Bone mineral density in French adults with early-treated phenylketonuria

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/m², p = 0.002), and were more likely to have never stopped their diet (58.8 % versus 31.8 %, p = 0.029). They also had higher total protein intake (1.1 versus 0.9 g/kg/day, p = 0.015), with more proteins from AA supplements (0.80 vs 0.53 g/kg/day, p = 0.010). In multivariate analysis, younger patients born after 1990 and who never stopped diet had a 4.7 times risk to have low BMD (p = 0.005), after adjustment on age, sex, BMI. In summary, our study identified a subgroup of PKU adult patients with low BMD and showed that prolonged low natural protein diet is associated with low BMD.