Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Research Article

Global Publication Trends and Research Hotspots of the Immune System and Osteoporosis: A Bibliometric and Visualization Analysis from 2012 to 2022

Author(s): Jinlong Zhao, Yaoxing Dou, Guihong Liang, Hetao Huang, Kunhao Hong, Weiyi Yang, Guanghui Zhou, Bangxin Sha, Jun Liu* and Lingfeng Zeng*

Volume 24, Issue 4, 2024

Published on: 20 October, 2023

Page: [455 - 467] Pages: 13

DOI: 10.2174/0118715303257269231011073100

Price: $65

Abstract

Background: Osteoporosis (OP) is a systemic bone metabolism disorder in which the immune system and bone metabolism interact.

Objective: The purpose of this study was to explore the research status, hot spots and trends regarding the influence of the immune system on OP and to provide a basis for research directions and applications in this field.

Methods: We searched and collected literature about the immune system and OP published from 2012 to 2022 in the Web of Science Core Collection database. All the included studies were subjected to bibliometrics analysis using Hiplot Pro, VOSviewer and CiteSpace software to produce statistics and visual analyses of the literature output, countries, institutions, authors, keywords and journals.

Results: A total of 1201 papers were included, and the number of citations of these articles reached 31,776. The number of publications and citations on the immune system and OP has increased year by year. The top three countries with the greatest number of papers published were China, the United States of America (USA) and Italy. The two institutions with the largest number of papers published were Sichuan University and Soochow University, both located in China. De Martinis Massimo (Italy) and Ginaldi Lia (Italy) are prolific authors in this field. The representative academic journals are Osteoporosis International, Frontiers in Immunology, Journal of Bone and Mineral Research, PloS One and Bone. The results of the keyword cooccurrence analysis showed that the research topics in this field mainly focused on T cells, cytokines, signaling pathways, vitamin D, postmenopausal OP and immune diseases. The keyword burst results showed that zoledronic acid, chain fatty acids and gut microbiota are the frontiers and trends of future research on this topic.

Conclusion: The influence of the immune system on OP has been widely studied, and the current research in this field focuses on the effect or mechanism of immune-related cytokines, signaling pathways and vitamin D on OP. Future research trends in this field should focus on the immune regulation mechanism and clinical transformation of zoledronic acid, chain fatty acids and the gut microbiota in OP.

Keywords: Bibliometrics, bone metabolism, immune system, osteoporosis, visualization, postmenopausal osteoporosis.

