Abstract The magnitude and direction to which alterations in non-fat components of musculoskeletal composition (bone, muscle) may disproportionately impact diverse populations of women with polycystic ovary syndrome (PCOS) are unknown, despite clinical relevance. The uncertainty stems, partly, from heterogeneity in PCOS diagnostic criteria used and technical barriers in the reliable assessment of PCOS. We evaluated whether musculoskeletal (total and regional lean body mass [LBM] and bone mineral density [BMD]) outcomes were different in PCOS (n=126) across 4 prospectively recruited groups matched for age, body mass index, waist to hip ratio, and lack of recent (<3 mos) hormonal contraceptive and metformin use: self-identified (1) White (n=86); (2) Black (n=17); (3) Asian (n=12); and, (4) Hispanic (n=11) women in 3 academic medical centers in NY. PCOS was defined by the Rotterdam criteria using the recommended thresholds of the most recent (2018) PCOS Guideline. Fat and lean tissue mass and BMD were evaluated by dual-energy X-ray absorptiometry. Within the PCOS group, percentages of total body, trunk fat, and appendicular lean mass were comparable across races and ethnicities (All: P≥0.40); in contrast, total LBM and total and regional BMD were different across the groups (All: P<0.002). Post hoc pairwise comparisons revealed Asian women (mean±standard deviation; 39.64±6.42) exhibited lower total LBM vs. Black (53.93±10.60) and White (49.47±8.87; All: P<0.01) but not vs. their Hispanic (46.30±8.77 kg; P=0.29) counterparts. Total, upper, and lower limb BMD were higher in Black women (1.28±1.13; 0.82±0.09; 1.28±0.12) vs. all other counterparts: (White [1.12±0.9; 0.75±0.09; 1.18±0.10;]; Asian [1.09±0.09; 0.67±0.03; 1.08±0.05]; and, Hispanic [1.09±0.09; 0.72±0.15; 1.07±0.10] g/cm2; All: P<0.04), respectively. Similarly, lower limb BMD was compromised in Asian and Hispanic vs. White women (All: P≤0.03). Groups exhibited comparable glucoregulatory status (insulin and glucose responses to a standard 75-g oral glucose tolerance test), blood pressure, androgen status (Ferriman-Gallwey scores, total, free, and bioavailable testosterone), and intermenstrual interval length (All: P≥0.14). Conversely, groups differed by insulin-like-growth-factor-1 (IGF-1) and IGF-2 levels (All: P≤0.05). Post hoc pairwise comparisons showed lower IGF-1 in Black (255.92±145.12) and White (325.42±140.25) vs. Hispanic (549.21±266.26 ng/mL) women (All: P≤0.04). Also, Black women (426.74±82.66) had lower IGF-2 vs. White women (553.07±111.10 ng/mL; P≤0.4). Collectively, Asian women with PCOS show the lowest LBM and BMD, whereas their Black counterparts exhibit higher BMD after matching for age, body mass index, waist to hip ratio, lack of hormonal contraceptive and metformin use, and percentages of total body and trunk fat. Future research should delineate the true effects of PCOS-specific endocrine milieu (e.g., IGF axis) and relevance of genetic variants and/or environmental determinants of musculoskeletal health in this understudied clinical population. If confirmed by larger studies, our observations support the need for population-specific preventative and management considerations in future Guideline recommendations (e.g., PCOS-specific physical activity) to improve musculoskeletal health and associated reproductive and metabolic comorbidities. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.