OSTEOPOROSIS IN AUTOIMMUNE DISEASES
Abstract
Introduction: Osteoporosis is one of the most common extra-articular complications in many chronic inflammatory rheumatic diseases, including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and systemic lupus erythematosus.
Methods: We searched the PubMed, Scopus, and Web of Science databases for studies published within the last 10 years. This is a review article.
Results: Most studies on postmenopausal women have found a correlation between high levels of pro-inflammatory markers and increased bone loss. Literature data indicate a link between a low risk of major osteoporotic fractures, hip fractures, and non-vertebral fractures in patients with PsA who are on disease-modifying therapies. Patient assessment in autoimmune rheumatic inflammatory diseases includes medical history, clinical examination, fracture risk assessment, laboratory tests, and bone densitometry. The lack of adequate diagnosis and treatment of osteoporosis is influenced by factors such as insufficient knowledge about osteoporosis and its therapeutic benefits, concerns about potential side effects of treatment, low motivation, and inadequate patient education on the subject. Several methods have been developed to reduce prescribing errors and oversights, with the Fracture Liaison Service proving to be the most effective. Strategies for managing osteoporosis include patient education, lifestyle modifications, fall prevention, proper nutrition, disease activity control, and the introduction of osteoporosis medication.
Conclusion: Despite significant advances in prevention, diagnosis, and treatment, the prevalence of osteoporosis remains high and requires timely recognition and a more comprehensive approach. Assessing risk factors for falls and fractures, as well as recovery potential, is crucial in patients with autoimmune rheumatic inflammatory diseases.
References
Kao FC, Hsu YC, Tu YK, Chen TS, Wang HH, Lin JC. Long-Term Use of Immunosuppressive Agents Increased the Risk of Fractures in Patients with Autoimmune Diseases: An 18-Year Population-Based Cohort Study. Biomed. 2023 Oct 12;11(10):2764. doi: 10.3390/biomedicines11102764.
Aibar-Almazán A, Voltes-Martínez A, Castellote-Caballero Y, Afanador-Restrepo DF, Carcelén-Fraile MDC, López-Ruiz E. Current Status of the Diagnosis and Management of Osteoporosis. Int J Mol Sci. 2022 Aug 21;23(16):9465. doi: 10.3390/ijms23169465.
Xiao PL, Cui AY, Hsu CJ, Peng R, Jiang N, Xu XH, et al. Global, regional prevalence, and risk factors of osteoporosis according to the World Health Organization diagnostic criteria: a systematic review and meta-analysis. Osteoporos Int. 2022 Oct;33(10):2137-53. doi: 10.1007/s00198-022-06454-3.
Compston JE, McClung MR, Leslie WD. Osteoporosis. Lancet. 2019 Jan 26;393(10169):364-76. doi: 10.1016/S0140-6736(18)32112-3.
Miller FW. The increasing prevalence of autoimmunity and autoimmune diseases: an urgent call to action for improved understanding, diagnosis, treatment, and prevention. Curr Opin Immunol. 2023 Feb;80:102266. doi: 10.1016/j.coi.2022.102266.
Lenti MV, Rossi CM, Melazzini F, Gastaldi M, Bugatti S, Rotondi M, et al. A Seronegative autoimmune disease: A challenging diagnosis. Autoimmun Rev. 2022 Sep;21(9):103143. doi: 10.1016/j.autrev.2022.103143.
Moshayedi S, Tasorian B, Almasi-Hashiani A. The prevalence of osteoporosis in rheumatoid arthritis patient: a systematic review and meta-analysis. Sci Rep. 2022 Sep 23;12(1):15844. doi: 10.1038/s41598-022-20016-x.
Chandran S, Aldei A, Johnson SR, Cheung AM, Salonen D, Gladman DD. Prevalence and risk factors of low bone mineral density in psoriatic arthritis: A systematic review. Semin Arthritis Rheum. 2016 Oct;46(2):174-82. doi: 10.1016/j.semarthrit.2016.05.005.
Takami K, Higashiyama M, Tsuji S. Osteoporosis and osteopenia in patients with psoriatic arthritis: A single-centre retrospective study. Mod Rheumatol. 2024 Oct 15;34(6):1252-7. doi: 10.1093/mr/roae028.
