Multinomial risk modeling of osteopenia and osteoporosis in Iraqi women: comparative contributions of osteoprotegerin and vitamin D3

Vitamin D status is frequently low among Iraqi women, which may limit its discriminatory value for osteopenia (ON) and osteoporosis (OP). We evaluated the vitamin D axis (VD3, DBP, and VDR), osteoprotegerin (OPG), and endocrine regulators (estradiol [E2] and parathyroid hormone [PTH]) in relation to ON/OP risk before and after menopause. In this cross-sectional study, 120 women were classified as control, ON, or OP (n = 40 each) based on DEXA-derived T-scores. Serum VD3, DBP, VDR, OPG, E2, and PTH were measured by ELISA. Group comparisons were conducted using ANOVA with post hoc testing, and adjusted odds ratios (OR) for ON and OP were estimated using multinomial logistic regression, controlling for age and BMI. In premenopausal women, E2 and OPG were significantly lower in ON and OP than in controls (E2: p < 0.001; OPG: p = 0.001), whereas VD3, VDR, and DBP did not differ significantly. In postmenopausal women, OPG was markedly lower in OP than in controls and ON (p < 0.001), while VDR and DBP remained non-significant; VD3 showed a decreasing trend in OP (p = 0.042). In adjusted multinomial regression, OPG was strongly protective against OP (OR 0.275; 95% CI 0.172–0.441; p < 0.001) and against ON (OR 0.724; 95% CI 0.538–0.973; p = 0.033). E2 was protective against OP (OR 0.491; 95% CI 0.356–0.676; p < 0.001) and against ON (OR 0.748; 95% CI 0.608–0.920; p = 0.006). VD3 showed a modest protective association with OP (OR 0.948; 95% CI 0.901–0.998; p = 0.040) but not with ON, while PTH was a slight risk factor for OP (OR 1.027; 95% CI 1.004–1.051; p = 0.021). In Iraqi women, particularly after menopause, OPG (and E2) showed a stronger and more consistent association with OP/ON risk than VD3, whereas DBP and VDR were not informative in this cohort. These findings support OPG as a promising biomarker for osteoporosis risk stratification in populations with prevalent vitamin D insufficiency.