Rheumatoid arthritis (RA) is characterized, by systemic bone loss, reaching ~50% prevalence of osteoporosis in postmenopausal women. This prevalence is found roughly double when compared with age-matched non-RA women. Postmenopausal RA women are more suitable to sero-positive for the anti-citrullinated peptide antibody (ACPA). The extensive review of recent scientific literature leads to propose several mechanisms as responsible for the accelerated bone loss in ACPA (+) RA postmenopausal women.

Estrogen deficiency associated with menopause is believed to play a significant role in the pathophysiology of osteoporosis. Withdrawal of Estrogen leads to immune dysregulation manifested in a skewed distribution of T-helper cell subsets, and enhanced reactivity of T-helper-17 (Th17) cells. It results in a shift toward elevated levels of inflammatory cytokines, especially TNFα, IL-17, and RANKL, as well as accelerated net bone loss.

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.

TNFα and IL-17 play a dual role in RA because they excite bone resorption and inhibit bone formation.

The RA-unique factor, the pathogenic appearance of ACPA, promotes an inflammation independent-mechanism, resulting in direct osteoclast genesis and bone resorption.