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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Autoimmunity / immunology*
  • Bone Diseases, Metabolic / complications*
  • Bone Diseases, Metabolic / immunology
  • Bone Diseases, Metabolic / pathology
  • Chronic Disease
  • Humans
  • Inflammation / complications*
  • Inflammation / immunology
  • Inflammation / pathology
  • Inflammatory Bowel Diseases / complications*
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / pathology
  • Multiple Sclerosis / complications*
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / pathology
  • Rheumatic Diseases / complications*
  • Rheumatic Diseases / immunology
  • Rheumatic Diseases / pathology