Cytokines and bone loss in a 5-year longitudinal study--hormone replacement therapy suppresses serum soluble interleukin-6 receptor and increases interleukin-1-receptor antagonist: the Danish Osteoporosis Prevention Study.
The proinflammatory cytokines interleukin-1 beta (IL-1 beta) and IL-6 may play a central role in the acceleration of postmenopausal bone loss, but observational studies have led to contradictory results. Estrogen-dependent changes in the production of IL-1 receptor antagonist (IL-1ra) and the soluble IL-6 receptor (sIL-6R) potentially modify cytokine bioactivity. We therefore assessed the impact of menopause and hormone replacement therapy (HRT) on cytokines and activity modifiers in serum within a 5-year longitudinal study. One hundred sixty perimenopausal women (age 50.1 +/- 2.8 years) were randomized to HRT or no treatment. Serum IL-6 increased with age (r = 0.16; p < 0.05), but cytokines did not correlate with baseline bone mineral density (BMD). HRT led to small increases in IL-1ra (p < 0.001) and IL-6 (p < 0.05), with a decrease in sIL-6R (p < 0.01) and no change in IL-1 beta. No changes were observed in the control group. IL-1ra was inversely correlated with bone loss at the ultradistal forearm (r = 0.29; p < 0.05) and to a lesser degree at the spine (r = 0.20; p = 0.09). In addition, there was a weak positive correlation between sIL-6R and bone loss at the ultradistal forearm (r = 0.26; p < 0.05). High IL-6 levels were associated with slower bone loss (spine r = 0.31, p < 0.01) and controlling for age did not diminish this association. The percent change in sIL-6R during HRT was correlated with the bone loss at the femoral neck (r = -0.29; p < 0.01) and weakly with bone loss in the spine (r = -0.16; p = 0.17). In conclusion, serum IL-1ra and sIL-6R are influenced by HRT and are associated with the rate of bone loss in perimenopausal women.
Abrahamsen
B
B
Department of Endocrinology, Odense University Hospital, Denmark.
Bonnevie-Nielsen
V
V
Ebbesen
E N
EN
Gram
J
J
Beck-Nielsen
H
H
D000328:Adult; D015519:Bone Density; D003718:Denmark; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008137:Longitudinal Studies; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D019947:Receptors, Interleukin-6 / Q000097:blood*; D012795:Sialoglycoproteins / Q000097:blood*; D013997:Time Factors
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D012795:Sialoglycoproteins