{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T22:33:24Z","timestamp":1762900404784,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,4]],"date-time":"2022-12-04T00:00:00Z","timestamp":1670112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>In advanced Rett syndrome (RTT), limited or complete loss of ambulation, nutritional problems and scoliosis are unfavorable factors for bone mineral density (BMD). Still, there are few data available in this research area. Spinal quantitative computed tomography (QCT) allows an exact measurement of the volumetric BMD (vBMD) in this patient group. Two examiners measured vBMD of thoracic and lumbar vertebrae on asynchronous calibrated CTs that were acquired prior to surgical scoliosis correction (n = 21, age 13.6 \u00b1 2.5 years). The values were compared to age- and sex-matched healthy controls to additionally derive Z-scores (n = 22, age 13.8 \u00b1 2.0 years). The results showed the most significant reduction of vBMD values in non-ambulatory RTT patients, with p &lt; 0.001 and average BMD-Z-score \u22121.5 \u00b1 0.2. In the subgroup comparison, non-ambulatory patients with valproate treatment had significant lower values (p &lt; 0.001) than ambulatory patients without valproate therapy, with an average BMD-Z-score of \u22122.3 \u00b1 0.2. Comparison of the Z-scores to critical BMD thresholds of 120 and 80 mg\/cm3 showed normal Z-scores in case of the ambulatory RTT subgroup, as opposed to BMD-Z-scores of the non-ambulatory RTT subgroups, which were partially below osteopenia-equivalent values. Furthermore, valproate treatment seems to have a direct effect on vBMD in RTT patients and when combined with loss of ambulation, BMD-Z-scores are reduced to osteoporosis-equivalent levels or even further.<\/jats:p>","DOI":"10.3390\/children9121902","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T02:56:26Z","timestamp":1670208986000},"page":"1902","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Reduced Volumetric Bone Mineral Density of the Spine in Adolescent Rett Girls with Scoliosis"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7102-5892","authenticated-orcid":false,"given":"Konstantinos","family":"Tsaknakis","sequence":"first","affiliation":[{"name":"Paediatric Orthopaedics, Department of Trauma, Orthopaedic and Plastic Surgery, University Medical Center, 37077 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan H.","family":"Kreuzer","sequence":"additional","affiliation":[{"name":"Paediatric Orthopaedics, Department of Trauma, Orthopaedic and Plastic Surgery, University Medical Center, 37077 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Friederike Luise","family":"Metzger","sequence":"additional","affiliation":[{"name":"Paediatric Orthopaedics, Department of Trauma, Orthopaedic and Plastic Surgery, University Medical Center, 37077 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3086-4278","authenticated-orcid":false,"given":"Katharina","family":"J\u00e4ckle","sequence":"additional","affiliation":[{"name":"Paediatric Orthopaedics, Department of Trauma, Orthopaedic and Plastic Surgery, University Medical Center, 37077 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katja A.","family":"L\u00fcders","sequence":"additional","affiliation":[{"name":"Paediatric Orthopaedics, Department of Trauma, Orthopaedic and Plastic Surgery, University Medical Center, 37077 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5178-826X","authenticated-orcid":false,"given":"Lena","family":"Braunschweig","sequence":"additional","affiliation":[{"name":"Paediatric Orthopaedics, Department of Trauma, Orthopaedic and Plastic Surgery, University Medical Center, 37077 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heiko M.","family":"Lorenz","sequence":"additional","affiliation":[{"name":"Paediatric Orthopaedics, Department of Trauma, Orthopaedic and Plastic Surgery, University Medical Center, 37077 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6655-7130","authenticated-orcid":false,"given":"Anna K.","family":"Hell","sequence":"additional","affiliation":[{"name":"Paediatric Orthopaedics, Department of Trauma, Orthopaedic and Plastic Surgery, University Medical Center, 37077 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1002\/ana.22124","article-title":"Rett Syndrome: Revised Diagnostic Criteria and Nomenclature","volume":"68","author":"Neul","year":"2010","journal-title":"Ann. Neurol."