Bone microarchitecture and strength in obese women with and without polycystic ovary syndrome (PCOS): a peripheral quantitative computed tomography (pQCT) study.

Background: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder, but its skeletal impact remains unclear due to confounding obesity. Areal bone mineral density (BMD) studies are conflicting, with body mass index (BMI) as a modifier. High-resolution peripheral quantitative computed tomography (HR-pQCT) data in PCOS are scarce, and no study has compared obese PCOS women to BMI-matched controls or tested hyperandrogenemia as a mediator. Methods: This cross-sectional study enrolled 23 obese women with PCOS (BMI ≥28 kg/m²), 21 BMI-matched obese women without PCOS, and 24 normal-weight controls. PCOS was diagnosed using Rotterdam criteria. Participants underwent anthropometric measurements, biochemical assays, and HR-pQCT scanning of distal radius and tibia with finite element analysis. Group comparisons employed ANOVA or Kruskal-Wallis tests with selective Bonferroni correction. Linear regression examined associations between bone parameters and metabolic/inflammatory markers, adjusting for age and BMI. Mediation analysis tested whether testosterone mediated group differences in bone parameters. Results: Compared with the BMI-matched obese (OB) group, the OB-PCOS group exhibited higher total volumetric BMD (vBMD) at both the radius (p = 0.036) and tibia (p = 0.018), and higher cortical vBMD (radius: p = 0.008; tibia: p = 0.017). At the tibia, OB-PCOS additionally showed higher trabecular vBMD (p = 0.008) and trabecular bone volume fraction (p = 0.008). Despite these density advantages, no significant differences in estimated bone strength (stiffness and failure load) were observed between the two obese groups at either skeletal site (all p > 0.05). Higher BMI was associated with improved trabecular microarchitecture at the radius and increased estimated bone strength at the tibia. No mediating effect of testosterone was found for the bone differences associated with PCOS. Conclusions: PCOS is associated with increased volumetric BMD independent of obesity; however, this advantage does not translate into enhanced estimated bone strength, suggesting alterations in bone material properties. No evidence was found that testosterone mediates these skeletal differences, implicating alternative PCOS-related mechanisms (e.g., chronic inflammation or insulin resistance) in their etiology. These findings highlight the complex interplay between PCOS and obesity in skeletal health and underscore the need for longitudinal studies to assess fracture risk in this population.