Cited by 412Bone Metabolism and DiseasesBone health and osteoporosis researchRheumatoid Arthritis Research and Therapies

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Osteoporosis, inflammation and ageing

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Ginaldi, Lia, Di Benedetto, Maria Cristina, De Martinis, Massimo·2005·Immunity & Ageing

DOI 10.1186/1742-4933-2-14PMC PMC1308846

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Abstract

Osteoporosis is a condition characterized by low bone mass and increased bone fragility, putting patients at risk of fractures, which are major causes of morbidity substantially in older people. Osteoporosis is currently attributed to various endocrine, metabolic and mechanical factors. However, emerging clinical and molecular evidence suggests that inflammation also exerts significant influence on bone turnover, inducing osteoporosis. Numerous proinflammatory cytokines have been implicated in the regulation of osteoblasts and osteoclasts, and a shift towards an activated immune profile has been hypothesized as important risk factor. Chronic inflammation and the immune system remodelling characteristic of ageing, as well as of other pathological conditions commonly associated with osteoporosis, may be determinant pathogenetic factors. The present article will review the current perspectives on the interaction between bone and immune system in the elderly, providing an interpretation of osteoporosis in the light of inflamm-ageing.

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BackgroundSelf-citation
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Background
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Background
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Background
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Background
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Background
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Background
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Background
Cell‐Tethered Ligands Modulate Bone Remodeling by Osteoblasts and Osteoclasts
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BackgroundResult
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Background
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Background
Lipocalin 2 Influences Bone and Muscle Phenotype in the MDX Mouse Model of Duchenne Muscular Dystrophy
Ponzetti, M., Ucci, A., Maurizi, A., Giacchi, L., Teti, A. M., & Rucci, N. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23020958 · Cited by 24
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Background
Potential Association of Osteoporosis and Not Osteoporotic Fractures in Patients with Gout: A Longitudinal Follow-Up Study
Kwon, M. J., Park, J.-Y., Kim, S. G., Kim, J.-K., Lim, H. S., Kim, J., Kim, J. H., Cho, S.-J., Nam, E. S., Park, H. Y., et al. (2022) · Nutrients · doi:10.3390/nu15010134 · Cited by 24
Serum levels of irisin in postmenopausal women with osteoporotic hip fractures
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Socioeconomic status, race, and bone turnover in the Midlife in the US Study
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Hassan, E. B., Alderghaffar, M., Wauquier, F., Coxam, V., Demontiero, O., Vogrin, S., Wittrant, Y., & Duque, G. (2019) · Aging · doi:10.18632/aging.102299 · Cited by 23
“The combined effects of inflammation and aging (inflammaging) on osteoporosis [16] and anemia [17] are well-known, and the above supports the concept that MAT can induce direct paracrine lipotoxicity and inflammation on bone and HBM tissues and drive their atrophy.”
Myocardial Infarction Risk Among Patients With Fractures Receiving Bisphosphonates
Pittman, C. B., Davis, L. A., Zeringue, A., Caplan, L., Wehmeier, K. R., Scherrer, J. F., Xian, H., Cunningham, F. E., McDonald, J. R., Arnold, A., et al. (2014) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2013.08.021 · Cited by 23
