Poster Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Osteocytes and their role in wear particle induced periprosthetic osteolysis (#331)

Renee T Ormsby 1 , Tania N Crotti 1 , David R Haynes 1 , David M Findlay 1 , Gerald J Atkins 1
  1. University of Adelaide, Adelaide, SOUTH AUSTRALIA, Australia

Periprosthetic osteolysis (PO) is a direct cause of implant failure in total hip replacements (THR). Aseptic loosening caused by osteolytic lesions has been associated with the production of bioactive wear particles from the articulating surfaces of implants. Wear particles infiltrate the surrounding tissue of implants and promote bone resorption as well as inducing inflammation. Osteocytes have been shown to play a key role in mediating osteoclastogenesis, and are capable of remodeling their perilacunar space in a process called ‘osteocytic osteolysis’. Through these mechanisms we hypothesise that osteocytes contribute to periprosthetic osteolysis through a pro-catabolic phenotype. Osteocyte responses to clinically relevant wear particles; ultra-high molecular weight polyethylene (PE) (UHMWPE, XLPE) particles and metal wear particles (TiAlV; CoCrMo), were examined in vitro in human primary osteocyte-like cultures. Additionally analysis of acetabulum bone biopsies from patients with evidence of periprothestic osteolysis (revision THR) was performed (8 patients per group) compared to primary THR controls. Osteocytes exposed to both PE and metal wear particles showed upregulated expression of catabolic markers, MMP13, carbonic anhydrase 2 (CA2), cathepsin K (CTSK) and tartrate resistant acid phosphatase (TRAP), as well as increases in the pro-osteoclastogenic ratio RANKL:OPG. Osteocytes exposed to metal wear particles showed upregulation of Caspase 3 activity and an increased pro-apoptotic BAX:BCL-2 ratio promoting cell death, however this was not induced with response to PE. Acetabular biopsies from patients with PO showed significantly increased osteocyte lacunar size in trabecular bone adjacent to PE particles, compared with osteocyte lacunar size from primary THR patients [1], with no change in lacunar occupancy. These findings suggest that osteocytes can sense and respond to wear particles by inducing pro-catabolic mediators that result in a loss of osteocyte perilacunar bone.

  1. [1] Ormsby RT, Cantley M, Kogawa M, Solomon LB, Haynes DR, Findlay DM, et al. Evidence that osteocyte perilacunar remodelling contributes to polyethylene wear particle induced osteolysis. Acta biomaterialia. 2016;33:242-51.