Progressive impact of polycystic ovary syndrome on hormonal alterations, bone microarchitecture, and mechanical properties

Polycystic ovary syndrome (PCOS) is characterized by reproductive and metabolic dysfunction that may also impact bone metabolism and its structural integrity. This study aims to assess the progressive impact of PCOS on bone health over time. It focuses on how the duration of the condition influences hormonal profiles, bone metabolism, and bone's microstructural and mechanical properties in the PCOS-induced mice model. Female BALB/c mice were separated into three groups, each further subdivided into PCOS-induced and age-matched control groups. PCOS was induced by letrozole (6 mg/kg b.w.) administered continuously for 21 days; among them, group II underwent a one-month observation period, while group III was observed for two months. Bone quality markers were assessed through hormonal profiling, serum bone turnover markers, micro-CT, three-point bending test, nanoindentation, and FTIR. Hormonal profiling revealed persistent hyperandrogenism, elevated luteinizing hormone/follicle-stimulating hormone ratio, reduced estrogen levels, and insulin resistance collectively affected bone health. Micro-CT analysis showed a decline in trabecular quality in the femur and tibia of the PCOS group. Three-point bending test pointed toward increased susceptibility to micro-damage and fracture. Nanoindentation indices, elasticity, and hardness were also decreased. FTIR analysis indicates alterations in bone material properties. These indices showed a slight improvement in the third month but deviated significantly from control. Our results suggest that PCOS has an adverse impact on bone's structural, mechanical, and compositional properties, and the negative impact of PCOS on skeletal integrity is not fully reversible in the short term. Overall, these findings highlight the importance of evaluating and monitoring bone health in PCOS individuals.