Bone mineral status in children with phenylketonuria— relationship to nutritional intake and phenylalanine control

McMurry, Martha P.; Chan, Gary M.; Leonard, Carly J.; Ernst, Sharon L.

doi:10.1093/ajcn/55.5.997

Cited by 55 publications

(68 citation statements)

References 28 publications

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“…Although different hypotheses have been proposed to explain the pathogenesis of bone impairment in PKU, such as the therapeutic protein-restricted diet (McMurry et al 2005) and the possible noxious role of high plasma Phe concentrations (Porta et al 2008;Yannicelli and Medeiros 2002), the mechanisms of this feature are still unknown. We hypothesized that an imbalance between bone formation and bone resorption could underlie the pathogenesis of reduced bone mass in PKU.…”

Section: Discussionmentioning

confidence: 99%

Increased spontaneous osteoclastogenesis from peripheral blood mononuclear cells in phenylketonuria

Porta

Roato²,

Mussa

et al. 2008

J of Inher Metab Disea

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Phenylketonuria (PKU) is commonly complicated by a progressive bone impairment of uncertain aetiology. The therapeutic phenylalanine (Phe)-restricted diet and the possible noxious effects of high plasma Phe concentrations on bone have previously been suggested as possible determinant factors. Since osteoclasts are involved in bone reabsorption, they could play a role in determining bone damage in PKU. The reported increased excretion of bone resorption markers in PKU patients is consistent with this hypothesis. Although different diseases characterized by bone loss have been related to increased spontaneous osteoclastogenesis from peripheral blood mononuclear cells (PBMCs), to date there is no evidence of increased osteoclast formation in PKU. In this study, we compared the spontaneous osteoclastogenesis from PBMCs in 20 patients affected by PKU with that observed in age- and sex-matched healthy subjects. Phenylketonuric patients showed the number of osteoclasts to be almost double that observed in controls (159.9 ± 79.5 and 87.8 ± 44.7, respectively; p = 0.001). Moreover, a strict direct correlation between the spontaneous osteoclastogenesis in PKU patients and the mean blood Phe concentrations in the preceding year was observed (r = 0.576; p = 0.010). An imbalance between bone formation and bone resorption might explain, at least in part, the pathogenesis of bone loss in this disease. These findings could provide new insights into the biological mechanisms underlying bone damage in PKU.

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Section: Discussionmentioning

confidence: 99%

Increased spontaneous osteoclastogenesis from peripheral blood mononuclear cells in phenylketonuria

Porta

Roato²,

Mussa

et al. 2008

J of Inher Metab Disea

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“…Other studies also find no correlations between dietary calcium, protein, and energy intake and BMD, BMD Z-score or BTM in patients of any age (Carson et al 1990;McMurry et al 1992;Hillman et al 1996;Modan-Moses et al 2007;Lage et al 2010). Positive correlations have been reported, however, between total calcium and phosphorus intake and BMD Z-score (PerezDuenas et al 2002) and calcium and protein from medical food and spine BMD (Geiger et al 2016).…”

Section: Discussionmentioning

confidence: 96%

Impact of Dietary Intake on Bone Turnover in Patients with Phenylalanine Hydroxylase Deficiency

et al. 2017

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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 Zscores. 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 >À2). Sixty-four percent had high resorption and normal formation indicating uncoupled bone turnover. CTx/P1NP was positively associated with food phenylalanine (r 2 ¼ 0.39; p-value ¼ 0.017), energy (r 2 ¼ 0.41; p-value ¼ 0.011) and zinc (r 2 ¼ 0.41; pvalue ¼ 0.014). CTx/P1NP was negatively associated with MF fat (r 2 ¼ À0.44; p-value ¼ 0.008), MF compliance (r 2 ¼ À0.34; p-value ¼ 0.056), and positively with food sodium (r 2 ¼ 0.43; p-value ¼ 0.014). CTx/ P1NP decreased significantly with age (p-value ¼ 0.002) and higher PTH (p-value ¼ 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. Synopsis: 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.

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“…Outro estudo relacionando fenilcetonúria com o distúrbio do metabolismo ósseo a partir dos oito anos de idade foi o de McMurry et al 44 , que avaliaram 26 crianças. Eles observaram aumento normal da densidade mineral óssea em crianças pré-escolares, enquanto as crianças maiores de oito anos apresentaram significativa redução dessa densidade.…”

Section: Fenilcetonúria E Perda óSseaunclassified

Metabolismo do cálcio na fenilcetonúria

et al. 2009

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A Fenilcetonúria é um erro inato do metabolismo do aminoácido fenilalanina. O tratamento é essencialmente dietético e envolve uma restrição severa no consumo de alimentos contendo aminoácido fenilalanina. Embora a alimentação seja complementada com fórmulas a fim de suprir as necessidades de vitaminas, minerais e aminoácidos essenciais, carências nutricionais ainda ocorrem. Isto se deve, principalmente, à restrição de fontes protéicas, que acarreta deficiência na ingestão de diversos nutrientes, dentre eles o cálcio. O cálcio possui importante relação com a formação mineral óssea. Estudos recentes demonstram que portadores de fenilcetonúria apresentam freqüentemente osteopenia e fraturas, sendo a maior incidência em crianças acima de 8 anos de idade. O rápido aumento da estatura, a dieta deficiente em cálcio e níveis de aminoácido fenilalanina elevados têm sido descritos como os principais fatores para a aquisição de massa óssea inadequada. A suplementação de cálcio em crianças saudáveis mostrou um efeito positivo sobre a aquisição de massa óssea na fase da pré-puberdade. Assim, torna-se relevante compreender a necessidade da suplementação de cálcio em pacientes fenilcetonúria, a fim de favorecer o desenvolvimento ósseo esperado. Termos de indexação: Densidade óssea. Fenilcetonúria. Metabolismo de cálcio. A B S T R A C T Phenylketonuria is an inborn error of the metabolism of the amino acid phenylalanine. The treatment is essentially dietetic and involves a severe restriction in the consumption of foods containing aminoacid phenylalanine. Although the diet is complemented with supplements in order to

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Bone mineral status in children with phenylketonuria— relationship to nutritional intake and phenylalanine control

Cited by 55 publications

References 28 publications

Increased spontaneous osteoclastogenesis from peripheral blood mononuclear cells in phenylketonuria

Increased spontaneous osteoclastogenesis from peripheral blood mononuclear cells in phenylketonuria

Impact of Dietary Intake on Bone Turnover in Patients with Phenylalanine Hydroxylase Deficiency

Metabolismo do cálcio na fenilcetonúria

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