adequate calcium and vitamin D intake, encourage safe weight-bearing exercise, and take a cautious approach to systemic corticosteroid use. The decision to perform bone densitometry should be individualized in the context of overall risk [1].

Conclusions

The analysis highlights several key points regarding extracutaneous risks in atopic dermatitis:

• A meta-analysis of 10 cohort studies found an association between atopic dermatitis and an increased risk of osteoporosis and fractures.
• The risk of osteoporosis was 56% higher in patients with atopic dermatitis, while the risk of fractures at all sites was 8% higher than in individuals without this diagnosis.
• A stronger association with fractures was observed in severe atopic dermatitis and for vertebral and lower-extremity fractures.
• The findings do not prove that atopic dermatitis directly causes osteoporosis or fractures: the studies differed substantially in participant characteristics, assessment methods, and adjustment for confounding factors.
• The data support an individualized assessment of bone health risk, particularly in patients with moderate-to-severe atopic dermatitis, at older age, and during long-term systemic glucocorticoid therapy.

References

1. Liu H., Ru H., Yu P. et al. Atopic dermatitis and the risk of osteoporosis and fractures: a meta-analysis of cohort studies. Ann Med 2026; 58(1): 2607193.
2. Sirufo M.M., De Pietro F., Bassino E.M. et al. Osteoporosis in skin diseases. Int J Mol Sci 2020; 21(13): 4749.
3. Hardy R.S., Zhou H., Seibel M.J. et al. Glucocorticoids and bone: consequences of endogenous and exogenous excess and replacement therapy. Endocr Rev. 2018; 39(5): 519–548.
4. Matthewman J., Mansfield K.E., Prieto-Alhambra D. et al. Atopic eczema-associated fracture risk and oral corticosteroids: a population-based cohort study. J Allergy Clin Immunol Pract 2022; 10(1): 257–266.e8.