Martínez-Vidal MP, Jovani V, Noguera-Pons JR, Álvarez-Cienfuegos A. Osteoporosis in psoriatic arthritis: Risk factors, insufficiency fractures and its association with the disease activity. Reumatol Clin (Engl Ed). 2024 Jan;20(1):8-13. doi: 10.1016/j.reumae.2023.05.007.
Sharif K, Tsur AM, Ben-Shabat N, Watad A, Cohen AD, Amital H. The risk of osteoporosis in patients with ankylosing spondylitis-A large retrospective matched cohort study. Med Clin (Barc). 2023 May 12;160(9):373-8. doi: 10.1016/j.medcli.2022.10.013.
Zheng B, Yu P, Liu H, Liang Y. Anti-Osteoporosis Is Imperative in Prevention of Progress of Ankylosing Spondylitis. Int J Gen Med. 2025 Jan 21;18:291-7. doi: 10.2147/IJGM.S509296.
Ramírez J, Nieto-González JC, Curbelo Rodríguez R, Castañeda S, Carmona L. Prevalence and risk factors for osteoporosis and fractures in axial spondyloarthritis: A systematic review and meta-analysis. Semin Arthritis Rheum. 2018 Aug;48(1):44-52. doi: 10.1016/j.semarthrit.2017.12.001.
Lai SW, Kuo YH, Liao KF. Bone health in patients with systemic lupus erythematosus. Ann Rheum Dis. 2021 Nov;80(11):e179. doi: 10.1136/annrheumdis-2019-216417.
Gu C, Zhao R, Zhang X, Gu Z, Zhou W, Wang Y, et al. A meta-analysis of secondary osteoporosis in systemic lupus erythematosus: prevalence and risk factors. Arch Osteoporos. 2019 Dec 4;15(1):1. doi:10.1007/s11657-019-0667-1.
Hong CX, Pan YZ, Dai FB. Potential association of rheumatic diseases with bone mineral density and fractures: a bi-directional mendelian randomization study. BMC Musculoskelet Disord. 2024 Jul 5;25(1):521. doi: 10.1186/s12891-024-07496-w.
Kim JW, Park S, Jung JY, Kim HA, Kwon SR, Choi ST, et al. Prevalence and Factors of Osteoporosis and High Risk of Osteoporotic Fracture in Patients with Ankylosing Spondylitis: A Multicenter Comparative Study of Bone Mineral Density and the Fracture Risk Assessment Tool. J Clin Med. 2022 May 17;11(10):2830. doi: 10.3390/jcm11102830.
Kwok TSH, Sutton M, Ye JY, Pereira D, Chandran V, Gladman DD. Prevalence and Factors Associated with Osteoporosis and Bone Mineral Density Testing in Psoriatic Arthritis. Arthritis Care Res (Hoboken). 2022 Jun;74(6):1006-12. doi: 10.1002/acr.24538.
Chen TL, Lu JW, Huang YW, Wang JH, Su KY. Bone Mineral Density, Osteoporosis, and Fracture Risk in Adult Patients with Psoriasis or Psoriatic Arthritis: A Systematic Review and Meta-Analysis of Observational Studies. J Clin Med. 2020 Nov 19;9(11):3712. doi: 10.3390/jcm9113712.
Schauer A, Uthayakumar AK, Boardman G, Bunker CB. The risk of osteopenia/osteoporosis and psoriatic disease: A systematic review. Skin Health Dis. 2022 Sep 21;3(1):e169. doi: 10.1002/ski2.169.
Halasi A, Szegedi A, Törőcsik D, Varga J, Farmasi N, Szűcs G, et al. Psoriatic arthritis and its special features predispose not only for osteoporosis but also for fractures and falls. J Dermatol. 2023 May;50(5):608-14. doi: 10.1111/1346-8138.16710.
Mei J, Hu H, Ding H, Huang Y, Zhang W, Chen X, et al. Investigating the causal relationship between ankylosing spondylitis and osteoporosis in the European population: a bidirectional Mendelian randomization study. Front Immunol. 2023 Jun 8;14:1163258. doi: 10.3389/fimmu.2023.1163258.
Yan F, Wu L, Lang J, Huang Z. Bone density and fracture risk factors in ankylosing spondylitis: a meta-analysis. Osteoporos Int. 2024 Jan;35(1):25-40. doi: 10.1007/s00198-023-06925-1.
Rella V, Rotondo C, Altomare A, Cantatore FP, Corrado A. Bone Involvement in Systemic Lupus Erythematosus. Int J Mol Sci. 2022 May 22;23(10):5804. doi: 10.3390/ijms23105804.
Salman-Monte TC, Torrente-Segarra V, Vega-Vidal AL, Corzo P, Castro-Dominguez F, Ojeda F, et al. Bone mineral density and vitamin D status in systemic lupus erythematosus (SLE): A systematic review. Autoimmun Rev. 2017 Nov;16(11):1155-9. doi: 10.1016/j.autrev.2017.09.011.
Cho SK, Sung YK. Update on Glucocorticoid Induced Osteoporosis. Endocrinol Metab (Seoul). 2021 Jun;36(3):536-43. doi: 10.3803/EnM.2021.1021.
Zerikly R, Demetriou EW. Use of Fracture Risk Assessment Tool in clinical practice and Fracture Risk Assessment Tool future directions. Womens Health (Lond). 2024 Jan-Dec;20:17455057241231387. doi: 10.1177/17455057241231387.
Hayes KN, Baschant U, Hauser B, Burden AM, Winter EM. When to Start and Stop Bone-Protecting Medication for Preventing Glucocorticoid-Induced Osteoporosis. Front Endocrinol (Lausanne). 2021 Dec 15;12:782118. doi: 10.3389/fendo.2021.782118. Erratum in: Front Endocrinol (Lausanne). 2022 Mar 14;13:877512. doi: 10.3389/fendo.2022.877512.
Zerbini CAF, Clark P, Mendez-Sanchez L, Pereira RMR, Messina OD, Uña CR, et al. Chronic Inflammation and Bone Structure (CIBS) Working Group. Biologic therapies and bone loss in rheumatoid arthritis. Osteoporos Int. 2017 Feb;28(2):429-46. doi: 10.1007/s00198-016-3769-2.
Lv F, Hu S, Lin C, Cai X, Zhu X, Ji L. Association between biologic therapy and fracture incidence in patients with selected rheumatic and autoimmune diseases: A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res. 2022 Jul;181:106278. doi: 10.1016/j.phrs.2022.106278.
Hu L, Liu R, Zhang L. Advance in bone destruction participated by JAK/STAT in rheumatoid arthritis and therapeutic effect of JAK/STAT inhibitors. Int Immunopharmacol. 2022 Oct;111:109095. doi: 10.1016/j.intimp.2022.109095.
Wu J, Huang H, Yu X. How does Hashimoto's thyroiditis affect bone metabolism? Rev Endocr Metab Disord. 2023 Apr;24(2):191-205. doi: 10.1007/s11154-022-09778-x.
Bjelica A, Vučaj Ćirilović V, Tomašević Todorović S, Filipović K. Postmenopausal osteoporosis. Med Pregl. 2018 May-Jun;71(5-6):201-5. doi: 10.2298/MPNS1806201B.
Tomasevic-Todorovic S, Vazic A, Issaka A, Hanna F. Comparative assessment of fracture risk among osteoporosis and osteopenia patients: a cross-sectional study. Open Access Rheumatol. 2018 May 30;10:61-6. doi: 10.2147/OARRR.S151307.
Morin SN, Feldman S, Funnell L, Giangregorio L, Kim S, McDonald-Blumer H, et al.; Osteoporosis Canada 2023 Guideline Update Group. Clinical practice guideline for management of osteoporosis and fracture prevention in Canada: 2023 update. CMAJ. 2023 Oct 10;195(39):E1333-48. doi: 10.1503/cmaj.221647.
Tomasević-Todorović S, Simić-Panić D, Knežević A, Demeši-Drljan Č, Marić D, Hanna F. Osteoporosis in patients with stroke: A cross-sectional study. Ann Indian Acad Neurol. 2016 Apr-Jun;19(2):286-8. doi: 10.4103/0972-2327.173409.
Arceo-Mendoza RM, Camacho PM. Postmenopausal Osteoporosis: Latest Guidelines. Endocrinol Metab Clin North Am. 2021 Jun;50(2):167-78. doi: 10.1016/j.ecl.2021.03.009.
Kanis JA, Johansson H, Harvey NC, Gudnason V, Sigurdsson G, Siggeirsdottir K, et al. Adjusting conventional FRAX estimates of fracture probability according to the recency of sentinel fractures. Osteoporos Int. 2020 Oct;31(10):1817-28. doi: 10.1007/s00198-020-05517-7.
