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Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_IV | Pages 510 - 510
1 Oct 2010
Bhabra G Cartwright L Case P Evans H Fisher B Saunders M Sood A Thawley S
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Increasing numbers of young people receive metal on metal (CoCr on CoCr) total hip replacements. These implants generate nano-particles and ions of Co and Cr. Previous studies have shown that micro-particles, nano-particles and ions of CoCr cause DNA damage and chromosomal abberrations in human fibroblasts in tissue culture, and in lymphocytes and bone marrow cells in patients with implants. Several surgeons have used these implants in women of child-bearing age who have subsequently had children. Significantly elevated levels of cobalt and cromium ions have been measured in cord blood of pregnant women with CoCr hip implants. The MHRA (Medicines and Healthcare products Regulatory Agency) subsequently stated that there is a need to determine whether exposure to cobalt and chromium represents a health risk during pregnancy.

In an attempt to investigate this risk, we used a well established in vitro model of the placental barrier comprised of BeWo cells (3 cells in thickness) derived from the chorion and exposed this barrier to nanometer (29nm) and micron (3.4μm) sized CoCr particles, as well as ions of Co2+ and Cr6+ individually or in combination. We monitored DNA damage in BJ fibroblasts beneath the barrier with the alkaline gel electrophoresis comet assay and with γH2AX staining.

The results showed evidence of DNA damage after all types of exposure. The indirect damage (through the barrier) was equal to the direct damage at the concentrations tested. The integrity of the barriers was checked with measurements of electrical resistance (TEER values) and permeability to sodium fluorescein (376Da) and found to be intact.

In light of these results and with the knowledge that BeWo cells express the transmembrane protein Connexin 43, we tested the theory that a damaging signal was being relayed via gap junctions or hemi channels in the BeWo cells to the underlying fibroblasts. We used the connexin mimetic peptides Gap19 and Gap26 (known to selectively block hemichannels and gap junctions respectively) and 18α-glycyrrhetinic acid (non-selective gap junction blocker). All of these compounds completely obliterated the indirect damaging effect seen in our previous experiments.

We conclude that CoCr particles can cause DNA damage through a seemingly intact barrier, and that this damage occurs via a bystander mechanism. It would be of interest to test whether this is simply a tissue culture effect or could be seen in vivo.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_IV | Pages 394 - 394
1 Apr 2004
Bergandi J Feinblatt J Rumi M Saunders M Naidu S Pellegrini V
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Introduction: By compromising bone structure, peri-prosthetic osteolysis may increase the risk of fracture and/or aseptic loosening of components leading to revision surgery. Our purpose was to develop a reproducible rabbit model of periprosthetic osteolysis and observe the effects of implant type and fixation on the latency to onset and size of the osteolytic lesions.

Methods: Thirty-seven New Zealand White rabbits (71 knees) underwent knee arthrotomy and placement of cylindrical intramedullary stainless steel or polymethylmethacrylate (PMMA) implants. Each knee contained both a metallic and PMMA implant in either the femur or tibia that communicated with a common synovial space. A suspension of polyethylene particles (size < 4.5 um and concentration of 1-5 x 106 particles/ul) was injected into each knee at two-week intervals for ten weeks to induce osteolysis. Serial radiographs were taken at 4, 8, 14, 18, and 22 weeks postoperatively to document the progression of osteolysis. Statistical analysis was performed utilizing a two-tailed, unpaired t-test and a Mantel-Cox test with the level of significance set a p < 0.05.

Results: Radiographic analysis revealed that 96.9% of the stainless steel implants had evidence of osteolysis by 22 weeks compared to 22.9% of the PMMA implants (p< 0.001). The earliest onset of lesions in the metal implant group occurred at four weeks compared to 14 weeks in the PMMA group. We also found the area and volume of the osteolytic lesions to be significantly larger in the metal implants when compared to the implants composed of PMMA (p < 0.01).

Conclusions: Onset of osteolysis around metal implants occurred in a significantly shorter period of time and more frequently when compared to implants composed of PMMA. Also, the area and volume of the osteolytic lesions around the metal implants was found to be significantly larger than those of the PMMA. We concluded that relative material effects on osteoclast induced bone resorption and differences in ease of transport of particulate debris along metallic compared to PMMA surfaces may account for observed differences in frequency and severity of osteolytic lesions.