成人生酮饮食治疗苯丙酮尿症患者的骨密度 meta 分析

Meta-analysis of bone mineral density in adults with phenylketonuria.

机构信息

NOVA Medical School/Faculdade de Ciências Médicas (NMS/FCM), Universidade NOVA de Lisboa, Lisboa, Portugal.

Reference Centre of Inherited Metabolic Diseases (RC-IMD), Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal.

出版信息

Orphanet J Rare Dis. 2024 Sep 12;19(1):338. doi: 10.1186/s13023-024-03223-9.

DOI:10.1186/s13023-024-03223-9

PMID:39267130

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11391789/

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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, n = 304), -0.63 (95% confidence interval (CI): -0.74, -0.52); femoral neck (four studies, n = 170), -0.74 (95% CI: -1.25, -0.22); radius (three studies, n = 114), -0.77 (95% CI: -1.21, -0.32); total body (four studies, n = 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, n = 221) and < -1.0 was 42% (95% CI: 35%, 51%; five studies, n = 144).

CONCLUSIONS

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. This meta-analysis was supported by BioMarin Pharmaceutical Inc., Novato, CA and is registered with the Research Registry (reviewregistry1476).

摘要

背景

苯丙酮尿症（PKU）的终身管理侧重于医学营养疗法，包括饮食苯丙氨酸（Phe）限制，以及无 Phe 或低 Phe 医学食品/蛋白质替代品。研究报告称，混合年龄 PKU 人群的骨矿物质密度（BMD）较低，可能与长期 Phe 限制有关。因此，进行了一项专门针对 PKU 成人 BMD 的荟萃分析。

方法

从系统文献综述中确定了报告 BMD 相关结果的研究，该综述评估了接受 Phe 限制饮食的 PKU 成人的躯体共病（于 2022 年 2 月 1 日搜索，更新于 2023 年 11 月 1 日）。评估了研究偏倚的风险（苏格兰校际指南网络清单）。荟萃分析的主要结果是不同骨骼的平均 BMD Z 分数的汇总。次要结果是在预定阈值下低 BMD Z 分数的患病率。对平均 BMD Z 分数的亚组分析（研究发表的十年、控制与未控制的血液 Phe 水平、性别）进行了分析。

结果

纳入了 10 项研究中来自 4097 名个体的 BMD 相关数据，这些研究的质量被评为至少为可接受的质量。与年龄匹配的对照或参考（非 PKU）人群相比，各骨骼的平均 BMD Z 分数明显较低，但仍在年龄预期范围内（> -2.0）：腰椎（7 项研究，n = 304），-0.63（95%置信区间[CI]：-0.74，-0.52）；股骨颈（4 项研究，n = 170），-0.74（95% CI：-1.25，-0.22）；桡骨（3 项研究，n = 114），-0.77（95% CI：-1.21，-0.32）；全身（4 项研究，n = 157），-0.61（95% CI：-0.77，-0.45）。亚组分析中的观察数量较少导致高度不确定性，限制了解释。BMD Z 分数≤-2.0 的估计患病率为 8%（95% CI：5%，13%；4 项研究，n = 221），< -1.0 的估计患病率为 42%（95% CI：35%，51%；5 项研究，n = 144）。

结论

PKU 成人的 BMD Z 分数低于参考（非 PKU）人群，但低于预期年龄的人数不足十分之一。研究数量较少，无法确定哪些人群特征对 BMD 的影响最大。这项荟萃分析得到了美国生物梅里安制药公司（BioMarin Pharmaceutical Inc.）的支持，该公司位于加利福尼亚州纳托马。并已在 Research Registry（reviewregistry1476）上注册。