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In the elderly, key features of diseases such as rheumatoid arthritis, particularly in its elderly onset form, and senile osteoporosis are characterized by a decline in sex hormones and the immunoregulatory IL-2; an increase in serum autoantibodies and pro-inflammatory mediators such as TNF-\u03b1, IL-6; and upregulation of bone-related factors RANKL, DKK1, and sclerostin, including the dysregulation of the IL-33\/IL-31 axis. The aim of this review is to examine the key molecular pathways of immunosenescence in osteoimmunology, as well as the potential for therapeutic modulation of inflammaging through biologic and target synthetic disease-modifying antirheumatic drugs, denosumab and romosozumab, with particular attention to their management in elderly patients.<\/jats:p>","DOI":"10.3390\/ijms26199268","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T10:27:53Z","timestamp":1758623273000},"page":"9268","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Rheumatoid Arthritis and Osteoporosis as Prototypes of Immunosenescence in Osteoimmunology: Molecular Pathways of Inflammaging and Targeted Therapies"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0452-3282","authenticated-orcid":false,"given":"Ernesto","family":"Aitella","sequence":"first","affiliation":[{"name":"Department of Life, Health and Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7891-0463","authenticated-orcid":false,"given":"Gianluca","family":"Azzellino","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5807-6601","authenticated-orcid":false,"given":"Ciro","family":"Romano","sequence":"additional","affiliation":[{"name":"Clinical Immunology Outpatient Clinic, Division of Internal Medicine, Department of Advanced Medical and Surgical Sciences, \u201cLuigi Vanvitelli\u201d University of Campania, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1841-2807","authenticated-orcid":false,"given":"Lia","family":"Ginaldi","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4253-1312","authenticated-orcid":false,"given":"Massimo","family":"De Martinis","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lee, K.-A., Flores, R.R., Jang, I.H., Saathoff, A., and Robbins, P.D. (2022). Immune Senescence, Immunosenescence and Aging. Front. Aging, 3.","DOI":"10.3389\/fragi.2022.900028"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0047-6374(02)00171-9","article-title":"Genetic Alterations in the Ageing Immune System: Impact on Infection and Cancer","volume":"124","author":"Effros","year":"2003","journal-title":"Mech. Ageing Dev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s00281-020-00806-z","article-title":"The Interplay between Immunosenescence and Age-Related Diseases","volume":"42","author":"Funchal","year":"2020","journal-title":"Semin. Immunopathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/s41392-023-01502-8","article-title":"Inflammation and Aging: Signaling Pathways and Intervention Therapies","volume":"8","author":"Li","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1186\/s13018-023-04320-4","article-title":"Modulation of the Vitamin D\/Vitamin D Receptor System in Osteoporosis Pathogenesis: Insights and Therapeutic Approaches","volume":"18","author":"Li","year":"2023","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.cca.2018.05.035","article-title":"Role of Nutritional Vitamin D in Osteoporosis Treatment","volume":"484","author":"Hou","year":"2018","journal-title":"Clin. Chim. Acta"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/s41574-018-0059-4","article-title":"Inflammaging: A New Immune\u2013Metabolic Viewpoint for Age-Related Diseases","volume":"14","author":"Franceschi","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s41232-023-00293-3","article-title":"Effect of JAK Inhibitors on the Three Forms of Bone Damage in Autoimmune Arthritis: Joint Erosion, Periarticular Osteopenia, and Systemic Bone Loss","volume":"43","author":"Komagamine","year":"2023","journal-title":"Inflamm. Regen."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1016\/S0047-6374(01)00289-5","article-title":"The Process of Aging Changes the Interplay of the Immune, Endocrine and Nervous Systems","volume":"122","author":"Straub","year":"2001","journal-title":"Mech. Ageing Dev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41392-023-01451-2","article-title":"Immunosenescence: Molecular Mechanisms and Diseases","volume":"8","author":"Liu","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1146\/annurev.biochem.76.060305.151318","article-title":"Structure and Function of Toll Receptors and Their Ligands","volume":"76","author":"Gay","year":"2007","journal-title":"Annu. Rev. Biochem."