{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:08:02Z","timestamp":1792804082944,"version":"4.5.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"University of Alberta University Hospital Foundation Medical Research Competition","award":["RES0056834"],"award-info":[{"award-number":["RES0056834"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Immune checkpoint inhibitors (ICIs) are widely used in cancer treatment, yet their impact on bone health remains unclear. This study aimed to perform a retrospective cohort study utilizing routine CT scans from patients with melanoma to perform opportunistic QCT analysis to investigate the effects of ICI treatment on skeletal health, including volumetric BMD (vBMD) measurements and osteoarthritis (OA) parameters. A previously established machine learning-assisted opportunistic QCT pipeline was used to estimate lumbar spine vBMD from baseline and 12-mo follow-up CT scans in patients with melanoma treated with ICI therapy and those not treated with ICI therapy. Facet joint OA, osteophyte formation, and endplate sclerosis were also graded. Independent and paired t tests were used to determine any differences in vBMD and OA parameters between ICI users and non-ICI users. Multivariable linear regression models were used to control for confounding variables. Non-ICI users had a significant decrease in vBMD of \u22126.96\u00a0mg\/cm3 from baseline to follow-up, whereas the ICI users had no significant change. There was a significant difference in change in vBMD from baseline to follow-up between the 2 groups, with the non-ICI users experiencing a 11.22\u00a0mg\/cm3 larger decrease in vBMD. After adjusting for baseline age, sex, baseline vBMD, and change in OA parameters, this difference remained significant at \u221213.04\u00a0mg\/cm3. Among the ICI users, those who had a decline in vBMD had a lower baseline vBMD compared with those who had increased vBMD. Neither group showed a significant change in OA parameters over the follow-up period, nor a difference in change between ICI and non-ICI users, even after adjusting for sex, age, and baseline OA parameters. While the effects of ICI treatment on vBMD may vary based on baseline bone health, ICIs do not significantly impact OA parameters in the short term.<\/jats:p>","DOI":"10.1093\/jbmr\/zjaf009","type":"journal-article","created":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T06:33:17Z","timestamp":1737095597000},"page":"396-403","source":"Crossref","is-referenced-by-count":8,"title":["Assessing the effects of immune checkpoint inhibitors on bone utilizing machine learning\u2013assisted opportunistic quantitative computed tomography"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6391-2567","authenticated-orcid":false,"given":"Bryn E","family":"Matheson","sequence":"first","affiliation":[{"name":"McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary , Calgary, AB T2N 4Z6,","place":["Canada"]},{"name":"Department of Biomedical Engineering, Schulich School of Engineering, University of Calgary , Calgary, AB T2N 1N4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob L","family":"Jaremko","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary , Calgary, AB T2N 4Z6,","place":["Canada"]},{"name":"Department of Radiology and Diagnostic Imaging, University of Alberta , Edmonton, AB T6G 2B7,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Dowhanik","sequence":"additional","affiliation":[{"name":"Department of Radiology and Diagnostic Imaging, University of Alberta , Edmonton, AB T6G 2B7,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine","family":"Gill","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Department of Medicine, University of Alberta , Edmonton, AB T6G 2G3,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra","family":"Gallant","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alberta , Edmonton, AB T6G 2G3 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alberta , Edmonton, AB T6G 2G3 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Armani","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alberta , Edmonton, AB T6G 2G3 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D","family":"Leslie","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine and Radiology, University of Manitoba , Winnipeg, MB R3A 1R9 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kolinsky","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alberta , Edmonton, AB T6G 2G3 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2930-5997","authenticated-orcid":false,"given":"Steven K","family":"Boyd","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary , Calgary, AB T2N 4Z6,","place":["Canada"]},{"name":"Department of Radiology, University