{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T08:48:25Z","timestamp":1788425305977,"version":"build-2803163510"},"reference-count":24,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,7,9]],"date-time":"2014-07-09T00:00:00Z","timestamp":1404864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methodology<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixteen studies met eligibility criteria. Meta\u2010analysis of three studies found that spine BMD was 0.100 g\/cm<jats:sup>2<\/jats:sup> lower (95% CI, \u20100.110, \u20100.090 g\/cm<jats:sup>2<\/jats:sup>) 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\u20106.1) 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Summary<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s10545-014-9735-2","type":"journal-article","created":{"date-parts":[[2014,7,8]],"date-time":"2014-07-08T11:13:48Z","timestamp":1404818028000},"page":"875-880","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["A systematic review of bone mineral density and fractures in phenylketonuria"],"prefix":"10.1002","volume":"37","author":[{"given":"Karen E.","family":"Hansen","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Rheumatology University of Wisconsin School of Medicine and Public Health Madison WI USA"},{"name":"Rheumatology Division University of Wisconsin School of Medicine &amp; Public Health Room 4124 MFCB, 1685 Highland Avenue Madison WI 53705\u20102281 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Ney","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences College of Agricultural &amp; Life Sciences Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,7,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-010-0216-x"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/59.2.419"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1998.tb00924.x"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-002-1091-9"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(53)90473-5"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02129064"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2012.01.006"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1515\/bchm2.1934.227.1-4.169"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocd.2007.12.005"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1997.tb08882.x"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7414.557"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00014234"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.5114\/aoms.2011.23417"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-010-9189-0"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/55.5.997"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2005.09.002"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-007-0462-9"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-151-4-200908180-00135"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2002.tb02852.x"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ultrasmedbio.2007.12.013"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e3182093b32"},{"key":"e_1_2_11_23_1","volume-title":"R: A language and environment for statistical computing","year":"2008"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2013.157"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocd.2012.01.004"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-014-9735-2","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T06:30:43Z","timestamp":1694759443000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-014-9735-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7,9]]},"references-count":24,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2014,11]]}},"alternative-id":["10.1007\/s10545-014-9735-2"],"URL":"https:\/\/doi.org\/10.1007\/s10545-014-9735-2","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7,9]]}}}