Graphical Abstract
[1]
Liang, B.; Burley, G.; Lin, S.; Shi, Y.C. Osteoporosis pathogenesis and treatment: Existing and emerging avenues. Cell. Mol. Biol. Lett., 2022, 27(1), 72.
[http://dx.doi.org/10.1186/s11658-022-00371-3] [PMID: 36058940]
[2]
Chin, K.Y.; Ng, B.N.; Rostam, M.K.I.; Muhammad F., N.F.D.; Raman, V.; Mohamed Y., F.; Syed H., S.A.; Ekeuku, S.O. A mini review on osteoporosis: From biology to pharmacological management of bone loss. J. Clin. Med., 2022, 11(21), 6434.
[http://dx.doi.org/10.3390/jcm11216434] [PMID: 36362662]
[3]
Carey, J.J.; Chih-Hsing Wu, P.; Bergin, D. Risk assessment tools for osteoporosis and fractures in 2022. Best Pract. Res. Clin. Rheumatol., 2022, 36(3), 101775.
[http://dx.doi.org/10.1016/j.berh.2022.101775] [PMID: 36050210]
[4]
Patel, D.; Wairkar, S. Bone regeneration in osteoporosis: Opportunities and challenges. Drug Deliv. Transl. Res., 2023, 13(2), 419-432.
[http://dx.doi.org/10.1007/s13346-022-01222-6] [PMID: 35994158]
[5]
Anam, A.K.; Insogna, K. Update on osteoporosis screening and management. Med. Clin. North Am., 2021, 105(6), 1117-1134.
[http://dx.doi.org/10.1016/j.mcna.2021.05.016] [PMID: 34688418]
[6]
Kim, J.M.; Lin, C.; Stavre, Z.; Greenblatt, M.B.; Shim, J.H. Osteoblast-osteoclast communication and bone homeostasis. Cells, 2020, 9(9), 2073.
[http://dx.doi.org/10.3390/cells9092073] [PMID: 32927921]
[7]
Chen, X.; Wang, Z.; Duan, N.; Zhu, G.; Schwarz, E.M.; Xie, C. Osteoblast–osteoclast interactions. Connect. Tissue Res., 2018, 59(2), 99-107.
[http://dx.doi.org/10.1080/03008207.2017.1290085] [PMID: 28324674]
[8]
Sieberath, A.; Della Bella, E.; Ferreira, A.M.; Gentile, P.; Eglin, D.; Dalgarno, K. A comparison of osteoblast and osteoclast in vitro co-culture models and their translation for preclinical drug testing applications. Int. J. Mol. Sci., 2020, 21(3), 912.
[http://dx.doi.org/10.3390/ijms21030912] [PMID: 32019244]
[9]
Angelopoulou, F.; Bogdanos, D.; Dimitroulas, T.; Sakkas, L.; Daoussis, D. Immune checkpoint inhibitor-induced musculoskeletal manifestations. Rheumatol. Int., 2021, 41(1), 33-42.
[http://dx.doi.org/10.1007/s00296-020-04665-7] [PMID: 32743706]
[10]
Generaal, E.; Vogelzangs, N.; Macfarlane, G.J.; Geenen, R.; Smit, J.H.; Dekker, J.; Penninx, B.W.J.H. Basal inflammation and innate immune response in chronic multisite musculoskeletal pain. Pain, 2014, 155(8), 1605-1612.
[http://dx.doi.org/10.1016/j.pain.2014.05.007] [PMID: 24813297]
[11]
Allenbach, Y.; Anquetil, C.; Manouchehri, A.; Benveniste, O.; Lambotte, O.; Lebrun-Vignes, B.; Spano, J.P.; Ederhy, S.; Klatzmann, D.; Rosenzwajg, M.; Fautrel, B.; Cadranel, J.; Johnson, D.B.; Moslehi, J.J.; Salem, J.E. Immune checkpoint inhibitor-induced myositis, the earliest and most lethal complication among rheumatic and musculoskeletal toxicities. Autoimmun. Rev., 2020, 19(8), 102586.
[http://dx.doi.org/10.1016/j.autrev.2020.102586] [PMID: 32535094]
[12]
Terashima, A.; Takayanagi, H. Overview of osteoimmunology. Calcif. Tissue Int., 2018, 102(5), 503-511.
[http://dx.doi.org/10.1007/s00223-018-0417-1] [PMID: 29589061]
[13]
