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

Abstract

Background: Low bone mineral density (BMD) and subsequent skeletal fragility have emerged as a long-term complication of phenylketonuria (PKU). Objective: To determine if there are differences in BMD and body composition between male and female participants with PKU. Methods: 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. Results: 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. Conclusions: 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. Keywords: Amino acid, Appendicular lean mass index, Glycomacropeptide, Medical food, Osteoporosis, Renal net acid, Trabecular bone score, Urinary calcium excretion