{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T19:49:34Z","timestamp":1787600974260,"version":"build-2736575974"},"reference-count":44,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background\/Objectives: Skeletal impairment has been reported as a common finding in Hyperphenylalaninemia (HPA)\/Phenylketonuria (PKU) patients regardless of age and method of diagnosis, both in children and adults. Quantitative Ultrasound (QUS) is a radiation-free and low-cost method for assessing bone quality, used in various chronic conditions. Methods: Bone quality was evaluated using a calcaneal QUS device. Auxological parameters, nutritional intakes, and plasma levels of key bone biomarkers were also registered. The population was divided into four groups: PKU patients under diet therapy and HPA patients on a free diet, both divided into receiving or not receiving single vitamin D supplementation. Results: All HPA\/PKU patients had median bone quality index (BQI) Z- and T-score values lower than \u22121, with slightly better values in HPA children and PKU-supplemented adults. Dietary vitamin D intake in PKU patients was significantly higher than in HPA subjects (p &lt; 0.001), due to protein substitute supplementation. However, plasma 25(OH) vitamin D levels, although increased compared to baseline, were still overlapping among groups (p = 0.845) after supplementation. Approximately a quarter of both pediatric and adult non-supplemented PKU patients had Z-score and T-score levels below \u22122, and this percentage decreased with vitamin D supplementation in all groups. In PKU-supplemented patients, the Broadband Ultrasound Attenuation (BUA) was significantly higher than in the other groups (p = 0.040). Conclusions: The improvement in BUA may represent preliminary evidence of the effect of vitamin D on bone architecture, which could encourage this supplementation to prevent the worsening of bone structure and reduce the risk of fractures.<\/jats:p>","DOI":"10.3390\/metabo15110754","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T15:00:17Z","timestamp":1763650817000},"page":"754","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Quantitative Ultrasound for the Assessment of Bone Quality in Hyperphenylalaninemia\/Phenylketonuria Patients: Vitamin D Supplementation Versus No Supplementation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8823-8061","authenticated-orcid":false,"given":"Albina","family":"Tummolo","sequence":"first","affiliation":[{"name":"Children Hospital Giovanni XXIII, Department of Inherited Metabolic Disorders and Clinical Genetics, Azienda Ospedaliero-Universitaria Consorziale, 70126 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada","family":"De Ruvo","sequence":"additional","affiliation":[{"name":"Children Hospital Giovanni XXIII, Department of Inherited Metabolic Disorders and Clinical Genetics, Azienda Ospedaliero-Universitaria Consorziale, 70126 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1748-1931","authenticated-orcid":false,"given":"Marta","family":"Di Nicola","sequence":"additional","affiliation":[{"name":"Laboratory of Biostatistics, Department of Medical, Oral and Biotechnological Sciences, University G. D\u2019Annunzio Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vito","family":"Di Tullio","sequence":"additional","affiliation":[{"name":"Children Hospital Giovanni XXIII, Department of Inherited Metabolic Disorders and Clinical Genetics, Azienda Ospedaliero-Universitaria Consorziale, 70126 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2592-8767","authenticated-orcid":false,"given":"Livio","family":"Melpignano","sequence":"additional","affiliation":[{"name":"Medical Direction, Giovanni XXIII Children Hospital, Azienda Ospedaliero-Universitaria Consorziale, 70126 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"De Giovanni","sequence":"additional","affiliation":[{"name":"Children Hospital Giovanni XXIII, Department of Inherited Metabolic Disorders and Clinical Genetics, Azienda Ospedaliero-Universitaria Consorziale, 70126 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Carella","sequence":"additional","affiliation":[{"name":"Children Hospital Giovanni XXIII, Department of Inherited Metabolic Disorders and Clinical Genetics, Azienda Ospedaliero-Universitaria Consorziale, 70126 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s44164-021-00007-4","article-title":"A culture model for the assessment of phenylalanine neurotoxicity in phenylketonuria","volume":"1","author":"Kylies","year":"2022","journal-title":"In Vitro Models"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/s41572-021-00267-0","article-title":"Phenylketonuria","volume":"7","author":"Blau","year":"2021","journal-title":"Nat. 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