Zhang, W.; Dang, K.; Huai, Y.; Qian, A. Osteoimmunology: The regulatory roles of t lymphocytes in osteoporosis. Front. Endocrinol., 2020, 11, 465.
[http://dx.doi.org/10.3389/fendo.2020.00465] [PMID: 32849268]
[14]
Arron, J.R.; Choi, Y. Bone versus immune system. Nature, 2000, 408(6812), 535-536.
[http://dx.doi.org/10.1038/35046196] [PMID: 11117729]
[15]
Ginaldi, L.; De Martinis, M. Osteoimmunology and beyond. Curr. Med. Chem., 2016, 23(33), 3754-3774.
[http://dx.doi.org/10.2174/0929867323666160907162546] [PMID: 27604089]
[16]
Marie, J.C.; Bonnelye, E. Effects of estrogens on osteoimmunology: A role in bone metastasis. Front. Immunol., 2022, 13, 899104.
[http://dx.doi.org/10.3389/fimmu.2022.899104] [PMID: 35677054]
[17]
Rauner, M.; Sipos, W.; Thiele, S.; Pietschmann, P. Advances in osteoimmunology: Pathophysiologic concepts and treatment opportunities. Int. Arch. Allergy Immunol., 2013, 160(2), 114-125.
[http://dx.doi.org/10.1159/000342426] [PMID: 23018236]
[18]
Pacifici, R. Osteoimmunology and its implications for transplantation. Am. J. Transplant., 2013, 13(9), 2245-2254.
[http://dx.doi.org/10.1111/ajt.12380]
[19]
Ragipoglu, D.; Dudeck, A.; Haffner-Luntzer, M.; Voss, M.; Kroner, J.; Ignatius, A.; Fischer, V. The role of mast cells in bone metabolism and bone disorders. Front. Immunol., 2020, 11, 163.
[http://dx.doi.org/10.3389/fimmu.2020.00163] [PMID: 32117297]
[20]
Kitaura, H.; Marahleh, A.; Ohori, F.; Noguchi, T.; Nara, Y.; Pramusita, A.; Kinjo, R.; Ma, J.; Kanou, K.; Mizoguchi, I. Role of the interaction of tumor necrosis factor-α and tumor necrosis factor receptors 1 and 2 in bone-related cells. Int. J. Mol. Sci., 2022, 23(3), 1481.
[http://dx.doi.org/10.3390/ijms23031481] [PMID: 35163403]
[21]
Kim, H.J.; Yoon, H.J.; Kim, S.Y.; Yoon, Y.R. A medium-chain fatty acid, capric acid, inhibits RANKL-induced osteoclast differentiation via the suppression of NF-κB signaling and blocks cytoskeletal organization and survival in mature osteoclasts. Mol. Cells, 2014, 37(8), 598-604.
[http://dx.doi.org/10.14348/molcells.2014.0153] [PMID: 25134536]
[22]
Ono, T.; Hayashi, M.; Sasaki, F.; Nakashima, T. RANKL biology: Bone metabolism, the immune system, and beyond. Inflamm. Regen., 2020, 40(1), 2.
[http://dx.doi.org/10.1186/s41232-019-0111-3] [PMID: 32047573]
[23]
Smith, D.R. Bibliometrics, dermatology and contact dermatitis. Contact Dermat., 2008, 59(3), 133-136.
[http://dx.doi.org/10.1111/j.1600-0536.2008.01405.x] [PMID: 18759892]
[24]
Chen, C.; Chen, Y. Searching for clinical evidence in CiteSpace. AMIA Annu. Symp. Proc., 2005, 2005, 121-125.
[PMID: 16779014]
[25]
Synnestvedt, M.B.; Chen, C.; Holmes, J.H. CiteSpace II: visualization and knowledge discovery in bibliographic databases. AMIA Annu. Symp. Proc., 2005, 2005, 724-728.
[PMID: 16779135]
[26]
Sirufo, M.M.; De Pietro, F.; Catalogna, A.; Ginaldi, L.; De Martinis, M. The microbiota-bone-allergy interplay. Int. J. Environ. Res. Public Health, 2021, 19(1), 282.
[http://dx.doi.org/10.3390/ijerph19010282] [PMID: 35010543]
[27]
De Martinis, M.; Allegra, A.; Sirufo, M.M.; Tonacci, A.; Pioggia, G.; Raggiunti, M.; Ginaldi, L.; Gangemi, S.; Vitamin, D. Vitamin D deficiency, osteoporosis and effect on autoimmune diseases and hematopoiesis: A review. Int. J. Mol. Sci., 2021, 22(16), 8855.
