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INTRODUCTION: Hypopituitary patients are at risk for bone loss. Hypothalamic-posterior pituitary hormones oxytocin and vasopressin are anabolic and catabolic, respectively, to the skeleton. Patients with hypopituitarism may be at risk for oxytocin deficiency. Whether oxytocin and/or vasopressin contribute to impaired bone homeostasis in hypopituitarism is unknown. OBJECTIVES: To determine the relationship between plasma oxytocin and vasopressin levels and bone characteristics (bone mineral density [BMD] and hip structural analysis [HSA]) in patients who have anterior pituitary deficiencies only (APD group) or with central diabetes insipidus (CDI group). METHODS: This is a cross-sectional study. Subjects included 37 men (17 CDI and 20 APD), aged 20-60 years. Main outcome measures were fasting plasma oxytocin and vasopressin levels, and BMD and HSA using dual X-ray absorptiometry. RESULTS: Mean BMD and HSA variables did not differ between the CDI and APD groups. Mean BMD Z-scores at most sites were lower in those participants who had fasting oxytocin levels below, rather than above, the median. There were positive associations between fasting oxytocin levels and (1) BMD Z-scores at the spine, femoral neck, total hip, and subtotal body and (2) favorable hip geometry and strength variables at the intertrochanteric region in CDI, but not APD, participants. No associations between vasopressin levels and bone variables were observed in the CDI or ADP groups. CONCLUSIONS: This study provides evidence for a relationship between oxytocin levels and BMD and estimated hip geometry and strength in hypopituitarism with CDI. Future studies will be important to determine whether oxytocin could be used therapeutically to optimize bone health in patients with hypopituitarism.