Abstract
Background Fracture risk assessment tool (FRAX) index was developed for estimating of the 10-year risk of major or hip osteoporotic fracture. To date, there is insufficient information regarding the correlation between FRAX and serum bone turnover markers (BTMs), such as soluble ligand of receptor activator of nuclear factor-κB (sRANKL), osteoprotegerin (OPG), and other molecules related with secondary osteoporosis in rheumatoid arthritis (RA). Therefore, this study is aimed at assessing the correlation between the FRAX and serum levels of sRANKL, OPG, sRANKL/OPG ratio, Dickkopf-1 (DKK-1), and sclerostin (SOST) in RA. Methods Cross-sectional study included 156 postmenopausal women with RA. Bone mineral density (BMD) was measured at lumbar spine (L1-L4) and total hip using dual-energy X-ray absorptiometry (DXA). RA patients were divided into (A) RA + osteoporosis and (B) RA without osteoporosis. FRAX scores were calculated including the total hip BMD. Serum sRANKL, OPG, DKK-1, and SOST levels were measured by ELISA. Pearson tests were used for assessing the correlation between serum levels of these molecules and FRAX scores in RA. Results The RA + osteoporosis group had elevated sRANKL levels (p = 0.005), higher sRANKL/OPG ratio (p = 0.017), decreased DKK-1 (p = 0.028), and lower SOST levels (p < 0.001). Low total hip BMD correlated with high sRANKL (p = 0.001) and sRANKL/OPG ratio (p = 0.005). Total hip and lumbar spine BMD correlated with DKK-1 (p = 0.009 and p = 0.05, respectively) and SOST levels (p < 0.001 and p < 0.001, respectively). Higher sRANKL levels and sRANKL/OPG ratio correlated with estimated 10-year risk of a major osteoporotic fractures (p = 0.003 and p = 0.003, respectively) and hip fracture (p = 0.002 and p = 0.006, respectively). High serum SOST levels were associated with a low estimated 10-year risk of a major osteoporotic fracture (p = 0.003) and hip fracture (p = 0.009). Conclusion High sRANKL levels and sRANKL/OPG ratio can be useful to detect a subgroup of RA patients who has an increased 10-year risk of major and hip osteoporotic fractures.
Highlights
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by an imbalance of cellular, proinflammatory mediators, and autoantibodies that lead to synovial joint inflammation and the destruction of cartilage and bone in severe cases [1, 2]
When we investigated the association between sRANKL levels and osteoporosis in rheumatoid arthritis (RA) patients, we found in the correlation analysis, a correlation between high sRANKL levels with a low total hip bone mineral density (BMD)
This study included the assessment of the correlation between these molecules with the FRAX scores of the 10-year risk of a major osteoporotic fractures and 10-year probability of a hip fracture. We identified that both sRANKL levels and sRANKL/OPG ratio can be used as biomarkers of osteoporosis, and an association with the estimated 10-years risk to the major osteoporotic and hip fracture assessed by FRAX in patients with RA was found
Summary
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by an imbalance of cellular, proinflammatory mediators, and autoantibodies that lead to synovial joint inflammation and the destruction of cartilage and bone in severe cases [1, 2]. Fracture risk assessment tool (FRAX) index was developed for estimating of the 10-year risk of major or hip osteoporotic fracture. This study is aimed at assessing the correlation between the FRAX and serum levels of sRANKL, OPG, sRANKL/OPG ratio, Dickkopf-1 (DKK-1), and sclerostin (SOST) in RA. Higher sRANKL levels and sRANKL/OPG ratio correlated with estimated 10-year risk of a major osteoporotic fractures (p = 0:003 and p = 0:003, respectively) and hip fracture (p = 0:002 and p = 0:006, respectively). High serum SOST levels were associated with a low estimated 10-year risk of a major osteoporotic fracture (p = 0:003) and hip fracture (p = 0:009). High sRANKL levels and sRANKL/OPG ratio can be useful to detect a subgroup of RA patients who has an increased 10-year risk of major and hip osteoporotic fractures
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