{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T11:00:31Z","timestamp":1783422031091,"version":"3.54.6"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T00:00:00Z","timestamp":1645660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","award":["766347"],"award-info":[{"award-number":["766347"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007229","name":"Bijzonder Onderzoeksfonds UGent","doi-asserted-by":"publisher","award":["BOF.ITN.2021.0012.001"],"award-info":[{"award-number":["BOF.ITN.2021.0012.001"]}],"id":[{"id":"10.13039\/501100007229","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007229","name":"Bijzonder Onderzoeksfonds UGent","doi-asserted-by":"publisher","award":["BOFGOA2021000407"],"award-info":[{"award-number":["BOFGOA2021000407"]}],"id":[{"id":"10.13039\/501100007229","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Osteogenesis imperfecta (OI) is a group of heritable disorders affecting bone and other connective tissues. Dominant OI forms are mainly caused by mutations in collagen type I. Patients suffer from skeletal deformities, fractures of long bones and vertebral compression fractures from early childhood onward. Altered collagen structure and excess mineralisation are the main causes for the bone phenotype. The <jats:italic>Chihuahua<\/jats:italic> (<jats:italic>Chi<\/jats:italic>\/+) zebrafish has become an important model for OI. Given that reduced dietary phosphorus (P) intake reduces the bone mineral content and promotes bone matrix formation in teleosts, including zebrafish, we tested whether a low dietary P (LP) intake mitigates the OI phenotype in the <jats:italic>Chi\/+<\/jats:italic> model. To answer this question, we characterised the <jats:italic>Chi\/+<\/jats:italic> vertebral column phenotype at a morphological, cellular and subcellular level. We present the first description of vertebral compression fractures in <jats:italic>Chi\/+<\/jats:italic> and assess the effects of LP diet on the <jats:italic>Chi\/+<\/jats:italic> phenotype (<jats:italic>Chi<\/jats:italic>\/+<jats:sub>LP<\/jats:sub>). Compared to untreated <jats:italic>Chi\/+<\/jats:italic>, two months of LP dietary treatment decreases vertebral deformities in the abdominal region and reduces shape variation of caudal vertebral bodies to a condition more similar to wild type (WT). At the histological level, the osteoid layer, covering the bone at the vertebral body endplates in WT zebrafish, is absent in <jats:italic>Chi\/+<\/jats:italic>, but it is partially restored with the LP diet. Whole mount-stained specimens and histological sections show various stages of vertebral compression fractures in <jats:italic>Chi\/+<\/jats:italic> and <jats:italic>Chi<\/jats:italic>\/+<jats:sub>LP<\/jats:sub> animals. Both <jats:italic>Chi\/+<\/jats:italic> and <jats:italic>Chi\/+<\/jats:italic><jats:sub>LP<\/jats:sub> show abundant osteoclast activity compared to WT. Finally, the ultrastructure analysis of WT, <jats:italic>Chi\/+<\/jats:italic> and <jats:italic>Chi<\/jats:italic>\/+<jats:sub>LP<\/jats:sub> shows <jats:italic>Chi\/+<\/jats:italic> and <jats:italic>Chi<\/jats:italic>\/+<jats:sub>LP<\/jats:sub> osteoblasts with enlarged endoplasmic reticulum cisternae and a high protein content, consistent with intracellular retention of mutated collagen. Nevertheless, the secreted collagen in <jats:italic>Chi<\/jats:italic>\/+<jats:sub>LP<\/jats:sub> appears better organised concerning fibre periodicity compared to <jats:italic>Chi\/+<\/jats:italic>. Our findings suggest that a reduced mineral content of <jats:italic>Chi\/+<\/jats:italic> bone could explain the lower frequency of vertebral column deformities and the restored shape of the vertebral bodies in <jats:italic>Chi<\/jats:italic>\/+<jats:sub>LP<\/jats:sub> animals. This, together with the improved quality of the bone extracellular matrix, suggests that two months of reduced dietary P intake can alleviate the severe bone phenotype in <jats:italic>Chi\/+<\/jats:italic> zebrafish.