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1000
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Abstract/Summary
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<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Lifelong management of phenylketonuria (PKU) centers on medical nutrition therapy, including dietary phenylalanine (Phe) restriction in addition to Phe-free or low-Phe medical foods/protein substitutes. Studies have reported low bone mineral density (BMD) in mixed-age PKU populations, possibly related to long-term Phe restriction. Therefore, a meta-analysis investigating BMD specifically in adults with PKU was conducted.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Studies reporting BMD-related outcomes were identified from a systematic literature review evaluating somatic comorbidities experienced by adults with PKU on a Phe-restricted diet (searched February 1, 2022, updated November 1, 2023). Risk of study bias was assessed (Scottish Intercollegiate Guidelines Network checklists). The primary outcome of the meta-analysis was pooled mean BMD Z-scores of different bones. Secondary outcomes were the prevalence of low BMD Z-scores at pre-specified thresholds. Subgroup analyses of mean BMD Z-scores (decade of study publication, controlled versus uncontrolled blood Phe levels, gender) were conducted.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>BMD-related data from 4097 individuals across 10 studies rated as at least acceptable quality were included. Mean BMD Z-scores were statistically significantly lower compared with an age-matched control or reference (non-PKU) population, across bones, but still within the expected range for age (> -2.0): lumbar spine (seven studies,<jats:italic>n</jats:italic> = 304), -0.63 (95% confidence interval (CI): -0.74, -0.52); femoral neck (four studies,<jats:italic>n</jats:italic> = 170), -0.74 (95% CI: -1.25, -0.22); radius (three studies,<jats:italic>n</jats:italic> = 114), -0.77 (95% CI: -1.21, -0.32); total body (four studies,<jats:italic>n</jats:italic> = 157), -0.61 (95% CI: -0.77, -0.45). The small number of observations in the subgroup analyses resulted in a high degree of uncertainty, limiting interpretation. Estimated prevalence of BMD Z-scores ≤ -2.0 was 8% (95% CI: 5%, 13%; four studies,<jats:italic>n</jats:italic> = 221) and < -1.0 was 42% (95% CI: 35%, 51%; five studies,<jats:italic>n</jats:italic> = 144).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Adults with PKU had lower BMD Z-scores than the reference (non-PKU) population but < 1 in 10 were below the expected range for age. The low number of studies prevents identification of which population characteristics are most impacting BMD.</jats:p><jats:p>This meta-analysis was supported by BioMarin Pharmaceutical Inc., Novato, CA and is registered with the Research Registry (reviewregistry1476).</jats:p></jats:sec>
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