The role of bone marrow adiposity in rheumatoid arthritis pathogenesis
DOI:
https://doi.org/10.18203/2320-6012.ijrms20261372Keywords:
Bone marrow adiposity, Rheumatoid arthritis, Adipokines, Osteoclastogenesis, Bone remodeling, InflammationAbstract
Bone marrow adiposity (BMA) has historically been thought of as a passive energy reserve in the medullary cavity, new research indicates that it is actually a dynamic endocrine organ that affects immunological responses, bone remodeling, and hematopoiesis. Changes in BMA composition and behavior have been increasingly identified in rheumatoid arthritis (RA), an autoimmune disorder marked by joint damage and synovial inflammation. Immune dysregulation, decreased osteoblastogenesis, and osteoclast activation may be caused by dysregulated adipokine production, changed lipid metabolism, and compromised bone marrow microenvironment function. The physiological function of BMA, its changes in RA, and the mechanisms relating marrow fat to joint pathogenesis are all summarized in this paper. In addition, we go over cutting-edge imaging techniques for measuring BMA in vivo, provide an overview of clinical data regarding its involvement in the course of the disease, and investigate possible treatment approaches that target BMA modulation to enhance muscles and joints outcomes in RA. Gaining insight into this little-known facet of RA pathophysiology may pave the way for the development of biomarkers and focused therapeutic approaches.
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aluchukwu EOO, Onubuogu AC, Ugochi CMJ, Tobechukwu OL. Status of erythrocyte sedimentation rate, platelet counts and serum phosphate in patients with rheumatoid arthritis in Owerri. Global Health Dynamics. 2025;1(1):14-9. DOI: https://doi.org/10.64229/yh1y6w35
Chen Y, Deng B, Nie Y. Global burden and trend of rheumatic heart disease among women of childbearing age, 1990-2021, with projection to 2040. BMC Cardiovascular Disorders. 2025;25(1):580. DOI: https://doi.org/10.1186/s12872-025-05021-y
Finckh A, Gilbert B, Hodkinson, B. Global epidemiology of rheumatoid arthritis. Nature Rev Rheumatol. 2022;18(10):591-602. DOI: https://doi.org/10.1038/s41584-022-00827-y
Chopra A. Disease burden of rheumatic diseases in India: COPCORD perspective. Indian J Rheumatol. 2015;10(2):70-7. DOI: https://doi.org/10.1016/j.injr.2015.04.002
Zúñiga A, Álvarez ALL, Carbal-Reyes L, Daniel R, Juan-Camilo D, Gloria V, et al. Survey to evaluate exposure to environmental factors in patients with rheumatoid arthritis. Reumatol Clín. 2025;21(6):501916. DOI: https://doi.org/10.1016/j.reumae.2025.501916
Kumari M, Sadhu P, Shah N, Talele C, Gohil D. Comprehensive review of rheumatoid arthritis: insights, challenges, and prospects. J Adv Zool. 2024;45(1):567-75. DOI: https://doi.org/10.17762/jaz.v45iS1.2892
Moscatelli F, Monda A, Messina G, Elisabetta P, Marcellino M, Marilena DP, et al. Exploring the interplay between bone marrow stem cells and obesity. Int J Molecular Sci. 2024;25(5):2715. DOI: https://doi.org/10.3390/ijms25052715
Gao C. Preclinical assessment of novel strategies to enhance bone regeneration. Montreal, QC: McGill University. 2014.