A scalable approach to characterize pleiotropy across thousands of human diseases and complex traits using GWAS summary statistics
Zhang, Z., Jung, J., Kim, A., Suboc, N., Gazal, S., & Mancuso, N. (2023) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2023.09.015 · Cited by 20
Bone aging and extracellular vesicles
Wang, J., Zhang, Y., Wang, S., Wang, X., Jing, Y., & Su, J. (2024) · 中国科学通报：英文版 · doi:10.1016/j.scib.2024.10.013 · Cited by 25
IL-23, but not IL-12, plays a critical role in inflammation-mediated bone disorders
Xu, J., Li, J., Hu, Y., Dai, K., Gan, Y., Zhao, J., Huang, M., & Zhang, X. (2020) · Theranostics · doi:10.7150/thno.41378 · Cited by 22
“Recent evidence suggests that inflammation is also a cause of senile osteoporosis [32,56].”
Background
Impact of HIV infection on aging and immune status
Blanco, J. R., Negredo, E., Bernal, E., & Blanco, J. (2020) · Expert Review of Anti-infective Therapy · doi:10.1080/14787210.2021.1848546 · Cited by 22
“The major inflammatory pathways involve cytokines that are increased during senescence [86].”
Background
Osteoporosis and the Risk of Parkinson’s Disease: A Nationwide, Propensity Score–Matched, Longitudinal Follow-up Study
Feng, S., Huang, Y., Yeh, K., & Pan, S. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa864 · Cited by 22
Fe3O4 Magnetic Nanoparticles Under Static Magnetic Field Improve Osteogenesis via RUNX-2 and Inhibit Osteoclastogenesis by the Induction of Apoptosis
Marycz, K., Sobierajska, P., Wiglusz, R. J., Idczak, R., Nédélec, J., Fal, A., & Kornicka‐Garbowska, K. (2020) · International Journal of Nanomedicine · doi:10.2147/ijn.s256542 · Cited by 22
A low-intensity lifelong exercise routine changes miRNA expression in aging and prevents osteosarcopenic obesity by modulating inflammation
Pedraza-Vázquez, G., Mena‐Montes, B., Hernández-Álvarez, D., Gómez-Verján, J. C., Toledo-Pérez, R., López-Teros, M. T., Königsberg, M., Gómez-Quiroz, L. E., & Luna‐López, A. (2022) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2022.104856 · Cited by 22
Identification of Aberrantly-Expressed Long Non-Coding RNAs in Osteoblastic Cells from Osteoporotic Patients
Centofanti, F., Santoro, M., Marini, M., Visconti, V. V., Rinaldi, A. M., Celi, M., D’Arcangelo, G., Novelli, G., Orlandi, A., Tancredi, V., et al. (2020) · Biomedicines · doi:10.3390/biomedicines8030065 · Cited by 22
“Numerous pro-inflammatory cytokines have been implicated in the regulation of osteoblasts and osteoclasts, and a shift towards an activated immune profile has been hypothesized as an important risk factor [35].”
Background
Decreased bone mineral density in adult familial Mediterranean fever patients: a pilot study
Suyanı, E., Öztürk, M. A., Değer, S. M., Demirağ, M. D., Göker, B., & Haznedaroğlu, Ş. (2008) · Clinical Rheumatology · doi:10.1007/s10067-008-0930-0 · Cited by 22
“Some proinflammatory cytokines such as IL-1, IL-6, and TNF-α and receptor activator of NF-κB (RANK), receptor activator of NF-κB ligand (RANKL), and osteoprotegerin (OPG) play a role in the pathogenesis of OP [10, 11].”
Background
Substance P blocks ovariectomy-induced bone loss by modulating inflammation and potentiating stem cell function
Piao, J., Park, J. S., Hwang, D. Y., Son, Y., & Hong, H. S. (2020) · Aging · doi:10.18632/aging.104008 · Cited by 21
“Aginginduced inflammation has been recognized as the main cause of bone microarchitecture impairment [15, 16].”
Background
Gene-metabolite profile integration to understand the cause of spaceflight induced immunodeficiency
Chakraborty, N., Cheema, A. K., Gautam, A., Donohue, D. E., Hoke, A. V., Conley, C., Jett, M., & Hammamieh, R. (2018) · npj Microgravity · doi:10.1038/s41526-017-0038-4 · Cited by 22