of Calgary , Calgary, AB T2N 1N4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9858-5398","authenticated-orcid":false,"given":"Carrie","family":"Ye","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary , Calgary, AB T2N 4Z6,","place":["Canada"]},{"name":"Department of Medicine, University of Alberta , Edmonton, AB T6G 2G3 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,1,24]]},"reference":[{"issue":"4","key":"2025031513015513600_ref1","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1007\/s00198-023-06690-1","article-title":"Fracture rate increases after immune checkpoint inhibitor treatment: a potential new immune related adverse event","volume":"34","author":"Ye","year":"2023","journal-title":"Osteoporos Int"},{"issue":"17","key":"2025031513015513600_ref2","doi-asserted-by":"publisher","first-page":"1974","DOI":"10.1200\/JCO.2014.59.4358","article-title":"Immune checkpoint blockade in cancer therapy","volume":"33","author":"Postow","year":"2015","journal-title":"J Clin Oncol"},{"issue":"6165","key":"2025031513015513600_ref3","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.1126\/science.342.6165.1432","article-title":"Breakthrough of the year 2013. Cancer immunotherapy","volume":"342","author":"Couzin-Frankel","year":"2013","journal-title":"Science"},{"issue":"2","key":"2025031513015513600_ref4","doi-asserted-by":"publisher","first-page":"166","DOI":"10.3899\/jrheum.190084","article-title":"Immune-related adverse events associated with cancer immunotherapy: a review for the practicing rheumatologist","volume":"47","author":"Jamal","year":"2020","journal-title":"J Rheumatol"},{"key":"2025031513015513600_ref5","doi-asserted-by":"publisher","first-page":"465","DOI":"10.3389\/fendo.2020.00465","article-title":"Osteoimmunology: the regulatory roles of T lymphocytes in osteoporosis","volume":"11","author":"Wenjuan, Zhang","year":"2020","journal-title":"Front Endocrinol"},{"issue":"7","key":"2025031513015513600_ref6","doi-asserted-by":"publisher","first-page":"e009309","DOI":"10.1136\/jitc-2024-009309","article-title":"Osteoporotic fractures: an unrecognized adverse event of immune checkpoint inhibitors?","volume":"12","author":"Elsayed","year":"2024","journal-title":"J Immunother Cancer"},{"issue":"5","key":"2025031513015513600_ref7","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2023-008669","article-title":"Favorable impact of PD1\/PD-L1 antagonists on bone remodeling: an exploratory prospective clinical study and ex vivo validation","volume":"12","author":"Gassner","year":"2024","journal-title":"J Immunother Cancer"},{"key":"2025031513015513600_ref8","doi-asserted-by":"publisher","first-page":"1199031","DOI":"10.3389\/fphar.2023.1199031","article-title":"Musculoskeletal adverse events induced by immune checkpoint inhibitors: a large-scale pharmacovigilance study","volume":"14","author":"Liu","year":"2023","journal-title":"Front Pharmacol"},{"issue":"1","key":"2025031513015513600_ref9","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/s40425-018-0417-8","article-title":"Immune-related adverse events with immune checkpoint inhibitors affecting the skeleton: a seminal case series","volume":"6","author":"Moseley","year":"2018","journal-title":"J Immunother Cancer"},{"key":"2025031513015513600_ref10","doi-asserted-by":"publisher","first-page":"100459","DOI":"10.1016\/j.jbo.2022.100459","article-title":"Changes in bone turnover markers in patients without bone metastases receiving immune checkpoint inhibitors: an exploratory analysis","volume":"37","author":"Pantano","year":"2022","journal-title":"J Bone Oncol"},{"issue":"10","key":"2025031513015513600_ref15","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1038\/s41584-018-0074-9","article-title":"Rheumatic immune-related adverse events from cancer immunotherapy","volume":"14","author":"Calabrese","year":"2018","journal-title":"Nat Rev Rheumatol"},{"issue":"11","key":"2025031513015513600_ref11","doi-asserted-by":"publisher","first-page":"1751","DOI":"10.1002\/acr.23177","article-title":"Rheumatic and musculoskeletal immune-related adverse events due to immune checkpoint inhibitors: a systematic review of the literature","volume":"69","author":"Cappelli","year":"2017","journal-title":"Arthritis Care Res (Hoboken)"},{"issue":"3","key":"2025031513015513600_ref12","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1136\/annrheumdis-2017-212257","article-title":"Rheumatic disorders associated with immune checkpoint inhibitors in patients with cancer-clinical aspects and relationship with tumour response: a single-centre prospective cohort study","volume":"77","author":"Kostine","year":"2018","journal-title":"Ann Rheum