},{"key":"ref_2","unstructured":"(2022, October 15). Online Mendelian Inheritance in Man\u2014Rett Syndrome. Available online: https:\/\/www.omim.org\/entry\/312750."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/13810","article-title":"Rett Syndrome Is Caused by Mutations in X-Linked MECP2, Encoding Methyl-CpG-Binding Protein 2","volume":"23","author":"Amir","year":"1999","journal-title":"Nat. Genet"},{"key":"ref_4","first-page":"723","article-title":"On a unusual brain atrophy syndrome in hyperammonemia in childhood","volume":"116","author":"Rett","year":"1966","journal-title":"Wien Med. Wochenschr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1007\/s10354-016-0492-8","article-title":"On a Remarkable Syndrome of Cerebral Atrophy Associated with Hyperammonaemia in Childhood","volume":"166","author":"Rett","year":"2016","journal-title":"Wien Med. Wochenschr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1053\/ejpn.2002.0612","article-title":"An Update on Clinically Applicable Diagnostic Criteria in Rett Syndrome","volume":"6","author":"Hagberg","year":"2002","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_7","unstructured":"(2022, October 15). What Are the Types & Phases of Rett Syndrome?, Available online: https:\/\/www.nichd.nih.gov\/health\/topics\/rett\/conditioninfo\/types."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1203\/01.PDR.0000155945.94249.0A","article-title":"Is the Early Development of Girls with Rett Disorder Really Normal?","volume":"57","author":"Einspieler","year":"2005","journal-title":"Pediatr. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.pediatrneurol.2017.01.032","article-title":"Scoliosis in Rett Syndrome: Progression, Comorbidities, and Predictors","volume":"70","author":"Killian","year":"2017","journal-title":"Pediatr. Neurol."},{"key":"ref_10","unstructured":"(2022, October 15). 2019 ISCD Official Positions Pediatric. Available online: https:\/\/iscd.org\/learn\/official-positions\/pediatric-positions\/."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1203\/PDR.0b013e318180ebcd","article-title":"Bone Mineral Content and Bone Mineral Density Are Lower in Older Than in Younger Females with Rett Syndrome","volume":"64","author":"Motil","year":"2008","journal-title":"Pediatr. Res."},{"key":"ref_12","first-page":"446","article-title":"Bone Mass in Rett Syndrome: Association with Clinical Parameters and MECP2 Mutations","volume":"68","author":"Shapiro","year":"2010","journal-title":"Pediatr. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/8756-3282(85)90399-0","article-title":"Quantitative Computed Tomography for Prediction of Vertebral Fracture Risk","volume":"6","author":"Cann","year":"1985","journal-title":"Bone"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1148\/radiology.166.2.3275985","article-title":"Quantitative CT for Determination of Bone Mineral Density: A Review","volume":"166","author":"Cann","year":"1988","journal-title":"Radiology"},{"key":"ref_15","first-page":"380","article-title":"Quantitative Spinal Mineral Analysis in Children","volume":"29","author":"Gilsanz","year":"1986","journal-title":"Ann. Radiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1148\/radiology.166.3.3340782","article-title":"Vertebral Bone Density in Children: Effect of Puberty","volume":"166","author":"Gilsanz","year":"1988","journal-title":"Radiology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1002\/jbmr.5650040218","article-title":"Models of Spinal Trabecular Bone Loss as Determined by Quantitative Computed Tomography","volume":"4","author":"Block","year":"1989","journal-title":"J. Bone Min. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.2214\/AJR.06.1006","article-title":"Volumetric Quantitative CT of the Spine and Hip Derived from Contrast-Enhanced MDCT: Conversion Factors","volume":"188","author":"Bauer","year":"2007","journal-title":"Am. J. Roentgenol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s12018-009-9064-4","article-title":"T-Scores and Z-Scores","volume":"8","author":"Carey","year":"2010","journal-title":"Clin. Rev. Bone Min. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1210\/jc.2009-2057","article-title":"Height Adjustment in Assessing Dual Energy X-Ray Absorptiometry Measurements of Bone Mass and Density in Children","volume":"95","author":"Zemel","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_21","unstructured":"The American College of Radiology (2018). ACR\u2013SPR\u2013SSR Practice Guideline for the Performance of Quantitative Computed Tomography (QCT) Bone, The American College of Radiology."