<\/jats:p>","DOI":"10.3389\/fendo.2022.851879","type":"journal-article","created":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T13:02:07Z","timestamp":1645707727000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Compression Fractures and Partial Phenotype Rescue With a Low Phosphorus Diet in the Chihuahua Zebrafish Osteogenesis Imperfecta Model"],"prefix":"10.3389","volume":"13","author":[{"given":"Silvia","family":"Cotti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Huysseune","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Larionova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Koppe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Forlino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul Eckhard","family":"Witten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00728-X","article-title":"Osteogenesis Imperfecta","volume":"387","author":"Forlino","year":"2016","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.16.2.101","article-title":"Genetic Heterogeneity in Osteogenesis Imperfecta","volume":"16","author":"Sillence","year":"1979","journal-title":"J Med Genet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"17052","DOI":"10.1038\/nrdp.2017.52","article-title":"Osteogenesis Imperfecta","volume":"3","author":"Marini","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-198109000-00020","article-title":"The Spine and Surgical Treatment in Osteogenesis Imperfecta","volume":"159","author":"Benson","year":"1981","journal-title":"Clin Orthop Relat Res"},{"key":"B5","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1097\/01.bpb.0000049567.52224.fa","article-title":"Modern Approach to Children With Osteogenesis Imperfecta","volume":"12","author":"Zeitlin","year":"2003","journal-title":"J Pediatr Orthop B"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1942","article-title":"Skeletal Clinical Characteristics of Osteogenesis Imperfecta Caused by Haploinsufficiency Mutations in COL1A1","volume":"28","author":"Ben Amor","year":"2013","journal-title":"J Bone Miner Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.5435\/JAAOS-D-15-00169","article-title":"The Spine in Patients With Osteogenesis Imperfecta","volume":"25","author":"Wallace","year":"2017","journal-title":"J Am Acad Orthop Surg"},{"key":"B8","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1302\/1863-2548.13.180185","article-title":"Complex Spine Deformities in Young Patients With Severe Osteogenesis Imperfecta: Current Concepts Review","volume":"13","author":"Castelein","year":"2019","journal-title":"J Child Orthop"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20429","article-title":"Consortium for Osteogenesis Imperfecta Mutations in the Helical Domain of Type I Collagen: Regions Rich in Lethal Mutations Align With Collagen Binding Sites for Integrins and Proteoglycans","volume":"28","author":"Marini","year":"2007","journal-title":"Hum Mutat"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2013.04.008","article-title":"A Molecular Ensemble in the rER for Procollagen Maturation","volume":"1833","author":"Ishikawa","year":"2013","journal-title":"Biochim Biophys Acta"},{"key":"B11","doi-asserted-by":"crossref","DOI":"10.1016\/B978-012529650-2\/50024-X","article-title":"Skeletal System","volume-title":"The Laboratory Fish. Part 4 Microscopic Functional Anatomy","author":"Huysseune","year":"2000"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/bs.mcb.2016.09.001","article-title":"Small Teleost Fish Provide New Insights Into Human Skeletal Diseases","volume":"138","author":"Witten","year":"2017","journal-title":"Methods Cell Biol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.00489","article-title":"Zebrafish: A Resourceful Vertebrate Model to Investigate Skeletal Disorders","volume":"11","author":"Tonelli","year":"2020","journal-title":"Front Endocrinol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4256","article-title":"Skeletal Biology and Disease Modeling in Zebrafish","volume":"36","author":"Dietrich","year":"2021","journal-title":"J Bone Miner Res"},{"key":"B15","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/s0012-1606(03)00399-3","article-title":"Radiographic Analysis of Zebrafish Skeletal Defects","volume":"264","author":"Fisher","year":"2003","journal-title":"Dev Biol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx171","article-title":"The Chaperone Activity of 4PBA Ameliorates the Skeletal Phenotype of Chihuahua, a Zebrafish Model for Dominant Osteogenesis Imperfecta","volume":"26","author":"Gioia","year":"2017","journal-title":"Hum Mol Genet"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3445","article-title":"Severely