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Erceg, N., Micic, M., Forouzan, E., and Knezevic, N.N. (2025). The Role of Cortisol and Dehydroepiandrosterone in Obesity, Pain, and Aging. Diseases, 13.","DOI":"10.3390\/diseases13020042"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1089\/rej.2013.1425","article-title":"A Review of Age-Related Dehydroepiandrosterone Decline and Its Association with Well-Known Geriatric Syndromes: Is Treatment Beneficial?","volume":"16","author":"Samaras","year":"2013","journal-title":"Rejuvenation Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1210\/clinem\/dgad225","article-title":"Hormones and Aging: An Endocrine Society Scientific Statement","volume":"108","author":"Cappola","year":"2023","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.maturitas.2022.10.006","article-title":"Adrenal Aging and Its Effects on the Stress Response and Immunosenescence","volume":"168","author":"Stamou","year":"2023","journal-title":"Maturitas"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Yalcinkaya, A., Yalcinkaya, R., Sardh, F., and Landegren, N. (2025). Immune Dynamics throughout Life in Relation to Sex Hormones and Perspectives Gained from Gender-Affirming Hormone Therapy. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1501364"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.iac.2010.09.005","article-title":"Neuroendocrine Effects of Stress on Immunity in the Elderly: Implications for Inflammatory Disease","volume":"31","author":"Heffner","year":"2011","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"De Martinis, M., Sirufo, M.M., Suppa, M., Di Silvestre, D., and Ginaldi, L. (2020). Sex and Gender Aspects for Patient Stratification in Allergy Prevention and Treatment. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041535"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.yhbeh.2016.11.017","article-title":"Sex Differences in Immune Responses: Hormonal Effects, Antagonistic Selection, and Evolutionary Consequences","volume":"88","author":"Roved","year":"2017","journal-title":"Horm. Behav."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1073\/pnas.1321060111","article-title":"Systems Analysis of Sex Differences Reveals an Immunosuppressive Role for Testosterone in the Response to Influenza Vaccination","volume":"111","author":"Furman","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.jamda.2013.05.009","article-title":"Proinflammatory Cytokines, Aging, and Age-Related Diseases","volume":"14","author":"Michaud","year":"2013","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Rea, I.M., Gibson, D.S., McGilligan, V., McNerlan, S.E., Alexander, H.D., and Ross, O.A. (2018). Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00586"},{"key":"ref_23","first-page":"319","article-title":"IL-2 and Its Bidirectional Regulatory Effect on Immune Activation and Immune Tolerance","volume":"29","author":"Zhai","year":"2013","journal-title":"Chin. Pharmacol. Bull."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"102884","DOI":"10.1016\/j.autrev.2021.102884","article-title":"Role of Interleukin-6 in Bone Destruction and Bone Repair in Rheumatoid Arthritis","volume":"20","author":"Takeuchi","year":"2021","journal-title":"Autoimmun. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1002\/iid3.364","article-title":"Low Dose IL-2 Suppress Osteoclastogenesis in Collagen-induced Arthritis via JNK Dependent Pathway","volume":"8","author":"Sun","year":"2020","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"102645","DOI":"10.1016\/j.autrev.2020.102645","article-title":"Low-Dose Interleukin-2: Biology and Therapeutic Prospects in Rheumatoid Arthritis","volume":"19","author":"Wu","year":"2020","journal-title":"Autoimmun. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s12016-015-8522-7","article-title":"Animal Models of Bone Loss in Inflammatory Arthritis: From Cytokines in the Bench to Novel Treatments for Bone Loss in the Bedside\u2014A Comprehensive Review","volume":"51","author":"Alves","year":"2016","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s00005-015-0377-3","article-title":"Inflammaging and Anti-Inflammaging: The Role of Cytokines in Extreme Longevity","volume":"64","author":"Minciullo","year":"2016","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1037\/hea0000629","article-title":"Diurnal Cortisol Profiles, Inflammation, and Functional Limitations in Aging: Findings from the MIDUS Study","volume":"37","author":"Piazza","year":"2018","journal-title":"Health Psychol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"191","DOI":"10.37349\/eemd.2024.00016","article-title":"Endogenous Glucocorticoids during Skeletal Ageing","volume":"1","author":"Macfarlane","year":"2024","journal-title":"Explor. Endocr. Metab. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wang, S., Huo, T., Lu, M., Zhao, Y., Zhang, J., He, W., and Chen, H. (2025). Recent Advances in Aging and Immunosenescence: Mechanisms and Therapeutic Strategies. Cells, 14.","DOI":"10.3390\/cells14070499"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1111\/j.1749-6632.2000.tb06651.x","article-title":"Inflamm-aging: An Evolutionary Perspective on Immunosenescence","volume":"908","author":"Franceschi","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s12016-021-08899-6","article-title":"Immunology of Aging: The Birth of Inflammaging","volume":"64","author":"Fulop","year":"2021","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Fransen, F., van Beek, A.A., Borghuis, T., El Aidy, S., Hugenholtz, F., van der Gaast\u2013de Jongh, C., Savelkoul, H.F.J., De Jonge, M.I., Boekschoten, M.V., and Smidt, H. (2017). Aged Gut Microbiota Contributes to Systemical Inflammaging after Transfer to Germ-Free Mice. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01385"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/nature21363","article-title":"Inflammation, Metaflammation and Immunometabolic Disorders","volume":"542","author":"Hotamisligil","year":"2017","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0167-5699(97)84663-4","article-title":"The Invertebrate Phagocytic Immunocyte: Clues to a Common Evolution of Immune and Neuroendocrine Systems","volume":"18","author":"Ottaviani","year":"1997","journal-title":"Immunol. Today"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"McGuire, P.J. (2019). Mitochondrial Dysfunction and the Aging Immune System. Biology, 8.","DOI":"10.3390\/biology8020026"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.coi.2014.05.002","article-title":"Hematopoietic Stem Cell Aging","volume":"29","author":"Geiger","year":"2014","journal-title":"Curr. Opin. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Pavlov-Dolijanovic, S., Bogojevic, M., Nozica-Radulovic, T., Radunovic, G., and Mujovic, N. (2023). Elderly-Onset Rheumatoid Arthritis: Characteristics and Treatment Options. Medicina, 59.","DOI":"10.3390\/medicina59101878"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wei, L., Chen, X., and Liu, M. (2025). Global, Regional, and National Burden and Trends of Rheumatoid Arthritis among the Elderly Population: An Analysis Based on the 2021 Global Burden of Disease Study. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1547763"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S0889-857X(05)70154-X","article-title":"ELDERLY-ONSET RHEUMATOID ARTHRITIS","volume":"26","author":"Yazici","year":"2000","journal-title":"Rheum. Dis. Clin. N. Am."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/0049-0172(94)90087-6","article-title":"Elderly-Onset Rheumatoid Arthritis","volume":"23","author":"Breedveld","year":"1994","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.reumae.2024.02.001","article-title":"Elderly-Onset Rheumatoid Arthritis Receives Less Aggressive Therapies than Young-Onset Rheumatoid Arthritis in an Argentinian Cohort","volume":"20","author":"Khoury","year":"2024","journal-title":"Reumatol. Cl\u00edn. (Engl. Ed.)"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s12979-020-00178-w","article-title":"Accelerated Immunosenescence in Rheumatoid Arthritis: Impact on Clinical Progression","volume":"17","author":"Bauer","year":"2020","journal-title":"Immun. Ageing"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1097\/BOR.0000000000000011","article-title":"T-Cell Aging in Rheumatoid Arthritis","volume":"26","author":"Weyand","year":"2014","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_46","first-page":"122","article-title":"Seronegative Rheumatoid Arthritis in Elderly and Polymyalgia Rheumatica Have Similar Patterns of HLA Association","volume":"28","author":"Hajeer","year":"2001","journal-title":"J. Rheumatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1177\/1759720X17740075","article-title":"An Autumn Tale: Geriatric Rheumatoid Arthritis","volume":"10","author":"Kobak","year":"2018","journal-title":"Ther. Adv. Musculoskelet. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1136\/ard.54.8.681","article-title":"Remitting Seronegative Symmetrical Synovitis with Pitting Oedema: Disease or Syndrome?","volume":"54","author":"Schaeverbeke","year":"1995","journal-title":"Ann. Rheum. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1093\/intimm\/dxae056","article-title":"Senescence-Associated T Cells in Immunosenescence and Diseases","volume":"37","author":"Fukushima","year":"2025","journal-title":"Int. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Targo\u0144ska-St\u0119pniak, B., Grzechnik, K., Kolarz, K., G\u0105go\u0142, D., and Majdan, M. (2021). Systemic Inflammatory Parameters in Patients with Elderly-Onset Rheumatoid Arthritis (EORA) and Young-Onset Rheumatoid Arthritis (YORA)\u2014An Observational Study. J. Clin. Med., 10.","DOI":"10.3390\/jcm10061204"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1093\/mr\/roac024","article-title":"Usefulness of Ultrasound as a Predictor of Elderly-Onset Rheumatoid Arthritis with Polymyalgia Rheumatica-like Onset","volume":"33","author":"Nawata","year":"2023","journal-title":"Mod. Rheumatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/S0531-5565(03)00090-1","article-title":"Immunosenescence, Autoimmunity, and Rheumatoid Arthritis","volume":"38","author":"Weyand","year":"2003","journal-title":"Exp. Gerontol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e40753","DOI":"10.1097\/MD.0000000000040753","article-title":"Comprehensive Analysis of Rheumatic Diseases, Comorbidities, and Mortality in Geriatric Population: Real-World Data of 515 Patients in a Single Rheumatology Clinic","volume":"103","author":"Tekeoglu","year":"2024","journal-title":"Medicine"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1093\/rheumatology\/key165","article-title":"Management of Inflammatory Rheumatic Conditions in the Elderly","volume":"58","author":"Lahaye","year":"2019","journal-title":"Rheumatology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1002\/acr.25466","article-title":"Incidence of and Risk of Mortality After Hip Fractures in Rheumatoid Arthritis Relative to the General Population","volume":"77","author":"Jones","year":"2025","journal-title":"Arthritis Care Res."