[http://dx.doi.org/10.3390/ijms22168855] [PMID: 34445560]
[28]
De Martinis, M.; Ginaldi, L.; Sirufo, M.M.; Bassino, E.M.; De Pietro, F.; Pioggia, G.; Gangemi, S. IL-33/Vitamin D crosstalk in psoriasis-associated osteoporosis. Front. Immunol., 2021, 11, 604055.
[http://dx.doi.org/10.3389/fimmu.2020.604055] [PMID: 33488605]
[29]
De Martinis, M.; Ginaldi, L.; Sirufo, M.M.; Pioggia, G.; Calapai, G.; Gangemi, S.; Mannucci, C. Alarmins in osteoporosis, RAGE, IL-1, and IL-33 pathways: A literature review. Medicina, 2020, 56(3), 138.
[http://dx.doi.org/10.3390/medicina56030138] [PMID: 32204562]
[30]
Fischer, L.; Herkner, C.; Kitte, R.; Dohnke, S.; Riewaldt, J.; Kretschmer, K.; Garbe, A.I. Foxp3+ regulatory T cells in bone and hematopoietic homeostasis. Front. Endocrinol., 2019, 10, 578.
[http://dx.doi.org/10.3389/fendo.2019.00578] [PMID: 31551927]
[31]
Yuan, F.L.; Li, X.; Lu, W.G.; Xu, R.S.; Zhao, Y.Q.; Li, C.W.; Li, J.P.; Chen, F.H. Regulatory T cells as a potent target for controlling bone loss. Biochem. Biophys. Res. Commun., 2010, 402(2), 173-176.
[http://dx.doi.org/10.1016/j.bbrc.2010.09.120] [PMID: 20920469]
[32]
Adeel, S.; Singh, K.; Vydareny, K.H.; Kumari, M.; Shah, E.; Weitzmann, M.N.; Tangpricha, V. Bone loss in surgically ovariectomized premenopausal women is associated with T lymphocyte activation and thymic hypertrophy. J. Investig. Med., 2013, 61(8), 1178-1183.
[http://dx.doi.org/10.2310/JIM.0000000000000016] [PMID: 24141238]
[33]
Shao, B.; Fu, X.; Yu, Y.; Yang, D. Regulatory effects of miRNA-181a on FasL expression in bone marrow mesenchymal stem cells and its effect on CD4+T lymphocyte apoptosis in estrogen deficiency-induced osteoporosis. Mol. Med. Rep., 2018, 18(1), 920-930.
[http://dx.doi.org/10.3892/mmr.2018.9026] [PMID: 29845202]
[34]
Lacey, D.L.; Boyle, W.J.; Simonet, W.S.; Kostenuik, P.J.; Dougall, W.C.; Sullivan, J.K.; Martin, J.S.; Dansey, R. Bench to bedside: Elucidation of the OPG–RANK–RANKL pathway and the development of denosumab. Nat. Rev. Drug Discov., 2012, 11(5), 401-419.
[http://dx.doi.org/10.1038/nrd3705] [PMID: 22543469]
[35]
Sun, M.; Cao, Y.; Yang, X.; An, F.; Wu, H.; Wang, J. DNA methylation in the OPG/RANK/RANKL pathway is associated with steroid-induced osteonecrosis of the femoral head. BMC Musculoskelet. Disord., 2021, 22(1), 599.
[http://dx.doi.org/10.1186/s12891-021-04472-6] [PMID: 34187427]
[36]
Ni, X.; Wu, B.; Li, S.; Zhu, W.; Xu, Z.; Zhang, G.; Cui, H.; Bai, Q.; Wang, J. Equol exerts a protective effect on postmenopausal osteoporosis by upregulating OPG/RANKL pathway. Phytomedicine, 2023, 108, 154509.
[http://dx.doi.org/10.1016/j.phymed.2022.154509] [PMID: 36288653]
[37]
Titanji, K. Beyond antibodies: B cells and the OPG/RANK-RANKL pathway in health, non-HIV disease and HIV-induced bone loss. Front. Immunol., 2017, 8, 1851.
[http://dx.doi.org/10.3389/fimmu.2017.01851] [PMID: 29312334]
[38]
Zhao, L.; Li, M.; Sun, H. Effects of dietary calcium to available phosphorus ratios on bone metabolism and osteoclast activity of the OPG/RANK/RANKL signalling pathway in piglets. J. Anim. Physiol. Anim. Nutr., 2019, 103(4), 1224-1232.
