{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T15:17:35Z","timestamp":1794410255107,"version":"4.9.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T00:00:00Z","timestamp":1647216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K23DK102659"],"award-info":[{"award-number":["K23DK102659"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL149722"],"award-info":[{"award-number":["R01HL149722"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5UL1TR001878"],"award-info":[{"award-number":["5UL1TR001878"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002108","name":"Friedreich's Ataxia Research Alliance","doi-asserted-by":"publisher","award":["GRT-00000432"],"award-info":[{"award-number":["GRT-00000432"]}],"id":[{"id":"10.13039\/100002108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Friedreich\u2019s Ataxia (FRDA) is a progressive neurological disorder caused by mutations in both alleles of the <jats:italic>frataxin (FXN)<\/jats:italic> gene. Impaired bone health is a complication of other disorders affecting mobility, but there is little information regarding bone health in FRDA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Dual energy X-ray absorptiometry (DXA) scan-based assessments of areal bone mineral density (aBMD) in individuals with FRDA were abstracted from four studies at the Children\u2019s Hospital of Philadelphia (CHOP). Disease outcomes, including the modified FRDA Rating Scale (mFARS), were abstracted from the FRDA Clinical Outcomes Measures Study (FACOMS), a longitudinal natural history study. A survey regarding bone health and fractures was sent to individuals in FACOMS-CHOP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Adults with FRDA (<jats:italic>n<\/jats:italic> = 24) have lower mean whole body (WB) (\u20130.45 vs. 0.33, <jats:italic>p<\/jats:italic> = 0.008) and femoral neck (FN) (\u20130.71 vs. 0.004, <jats:italic>p<\/jats:italic> = 0.02) aBMD Z-scores than healthy controls (<jats:italic>n<\/jats:italic> = 24). Children with FRDA (<jats:italic>n<\/jats:italic> = 10) have a lower WB-less-head (\u20132.2 vs. 0.19, <jats:italic>p<\/jats:italic> &amp;lt; 0.0001) and FN (\u20131.1 vs. 0.04, <jats:italic>p<\/jats:italic> = 0.01) aBMD than a reference population (<jats:italic>n<\/jats:italic> = 30). In adults, lower FN aBMD correlated with functional disease severity, as reflected by mFARS (<jats:italic>R<\/jats:italic> = \u20130.56, <jats:italic>p<\/jats:italic> = 0.04). Of 137 survey respondents (median age 27 y, 50% female), 70 (51%) reported using wheelchairs as their primary ambulatory device: of these, 20 (29%) reported a history of potentially pathologic fracture and 11 (16%) had undergone DXA scans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Low aBMD is prevalent in FRDA, but few of even the highest risk individuals are undergoing screening. Our findings highlight potential missed opportunities for the screening and treatment of low aBMD in FRDA.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnins.2022.818750","type":"journal-article","created":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T14:11:34Z","timestamp":1647267094000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Bone Mineral Density and Current Bone Health Screening Practices in Friedreich\u2019s Ataxia"],"prefix":"10.3389","volume":"16","author":[{"given":"Julia","family":"Dunn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaclyn","family":"Tamaroff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"DeDio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Wade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolette","family":"Cilenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Lynch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shana E.","family":"McCormack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,14]]},"reference":[{"key":"B1","first-page":"479","article-title":"Pathologic bone fractures: definition and classification.","author":"Adler","year":"1989","journal-title":"Langenbecks Arch. Chir. Suppl. II Verh. Dtsch. Ges. Chir."},{"key":"B2","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.jocd.2019.07.009","article-title":"Bone Health in Patients With Inflammatory Bowel Diseases.","volume":"23","author":"Chedid","year":"2020","journal-title":"J. Clin. Densitometr."},{"key":"B3","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1002\/1531-8249(199902)45:2<200::aid-ana10gt;3.0.co;2-u","article-title":"Friedreich\u2019s ataxia: point mutations and clinical presentation of compound heterozygotes.","volume":"45","author":"Coss\u00e9e","year":"1999","journal-title":"Ann. Neurol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.bone.2016.12.016","article-title":"Use of dual-energy X-ray absorptiometry (DXA) for diagnosis and fracture risk assessment; WHO-criteria, T- and Z-score, and reference databases.","volume":"104","author":"Dimai","year":"2017","journal-title":"Bone"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-68566-2","article-title":"Mitochondrial dysfunction impairs osteogenesis, increases osteoclast activity, and accelerates age related bone loss.","volume":"10","author":"Dobson","year":"2020","journal-title":"Sci. Rep."