Injectable natural Tremella-derived hydrogel for reversing ferroptosis-mediated osteoporotic microenvironment imbalance and promoting osteoregeneration
Ye, C., Xu, J., Shi, L., Zong, C., Ji, W., Lu, Y., Tao, R., Han, F., & Ma, H. (2025) · Biomaterials · doi:10.1016/j.biomaterials.2025.123532 · Cited by 21
Anti-Inflammatory Effects of Adenine Enhance Osteogenesis in the Osteoblast-Like MG-63 Cells
Chen, Y., Chu, Y.-L., Tsuang, Y., Wu, Y., Kuo, C., & Kuo, Y. (2020) · Life · doi:10.3390/life10070116 · Cited by 20
“Pathogenesis of osteoporosis is multifactorial which involves inflammation [9].”
Background
Endocrine, Metabolic, and Immune Pathogenesis of Postmenopausal Osteoporosis. Is there a Therapeutic Role in Natural Products?
Lisco, G., Triggiani, D., Giagulli, V. A., Pergola, G. D., Guastamacchia, E., Piazzolla, G., Jirillo, E., & Triggiani, V. (2023) · Endocrine Metabolic & Immune Disorders - Drug Targets · doi:10.2174/1871530323666230330121301 · Cited by 20
Screening and validation of serum protein biomarkers for early postmenopausal osteoporosis diagnosis
Wang, L., Hu, Y., Zhao, Z.-J., Zhang, H., Gao, B., Lu, W., Xu, X., Lin, X., Wang, J., Jie, Q., et al. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.7620 · Cited by 21
“COPD and RA are associated with systemic chronic inflammation and it has previously been demonstrated that dysregulation of immunity contributes to postmenopausal osteoporosis (28).”
Impact of osteopenia on surgical and oncological outcomes in patients with pancreatic cancer
Abe, K., Furukawa, K., Okamoto, T., Matsumoto, M., Futagawa, Y., Haruki, K., Shirai, Y., & Ikegami, T. (2021) · International Journal of Clinical Oncology · doi:10.1007/s10147-021-01986-w · Cited by 20
“As sarcopenia and osteopenia progress because of inflammatory reactions [9, 30], they are considered to be affected Table 2 Patient characteristics in relation to osteopenia”
Background
Rheumatoid Arthritis and Osteoporosis as Prototypes of Immunosenescence in Osteoimmunology: Molecular Pathways of Inflammaging and Targeted Therapies
Aitella, E., Azzellino, G., Romano, C. P., Ginaldi, L., & Martinis, M. D. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26199268 · Cited by 20
Self-citation
The Skeletal Effects of Tanshinones: A Review
Ekeuku, S. O., Pang, K.-L., & Chin, K. (2021) · Molecules · doi:10.3390/molecules26082319 · Cited by 19
“Inflammation also directly affects bone remodelling because proinflammatory cytokines have been implicated in the regulation of osteoblasts and osteoclasts [58].”
Background
Cardiotrophin Like Cytokine Factor 1 (CLCF1) alleviates bone loss in osteoporosis mouse models by suppressing osteoclast differentiation through activating interferon signaling and repressing the nuclear factor-κB signaling pathway
Yokota, S., Matsumae, G., Shimizu, T., Hasegawa, T., Ebata, T., Takahashi, D., Heguo, C., Tian, Y., Alhasan, H., Takahata, M., et al. (2021) · Bone · doi:10.1016/j.bone.2021.116140 · Cited by 19
The association between dietary inflammation index and bone mineral density: results from the United States National Health and nutrition examination surveys
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Haptoglobin Acts as a TLR4 Ligand to Suppress Osteoclastogenesis via the TLR4–IFN-β Axis
Kwon, J., Jin, W. J., Kim, B., Ha, H., Kim, H., & Lee, Z. H. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1800661 · Cited by 18
Effects of endurance exercise training on risk components for metabolic syndrome, interleukin-6, and the exercise capacity of postmenopausal women
Wang, C., Chung, M., Chan, P., Tsai, J.-C., & Chen, F.-C. (2014) · Geriatric Nursing · doi:10.1016/j.gerinurse.2014.02.001 · Cited by 19
Clinical implications of addiction related immunosuppression
Reece, A. S. (2008) · Journal of Infection · doi:10.1016/j.jinf.2008.03.003 · Cited by 19
The long pentraxin PTX3: a novel serum marker to improve the prediction of osteoporosis and osteoarthritis bone-related phenotypes
