Dybal Elisa, Maillot François, Feillet François, Fouilhoux Alain, Astudillo Leonardo, Lavigne Christian, Arnoux Jean-Baptiste, Odent Sylvie, Gay Claire, Schiff Manuel, Mazodier Karin, Kuster Alice, Rigalleau Vincent, Thauvin-Robinet Christel, Leguy-Seguin Vanessa, Douillard Claire, Charrière Sybil
Fédération d'Endocrinologie, Maladies Métaboliques, Diabète, et Nutrition, Hôpital Louis Pradel, Hospices Civils de Lyon, 69677 Bron Cedex, France.
Service de Médecine Interne et d'Immunologie Clinique, CHU Tours, INSERM 1253 « iBrain », Bretonneau, 37000 Tours, France.
Mol Genet Metab. 2025 Mar;144(3):109044. doi: 10.1016/j.ymgme.2025.109044. Epub 2025 Jan 27.
Phenylketonuria (PKU) treatment requires a low-phenylalanine (Phe) diet limiting natural protein intake, using medical low-protein foods and Phe-free amino acids (AA) supplements along with micronutriments' supplies. Current recommendations suggest maintaining this diet for life to prevent neuro-psychological effects of high Phe concentrations. The long-term consequences of such a diet are poorly understood, particularly on bone health. Our study aimed to assess the prevalence of low bone mineral density (BMD) (Z-score ≤ -2, for vertebral and/or femoral site) in adults with PKU and to investigate associated risk factors, in the French ECOPHEN cohort. The study included 171 patients with 67.3 % of women and a median age of 27 years old. The median femoral and vertebral Z-scores of BMD were both - 0.6. Only 11.4 % of patients had a low BMD. Compared to patients with normal BMD, patients with low BMD had a lower body mass index (BMI) (median 20.4 versus 24.4 kg/m, p = 0.002), and were more likely to have never stopped their diet (58.8 % versus 31.8 %, p = 0.029). They also had higher total protein intake (1.1 versus 0.9 g/kg/day, p = 0.015), with more proteins from AA supplements (0.80 vs 0.53 g/kg/day, p = 0.010). In multivariate analysis, younger patients born after 1990 and who never stopped diet had a 4.7 times risk to have low BMD (p = 0.005), after adjustment on age, sex, BMI. In summary, our study identified a subgroup of PKU adult patients with low BMD and showed that prolonged low natural protein diet is associated with low BMD.
苯丙酮尿症（PKU）的治疗需要低苯丙氨酸（Phe）饮食，限制天然蛋白质的摄入，使用医用低蛋白食品和无苯丙氨酸氨基酸（AA）补充剂以及微量营养素供应。目前的建议是终身维持这种饮食，以预防高苯丙氨酸浓度对神经心理的影响。这种饮食的长期后果，尤其是对骨骼健康的影响，人们了解甚少。我们的研究旨在评估法国ECOPHEN队列中成年苯丙酮尿症患者低骨矿物质密度（BMD）（脊柱和/或股骨部位Z评分≤ -2）的患病率，并调查相关危险因素。该研究纳入了171名患者，其中67.3%为女性，中位年龄为27岁。BMD的股骨和脊柱Z评分中位数均为 -0.6。只有11.4%的患者骨密度低。与骨密度正常的患者相比，骨密度低的患者体重指数（BMI）较低（中位数分别为20.4和24.4kg/m²，p = 0.002），并且更有可能从未停止过饮食（58.8%对31.8%，p = 0.029）。他们的总蛋白质摄入量也更高（1.1对0.9g/kg/天，p = 0.015），来自AA补充剂的蛋白质更多（0.80对0.53g/kg/天，p = 0.010）。在多变量分析中，1990年后出生且从未停止饮食的年轻患者在调整年龄、性别、BMI后，骨密度低的风险是其他人的4.7倍（p = 0.005）。总之，我们的研究确定了一组骨密度低的成年苯丙酮尿症患者亚组，并表明长期低天然蛋白质饮食与低骨密度有关。
