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

Bridget M Stroup, Karen E Hansen, Diane Krueger, Neil Binkley, Denise M Ney, Bridget M Stroup, Karen E Hansen, Diane Krueger, Neil Binkley, Denise M Ney

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 16-35 y) provided a 24-h urine collection after consuming AA-MF or GMP-MF for 1-3 weeks 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 ± 6 g, females: 52 ± 4 g; 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 ± 75 mg/d, females: 228 ± 69 mg/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: AA-MF, Amino acid medical foods; ALM, Appendicular lean mass; Amino acid; Appendicular lean mass index; BMD, Bone mineral density; DXA, Dual-energy X-ray absorptiometry; GMP-MF, Glycomacropeptide medical foods; Glycomacropeptide; MF, Medical foods; Medical food; Osteoporosis; PAH, Phenylalanine hydroxylase; PE, Protein equivalent; PKU, Phenylketonuria; PRAL, Potential renal acid load; Phe, Phenylalanine; RDN, Registered Dietitian Nutritionist; Renal net acid; TBS, Trabecular bone score; Trabecular bone score; Tyr, Tyrosine; Urinary calcium excretion.

Figures

Fig. 1
Fig. 1
Comparison of BMD Z-scores of male and female participants with classical and variant PKU. Male participants had significantly lower total body BMD Z-Scores (p = 0.01; males, n = 6; females, n = 9) and tended to have lower L1–4 spine (p = 0.13; males, n = 6; females, n = 9) and total femur BMD Z-Scores (p = 0.08; males, n = 4; females, n = 8) compared to female participants. Values are means ± SE. BMD, bone mineral density; PKU, phenylketonuria.
Fig. 2
Fig. 2
Total femur BMD Z-scores and intake of PE from AA-MF were negatively correlated (r = − 0.58, p = 0.048) based on 13 participants with PKU. AA-MF, amino acid medical foods; BMD, bone mineral density; PE, protein equivalent; PKU, phenylketonuria.

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