Impaired Bone Material Quality in Chihuahua Zebrafish Resembles Classical Dominant Human Osteogenesis Imperfecta","volume":"33","author":"Fiedler","year":"2018","journal-title":"J Bone Miner Res"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9290(03)00124-6","article-title":"The Many Adaptations of Bone","volume":"36","author":"Currey","year":"2003","journal-title":"J Biomech"},{"key":"B19","doi-asserted-by":"crossref","DOI":"10.1515\/9781501509346-014","article-title":"Mineralization in Organic Matrix Frameworks","volume-title":"Biomineralization. Reviews in Mineralogy and Geochemistry","author":"Veis","year":"2003"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.69B3.3584190","article-title":"Osteomalacia and Femoral Neck Fractures in the Elderly Patient","volume":"69","author":"Wilton","year":"1987","journal-title":"J Bone Joint Surg Br"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1148\/rg.315105712","article-title":"Integrated Imaging Approach to Osteoporosis: State-of-the-Art Review and Update","volume":"31","author":"Guglielmi","year":"2011","journal-title":"Radiographics"},{"key":"B22","doi-asserted-by":"publisher","first-page":"5429","DOI":"10.3390\/ijms21155429","article-title":"More Bone With Less Minerals? The Effects of Dietary Phosphorus on the Post-Cranial Skeleton in Zebrafish","volume":"21","author":"Cotti","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B23","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1111\/jfb.12870","article-title":"A Primary Phosphorus-Deficient Skeletal Phenotype in Juvenile Atlantic Salmon Salmo Salar: The Uncoupling of Bone Formation and Mineralization","volume":"88","author":"Witten","year":"2016","journal-title":"J Fish Biol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.188763","article-title":"Bone Without Minerals and its Secondary Mineralization in Atlantic Salmon","volume":"222","author":"Witten","year":"2019","journal-title":"J Exp Biol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquaculture.2021.736776","article-title":"Vertebral Column Adaptations in Juvenile Atlantic Salmon Salmo Salar, L. As a Response to Dietary Phosphorus","volume":"541","author":"Dr\u00e1bikov\u00e1","year":"2021","journal-title":"Aquaculture"},{"key":"B26","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1038\/s41413-021-00156-y","article-title":"3D Assessment of Intervertebral Disc Degeneration in Zebrafish Identifies Changes in Bone Density That Prime Disc Disease","volume":"9","author":"Kague","year":"2021","journal-title":"Bone Res"},{"key":"B27","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1002\/jmor.1065","article-title":"Features of Mono- and Multinucleated Bone Resorbing Cells of the Zebrafish Danio Rerio and Their Contribution to Skeletal Development, Remodeling, and Growth","volume":"250","author":"Witten","year":"2001","journal-title":"J Morphol"},{"key":"B28","article-title":"The Ancient, Segmented, Active and Permanent Notochord","volume-title":"Ancient Fishes and Their Living Relatives: A Tribute to John G. Maisey","author":"Witten","year":"2021"},{"key":"B29","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-030-42527-2_13","article-title":"Osteogenesis Imperfecta in the Spine","volume-title":"Osteogenesis Imperfecta. A Case-Based Guide to Surgical Decision-Making and Care","author":"Shah","year":"2020"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-197860070-00009","article-title":"The Spine in Osteogenesis Imperfecta","volume":"60","author":"Benson","year":"1978","journal-title":"J\u00a0Bone Joint Surg Am"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/BF00441849","article-title":"Heterogeneity of Osteogenesis Imperfecta. Biochemical and Morphological Findings in a Case of Type III According to Sillence","volume":"145","author":"St\u00f6\u00df","year":"1986","journal-title":"Eur J Pediatr"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s007740200025","article-title":"Increased Bone Resorption With Decreased Activity and Increased Recruitment of Osteoblasts in Osteogenesis Imperfecta Type I","volume":"20","author":"Iwamoto","year":"2002","journal-title":"J Bone Miner Metab"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1210\/endo.143.5.8807","article-title":"Osteoblastic Response to the Defective Matrix in the