High prevalence of low bone mineral density in young adults with phenylketonuria.

Background: It has been reported that phenylalanine (Phe)-restricted diets may have negative effects on bone health in patients with classical phenylketonuria (cPKU). We aimed to evaluate bone mineral density (BMD) in adults with cPKU and determine the risk factors associated with low BMD.

Methods: Eighty adult patients with cPKU were examined, including 41 women and 39 men. The age range was 18.3-39.4 years (median 22.8). The femoral and lumbar BMD were measured by dual energy X-ray absorptiometry. The patients were evaluated in two groups with low (Z-score ≤-2) and normal BMD (Z-score > -2).

Results: Low BMD was detected in 20 patients (25%). The low BMD group had significantly more males (75% vs 40%, p < 0.01) and lower mean body mass index (BMI, 22.4 vs 24.5 kg/m², p = 0.02). Paradoxically, mean blood calcium and 25-hydroxy vitamin D levels were higher in the low BMD group, but only marginally (10.0 vs 9.8 mg/dl and 25.1 vs 21.0 µg/L respectively, p < 0.05). The groups did not differ significantly with regards to age, mean Phe levels at diagnosis, median Phe levels above the age of 12 years, other nutritional parameters or vitamin-mineral supplementation. There was no history of clinical fractures.

Discussion: Although osteopenia, osteoporosis and low BMD have been reported in PKU, conflicting data also exist. Our study of a large adult cPKU cohort strongly supports previously published limited data that suggest male sex and low BMI confer a higher risk for low BMD in cPKU; and age, Phe levels and dietary adherence do not. In our study, although the patients were young, low BMD was quite common (25%). Bone health should be evaluated even in young adults with cPKU, especially in males and those with low BMI, regardless of treatment compliance and vitamin-mineral status. Prospective studies reporting on clinical outcomes such as bone pain or fractures will be valuable in the coming years.