{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T19:44:06Z","timestamp":1775936646664,"version":"3.50.1"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2013,10,4]],"date-time":"2013-10-04T00:00:00Z","timestamp":1380844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,4,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Hypophosphatasia (HPP) is the inborn error of metabolism that features low serum alkaline phosphatase (ALP) activity caused by loss-of-function mutation(s) within the gene for the tissue nonspecific isoenzyme of ALP (TNSALP). In HPP, extracellular accumulation of inorganic pyrophosphate (PPi), a TNSALP substrate and inhibitor of mineralization, leads frequently to premature tooth loss and often to rickets or osteomalacia. In affected adults, the excess PPi sometimes also causes calcium pyrophosphate dihydrate (CPPD) deposition, PPi arthropathy, or pseudogout, or seemingly paradoxical deposition of hydroxyapatite crystals in ligaments or around joints when the condition is called calcific periarthritis (CP). We report three middle-aged sisters with CP as the only clinical manifestation of HPP. Each presented during early adult life with recurrent episodes of pain principally around the shoulders, elbows, wrists, hips, or Achilles tendon. Otherwise, they were in good health, including no history of unusual dental disease, fractures, or pseudofractures. Calcific deposits were identified in symptomatic areas principally by ultrasonographic assessment but also confirmed radiographically. All three sisters had low serum levels of total and bone-specific ALP, hyperphosphatemia, and increased serum concentrations of the TNSALP substrate pyridoxal 5\u2032-phosphate together characteristic of HPP. Mutation analysis revealed that each carried a single unique 18-bp duplication within TNSALP (c.188_205dup18, p.Gly63_Thr68dup) as did two of their healthy sons and their mother, who was without signs of CPPD deposition or CP but had knee osteoarthritis. We find that CP can be the only complication of HPP in adults. Thus, multiple juxta-articular deposits of hydroxyapatite causing CP may be a useful sign of HPP, especially when the CP is familial. \u00a9 2014 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.2110","type":"journal-article","created":{"date-parts":[[2013,10,12]],"date-time":"2013-10-12T02:05:25Z","timestamp":1381543525000},"page":"929-934","source":"Crossref","is-referenced-by-count":71,"title":["Calcific Periarthritis as the Only Clinical Manifestation of Hypophosphatasia in Middle-Aged Sisters"],"prefix":"10.1093","volume":"29","author":[{"given":"N\u00faria","family":"Gua\u00f1abens","sequence":"first","affiliation":[{"name":"Metabolic Bone Diseases UnitDepartment of RheumatologyHospital ClinicIDIBAPSCIBERehd, University of BarcelonaBarcelonaSpain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Mumm","sequence":"additional","affiliation":[{"name":"Division of Bone and Mineral DiseasesWashington University School of MedicineSt. LouisMOUSA"},{"name":"Center for Metabolic Bone Disease and Molecular ResearchShriners Hospital for ChildrenSt. LouisMOUSA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid","family":"M\u00f6ller","sequence":"additional","affiliation":[{"name":"Institute Poal of RheumatologyBarcelonaSpain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Gonz\u00e1lez-Roca","sequence":"additional","affiliation":[{"name":"Immunology DepartmentHospital ClinicBarcelonaSpain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pilar","family":"Peris","sequence":"additional","affiliation":[{"name":"Metabolic Bone Diseases UnitDepartment of RheumatologyHospital ClinicIDIBAPSCIBERehd, University of BarcelonaBarcelonaSpain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer L","family":"Demertzis","sequence":"additional","affiliation":[{"name":"Musculoskeletal Disease SectionMallinckrodt Institute of Radiology at Barnes-Jewish HospitalSt. LouisMOUSA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael P","family":"Whyte","sequence":"additional","affiliation":[{"name":"Division of Bone and Mineral DiseasesWashington University School of MedicineSt. LouisMOUSA"},{"name":"Center for Metabolic Bone Disease and Molecular ResearchShriners Hospital for ChildrenSt. LouisMOUSA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,10,4]]},"reference":[{"key":"2024020318544099300_jbmr2110-bib-0001","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/B978-0-12-387829-8.00022-6","volume-title":"Genetics of bone biology and skeletal disease","author":"Whyte","year":"2013"},{"key":"2024020318544099300_jbmr2110-bib-0002","author":"Mornet"},{"key":"2024020318544099300_jbmr2110-bib-0003","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1056\/NEJMoa1106173","article-title":"Enzyme-replacement therapy in life-threatening hypophosphatasia","volume":"366","author":"Whyte","year":"2012","journal-title":"N Engl J Med."},{"key":"2024020318544099300_jbmr2110-bib-0004","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1002\/jbmr.454","article-title":"Hypophosphatasia: nonlethal disease despite skeletal presentation in utero (17 new cases and literature review)","volume":"26","author":"Wenkert","year":"2011","journal-title":"J Bone Miner Res."},{"key":"2024020318544099300_jbmr2110-bib-0005","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3109\/10408369109106862","article-title":"Hypophosphatasia and the extracellular metabolism of inorganic pyrophosphate: clinical and laboratory aspects","volume":"28","author":"Caswell","year":"1991","journal-title":"Crit Rev Clin Lab Sci."},{"key":"2024020318544099300_jbmr2110-bib-0006","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1177\/154405910508401110","article-title":"Cementum and dentin in hypophosphatasia","volume":"84","author":"Van den Bos","year":"2005","journal-title":"J Dent Res."},{"key":"2024020318544099300_jbmr2110-bib-0007","doi-asserted-by":"crossref","first-page":"676","DOI":"10.4158\/EP.12.6.676","article-title":"Low serum alkaline phosphatase activity and pathologic fracture: case report and brief review of hypophosphatasia diagnosed in adulthood","volume":"12","author":"Khandwala","year":"2006","journal-title":"Endocr Pract."},{"key":"2024020318544099300_jbmr2110-bib-0008","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1002\/jbmr.1565","article-title":"Atypical femoral fractures\u201d during bisphosphonate exposure in adult hypophosphatasia","volume":"27","author":"Sutton","year":"2012","journal-title":"J Bone Miner Res."},{"key":"2024020318544099300_jbmr2110-bib-0009","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/0002-9343(82)90474-0","article-title":"Adult hypophosphatasia with chondrocalcinosis and arthropathy. 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