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The disease manifests as early\u2010onset osteoporosis or a more severe skeletal dysplasia with low bone mineral density, frequent fractures, long\u2010bone deformities, and multiple sclerotic cranial lesions. The exact underlying molecular features and skeletal consequences, however, remain elusive. This study investigated bone tissue characteristics in two adult males with a heterozygous\n                    <jats:italic>SGMS2<\/jats:italic>\n                    mutation p.Arg50* and significant bone fragility. Transiliac bone biopsy samples from both (patient 1: 61\u2009years; patient 2: 29\u2009years) were analyzed by bone histomorphometry, confocal laser scanning microscopy, and quantitative backscattered electron imaging (qBEI). Bone histomorphometry portrayed largely normal values for structural and turnover parameters, but in both patient 1 and patient 2, respectively, osteoid thickness (\u22121.80 SD, \u22121.37 SD) and mineralizing surface (\u22121.03 SD, \u22122.73 SD) were reduced and osteoid surface increased (+9.03 SD, +0.98 SD), leading to elevated mineralization lag time (+8.16 SD, +4.10 SD). qBEI showed low and heterogeneous matrix mineralization (CaPeak \u22122.41 SD, \u22123.72 SD; CaWidth +7.47 SD, +4.41 SD) with a chaotic arrangement of collagenous fibrils under polarized light. Last, osteocyte lacunae appeared abnormally large and round in shape and the canalicular network severely disturbed with short\u2010spanned canaliculi lacking any orderliness or continuity. Taken together, these data underline a central role for functional SMS2 in bone matrix organization and mineralization, lacunocanalicular network, and in maintaining skeletal strength and integrity. These data bring new knowledge on changes in bone histology resulting from abnormal sphingomyelin metabolism and aid en route to better understanding of sphingolipid\u2010related skeletal disorders. \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\/jbm4.10537","type":"journal-article","created":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T07:29:18Z","timestamp":1628494158000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Abnormal Bone Tissue Organization and Osteocyte Lacunocanalicular Network in Early\u2010Onset Osteoporosis Due to\n                    <scp>\n                      <i>SGMS2<\/i>\n                    <\/scp>\n                    Mutations"],"prefix":"10.1093","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2907-3348","authenticated-orcid":false,"given":"Riikka E.","family":"M\u00e4kitie","sequence":"first","affiliation":[{"name":"Folkh\u00e4lsan Institute of Genetics  Helsinki Finland"},{"name":"Research Program for Clinical and Molecular Metabolism, Faculty of Medicine University of Helsinki  Helsinki Finland"},{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery Helsinki University Hospital and University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Blouin","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, 1st Medical Department Hanusch Hospital  Vienna Austria"},{"name":"Vienna Bone and Growth Center  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ville\u2010Valtteri","family":"V\u00e4lim\u00e4ki","sequence":"additional","affiliation":[{"name":"Pohjola Hospital  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Pihlstr\u00f6m","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Institute of Genetics  Helsinki Finland"},{"name":"Research Program for Clinical and Molecular Metabolism, Faculty of Medicine University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsi","family":"M\u00e4\u00e4tt\u00e4","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Institute of Genetics  Helsinki Finland"},{"name":"Research Program for Clinical and Molecular Metabolism, Faculty of Medicine University of Helsinki  Helsinki 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