Visconti, V. V., Greggi, C., Fittipaldi, S., Casamassima, D., Tallarico, M., Romano, F., Botta, A., & Tarantino, U. (2021) · Journal of Orthopaedic Surgery and Research · doi:10.1186/s13018-021-02440-3 · Cited by 18
“Although these are two different diseases, both are characterized by lowgrade chronic inflammation promoted by ageing, resulting in elevated cytokine production [14, 27].”
Background
Changes in Bone Mineral Density of the Femur and Tibia Before Injury to 2 Years After Anterior Cruciate Ligament Reconstruction in Division I Collegiate Athletes
Knurr, K. A., Kliethermes‌, S., Haack, C. R., Olson, J., Binkley, N., Scerpella, T. A., & Heiderscheit, B. C. (2022) · The American Journal of Sports Medicine · doi:10.1177/03635465221099456 · Cited by 18
“Site-specific loss in BMD is multifactorial, likely being influenced by the initial injury, subsequent surgical procedure, local inflammation, period of immobilization, and disuse of the involved lower extremity.(14,17,20,26,45) The combination of reduced lower extremity loading, altered movement mechanics, and quadri…”
Background
Anthraquinones and Aloe Vera Extracts as Potential Modulators of Inflammaging Mechanisms: A Translational Approach from Autoimmune to Onco-Hematological Diseases
Cordiano, R., Caserta, S., Minciullo, P. L., Allegra, A., & Gangemi, S. (2025) · Molecules · doi:10.3390/molecules30061251 · Cited by 23
“…defenses—such as antioxidant mechanisms, DNA repair systems, programmed cell death, and autophagy—become overwhelmed, the mechanisms driving inflammaging contribute to the onset of age-related diseases, including cardiovascular disorders, osteoporosis, neurodegeneration, and cancer [4–10].”
The impact of inflammation on bone mass in children
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“Although some of the mechanisms of skeletal remodeling are shared among these diseases, each disease has a unique impact on articular bone or on the axial or appendicular skeleton [45, 46].”
Background
Linkage to chromosome 11p12 in two Maltese families with a highly penetrant form of osteoporosis
Vidal, C., Galea, R. P., Brincat, M., & Xuereb‐Anastasi, A. (2007) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5201814 · Cited by 18
Protective effect of liquiritigenin against methylglyoxal cytotoxicity in osteoblastic MC3T3-E1 cells.
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Impact of patient programs on adherence and persistence in inflammatory and immunologic diseases: a meta-analysis
Burudpakdee, C., Khan, Z. M., Nanavaty, M., Kaura, S., & Gala, S. (2015) · Patient Preference and Adherence · doi:10.2147/ppa.s77053 · Cited by 18
“Although osteoporosis has not been categorized as an I&I disease, emerging molecular and clinical evidence highlights that inflammation exerts significant influence on bone turnover, which induces osteoporosis.(35) Transplantation was not included in this analysis, due to the unique clinical and treatment characterist…”
Anti-osteoporosis Effect of Fisetin against Ovariectomy Induced Osteoporosis in Rats: In silico, in vitro and in vivo Activity
Feng, P., Shu, S., & Zhao, F. (2022) · Journal of Oleo Science · doi:10.5650/jos.ess21252 · Cited by 17
Melatonin attenuates inflammatory bone loss by alleviating mitophagy and lactate production
Lin, Z., Gu, Y., Liu, Y.-S., Chen, Z.-L., Fang, S., Wang, Z., Liu, Z., Lin, Q., Hu, Y., Jiang, N., et al. (2025) · Apoptosis · doi:10.1007/s10495-025-02096-y · Cited by 19
“…the mtROS/HIF-1α/PDK1 axis, resulting in reduced lactate Chronic inflammation has been reported to induce the imbalance of osteogenesis and osteoclastogenesis by activating various cell populations of the immune system to produce inflammatory cytokines and eventually lead to bone loss [2, 61].”
