{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T18:02:02Z","timestamp":1788804122859,"version":"build-2803163510"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2024,8,10]],"date-time":"2024-08-10T00:00:00Z","timestamp":1723248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006396","name":"Alexion Pharmaceuticals Inc.","doi-asserted-by":"crossref","award":["ISR 100252"],"award-info":[{"award-number":["ISR 100252"]}],"id":[{"id":"10.13039\/100006396","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hypophosphatasia (HPP) is characterized by low activity of tissue nonspecific alkaline phosphatase (TNSALP). The enzyme replacement therapy asfotase alfa has been approved for childhood-onset forms of HPP. MicroRNAs (miRNAs) have emerged as a novel disease biomarker, with potential application in therapy monitoring. Circulating miRNAs were analyzed at baseline, months 1, 2, 4, and 16 in a 49-yr-old woman with childhood-onset HPP, chronic musculoskeletal pain, and non-traumatic fractures prior to enzyme replacement therapy. Serum RNA was extracted and sequenced using miRNeasy Mini Kit (Qiagen, Germany), RealSeq Biosciences Kit (Santa Cruz, US) together with miND spike-in control kit (TAmiRNA, Austria) and Illumina NovaSeq 6000 SP1 flow cell (San Diego, US). Brief Pain Inventory Severity and Interference scores (BPI-S\/BPI-I), fatigue severity scale (FSS), Patient Global Impression of Improvement (PGI-I), Western Ontario and McMaster university hip disability and osteoarthritis outcome score (WOMAC), fibromyalgia impact questionnaire (FIQ), 6-Minute Walking Test (6-MWT), chair-rise-test (CRT), and handgrip dynamometry (HD) were performed at baseline and different timepoints during the therapy. Out of &amp;gt;800 screened, 84 miRNAs were selected based on differences in expression profiles between 24 HPP patients and 24 healthy controls. Six miRNAs showed a clear graphic trend and were up- or downregulated by \u226550% reads per million (rpm). These included hsa-let-7i-5p (+50%), hsa-miR-1-3p (\u221266.66%), hsa-miR-1294 (+63.63%), hsa-miR-206 (\u221285.57%), hsa-miR-375-3p (\u221271.43%), and hsa-miR-624-5p (+69.44%). hsa-miR-1-3p and hsa-miR-206 were identified as muscle-specific miRNAs. hsa-mir-375-3p, which negatively regulates osteogenesis, was significantly downregulated. In terms of patient-reported outcomes, BPI-S, BPI-I, FSS, PGI-I, WOMAC, and FIQ showed a reduction by \u221258.62%, \u221268.29%, \u221233.33%, \u221275.00%, \u221263.29%, and \u221243.02%, respectively. 6-MWT improved by +33.89% and CRT by \u221244.46%. Mean hand grip strength of the right\/left hand measured by HD improved by +12.50% and\u2009+\u200923.53%, respectively. miRNA profile changes during the therapy with asfotase alfa, accompanying improvements in functionality tests and quality of life scores.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziae107","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T02:31:36Z","timestamp":1723170696000},"source":"Crossref","is-referenced-by-count":2,"title":["Longitudinal course of circulating miRNAs in a patient with hypophosphatasia and asfotase alfa treatment: a case report"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8079-2973","authenticated-orcid":false,"given":"Benjamin","family":"Hadzimuratovic","sequence":"first","affiliation":[{"name":"1st Medical Department, Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, Hanusch Hospital , 1140, Vienna, Austria"},{"name":"1st Medical Department, Hanusch Hospital , 1140, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Haschka","sequence":"additional","affiliation":[{"name":"1st Medical Department, Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, Hanusch Hospital , 1140, Vienna, Austria"},{"name":"1st Medical Department, Hanusch Hospital , 1140, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Hackl","sequence":"additional","affiliation":[{"name":"TAmiRNA GmbH , 1110, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas B","family":"Diendorfer","sequence":"additional","affiliation":[{"name":"TAmiRNA GmbH , 1110, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Mittelbach","sequence":"additional","affiliation":[{"name":"Institute of Physical Medicine at Hanusch Hospital , 1140, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Feurstein","sequence":"additional","affiliation":[{"name":"1st Medical Department, Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, Hanusch Hospital , 1140, Vienna, Austria"},{"name":"1st Medical Department, Hanusch Hospital , 1140, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Zwerina","sequence":"additional","affiliation":[{"name":"1st Medical Department, Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, Hanusch Hospital , 1140, Vienna, Austria"},{"name":"1st Medical Department, Hanusch Hospital , 1140, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinrich","family":"Resch","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine - VINFORCE, St. Vincent Hospital , 1060, Vienna, Austria"},{"name":"Medical Faculty of Bone Diseases, Sigmund Freud University , 1020, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Kocijan","sequence":"additional","affiliation":[{"name":"1st Medical Department, Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, Hanusch Hospital , 1140, Vienna, Austria"},{"name":"1st Medical Department, Hanusch Hospital , 1140, Vienna, Austria"},{"name":"Medical Faculty of Bone Diseases, Sigmund Freud University , 1020, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,8,10]]},"reference":[{"issue":"4","key":"2024090106014350300_ref1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/nrendo.2016.14","article-title":"Hypophosphatasia-aetiology, nosology, pathogenesis, diagnosis and 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