title: Impact of Dietary Intake on Bone Turnover in Patients with Phenylalanine Hydroxylase Deficiency.
abstract: Phenylalanine hydroxylase (PAH) deficiency is a genetic disorder characterized by deficiency of the PAH enzyme. Patients follow a phenylalanine-restricted diet low in intact protein, and must consume synthetic medical food (MF) to supply phenylalanine-free protein. We assessed relationships between dietary intake and nutrient source (food or MF) on bone mineral density (BMD) and bone turnover markers (BTM) in PAH deficiency. Blood from 44 fasted females 11-52 years of age was analyzed for plasma phenylalanine, serum BTM [CTx (resorption), P1NP (formation)], vitamin D, and parathyroid hormone (PTH). BTM ratios were calculated to assess resorption relative to formation (CTx/P1NP). Dual energy X-ray absorptiometry measured total BMD and age-matched Z-scores. Three-day food records were analyzed for total nutrient intake, nutrients by source (food, MF), and compliance with MF prescription. Spearman's partial coefficients (adjusted for age, BMI, energy intake, blood phenylalanine) assessed correlations. All had normal BMD for age (Z-score >-2). Sixty-four percent had high resorption and normal formation indicating uncoupled bone turnover. CTx/P1NP was positively associated with food phenylalanine (r2= 0.39; p-value = 0.017), energy (r2= 0.41; p-value = 0.011) and zinc (r2= 0.41; p-value = 0.014). CTx/P1NP was negatively associated with MF fat (r2= -0.44; p-value = 0.008), MF compliance (r2= -0.34; p-value = 0.056), and positively with food sodium (r2= 0.43; p-value = 0.014). CTx/P1NP decreased significantly with age (p-value = 0.002) and higher PTH (p-value = 0.0002). Phenylalanine was not correlated with any bone indicator. Females with PAH deficiency had normal BMD but elevated BTM, particularly resorption. More favorable ratios were associated with nutrients from MF and compliance. Younger females had less favorable BTM ratios. Promoting micronutrient intake through compliance with MF may impact bone metabolism in patients with PAH deficiency.
  
  
  CONCLUSIONS
  Bone mineral density was normal in 44 females with PAH deficiency; however, bone turnover markers suggested uncoupling of bone resorption and formation, particularly in younger patients. Adequate nutrient intake from medical food and overall medical food compliance may positively impact bone turnover.
authors.affiliation: Nutrition and Health Sciences and Molecules to Mankind Programs, Laney Graduate School, Emory University, Atlanta, GA, USA. kcoakley@unm.edu.|Department of Individual, Family and Community Education, University of New Mexico, 604 Cagua Dr SE, Albuquerque, NM, 87108, USA. kcoakley@unm.edu.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Coakley
authors.affiliation: Division of Pediatric Endocrinology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Eric I
authors.initials: EI
authors.lastname: Felner
authors.affiliation: Division of Endocrinology, Metabolism and Lipids, Atlanta VA Medical Center, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Vin
authors.initials: V
authors.lastname: Tangpricha
authors.affiliation: Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Peter W F
authors.initials: PWF
authors.lastname: Wilson
authors.affiliation: Metabolic Nutrition Program, Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Rani H
authors.initials: RH
authors.lastname: Singh
keywords: Bone metabolism; Bone mineral density; Bone turnover markers; Dietary intake; Medical food; Phenylalanine hydroxylase deficiency