Researchers have shown that estrogen deficiency leads to osteoporosis by promoting the release of cytokines from T-cells that, in turn, stimulate osteoclastogenesis.
The ability of estrogen to prevent bone resorption is well studied and the decline in estrogen concentrations post-menopause has been definitively linked to osteoporosis. Further, it is known that the bone resorption resulting from estrogen deficiency is due to an increase in cytokine activity and subsequent osteoclast formation. However, the factors in this pathway are not completely understood.
Patrizia D'Amelio (University of Torino, Italy) and colleagues compared bone health and the activity of cytokines involved in oseoclastogenesis among 25 post-menopausal women with osteoporosis, 23 healthy post-menopausal women, and 10 healthy pre-menopausal women.
Analysis revealed that the rate of osteoclast production by isolated peripheral blood mononuclear cells was significantly higher in cells from women with osteoporosis than those from healthy post-menopausal and pre-menopausal women. However, the differences in production rate were eliminated when peripheral blood mononuclear cells were stimulated by cytokines involved in osteoclastogenesis such as RANKL.
Further investigation revealed that the production of osteoclastogenic cytokines was higher in patients than in control volunteers and that these factors were primarily produced by T-cells.
Of note, T-cells were shown to be essential to osteoclast formation, completing a clinical picture whereby estrogen deficiency leads to increased release of osteoclastogenic cytokines from T-cells, the production of osteoclastogenetic cytokines and, eventually, osteoporosis.
"To our knowledge, this report is the first to demonstrate the contribution of T-cells to cytokine-driven osteoclastogenesis in post-menopausal osteoporosis," write the investigators in the journal Bone.
In addition to revealing the role of T-cells in osteoporosis, the findings "also suggest that the factors predictive of osteoclastogenesis are to be sought in both the greater marrow output of precursors committed in the osteoclast direction and in the cytokine production," the authors add.
Free abstract