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Document Type

Original Article

Abstract

Osteoporosis represents an international public health issue primarily affecting postmenopausal females, characterized by an imbalance between bone resorption and bone formation. Numerous cytokines are implicated in its development. To date, however, the role of IL-40 in osteoporosis has not been investigated. IL-40 is a pro-inflammatory cytokine involved in immune processes; its role in various autoimmune and inflammatory disorders is now emerging. This pilot study sought to assess serum IL-40 levels in postmenopausal osteoporotic women and to explore its potential associations with soluble RANKL, Osteoprotegerin (OPG), and 17β-estradiol. A total of 69 postmenopausal women participated; bone mineral density was assessed via dual-energy X-ray absorptiometry (DEXA). According to WHO criteria, 39 were diagnosed with postmenopausal osteoporosis (PMO), and 30 served as healthy controls (HC). Blood samples were analyzed for markers; serum concentrations of IL-40, sRANKL, and OPG were assessed by ELISA, and Estradiol by CLIA. Notably, IL-40 concentrations were significantly higher in the PMO women, showing significant positive correlations with sRANKL and with the sRANKL/OPG ratio. In contrast, weak and non-significant negative correlations were observed with OPG and 17β-estradiol. The PMO group had significantly higher sRANKL and OPG concentrations than the HC group, whereas 17β-estradiol was higher in the HC group. The two groups also differed significantly in age and BMI; the principal comparisons were therefore repeated in multivariable models adjusted for both variables, in which IL-40 remained independently associated with osteoporosis (adjusted odds ratio 8.02 per ng/L, 95% CI 2.44-26.35, p = 0.001).   In an exploratory ROC analysis, IL-40 showed acceptable discrimination between the two groups (AUC = 0.845; sensitivity 92.31%, and specificity 68.97%; P < 0.0001). These preliminary findings suggest that IL-40 may be relevant to osteoimmunology and warrant further investigation as a potential diagnostic biomarker of postmenopausal osteoporosis. Due to the pilot and cross-sectional design of the study, these results should be viewed as hypothesis-generating and do not allow for causal conclusions.

Receive Date

30 June 2026

Revise Date

17 Sep 2026

Accept Date

24 Sep 2026

Publication Date

2026

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