Bone Marker Proteins in Women With and Without Polycystic Ovary Syndrome

Hormonal alterations associated with polycystic ovary syndrome (PCOS) also impact bone metabolism, though it is unclear if this is bone-protective or not. Bone marker dysfunction has been reported in PCOS and appears to be associated with obesity. This study sought to determine whether a panel of bone marker proteins (BMPs) would be dysregulated in PCOS stratified by BMI as a potential biomarker for bone in PCOS. In this exploratory cross-sectional study, plasma was collected from 234 women (137 with PCOS and 97 controls) from a biobank cohort and compared to a nonobese, non-insulin resistant population (24 with PCOS and 24 controls). Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was undertaken for the following BMPs: sclerostin; Dickkopf-related protein-1; glycogen synthase kinase-3 alpha/beta; periostin; tumor necrosis factor ligand superfamily member 11; fibroblast growth factor 23; sphingosine kinase 1; sphingosine kinase 2; cathepsins A, B, D, E, G, L2, S and Z; parathyroid hormone; osteocalcin; tumor necrosis factor ligand superfamily member 11 (sRANKL) and interleukin-1 beta. Four BMPs differed in the PCOS cohort (whole set without matching for body mass index (BMI) or insulin resistance (IR)): periostin (<i>p</i> = 0.05), cathepsin L (<i>p</i> = 0.05) and osteocalcin (<i>p</i> = 0.02) decreased in PCOS, whilst cathepsin D (<i>p</i> = 0.02) increased; however, linear regression showed that only cathepsins D and L and osteocalcin differed. None of the BMPs differed in the nonobese women with and without PCOS, nor in obese PCOS and controls stratified by BMI greater than 30 kg/m². In subgroup analysis, periostin (<i>p</i> = 0.001), sphingosine kinase 2 (<i>p</i> = 0.01) and cathepsin L (<i>p</i> = 0.001) were higher in obese versus nonobese PCOS (<i>p</i> = 0.01). Cathepsin Z (<i>p</i> = 0.02), sphingosine kinase 2 (<i>p</i> = 0.04) and lysosomal protective protein (<i>p</i> = 0.05) were lower in obese versus nonobese controls. Changes in BMPs indicative of impaired bone physiology were associated with BMI in both controls and PCOS, but did not differ between women with and without PCOS when BMI was matched. Hyperandrogenemia in PCOS did not affect BMP levels.