Hansen Karen E, Ney Denise
Department of Medicine, Division of Rheumatology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA,
J Inherit Metab Dis. 2014 Nov;37(6):875-80. doi: 10.1007/s10545-014-9735-2. Epub 2014 Jul 9.
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.
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.
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.
我们的目的是系统回顾和分析已发表的关于苯丙酮尿症（PKU）患者骨矿物质密度（BMD）和骨折率的数据，以及BMD与苯丙氨酸水平之间的关系。
我们检索了1966年1月至2013年11月期间的PubMed、CINAHL和Cochrane数据库，以查找关于PKU患者和对照受试者脊柱BMD或骨折的研究。我们排除了通过超声或外周定量计算机断层扫描评估骨骼健康的研究。两位作者对摘要进行了纳入审查，并阅读全文以提取数据。
16项研究符合纳入标准。对三项研究的荟萃分析发现，与161名对照相比，67名PKU患者的脊柱BMD低0.100 g/cm²（95%CI，-0.110，-0.090 g/cm²）。在六项研究中，20%（263名中的53名）的PKU受试者发生了临床骨折。在有对照的单项研究中，与健康同胞对照相比，PKU受试者8岁后骨折率高2.6倍（95%CI，1.1-6.1）。在412名受试者的12项研究中，9项（占研究受试者的71%）报告苯丙氨酸水平与BMD之间无关联。PKU患者的脊柱BMD低于对照受试者，但只有一项研究对较小体型进行了校正。现有研究表明PKU受试者的临床骨折率为20%，但缺乏对照的骨折率数据。最后，现有数据显示苯丙氨酸水平与BMD之间没有一致的关系。需要进一步的研究来阐明PKU患者低BMD的病因和健康后果。