Shin E, Koo JS. The role of adipokines and bone marrow adipocytes in breast cancer bone metastasis. Int J Molecular Sci. 2020;21(14):4967. DOI: https://doi.org/10.3390/ijms21144967
Li Y, Cao S, Gaculenko A, Yifan Z, Aline B, Xiaoxiang C. Distinct metabolism of bone marrow adipocytes and their role in bone metastasis. Front Endocrinol. 2022;13:902033. DOI: https://doi.org/10.3389/fendo.2022.902033
Hawkes CP, Mostoufi-Moab S. Fat-bone interaction within the bone marrow milieu: impact on hematopoiesis and systemic energy metabolism. Bone. 2019;119:57-64. DOI: https://doi.org/10.1016/j.bone.2018.03.012
Riaz M, Rasool G, Yousaf R, Hina F, Naveed M, Hasan E. Anti-rheumatic potential of biological DMARDs and protagonistic role of biomarkers in early detection and management of rheumatoid arthritis. Innate Immunity. 2025;31:17534259251324820. DOI: https://doi.org/10.1177/17534259251324820
Wang L, Zhang H, Wang S, Chen X, Su J. Bone marrow adipocytes: a critical player in the bone marrow microenvironment. Front Cell Developmental Biol. 2021;9:770705. DOI: https://doi.org/10.3389/fcell.2021.770705
Mercier FE, Ragu C, Scadden DT. The bone marrow at the crossroads of blood and immunity. Nature Rev Immunol. 2012;12(1):49-60. DOI: https://doi.org/10.1038/nri3132
Pierce JL, Begun DL, Westendorf JJ, McGee-Lawrence ME. Defining osteoblast and adipocyte lineages in the bone marrow. Bone. 2019;118:2-7. DOI: https://doi.org/10.1016/j.bone.2018.05.019
Zhang X, Tian L, Majumdar A, Scheller EL. Function and regulation of bone marrow adipose tissue in health and disease: state of the field and clinical considerations. Comprehensive Physiol. 2024;14(3):5521-79. DOI: https://doi.org/10.1002/j.2040-4603.2024.tb00300.x
Tencerova M, Ferencakova M, Kassem M. Bone marrow adipose tissue: role in bone remodeling and energy metabolism. Best Pract Res Clin Endocrinol Metabol. 2021;35(4):101545. DOI: https://doi.org/10.1016/j.beem.2021.101545
Nisar A, Jagtap S, Vyavahare S, Manasi D, Abhay H, Prabhakar R, et al. Phytochemicals in the treatment of inflammation-associated diseases: the journey from preclinical trials to clinical practice. Front Pharmacol. 2023;14:1177050. DOI: https://doi.org/10.3389/fphar.2023.1177050
Toussirot E. The contribution of adipokines to joint inflammation in inflammatory rheumatic diseases. Front Endocrinol. 2020;11:606560. DOI: https://doi.org/10.3389/fendo.2020.606560
Bilski J, Schramm-Łuc A, Szczepanik M, Agnieszka Irena MB, Joanna B, Kevin L, et al. Adipokines in rheumatoid arthritis: emerging biomarkers and therapeutic targets. Biomedicines. 2023;11(11):2998. DOI: https://doi.org/10.3390/biomedicines11112998
Zhu J, Ruan G, Cen H, Tao M, Shuang Z, Yuanyuan W, et al. Association of serum levels of inflammatory markers and adipokines with joint symptoms and structures in participants with knee osteoarthritis. Rheumatology (Oxford). 2022;61(3):1044-52. DOI: https://doi.org/10.1093/rheumatology/keab479
Roy PK, Islam J, Lalhlenmawia H. Prospects of potential adipokines as therapeutic agents in obesity-linked atherogenic dyslipidemia and insulin resistance. Egyptian Heart J. 2023;75(1):24. DOI: https://doi.org/10.1186/s43044-023-00352-7
Hu Y, Li X, Zhi X, Wei C, Biaotong H, Huiwen C, et al. RANKL from bone marrow adipose lineage cells promotes osteoclast formation and bone loss. EMBO Rep. 2021;22(7):e52481. DOI: https://doi.org/10.15252/embr.202152481