},{"key":"B6","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1007\/s12311-014-0568-1","article-title":"Low bone mineral density in Friedreich ataxia.","volume":"13","author":"Eigentler","year":"2014","journal-title":"Cerebellum"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1002\/jbmr.3228","article-title":"Fracture Incidence and Characteristics in Young Adults Aged 18 to 49 Years: a Population-Based Study.","volume":"32","author":"Farr","year":"2017","journal-title":"J. Bone Miner. Res."},{"key":"B8","first-page":"554","article-title":"The relationship between trinucleotide (GAA) repeat length and clinical features in Friedreich ataxia.","volume":"59","author":"Filla","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09989-y","article-title":"Structure of the human frataxin-bound iron-sulfur cluster assembly complex provides insight into its activation mechanism.","volume":"10","author":"Fox","year":"2019","journal-title":"Nat. Commun."},{"key":"B10","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1007\/s10545-017-0046-2","article-title":"Risk factors for poor bone health in primary mitochondrial disease.","volume":"40","author":"Gandhi","year":"2017","journal-title":"J. Inherit. Metab. Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.jbi.2008.08.010","article-title":"Research electronic data capture (REDCap)\u2013a metadata-driven methodology and workflow process for providing translational research informatics support.","volume":"42","author":"Harris","year":"2009","journal-title":"J. Biomed. Inf."},{"key":"B12","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.bone.2006.07.006","article-title":"Weight-bearing exercise and bone mineral accrual in children and adolescents: a review of controlled trials.","volume":"40","author":"Hind","year":"2007","journal-title":"Bone"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0222758","article-title":"Does a spinal implant alter dual energy X-ray absorptiometry body composition measurements?","volume":"14","author":"Hsiao","year":"2019","journal-title":"PLoS One"},{"key":"B14","article-title":"Committee to Review Dietary Reference Intakes for Vitamin D and Calcium","author":"Ross","year":"2011","journal-title":"Dietary Reference Intakes for Calcium and Vitamin D"},{"key":"B15","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1111\/j.1365-2265.2006.02683.x","article-title":"Mechanisms of osteoporosis in spinal cord injury.","volume":"65","author":"Jiang","year":"2006","journal-title":"Clin. Endocrinol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2087","DOI":"10.1210\/jc.2006-2553","article-title":"The bone mineral density in childhood study: bone mineral content and density according to age, sex, and race.","volume":"92","author":"Kalkwarf","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B17","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1016\/B978-0-12-415853-5.00068-6","article-title":"Fracture Risk Assessment: The Development and Application of FRAX\u00ae","author":"Kanis","year":"2013","journal-title":"Osteoporosis"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2279","DOI":"10.1002\/jbmr.1692","article-title":"Iron overload accelerates bone loss in healthy postmenopausal women and middle-aged men: a 3-year retrospective longitudinal study.","volume":"27","author":"Kim","year":"2012","journal-title":"J. Bone Miner. Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"e3529","DOI":"10.1210\/clinem\/dgaa380","article-title":"Pediatric Reference Ranges for Ultradistal Radius Bone Density: Results from the Bone Mineral Density in Childhood Study.","volume":"105","author":"Kindler","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1210\/jc.2018-01693","article-title":"Lumbar Spine Bone Mineral Apparent Density in Children: Results From the Bone Mineral Density in Childhood Study.","volume":"104","author":"Kindler","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101791","article-title":"The Nrf2 induction prevents ferroptosis in Friedreich\u2019s Ataxia.","volume":"38","author":"La Rosa","year":"2021","journal-title":"Redox Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1002\/ana.25934","article-title":"Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study).","volume":"89","author":"Lynch","year":"2021","journal-title":"Ann. Neurol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e45","DOI":"10.1097\/BPO.0000000000000595","article-title":"Epidemiology of Pediatric Fractures Presenting to Emergency Departments in the United States.","volume":"36","author":"Naranje","year":"2016","journal-title":"J. Pediatr. Orthop."},{"key":"B24","doi-asserted-by":"crossref","DOI":"10.17226\/25353","article-title":"Committee to Review the Dietary Reference Intakes for Sodium and Potassium","author":"Stallings","year":"2019","journal-title":"Dietary Reference Intakes for Sodium and Potassium"},{"key":"B25","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/jnc.12300","article-title":"Deferiprone for the treatment of Friedreich\u2019s ataxia.","volume":"126","author":"Pandolfo","year":"2013","journal-title":"J. Neurochem."