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Avalos-Salgado, F.A., Gonzalez-Lopez, L., Gonzalez-Vazquez, S., Ponce-Guarneros, J.M., Santiago-Garcia, A.P., Amaya-Cabrera, E.L., Arellano-Cervantes, R., Guti\u00e9rrez-Aceves, J.A., Alcaraz-Lopez, M.F., and Nava-Valdivia, C.A. (2024). Risk Factors Associated with Adverse Events Leading to Methotrexate Withdrawal in Elderly Rheumatoid Arthritis Patients: A Retrospective Cohort Study. J. Clin. Med., 13.","DOI":"10.3390\/jcm13071863"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"723","DOI":"10.2165\/00002512-200320100-00002","article-title":"Methotrexate Intolerance in Elderly Patients with Rheumatoid Arthritis","volume":"20","author":"Drosos","year":"2003","journal-title":"Drugs Aging"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Li, Y., Liu, Y., Tian, Y., Gu, H., Meng, Q., Cui, J., and Ma, J. (2025). The Research Progress of Biologics in Elderly-Onset Rheumatoid Arthritis (EORA). Front. Aging, 5.","DOI":"10.3389\/fragi.2024.1511812"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1093\/mr\/road031","article-title":"Risk of Hospitalized Infections in Older Elderly Patients with Rheumatoid Arthritis Treated with Tocilizumab or Other Biological\/Targeted Synthetic Disease-Modifying Antirheumatic Drugs: Evaluation of Data from a Japanese Claims Database","volume":"34","author":"Harigai","year":"2024","journal-title":"Mod. Rheumatol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/s40266-020-00782-x","article-title":"Does Older Age Have an Impact on Rituximab Efficacy and Safety? Results from the NOR-DMARD Register","volume":"37","author":"Mielnik","year":"2020","journal-title":"Drugs Aging"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1002\/acr.23781","article-title":"Long-Term Safety of Rituximab in Patients With Rheumatoid Arthritis: Results of a Five-Year Observational Study","volume":"71","author":"Winthrop","year":"2019","journal-title":"Arthritis Care Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1093\/rheumatology\/kev437","article-title":"Effectiveness and Safety of Abatacept in Elderly Patients with Rheumatoid Arthritis Enrolled in the French Society of Rheumatology\u2019s ORA Registry","volume":"55","author":"Lahaye","year":"2016","journal-title":"Rheumatology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1002\/art.39399","article-title":"Comparative Risk of Hospitalized Infection Associated With Biologic Agents in Rheumatoid Arthritis Patients Enrolled in Medicare","volume":"68","author":"Yun","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nrrheum.2017.23","article-title":"The Emerging Safety Profile of JAK Inhibitors in Rheumatic Disease","volume":"13","author":"Winthrop","year":"2017","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1056\/NEJMoa2109927","article-title":"Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis","volume":"386","author":"Ytterberg","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"102528","DOI":"10.1016\/j.autrev.2020.102528","article-title":"Rheumatoid Arthritis in the Elderly: Characteristics and Treatment Considerations","volume":"19","author":"Serhal","year":"2020","journal-title":"Autoimmun. Rev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1136\/annrheumdis-2013-204993","article-title":"Risk of High-Grade Cervical Dysplasia and Cervical Cancer in Women with Systemic Inflammatory Diseases: A Population-Based Cohort Study","volume":"74","author":"Kim","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1136\/annrheumdis-2015-eular.2956","article-title":"FRI0061 Cervical Dysplasia and Cervical Cancer in Women with Rheumatoid Arthritis","volume":"74","author":"Frisell","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_69","first-page":"9","article-title":"Prevalence and Cervical Human Papilloma Virus Associated Factors in Patients with Rheumatoid Arthritis","volume":"76","author":"Trujillo","year":"2008","journal-title":"Ginecol. Obstet. Mex."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1002\/art.39689","article-title":"Biologic Disease-Modifying Antirheumatic Drugs and Risk of High-Grade Cervical Dysplasia and Cervical Cancer in Rheumatoid Arthritis: A Cohort Study","volume":"68","author":"Kim","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1001\/jamainternmed.2017.4332","article-title":"Malignant Neoplasms in Patients With Rheumatoid Arthritis Treated With Tumor Necrosis Factor Inhibitors, Tocilizumab, Abatacept, or Rituximab in Clinical Practice","volume":"177","author":"Frisell","year":"2017","journal-title":"JAMA Intern. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1158\/1055-9965.EPI-21-0125","article-title":"Tumor Necrosis Factor Inhibitors and the Risk of Cancer among Older Americans with Rheumatoid Arthritis","volume":"30","author":"Beachler","year":"2021","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"6647","DOI":"10.18632\/oncotarget.2160","article-title":"Denosumab Mimics the Natural Decoy Receptor Osteoprotegerin by Interacting with Its Major Binding Site on RANKL","volume":"5","author":"Schieferdecker","year":"2014","journal-title":"Oncotarget"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1007\/s00774-020-01178-y","article-title":"Regulation of T Cell-Associated Tissues and T Cell Activation by RANKL-RANK-OPG","volume":"39","author":"Walsh","year":"2021","journal-title":"J. Bone Miner. Metab."