Dis"},{"issue":"3","key":"2025031513015513600_ref13","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1136\/annrheumdis-2019-216109","article-title":"Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation","volume":"79","author":"Braaten","year":"2020","journal-title":"Ann Rheum Dis"},{"key":"2025031513015513600_ref14","doi-asserted-by":"publisher","DOI":"10.1177\/2058738418820760","article-title":"Blocking of checkpoint receptor PD-L1 aggravates osteoarthritis in macrophage-dependent manner in the mice model","volume":"33","author":"Liu","year":"2019","journal-title":"Int J Immunopathol Pharmacol"},{"issue":"9","key":"2025031513015513600_ref38","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003260","article-title":"Activated osteoarthritis following immune checkpoint inhibitor treatment: an observational study","volume":"9","author":"Reid","year":"2021","journal-title":"J Immunother Cancer"},{"issue":"8","key":"2025031513015513600_ref16","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.1007\/s00198-021-05863-0","article-title":"Opportunistic CT screening predicts individuals at risk of major osteoporotic fracture","volume":"32","author":"Michalski","year":"2021","journal-title":"Osteoporos Int"},{"issue":"1","key":"2025031513015513600_ref17","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/s11914-022-00764-5","article-title":"Opportunistic screening techniques for analysis of CT scans","volume":"21","author":"Engelke","year":"2023","journal-title":"Curr Osteoporos Rep"},{"issue":"9","key":"2025031513015513600_ref18","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1007\/s00198-008-0820-y","article-title":"Comparison of QCT-derived and DXA-derived areal bone mineral density and T scores","volume":"20","author":"Khoo","year":"2009","journal-title":"Osteoporos Int"},{"issue":"1","key":"2025031513015513600_ref19","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.jocd.2014.03.002","article-title":"Comparison of femoral neck BMD evaluation obtained using lunar DXA and QCT with asynchronous calibration from CT colonography","volume":"18","author":"Pickhardt","year":"2015","journal-title":"J Clin Densitom"},{"issue":"3","key":"2025031513015513600_ref20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0091904","article-title":"CTXA hip--an extension of classical DXA measurements using quantitative CT","volume":"9","author":"Cann","year":"2014","journal-title":"PLoS One"},{"issue":"1","key":"2025031513015513600_ref21","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1148\/radiol.2015141984","article-title":"Comprehensive assessment of osteoporosis and bone fragility with CT colonography","volume":"278","author":"Fidler","year":"2016","journal-title":"Radiology"},{"key":"2025031513015513600_ref22","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.medengphy.2020.01.009","article-title":"CT-based internal density calibration for opportunistic skeletal assessment using abdominal CT scans","volume":"78","author":"Michalski","year":"2020","journal-title":"Med Eng Phys"},{"key":"2025031513015513600_ref23","doi-asserted-by":"publisher","DOI":"10.1016\/j.medengphy.2024.104109","article-title":"Establishing error bounds for internal calibration of quantitative computed tomography","volume":"124","author":"Matheson","year":"2024","journal-title":"Med Eng Phys"},{"issue":"1","key":"2025031513015513600_ref24","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1007\/BF03168013","article-title":"Precise measurement of vertebral bone density using computed tomography without the use of an external reference phantom","volume":"2","author":"Boden","year":"1989","journal-title":"J Digit Imaging"},{"issue":"2","key":"2025031513015513600_ref25","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41592-020-01008-z","article-title":"nnU-Net: a self-configuring method for deep learning-based biomedical image segmentation","volume":"18","author":"Fabian Isensee","year":"2021","journal-title":"Nat Methods"},{"issue":"2","key":"2025031513015513600_ref26","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1007\/s11263-006-7934-5","article-title":"Graph cuts and efficient N-D image segmentation","volume":"70","author":"Yuri Boykov","year":"2006","journal-title":"Int J Comput Vis"},{"key":"2025031513015513600_ref27","doi-asserted-by":"publisher","first-page":"101887","DOI":"10.1016\/j.media.2020.101887","article-title":"Bone and joint enhancement filtering: application to proximal femur segmentation from uncalibrated computed tomography datasets","volume":"67","author":"Besler","year":"2021","journal-title":"Med Image Anal"},{"issue":"3","key":"2025031513015513600_ref28","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/j.bone.2007.11.001","article-title":"A reference standard for the description of