},{"key":"B26","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1136\/jcp.51.2.117","article-title":"Age related somatic mitochondrial DNA deletions in bone.","volume":"51","author":"Papiha","year":"1998","journal-title":"J. Clin. Pathol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1002\/mus.26610","article-title":"Open-label pilot study of oral methylprednisolone for the treatment of patients with friedreich ataxia.","volume":"60","author":"Patel","year":"2019","journal-title":"Muscle Nerve"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1177\/0883073812448462","article-title":"Friedreich ataxia clinical outcome measures: natural history evaluation in 410 participants.","volume":"27","author":"Regner","year":"2012","journal-title":"J. Child Neurol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.1002\/acn3.51118","article-title":"Test-retest reliability of the Friedreich\u2019s ataxia rating scale.","volume":"7","author":"Rummey","year":"2020","journal-title":"Ann. Clin. Trans. Neurol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1177\/0883073816643408","article-title":"Comorbid Medical Conditions in Friedreich Ataxia: association With Inflammatory Bowel Disease and Growth Hormone Deficiency.","volume":"31","author":"Shinnick","year":"2016","journal-title":"J. Child Neurol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/j.jocd.2019.07.001","article-title":"Executive Summary of the 2019 ISCD Position Development Conference on Monitoring Treatment, DXA Cross-calibration and Least Significant Change, Spinal Cord Injury, Peri-prosthetic and Orthopedic Bone Health, Transgender Medicine, and Pediatrics.","volume":"22","author":"Shuhart","year":"2019","journal-title":"J. Clin. Densitometr."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bone.2014.12.066","article-title":"Deletion of Nrf2 reduces skeletal mechanical properties and decreases load-driven bone formation.","volume":"74","author":"Sun","year":"","journal-title":"Bone"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-015-0212-5","article-title":"Role of Nrf2 in bone metabolism.","volume":"22","author":"Sun","year":"","journal-title":"J. Biomed. Sci."},{"key":"B34","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/S0950-3579(96)80056-2","article-title":"DXA scanning.","volume":"10","author":"Truscott","year":"1996","journal-title":"Baillieres Clin. Rheumatol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"S34","DOI":"10.1542\/peds.2018-0333E","article-title":"Bone Health and Osteoporosis Management of the Patient With Duchenne Muscular Dystrophy.","volume":"142","author":"Ward","year":"2018","journal-title":"Pediatrics"},{"key":"B36","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1111\/cen.13614","article-title":"Bone fragility in Turner syndrome: fracture prevalence and risk factors determined by a national patient survey.","volume":"89","author":"Wasserman","year":"2018","journal-title":"Clin. Endocrinol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.2337\/dc15-0783","article-title":"Type 1 diabetes is associated with an increased risk of fracture across the life span: a population-based cohort study using The Health Improvement Network (THIN).","volume":"38","author":"Weber","year":"2015","journal-title":"Diabetes Care"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1016\/j.jpeds.2012.07.054","article-title":"Racial disparity in fracture risk between white and nonwhite children in the United States.","volume":"161","author":"Wren","year":"2012","journal-title":"J. Pediatr."},{"key":"B39","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.toxlet.2009.08.023","article-title":"Excess iron inhibits osteoblast metabolism.","volume":"191","author":"Yamasaki","year":"2009","journal-title":"Toxicol. Lett."},{"key":"B40","doi-asserted-by":"publisher","first-page":"2328","DOI":"10.1210\/clinem\/dgab302","article-title":"Randomized Controlled Trial Evaluating the Use of Zoledronic Acid in Duchenne Muscular Dystrophy.","volume":"106","author":"Zacharin","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B41","doi-asserted-by":"publisher","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":"B42","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s00198-016-3769-2","article-title":"Biologic therapies and bone loss in rheumatoid arthritis.","volume":"28","author":"Zerbini","year":"2017","journal-title":"Osteopor. Int."}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2022.818750\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T14:11:58Z","timestamp":1647267118000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2022.818750\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,14]]},"references-count":42,"alternative-id":["10.3389\/fnins.2022.818750"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2022.818750","relation":{"has-part":[{"id-type":"doi","id":"https:\/\/doi.org\/10.3389\/fnins.2022.818750.s001","asserted-by":"subject"},{"id-type":"doi","id":"https:\/\/doi.org\/10.3389\/fnins.2022.818750.s002","asserted-by":"subject"}]},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,14]]},"article-number":"818750"}}