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1159\/000371845","article-title":"The RANKL-RANK Story","volume":"61","author":"Nagy","year":"2015","journal-title":"Gerontology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1007\/s00198-019-05051-1","article-title":"Denosumab Utilization among Older Adults in Ontario: Patient Characteristics, Persistence with Therapy, and Return to Therapy after an Extended Gap","volume":"30","author":"Ban","year":"2019","journal-title":"Osteoporos. Int."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s11657-020-00796-3","article-title":"Bisphosphonate and Denosumab Initiation in Older Adults in Ontario, Canada: A Population-Based Cohort Study","volume":"15","author":"Clemens","year":"2020","journal-title":"Arch. Osteoporos."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s00198-011-1755-2","article-title":"Infections in Postmenopausal Women with Osteoporosis Treated with Denosumab or Placebo: Coincidence or Causal Association?","volume":"23","author":"Watts","year":"2012","journal-title":"Osteoporos. Int."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"47","DOI":"10.3803\/EnM.2024.2125","article-title":"Long-Term Efficacy and Safety of Denosumab: Insights beyond 10 Years of Use","volume":"40","author":"Ha","year":"2025","journal-title":"Endocrinol. Metab."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"453","DOI":"10.31616\/asj.2019.0230","article-title":"Persistence of Denosumab Therapy among Patients with Osteoporosis","volume":"14","author":"Kobayashi","year":"2020","journal-title":"Asian Spine J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s11657-018-0491-z","article-title":"Persistence at 24 Months with Denosumab among Postmenopausal Women with Osteoporosis: Results of a Prospective Cohort Study","volume":"13","author":"Silverman","year":"2018","journal-title":"Arch. Osteoporos."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1186\/s13063-019-3589-8","article-title":"Comparative Study of the Inhibitory Effect on Bone Erosion Progression with Denosumab Treatment and Conventional Treatment in Rheumatoid Arthritis Patients: Study Protocol for an Open-Label Randomized Controlled Trial by HR-PQCT","volume":"20","author":"Iwamoto","year":"2019","journal-title":"Trials"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"195","DOI":"10.2217\/fon-2017-0403","article-title":"Denosumab for The Treatment of Bone Disease in Solid Tumors and Multiple Myeloma","volume":"14","author":"Yee","year":"2018","journal-title":"Future Oncol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"136","DOI":"10.4103\/ijc.IJC_16_20","article-title":"Denosumab in Breast Cancer Patients Receiving Aromatase Inhibitors: A Single-Center Observational Study of Effectiveness in Adjuvant Setting","volume":"58","author":"Irelli","year":"2021","journal-title":"Indian J. Cancer"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1056\/NEJMoa1708322","article-title":"Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis","volume":"377","author":"Saag","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2649","DOI":"10.1007\/s40618-024-02395-2","article-title":"A Practical Approach for Anabolic Treatment of Bone Fragility with Romosozumab","volume":"47","author":"Cianferotti","year":"2024","journal-title":"J. Endocrinol. Investig."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.1210\/jc.2017-02163","article-title":"A Phase III Randomized Placebo-Controlled Trial to Evaluate Efficacy and Safety of Romosozumab in Men With Osteoporosis","volume":"103","author":"Lewiecki","year":"2018","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1007\/s10067-024-06932-5","article-title":"The Interplay of Rheumatoid Arthritis and Osteoporosis: Exploring the Pathogenesis and Pharmacological Approaches","volume":"43","author":"Gupta","year":"2024","journal-title":"Clin. Rheumatol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Zheng, M., Wan, Y., Liu, G., Gao, Y., Pan, X., You, W., Yuan, D., Shen, J., Lu, J., and Wang, X. (2023). Differences in the Prevalence and Risk Factors of Osteoporosis in Chinese Urban and Rural Regions: A Cross-Sectional Study. BMC Musculoskelet. Disord., 24.","DOI":"10.1186\/s12891-023-06147-w"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"750","DOI":"10.5534\/wjmh.200099","article-title":"Gender Differences in Osteoporosis: A Single-Center Observational Study","volume":"39","author":"Sirufo","year":"2021","journal-title":"World J. Mens. Health"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1097\/GME.0000000000001831","article-title":"Management of Osteoporosis in Postmenopausal Women: The 2021 Position Statement of The North American Menopause Society","volume":"28","author":"Blake","year":"2021","journal-title":"Menopause"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1111\/cen.14644","article-title":"Genetics of Monogenic Disorders of Calcium and Bone Metabolism","volume":"97","author":"Newey","year":"2022","journal-title":"Clin. Endocrinol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s43042-020-00057-5","article-title":"Vitamin D Receptor (VDR) Gene FokI, BsmI, ApaI, and TaqI Polymorphisms and Osteoporosis Risk: A Meta-Analysis","volume":"21","author":"Yadav","year":"2020","journal-title":"Egypt. J. Med. Hum. Genet."