{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T13:59:41Z","timestamp":1780581581929,"version":"3.54.1"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T00:00:00Z","timestamp":1740096000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007607","name":"University Research Council, Aga Khan University","doi-asserted-by":"publisher","award":["711040-201-20102-501-70381-0000"],"award-info":[{"award-number":["711040-201-20102-501-70381-0000"]}],"id":[{"id":"10.13039\/100007607","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Introduction<\/jats:title>\n<jats:p>Children with beta-thalassemia major (\u03b2-TM) commonly experience metabolic bone diseases. Understanding fibroblast growth factor 23 (FGF-23) levels in these children can shed light on phosphate dysregulation. This study aimed to assess changes in phosphate homeostasis and associated factors, including FGF-23 and explore relationships between iron overload, FGF23 levels, and phosphorus regulation for clinical management of phosphate disorders, in children with \u03b2-TM.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>143 \u03b2-TM patients (57.3% male, median age 12 years) were recruited from Fatimid Foundation Karachi, a blood transfusion facility from January to October 2022. Clinical and biochemical evaluations were conducted at Aga Khan University Hospital, including serum ferritin, calcium (Ca), phosphate (P), vitamin D levels, and FGF-23. Descriptive and inferential statistics including multivariable analysis were applied.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>This study enrolled 143 patients, with 57.3% males. The median age was 12 years, with 53% underweight. Blood transfusion rates varied, with 66.4% receiving 2\/month. Bone\/joint pain was reported by 76.2%, with 60.8% requiring analgesics. Median serum ferritin was 2768.3 ng\/mL. Hypophosphatemia and hyperphosphatemia were observed in 5.6% and 3.5% of participants, respectively. Vitamin D deficiency\/insufficiency affected 92.3%. Plasma c-FGF23 was elevated in 60.8%, while i-FGF23 was high in 14%. A low TMP-GFR (glomerular filtration rate) was associated with high c-FGF23 and low i-FGF23. Multivariable regression revealed c-FGF23, TMP:GFR, Corrected Ca, iPTH, and an interaction term between corrected Ca and iPTH as predictors of serum P variability (~75%).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>The study identified contributors to the variations observed in serum P levels in individuals with \u03b2-TM and recommends multidisciplinary care and prospective future studies to form targeted interventions for this population.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0316566","type":"journal-article","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T18:36:53Z","timestamp":1740163013000},"page":"e0316566","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Factors associated with phosphate homeostasis in children with beta-thalassemia major: An analytical cross sectional study from Pakistan"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6807-5429","authenticated-orcid":true,"given":"Lena","family":"Jafri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arsala","family":"Jameel Farooqui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bushra","family":"Moiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisha","family":"Sheikh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hafsa","family":"Majid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Nadeem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4538-8788","authenticated-orcid":true,"given":"Ruhul","family":"Quddus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samia","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qurat-ul-Ain","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aysha","family":"Habib Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,2,21]]},"reference":[{"issue":"1","key":"pone.0316566.ref001","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1182\/hematology.2021000313","article-title":"\u03b2-Thalassemia: evolving treatment options beyond transfusion and iron chelation.","volume":"2021","author":"AL Langer","year":"2021","journal-title":"Hematology"},{"issue":"1","key":"pone.0316566.ref002","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1080\/03630269.2022.2059670","article-title":"Thalassemia in Pakistan","volume":"46","author":"S. Khaliq","year":"2022","journal-title":"Hemoglobin"},{"issue":"2","key":"pone.0316566.ref003","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1097\/MPH.0b013e31823752f3","article-title":"beta-Thalassemia