{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:33:18Z","timestamp":1787567598526,"version":"build-2736575974"},"reference-count":39,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003356","name":"Gazi University Scientific Research Projects Coordination Unit","doi-asserted-by":"publisher","award":["TDK-2025-9959"],"award-info":[{"award-number":["TDK-2025-9959"]}],"id":[{"id":"10.13039\/501100003356","id-type":"DOI","asserted-by":"publisher"}]},{"award":["TDK-2025-9959"],"award-info":[{"award-number":["TDK-2025-9959"]}],"id":[{"id":"https:\/\/ror.org\/054xkpr46","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Inherited metabolic disorders (IMDs) are a heterogeneous group of genetic diseases, some of which require lifelong disease-specific dietary management. Children with phenylketonuria (PKU), organic acidemias (OAs), and glycogen storage diseases (GSDs) are particularly susceptible to nutritional imbalances and metabolic disturbances that may adversely affect bone metabolism and skeletal health. However, data regarding bone turnover markers and bone health in these pediatric IMD populations remain limited. Objective: This study aimed to evaluate bone metabolism by assessing biochemical parameters, bone turnover markers, and bone mineral density in children with PKU, OA, and GSD receiving long-term dietary treatment. Methods: This cross-sectional study included 95 children, comprising 25 patients with PKU, 20 patients with organic acidemias, 20 patients with glycogen storage diseases, and 30 healthy age-matched controls. Demographic characteristics, anthropometric measurements, and dietary intake were recorded. Biochemical evaluation included serum calcium, phosphorus, alkaline phosphatase (ALP), parathyroid hormone (PTH), and 25-hydroxyvitamin D levels. Bone turnover was assessed using C-terminal telopeptide of type I collagen (CTX), procollagen type I N-terminal propeptide (P1NP), and osteocalcin (OC) levels. Bone mineral density was evaluated by dual-energy X-ray absorptiometry (DXA). Results: Age and sex distributions were similar among the groups. Height was lower in OA than in controls and PKU, and in GSD than in PKU; weight and BMI were lower in both OA and GSD than in controls and PKU (p &lt; 0.05). Significant differences were observed in dietary energy and macronutrient intake according to disease-specific nutritional regimens. Serum calcium, phosphorus, and 25-hydroxyvitamin D levels were significantly lower in all IMD groups compared with healthy controls (p &lt; 0.001). ALP and PTH levels were significantly higher in PKU, OA, and GSD patients than in controls (p &lt; 0.001). Among bone turnover markers, P1NP and osteocalcin levels significantly differed among groups, with the highest values observed in PKU patients (p = 0.006 and p = 0.028, respectively). CTX levels did not significantly differ among the groups (p = 0.183). DXA Z-scores were significantly lower in all IMD groups than in controls, with the lowest mean Z-scores observed in GSD patients. Conclusions: Children with PKU, OA, and GSD receiving long-term dietary treatment exhibited significant alterations in bone metabolism, characterized by lower vitamin D, calcium, and phosphorus levels, higher ALP and PTH concentrations, differences in bone formation markers, and lower DXA Z-scores compared with controls. Significant differences were observed in the bone formation markers P1NP and osteocalcin, whereas CTX levels remained comparable among the study groups. These findings underscore the importance of regular assessment of bone health and optimization of nutritional management in children under dietary treatment, while acknowledging that disease-specific mechanisms of skeletal involvement may differ among these conditions.<\/jats:p>","DOI":"10.3390\/nu18172751","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:20:02Z","timestamp":1787563202000},"page":"2751","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biochemical Evaluation of Bone Health in Children with Phenylketonuria, Organic Acidemias, and Glycogen Storage Diseases Under Dietary Management"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5383-5632","authenticated-orcid":false,"given":"Sabire","family":"Gokalp","sequence":"first","affiliation":[{"name":"Department of Pediatric Metabolic Disorders, Etlik City Hospital, Ankara 06170, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatice","family":"Pasaoglu","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Gazi University, Ankara 06560, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"de Castro, M.J., de Lamas, C., Sanchez-Pintos, P., Gonzalez-Lamuno, D., and Couce, M.L. (2020). Bone Status in Patients with Phenylketonuria: A Systematic Review. Nutrients, 12.","DOI":"10.3390\/nu12072154"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/jimd.12177","article-title":"Bone mineral density is within normal range in most adult phenylketonuria patients","volume":"43","author":"Lubout","year":"2020","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Tummolo, A., De Ruvo, G., Di Nicola, M., Di Tullio, V., Melpignano, L., De Giovanni, D., and Carella, R. (2025). Quantitative Ultrasound for the Assessment of Bone Quality in Hyperphenylalaninemia\/Phenylketonuria Patients: Vitamin D Supplementation Versus No Supplementation. Metabolites, 15.","DOI":"10.3390\/metabo15110754"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Hanusch, B., Schlegtendal, A., Lucke, T., and Sinningen, K. (2025). Ex Vivo Osteoclastogenesis from Peripheral Blood Mononuclear Cells Is Unchanged in Adults with Phenylketonuria, Regardless of Dietary Compliance. