{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T18:27:58Z","timestamp":1790101678841,"version":"4.0.1"},"reference-count":90,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2009,8,1]],"date-time":"2009-08-01T00:00:00Z","timestamp":1249084800000},"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":[[2009,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hypophosphatasia (HPP) is the inborn error of metabolism characterized by low serum alkaline phosphatase (ALP) activity caused by inactivating mutations within TNSALP, the gene that encodes the \u201ctissue-nonspecific\u201d isoenzyme of ALP (TNSALP). In HPP, extracellular accumulation of inorganic pyrophosphate, a TNSALP substrate, inhibits hydroxyapatite crystal growth leading to rickets or osteomalacia. Chronic recurrent multifocal osteomyelitis (CRMO) is the pediatric syndrome of periarticular pain and radiographic changes resembling infectious osteomyelitis but without lesional pathogens. Some consider CRMO to be an autoinflammatory disease. An unrelated boy and girl with the childhood form of HPP suffered chronic, multifocal, periarticular pain, and soft tissue swelling. To investigate this unusual complication, we evaluated their cumulative clinical, biochemical, radiological, and histopathological findings and performed mutation analysis of their TNSALP alleles. The earliest radiographic disturbances were typical of childhood HPP. Subsequently, changes consistent with CRMO developed at sites where there was pain, including lucencies, osteosclerosis, and marked expansion of the underlying metaphyses. Bone marrow edema was shown by MRI. Biopsies of affected bone showed nonspecific histopathological findings and no pathogens. The boy was heterozygous (c.1133A&amp;gt;T, p.D378V) and the girl compound heterozygous (c.350A&amp;gt;G, p.Y117C, c.400_401AC&amp;gt;CA, p.T134H) for different TNSALP missense mutations. Nonsteroidal anti-inflammatory drugs diminished their pain, which improved or resolved at maturity. HPP should be considered when CRMO is a diagnostic possibility. Metaphyseal radiographic changes and marrow edema associated with periarticular bone pain and soft tissue swelling suggestive of osteomyelitis can complicate childhood HPP.<\/jats:p>","DOI":"10.1359\/jbmr.090308","type":"journal-article","created":{"date-parts":[[2009,3,31]],"date-time":"2009-03-31T18:58:36Z","timestamp":1238525916000},"page":"1493-1505","source":"Crossref","is-referenced-by-count":66,"title":["Chronic Recurrent Multifocal Osteomyelitis Mimicked in Childhood Hypophosphatasia"],"prefix":"10.1093","volume":"24","author":[{"given":"Michael P","family":"Whyte","sequence":"first","affiliation":[{"name":"Division of Bone and Mineral Diseases, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, Missouri, USA"},{"name":"Center for Metabolic Bone Disease and Molecular Research, Shriners Hospitals for Children, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Wenkert","sequence":"additional","affiliation":[{"name":"Center for Metabolic Bone Disease and Molecular Research, Shriners Hospitals for Children, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William H","family":"McAlister","sequence":"additional","affiliation":[{"name":"Mallinckrodt Institute of Radiology, Washington University School of Medicine at St. Louis Children's Hospital, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Zulf","family":"Mughal","sequence":"additional","affiliation":[{"name":"Central Manchester & Manchester Children's Hospitals, National Health Service Trust; Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J","family":"Freemont","sequence":"additional","affiliation":[{"name":"The Medical School, University of Manchester; Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Whitehouse","sequence":"additional","affiliation":[{"name":"Central Manchester & Manchester Children's Hospitals, National Health Service Trust; Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen M","family":"Baildam","sequence":"additional","affiliation":[{"name":"Royal Liverpool Children's Hospital, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P","family":"Coburn","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Indiana University\u2013Purdue University, Fort Wayne, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence M","family":"Ryan","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Mumm","sequence":"additional","affiliation":[{"name":"Division of Bone and Mineral Diseases, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, Missouri, USA"},{"name":"Center for Metabolic Bone Disease and Molecular Research, Shriners Hospitals for Children, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,4]]},"reference":[{"key":"2024020319590432200_bib1","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1001\/archpedi.1948.02030020840003","article-title":"Hypophosphatasia: A new developmental anomaly","volume":"75","author":"Rathbun","year":"1948","journal-title":"Am J Dis Child"},{"key":"2024020319590432200_bib2","first-page":"5313","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Whyte","year":"2001","edition":"8th ed"},{"key":"2024020319590432200_bib3","doi-asserted-by":"crossref","first-page":"7666","DOI":"10.1073\/pnas.85.20.7666","article-title":"A missense mutation in the human liver\/bone\/kidney alkaline phosphatase gene causing a lethal form of hypophosphatasia","volume":"85","author":"Weiss","year":"1988","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024020319590432200_bib4","author":"Mornet","year":"2006"},{"key":"2024020319590432200_bib5","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1016\/B978-0-12-373884-4.00080-X","volume-title":"Principles of Bone Biology","author":"Whyte","year":"2008","edition":"3rd ed"},{"key":"2024020319590432200_bib6","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1038\/212901a0","article-title":"Effect of pyrophosphate on hydroxyapatite and its implications in calcium homeostasis","volume":"212","author":"Fleisch","year":"1966","journal-title":"Nature"},{"key":"2024020319590432200_bib7","volume-title":"From Biology to Applications in Medicine and Biotechnology","author":"Mill\u00e1n","year":"2006"},{"key":"2024020319590432200_bib8","first-page":"1555","article-title":"Matrix vesicles in osteomalacic hypophosphatasia bone contain apatite-like mineral crystals","volume":"151","author":"Anderson","year":"1997","journal-title":"Am J Pathol"},{"key":"2024020319590432200_bib9","doi-asserted-by":"crossref","first-page":"9445","DOI":"10.1073\/pnas.142063399","article-title":"Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization","volume":"99","author":"Hessle","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024020319590432200_bib10","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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