in Pakistan: a pilot program on prenatal diagnosis in Multan.","volume":"34","author":"S Mahmood Baig","year":"2012","journal-title":"J Pediatr Hematol Oncol"},{"issue":"2","key":"pone.0316566.ref004","first-page":"32","article-title":"Prevalence of heterozygous beta-thalassemia in northern areas of Pakistan.","volume":"42","author":"MF Khattak","year":"1992","journal-title":"J Pak Med Assoc"},{"issue":"4","key":"pone.0316566.ref005","doi-asserted-by":"crossref","first-page":"333","DOI":"10.3109\/03630269809071528","article-title":"Molecular characterization of beta-thalassemia in Pakistan","volume":"22","author":"SN Khan","year":"1998","journal-title":"Hemoglobin"},{"issue":"7","key":"pone.0316566.ref006","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1007\/s40618-022-01780-z","article-title":"GH\/IGF-1 axis in a large cohort of \u00df-thalassemia major adult patients: a cross-sectional study","volume":"45","author":"I Gagliardi","year":"2022","journal-title":"Journal of Endocrinological Investigation"},{"issue":"4","key":"pone.0316566.ref007","first-page":"248","article-title":"Anthropometric measurements in children having transfusion-dependent beta thalassemia.","volume":"23","author":"B Moiz","journal-title":"Hematology. 2018 May"},{"key":"pone.0316566.ref008","doi-asserted-by":"crossref","first-page":"5437609","DOI":"10.1155\/2016\/5437609","article-title":"Biochemical Markers of Bone Turnover in Patients with beta-Thalassemia Major: A Single Center Study from Southern Pakistan.","volume":"2016","author":"S Sultan","year":"2016","journal-title":"Adv Hematol"},{"key":"pone.0316566.ref009","doi-asserted-by":"crossref","first-page":"1393865","DOI":"10.3389\/fendo.2024.1393865","article-title":"Prevalence and risk factors predisposing low bone mineral density in patients with thalassemia","volume":"15","author":"N Ananvutisombat","year":"2024","journal-title":"Frontiers in Endocrinology"},{"key":"pone.0316566.ref010","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11657-020-00811-7","article-title":"Bone mineral density in transfusion-dependent thalassemia patients and its associated factors in Southern Iran","volume":"15","author":"M Bordbar","year":"2020","journal-title":"Archives of Osteoporosis"},{"key":"pone.0316566.ref011","author":"SA Jaffri","journal-title":"Bone Mineral Density among adolescent\u2019s patients with \u03b2-thalassemia major"},{"issue":"2","key":"pone.0316566.ref012","doi-asserted-by":"crossref","first-page":"121","DOI":"10.4274\/tod.galenos.2020.85520","article-title":"The relationship between iron accumulation, Vitamin D deficiency and bone mineral density in patients with thalassemia major, thalassemia intermedia and sickle cell.","volume":"26","author":"M B\u00fcy\u00fck\u015fim\u015fek","year":"2020","journal-title":"Turk J Osteoporos."},{"issue":"24","key":"pone.0316566.ref013","doi-asserted-by":"crossref","first-page":"3656","DOI":"10.3390\/diagnostics13243656","article-title":"Low Vitamin D Levels Are Associated with Increased Cardiac Iron Uptake in Beta-Thalassemia Major.","volume":"13","author":"A Meloni","year":"2023","journal-title":"Diagnostics"},{"issue":"4","key":"pone.0316566.ref014","article-title":"Analysis of VDR Gene Polymorphism in Beta Thalassemia Major (Beta Thalassemia Major\/Vitamin D\/Calcium\/825T\/T Vitamin D Receptor Gene).","volume":"11","author":"E Riyanti","year":"2020","journal-title":"Systematic Reviews in Pharmacy."},{"issue":"1","key":"pone.0316566.ref015","doi-asserted-by":"crossref","DOI":"10.4084\/mjhid.2020.037","article-title":"Association of VDBP rs4701 variant, but not VDR\/RXR-\u03b1 over-expression with bone mineral density in pediatric well-chelated \u03b2-Thalassemia patients.","volume":"12","author":"S Sahmoud","year":"2020","journal-title":"Mediterranean Journal of Hematology and Infectious Diseases"},{"key":"pone.0316566.ref016","first-page":"164","article-title":"Vitamin D Receptor (VDR) Gene Polymorphism Rs 1544410 and Relation to Hypocalcemia in Iraqi Pediatrics Beta Thalassemia Major.","volume":"50","author":"A Ali","year":"2023","journal-title":"Indian Journal of Ecology"},{"issue":"10","key":"pone.0316566.ref017","first-page":"2013","article-title":"Spectrum of HBB gene variants and major endocrine complications in thalassemia patients of Pakistan","volume":"73","author":"MB Ghafoor","year":"2023","journal-title":"JPMA. The Journal of the Pakistan Medical Association"},{"issue":"1","key":"pone.0316566.ref018","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s13052-022-01290-x","article-title":"Assessment