Early effects of IL-6 receptor inhibition on bone homeostasis: a pilot study in women with rheumatoid arthritis.

作者：Evangelos Terpos, Kalliopi Fragiadaki, Maria Anna Polyzou Konsta, Cornelia Bratengeier, Αθανάσιος Παπαθεοδώρου, Petros Paul Sfikakis · 发表于：PubMed · 年份：2012 · 被引用次数：84 · 研究领域：Rheumatoid Arthritis Research and Therapies、Bone Metabolism and Diseases、Bone health and osteoporosis research

OBJECTIVES: A critical role of interleukin-6 (IL-6) in bone homeostasis has been suggested in experimental studies. We examined whether inhibition of IL-6 receptor in patients with rheumatoid arthritis (RA) results in early alterations of circulating markers of bone remodelling. METHODS: Circulating levels of osteoprotegerin, receptor activator of nuclear factor-kappaB ligand (RANKL), Wnt signalling pathway inhibitors Dickkopf-1 (Dkk-1) and sclerostin, markers of bone resorption (C-terminal cross-linking telopeptide of collagen type-I (CTX), tartrate-resistant acid phosphatase isoform-5b) and bone formation (bone-specific alkaline-phosphatase, osteocalcin) were examined in 22 women with active RA before and after two monthly infusions of tocilizumab (8mg/kg each); 'healthy', non-osteopenic, 1:1 age-matched women served as controls. RESULTS: At baseline, osteoprotegerin/RANKL ratio in patients was lower than controls by 5-fold; circulating osteoprotegerin correlated negatively with corresponding 28-joint-count disease activity scores and circulating RANKL correlated positively with C-reactive protein. Also, Dkk-1, sclerostin, CTX and osteocalcin levels were higher in RA than controls. After two months, osteoprotegerin/RANKL ratio increased, Dkk-1 decreased and sclerostin increased comparing to baseline; other markers did not change significantly. Increases of osteoprotegerin/RANKL ratio were more prominent in 10 patients who achieved remission or low disease activity after toc...