title: Bone Health in Classic Galactosemia: Systematic Review and Meta-Analysis.
abstract: BACKGROUND
  Previous studies have reported an association between classic galactosemia (CG) and decreased bone mass. The primary objective of this systematic review with meta-analysis was to determine the extent of bone mineral density (BMD) Z-score reduction. Low BMD was defined as a Z-score ≤-2 standard deviations (SD). The secondary objective was to evaluate other indicators of bone status through a descriptive analysis.
  
  
  METHODS
  Systematic search strategies were developed by an experienced clinical librarian. Selection of relevant manuscripts, risk of bias assessment, and data extraction were performed independently by two investigators.
  
  
  RESULTS
  Four studies were included in the meta-analysis. BMD Z-scores in children and adults with CG measured at the lumbar spine (LBMD; 4 studies; n  = 112), total hip (HBMD; 2 studies; n = 58), and femoral neck (FBMD; 2 studies; n = 73) were assessed. Mean BMD Z-scores in the CG population were LBMD -0.70 (95% CI: -0.88, -0.52); HBMD -0.89 (95% CI: -1.14, -0.64); and FBMD -0.63 (95% CI -1.29, 0.02). Results from studies included in the descriptive analysis (n = 7) show that vitamin D levels were frequently in the low reference range, whereas serum calcium levels were within reference range.
  
  
  CONCLUSIONS
  The mean BMD Z-score in the CG population is -0.7, which is lower than in the general population, though still within two SD of the reference mean of zero. This indicates that bone health is mildly affected in CG and that more patients, compared to the general population, are at risk for a BMD Z-score ≤-2 SD. In conclusion, clinicians should ensure appropriate preventive and therapeutic measures for CG patients.
authors.affiliation: Department of Pediatrics and Department of Clinical Genetics, Maastricht University Medical Center, PO Box 5800, 6202, Maastricht, The Netherlands.
authors.forename: Britt
authors.initials: B
authors.lastname: van Erven
authors.affiliation: Department of Pediatrics, Academic Medical Center, Emma Children's Hospital, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Welling
authors.affiliation: Department of Molecular and Medical Genetics, School of Medicine, Oregon Health and Science University, Portland, Oregon, USA.
authors.forename: Sandra C
authors.initials: SC
authors.lastname: van Calcar
authors.affiliation: Department of Bone and Mineral Metabolism, Institute of Child Health, Agia Sophia Children's Hospital, Athens, Greece.
authors.forename: Artemis
authors.initials: A
authors.lastname: Doulgeraki
authors.affiliation: Department of Metabolic Disorders in Children, Antwerp University Hospital UZA, Edegem, Belgium.|Center of Inherited Metabolic Diseases, Metabolic Lab PCMA, Wilrijk, Belgium.
authors.forename: François
authors.initials: F
authors.lastname: Eyskens
authors.affiliation: Nutrition & Dietetics Department, Guy's & St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Gribben
authors.affiliation: Mater Misericordiae University Hospital, Trinity College Dublin, Dublin, Ireland.|University College Dublin, Dublin, Ireland.
authors.forename: Eileen P
authors.initials: EP
authors.lastname: Treacy
authors.affiliation: Department of Methodology and Statistics, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.|CAPHRI School for Public Health and Primary Care, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Rein
authors.initials: R
authors.lastname: Vos
authors.affiliation: Division of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Waisbren
authors.affiliation: Department of Pediatrics and Department of Clinical Genetics, Maastricht University Medical Center, PO Box 5800, 6202, Maastricht, The Netherlands. estela.rubio@mumc.nl.
authors.forename: M Estela
authors.initials: ME
authors.lastname: Rubio-Gozalbo
authors.affiliation: Department of Pediatrics, Academic Medical Center, Emma Children's Hospital, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Annet M
authors.initials: AM
authors.lastname: Bosch
keywords: Bone mass; Bone mineral density; Bone turnover markers; Classic galactosemia; DXA; GALT deficiency; Vitamin D