osteoporosis","volume":"42","author":"Kanis","year":"2008","journal-title":"Bone"},{"issue":"6","key":"2025031513015513600_ref29","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1007\/s00586-005-1029-9","article-title":"Validity and interobserver agreement of a new radiographic grading system for intervertebral disc degeneration: part I. lumbar spine","volume":"15","author":"Wilke","year":"2006","journal-title":"Eur Spine J"},{"issue":"23","key":"2025031513015513600_ref30","doi-asserted-by":"publisher","first-page":"2560","DOI":"10.1097\/BRS.0b013e318184ef95","article-title":"Facet joint osteoarthritis and low back pain in the community-based population","volume":"33","author":"Kalichman","year":"2008","journal-title":"Spine (Phila Pa 1976)"},{"issue":"1","key":"2025031513015513600_ref31","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1148\/radiology.164.1.3588910","article-title":"Osteoarthritis of the facet joints: accuracy of oblique radiographic assessment","volume":"164","author":"Pathria","year":"1987","journal-title":"Radiology"},{"key":"2025031513015513600_ref32","first-page":"1004","volume-title":"Annual Meeting of the American Society for Bone and Mineral Research","author":"Joseph","year":"2023"},{"issue":"3","key":"2025031513015513600_ref33","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1002\/ijc.33592","article-title":"Bone fracture as a novel immune-related adverse event with immune checkpoint inhibitors: case series and large-scale pharmacovigilance analysis","volume":"149","author":"Filippini","year":"2021","journal-title":"Int J Cancer"},{"key":"2025031513015513600_ref34","first-page":"75","article-title":"Increase in major osteoporotic fractures after therapy with immune checkpoint inhibitors [abstract]","author":"Ye","year":"2023","journal-title":"Arthritis Rheumatol"},{"issue":"1","key":"2025031513015513600_ref35","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/s00198-015-3224-9","article-title":"Effect of IV contrast on lumbar trabecular attenuation at routine abdominal CT: correlation with DXA and implications for opportunistic osteoporosis screening","volume":"27","author":"Pickhardt","year":"2016","journal-title":"Osteoporos Int"},{"issue":"2","key":"2025031513015513600_ref36","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.jocd.2017.09.001","article-title":"The influence of reconstruction kernel on bone mineral and strength estimates using quantitative computed tomography and finite element analysis","volume":"22","author":"Michalski","year":"2019","journal-title":"J Clin Densitom"},{"issue":"1","key":"2025031513015513600_ref37","doi-asserted-by":"publisher","first-page":"165","DOI":"10.2214\/AJR.16.16744","article-title":"Variation in attenuation in L1 trabecular bone at different tube voltages: caution is warranted when screening for osteoporosis with the use of opportunistic CT","volume":"208","author":"Garner","year":"2017","journal-title":"AJR Am J Roentgenol"},{"issue":"3","key":"2025031513015513600_ref39","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1080\/02841850510012661","article-title":"Effect of spinal degenerative changes on volumetric bone mineral density of the central skeleton as measured by quantitative computed tomography","volume":"46","author":"Guglielmi","year":"2005","journal-title":"Acta Radiol"},{"issue":"3","key":"2025031513015513600_ref40","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1007\/s00198-022-06631-4","article-title":"Fracture risk and assessment in adults with cancer","volume":"34","author":"Ye","year":"2023","journal-title":"Osteoporos Int"},{"issue":"4","key":"2025031513015513600_ref41","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1007\/s00198-011-1724-9","article-title":"Prevalence of osteoporosis among cancer patients in Germany: prospective data from an oncological rehabilitation clinic","volume":"23","author":"Reuss-Borst","year":"2012","journal-title":"Osteoporos Int"}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jbmr\/advance-article-pdf\/doi\/10.1093\/jbmr\/zjaf009\/61614088\/zjaf009.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/40\/3\/396\/61614088\/zjaf009.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/40\/3\/396\/61614088\/zjaf009.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,15]],"date-time":"2025-03-15T09:02:14Z","timestamp":1742029334000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/40\/3\/396\/7978005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,24]]},"references-count":41,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,1,24]]},"published-print":{"date-parts":[[2025,3,15]]}},"URL":"https:\/\/doi.org\/10.1093\/jbmr\/zjaf009","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,3]]},"published":{"date-parts":[[2025,1,24]]}}}