Aminopropyltriethoxysilane (APTES)-Modified Nanohydroxyapatite (nHAp) Incorporated with Iron Oxide (IO) Nanoparticles Promotes Early Osteogenesis, Reduces Inflammation and Inhibits Osteoclast Activity
Marycz, K., Kornicka‐Garbowska, K., Patej, A., Sobierajska, P., Kotela, A., Turlej, E., Kępska, M., Bieńko, A., & Wiglusz, R. J. (2022) · Materials · doi:10.3390/ma15062095 · Cited by 16
“It has been demonstrated that under osteoporosis conditions, the higher expression of IL-1, IL-6 and TNFα in monocytes and/or osteoblasts and stromal cells occurs, which suggests that the bone inflammation becomes an integrative part of OP [7].”
Background
Associations of long chain polyunsaturated fatty acids with bone mineral density and bone turnover in postmenopausal women
Feehan, O., Magee, P. J., Pourshahidi, L. K., Armstrong, D., Slevin, M. M., Allsopp, P. J., Conway, M. C., Strain, J., & McSorley, E. M. (2022) · European Journal of Nutrition · doi:10.1007/s00394-022-02933-9 · Cited by 16
Attenuation of Alzheimer’s brain pathology in 5XFAD mice by PTH1-34, a peptide of parathyroid hormone
Chen, L., Xiong, L., Yao, L., Pan, J., Arzola, E. P., Zhu, X., Mei, L., & Xiong, W. (2023) · Alzheimer s Research & Therapy · doi:10.1186/s13195-023-01202-z · Cited by 17
Osteoporosis and inflammation: Cause to effect or comorbidity?
Khoury, M. O. (2024) · International Journal of Rheumatic Diseases · doi:10.1111/1756-185x.15357 · Cited by 16
Effects of Hot Water Extracts from Polygonum multiflorum on Ovariectomy Induced Osteopenia in Mice
Hwang, Y.-H., Kang, K.-Y., Kim, J.-J., Lee, S.-J., Son, Y., Paik, S., & Yee, S. (2016) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2016/8970585 · Cited by 16
“Osteoporosis is associated with inflammation and production of inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin- (IL-) 6, and IL1, which stimulate osteoclast activity [6].”
Background
Mind the Gap: Unraveling the Intricate Dance Between Alzheimer’s Disease and Related Dementias and Bone Health
Karnik, S. J., Margetts, T. J., Wang, H. S., Movilă, A., Oblak, A. L., Fehrenbacher, J. C., Kacena, M. A., & Plotkin, L. I. (2024) · Current Osteoporosis Reports · doi:10.1007/s11914-023-00847-x · Cited by 15
“Additionally, the molecular hallmarks intrinsic to ADRD, such as chro-nicinflammation, oxidative stress, and the accumulation of amyloid-beta (Aβ) and tau proteins, have been linked with dysregulated bone metabolism and elevated fracture risk [33, 34, 35, 36, 37, 38, 39, 40, 41].”
Senoinflammation as the underlying mechanism of aging and its modulation by calorie restriction
Noh, S. G., Kim, H., Kim, S., Chung, K. W., Jung, Y.-S., Yoon, J.-H., Yu, B. P., Lee, J., & Chung, H. Y. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102503 · Cited by 16

Authors: Ginaldi, L., Di Benedetto, M. C., & De Martinis, M.
Affiliations: University of L'Aquila (IT)
Corresponding author: Ginaldi, Lia
ORCID: Ginaldi, Lia
Venue: Immunity & Ageing
Publisher: Springer Science and Business Media LLC
Published: 2005-11-04
Volume: 2
Issue: 1
Pages: 14-14
ISSN: 1742-4933 (ISSN-L)
DOI: 10.1186/1742-4933-2-14
PMC: PMC1308846
OpenAlex: W2168242208
Cited by: 412
References: 164
Citations by year: 2026: 21 · 2025: 27 · 2024: 31 · 2023: 28 · 2022: 37 · 2021: 33 · 2020: 44 · 2019: 29 · 2018: 28 · 2017: 22 · 2016: 10 · 2015: 12 · 2014: 16 · 2013: 14 · 2012: 10
FWCI: 2.52
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Immunity & Ageing (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Archivio Istituzionale della Ricerca - Università degli Studi dell Aquila (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
Keywords: osteoporosis, chronic inflammation, aging, bone turnover, inflammatory cytokines, osteoblasts, osteoclasts, bone-immune interaction, fracture risk, older adults

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Osteoporosis, inflammation and ageing

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