Osteosarcopenia is defined by the loss of skeletal muscle and bone mass and/or function usually associated with aging. Osteosarcopenia shares common risk factors and pathophysiological mechanisms with polycystic ovary syndrome (PCOS), including obesity and endocrine aberrations. Relationship between osteosarcopenia and PCOS has biological plausibility yet remains unclear. We hypothesized (1) reproductive-aged women with PCOS would exhibit early signs of osteosarcopenia evidenced by decreased appendicular skeletal muscle index (appendicular skeletal muscle mass/weight (kg) × 100 = SMI%), and bone mineral density (BMD); and (2) SMI% and BMD are aggravated by endocrine disruptions in PCOS. The SMI% and BMD of 203 women (18 – 48 y) were compared across 4 groups: (1) PCOS (hyperandrogenism and oligoamenorrhea), (2) hyperandrogenism and eumenorrhea (HA), (3) normoandrogenic oligoamenorrhea (OA), and (4) Controls. Associations between endocrine measures and SMI% and BMD were evaluated by partial correlations and all comparisons were adjusted for age and obesity. Women with PCOS exhibited reduced total SMI% (mean [95% confidence interval]; 26.2% [25.1 – 27.3] vs. 28.8% [27.7 – 29.8]), lower-extremity SMI% (LESMI%; 57.6% [56.7 – 60.0] vs. 62.5% [60.3 – 64.6]), and total BMD (1.11 [1.08 – 1.14] vs. 1.17 [1.14 – 1.20] g/cm2) compared to Controls. Women with PCOS also had decreased upper (0.72 [0.70 – 0.74] vs. 0.73 [0.71 – 0.76] g/cm2) and lower (1.13 [1.10 – 1.16] vs. 1.15 [1.12–1.18] g/cm2) limb BMD compared to the HA group. Insulin sensitivity evidenced by Matsuda index was declined in PCOS group compared to Controls, yet was positively associated with SMI% in all groups (All: P ≤ 0.05). The OA group exhibited exaggerated insulin-like-growth-factor-1 (IGF-1) compared to Controls (P = 0.01) that had negative associations with LESMI% (r = -0.90; P < 0.01). Only Controls showed positive associations between IGF-1 and upper (r = 0.84) and lower (r = 0.72) limb BMD (All: P < 0.01). Unlike PCOS group, estradiol (r = 0.64) and the ratio of luteinizing hormone to follicle-stimulating hormone (r = 0.54) were positively associated with BMD (All: P < 0.05) in OA group. Also, unlike PCOS group, IGF binding protein-2 (IGFBP-2) was positively associated with muscle or bone mass in other groups. Specifically, IGFBP2 was associated with SMI% in Controls (r = 0.45) and HA (r = 0.67), with LESMI% in OA (r = 0.91), and with upper limb BMD (r = 0.98) in HA groups (All: P < 0.05). Reproductive-aged women with PCOS exhibited early signs of osteosarcopenia likely owing to their unique metabolic and endocrine alterations. Perturbations in insulin signaling and function may drive muscle and bone loss in PCOS. Understanding the biological mechanisms and management strategies that may delay or prevent the development of osteosarcopenia is recommended to improve the musculoskeletal health and associated long-term comorbidities of PCOS.