This study shows that a blood test for the bone‑breakdown marker β‑CTX (≥0.3 ng/mL) together with low estradiol (≤62.7 pmol/L) can reliably flag perimenopausal women who are starting to lose bone, even before a DXA scan would catch it. IGF‑1 didn’t relate to bone loss in this group.

Increasing evidence has demonstrated accelerated bone loss during perimenopause. The detection of bone loss relies heavily on dual-energy X-ray absorptiometry (DXA). However, DXA is not sensitive enough for early bone loss. Therefore, an easy and sensitive method is urgently needed for identifying high-risk women before irreversible bone loss occurs. To 1) define a clinically meaningful β-CTX threshold (≥ 0.3 ng/mL) for perimenopausal bone loss prediction, 2) assess the predictive value of E2 and β-CTX, both individually and in combination, for bone loss in perimenopausal women. One hundred and thirty female participants met the inclusion/exclusion criteria were enrolled in this study from March 2024 to March 2025. Enrolled subjects underwent DXA examination and blood tests, including measurements of E2, β-CTX, TP1NP, D3, and IGF-1. The correlations between E2, β-CTX, TP1NP, D3, IGF-1 and T-scores were performed using Spearman correlation analysis. The predicting value of E2, β-CTX and combination for perimenopausal bone loss were studied by ROC curve analysis. There were significant correlations between E2, β-CTX, TP1NP and T-scores, but not between D3, IGF-1 and T-scores. The threshold value of E2 alone in predicting perimenopausal bone loss was 62.7 pmol/L. Its sensitivity and specificity were 79.1% and 93.2%, respectively. The threshold value of β-CTX alone in predicting perimenopausal bone loss was 0.30 ng/mL. Its sensitivity and specificity were 79.3% and 96.4%, respectively. The ROC curve of E2 combined with β-CTX showed that the AUC was 0.950. Its sensitivity and specificity were 88.4% and 97.7%, respectively, which were higher than that in E2 and β-CTX alone. A clinically meaningful β-CTX threshold (≥ 0.3 ng/mL) was defined for perimenopausal bone loss prediction, and the combination of E2 and β-CTX is a simple and reliable method for predicting perimenopausal bone loss, with high sensitivity and specificity. A threshold of β-CTX (0.3 ng/mL) with low estradiol identifies high-risk perimenopausal women for bone loss.