Osteogenesis Imperfecta Murine (Oim) Mouse","volume":"143","author":"Kalajzic","year":"2002","journal-title":"Endocrinology"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.080804","article-title":"Cellular Mechanism of Decreased Bone in Brtl Mouse Model of OI: Imbalance of Decreased Osteoblast Function and Increased Osteoclasts and Their Precursors","volume":"23","author":"Uveges","year":"2008","journal-title":"J\u00a0Bone Miner Res"},{"key":"B35","doi-asserted-by":"publisher","first-page":"41","DOI":"10.2147\/ORR.S85198","article-title":"Animal Models of Osteogenesis Imperfecta: Applications in Clinical Research","volume":"8","author":"Enderli","year":"2016","journal-title":"Orthop Res Rev"},{"key":"B36","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.matbio.2020.03.004","article-title":"Crtap and P3h1 Knock Out Zebrafish Support Defective Collagen Chaperoning as the Cause of Their Osteogenesis Imperfecta Phenotype","volume":"90","author":"Tonelli","year":"2020","journal-title":"Matrix Biol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1079\/BJN20061838","article-title":"High Phosphorus Intakes Acutely and Negatively Affect Ca and Bone Metabolism in a Dose-Dependent Manner in Healthy Young Females","volume":"96","author":"Kemi","year":"2006","journal-title":"Br J Nutr"},{"key":"B38","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.jtemb.2015.06.005","article-title":"Effects of Thirty Elements on Bone Metabolism","volume":"32","author":"Dermience","year":"2015","journal-title":"J Trace Elem Med Biol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1359\/jbmr.061009","article-title":"High Dietary Phosphate Intake Reduces Bone Strength in the Growing Rat Skeleton","volume":"22","author":"Huttunen","year":"2007","journal-title":"J Bone Miner Res"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1259\/0007-1285-16-185-129","article-title":"Osteogenesis Imperfecta","volume":"16","author":"Brailsford","year":"1943","journal-title":"Br J Radiol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0b013e31811ec2d9","article-title":"Correlation of Scoliotic Curvature With Z-Score Bone Mineral Density and Body Mass Index in Patients With Osteogenesis Imperfecta","volume":"32","author":"Watanabe","year":"2007","journal-title":"Spine"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2015.08.001","article-title":"Behavioral Signs of Pain and Functional Impairment in a Mouse Model of Osteogenesis Imperfecta","volume":"81","author":"Abdelaziz","year":"2015","journal-title":"Bone"},{"key":"B43","volume-title":"Heritable Disorders of Connective Tissue","author":"McKusick","year":"1972"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-199602000-00007","article-title":"Vertebral Body Shape as a Predictor of Spinal Deformity in Osteogenesis Imperfecta","volume":"78","author":"Ishikawa","year":"1996","journal-title":"J Bone Joint Surg Am"},{"key":"B45","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-030-42527-2_2","article-title":"Patient Evaluation and Medical Treatment for Osteogenesis Imperfecta","volume-title":"Osteogenesis Imperfecta. A Case-Based Guide to Surgical Decision-Making and Care","author":"McGreal","year":"2020"},{"key":"B46","doi-asserted-by":"publisher","first-page":"2975","DOI":"10.1002\/dvdy.22113","article-title":"Studies of the Acellular Bone of Teleost Fish. II. Response to Fracture Under Normal and Acalcemic Conditions","volume":"48","author":"Moss","year":"1962","journal-title":"Acta Anat"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-198303000-00007","article-title":"Increased Bone Turnover With Decreased Bone Formation by Osteoblasts in Children With Osteogenesis Imperfecta Tarda","volume":"17","author":"Baron","year":"1983","journal-title":"Pediatr Res"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/s8756-3282(00)00269-6","article-title":"Static and Dynamic Bone Histomorphometry in Children With Osteogenesis Imperfecta","volume":"26","author":"Rauch","year":"2000","journal-title":"Bone"},{"key":"B49","first-page":"45","article-title":"Osteoblast\/osteoclast Development and Function in Osteogenesis Imperfecta","volume-title":"Osteogenesis Imperfecta. A Translational Approach to Brittle Bone Disease","author":"Fedarko","year":"2014"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-185X.2009.00077.x","article-title":"A