Parthenolide inhibits polyethylene particle-induced mouse calvarial osteolysis in vivo

Background: Periprosthetic osteolysis and aseptic loosening (AL) after joint arthroplasty are serious problems encountered after an implant surgery. AL is possibly caused by osteolysis or local bone resorption induced by implant-derived wear particles. However, effective treatments for osteoclastic bone resorption and AL mediated by wear particles have not been developed except surgical revision. Therefore, a new strategy should be developed to improve osteolysis associated with AL via pharmacologic intervention. Materials and methods: The effects of parthenolide (PTN), a nuclear factor-kappa B inhibitor and sesquiterpene lactone, on polyethylene particle-induced osteolysis in vivo were investigated using a mouse calvarial model. Bone volume/tissue volume (BV/TV, %), bone surface/bone volume (BS/BV, 1/mm), osteoclast number per bone perimeter (N.Oc/B.Pm, /mm), and eroded surface per bone surface (ES/BS, %) were determined by micro-computed tomography and histologic analyses. Results: Severe bone resorption and rapid osteoclast formation were found in the cranium of the subjects after polyethylene particles were implanted. ES/BS (P < 0.001), N.Oc/B.Pm (group III, P < 0.05; group IV, P < 0.001), and BS/BV (P < 0.001) increased compared with those in group II; BS/BV (P < 0.001) decreased in group II but was improved in groups III and IV, which were treated with PTN. No significant difference in these parameters was observed among groups I, III, and IV. Conclusions: PTN possibly elicited therapeutic effects on osteolysis induced by wear particles, indicating that PTN could be used as a therapeutic agent of AL induced by wear particles. (C) 2014 Elsevier Inc. All rights reserved.