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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
Author(s) -
Abrahamsen Bo,
BonnevieNielsen Vagn,
Ebbesen Ebbe Nils,
Gram Jeppe,
BeckNielsen Henning
Publication year - 2000
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2000.15.8.1545
Subject(s) - medicine , endocrinology , menopause , interleukin 1 receptor antagonist , osteoporosis , proinflammatory cytokine , bone mineral , osteopenia , bone remodeling , cytokine , receptor antagonist , hormone replacement therapy (female to male) , interleukin , bone density , receptor , antagonist , testosterone (patch) , inflammation
Abstract The proinflammatory cytokines interleukin‐1β (IL‐1β) 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‐1β. 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.