Background Sclerostin (SOST) and dickkopf-1 (DKK1) are involved in the development of primary osteoporosis. Although to date, it is controverted does exist about if serum levels of these molecules may reflex adequately a subgroup of patients with decrement of Bone Mineral Density (BMD) being useful as clinical biomarkers. Some non-conclusive observations made in postmenopausal osteoporosis have shown abnormalities in serum levels. To date, there is a lack of information about if these serum molecules are associated with a decrease of BMD in RA. This information is relevant for to know if the measurement of these serum molecules could be useful in the clinical care to identify a subgroup of patients with low BMD.
Objectives To evaluate if serum levels of SOST and DKK1 correlate with bone mineral density and other bone markers in RA.
Methods In this Cross-sectional study, we included 115 women with RA >40 years old. All patients were assessed for clinical characteristics disease activity (DAS28) and functioning (HAQ-Di). BMD was measured in lumbar spine, hip and forearm using DXA. According to their results, osteoporosis was identified if the BMD in a patient had a T-score with a decrement of ≤-2.5 standard deviation (SD). According to their results we classified these patients in two groups: a) low BMD (T-score≤-1SD on lumbar spine or total hip) and b)normal BMD (T-score>-1SD). Serum SOST, DKK1, including serum Receptor Activator of NF-κB Ligand (sRANKL) and osteoprotegerin (OPG) were quantified by ELISA. We compared serum levels between the groups using Student t-tests. For comparisons between proportions we performed Chi-square test (or Fisher exact test if required). Correlations between serum levels of SOST, DKK1, with BMD, clinical variables, sRANKL and OPG we performed Pearson correlation tests.
Results From the 115 women with RA, 58 patients had low BMD (50.4%), from them 44 patients (38.3%) had osteoporosis. Patients in the group with low BMD had higher age (63±8 vs 53±9,p<0.0001), DAS28 (4.1±1.5 vs 3.3±1.4, p=0.011), and HAQ-Di score (0.69±0.53 vs 0.36±0.47, p=0.001) compared with normal BMD; whereas lower serum levels of sclerostin was observed in the low BMD group (128.5±75.0 vs 178.2±103.3, p=0.004). SOST levels were correlated with BMD in lumbar spine (r=0.393, p<0.0001), hip (r=0.388,p<0.0001) and forearm (r=0.319, p=0.001). sRANKL serum levels had a negative correlation with BMD in hip (r=-0.17, p=0.03). No correlations were observed between serum DKK1 and OPG with BMD in hip or lumbar spine.
Conclusions These results indicate that SOST, and RANKL are biomarkers may associated with abnormal BMD in RA. Further long-term follow-up studies should evaluate if high levels of these serum biomarkers could be useful as tests to predict the future development of osteoporotic fractures.
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Acknowledgements This project was supported by grant from the Fondo de Investigaciόn en Salud del Instituto Mexicano del Seguro Social: FIS/IMSS/PROT/GIS/1455.
Disclosure of Interest C. Nava-Valdivia: None declared, E. Corona-Sanchez: None declared, J. Ponce-Guarneros: None declared, A. Saldaña-Cruz: None declared, J. Murillo-Vazquez: None declared, E. Perez-Guerrero: None declared, P. Hernandez-Cuervo: None declared, M. Salazar-Paramo: None declared, D. Cardona-Müller: None declared, E. Cardona-Muñoz: None declared, L. Gonzalez-Lopez Grant/research support from: Is a recipient of a Fundaciόn IMSS Scholarship, México., J. Gamez-Nava: None declared