Background Osteoporosis and related fragility fractures are one of the most common complications seen in patients with rheumatoid arthritis (RA). Increased osteoclast activity contributes to local and systemic abnormalities of bone remodelling, including bone erosions and focal and systemic osteoporosis. Receptor Activator of Nuclear Factor Kappa Beta Ligand (RANKL) is essential for osteoclast formation, function, and survival, and it is a key mediator of increased osteoclast activity in RA. As fracture prevention is the major target in prevention and diagnosis of osteoporosis, we are evaluating fracture risk in RA patients using the fracture risk assessment (FRAX) tool developed by the WHO. Moreover, we are searching for a potential association between serum RANKL and fracture risk aiming at identifying patients at high risk of fractures.
Objectives To assess the level of serum RANKL in post-menopausal rheumatoid arthritis patients and its correlation with fracture risk using Fracture Risk Assessment Tool (FRAX).
Methods We recruited 116 individuals (78 postmenopausal RA patients and 38 age-matched post-menopausal control subjects). All patients and controls were not receiving osteoporosis treatment. We measured serum RANKL, C reactive protein (CRP) and Rheumatoid Factor (RF). Disease activity score (DAS)-28 was used to assess RA activity. We measured bone mineral density (BMD) at lumbar spine (L1- L4), right femur neck and right forearm radius with dual-energy X-ray absorptiometry. We have calculated the absolute 10-year major osteoporotic fracture and hip fracture risks with FRAX tool.
Results Mean age was 54.83± 6.6 years in RA patients versus 55.05± 6.2 years in controls. Mean body mass index (BMI) of the patients was 30± 5.6. Mean disease duration was 10.53± 6.6 years. Mean DAS was 3.94± 1.3, mean CRP level was 8± 5.2 mg/L and 76.9% of patients were on steroids. Two of the patients were smokers and no one was taking alcohol. One of the patients reported history of fragility fracture at the forearm but no one reported parent hip fracture. Serum RANKL was significantly higher in RA patients versus controls (971.0pmol/L vs. 177.85 pmol/L, P value <0.0001). Mean BMD of RA patients at lumbar spine was 0.990± 0.2 g/cm2, at femur neck was 0.870±0.19 g/cm2 and at forearm was 0.568± 0.14 g/cm2. Prevalence of osteoporosis in RA patients at lumbar spine was 34.6%, at femur neck was 23.1% and at forearm was 42.3%. Risk of major osteoporotic fracture in RA patients was 8.62% and the risk of hip fracture was 3.3%. There was a highly significant positive correlation between serum RANKL and the risk of major osteoporotic fracture (r =0.736, P value<0.0001). There was a highly significant positive correlation between serum RANKL and the risk of hip fracture (r =0. 859, P value <0.0001). Serum RANKL was negatively correlated with femur neck BMD (r= -0.529, P value <0.001) and negatively correlated with forearm BMD (r= -0.289, P value <0.01). No significant correlation was found between serum RANKL and BMD at lumbar spine, RF, CRP level or DAS-28.
Conclusions In post-menopausal RA patients, increased serum RANKL level is associated with an increased risk of major osteoporotic and hip fractures. Therefore, serum RANKL could be a marker to identify post-menopausal RA patients at high risk of fractures.
Disclosure of Interest None declared
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