Impact of metabolic control on bone quality in phenylketonuria and mild hyperphenylalaninemia

A reduction of bone mineral density of unknown etiology has been reported in phenylketonuria (PKU) by radiological techniques, whereas no data on bone density in mild hyperphenylalaninemia (HPA) are available. We aimed to assess bone condition in PKU and HPA by quantitative ultrasound (QUS), taking into account patients' clinical and biochemical features.

Phalangeal QUS has been used for bone assessment in 78 patients affected by PKU (n = 42) or mild HPA (n = 36). For each patient, blood phenylalanine concentrations in the 2 years before the study have been recorded and related to bone assessment.

Overall normal bone quality has been observed in the whole study group (AD-SoS standard deviation score [SDS] 0.25 ± 1.29; BTT SDS -0.13 ± 1.08). PKU adolescents (age older than 15 years, AD-SoS SDS -0.54 ± 1.33; BTT SDS -0.85 ± 1.21) and patients with poor compliance with treatment (blood phenylalanine >10 mg/dL, AD-SoS SDS -0.47 ± 1.39; BTT SDS -0.97 ± 1.14) showed lower BTT SDS with respect to normal population (P = 0.003 and P < 0.001, respectively). Patients with PKU with good compliance with treatment (blood phenylalanine < 10 mg/dL, AD-SoS SDS 0.65 ± 1.33; BTT SDS 0.15 ± 0.94) and patients with mild HPA (AD-SoS SDS 0.44 ± 1.06 and BTT SDS 0.19 ± 0.85) showed normal bone mineral density and cortical thickness.

Good compliance with treatment in PKU during adolescence and adulthood is desirable because diet discontinuation is associated with bone loss. Mild HPA seems not to be complicated by bone damage.