{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:55:51Z","timestamp":1787064951343,"version":"build-2736575974"},"reference-count":26,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2021YFC2501700"],"award-info":[{"award-number":["2021YFC2501700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Natural Science Fund","award":["82200993"],"award-info":[{"award-number":["82200993"]}]},{"DOI":"10.13039\/501100019018","name":"CAMS Innovation Fund for Medical Sciences","doi-asserted-by":"publisher","award":["2021-I2M-1-002"],"award-info":[{"award-number":["2021-I2M-1-002"]}],"id":[{"id":"10.13039\/501100019018","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018609","name":"National High Level Hospital Clinical Research Funding","doi-asserted-by":"publisher","award":["2022-PUMCH-D-006"],"award-info":[{"award-number":["2022-PUMCH-D-006"]}],"id":[{"id":"10.13039\/501100018609","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018609","name":"National High Level Hospital Clinical Research Funding","doi-asserted-by":"publisher","award":["2022-PUMCH-B-014"],"award-info":[{"award-number":["2022-PUMCH-B-014"]}],"id":[{"id":"10.13039\/501100018609","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences","award":["2023-PT320-10"],"award-info":[{"award-number":["2023-PT320-10"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Osteopetrosis (OPT) is a rare skeletal disease characterized by high bone mass that has 2 major inheritance patterns: autosomal dominant osteopetrosis and autosomal recessive osteopetrosis (ARO). However, comprehensive descriptions of bone microarchitecture in OPT patients are limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The aim of this study was to comprehensively investigate the bone microarchitecture of OPT patients, explore age-related bone alterations, and describe the skeletal heterogeneity among different genotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Nine OPT patients, including 7 with autosomal dominant osteopetrosis and CLCN7 mutations, 1 ARO patient with CAII mutation, and 1 ARO patient with TCIRG1 mutation, were retrospectively enrolled in this study. Clinical and biochemical examinations were performed. Bone microstructure was investigated by high-resolution peripheral quantitative computed tomography.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with age- and sex-matched healthy controls, OPT patients had greater total volumetric bone mineral density. In addition, trabecular bone was denser, with greater trabecular volumetric bone mineral density, increased trabecular number, and decreased trabecular separation. However, the cortical bone in OPT patients was weaker, characterized by increased cortical thickness and porosity. OPT patients exhibited characteristic patterns, including bone islets and uneven dense structures, on the representative reconstruction high-resolution peripheral quantitative computed tomography images. Skeletal heterogeneity across different genotypes was observed, with looser cortical bone in 1 OPT patient with CAII mutation and thicker cortical bone in 1 OPT patient with TCIRG1 mutation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Compared with healthy controls, OPT patients presented with denser trabecular bone, thicker but looser cortical bone, unique bone patterns, and skeletal heterogeneity. These results provide new insights into bone alterations in OPT patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf084","type":"journal-article","created":{"date-parts":[[2025,2,9]],"date-time":"2025-02-09T23:13:23Z","timestamp":1739142803000},"page":"e3215-e3224","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of Quality and Bone Microarchitecture Alterations in Osteopetrosis Patients: Assessed by HR-PQCT"],"prefix":"10.1210","volume":"110","author":[{"given":"Ruotong","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, NHC, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences , Beijing 100730 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4028-5560","authenticated-orcid":false,"given":"Qianqian","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, NHC, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences , Beijing 100730 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, NHC, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences , Beijing 100730 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushuo","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, NHC, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences , Beijing 100730 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, NHC, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences , Beijing 100730 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijia","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, NHC, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences , Beijing 100730 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruizhi","family":"Jiajue","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, NHC, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences , Beijing 100730 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, NHC, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences , Beijing 100730 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8634-2252","authenticated-orcid":false,"given":"Mei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, NHC, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences , Beijing 100730 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4434-3462","authenticated-orcid":false,"given":"Yan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, NHC, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences , Beijing 100730 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0395-8789","authenticated-orcid":false,"given":"Ou","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, NHC, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences , Beijing 100730 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, NHC, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences , Beijing 100730 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, NHC, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences , Beijing 100730 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7768-5536","authenticated-orcid":false,"given":"Weibo","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, NHC, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences , Beijing 100730 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"issue":"9","key":"2025091917013278500_dgaf084-B1","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/nrendo.2013.137","article-title":"Osteopetrosis: genetics, treatment and new insights into osteoclast function","volume":"9","author":"Sobacchi","year":"2013","journal-title":"Nat Rev Endocrinol"},{"issue":"1","key":"2025091917013278500_dgaf084-B2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s11914-018-0415-2","article-title":"Genetics of osteopetrosis","volume":"16","author":"Palagano","year":"2018","journal-title":"Curr Osteoporos Rep"},{"issue":"1","key":"2025091917013278500_dgaf084-B3","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.bone.2007.08.029","article-title":"Genetics, pathogenesis and complications of osteopetrosis","volume":"42","author":"Del Fattore","year":"2008","journal-title":"Bone"},{"issue":"11","key":"2025091917013278500_dgaf084-B4","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.3390\/genes13111965","article-title":"Spectrum of skeletal imaging features in osteopetrosis: inheritance pattern and radiological associations","volume":"13","author":"Spinnato","year":"2022","journal-title":"Genes (Basel)"},{"key":"2025091917013278500_dgaf084-B5","doi-asserted-by":"crossref","first-page":"116560","DOI":"10.1016\/j.bone.2022.116560","article-title":"Imaging in osteopetrosis","volume":"165","author":"Calder","year":"2022","journal-title":"Bone"},{"issue":"3","key":"2025091917013278500_dgaf084-B6","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/8756-3282(89)90048-3","article-title":"Biomechanical competence of iliac crest trabecular bone in autosomal dominant osteopetrosis type I","volume":"10","author":"Bollerslev","year":"1989","journal-title":"Bone"},{"issue":"1","key":"2025091917013278500_dgaf084-B7","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0002-9440(10)63798-4","article-title":"Genotype-phenotype relationship in human ATP6i-dependent autosomal recessive osteopetrosis","volume":"162","author":"Taranta","year":"2003","journal-title":"Am J Pathol"},{"issue":"12","key":"2025091917013278500_dgaf084-B8","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1002\/jbmr.2289","article-title":"Rapid skeletal turnover in a radiographic mimic of osteopetrosis","volume":"29","author":"Whyte","year":"2014","journal-title":"J Bone Miner Res"},{"issue":"5","key":"2025091917013278500_dgaf084-B9","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.beem.2008.07.006","article-title":"Bone remodelling: its local regulation and the emergence of bone fragility","volume":"22","author":"Martin","year":"2008","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"issue":"5","key":"2025091917013278500_dgaf084-B10","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/nrrheum.2014.23","article-title":"High-resolution in vivo imaging of bone and joints: a window to microarchitecture","volume":"10","author":"Geusens","year":"2014","journal-title":"Nat Rev Rheumatol"},{"issue":"3","key":"2025091917013278500_dgaf084-B11","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1002\/jbmr.2715","article-title":"Bone mineral density and microarchitecture in patients with autosomal dominant osteopetrosis: a report of two cases","volume":"31","author":"Arruda","year":"2016","journal-title":"J Bone Miner Res"},{"issue":"6","key":"2025091917013278500_dgaf084-B12","doi-asserted-by":"crossref","first-page":"e10616","DOI":"10.1002\/jbm4.10616","article-title":"Unusual cortical phenotype after hematopoietic stem cell transplantation in a patient with osteopetrosis","volume":"6","author":"Afshariyamchlou","year":"2022","journal-title":"JBMR Plus"},{"issue":"1","key":"2025091917013278500_dgaf084-B13","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s00223-017-0332-x","article-title":"Clinical significance of DXA and HR-pQCT in autosomal dominant osteopetrosis (ADO II)","volume":"102","author":"Butscheidt","year":"2018","journal-title":"Calcif