Orthopaedic cobalt chromium particles and ions can induce indirect DNA damage and chromosome aberrations in human cells on the other side of a cellular barrier in tissue culture. This occurs by intercellular signalling across the barrier. We now show that the threshold for this effect depends on the metal form and the particle composition. Ionic cobalt and chromium induced single strand breaks at concentrations equivalent to those found in the blood of patients with well functioning metal on metal hip prostheses. However, they only caused double strand breaks if the chromium was present as chromium (VI), and did not induce chromosome aberrations. Nanoparticles of cobalt chromium alloy caused DNA double strand breaks and chromosome aberrations, of which the majority were tetraploidy. Ceramic nanoparticles induced only single strand breaks and/or alkaline labile sites when indirectly exposed to human fibroblasts. The assessment of reproductive risk from maternal exposure to biomaterials, especially those liberated by orthopaedic implants, is not yet possible with epidemiology. Whilst the barrier model used here differs from the in vivo situation in several respects, it may be useful as a framework to evaluate biomaterial induced damage across physiological barriers.
It is generally accepted that urgent debridement and fixation of open tibial fractures minimizes the risk of infection. Traditionally surgeons follow the unwritten six hour rule. The purpose of this study was to determine the association between time to definite surgical management and rates of infection in open fractures of the tibia. One hundred and twenty-seven patients with one hundred and twenty-eight open tibia fractures were retrospectively reviewed. Of these ninety patients with ninety-one one fractures were available for this study. All patients were followed up to clinical and radiological fracture union or until a definitive procedure for infection or non-union had been carried out. The time from injury to surgery ranged from 2 hours 35 minutes to 12 hours with an average time of 5 hours 40 minutes. There were 24 Gustillo type I fractures (26.37%), 11 type II fractures (12.08%), 23 type IIIA fractures (25.27%) and 33 type IIIB fractures (36.26%). 5 patients (5.49%) in this study went onto develop a deep infection and there were 4(4.39%) non-unions. No infection occurred when the surgery was done within 2 hours. All the 5 infections in this study occurred in patients operated between 3 to 8 hours of the injury and were all in Gustillo Grade III fractures. The average time to treatment was not significantly different between the infected versus non infected group across all fracture types. There was no increase in infection rate in those treated after 6 hours compared to those treated within 6 hours. The risk of developing an infection was not increased if the primary surgical management was delayed more than 6 hours after injury provided intravenous antibiotics were administered on presentation to the emergency department. The Gustillo grading of open fractures is a more accurate prognostic indicator for developing an infection.
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.
Limited wrist arthrodesis has been shown to be an effective treatment for the degenerative and unstable wrist, abolishing pain but limiting motion. The aim of the study was to assess the effect of excision of the scaphoid and triquetrum on wrist joint range of motion, in the setting of a limited midcarpal arthrodesis. Twelve cadaveric wrists had the range of motion measured, before and after, ulnar four-corner fusion (lunate, capitate, triquetrum and hamate fusion). This was measured again following sequential scaphoid and triquetral resection. Scaphoid excision after four-corner arthrodesis resulted in a 12 degrees increase in the radio-ulnar (R-U) arc and 10 degrees increase in the flexion-extension (F-E) arc range of motion. Subsequent excision of the triquetrum, to produce a three-corner fusion, further increased R-U arc by seven degrees and F-E arc by six degrees. These results demonstrate that three-corner fusion with excision of scaphoid and triquetrum results in improvement in wrist motion when compared to four-corner fusion with scaphoid excision alone. From this we conclude that triquetrum excision should be considered in Scapholunate advanced collapse (SLAC) wrist reconstruction to improve residual wrist range of motion.
Joint replacement failure is usually caused by the formation of wear debris resulting in aseptic loosening. Particulate metal and soluble metal ions from orthopaedic alloys (cobalt chromium or vanadium titanium aluminium) that are used in medical prostheses can accumulate in tissues and blood leading to increased chromosome aberrations in bone marrow and peripheral blood lymphocytes. This paper demonstrates that two of the metals used in orthopaedic prostheses, chromium and vanadium can produce delayed as well as immediate effects on the chromosomes of human fibroblasts in vitro. Fibroblasts were exposed to metal ions for only 24 hours and were then expanded over 30 population doublings involving ten passages. The initial increase of chromosomal aberrations, micronuclei formation and cell loss due to lethal mutations persisted over multiple population doublings, thereby demonstrating genomic instability. Differences were seen in the reactions of normal human fibroblasts and those infected with a retrovirus carrying the cDNA encoding hTERT that rendered the normal human fibroblasts telomerase-positive and replicatively immortal. This suggests that chromosomal instability caused by metal ions is influenced by telomere length or telomerase activity. Formerly this syndrome of genomic instability has been demonstrated in two forms following irradiation. One type is non-clonal and involves the appearance of lethal aberrations that cannot have been carried by the surviving cells. The other type is clonal and the aberrations are not lethal. These may arise as a result of complex rearrangements occurring at a high rate post-insult in surviving cells. The consequences of genomic instability are not yet known but it is possible that the increase of chromosomal aberrations that have been previously observed in human patients could be due to immediate and delayed expression of cellular damage after exposure to orthopaedic metals.
Previous research has shown an increase in chromosomal aberrations in patients with worn implants. The type of aberration depended on the type of metal alloy in the prosthesis. We have investigated the metal-specific difference in the level of DNA damage (DNA stand breaks and alkali labile sites) induced by culturing human fibroblasts in synovial fluid retrieved at revision arthroplasty. All six samples from revision cobalt-chromium metal-on-metal and four of six samples from cobalt-chromium metal-on-polyethylene prostheses caused DNA damage. By contrast, none of six samples from revision stainless-steel metal-on-polyethylene prostheses caused significant damage. Samples of cobalt-chromium alloy left to corrode in phosphate-buffered saline also caused DNA damage and this depended on a synergistic effect between the cobalt and chromium ions. Our results further emphasise that epidemiological studies of orthopaedic implants should take account of the type of metal alloy used.