Kanis JA, Johansson H, Harvey NC, Lorentzon M, Liu E, Vandenput L, et al. Adjusting conventional FRAX estimates of fracture probability according to the number of prior falls in the preceding year. Osteoporos Int. 2023 Mar;34(3):479-87. doi: 10.1007/s00198-022-06633-2.
Johansson H, Kanis JA, Odén A, Leslie WD, Fujiwara S, Glüer CC, et al. Impact of femoral neck and lumbar spine BMD discordances on FRAX probabilities in women: a meta-analysis of international cohorts. Calcif Tissue Int. 2014 Nov;95(5):428-35. doi: 10.1007/s00223-014-9911-2.
McCloskey EV, Odén A, Harvey NC, Leslie WD, Hans D, Johansson H, et al. A Meta-Analysis of Trabecular Bone Score in Fracture Risk Prediction and Its Relationship to FRAX. J Bone Miner Res. 2016 May;31(5):940-8. doi: 10.1002/jbmr.2734.
Puksun K, Pongchaiyakul C, Pakchotanon R, Narongroeknawin P, Leosuthamas P, Arunthanachaikul T, et al. Comparison of different intervention thresholds for the treatment of glucocorticoid-induced osteoporosis: a cross-sectional study. BMC Rheumatol. 2025 Apr 2;9(1):38. doi: 10.1186/s41927-025-00488-w.
Rotta D, Fassio A, Rossini M, Giollo A, Viapiana O, Orsolini G, et al. Osteoporosis in Inflammatory Arthritides: New Perspective on Pathogenesis and Treatment. Front Med (Lausanne). 2020 Dec 1;7:613720. doi: 10.3389/fmed.2020.613720.
Kanis JA, Johansson H, McCloskey EV, Liu E, Schini M, Vandenput L, et al. Rheumatoid arthritis and subsequent fracture risk: an individual person meta-analysis to update FRAX. Osteoporos Int. 2025 Apr;36(4):653-671. doi: 10.1007/s00198-025-07397-1.
Seabra Rato M, Oliveira Pinheiro F, Garcia S, Fernandes B, Bernardo A, Gaio R, et al. FRAX 10-year fracture risk in rheumatoid arthritis assessed with and without bone mineral density – are we treating our patients under bDMARDs? ARP Rheumatol [Internet]. 2023 Jan-Mar;2(1):47-52. Available from: https://www.arprheumatology.com/article_download.php?id=1613
Yu SF, Chen JF, Chen YC, Lai HM, Ko CH, Chiu WC, et al. Beyond bone mineral density, FRAX-based tailor-made intervention thresholds for therapeutic decision in subjects on glucocorticoid: A nationwide osteoporosis survey. Medicine (Baltimore). 2017 Feb;96(5):e5959. doi: 10.1097/MD.0000000000005959.
Kates SL, Miclau T. The fracture liaison service: its history, current state, how it works, and future directions. OTA Int. 2022 Jun 9;5(3 Suppl):e192. doi: 10.1097/OI9.0000000000000192.
Muniyasamy R, Manjubala I. Insights into the Mechanism of Osteoporosis and the Available Treatment Options. Curr Pharm Biotechnol. 2024;25(12):1538-51. doi: 10.2174/0113892010273783231027073117.
Camacho PM, Petak SM, Binkley N, Diab DL, Eldeiry LS, Farooki A, et al. American Association of Clinical Endocrinologists. Clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis – 2020 Update. Endocr Pract. 2020 May;26(Suppl 1):1-46. doi: 10.4158/GL-2020-0524SUPPL.
Gupta N, Kanwar N, Arora A, Khatri K, Kanwal A. The interplay of rheumatoid arthritis and osteoporosis: exploring the pathogenesis and pharmacological approaches. Clin Rheumatol. 2024 May;43(5):1421-33. doi: 10.1007/s10067-024-06932-5.
Humphrey MB, Russell L, Danila MI, Fink HA, Guyatt G, Cannon M, et al. 2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Rheumatol. 2023 Dec;75(12):2088-2102. doi: 10.1002/art.42646.
Andreasen C, Dahl C, Frihagen F, Borgen TT, Basso T, Gjertsen JE, et al. Fracture liaison service (FLS) is associated with lower subsequent fragility fracture risk and mortality: NoFRACT (the Norwegian capture the fracture initiative). Osteoporos Int. 2025 Mar;36(3):501-12. doi: 10.1007/s00198-024-07376-y.
