EFFECT OF TOCILIZUMAB ON BONE REGENERATION: SELECTIVE INHIBITION OF THE IL-6 RECEPTOR IN CRITICAL BONE DEFECTS
Interleukin-6; bone regeneration; tocilizumab; critical-size bone defects; inflammation; bone remodeling
Interleukin-6 (IL-6) plays a biphasic role in bone biology—essential for early repair yet potentially deleterious when chronically elevated, favoring osteoclastogenesis and pathological resorption. Given the lack of consensus on the impact of selective IL-6 receptor (IL-6R) inhibition on bone remodeling and the scarcity of studies in large bone defects, this study evaluated the effect of tocilizumab (TCZ), a selective IL-6R inhibitor, in an experimental rat model of a critical-size calvarial defect. In this in vivo preclinical study, 24 male Wistar rats were randomly assigned to two groups (n = 12/group): a control group (collagen sponge) and a TCZ group (collagen sponge impregnated with 2 mg/kg tocilizumab). An 8-mm critical parietal defect was created in each animal. After 90 days, specimens were analyzed by micro-computed tomography (micro-CT), histology, immunohistochemistry (IHC), ELISA, and RT-qPCR. Tocilizumab significantly reduced mononuclear inflammatory infiltration (P < 0.05) and tumor necrosis factor-alpha levels (TNF-α, P < 0.01). However, downregulation of osteogenic gene markers was observed, including BMP-2 (P < 0.001), RUNX-2 (P < 0.05), and IL-6 (P < 0.05). Additionally, increased immunostaining was detected for markers associated with bone resorption—namely cathepsin and RANKL (P < 0.05). Micro-CT and histologic analyses showed no significant impact on overall bone formation (P > 0.05), with similar counts of osteoblasts, osteoclasts, and osteocytes between groups (P > 0.05). It is concluded that inhibition of the IL-6 pathway by tocilizumab effectively reduces local inflammation and impairs molecular signaling pathways involved in osteoclastogenesis and osteogenesis.