title: Evolutionary medicine and bone loss in chronic inflammatory diseases--A theory of inflammation-related osteopenia.
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.
authors.affiliation: Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, Department of Internal Medicine I, University Hospital Regensburg, 93042 Regensburg, Germany. Electronic address: rainer.straub@ukr.de.
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Straub
authors.affiliation: Department of Internal Medicine and Medical Specialties, University of Genova, Genova, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cutolo
authors.affiliation: Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, GA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pacifici
mesh_terms: D015551:Autoimmunity / Q000276:immunology*; D001851:Bone Diseases, Metabolic / Q000150:complications* / Q000276:immunology / Q000473:pathology; D002908:Chronic Disease; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000276:immunology / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000150:complications* / Q000276:immunology / Q000473:pathology; D009103:Multiple Sclerosis / Q000150:complications* / Q000276:immunology / Q000473:pathology; D012216:Rheumatic Diseases / Q000150:complications* / Q000276:immunology / Q000473:pathology
keywords: bone loss; calcium physiology; chronic inflammation; evolutionary medicine; osteopenia; osteoporosis