Evolutionary medicine and bone loss in chronic inflammatory diseases—A theory of inflammation-related osteopenia
Open accessAbstract
OBJECTIVE: Bone loss is typical in chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel diseases, pemphigus vulgaris, and others. It is also typical in transplantation-related inflammation and during the process of aging. While we recognized that bone loss is tightly linked to immune system activation or inflamm-aging in the form of acute, chronic active, or chronic smoldering inflammation, bone loss is typically discussed to be an "accident of inflammation." METHODS: Extensive literature search in PubMed central. RESULTS: Using elements of evolutionary medicine, energy regulation, and neuroendocrine regulation of homeostasis and immune function, we work out that bone waste is an adaptive, evolutionarily positively selected program that is absolutely necessary during acute inflammation. However, when acute inflammation enters a chronic state due to the inability to terminate inflammation (e.g., in autoimmunity or in continuous immunity against microbes), the acute program of bone loss is a misguided adaptive program. CONCLUSIONS: The article highlights the complexity of interwoven pathways of osteopenia.
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Depending on the inflammatory response, metabolic and neuroendocrine changes can occur to conserve energy and direct nutrients to the activated immune system.
“Depending on the degree and extent of the inflammatory response, including whether it is systemic or local, metabolic and neuroendocrine changes can occur to conserve metabolic energy and allocate more nutrients to the activated immune system9–12.”
From Chronic inflammation in the etiology of disease across the life span (2019) · cites this paper as [11]
A shift from short-lived to long-lived inflammation can break immune tolerance and alter tissues, organs, and cellular physiology, raising the risk of non-communicable diseases in both young and older people.
“Shifts in the inflammatory response from short- to long-lived can cause a breakdown of immune tolerance9,15 and lead to major alterations in all tissues and organs, as well as normal cellular physiology, which can increase the risk for various non-communicable diseases in both young and older individuals1,9–11,15,17–21.”
From Chronic inflammation in the etiology of disease across the life span (2019) · cites this paper as [11]
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References 92 · Cited by 132
- Authors
- Straub, R. H., Cutolo, M., & Pacifici, R.
- Affiliations
- University Hospital Regensburg (DE)
- University of Genoa (IT)
- Emory University (US)
- Corresponding author
- Straub, Rainer H.
- Venue
- Seminars in Arthritis and Rheumatism
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 45
- Issue
- 2
- Pages
- 220-228
- ISSN
- 0049-0172 (ISSN-L)
- PMC
- PMC4570856
- OpenAlex
- W2052006027
- Cited by
- 132
- References
- 92
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 11 · 2023: 8 · 2022: 9 · 2021: 22 · 2020: 13 · 2019: 11 · 2018: 11 · 2017: 13 · 2016: 6 · 2015: 1
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Seminars in Arthritis and Rheumatism (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion, other-oa)
- Funders
- Deutsche Forschungsgemeinschaft
- Ministero della Salute
- National Institutes of Health (AR54625)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR054625, AR49659, R01AR049659, AR54625)
- National Center for Research Resources (RR028009, S10RR028009)
- 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 › Osteomyelitis and Bone Disorders Research
- Keywords
- bone loss, chronic inflammation, evolutionary medicine, acute inflammation, autoimmunity, inflammaging, energy regulation, neuroendocrine regulation, immune homeostasis, rheumatoid arthritis, psoriasis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease, pemphigus vulgaris, aging
- MeSH terms
- Bone Diseases, Metabolic, Chronic Disease, Humans, Inflammation, Multiple Sclerosis, Rheumatic Diseases, Inflammatory Bowel Diseases, Autoimmunity
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