Sex differences in body composition and bone mineral density in phenylketonuria: A cross-sectional study

Low bone mineral density (BMD) and subsequent skeletal fragility have emerged as a long-term complication of phenylketonuria (PKU). To determine if there are differences in BMD and body composition between male and female participants with PKU. From our randomized, crossover trial [1] of participants with early-treated PKU who consumed a low-phenylalanine (Phe) diet combined with amino acid medical foods (AA-MF) or glycomacropeptide medical foods (GMP-MF), a subset of 15 participants (6 males, 9 females, aged 15–50 y, 8 classical and 7 variant PKU) completed one dual energy X-ray absorptiometry (DXA) scan and 3-day food records after each dietary treatment. Participants reported lifelong compliance with AA-MF. In a crossover design, 8 participants (4 males, 4 females, aged 16–35y) provided a 24-h urine collection after consuming AA-MF or GMP-MF for 1–3weeks each. Male participants had significantly lower mean total body BMD Z-scores (means±SE, males=−0.9±0.4; females, 0.2±0.3; p=0.01) and tended to have lower mean L1–4 spine and total femur BMD Z-scores compared to female participants. Only 50% percent of male participants had total body BMD Z-scores above −1.0 compared to 100% of females (p=0.06). Total femur Z-scores were negatively correlated with intake of AA-MF (r=−0.58; p=0.048). Males tended to consume more grams of protein equivalents per day from AA-MF (means±SE, males: 67±6g, females: 52±4g; p=0.057). Males and females demonstrated similar urinary excretion of renal net acid, magnesium and sulfate; males showed a trend for higher urinary calcium excretion compared to females (means ± SE, males: 339±75mg/d, females: 228±69mg/d; p=0.13). Females had a greater percentage of total fat mass compared to males (means±SE, males: 24.5±4.8%, females: 36.5±2.5%; p=0.047). Mean appendicular lean mass index was similar between males and females. Male participants had low-normal lean mass based on the appendicular lean mass index. Males with PKU have lower BMD compared with females with PKU that may be related to higher intake of AA-MF and greater calcium excretion. The trial was registered at www.clinicaltrials.gov as NCT01428258. •Males with PKU showed lower total body BMD and tended to excrete more calcium in urine compared to females with PKU.•Males with PKU had low-normal lean body mass and females with PKU had greater fat mass than males.•Our data suggest that males with PKU may be at greater risk for osteoporosis than females with PKU.