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.

Amino Acid Medical Foods Provide a High Dietary Acid Load and Increase Urinary Excretion of Renal Net Acid, Calcium, and Magnesium Compared with Glycomacropeptide Medical Foods in Phenylketonuria

“…This lack of difference may reflect the 3-wk GMP-MF treatment being too short and/or the PKU genotype as the predominant driver of elevated cytokine concentrations. Second, bone-muscle functional interactions demonstrate that reduced lean mass or muscular abnormalities can contribute to bone resorption, reduced bone strength, and increased risk for fracture [6, 18]. For example, in healthy young adults at bedrest, a high dietary acid load induced by AA supplementation increased urinary markers of bone resorption (NTX and deoxypyridinoline) and calcium excretion [18].…”

“…Skeletal fragility, characterized by low bone mineral density (BMD) and increased fracture risk, has emerged as a poorly understood chronic complication of PKU managed with AA-MF [4–6]. There is no consensus on the incidence, etiology, implications, and risk factors for low BMD in PKU.…”

“…There is no consensus on the incidence, etiology, implications, and risk factors for low BMD in PKU. Low BMD is reported in 40–50% of adults with PKU [6]. Likewise, 33% of children with PKU have BMD at least two standard deviations ( Z -score ≤ −2) below the expected range for age [7].…”

Response to the Letter to the Editor Regarding “Micronutrients, Essential Fatty Acids and Bone Health in Phenylketonuria”

“…Hansen et al [2] state that the fracture prevalence in our population is twice as high as that reported in other studies, referring to Choukair et al [4] report that 24/56 patients (43%) have had a fracture at least once in their lifetime. Importantly, this is comparable to the percentage reported by us [1], even though they describe a population with mainly adult patients.…”

High Fracture Rates in Young Patients with Phenylketonuria

“…Two recent studies described fractures in PKU. In a cross-sectional study [5], it is indicated that 43% of 56 PKU patients aged 12-42 sustained fractures. According to a systematic review [6], clinical fractures affected 20% (53 of 263) of PKU patients across 6 studies.…”