Effect of bisphosphonates treatment on cytokine imbalance between TH17 and Treg in osteoporosis

Imbalance of T-helper-cell (TH) subsets (TH1/TH2/TH17) and regulatory T cells (Tregs) is suggested to contribute to the pathogenesis of osteoporosis. Broken TH17/Treg balance has been reported contributing to several inflammatory diseases. Although bisphosphonates are well-recognized inhibitors of osteoclastic activity, there is no serious examination of their effect on T cell subset (TH1/TH2/TH17/Treg) balances. Patients were categorized into 20 osteopenic and 20 osteoporotic patients treated with bisphosphonates for 1 year. We studied plasma levels of interleukins 4 (IL-4), IL-6, IL-10, IL-12, IL-17, IL-23, and interferon-gamma (IFN-γ), and transforming growth factor-beta (TGF-β) and their interrelations and correlation with osteoporosis treatment were evaluated. Treated osteoporotic patients have a significant reduction of plasma IL-6 (p < 0.05), IL-17 (p < 0.05), IL-23 (p < 0.05), and IFN-γ (p < 0.05), a significant increase in IL-4 (p < 0.05), IL-10 (p < 0.05), and TGF-β (p < 0.001), and comparable IL-12 levels as compared to controls. In conclusion, the significant reduction of Th17 cell cytokine cascade (IL-6, IL-17, and IL-23) and elevation of Treg cytokine cascade (IL-10 and TGF-β) might be considered as a very important observation about the effect of bisphosphonates on TH17/Treg imbalance in osteoporosis.