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Review
. 2015 Oct;45(2):220-8.
doi: 10.1016/j.semarthrit.2015.04.014. Epub 2015 Apr 30.

Evolutionary medicine and bone loss in chronic inflammatory diseases--A theory of inflammation-related osteopenia

Rainer H Straub  1 , Maurizio Cutolo  2 , Roberto Pacifici  3
Affiliations
Review

Evolutionary medicine and bone loss in chronic inflammatory diseases--A theory of inflammation-related osteopenia

Rainer H Straub et al. Semin Arthritis Rheum. 2015 Oct.

Abstract

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.

Keywords: bone loss; calcium physiology; chronic inflammation; evolutionary medicine; osteopenia; osteoporosis.

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Conflict of interest statement

Conflict of interest

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Calcium homeostasis in physiology (A) and inflammation (B). The major hormonal regulators are given in red. Doted arrows indicate strong reduction of calcium shifts due to anorexia. The numbers for the immune system (IS) demonstrate the total amount of calcium within all immune cells. Note that the activated immune system contains 10 times more calcium compared to the inactive immune system when all cells would be involved (which is not the case in reality). Numbers are derived from information of refs. (1,27,28,30,31). Abbreviations: calcit., calcitonin; IGF-1, insulin-like growth factor 1; IS, immune system; PTH, parathyroid hormone; PTHrP, PTH-related peptide; Vit. D3, vitamin D3.
Figure 2
Figure 2
Disease sequelae of inflammation leading to osteopenia. The number in the pink middle area of 250 mmol represents the accessible amount of calcium provided from the bone (27). Abbreviations: CID-anemia; inflammation-related anemia of chronic inflammatory diseases; HPG axis, hypothalamic-pituitary-gonadal axis; HPA axis; hypothalamic-pituitary-adrenal axis; HPS axis, hypothalamic-pituitary-somatic axis (growth hormone, IGF-1); IGF-1, insulin-like growth factor 1; PSNS, parasympathetic nervous system; PTH, parathyroid hormone; PTHrP, PTH-related peptide; RES, reticuloendothelial system; SNS, sympathetic nervous system.
See this image and copyright information in PMC

Comment in

  • Bone marrow fat: What is it good for?
    van Niekerk G, Davis T, Engelbrecht AM. van Niekerk G, et al. Semin Arthritis Rheum. 2016 Apr;45(5):e14. doi: 10.1016/j.semarthrit.2015.09.011. Epub 2015 Oct 3. Semin Arthritis Rheum. 2016. PMID: 26525110 No abstract available.

References

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    1. Straub RH. Evolutionary medicine and chronic inflammatory state – known and new concepts in pathophysiology. J Mol Med. 2012;90:523–34. - PMC - PubMed
    1. Besedovsky HO, del Rey A. Immune-neuro-endocrine interactions. Endocr Rev. 1996;17:64–102. - PubMed

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