[http://dx.doi.org/10.1111/jpn.13115] [PMID: 31062421]
[39]
Rattazzi, M.; Faggin, E.; Buso, R.; Di Virgilio, R.; Puato, M.; Plebani, M.; Zaninotto, M.; Palmosi, T.; Bertacco, E.; Fadini, G.P.; Pauletto, P. Atorvastatin reduces circulating osteoprogenitor cells and T-Cell RANKL expression in osteoporotic women: Implications for the bone-vascular axis. Cardiovasc. Ther., 2016, 34(1), 13-20.
[http://dx.doi.org/10.1111/1755-5922.12163] [PMID: 26506085]
[40]
Figeac, F.; Andersen, D.C.; Nipper Nielsen, C.A.; Ditzel, N.; Sheikh, S.P.; Skjødt, K.; Kassem, M.; Jensen, C.H.; Abdallah, B.M. Antibody-based inhibition of circulating DLK1 protects from estrogen deficiency-induced bone loss in mice. Bone, 2018, 110, 312-320.
[http://dx.doi.org/10.1016/j.bone.2018.02.030] [PMID: 29499415]
[41]
D’Amelio, P. The immune system and postmenopausal osteoporosis. Immunol. Invest., 2013, 42(7), 544-554.
[http://dx.doi.org/10.3109/08820139.2013.822764] [PMID: 24004058]
[42]
Faienza, M.F.; Ventura, A.; Marzano, F.; Cavallo, L. Postmenopausal osteoporosis: The role of immune system cells. Clin. Dev. Immunol., 2013, 2013, 1-6.
[http://dx.doi.org/10.1155/2013/575936] [PMID: 23762093]
[43]
D’Amelio, P.; Sassi, F.; Buondonno, I.; Fornelli, G.; Spertino, E.; D’Amico, L.; Marchetti, M.; Lucchiari, M.; Roato, I.; Isaia, G.C. Treatment with intermittent PTH increases Wnt10b production by T cells in osteoporotic patients. Osteoporos. Int., 2015, 26(12), 2785-2791.
[http://dx.doi.org/10.1007/s00198-015-3189-8] [PMID: 26068297]
[44]
Fernandez Lahore, G.; Raposo, B.; Lagerquist, M.; Ohlsson, C.; Sabatier, P.; Xu, B.; Aoun, M.; James, J.; Cai, X.; Zubarev, R.A.; Nandakumar, K.S.; Holmdahl, R. Vitamin D3 receptor polymorphisms regulate T cells and T cell-dependent inflammatory diseases. Proc. Natl. Acad. Sci., 2020, 117(40), 24986-24997.
[http://dx.doi.org/10.1073/pnas.2001966117] [PMID: 32958661]
[45]
Al-Jaberi, F.A.H.; Kongsbak-Wismann, M.; Aguayo-Orozco, A.; Krogh, N.; Buus, T.B.; Lopez, D.V.; Rode, A.K.O.; Gravesen, E.; Olgaard, K.; Brunak, S.; Woetmann, A.; Ødum, N.; Bonefeld, C.M.; Geisler, C. Impaired vitamin D signaling in T cells from a family with hereditary vitamin D resistant rickets. Front. Immunol., 2021, 12, 684015.
[http://dx.doi.org/10.3389/fimmu.2021.684015] [PMID: 34093587]
[46]
Bold, A.; Gross, H.; Holzmann, E.; Smetak, M.; Birkmann, J.; Bertsch, T.; Triebel, J.; Sauer, K.; Wilhelm, M.; Hoeres, T. Immune activating and inhibiting effects of calcitriol on γδ T cells and NK cells. Immunobiology, 2022, 227(6), 152286.
[http://dx.doi.org/10.1016/j.imbio.2022.152286] [PMID: 36244091]
[47]
Harrison, S.R.; Li, D.; Jeffery, L.E.; Raza, K.; Hewison, M.; Vitamin, D. Vitamin D, autoimmune disease and rheumatoid arthritis. Calcif. Tissue Int., 2020, 106(1), 58-75.
[http://dx.doi.org/10.1007/s00223-019-00577-2] [PMID: 31286174]
[48]
Gallone, G.; Haerty, W.; Disanto, G.; Ramagopalan, S.V.; Ponting, C.P.; Berlanga-Taylor, A.J. Identification of genetic variants affecting vitamin D receptor binding and associations with autoimmune disease. Hum. Mol. Genet., 2017, 26(11), 2164-2176.