Fan Y, Elkhalek M, Zhang Y, Lu L, Qi T, Nareekarn C, et al. Bone marrow adipocytes: key players in vascular niches, aging, and disease. Front Cell Developmental Biol. 2025;13:1633801. DOI: https://doi.org/10.3389/fcell.2025.1633801
Mukohira H, Hara T, Abe S, Tani-Ichi S, Sehara-Fujisawa A, Nagasawa T, et al. Mesenchymal stromal cells in bone marrow express adiponectin and are efficiently targeted by an adiponectin promoter-driven Cre transgene. Int Immunol. 2019;31(11):729-42. DOI: https://doi.org/10.1093/intimm/dxz042
Comazzetto S, Shen B, Morrison SJ. Niches that regulate stem cells and hematopoiesis in adult bone marrow. Developmental Cell. 2021;56(13):1848-60. DOI: https://doi.org/10.1016/j.devcel.2021.05.018
Lundgren H, Martinsson K, Cederbrant K, Johan J, Daniel M, Madeyski-Bengtson K, et al. HLA-DR7 and HLA-DQ2: transgenic mouse strains tested as a model system for ximelagatran hepatotoxicity. PLoS ONE. 2019;12(9):e0184744. DOI: https://doi.org/10.1371/journal.pone.0184744
Catrina A, Krishnamurthy A, Rethi B. Current view on the pathogenic role of anti-citrullinated protein antibodies in rheumatoid arthritis. RMD Open. 2021;7(1):e001228. DOI: https://doi.org/10.1136/rmdopen-2020-001228
Ranneh Y, Ali F, Akim AM. Crosstalk between reactive oxygen species and pro-inflammatory markers in developing various chronic diseases: a review. Applied Biolog Chem. 2017;60(3):327-38. DOI: https://doi.org/10.1007/s13765-017-0285-9
Zhang S, Paul S, Kundu P. NF-κB regulation by gut microbiota decides homeostasis or disease outcome during ageing. Front Cell Developmental Biol. 2022;10:874940. DOI: https://doi.org/10.3389/fcell.2022.874940
Melincovici CS, Boşca AB, Şuşman S, Mariana M, Carina M, Mihnea I, et al. Vascular endothelial growth factor (VEGF)-key factor in normal and pathological angiogenesis. Roma J Morphol Embryol. 2018;59(2):455-67.
Han L, Wang B, Wang R, Song G, Guo C, Weihua X, et al. The shift in the balance between osteoblastogenesis and adipogenesis of mesenchymal stem cells mediated by glucocorticoid receptor. Stem Cell Res Therapy. 2019;10(1):377. DOI: https://doi.org/10.1186/s13287-019-1498-0
Sheu Y, Amati F, Schwartz AV, Michelle ED, Xiaojuan L, Robert B, et al. Vertebral bone marrow fat, bone mineral density and diabetes: the Osteoporotic Fractures in Men (MrOS) study. Bone. 2017;97:299-305. DOI: https://doi.org/10.1016/j.bone.2017.02.001
Kadri A, Binkley N, Daffner SD, Anderson PA. Clinical risk factor status in patients with vertebral fracture but normal bone mineral density. Spine J. 2022;22(10):1634-41. DOI: https://doi.org/10.1016/j.spinee.2022.05.019
Labella R, Vujačić M, Trivanović D. Bone marrow adipose tissue: regulation of osteoblastic niche, hematopoiesis and hematological malignancies. Stem Cell Rev Rep. 2023;19(5):1135-51. DOI: https://doi.org/10.1007/s12015-023-10531-3
Zerbini CAF, Clark P, Mendez-Sanchez L, Pereira RMR, Messina OD, Uña CR, et al. Biologic therapies and bone loss in rheumatoid arthritis. Osteoporosis Int. 2017;28(2):429-46. DOI: https://doi.org/10.1007/s00198-016-3769-2
Seo SS, Lee IS, Lee GH. Intra-articular injection therapy and biologic treatment. In A Strategic Approach to Knee Arthritis Treatment: From Non-Pharmacologic Management to Surgery. Singapore: Springer Singapore. 2021;171-212. DOI: https://doi.org/10.1007/978-981-16-4217-3_10
Veldhuis-Vlug AG, Rosen CJ. Clinical implications of bone marrow adiposity. J Internal Med. 2018;283(2):121-39. DOI: https://doi.org/10.1111/joim.12718
