Background/Purpose: Ankylosing Spondylitis (AS) is a chronic inflammatory disease characterized by new bone growth that leads to syndesmophyte formation and subsequent vertebral ankyloses, although AS patients frequently present with low bone mineral density and fractures that can be associated with systemic inflammation and decreased mobility. In fact, acute stages of inflammation in these patients showed mononuclear cell infiltrates, including increased number of osteoclasts (OCs). However, studies that evaluated osteoclastogenesis in AS patients presented different results, and some of them have demonstrated a decrease in osteoclast differentiation in AS patients. There is no data regarding the influence of clinical disease parameters, inflammatory markers and therapy in AS osteoclastogenesis. Thus, the main objective of this study is to determine if the osteoclastogenic capacity of peripheral blood mononuclear cells (PBMCs) is different in male patients with AS compared to healthy controls and to investigate the relationship between osteoclastogenesis and clinical parameters.

Methods: Eigth-five male AS patients had mean of age 42.6±9.0yrs and a mean of disease duration 17.4±9.7yrs. PBMCs from AS patients and 59 healthy controls were tested for CD16+ cells and induced to differentiation. After 21 days, the cells were tested to TRAP (tartrate-resistant acid phosphatase) and the apoptosis was detected using TACs TdT blue in situ. Serum levels of nuclear factor-kB ligand (RANKL) and osteoprotegerin (OPG) were evaluated in both groups.

Results: PBMCs from male AS patients had fewer CD16+ cells (25.06±8.59 vs 28.59±10.20, p=0.026) and produced fewer osteoclasts (647.66±669.4 vs 764.43±561.9, p=0.014) compared to controls. Apoptosis occurred less frequently in osteoclasts obtained from AS patients than in osteoclasts from the control group. A lower RANKL/OPG was observed in AS patients compared to controls (0.046±0.035 vs 0.068±0.071, p=0.046). AS patients taking NSAID (non-steroidal anti-inflammatory drugs) presented no difference regarding the number of OCs produced and the percentage of CD16+ cells compared to controls (p>0.05). However, patients taking TNF inhibitors (TNFi) presented with lower OC numbers than the control group. A generalized linear model with gamma distribution analysis (including disease duration, NSAID and TNFi use) demonstrated that disease duration was negatively associated with osteoclastogenesis: for each year of disease duration, a decrease of 16.6% in the mean osteoclast number was found (p<0.001).

Conclusion: Monocytes from male AS patients display a lower capacity to generate osteoclasts in vitro compared to cells from controls. This difference was not observed in AS patients taking NSAIDs, differently osteoclastogenesis in AS patients using TNFi. Osteoclastogenesis was negatively correlated with disease duration. These finding supports the idea that osteoclasts play a role in the physiopathology of bone disease in AS patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/monocytes-from-male-patients-with-ankylosing-spondylitis-display-decreased-osteoclastogenesis-and-decreased-ranklopg-ratio/