[http://dx.doi.org/10.1093/hmg/ddx092] [PMID: 28335003]
[49]
Hayes, C.E.; Hubler, S.L.; Moore, J.R.; Barta, L.E.; Praska, C.E.; Nashold, F.E.; Vitamin, D. Vitamin D actions on CD4+ T cells in autoimmune disease. Front. Immunol., 2015, 6, 100.
[http://dx.doi.org/10.3389/fimmu.2015.00100] [PMID: 25852682]
[50]
Sarhan, D.; Leijonhufvud, C.; Murray, S.; Witt, K.; Seitz, C.; Wallerius, M.; Xie, H.; Ullén, A.; Harmenberg, U.; Lidbrink, E.; Rolny, C.; Andersson, J.; Lundqvist, A. Zoledronic acid inhibits NFAT and IL-2 signaling pathways in regulatory T cells and diminishes their suppressive function in patients with metastatic cancer. OncoImmunology, 2017, 6(8), e1338238-e1338238.
[http://dx.doi.org/10.1080/2162402X.2017.1338238] [PMID: 28920001]
[51]
Cui, M.; Zhang, N.; Zhang, G.; Han, L.; Yu, L.Z. Investigation of intravenous zoledronic acid therapy on circulating lymphocyte subpopulation in patients with primary osteoporosis: A pilot study. Curr. Ther. Res. Clin. Exp., 2021, 94, 100634.
[http://dx.doi.org/10.1016/j.curtheres.2021.100634] [PMID: 34306272]
[52]
Wang, N.; Ma, S.; Fu, L. Gut microbiota feature of senile osteoporosis by shallow shotgun sequencing using aged rats model. Genes, 2022, 13(4), 619.
[http://dx.doi.org/10.3390/genes13040619] [PMID: 35456425]
[53]
Seely, K.D.; Kotelko, C.A.; Douglas, H.; Bealer, B.; Brooks, A.E. The human gut microbiota: A key mediator of osteoporosis and osteogenesis. Int. J. Mol. Sci., 2021, 22(17), 9452.
[http://dx.doi.org/10.3390/ijms22179452] [PMID: 34502371]
[54]
Rizzoli, R. Nutritional influence on bone: Role of gut microbiota. Aging Clin. Exp. Res., 2019, 31(6), 743-751.
[http://dx.doi.org/10.1007/s40520-019-01131-8] [PMID: 30710248]
[55]
Dar, H.Y.; Pal, S.; Shukla, P.; Mishra, P.K.; Tomar, G.B.; Chattopadhyay, N.; Srivastava, R.K. Bacillus clausii inhibits bone loss by skewing Treg-Th17 cell equilibrium in postmenopausal osteoporotic mice model. Nutrition, 2018, 54, 118-128.
[http://dx.doi.org/10.1016/j.nut.2018.02.013] [PMID: 29793054]
[56]
Egawa, G.; Honda, T.; Kabashima, K. SCFAs control skin immune responses via increasing tregs. J. Invest. Dermatol., 2017, 137(4), 800-801.
[http://dx.doi.org/10.1016/j.jid.2016.12.022] [PMID: 28340682]
[57]
Parada Venegas, D.; De la Fuente, M.K.; Landskron, G.; González, M.J.; Quera, R.; Dijkstra, G.; Harmsen, H.J.M.; Faber, K.N.; Hermoso, M.A. Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Front. Immunol., 2019, 10, 277.
[http://dx.doi.org/10.3389/fimmu.2019.00277] [PMID: 30915065]
[58]
Massy, Z.A.; Drueke, T.B. Gut microbiota orchestrates PTH action in bone: Role of butyrate and T cells. Kidney Int., 2020, 98(2), 269-272.
[http://dx.doi.org/10.1016/j.kint.2020.03.004] [PMID: 32600825]
[59]
Li, Y.; Toraldo, G.; Li, A.; Yang, X.; Zhang, H.; Qian, W.P.; Weitzmann, M.N. B cells and T cells are critical for the preservation of bone homeostasis and attainment of peak bone mass in vivo. Blood, 2007, 109(9), 3839-3848.
[http://dx.doi.org/10.1182/blood-2006-07-037994] [PMID: 17202317]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy