Postmenopausal osteoporosis in rheumatoid arthritis: The estrogen deficiency-immune mechanisms link

Rony Sapir-Koren, Gregory Livshits

Research output: Contribution to journalReview articlepeer-review

Abstract

Rheumatoid arthritis (RA) is characterized, among other factors, by systemic bone loss, reaching ~ 50% prevalence of osteoporosis in postmenopausal women. This is roughly a doubled prevalence in comparison with age-matched non-RA women. Postmenopausal RA women are more likely to be sero-positive for the anti-citrullinated peptide antibody (ACPA). Our extensive review of recent scientific literature enabled us to propose several mechanisms as responsible for the accelerated bone loss in ACPA(+) RA postmenopausal women. Menopause-associated estrogen deficiency plays a major role in these pathological mechanisms, as follows: 1) Estrogen withdrawal causes immune dysregulation manifested in a skewed distribution of T helper-cell subsets, and enhanced reactivity of T helper-17 (Th17) cells. This results in a shift toward elevated levels of inflammatory cytokines, especially TNFα, IL-17, and RANKL, as well as accelerated net bone loss.2) The proposed interaction between estrogen deficiency and RA-genetic risk alleles promotes enhanced Th17-cell autoreactivity, manifested by ACPA(+) RA. Such interactions exacerbate the inflammatory conditions and cause massive bone destruction.3) TNFα and IL-17 play a dual role in RA because they stimulate bone resorption and inhibit bone formation.4) An RA-unique factor, the pathogenic appearance of ACPA, promotes an inflammation independent-mechanism, resulting in direct osteoclastogenesis and bone resorption.

Original languageEnglish
Pages (from-to)102-115
Number of pages14
JournalBone
Volume103
DOIs
StatePublished - Oct 2017

Keywords

  • ACPA
  • CD + T-cells
  • Inflammatory cytokines
  • Postmenopausal osteoporosis
  • Postmenopausal rheumatoid arthritis
  • RANKL

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