Tissue Int"},{"issue":"11","key":"2025091917013278500_dgaf084-B14","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1002\/jbmr.4116","article-title":"Age-, site-, and sex-specific normative centile curves for HR-pQCT-derived microarchitectural and bone strength parameters in a Chinese mainland population","volume":"35","author":"Yu","year":"2020","journal-title":"J Bone Miner Res"},{"key":"2025091917013278500_dgaf084-B15","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.bone.2016.12.016","article-title":"Use of dual-energy X-ray absorptiometry (DXA) for diagnosis and fracture risk assessment; WHO-criteria, T- and Z-score, and reference databases","volume":"104","author":"Dimai","year":"2017","journal-title":"Bone"},{"issue":"3","key":"2025091917013278500_dgaf084-B16","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1002\/jbmr.4488","article-title":"Bone geometry, density, microstructure, and biomechanical properties in the distal tibia in patients with primary hypertrophic osteoarthropathy assessed by second-generation high-resolution peripheral quantitative computed tomography","volume":"37","author":"Pang","year":"2022","journal-title":"J Bone Miner Res"},{"issue":"2","key":"2025091917013278500_dgaf084-B17","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0092-8674(01)00206-9","article-title":"Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man","volume":"104","author":"Kornak","year":"2001","journal-title":"Cell"},{"issue":"9","key":"2025091917013278500_dgaf084-B18","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1007\/s00198-020-05438-5","article-title":"Guidelines for the assessment of bone density and microarchitecture in vivo using high-resolution peripheral quantitative computed tomography","volume":"31","author":"Whittier","year":"2020","journal-title":"Osteoporos Int"},{"issue":"4","key":"2025091917013278500_dgaf084-B19","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1002\/jbmr.2100","article-title":"CLCN7 and TCIRG1 mutations differentially affect bone matrix mineralization in osteopetrotic individuals","volume":"29","author":"Barvencik","year":"2014","journal-title":"J Bone Miner Res"},{"issue":"2","key":"2025091917013278500_dgaf084-B20","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.ecl.2021.03.008","article-title":"Assessment of skeletal strength: bone density testing and beyond","volume":"50","author":"Lewiecki","year":"2021","journal-title":"Endocrinol Metab Clin North Am"},{"issue":"9727","key":"2025091917013278500_dgaf084-B21","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1016\/S0140-6736(10)60320-0","article-title":"Intracortical remodelling and porosity in the distal radius and post-mortem femurs of women: a cross-sectional study","volume":"375","author":"Zebaze","year":"2010","journal-title":"Lancet"},{"issue":"1","key":"2025091917013278500_dgaf084-B22","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s00223-007-9098-x","article-title":"Phenotypic characteristics of bone in carbonic anhydrase II-deficient mice","volume":"82","author":"Margolis","year":"2008","journal-title":"Calcif Tissue Int"},{"issue":"9","key":"2025091917013278500_dgaf084-B23","doi-asserted-by":"crossref","first-page":"2752","DOI":"10.1073\/pnas.80.9.2752","article-title":"Carbonic anhydrase II deficiency identified as the primary defect in the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification","volume":"80","author":"Sly","year":"1983","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"2025091917013278500_dgaf084-B24","first-page":"409","article-title":"[Osteopetrosis with carbonic anhydrase II deficiency: report of 24 cases]","volume":"83","author":"Sonia","year":"2005","journal-title":"Tunis Med"},{"issue":"8","key":"2025091917013278500_dgaf084-B25","doi-asserted-by":"crossref","first-page":"e0237354","DOI":"10.1371\/journal.pone.0237354","article-title":"Knockdown of tcirg1 inhibits large-osteoclast generation by down-regulating NFATc1 and IP3R2 expression","volume":"15","author":"Zhang","year":"2020","journal-title":"PLoS One"},{"key":"2025091917013278500_dgaf084-B26","doi-asserted-by":"crossref","first-page":"116229","DOI":"10.1016\/j.bone.2021.116229","article-title":"Clinical presentation and analysis of genotype-phenotype correlations in patients with malignant infantile osteopetrosis","volume":"154","author":"Even-Or","year":"2022","journal-title":"Bone"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgaf084\/61839234\/dgaf084.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/110\/10\/e3215\/61839234\/dgaf084.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/110\/10\/e3215\/61839234\/dgaf084.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T21:01:39Z","timestamp":1758315699000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/110\/10\/e3215\/8008325"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,11]]},"references-count":26,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,2,11]]},"published-print":{"date-parts":[[2025,9,16]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgaf084","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,10]]},"published":{"date-parts":[[2025,2,11]]}}}