},{"key":"ref_22","first-page":"261","article-title":"Outlines for the Study of Scoliosis","volume":"5","author":"Cobb","year":"1948","journal-title":"J. Bone Jt. Surg. Am. Vol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1007\/s001120170107","article-title":"Perzentile f\u00fcr den Body-mass-Index f\u00fcr das Kindes- und Jugendalter unter Heranziehung verschiedener deutscher Stichproben","volume":"149","author":"Wabitsch","year":"2001","journal-title":"Mon. Kinderheilkd."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Writing Group for the ISCD Position Development Conference (2004). Nomenclature and Decimal Places in Bone Densitometry. J. Clin. Densitom., 7, 45\u201350.","DOI":"10.1385\/JCD:7:1:45"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S189","DOI":"10.1016\/j.jacr.2017.02.018","article-title":"ACR Appropriateness Criteria \u00ae Osteoporosis and Bone Mineral Density","volume":"14","author":"Ward","year":"2017","journal-title":"J. Am. Coll. Radiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1203\/PDR.0b013e31820bc6d3","article-title":"Patients with Rett Syndrome Sustain Low-Energy Fractures","volume":"69","author":"Roende","year":"2011","journal-title":"Pediatr. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1136\/adc.2008.148932","article-title":"Valproate and Risk of Fracture in Rett Syndrome","volume":"95","author":"Leonard","year":"2010","journal-title":"Arch. Dis. Child."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1046\/j.1528-1157.2001.416800.x","article-title":"Long-Term Valproate and Lamotrigine Treatment May Be a Marker for Reduced Growth and Bone Mass in Children with Epilepsy","volume":"42","author":"Guo","year":"2002","journal-title":"Epilepsia"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jns.2009.12.015","article-title":"Effect of Long-Term Valproate Monotherapy on Bone Mineral Density in Adults with Epilepsy","volume":"290","author":"Triantafyllou","year":"2010","journal-title":"J. Neurol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.ejps.2014.05.018","article-title":"Raloxifene Preserves Phenytoin and Sodium Valproate Induced Bone Loss by Modulating Serum Estradiol and TGF-\u03923 Content in Bone of Female Mice","volume":"62","author":"Anwar","year":"2014","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_31","unstructured":"Weltgesundheitsorganisation (2003). Prevention and Management of Osteoporosis: Report of a WHO Scientific Group, World Health Organization. WHO Scientific Group Meeting on Prevention and Management of Osteoporosis, Geneva, 7\u201310 April."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"19691","DOI":"10.1002\/jcp.28569","article-title":"Differential Effects of Antiepileptic Drugs on Human Bone Cells","volume":"234","author":"Rocha","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1000031","DOI":"10.3389\/fsurg.2022.1000031","article-title":"Hounsfield Unit for Assessing Asymmetrical Loss of Vertebral Bone Mineral Density and Its Correlation with Curve Severity in Adolescent Idiopathic Scoliosis","volume":"9","author":"Cheng","year":"2022","journal-title":"Front. Surg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1007\/s00198-022-06416-9","article-title":"Reduced Bone Mineral Density in Adolescents with Duchenne Muscular Dystrophy (DMD) and Scoliosis","volume":"33","author":"Tsaknakis","year":"2022","journal-title":"Osteoporos. Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e0186941","DOI":"10.1371\/journal.pone.0186941","article-title":"Lower Incidence of Fracture after IV Bisphosphonates in Girls with Rett Syndrome and Severe Bone Fragility","volume":"12","author":"Lambert","year":"2017","journal-title":"PLoS ONE"}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/9\/12\/1902\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:33:45Z","timestamp":1760146425000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/9\/12\/1902"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,4]]},"references-count":35,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["children9121902"],"URL":"https:\/\/doi.org\/10.3390\/children9121902","relation":{},"ISSN":["2227-9067"],"issn-type":[{"type":"electronic","value":"2227-9067"}],"subject":[],"published":{"date-parts":[[2022,12,4]]}}}