Phenylketonuria (PKU) treatment requires a low-phenylalanine (Phe) diet limiting natural protein intake, using medical low-protein foods and Phe-free amino acids (AA) supplements along with micronutriments' supplies. Current recommendations suggest maintaining this diet for life to prevent neuro-psychological effects of high Phe concentrations. The long-term consequences of such a diet are poorly understood, particularly on bone health. Our study aimed to assess the prevalence of low bone mineral density (BMD) (Z-score ≤ -2, for vertebral and/or femoral site) in adults with PKU and to investigate associated risk factors, in the French ECOPHEN cohort. The study included 171 patients with 67.3 % of women and a median age of 27 years old. The median femoral and vertebral Z-scores of BMD were both - 0.6. Only 11.4 % of patients had a low BMD. Compared to patients with normal BMD, patients with low BMD had a lower body mass index (BMI) (median 20.4 versus 24.4 kg/m