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.
The authors “Britt van Erven” and “Lindsey Welling” are equal first authors.
The authors “M. Estela Rubio-Gozalbo” and “Annet M. Bosch” are equal first authors.
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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.
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Communicated by: Alberto B. Burlina, MD
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Take-Home Message
It is important that treating physicians are aware that patients with CG are at risk for having or developing low bone mass, warranting appropriate screening and treatment.
Contributions of Individual Authors
Britt van Erven: conception and design, acquisition of data, analysis and interpretation of data, drafting the chapter, revising the chapter critically for important intellectual content.
Lindsey Welling: conception and design, acquisition of data, analysis and interpretation of data, drafting the chapter, revising the chapter critically for important intellectual content.
Sandra C. van Calcar: analysis and interpretation of data, revising the chapter critically for important intellectual content.
Artemis Doulgeraki: acquisition of data, revising the chapter critically for important intellectual content.
François Eyskens: analysis and interpretation of data, revising the chapter critically for important intellectual content.
Joanna Gribben: acquisition of data, revising the chapter critically for important intellectual content.
Eileen P. Treacy: acquisition of data, revising the chapter critically for important intellectual content.
Rein Vos: statistical design, revising the chapter critically for important intellectual content.
Susan E. Waisbren: acquisition of data, revising the chapter critically for important intellectual content.
M. Estela Rubio-Gozalbo: conception and design, analysis and interpretation of data, drafting the chapter, revising the chapter critically for important intellectual content.
Annet M. Bosch: conception and design, analysis and interpretation of data, drafting the chapter, revising the chapter critically for important intellectual content.
All authors read and approved the manuscript before submission.
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M. Estela Rubio-Gozalbo.
Conflict of Interest Statement
Annet M. Bosch is in receipt of research grants from Nutricia and was a member of an advisory board for Nutricia.
Sandra C. van Calcar declares that she has no conflict of interest.
Artemis Doulgeraki declares that she has no conflict of interest.
Britt van Erven declares that she has no conflict of interest.
François Eyskens declares that he has no conflict of interest.
Joanna Gribben declares that she has no conflict of interest.
M. Estela Rubio-Gozalbo declares that she has no conflict of interest.
Eileen P. Treacy declares that she has no conflict of interest.
Rein Vos declares that he has no conflict of interest.
Susan E. Waisbren declares that she has no conflict of interest.
Lindsey Welling declares that she has no conflict of interest.
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van Erven, B. et al. (2017). Bone Health in Classic Galactosemia: Systematic Review and Meta-Analysis. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 35. JIMD Reports, vol 35. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2016_28
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