Low bone strength is a manifestation of phenylketonuria in mice and is attenuated by a glycomacropeptide diet. PLoS One 2012;7(9):e45165
Date
10/03/2012Pubmed ID
23028819Pubmed Central ID
PMC3445501DOI
10.1371/journal.pone.0045165Scopus ID
2-s2.0-84866509174 (requires institutional sign-in at Scopus site) 55 CitationsAbstract
PURPOSE: Phenylketonuria (PKU), caused by phenylalanine (phe) hydroxylase loss of function mutations, requires a low-phe diet plus amino acid (AA) formula to prevent cognitive impairment. Glycomacropeptide (GMP), a low-phe whey protein, provides a palatable alternative to AA formula. Skeletal fragility is a poorly understood chronic complication of PKU. We sought to characterize the impact of the PKU genotype and dietary protein source on bone biomechanics.
PROCEDURES: Wild type (WT; Pah(+/+)) and PKU (Pah(enu2/enu2)) mice on a C57BL/6J background were fed high-phe casein, low-phe AA, and low-phe GMP diets between 3 to 23 weeks of age. Following euthanasia, femur biomechanics were assessed by 3-point bending and femoral diaphyseal structure was determined. Femoral ex vivo bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry. Whole bone parameters were used in principal component analysis. Data were analyzed by 3-way ANCOVA with genotype, sex, and diet as the main factors.
FINDINGS: Regardless of diet and sex, PKU femora were more brittle, as manifested by lower post-yield displacement, weaker, as manifested by lower energy and yield and maximal loads, and showed reduced BMD compared with WT femora. Four principal components accounted for 87% of the variance and all differed significantly by genotype. Regardless of genotype and sex, the AA diet reduced femoral cross-sectional area and consequent maximal load compared with the GMP diet.
CONCLUSIONS: Skeletal fragility, as reflected in brittle and weak femora, is an inherent feature of PKU. This PKU bone phenotype is attenuated by a GMP diet compared with an AA diet.
Author List
Solverson P, Murali SG, Litscher SJ, Blank RD, Ney DMAuthor
Robert D. Blank PhD, MD Emeritus Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Absorptiometry, PhotonAnimals
Biomechanical Phenomena
Bone Density
Caseins
Diet, Protein-Restricted
Elastic Modulus
Female
Femur
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Peptide Fragments
Phenotype
Phenylalanine
Phenylalanine Hydroxylase
Phenylketonurias
