Bone Health in Classic Galactosemia: Systematic Review and Meta-Analysis

  • Britt van Erven
  • Lindsey Welling
  • Sandra C. van Calcar
  • Artemis Doulgeraki
  • François Eyskens
  • Joanna Gribben
  • Eileen P. Treacy
  • Rein Vos
  • Susan E. Waisbren
  • M. Estela Rubio-Gozalbo
  • Annet M. Bosch
Research Report
First Online:
Received:
Revised:
Accepted:
Part of the JIMD Reports book series (JIMD, volume 35)

Abstract

Introduction: 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.

Conclusion: 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.

Keywords

Bone mass Bone mineral density Bone turnover markers Classic galactosemia DXA GALT deficiency Vitamin D 
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Notes

Acknowledgements

The authors would like to thank the clinical librarian A.G.E. Leenders (Academic Medical Center, Amsterdam, the Netherlands) for developing the search strategies for this review, as well as Dr. M.J. van Kroonenburgh (Maastricht University Medical Center, Department of Nuclear Medicine) for answering queries on the technical aspects of bone mass evaluation.

Supplementary material

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Copyright information

© Society for the Study of Inborn Errors of Metabolism (SSIEM) 2017

Authors and Affiliations

  • Britt van Erven
    • 1
  • Lindsey Welling
    • 2
  • Sandra C. van Calcar
    • 3
  • Artemis Doulgeraki
    • 4
  • François Eyskens
    • 5
    • 6
  • Joanna Gribben
    • 7
  • Eileen P. Treacy
    • 8
    • 9
  • Rein Vos
    • 10
    • 11
  • Susan E. Waisbren
    • 12
  • M. Estela Rubio-Gozalbo
    • 1
  • Annet M. Bosch
    • 2
  1. 1.Department of Pediatrics and Department of Clinical GeneticsMaastricht University Medical CenterMaastrichtThe Netherlands
  2. 2.Department of PediatricsAcademic Medical Center, Emma Children’s Hospital, University of AmsterdamAmsterdamThe Netherlands
  3. 3.Department of Molecular and Medical GeneticsSchool of Medicine, Oregon Health and Science UniversityOregonUSA
  4. 4.Department of Bone and Mineral MetabolismInstitute of Child Health, Agia Sophia Children’s HospitalAthensGreece
  5. 5.Department of Metabolic Disorders in ChildrenAntwerp University Hospital UZAEdegemBelgium
  6. 6.Center of Inherited Metabolic Diseases, Metabolic Lab PCMAWilrijkBelgium
  7. 7.Nutrition & Dietetics DepartmentGuy’s & St. Thomas’ NHS Foundation TrustLondonUK
  8. 8.Mater Misericordiae University Hospital, Trinity College DublinDublinIreland
  9. 9.University College DublinDublinIreland
  10. 10.Department of Methodology and Statistics, Faculty of Health, Medicine and Life SciencesMaastricht UniversityMaastrichtThe Netherlands
  11. 11.CAPHRI School for Public Health and Primary Care, Maastricht University Medical CenterMaastrichtThe Netherlands
  12. 12.Division of Genetics and GenomicsBoston Children’s Hospital and Harvard Medical SchoolBostonUSA

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