{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:28:18Z","timestamp":1790882898391,"version":"4.1.0"},"reference-count":15,"publisher":"National Academy of Sciences","issue":"8","license":[{"start":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T00:00:00Z","timestamp":1707696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003716","name":"Korea Basic Science Institute","doi-asserted-by":"publisher","award":["C270300"],"award-info":[{"award-number":["C270300"]}],"id":[{"id":"10.13039\/501100003716","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2021R1A2C1008663"],"award-info":[{"award-number":["NRF-2021R1A2C1008663"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,2,20]]},"abstract":"<jats:p>Postmenopausal osteoporosis arises from imbalanced osteoclast and osteoblast activity, and mounting evidence suggests a role for the osteoimmune system in bone homeostasis. Bisphosphonate (BP) is an antiresorptive agent, but its treatment failure rate can be as high as 40%. Here, we performed single-cell RNA sequencing on peripheral immune cells from carefully selected postmenopausal women: non-osteoporotic, osteoporosis improved after BP treatment, and BP-failed cases. We found an increase in myeloid cells in patients with osteoporosis (specifically, T cell receptor+ macrophages). Furthermore, lymphoid lineage cells varied significantly, notably elevated natural killer cells (NKs) in the BP-failed group. Moreover, we provide fruitful lists of biomarkers within the immune cells that exhibit condition-dependent differences. The existence of osteoporotic- and BP-failure-specific cellular information flows was revealed by cell\u2013cell interaction analysis. These findings deepen our insight of the osteoporosis pathology enhancing comprehension of the role of immune heterogeneity in postmenopausal osteoporosis and BP treatment failure.<\/jats:p>","DOI":"10.1073\/pnas.2316871121","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T15:05:17Z","timestamp":1707750317000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":10,"title":["Heterogeneous osteoimmune profiles via single-cell transcriptomics in osteoporotic patients who fail bisphosphonate treatment"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3732-7547","authenticated-orcid":false,"given":"Byeong-Rak","family":"Keum","sequence":"first","affiliation":[{"name":"Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Korea"},{"name":"Research Center for drug development, CYPHARMA Co., Ltd., Daejeon 34133, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8162-9585","authenticated-orcid":false,"given":"Hong Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Inje University Sanggye Paik Hospital, College of Medicine, Seoul 01757, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2749-8665","authenticated-orcid":false,"given":"Juhun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minji","family":"Lee","sequence":"additional","affiliation":[{"name":"Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Cheongju 28119, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sin-Hyoung","family":"Hong","sequence":"additional","affiliation":[{"name":"Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Cheongju 28119, Korea"},{"name":"Department of Bio-Analytical Science, University of Science and Technology, Daejeon 34113, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ha Kyun","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Korea University Ansan Hospital, College of Medicine, Seoul 15355, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Kwan","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3449-3814","authenticated-orcid":false,"given":"Sanguk","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Korea"},{"name":"Institute of Convergence Science, Yonsei University, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Gune","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Inje University Sanggye Paik Hospital, College of Medicine, Seoul 01757, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0360-4435","authenticated-orcid":false,"given":"Gun-Hwa","family":"Kim","sequence":"additional","affiliation":[{"name":"Research Center for drug development, CYPHARMA Co., Ltd., Daejeon 34133, Korea"},{"name":"Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Cheongju 28119, Korea"},{"name":"Department of Bio-Analytical Science, University of Science and Technology, Daejeon 34113, Korea"},{"name":"Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 34134, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,2,12]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-008-0566-6"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-014-2619-3"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-012-2093-8"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.00465"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000016793"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.687037"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-19196-2"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00657"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0000000000000103"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)01141-8"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.159107"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2021.0699"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1222129"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-015-0233-4"},{"key":"e_1_3_4_15_2","unstructured":"B.-R. Keum Data from \u201cHeterogeneous osteoimmune profiles via single-cell transcriptomics in osteoporotic patients who fail bisphosphonate treatment.\u201d OSF. https:\/\/osf.io\/qwgfr\/?view_only=47c91e2d61f74ea2baf801dfa209e507. Deposited 27 September 2023."}],"updated-by":[{"DOI":"10.1073\/pnas.2404416121","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T00:00:00Z","timestamp":1711584000000}}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2316871121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T13:16:22Z","timestamp":1711631782000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2316871121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,12]]},"references-count":15,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,2,20]]}},"alternative-id":["10.1073\/pnas.2316871121"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2316871121","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,12]]},"assertion":[{"value":"2023-10-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2316871121"}}