{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:02:14Z","timestamp":1788447734590,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background and Objectives: People living with HIV (PLWH) have excess fragility fractures not fully explained by areal DXA. We reviewed bone \u201cquality\u201d in PLWH\u2014microarchitecture, estimated strength, tissue-level properties\u2014and vertebral fractures (VFs). Methods: PRISMA-conform systematic review (2000\u20132025) of randomized, cohort, and cross-sectional studies assessing HR-pQCT (\u00b1finite-element analysis), trabecular bone score (TBS), impact microindentation (BMSi), femoral QCT\/MRI, and VF imaging (DXA-VFA or radiography). Risk of bias used ROBINS-I (non-randomized) and RoB 2 (randomized\/switch). No meta-analysis was performed due to clinical\/methodological heterogeneity; evidence was synthesized narratively per SWiM. Results: Fourteen studies met criteria. HR-pQCT showed cortical\/trabecular deficits with lower finite-element\u2013estimated strength in PLWH. BMSi was 3\u20134 units lower; it declined after ART initiation but improved after TDF\u2192TAF switch. TBS was modestly lower and reclassified risk when BMD was non-osteoporotic. VF prevalence was 12\u201325% and frequently occurred at non-osteoporotic BMD. Signals aligned with modifiable risks (smoking, glucocorticoids) and specific ART exposures. Conclusions: Beyond DXA, PLWH exhibit quantifiable decrements in microarchitecture, estimated strength, and tissue-level properties alongside a meaningful VF burden. TBS and VFA are pragmatic, scalable adjuncts to refine risk; HR-pQCT\/BMSi add mechanistic value in research\/tertiary settings. Prospective studies linking these metrics to incident fractures are warranted.<\/jats:p>","DOI":"10.3390\/jcm14217669","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T03:44:39Z","timestamp":1761795879000},"page":"7669","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Bone Quality Beyond DXA in People Living with HIV: A Systematic Review of HR-pQCT, TBS, Microindentation, and Vertebral Fractures"],"prefix":"10.3390","volume":"14","author":[{"given":"David Vladut","family":"Razvan","sequence":"first","affiliation":[{"name":"Doctoral School, Faculty of Medicine, Victor Babes University of Medicine and Pharmacy, 300041 Timisoara, Romania"},{"name":"Methodological and Infectious Diseases Research Center, Department of Infectious Diseases, Victor Babes University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8236-2205","authenticated-orcid":false,"given":"Ovidiu","family":"Rosca","sequence":"additional","affiliation":[{"name":"Methodological and Infectious Diseases Research Center, Department of Infectious Diseases, Victor Babes University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4711-4315","authenticated-orcid":false,"given":"Felix","family":"Bratosin","sequence":"additional","affiliation":[{"name":"Methodological and Infectious Diseases Research Center, Department of Infectious Diseases, Victor Babes University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vlad","family":"Predescu","sequence":"additional","affiliation":[{"name":"Orthopaedics and Traumatology Department, Ponderas Academic Hospital, 014142 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silviu Valentin","family":"Vlad","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine, University of Oradea, 410073 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1824-2628","authenticated-orcid":false,"given":"Adrian","family":"Vlad","sequence":"additional","affiliation":[{"name":"Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, Victor Babes University of Medicine and Pharmacy, 300041 Timisoara, Romania"},{"name":"Department of Internal Medicine II, Division of Diabetes, Nutrition and Metabolic Diseases, Victor Babes University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e0233501","DOI":"10.1371\/journal.pone.0233501","article-title":"Bone fracture among people living with HIV: A systematic review and meta-regression of prevalence, incidence, and risk factors","volume":"15","author":"Pramukti","year":"2020","journal-title":"PLoS ONE"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1093\/cid\/civ010","article-title":"Recommendations for evaluation and management of bone disease in HIV","volume":"60","author":"Brown","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1002\/jbmr.3183","article-title":"Immediate Initiation of Antiretroviral Therapy for HIV Infection Accelerates Bone Loss Relative to Deferring Therapy: Findings from the START Bone Mineral Density Substudy, a Randomized Trial","volume":"32","author":"Hoy","year":"2017","journal-title":"J. Bone Miner. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1111\/hiv.12796","article-title":"The rate of bone loss slows after 1-2 years of initial antiretroviral therapy: Final results of the Strategic Timing of Antiretroviral Therapy (START) bone mineral density substudy","volume":"21","author":"Carr","year":"2020","journal-title":"HIV Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e195","DOI":"10.1016\/S2352-3018(17)30031-0","article-title":"Switching from tenofovir disoproxil fumarate to tenofovir alafenamide coformulated with rilpivirine and emtricitabine in virally suppressed adults with HIV-1 infection: A randomised, double-blind, multicentre, phase 3b, non-inferiority study","volume":"4","author":"Orkin","year":"2017","journal-title":"Lancet HIV"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1097\/QAI.0000000000001186","article-title":"Brief Report: Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Adults With Renal Impairment: 96-Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study","volume":"74","author":"Post","year":"2017","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1097\/QAD.0000000000003811","article-title":"Bone turnover change after randomized switch from tenofovir disoproxil to tenofovir alafenamide fumarate in men with HIV","volume":"38","author":"Moore","year":"2024","journal-title":"AIDS"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1002\/jbmr.2734","article-title":"A Meta-Analysis of Trabecular Bone Score in Fracture Risk Prediction and Its Relationship to FRAX","volume":"31","author":"McCloskey","year":"2016","journal-title":"J. Bone Miner. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"694","DOI":"10.20945\/2359-3997000000559","article-title":"Update on trabecular bone score","volume":"66","author":"Palomo","year":"2022","journal-title":"Arch. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1002\/jbmr.3105","article-title":"Bone Microarchitecture Assessed by HR-pQCT as Predictor of Fracture Risk in Postmenopausal Women: The OFELY Study","volume":"32","author":"Boutroy","year":"2017","journal-title":"J. Bone Miner. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1093\/jbmr\/zjae033","article-title":"Fracture risk based on high-resolution peripheral quantitative computed tomography measures does not vary with age in older adults-the bone microarchitecture international consortium prospective cohort study","volume":"39","author":"Szulc","year":"2024","journal-title":"J. Bone Miner. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"101797","DOI":"10.1016\/j.bonr.2024.101797","article-title":"Trabecular bone score assessed by dual-energy X ray absorption predicts vertebral fractures in HIV infected young adults","volume":"22","author":"Mannarino","year":"2024","journal-title":"Bone Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1111\/hiv.13542","article-title":"Major revision version 12.0 of the European AIDS Clinical Society guidelines 2023","volume":"24","author":"Ambrosioni","year":"2023","journal-title":"HIV Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Biz, C., Khamisy-Farah, R., Puce, L., Szarpak, L., Converti, M., Ceylan, H.\u0130., Crim\u00ec, A., Bragazzi, N.L., and Ruggieri, P. (2024). Investigating and Practicing Orthopedics at the Intersection of Sex and Gender: Understanding the Physiological Basis, Pathology, and Treatment Response of Orthopedic Conditions by Adopting a Gender Lens: A Narrative Overview. Biomedicines, 12.","DOI":"10.3390\/biomedicines12050974"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s13643-021-01626-4","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"10","author":"Page","year":"2021","journal-title":"Syst. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1007\/s00198-012-2189-1","article-title":"Long-term HIV infection and antiretroviral therapy are associated with bone microstructure alterations in premenopausal women","volume":"24","author":"Calmy","year":"2013","journal-title":"Osteoporos. Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1097\/QAD.0000000000000445","article-title":"Microstructural alterations of trabecular and cortical bone in long-term HIV-infected elderly men on successful antiretroviral therapy","volume":"28","author":"Biver","year":"2014","journal-title":"AIDS"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"115509","DOI":"10.1016\/j.bone.2020.115509","article-title":"Deficits in bone strength, density and microarchitecture in women living with HIV: A cross-sectional HR-pQCT study","volume":"138","author":"Macdonald","year":"2020","journal-title":"Bone"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"115210","DOI":"10.1016\/j.bone.2019.115210","article-title":"Factors associated with bone microstructural alterations assessed by HR-pQCT in long-term HIV-infected individuals","volume":"133","author":"Foreman","year":"2020","journal-title":"Bone"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1097\/QAI.0000000000000965","article-title":"Brief Report: HIV Infection Is Associated with Worse Bone Material Properties, Independently of Bone Mineral Density","volume":"72","author":"Molina","year":"2016","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1093\/jac\/dkz014","article-title":"Inflammation status in HIV-positive individuals correlates with changes in bone tissue quality after initiation of ART","volume":"74","author":"Knobel","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Soldado-Folgado, J., Chillar\u00f3n, J.J., Ca\u00f1as-Ruano, E., Arrieta-Aldea, I., Gonz\u00e1lez-Mena, A., Blasco-Hernando, F., Knobel, H., Garcia-Giralt, N., and G\u00fcerri-Fern\u00e1ndez, R. (2022). An Abnormal Inflammatory Pattern Associated with Long-Term Non-Progression of HIV Infection Impacts Negatively on Bone Quality. J. Clin. Med., 11.","DOI":"10.3390\/jcm11102927"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1076739","DOI":"10.3389\/fendo.2023.1076739","article-title":"Changes in bone quality after switching from a TDF to a TAF based ART: A pilot randomized study","volume":"14","author":"Knobel","year":"2023","journal-title":"Front. