{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T03:50:44Z","timestamp":1784173844864,"version":"3.55.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T00:00:00Z","timestamp":1700438400000},"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":[[2023,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hypophosphatasia (HPP) is an inherited disease caused by variants of the\n                    <jats:italic>ALPL<\/jats:italic>\n                    gene encoding tissue\u2010nonspecific alkaline phosphatase. Adult\u2010onset HPP (adult HPP), known as a mild form of HPP, develops symptoms involving osteomalacia after the age of 18\u2009years. Asfotase alfa (AA) is a modulated recombinant human alkaline phosphatase (ALP) that has been established as a first\u2010line therapy for severe forms of HPP, such as perinatal and infantile forms. We described a 64\u2010year\u2010old female who presented with pseudofractures in bilateral femur diaphyses and impaired mobility. Low serum ALP activity and a high concentration of urine phosphoethanolamine indicated the diagnosis of HPP, which was confirmed by the identification of a homozygous variant in the\n                    <jats:italic>ALPL<\/jats:italic>\n                    gene (c.319G\u2009&gt;\u2009A; p.Val107Ile). An in vitro transfection experiment to measure the ALP activity of this novel variant protein was performed, resulting in 40% of the residual enzymatic activity compared with the wild type. AA was initiated to facilitate the union of pseudofracture and to improve mobility. After 6\u2009months, radiographic images revealed the disappearance of fracture lines, and improvement of ambulatory ability was confirmed by the 6\u2010minute walk test (525 to 606\u2009m). The EQ\u20105D\u20105L index was also improved (0.757 to 0.895). Within a follow\u2010up period, the levels of urine pyrophosphate corrected by urine creatinine (uPPi\/Cre) declined in parallel with the level of plasma PPi (plasma PPi: 6.34 to 1.04\u2009\u03bcM, uPPi\/Cre: 226.8 to 75.4\u2009nmol\/mg). The beneficial effect of AA on pseudofracture healing in adult HPP was presented, although the application of AA should be restricted to patients exhibiting relatively severe manifestations. In addition, a novel pathogenic variant of the\n                    <jats:italic>ALPL<\/jats:italic>\n                    gene was identified with the supportive result of functional analysis. Furthermore, when monitoring patients with HPP treated with AA, uPPi\/Cre might be a convenient substitute for plasma PPi, which requires immediate filtration after blood sampling. \u00a9 2023 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\/jbm4.10842","type":"journal-article","created":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T13:48:24Z","timestamp":1700660904000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Effect of Asfotase Alfa on Plasma and Urine Pyrophosphate Levels and Pseudofractures in a Patient With Adult\u2010Onset Hypophosphatasia"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5450-2247","authenticated-orcid":false,"given":"Naoko","family":"Hidaka","sequence":"first","affiliation":[{"name":"Division of Nephrology and Endocrinology The University of Tokyo Hospital  Tokyo Japan"},{"name":"Osteoporosis Center The University of Tokyo Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Murata","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Panasonic Health Insurance Organization Matsushita Memorial Hospital  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanako","family":"Tachikawa","sequence":"additional","affiliation":[{"name":"Department of Bone and Mineral Research, Research Institute Osaka Women's and Children's Hospital  Osaka 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