Rapid repair of titanium particle-induced osteolysis is dramatically reduced in aged mice†
Scott G. Kaar
Department of Orthopaedics, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Search for more papers by this authorAshraf A. Ragab
Department of Orthopaedics, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Search for more papers by this authorSarah J. Kaye
Department of Orthopaedics, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Search for more papers by this authorB. Alper Kilic
Department of Orthopaedics, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Department of Orthopaedics, Pamukkale University School of Medicine, Denizli, Turkey
Search for more papers by this authorTetsuya Jinno
Department of Orthopaedics, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Department of Orthopaedic Surgery, Toride Kyodo General Hospital, 2-1-1 Hongo, Toride-shi, Ibaraki 302-0022, Japan
Search for more papers by this authorVictor M. Goldberg
Department of Orthopaedics, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Search for more papers by this authorYanming Bi
Department of Orthopaedics, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Department of Pathology, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Search for more papers by this authorMatthew C. Stewart
Department of Orthopaedics, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Search for more papers by this authorJohn R. Carter
Department of Orthopaedics, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Department of Pathology, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Search for more papers by this authorCorresponding Author
Edward M. Greenfield
Department of Orthopaedics, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Department of Pathology, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Department of Physiology and Biophysics, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Department of Orthopaedics, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA, Tel.: +1-216-368-1331; fax: +1-216-368-1332Search for more papers by this authorScott G. Kaar
Department of Orthopaedics, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Search for more papers by this authorAshraf A. Ragab
Department of Orthopaedics, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Search for more papers by this authorSarah J. Kaye
Department of Orthopaedics, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Search for more papers by this authorB. Alper Kilic
Department of Orthopaedics, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Department of Orthopaedics, Pamukkale University School of Medicine, Denizli, Turkey
Search for more papers by this authorTetsuya Jinno
Department of Orthopaedics, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Department of Orthopaedic Surgery, Toride Kyodo General Hospital, 2-1-1 Hongo, Toride-shi, Ibaraki 302-0022, Japan
Search for more papers by this authorVictor M. Goldberg
Department of Orthopaedics, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Search for more papers by this authorYanming Bi
Department of Orthopaedics, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Department of Pathology, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Search for more papers by this authorMatthew C. Stewart
Department of Orthopaedics, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Search for more papers by this authorJohn R. Carter
Department of Orthopaedics, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Department of Pathology, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Search for more papers by this authorCorresponding Author
Edward M. Greenfield
Department of Orthopaedics, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Department of Pathology, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Department of Physiology and Biophysics, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA
Department of Orthopaedics, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA, Tel.: +1-216-368-1331; fax: +1-216-368-1332Search for more papers by this authorThis work was supported in part by NIH RO1AR43769 to EMG. SGK was supported in part by a CWRU Office of Geriatric Medicine Summer Research Fellowship. AAR was supported by NIH Institutional Training Grant AR07505.
Abstract
Aseptic loosening is the most common cause of orthopaedic implant failure. This process is thought to be due to osteolysis induced by implant-derived wear particles. Teitelbaum and colleagues have recently developed a promising murine calvarial model of wear particle-induced osteolysis. However, prior to this study, this model had only been assessed qualitatively. We now report a reproducible, quantitative version of the calvarial model of wear particle-induced osteolysis, in which the extent of osteolysis (and repair) of entire parietal bones is assessed by histomorphometry of contact microradiographs. Using this model, we found that the osteolytic response is transient and rapidly repaired in one month old mice. The extent of osteolysis peaks 7 days after particle implantation and returns to baseline levels by 13 days. A similar amount of osteolysis and even more extensive repair is observed when particles are implanted repeatedly. In contrast, aged mice develop progressive osteolysis with no detectable repair. As a result, 26 month old mice have approximately 17-fold more osteolysis than one month old mice 21 days after particle implantation. Skeletally mature, adult mice (4–16 months old) show an intermediate pattern of response. Osteolysis in these mice peaks at 7 days after particle implantation but it is repaired more slowly than in the one month old mice. Taken together, these results underscore the role of an imbalance between bone resorption and bone formation in the development of aseptic loosening and suggest that agents that stimulate bone formation maybe useful in prevention or treatment of aseptic loosening. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
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