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2236","DOI":"10.1210\/clinem\/dgae786","article-title":"Impaired Bone Tissue Quality Associated With Inflammation in HIV-immunological Nonresponders: A Cross-sectional Analysis","volume":"110","author":"Suaya","year":"2025","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e0213440","DOI":"10.1371\/journal.pone.0213440","article-title":"Assessment of trabecular bone score, an index of bone microarchitecture, in HIV positive and HIV negative persons within the HIV UPBEAT cohort","volume":"14","author":"McGinty","year":"2019","journal-title":"PLoS ONE"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1097\/QAI.0000000000001692","article-title":"HIV Infection Is Associated With Abnormal Bone Microarchitecture: Measurement of Trabecular Bone Score in the Women\u2019s Interagency HIV Study","volume":"78","author":"Sharma","year":"2018","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.jot.2021.04.002","article-title":"Changes in trabecular bone score and bone mineral density in Chinese HIV-Infected individuals after one year of antiretroviral therapy","volume":"29","author":"Guan","year":"2021","journal-title":"J. Orthop. Translat."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1007\/s11657-018-0464-2","article-title":"Increased prevalence of asymptomatic vertebral fractures in HIV-infected patients over 50 years of age","volume":"13","author":"Llop","year":"2018","journal-title":"Arch. Osteoporos."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1111\/hiv.12267","article-title":"Assessment of radiological vertebral fractures in HIV-infected patients: Clinical implications and predictive factors","volume":"16","author":"Gazzola","year":"2015","journal-title":"HIV Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/s00223-013-9716-8","article-title":"Trabecular and cortical microarchitecture in postmenopausal HIV-infected women","volume":"92","author":"Yin","year":"2013","journal-title":"Calcif. Tissue Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1111\/hiv.12380","article-title":"Disrupted trabecular bone micro-architecture in middle-aged male HIV-infected treated patients","volume":"17","author":"Sellier","year":"2016","journal-title":"HIV Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1186\/s12891-016-1238-x","article-title":"In vivo precision of three HR-pQCT-derived finite element models of the distal radius and tibia in postmenopausal women","volume":"17","author":"Kawalilak","year":"2016","journal-title":"BMC Musculoskelet. Disord."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1007\/s11904-022-00613-1","article-title":"Bone Quality in Relation to HIV and Antiretroviral Drugs","volume":"19","author":"Olali","year":"2022","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7838","DOI":"10.1038\/s41598-018-26312-9","article-title":"HIV and Vertebral Fractures: A Systematic Review and Metanalysis","volume":"8","author":"Ilha","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Atteritano, M., Mirarchi, L., Venanzi-Rullo, E., Santoro, D., Iaria, C., Catalano, A., Lasco, A., Arcoraci, V., Lo Gullo, A., and Bitto, A. (2018). Vitamin D Status and the Relationship with Bone Fragility Fractures in HIV-Infected Patients: A Case Control Study. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010119"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2606","DOI":"10.1016\/S0140-6736(15)60616-X","article-title":"Tenofovir alafenamide versus tenofovir disoproxil fumarate coformulated with elvitegravir cobicistat emtricitabine for initial treatment of HIV-1 infection: Two randomised double-blind phase 3, non-inferiority trials","volume":"385","author":"Sax","year":"2015","journal-title":"Lancet"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1097\/COH.0000000000000260","article-title":"The protease inhibitors and HIV-associated bone loss","volume":"11","author":"Moran","year":"2016","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1002\/jbm4.10055","article-title":"The Hidden Burden of Fractures in People Living with HIV","volume":"2","author":"Premaor","year":"2018","journal-title":"JBMR Plus."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1007\/s00198-022-06405-y","article-title":"People living with HIV have low trabecular bone mineral density, high bone marrow adiposity, and poor trabecular bone microarchitecture at the proximal femur","volume":"33","author":"Posadzy","year":"2022","journal-title":"Osteoporos. Int."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/21\/7669\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T04:10:49Z","timestamp":1761797449000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/21\/7669"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,29]]},"references-count":39,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["jcm14217669"],"URL":"https:\/\/doi.org\/10.3390\/jcm14217669","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,29]]}}}