of biochemical bone markers of osteoporosis in children with thalassemia major","volume":"48","author":"T \u00c7elik","year":"2022","journal-title":"Italian Journal of Pediatrics"},{"issue":"2","key":"pone.0316566.ref019","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3329\/bsmmcj.v2i2.69841","article-title":"Serum Calcium, Phosphate and Ferritin Level in Adult Male Patients with Transfusion Dependent Thalassemia.","volume":"2","author":"SF Urmi","year":"2023","journal-title":"Bangabandhu Sheikh Mujib Medical College Journal"},{"key":"pone.0316566.ref020","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.amsu.2019.07.016","article-title":"Unique classification of parathyroid dysfunction in patients with transfusion dependent thalassemia major using Nomogram-A cross sectional study","volume":"45","author":"H Majid","year":"2019","journal-title":"Annals of Medicine and Surgery"},{"issue":"7","key":"pone.0316566.ref021","doi-asserted-by":"crossref","first-page":"3531","DOI":"10.1007\/s12325-021-01770-2","article-title":"Intravenous iron-induced hypophosphatemia: an emerging syndrome.","volume":"38","author":"JA Glaspy","year":"2021","journal-title":"Advances in therapy."},{"issue":"5","key":"pone.0316566.ref022","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1111\/bcp.14643","article-title":"Hypophosphataemia after treatment of iron deficiency with intravenous ferric carboxymaltose or iron isomaltoside\u2014a systematic review and meta\u2010analysis","volume":"87","author":"B Schaefer","year":"2021","journal-title":"British Journal of Clinical Pharmacology"},{"issue":"1","key":"pone.0316566.ref023","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12882-020-02101-3","article-title":"Association of vitamin D and FGF23 with serum ferritin in hypoparathyroid thalassemia: a case control study.","volume":"21","author":"F Saki","year":"2020","journal-title":"BMC nephrology."},{"issue":"6","key":"pone.0316566.ref024","first-page":"806","article-title":"Co-existing iron deficiency\/overload in beta-thalassemia trait.","volume":"69","author":"YM Yousafzai","year":"2019","journal-title":"JPMA"},{"issue":"1","key":"pone.0316566.ref025","doi-asserted-by":"crossref","first-page":"5","DOI":"10.2478\/amb-2023-0001","article-title":"Biochemical Control of 78 Patients with Chronic Hypoparathyroidism Referred between 2006 and 2020\u2013Where do We Actually Stand?.","volume":"50","author":"M Boyanov","year":"2023","journal-title":"Acta Medica Bulgarica"},{"issue":"4","key":"pone.0316566.ref026","doi-asserted-by":"crossref","first-page":"e1015","DOI":"10.1210\/clinem\/dgz309","article-title":"Iron overload associated endocrine dysfunction leading to lower bone mineral density in thalassemia major","volume":"105","author":"WP Yang","year":"2020","journal-title":"The Journal of Clinical Endocrinology & Metabolism"},{"issue":"6","key":"pone.0316566.ref027","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.51248\/.v42i6.2394","article-title":"Hypoparathyroidism due to iron overload in beta-thalassemia patients.","volume":"42","author":"MR Mohammed","year":"2022","journal-title":"Biomedicine"},{"key":"pone.0316566.ref028","article-title":"Prevalence of hypoparathyroidism, growth retardation in patients of \u03b2-thalassemia major.","volume":"10","author":"N Manne","year":"2020","journal-title":"Age."},{"key":"pone.0316566.ref029","first-page":"1","article-title":"Regulation of FGF23 Production in Osteocytes","volume":"9","author":"S. Fukumoto","year":"2024","journal-title":"Current Osteoporosis Reports."},{"issue":"03","key":"pone.0316566.ref030","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1055\/a-1104-5326","article-title":"Fibroblast growth factor 23 (FGF23) and klotho protein in beta-Thalassemia.","volume":"52","author":"D Stefanopoulos","year":"2020","journal-title":"Horm Metab Res"},{"issue":"9","key":"pone.0316566.ref031","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.29271\/jcpsp.2022.09.1235","article-title":"An Urgent Need for Local Guidelines to Address Phosphate Homeostasis in Children with Transfusion-dependent \u03b2-thalassemia Major.","volume":"32","author":"L Jafri","year":"2022","journal-title":"J Coll Physicians Surg\u2014Pak JCPSP."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0316566","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T18:37:03Z","timestamp":1740163023000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0316566"}},"subtitle":[],"editor":[{"given":"Nihad A. 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