Cytokine profiles in osteoporosis suggest a proresorptive bias

Objective: As the immune system is suggested to contribute to the pathophysiology of osteoporosis in menopause, we compared the levels of proresorptive and antiresorptive cytokines produced by peripheral blood mononuclear cells (PBMCs) from postmenopausal women with normal and low bone mineral density (BMD). Methods: Seventy-one postmenopausal women were studied; 25 had normal BMD and 46 had low BMD. Participants were categorized as normal (n=25), osteopenic (n=31), and osteoporotic (n=15) based on T-scores. Levels of 10 cytokines produced by mitogen-stimulated PBMCs were measured by Multiplex ELISA. Results: PBMCs from women with low BMD produced higher levels of the proresorptive cytokines tumor necrosis factor-alpha, interleukin (IL)-6, IL-12, and IL-17 (P=0.014, 0.012, 0.011, and 0.049), and lower levels of the antiresorptive cytokines IL-4, IL-10, and IL-23 (P=0.003, 0.018, and 0.025) compared with women with normal BMD. Proresorptive cytokines were similar in osteopenic and osteoporotic women, but both had higher levels than women with normal BMD. Osteoporotic women produced lower levels of the antiresorptive cytokines IL-4, IL-10, IL-13, and IL-23 compared with the normal BMD group (P=0.001, 0.05, 0.05, and 0.026), and lower levels of IL-4 as compared with osteopenic women (P=0.05). Osteopenic women produced lower levels of IL-4 and IL-10 compared with the normal BMD group (P=0.025 and 0.038). Ratios of proresorptive to antiresorptive cytokines suggest a stronger proresorptive cytokine bias in women with low BMD. Most of the ratios are lowest in the normal BMD group, modest in osteopenic women, and highest in the osteoporotic group. Conclusions: Women with low BMD have a proresorptive cytokine bias.