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Colombini, A., Brayda-Bruno, M., Lombardi, G., Croiset, S.J., Vrech, V., Maione, V., Banfi, G., and Cauci, S. (2014). FokI Polymorphism in the Vitamin D Receptor Gene (VDR) and Its Association with Lumbar Spine Pathologies in the Italian Population: A Case-Control Study. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0097027"},{"key":"ref_95","first-page":"224","article-title":"Association of COL1A1 SP1 and FOK-I VDR Genetic Polymorphisms in Young Male Idiopathic Osteoporosis","volume":"13","author":"Man","year":"2017","journal-title":"Acta Endocrinol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"434","DOI":"10.5114\/pg.2024.145481","article-title":"The Other Side of Celiac Disease\u2014Assessment of Bone Mineral Density and Body Composition in Patients with Celiac Disease","volume":"19","author":"Kinga","year":"2024","journal-title":"Gastroenterol. Rev."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Aitella, E., Cozzolino, D., Ginaldi, L., and Romano, C. (2025). Celiac Disease: A Transitional Point of View. Nutrients, 17.","DOI":"10.3390\/nu17020234"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s11914-025-00901-w","article-title":"Management of Bone Health in Adult Mastocytosis","volume":"23","author":"Nezzar","year":"2025","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1759720X20929443","DOI":"10.1177\/1759720X20929443","article-title":"Postmenopausal Osteoporosis Is a Musculoskeletal Disease with a Common Genetic Trait Which Responds to Strength Training: A Translational Intervention Study","volume":"12","author":"Olstad","year":"2020","journal-title":"Ther. Adv. Musculoskelet. Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"101750","DOI":"10.1016\/j.bonr.2024.101750","article-title":"The Multi-Faceted Nature of Age-Associated Osteoporosis","volume":"20","author":"Smit","year":"2024","journal-title":"Bone Rep."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Liang, X., Shi, W., Zhang, X., Pang, R., Zhang, K., Xu, Q., Xu, C., Wan, X., Cui, W., and Li, D. (2023). Causal Association of Epigenetic Aging and Osteoporosis: A Bidirectional Mendelian Randomization Study. BMC Med. Genom., 16.","DOI":"10.1186\/s12920-023-01708-3"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"495","DOI":"10.5483\/BMBRep.2008.41.7.495","article-title":"Osteoimmunology: Cytokines and the Skeletal System","volume":"41","author":"Lee","year":"2008","journal-title":"BMB Rep."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e408","DOI":"10.1002\/edm2.408","article-title":"The Relationship between Adipokine Levels and Bone Mass\u2014A Systematic Review","volume":"6","author":"Mangion","year":"2023","journal-title":"Endocrinol. Diabetes Metab."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Deepika, F., Bathina, S., and Armamento-Villareal, R. (2023). Novel Adipokines and Their Role in Bone Metabolism: A Narrative Review. Biomedicines, 11.","DOI":"10.3390\/biomedicines11020644"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3754","DOI":"10.2174\/0929867323666160907162546","article-title":"Osteoimmunology and Beyond","volume":"23","author":"Ginaldi","year":"2016","journal-title":"Curr. Med. Chem."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1007\/s40618-022-01760-3","article-title":"Role of Wnt-Signaling Inhibitors DKK-1 and Sclerostin in Bone Fragility Associated with Turner Syndrome","volume":"45","author":"Chiarito","year":"2022","journal-title":"J. Endocrinol. Investig."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s41232-019-0111-3","article-title":"RANKL Biology: Bone Metabolism, the Immune System, and Beyond","volume":"40","author":"Ono","year":"2020","journal-title":"Inflamm. Regen."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"125705","DOI":"10.1155\/2013\/125705","article-title":"The Role of Inflammatory Cytokines, the RANKL\/OPG Axis, and the Immunoskeletal Interface in Physiological Bone Turnover and Osteoporosis","volume":"2013","author":"Weitzmann","year":"2013","journal-title":"Scientifica"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Tobeiha, M., Moghadasian, M.H., Amin, N., and Jafarnejad, S. (2020). RANKL\/RANK\/OPG Pathway: A Mechanism Involved in Exercise-Induced Bone Remodeling. BioMed Res. Int., 2020.","DOI":"10.1155\/2020\/6910312"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Wang, Y. (2014). Wnt and the Wnt Signaling Pathway in Bone Development and Disease. Front. Biosci., 19.","DOI":"10.2741\/4214"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.maturitas.2014.04.013","article-title":"Wnt Signaling and Osteoporosis","volume":"78","author":"Manolagas","year":"2014","journal-title":"Maturitas"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Gao, Y., Chen, N., Fu, Z., and