de Sousa RN, Tascilar K, Corte G, Armin A, Ioanna M, Sarah O, et al. Metabolic and molecular imaging in inflammatory arthritis. RMD Open. 2024;10(1):e003880. DOI: https://doi.org/10.1136/rmdopen-2023-003880
Chakraborty R, Majhail NS. Treatment and disease-related complications in multiple myeloma: implications for survivorship. Am J Hematol. 2020;95(6):672-90. DOI: https://doi.org/10.1002/ajh.25764
Lana JF, Purita J, Jeyaraman M, de Souza BF, Rodrigues BL, Huber SC, et al. Innovative approaches in knee osteoarthritis treatment: a comprehensive review of bone marrow-derived products. Biomedicines. 2024;12(12):2812. DOI: https://doi.org/10.3390/biomedicines12122812
Marinelli Busilacchi E, Morsia E, Poloni A. Bone marrow adipose tissue. Cells. 2024;13(9):724. DOI: https://doi.org/10.3390/cells13090724
Gardinier JD, Rostami N, Juliano L, Zhang C. Bone adaptation in response to treadmill exercise in young and adult mice. Bone Rep. 2018;8:29-37. DOI: https://doi.org/10.1016/j.bonr.2018.01.003
Shi Z, Wang L, Luan J, Liqin Y, Xiaohui J, Wenqian Z, et al. Exercise promotes bone marrow microenvironment by inhibiting adipsin in diet-induced male obese mice. Nutrients. 2022;15(1):19. DOI: https://doi.org/10.3390/nu15010019
Li Y, Jin D, Xie W, Longfei W, Weijian C, Jixi X, et al. PPAR-γ and Wnt regulate the differentiation of MSCs into adipocytes and osteoblasts respectively. Current Stem Cell Res Therapy. 2018;13(3):185-92. DOI: https://doi.org/10.2174/1574888X12666171012141908
Mu W, Liang G, Feng Y, Jiang Y, Qu F. The potential therapeutic role of metformin in diabetic and non-diabetic bone impairment. Pharmaceuticals (Basel). 2022;15(10):1274. DOI: https://doi.org/10.3390/ph15101274
Chamani S, Liberale L, Mobasheri L, Fabrizio M, Al-Rasadi K, Jamialahmadi T, et al. The role of statins in the differentiation and function of bone cells. Europ J Clin Investigat. 2021;51(7):e13534. DOI: https://doi.org/10.1111/eci.13534
Abshirini M, Ilesanmi-Oyelere BL, Kruger MC. Potential modulatory mechanisms of action by long-chain polyunsaturated fatty acids on bone cell and chondrocyte metabolism. Progress Lipid Res. 2021;83:101113. DOI: https://doi.org/10.1016/j.plipres.2021.101113
Sirico F, Bianco A, D'Alicandro G, Clotilde C, Stefania M, Rocco S, et al. Effects of physical exercise on adiponectin, leptin, and inflammatory markers in childhood obesity: systematic review and meta-analysis. Childhood Obesity. 2018;14(4):207-17. DOI: https://doi.org/10.1089/chi.2017.0269
Xu D, Gao HJ, Lu CY, Tian HM, Yu XJ. Vitamin D inhibits bone loss in mice with thyrotoxicosis by activating the OPG/RANKL and Wnt/β-catenin signaling pathways. Front Endocrinol. 2022;13:1066089. DOI: https://doi.org/10.3389/fendo.2022.1066089
Blaess J, Walther J, Petitdemange A, Jacques-Eric G, Jean S, Laurent A, et al. Immunosuppressive agents for rheumatoid arthritis: a systematic review of clinical trials and their current development stage. Therapeutic Adv Musculoskeletal Dis. 2020;12:1759720X20959971. DOI: https://doi.org/10.1177/1759720X20959971
Li J, Wu J, Xie Y, Yu X. Bone marrow adipocytes and lung cancer bone metastasis: unraveling the role of adipokines in the tumor microenvironment. Front Oncol. 2024;14:1360471. DOI: https://doi.org/10.3389/fonc.2024.1360471
Howlader MSL, Das H. Multifaceted Role of Osteoclast in Bone Regeneratiom. In: Das, H. (eds) Tissue Repair and Regeneration. Springer, Cham. 2025. DOI: https://doi.org/10.1007/978-3-031-93677-7_6
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