Comparative View on Mechanisms and Functions of Skeletal Remodelling in Teleost Fish, With Special Emphasis on Osteoclasts and Their Function","volume":"84","author":"Witten","year":"2009","journal-title":"Biol Rev Camb Philos Soc"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.21337","article-title":"Increased Resorptive Activity and Accompanying Morphological Alterations in Osteoclasts Derived From the Oim\/Oim Mouse Model of Osteogenesis Imperfecta","volume":"102","author":"Zhang","year":"2007","journal-title":"J Cell Biochem"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.matbio.2021.03.001","article-title":"Targeting Cellular Stress In Vitro Improves Osteoblast Homeostasis, Matrix Collagen Content and Mineralization in Two Murine Models of Osteogenesis Imperfecta","volume":"98","author":"Garibaldi","year":"2021","journal-title":"Matrix Biol"},{"key":"B53","volume-title":"Biological Calcification. Normal and Pathologicalpprocesses in the Early Stages","author":"Bonucci","year":"2007"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquaculture.2018.06.036","article-title":"Effect of Different Inorganic Phosphorus Sources on Growth Performance, Digestibility, Retention Efficiency and Discharge of Nutrients in Rainbow Trout (Oncorhynchus Mykiss)","volume":"495","author":"Morales","year":"2018","journal-title":"Aquaculture"},{"key":"B55","article-title":"Revised Procedures for Staining and Clearing Small Fishes and Other Vertebrates for Bone and Cartilage Study","volume":"9","author":"Taylor","year":"1985","journal-title":"Cybium"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1111\/jfb.14272","article-title":"Plasticity of the Skeleton and Skeletal Deformities in Zebrafish (Danio Rerio) Linked to Rearing Density","volume":"98","author":"Martini","year":"2020","journal-title":"J\u00a0Fish Biol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.otsr.2018.12.008","article-title":"Computed Tomography Method for Characterising the Zebrafish Spine","volume":"105","author":"Marie-Hardy","year":"2019","journal-title":"Orthop Traumatol Surg Res"},{"key":"B58","doi-asserted-by":"publisher","first-page":"2975","DOI":"10.1002\/dvdy.22113","article-title":"Normal Table of Postembryonic Zebrafish Development: Staging by Externally Visible Anatomy of the Living Fish","volume":"238","author":"Parichy","year":"2009","journal-title":"Dev Dyn"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.10387","article-title":"Developmental Morphology of the Axial Skeleton of the Zebrafish, Danio Rerio (Ostariophysi: Cyprinidae)","volume":"228","author":"Bird","year":"2003","journal-title":"Dev Dyn"},{"key":"B60","doi-asserted-by":"crossref","DOI":"10.1017\/S1089332600001868","article-title":"A Practical Introduction to Landmark-Based Geometric Morphometrics","volume-title":"The Paleontological Society Papers","author":"Webster","year":"2010"},{"key":"B61","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.carj.2009.12.012","article-title":"Combined Vertebral Fracture Assessment and Bone Mineral Density Measurement: A Patient-Friendly New Tool With an Important Impact on the Canadian Risk Fracture Classification","volume":"61","author":"Jager","year":"2010","journal-title":"Can Assoc Radiol J"},{"key":"B62","first-page":"1","article-title":"Past: Paleontological Statistics Software Package for Education and Data Analysis","volume":"4","author":"Hammer","year":"2001","journal-title":"Palaeontol Electron"},{"key":"B63","volume-title":"Humason\u2019s Animal Tissue Techniques","author":"Humason","year":"1997"},{"key":"B64","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/S0022-5320(69)90033-1","article-title":"A Low-Viscosity Epoxy Resin Embedding Medium for Electron Microscopy","volume":"26","author":"Spurr","year":"1969","journal-title":"J Ultrastruct Res"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.851879\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T13:02:25Z","timestamp":1645707745000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.851879\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,24]]},"references-count":64,"alternative-id":["10.3389\/fendo.2022.851879"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.851879","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,24]]},"article-number":"851879"}}