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.
- CD + T-cells
- Inflammatory cytokines
- Postmenopausal osteoporosis
- Postmenopausal rheumatoid arthritis