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Orphanet J Rare Dis. 2015 Feb 15;10:17. doi: 10.1186/s13023-015-0232-y.

Bone health in phenylketonuria: a systematic review and meta-analysis.

Author information

1
Department of Paediatrics, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. s.demirdas@amc.uva.nl.
2
Nutrition and Health Sciences and Molecules to Mankind Programs, Laney Graduate School and Department of Human Genetics, Emory University, Atlanta, GA, USA. kcoakle@emory.edu.
3
Department of Internal Medicine, Division of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. p.h.bisschop@amc.uva.nl.
4
Department of Internal Medicine, Division of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. c.e.hollak@amc.uva.nl.
5
Department of Paediatrics, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. a.m.bosch@amc.uva.nl.
6
Metabolic Nutrition and Genetics Program Department of Human Genetics, Emory University Atlanta GA United States, Atlanta, GA, USA. rsingh@emory.edu.

Abstract

Patients with Phenylketonuria (PKU) reportedly have decreased bone mineral density (BMD). The primary aim of this study was to perform a systematic review and meta-analysis to determine the extent and significance of low BMD in early treated patients with PKU. Secondary aims were to assess other bone status indicators including bone turnover markers (BTM) and to define areas for future research. Two research teams (Amsterdam, Netherlands and Atlanta, USA) performed literature searches for articles reporting data on BMD, osteopenia and osteoporosis, BTM or other bone indicators in patients with PKU. Included articles were compared between research teams and assessed for quality and risk of bias. A total of 13 unique articles were included; 11/13 articles reported BMD including a total of 360 patients. Ten out of 11 articles found BMD was significantly lower in patients with PKU. Meta-analyses for total BMD (TBMD; 3 studies; n = 133), lumbar spine BMD (LBMD; 7 studies; n = 247), and femoral neck BMD (FBMD; 2 studies; n = 78) Z-scores were performed. Overall effect sizes were: TBMD -0.45 (95% CI -0.61, -0.28); LBMD -0.70 (95% CI -0.82, -0.57); FBMD -0.96 (95% CI -1.42, -0.49). Definitions of osteopenia and osteoporosis were highly heterogeneous between studies and did not align with World Health Organization standards and the International Society for Clinical Densitometry positions on BMD measurement. Despite individual study findings of low BMD indicating higher risk of osteoporosis, pooled available data suggest reduction in BMD is not clinically important when using standard definitions of low BMD. Results from studies evaluating BTM are inconclusive. Phenylalanine concentration, vitamin D, PTH, and nutrient intake do not correlate with BMD or BTM. We recommend forthcoming studies use standard definitions of low BMD to determine clinical implications of BMD Z-scores below 0, explore cause of low BMD in the subset of patients with low BMD for chronological age (Z-score < -2) and assess fracture risk in patients with PKU.

PMID:
25758373
PMCID:
PMC4340652
DOI:
10.1186/s13023-015-0232-y
[Indexed for MEDLINE]
Free PMC Article

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