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Elevated plasma phenylalanine concentrations may adversely affect bone status of phenylketonuric mice
1Department of Human Nutrition and Food Management, College of Human Ecology, The Ohio State University, Columbus, USA.
Insights
High phenylalanine levels in phenylketonuria (PKU) may negatively impact bone health in children. This study in PKU mice suggests hyperphenylalaninaemia adversely affects bone status, increasing fracture risk.
Area of Science:
- Biochemistry
- Orthopedics
- Genetics
Background:
- Children with phenylketonuria (PKU) face an increased risk of fractures.
- Elevated plasma phenylalanine (Phe) is a hallmark of PKU.
- The impact of hyperphenylalaninaemia on bone status requires further investigation.
Purpose of the Study:
- To evaluate the effects of moderate dietary protein restriction and elevated plasma phenylalanine on bone status in a PKU murine model (PAH(enu-2)).
Main Methods:
- Fifty-four male weanling PKU and control mice were fed either a Phe-restricted or Phe-unrestricted diet for 56 days.
- Plasma Phe, osteocalcin, and urine deoxypyridinoline (DPD)/creatinine were measured.
- Femur strength, bone mineral density (BMD), and bone mineral content (BMC) were assessed.
Main Results:
- Untreated PKU mice had significantly higher plasma Phe concentrations and lower body weight and femur dimensions compared to controls.
- Femur strength was greater in treated PKU mice than controls, but not significantly different from untreated PKU mice.
- No significant differences in BMD or BMC were observed; however, a trend towards higher urine DPD/creatinine excretion was noted in untreated PKU mice, correlating positively with plasma Phe.
Conclusions:
- Moderate protein restriction did not significantly alter bone status in this model.
- Hyperphenylalaninaemia in PKU mice appears to adversely affect bone status, potentially increasing fracture risk.
- Further research is warranted to elucidate the mechanisms linking hyperphenylalaninaemia to bone abnormalities in PKU.
Abstract:
Children with phenylketonuric (PKU) are at risk for fractures. This study used a PKU murine model (PAH(enu-2)) to evaluate effects of moderate dietary protein restriction and elevated plasma phenylalanine concentration impact upon bone status. Fifty-four male weanling PKU and control mice were assigned to either an elemental phenylalanine (Phe)-restricted diet (treated) or Phe-unrestricted diet (untreated) with low or normal protein levels for 56 days. Untreated mice and control mice received equal amounts of dietary Phe; treated mice consumed prescribed dietary Phe to maintain plasma Phe concentrations between 120 and 480micromol/L. Plasma Phe, osteocalcin, and urine deoxypyridinoline (DPD)/creatinine were analysed at baseline and at days 28 and 56. Femur strength, bone mineral density (BMD) and bone mineral content (BMC) were analysed at day 56. Moderate protein restriction did not significantly affect bone status. Mean plasma Phe concentrations were significantly greater in untreated vs treated and control mice (p < 0.0001). Total body weight was significantly less in untreated vs control mice (p < 0.01). Mean femur weight was reduced in untreated mice vs both treated and control mice (p < 0.03). Untreated mice had smaller mean femur length than control mice (p < 0.002). Femur strength was greater in treated mice compared to control mice (p < 0.01) but not compared to untreated mice. No significant difference among groups was found in BMD and BMC. At day 56 there was a statistical trend (p < 0.056) towards higher urine DPD/creatinine excretion in untreated mice than in treated mice. Plasma Phe concentration was positively correlated with urine DPD/creatinine. These data suggested that hyperphenylalaninaemia may adversely affect bone status in PKU mice.