Zhang, Q. (2023). Progress of Wnt Signaling Pathway in Osteoporosis. Biomolecules, 13.","DOI":"10.3390\/biom13030483"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"De Martinis, M., Ginaldi, L., Sirufo, M.M., Pioggia, G., Calapai, G., Gangemi, S., and Mannucci, C. (2020). Alarmins in Osteoporosis, RAGE, IL-1, and IL-33 Pathways: A Literature Review. Medicina, 56.","DOI":"10.3390\/medicina56030138"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Ginaldi, L., De Martinis, M., Ciccarelli, F., Saitta, S., Imbesi, S., Mannucci, C., and Gangemi, S. (2015). Increased Levels of Interleukin 31 (IL-31) in Osteoporosis. BMC Immunol., 16.","DOI":"10.1186\/s12865-015-0125-9"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Sirufo, M.M., De Pietro, F., Bassino, E.M., Ginaldi, L., and De Martinis, M. (2020). Osteoporosis in Skin Diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134749"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Aitella, E., De Martinis, M., Romano, C., Azzellino, G., and Ginaldi, L. (2025). Neurogenic Inflammation in Allergic Contact Dermatitis. Biomedicines, 13.","DOI":"10.3390\/biomedicines13030656"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s40266-015-0246-0","article-title":"Chronic Pruritus in the Elderly: Pathophysiology, Diagnosis and Management","volume":"32","author":"Stull","year":"2015","journal-title":"Drugs Aging"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Ginaldi, L., De Martinis, M., Saitta, S., Sirufo, M.M., Mannucci, C., Casciaro, M., Ciccarelli, F., and Gangemi, S. (2019). Interleukin-33 Serum Levels in Postmenopausal Women with Osteoporosis. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-40212-6"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"De Martinis, M., Sirufo, M.M., Suppa, M., and Ginaldi, L. (2020). IL-33\/IL-31 Axis in Osteoporosis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041239"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Mannucci, C., Calapai, G., and Gangemi, S. (2019). Commentary: Circulatory Pattern of Cytokines, Adipokines and Bone Markers in Postmenopausal Women with Low BMD. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02666"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Xu, J., Yu, L., Liu, F., Wan, L., and Deng, Z. (2023). The Effect of Cytokines on Osteoblasts and Osteoclasts in Bone Remodeling in Osteoporosis: A Review. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1222129"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"e220209","DOI":"10.1530\/JOE-22-0209","article-title":"Novel Insights on the Effect of Sclerostin on Bone and Other Organs","volume":"257","author":"Dreyer","year":"2023","journal-title":"J. Endocrinol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"102224","DOI":"10.1016\/j.isci.2021.102224","article-title":"Mice Lacking DKK1 in T Cells Exhibit High Bone Mass and Are Protected from Estrogen-Deficiency-Induced Bone Loss","volume":"24","author":"Lehmann","year":"2021","journal-title":"iScience"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Peng, J., Dong, Z., Hui, Z., Aifei, W., Lianfu, D., and Youjia, X. (2021). Bone Sclerostin and Dickkopf-Related Protein-1 Are Positively Correlated with Bone Mineral Density, Bone Microarchitecture, and Bone Strength in Postmenopausal Osteoporosis. BMC Musculoskelet. Disord., 22.","DOI":"10.1186\/s12891-021-04365-8"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Umur, E., Bulut, S.B., Yi\u011fit, P., Bayrak, E., Arkan, Y., Arslan, F., Baysoy, E., Kaleli-Can, G., and Ayan, B. (2024). Exploring the Role of Hormones and Cytokines in Osteoporosis Development. Biomedicines, 12.","DOI":"10.3390\/biomedicines12081830"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1080\/14656566.2025.2489122","article-title":"An Update on the Pharmacotherapy of Osteoporosis","volume":"26","author":"Shashidhara","year":"2025","journal-title":"Expert. Opin. Pharmacother."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1001\/jama.2025.6003","article-title":"Osteoporosis","volume":"334","author":"Morin","year":"2025","journal-title":"JAMA"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1056\/NEJMoa1607948","article-title":"Romosozumab Treatment in Postmenopausal Women with Osteoporosis","volume":"375","author":"Cosman","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"110574","DOI":"10.1016\/j.vetimm.2023.110574","article-title":"Laboratory Safety Evaluation of Lokivetmab, a Canine Anti-Interleukin-31 Monoclonal Antibody, in Dogs","volume":"258","author":"Krautmann","year":"2023","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1007\/s40265-022-01741-z","article-title":"Nemolizumab: First Approval","volume":"82","author":"Keam","year":"2022","journal-title":"Drugs"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"England, E., Rees, D.G., Scott, I.C., Carmen, S., Chan, D.T.Y., Chaillan Huntington, C.E., Houslay, K.F., Erngren, T., Penney, M., and Majithiya, J.B. (2023). Tozorakimab (MEDI3506): An Anti-IL-33 Antibody That Inhibits IL-33 Signalling via ST2 and RAGE\/EGFR to Reduce Inflammation and Epithelial Dysfunction. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-36642-y"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2402231","DOI":"10.1183\/13993003.02231-2024","article-title":"A Phase 2a Trial of the IL-33 Monoclonal Antibody Tozorakimab in Patients with COPD: FRONTIER-4","volume":"66","author":"Singh","year":"2025","journal-title":"Eur. Respir. J."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1007\/s00296-025-05908-1","article-title":"Late-Onset Rheumatoid Arthritis: Clinical Features, Diagnostic Challenges, and Treatment Approaches","volume":"45","author":"Zimba","year":"2025","journal-title":"Rheumatol. Int."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s11657-020-0706-y","article-title":"Fragility Fractures in Europe: Burden, Management and Opportunities","volume":"15","author":"Karlsson","year":"2020","journal-title":"Arch. Osteoporos."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.bone.2017.01.024","article-title":"The Impact of Fragility Fracture and Approaches to Osteoporosis Risk Assessment Worldwide","volume":"104","author":"Curtis","year":"2017","journal-title":"Bone"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"16","DOI":"10.5152\/j.aott.2021.20071","article-title":"Analysis of Factors among 30-Day and 1-Year Mortality Rates in Patients with Borderline Stable-Unstable Intertrochanteric Hip Fracture","volume":"55","author":"Canbeyli","year":"2021","journal-title":"Acta Orthop. Traumatol. Turc."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Morri, M., Ambrosi, E., Chiari, P., Orlandi Magli, A., Gazineo, D., D\u2019 Alessandro, F., and Forni, C. (2019). One-Year Mortality after Hip Fracture Surgery and Prognostic Factors: A Prospective Cohort Study. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-55196-6"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Blanco, J.F., da Casa, C., Pablos-Hern\u00e1ndez, C., Gonz\u00e1lez-Ram\u00edrez, A., Juli\u00e1n-Enr\u00edquez, J.M., and D\u00edaz-\u00c1lvarez, A. (2021). 30-Day Mortality after Hip Fracture Surgery: Influence of Postoperative Factors. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0246963"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"739","DOI":"10.20945\/2359-3997000000563","article-title":"Male Osteoporosis","volume":"66","author":"Bandeira","year":"2022","journal-title":"Arch. Endocrinol. Metab."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"70","DOI":"10.5114\/pm.2017.68596","article-title":"Osteoporosis in Men","volume":"2","author":"Misiorowski","year":"2017","journal-title":"Menopause Rev."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1007\/s40618-021-01702-5","article-title":"Testosterone Supplementation and Bone Parameters: A Systematic Review and Meta-Analysis Study","volume":"45","author":"Corona","year":"2022","journal-title":"J. Endocrinol. Investig."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s40618-014-0155-9","article-title":"Outcomes of Androgen Replacement Therapy in Adult Male Hypogonadism: Recommendations from the Italian Society of Endocrinology","volume":"38","author":"Isidori","year":"2015","journal-title":"J. Endocrinol. Investig."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.clnesp.2025.07.002","article-title":"Impact of Alcohol Consumption and Muscle Mass on Bone Mineral Density in Metabolic Dysfunction and Alcohol-Associated Liver Disease (MetALD) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)","volume":"69","author":"Yokoyama","year":"2025","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1080\/17474124.2025.2537187","article-title":"Gender-Related Differences in Celiac Disease Presentation and Follow-up in Adult Patients","volume":"19","author":"Rossi","year":"2025","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s10654-024-01195-5","article-title":"Prevalence and Incidence of Mastocytosis in Adults: A Danish Nationwide Register Study","volume":"40","author":"Jensen","year":"2025","journal-title":"Eur. J. Epidemiol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1742-4933-2-14","article-title":"Osteoporosis, Inflammation and Ageing","volume":"2","author":"Ginaldi","year":"2005","journal-title":"Immun. Ageing"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"170","DOI":"10.3899\/jrheum.161270","article-title":"Occurrence of Serious Infection in Patients with Rheumatoid Arthritis Treated with Biologics and Denosumab Observed in a Clinical Setting","volume":"45","author":"Lau","year":"2018","journal-title":"J. Rheumatol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1136\/pgmj.76.902.787","article-title":"Safety of Low Dose Methotrexate in Elderly Patients with Rheumatoid Arthritis","volume":"76","author":"Hirshberg","year":"2000","journal-title":"Postgrad. Med. J."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"471","DOI":"10.2165\/11536530-000000000-00000","article-title":"Management of Chronic Arthritis Pain in the Elderly","volume":"27","author":"Fitzcharles","year":"2010","journal-title":"Drugs Aging"},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Yi, S.-J., Lim, J., and Kim, K. (2024). Exploring Epigenetic Strategies for the Treatment of Osteoporosis. Mol. Biol. Rep., 51, Erratum in Mol. Biol. 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