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26125776"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Hanusch, B., Schlegtendal, A., Grasemann, C., Lucke, T., and Sinningen, K. (2025). Adults with Phenylketonuria have suboptimal bone mineral density apart from vitamin D and calcium sufficiency. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1488215"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1186\/s13023-024-03223-9","article-title":"Meta-analysis of bone mineral density in adults with phenylketonuria","volume":"19","author":"Rocha","year":"2024","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Jacoby, J.T., Bento Dos Santos, B., Nalin, T., Colonetti, K., Farret Refosco, L., de Souza, C.F.M., Spritzer, P.M., Poloni, S., Hack-Mendes, R., and Schwartz, I.V.D. (2021). Bone Mineral Density in Patients with Hepatic Glycogen Storage Diseases. Nutrients, 13.","DOI":"10.3390\/nu13092987"},{"key":"ref_8","first-page":"101173","article-title":"Evaluation of bone mineral density and biochemical markers in pediatric patients with phenylketonuria","volume":"41","author":"Haghtalab","year":"2024","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.jocd.2017.02.001","article-title":"Effects of Short-Term Calcium Supplementation in Children and Adolescents with Phenylketonuria","volume":"21","author":"Tanaka","year":"2018","journal-title":"J. Clin. Densitom."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wang, Y., Hu, H., and Huang, Y. (2025). Advances in the application of bone turnover markers for pediatric growth and developmental disorders: A review. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1615712"},{"key":"ref_11","first-page":"100998","article-title":"Low bone mineralization in phenylketonuria may be due to undiagnosed metabolic acidosis","volume":"36","author":"Rovelli","year":"2023","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_12","first-page":"23","article-title":"Relationship between Biochemical Bone Markers and Bone Mineral Density in Patients with Phenylketonuria under Restricted Diet","volume":"24","author":"Koura","year":"2014","journal-title":"Iran. J. Pediatr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s10545-011-9412-7","article-title":"Bone development in children and adolescents with PKU","volume":"35","author":"Mendes","year":"2012","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s13023-015-0232-y","article-title":"Bone health in phenylketonuria: A systematic review and meta-analysis","volume":"10","author":"Demirdas","year":"2015","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"109044","DOI":"10.1016\/j.ymgme.2025.109044","article-title":"Bone mineral density in French adults with early-treated phenylketonuria","volume":"144","author":"Dybal","year":"2025","journal-title":"Mol. Genet. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s10545-009-1191-12","article-title":"Long-term needs of adult patients with organic acidaemias: Outcome and prognostic factors","volume":"32","author":"Lee","year":"2009","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1007\/s00431-006-0089-0","article-title":"Osteoporotic femoral fracture in a child with propionic acidaemia presenting as non-accidental injury","volume":"165","author":"Talbot","year":"2006","journal-title":"Eur. J. Pediatr."},{"key":"ref_18","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. (1993). Isolated Methylmalonic Acidemia. GeneReviews((R)), University of Washington."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s00223-024-01302-4","article-title":"Glycogen Storage Disease Type I and Bone: Clinical and Cellular Characterization","volume":"115","author":"Vai","year":"2024","journal-title":"Calcif. Tissue Int."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1023\/A:1025111220095","article-title":"Bone mineral density in children, adolescents and adults with glycogen storage disease type Ia: A cross-sectional and longitudinal study","volume":"26","author":"Rake","year":"2003","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.bone.2016.02.012","article-title":"Reduced bone mineral density in glycogen storage disease type III: Evidence for a possible connection between metabolic imbalance and bone homeostasis","volume":"86","author":"Melis","year":"2016","journal-title":"Bone"},{"key":"ref_22","first-page":"S50","article-title":"The muscle-bone relationship: Methods and management\u2014Perspectives in glycogen storage disease","volume":"161","author":"Schonau","year":"2002","journal-title":"Eur. J. Pediatr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e24656","DOI":"10.1002\/jcla.24656","article-title":"Broad application prospects of bone turnover markers in pediatrics","volume":"36","author":"Zhang","year":"2022","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.ecl.2018.07.003","article-title":"Physiology of Parathyroid Hormone","volume":"47","author":"Goltzman","year":"2018","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1056\/NEJMra070553","article-title":"Vitamin D deficiency","volume":"357","author":"Holick","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1210\/er.2018-00126","article-title":"Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions","volume":"40","author":"Bouillon","year":"2019","journal-title":"Endocr. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.2215\/CJN.05910809","article-title":"Calcium metabolism in health and disease","volume":"5","author":"Peacock","year":"2010","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1007\/s00198-015-3440-3","article-title":"The National Osteoporosis Foundation\u2019s position statement on peak bone mass development and lifestyle factors: A systematic review and implementation recommendations","volume":"27","author":"Weaver","year":"2016","journal-title":"Osteoporos. Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.bone.2009.10.005","article-title":"Maximizing bone mineral mass gain during growth for the prevention of fractures in the adolescents and the elderly","volume":"46","author":"Rizzoli","year":"2010","journal-title":"Bone"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"144855","DOI":"10.1016\/j.gene.2020.144855","article-title":"Alkaline phosphatase: Structure, expression and its function in bone mineralization","volume":"754","author":"Vimalraj","year":"2020","journal-title":"Gene"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1007\/s12020-016-0900-2","article-title":"The use of biochemical markers of bone turnover in the clinical management of primary and secondary osteoporosis","volume":"52","author":"Vasikaran","year":"2016","journal-title":"Endocrine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"R19","DOI":"10.1530\/EJE-17-0585","article-title":"Diagnosis of Endocrine Disease: Bone turnover markers: Are they clinically useful?","volume":"178","author":"Eastell","year":"2018","journal-title":"Eur. J. Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1152\/physrev.1989.69.3.990","article-title":"Osteocalcin and matrix Gla protein: Vitamin K-dependent proteins in bone","volume":"69","author":"Hauschka","year":"1989","journal-title":"Physiol. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.cell.2007.05.047","article-title":"Endocrine regulation of energy metabolism by the skeleton","volume":"130","author":"Lee","year":"2007","journal-title":"Cell"},{"key":"ref_35","first-page":"510","article-title":"Bone turnover markers in children and adolescents with type 1 diabetes\u2014A systematic review","volume":"20","author":"Madsen","year":"2019","journal-title":"Pediatr. Diabetes"},{"key":"ref_36","unstructured":"Nana, M., Anastasopoulou, C., Parikh, N.S., and Ahlawat, R. (2026). Glycogen Storage Disease Type I. StatPearls, StatPearls."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.jocd.2014.01.003","article-title":"Dual-energy X-ray absorptiometry interpretation and reporting in children and adolescents: The revised 2013 ISCD Pediatric Official Positions","volume":"17","author":"Crabtree","year":"2014","journal-title":"J. Clin. Densitom."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3160","DOI":"10.1210\/jc.2011-1111","article-title":"Revised reference curves for bone mineral content and areal bone mineral density according to age and sex for black and non-black children: Results of the bone mineral density in childhood study","volume":"96","author":"Zemel","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.jocd.2014.01.007","article-title":"2013 Pediatric Position Development Conference: Executive summary and reflections","volume":"17","author":"Gordon","year":"2014","journal-title":"J. Clin. Densitom."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/17\/2751\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:28:08Z","timestamp":1787563688000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/17\/2751"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,22]]},"references-count":39,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["nu18172751"],"URL":"https:\/\/doi.org\/10.3390\/nu18172751","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,22]]}}}