{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:14:17Z","timestamp":1791429257072,"version":"4.3.3"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T00:00:00Z","timestamp":1617321600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JBMR Plus"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hypophosphatasia (HPP) is caused by loss\u2010of\u2010function mutations in\n                    <jats:italic>ALPL<\/jats:italic>\n                    resulting in decreased alkaline phosphatase (ALP) activity. Metatarsal stress fracture (MSF) is a common clinical feature of hypophosphatasia in adults. In this study, the primary objectives were to determine whether new cases of\n                    <jats:italic>ALPL<\/jats:italic>\n                    variants could be identified in patients with MSF and who also had serum ALP concentration below the reference range and to phenotype their clinical course. Electronic health records were queried for adult patients with MSF using International Classification of Disease codes (ICD\u20109, ICD\u201010CM) and ALP measurements. Patients with ALP levels below the normal limit were invited to receive mutational analysis of\n                    <jats:italic>ALPL<\/jats:italic>\n                    and to complete the following surveys: the Short Form 36 version 2 (SF36v2), the Brief Pain Inventory\u2010Short Form (BPI), and the Health Assessment Questionnaire Disability Index (HAQ\u2010DI). Cases with and controls without\n                    <jats:italic>ALPL<\/jats:italic>\n                    pathogenic variants were compared by survey scores and clinical variables relevant to fracture. In 1611 patients with MSF presenting to a podiatry clinic (10\/1\/2011\u201310\/1\/2017), 937 had ALP measurement, of whom 13 (1.4%) had ALP levels below the lower normal limit. In eight patients consenting to participate, two had heterozygous pathogenic\n                    <jats:italic>ALPL<\/jats:italic>\n                    variants.\n                    <jats:italic>ALPL<\/jats:italic>\n                    variants were found in 2 of 1611 patients (0.12%) with MSF, 2 patients of 937 (0.21%) in those with MSF and any ALP measurement, and 2 of 13 patients (15%) in MSF and decreased ALP level. Cases versus controls rated lower scores on eight of eight SF36v2 scales (range, 0\u2013100); higher scores for worst pain (8.0 vs. 0.8) and average pain (6.0 vs. 0.7) on the BPI (range, 0\u201310); and higher standard disability score (1.4 vs. 0) on the HAQ\u2010DI (range, 0\u20133). These data provide proof\u2010of\u2010concept for HPP case identification in patients presenting to a podiatry clinic with MSF, suggesting a search for historically low ALP levels may be a useful step for consideration of HPP diagnosis, and supports a prospective study to determine an optimal case\u2010finding strategy. \u00a9 2021 The Authors.\n                    <jats:italic>JBMR Plus<\/jats:italic>\n                    published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.\n                  <\/jats:p>","DOI":"10.1002\/jbm4.10495","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T12:25:08Z","timestamp":1616415908000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Diagnosis of Hypophosphatasia in Adults Presenting With Metatarsal Stress Fracture: Proof\u2010of\u2010Concept for a Case\u2010Finding Strategy"],"prefix":"10.1093","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8358-6988","authenticated-orcid":false,"given":"Kenna","family":"Koehler","sequence":"first","affiliation":[{"name":"Ohio State University College of Medicine  Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Said","family":"Atway","sequence":"additional","affiliation":[{"name":"Division of Podiatry Ohio State University Wexner Medical Center  Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Pipes","sequence":"additional","affiliation":[{"name":"Division of Podiatry Ohio State University Wexner Medical Center  Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4343-6723","authenticated-orcid":false,"given":"Steven","family":"Ing","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism Ohio State University Wexner Medical Center  Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,4,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpedi.1948.02030020840003"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.14"},{"key":"e_1_2_9_4_1","unstructured":"http:\/\/www.sesep.uvsq.fr\/03_hypo_mutations.php. [7 August 2020]."},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2010.05387.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2013.01.024"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000286"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.4158\/EP.12.6.676"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bonr.2015.10.005"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2015-212827"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.2011.00642.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2178"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1565"},{"key":"e_1_2_9_14_1","volume-title":"The Brief Pain Inventory User Guide","author":"Cleeland CS","year":"2009"},{"key":"e_1_2_9_15_1","unstructured":"Wolfe F. A brief clinical health assessment instrument: CLINHAQ. Arthritis Rheum.1989;32(suppl):S9."},{"key":"e_1_2_9_16_1","first-page":"227","volume-title":"Quality of Life and Pharmacoeconomics in Clinical Trials","author":"Ramey D","year":"1996"},{"key":"e_1_2_9_17_1","volume-title":"How to Score Version 2 of the SF\u201036 Health Survey (Standard & Acute Forms)","author":"Ware ME","year":"2001"},{"key":"e_1_2_9_18_1","volume-title":"User's Manual for the SF\u201012v2TM Health Survey (with a Supplement Documenting SF\u201012 Health Survey)","author":"Ware JE","year":"2007"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-019-00991-4"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4130"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-009-9012-y"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1154"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.2001.3283"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-10-51"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-1902"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-1965"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-1168"},{"key":"e_1_2_9_28_1","first-page":"40","article-title":"Evaluation of serum alkaline phosphatase as a biomarker of healing process progression of simple diaphyseal fractures in adult patients","volume":"2","author":"Ajai S","year":"2013","journal-title":"Int Res J Biol Sci."},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2015.12.019"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112031"}],"container-title":["JBMR Plus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm4.10495","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbm4.10495","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm4.10495","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T09:56:09Z","timestamp":1710410169000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmrplus\/article\/7486284"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,2]]},"references-count":29,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1002\/jbm4.10495"],"URL":"https:\/\/doi.org\/10.1002\/jbm4.10495","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/JBM4.10495\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10495\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10495\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10495\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10495\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10495\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10495\/v2\/response1","asserted-by":"object"}]},"ISSN":["2473-4039","2473-4039"],"issn-type":[{"value":"2473-4039","type":"print"},{"value":"2473-4039","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,2]]},"assertion":[{"value":"2020-11-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e10495"}}