title: Analysis of the functional muscle-bone unit of the forearm in patients with phenylketonuria by peripheral quantitative computed tomography.
abstract: Bone disease in patients with phenylketonuria (PKU) is incompletely characterized. We therefore analyzed, in a cross-sectional study radius macroscopic bone architecture and forearm muscle size by peripheral quantitative computed tomography (pQCT) and muscle strength by hand dynamometry in a large cohort (n = 56) of adolescent and adult patients with PKU aged 26.0 ± 8.9 (range, 11.8-41.5) years. Data were compared with a reference population (n = 700) from the DONALD study using identical methodology. We observed a significant reduction of cortical thickness (z-score -1.01 ± 0.79), Strength-Strain Index (SSI) (z-score -0.81 ± 1.03), and total bone mineral density (BMD) of the distal radius (z-score -1.05 ± 1.00). Mean muscle cross-sectional area (z-score -0.98 ± 1.19) and muscle grip force (z-score -0.64 ± 1.26) were also significantly reduced, indicating an impaired muscular system as part of the clinical phenotype of PKU. SSI positively correlated (r = 0.53, P < 0.001) with the corresponding muscle cross-sectional area in the reference population; however, the regression line slope in PKU patients was less steep (P < 0.001), indicating that bone strength is not adequately adapted to muscle force. In conclusion, the radial bone in PKU patients is characterized by reduced bone strength in relation to muscular force, decreased cortical thickness, and impaired total BMD at the metaphyseal site. These alterations indicate a mixed bone defect in PKU, both of which are due to primary alterations of bone metabolism and to secondary alterations in response to neuromuscular abnormalities.
authors.affiliation: Department of Pediatrics I, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany. daniela.choukair@med.uni-heidelberg.de.
authors.forename: Daniela
authors.identifier: 0000-0002-1631-3883
authors.initials: D
authors.lastname: Choukair
authors.affiliation: Department of Pediatrics I, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Kneppo
authors.affiliation: Department of Pediatrics I, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany.|ICON Clinical Research GmbH, Langen, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Feneberg
authors.affiliation: University Children's Hospital Cologne, Cologne, Germany.
authors.forename: Eckhard
authors.initials: E
authors.lastname: Schönau
authors.affiliation: Division of Neuropediatrics and Metabolic Medicine, Department of Pediatrics I, University Children's Hospital Heidelberg, Heidelberg, Germany.|University Children's Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Lindner
authors.affiliation: Division of Neuropediatrics and Metabolic Medicine, Department of Pediatrics I, University Children's Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kölker
authors.affiliation: Department of Pediatrics I, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany.|Division of Neuropediatrics and Metabolic Medicine, Department of Pediatrics I, University Children's Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Georg F
authors.initials: GF
authors.lastname: Hoffmann
authors.affiliation: Department of Pediatrics I, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Tönshoff
mesh_terms: D000293:Adolescent; D000328:Adult; D015519:Bone Density / Q000502:physiology; D001842:Bone and Bones / Q000503:physiopathology*; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D005542:Forearm / Q000503:physiopathology*; D018737:Hand Strength / Q000502:physiology; D006801:Humans; D008297:Male; D053580:Muscle Strength / Q000502:physiology; D018482:Muscle, Skeletal / Q000503:physiopathology*; D010661:Phenylketonurias / Q000503:physiopathology*; D011446:Prospective Studies; D011884:Radius / Q000503:physiopathology; D014057:Tomography, X-Ray Computed / Q000379:methods; D055815:Young Adult