Antioxidant impregnated ultra-high molecular weight polyethylene wear debris particles display increased bone remodeling and a superior osteogenic:osteolytic profile vs. conventional UHMWPE particles in a murine calvaria model.
Periprosthetic osteolysis remains a major limitation of long-term successful total hip replacements with ultra-high molecular weight polyethylene (UHMWPE) bearings. As intra and extracellular reactive oxygen species are know to contribute to wear debris-induced osteoclastic bone resorption and decreased osteoblastic bone formation, antioxidant doped UHMWPE has emerged as an approach to reduce the osteolytic potential of wear debris and maintain coupled bone remodeling. To test this hypothesis in vivo, we evaluated the effects of crosslinked UHMWPE wear debris particles (AltrX(™) ), versus similar wear particles made from COVERNOX(™) containing UHMWPE (AOX(™) ), in an established murine calvaria model. Eight-week-old female C57B/6 mice (n = 10/Group) received a pre-op micro-CT scan prior to surgical implantation of the UHMWPE particles (2mg), or surgery without particles (sham). Dynamic labeling was performed by intraperitoneal injection of calcein on day 7 and alizarin on day 9, and the calvaria were harvested for micro-CT and histology on day 10. Surprisingly, we found that AOX particles induced significantly more bone resorption (1.72-fold) and osteoclast numbers (1.99-fold) vs. AltrX (p < 0.001). However, AOX also significantly induced 1.64-fold more new bone formation vs. AltrX (p < 0.01). Moreover, while the osteolytic:osteogenic ratio of both particles was very close to 1.0, which is indicative of coupled remodeling, AOX was more osteogenic (Slope = 1.13 ± 0.10 vs. 0.97 ± 0.10). Histomorphometry of the metabolically labeled undecalcified calvaria revealed a consistent trend of greater MAR in AOX vs. AltrX. Collectively, these results demonstrate that anti-oxidant impregnated UHMWPE particles have decreased osteolytic potential due to their increased osteogenic properties that support coupled bone remodeling. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:845-851, 2016.
Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642.|Department of Orthopaedics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642.
Yu
Y
Chen
Department of Orthopaedics, Rush University, 1735 W Harrison, Chicago, Illinois 60612.
Nadim J
NJ
Hallab
DePuy, Johnson & Johnson Inc., 700 Orthopaedic Drive, Warsaw, Indiana 46581.
Yen-Shuo
YS
Liao
DePuy, Johnson & Johnson Inc., 700 Orthopaedic Drive, Warsaw, Indiana 46581.
Venkat
V
Narayan
Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642.|Department of Orthopaedics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642.
Edward M
EM
Schwarz
Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642.|Department of Orthopaedics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642.
Chao
C
Xie
D000818:Animals; D005260:Female; D007595:Joint Prosthesis / Q000009:adverse effects*; D008810:Mice, Inbred C57BL; D010012:Osteogenesis / Q000187:drug effects*; D010014:Osteolysis / Q000209:etiology / Q000517:prevention & control*; D010666:Phenylpropionates / Q000494:pharmacology / Q000627:therapeutic use*; D011095:Polyethylenes / Q000494:pharmacology / Q000627:therapeutic use*; D011409:Propylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D012886:Skull; D055114:X-Ray Microtomography
D010666:Phenylpropionates; D011095:Polyethylenes; D011409:Propylene Glycols; C000622239:pentaerythritol tetrakis(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate); C111601:ultra-high molecular weight polyethylene
UHMWPE; antioxidant; osteogenesis; osteolysis; wear