Total hip replacements (THR) are a common and successful procedure for relieving pain and restoring movement in patients with progressive bone disease. However, implant failure can occur due to the development of osteolytic lesions, where the loss of bone causes aseptic loosening. Osteolytic lesions have been associated with the production of bioactive wear particles from the prosthetic components. Wear particles induce inflammation and stimulate bone resorption, and have been detected in the mineralised bone matrix. Osteocytes reside within the bone matrix, forming a lacunocanalicular syncytium that extends into the bone marrow. Through this network, osteocytes are capable of regulating osteoclastic bone resorption. Osteocytes can also undergo perilacunar resorption, through the production of bone degrading enzymes. Therefore, osteocytes may play a key role in the loss of bone associated with osteolysis. To investigate this, we obtained acetabular bone biopsies from revision THR patients with confirmed osteolysis, as well as control bone from primary THR patients. Histological analysis confirmed the presence of both metal and PE wear particles in the revision biopsies. Revision THR biopsies showed significant enlargement of the osteocyte lacunar areas compared to primary THR. Further in depth analysis revealed a significant increase in osteocyte lacunar areas in the female revision THR biopsies, whereas male revision biopsies showed an increase in the % lacunar area /total bone area, indicative of increased osteoclastogenesis. This study suggests the female osteocyte response to particles may be preferentially directed towards perilacunar resorption. This is the first evidence of osteocytes contributing to wear particle induced osteolysis, as well as a gender specific response to wear particles. In conclusion, osteocytes may play a key role in the development of osteolysis, through stimulation of resorptive pathways in response to wear particles, contributing to the aseptic loosening of implants, in a gender-specific manner.