The balance between soluble receptors regulating IL-6 trans-signaling is predictive for the RANKL/osteoprotegerin ratio in postmenopausal women with rheumatoid arthritis.

Abstract

The objective of this study is to investigate the relationship between soluble components of the interleukin 6 (IL-6) system mediating and modifying IL-6 trans-signaling and the RANKL-RANK-osteoprotegerin system in postmenopausal women with rheumatoid arthritis (RA). The following parameters were investigated in 126 postmenopausal women with RA: IL-6, soluble IL-6-receptor (sIL-6R), soluble glycoprotein 130 (sgp130), sRANKL, osteoprotegerin (OPG), osteocalcin, erythrocyte sedimentation rate and C-reactive protein in sera, pyridinolin and desoxypyridinolin crosslinks in the morning urine. Bone mineral density (BMD) was measured by dual X-ray absorptiometry at the lumbar spine (BMD-LS) and at the femoral neck (BMD-FN). Predictors of RANKL/OPG ratio and BMD were evaluated by multiple linear regression analysis. The following determinants of the RANKL/OPG ratio were identified: sIL-6R/sgp130 ratio and daily glucocorticoid (GC) dose as positive determinants in the whole group (R (2) = 0.56; P = 0.001), sIL-6R/sgp130 ratio as the exclusive positive determinant in patients with GC therapy (R (2) = 0.48; P = 0.001) and sgp130 as negative determinant in patients without GC (R (2) = 0.42; P = 0.031). Sgp130 was highly significantly positively correlated with OPG in the whole group (P < 0.001) as well as in patients with (n = 70; P < 0.05) and without GC therapy (n = 56; P < 0.01). sIL-6R was the main negative predictor of BMD-LS (R (2) = 0.41; P = 0.019). High sIL-6R/sgp130 ratio and/or low sgp130 are associated with a high sRANKL/OPG ratio in sera of postmenopausal women with RA indicating the critical significance of IL-6 trans-signaling for an increase in the RANKL/OPG ratio and of bone resorption. Inhibition of IL-6 trans-signaling may be an effective bone-protecting principle in postmenopausal women with RA.

• Authors: Peter Oelzner, Sybille Franke, Gabriele Lehmann, Thorsten Eidner, Gert Hein, Gunter Wolf
• Journal: Rheumatology international (Rheumatol Int) Vol. 32 Issue 1 Pg. 199-206 (Jan 2012) ISSN: 1437-160X [Electronic] Germany
• PMID: 20821212 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Glucocorticoids
• Interleukin-6
• Osteoprotegerin
• RANK Ligand
• Receptors, Interleukin-6
• Cytokine Receptor gp130

Topics

• Adult
• Aged
• Aged, 80 and over
• Arthritis, Rheumatoid (blood, drug therapy)
• Biomarkers (blood)
• Bone Density (physiology)
• Cytokine Receptor gp130 (blood)
• Female
• Glucocorticoids (adverse effects, therapeutic use)
• Humans
• Interleukin-6 (blood)
• Linear Models
• Middle Aged
• Osteoporosis, Postmenopausal (blood, chemically induced, epidemiology)
• Osteoprotegerin (blood)
• Postmenopause (blood)
• Predictive Value of Tests
• RANK Ligand (blood)
• Receptors, Interleukin-6 (blood)
• Risk Factors
• Signal Transduction (physiology)