Linking gestational RBP4 to bone resorption via postprandial glycemic pathways: A cross-sectional mediation analysis

Retinol-binding protein 4 (RBP4), a key adipokine associated with glucose metabolism, is elevated during pregnancy and linked to gestational diabetes mellitus (GDM). However, its relationship with gestational bone resorption remains unclear. This study aimed to investigate the association between RBP4 and bone resorption (measured by β-C-terminal telopeptide of type I collagen [β-CTX]) and explore potential mediation pathways involving glycemic dysregulation in pregnancy.

In this cross-sectional study, we analyzed serum RBP4, β-CTX, glucose metrics (fasting blood glucose, 1-hour [GLU1h], 2-hour [GLU2h] post-load glucose), insulin resistance indices (IR), and GDM status in pregnant women. Mediation analyses were performed to identify statistical pathways connecting RBP4 and β-CTX.

After adjusting for maternal age, gestational age, and body mass index, each 1 mg/L increase in RBP4 was associated with a 10.7 ng/L rise in β-CTX (explaining 7 % of variance). Single-mediator models indicated that GLU1h and GLU2h independently accounted for approximately 50 % of the RBP4-β-CTX association (indirect effects: 5.33 and 5.40, respectively). In serial mediation, the combined glycemic pathways mediated 0.502 of the total association (Indirect_All = 5.42), while individual paths were non-significant, suggesting potential interplay between postprandial phases. Notably, GDM status and IR showed no mediation, likely reflecting limitations of dichotomous diagnostic thresholds and pregnancy-adapted insulin resistance.

The association between RBP4 and bone resorption in pregnancy is largely linked to dynamic postprandial glucose fluctuations rather than categorical GDM. These findings highlight the importance of continuous glucose monitoring and tailored interventions in women with elevated RBP4, even below GDM thresholds, to address potential bone health risks.