Assessment of Serum sRANKL, sRANKL/OPG Ratio, and Other Bone Turnover Markers with the Estimated 10-Year Risk of Major and Hip Osteoporotic Fractures in Rheumatoid Arthritis: A Cross-Sectional Study

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.