New insights into immunoporosis: the impact of ovariectomy on immune cell population in lymph nodes and spleen

It is increasingly appreciated that the immune cells and inflammatory mediators contribute to the impaired osteogenic potential under osteoporotic conditions. Previous studies in experimental animals focused on immune cells isolated from blood or bone marrow. Here we highlight the importance of unraveling the interactions between peripheral tissues, such as spleen and lymph nodes, and bone morphologic markers. OVX animals underwent bilateral ovariectomy at the age of 9 months. Four, 8, and 12 weeks post-ovariectomy, osteoporotic parameters and the immunoprofile were investigated by flow cytometric analysis of blood, lymph node, and spleen paired with immunohistochemistry. Ex vivo high resolution μCT and hard tissue histology was performed on the excised tibiae. We observed trabecular bone loss, with corresponding decreases in BV/TV, Tb.N, and Conn.D, as well as an increase in Tb.Sp in the OVX rats after 12 weeks. Quantitative FACS analysis revealed significantly decreased percentage of granulocytes in lymph nodes at 12 weeks in OVX. Correlation of distinct immune cell populations to bone morphologic markers showed that the percentage of granulocytes positively correlated with the Tb.N and Conn.Dn, and negatively with the Tb.Sp both in the lymph nodes and in the spleen at 8 weeks. At 12 weeks post-ovariectomy, however, the percentage of granulocytes correlated negatively with BV/TV, Tb.Th and Tb. N. There was no correlation between distinct immune cells in the blood and bone morphologic markers. Hence, the presented data highlights the unmet need to investigate other compartments rather than blood and bone marrow.