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Meta-Analysis
. 2014 Nov;37(6):875-80.
doi: 10.1007/s10545-014-9735-2. Epub 2014 Jul 9.

A systematic review of bone mineral density and fractures in phenylketonuria

Karen E Hansen  1 , Denise Ney
Affiliations
Meta-Analysis

A systematic review of bone mineral density and fractures in phenylketonuria

Karen E Hansen et al. J Inherit Metab Dis. 2014 Nov.

Abstract

Introduction: Our objective was to systematically review and analyze published data on bone mineral density (BMD) and fracture rates in patients with phenylketonuria (PKU), and relationships between BMD and phenylalanine levels.

Methodology: We searched PubMed, CINAHL, and Cochrane databases from January 1966 to November 2013 for studies of spine BMD or fracture in PKU and control subjects. We excluded studies assessing skeletal health by ultrasound or peripheral quantitative computer tomography. Both authors reviewed abstracts for inclusion, and read full text papers to extract data.

Results: Sixteen studies met eligibility criteria. Meta-analysis of three studies found that spine BMD was 0.100 g/cm(2) lower (95% CI, -0.110, -0.090 g/cm(2)) in 67 subjects with PKU, compared to 161 controls. Among six studies, 20% (53 of 263) of PKU subjects experienced clinical fractures. In the single study with controls, the fracture rate was 2.6 fold higher (95% CI, 1.1-6.1) after age 8 in PKU subjects, compared to healthy sibling controls. When considering a total of 12 studies in 412 subjects, nine or 75% of studies representing 71% of studied subjects reported no association between phenylalanine levels and BMD. Spine BMD is lower in PKU than control subjects, but only one study controlled for smaller body size. Existing studies suggest a clinical fracture rate of 20% among PKU subjects, but fracture rates in controls are lacking. Finally, existing data shows no consistent relationship between phenylalanine levels and BMD. Future studies are needed to clarify the etiology and health consequences of low BMD in PKU.

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Conflict of interest statement

Conflicts of Interest:

Karen Hansen is a consultant to Takeda Pharmaceuticals and Deltanoid Pharmaceuticals.

Denise Ney is a co-inventor on US Patent 8,604,168 B2, Glycomacropeptide Medical Foods for Nutritional Management of Phenylketonuria and other Metabolic Disorders, held by the Wisconsin Alumni Research Foundation and licensed to Cambrooke Therapeutics, LLC.

Figures

Figure 1
Figure 1. Summary of Literature Review
Three spine bone mineral density and two fracture studies also reported phenylalanine levels.
Figure 2
Figure 2. Spine Bone Mineral Density in Subjects with and without PKU
Figure 2
Figure 2. Spine Bone Mineral Density in Subjects with and without PKU
Figure 3
Figure 3
Height in Subjects with and without PKU
Figure 3
Figure 3
Height in Subjects with and without PKU
See this image and copyright information in PMC

References

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    1. Allen JR, Humphries IR, Waters DL, et al. Decreased bone mineral density in children with phenylketonuria. Am J Clin Nutr. 1994;59(2):419–422. - PubMed
    1. Allen JR, Humphries IR, Waters DL, et al. Decreased bone mineral density in children with phenylketonuria. The American journal of clinical nutrition. 1994;59(2):419–422. - PubMed

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