Background and purposeAseptic loosening is a major cause of failure in total ankle arthroplasty (TAA). In contrast to other total joint replacements, large periarticular cysts (ballooning osteolysis) have frequently been observed in this context. We investigated periprosthetic tissue responses in failed TAA, and performed an element analysis of retrieved tissues in failed TAA.Patients and methodsThe study cohort consisted of 71 patients undergoing revision surgery for failed TAA, all with hydroxyapatite-coated implants. In addition, 5 patients undergoing primary TAA served as a control group. Radiologically, patients were classified into those with ballooning osteolysis and those without, according to defined criteria. Histomorphometric, immunohistochemical, and elemental analysis of tissues was performed. Von Kossa staining and digital microscopy was performed on all tissue samples.ResultsPatients without ballooning osteolysis showed a generally higher expression of lymphocytes, and CD3+, CD11c+, CD20+, and CD68+ cells in a perivascular distribution, compared to diffuse expression. The odds of having ballooning osteolysis was 300 times higher in patients with calcium content >0.5 mg/g in periprosthetic tissue than in patients with calcium content ≤0.5 mg/g (p < 0.001).InterpretationThere have been very few studies investigating the pathomechanisms of failed TAA and the cause-effect nature of ballooning osteolysis in this context. Our data suggest that the hydroxyapatite coating of the implant may be a contributory factor.

CXCR4, the chemokine receptor for CXCL12, also known as SDF-1 (stromal cell derived factor-1), has been shown to play a pivotal role in bone metastasis, inflammatory, and autoimmune conditions but has not been investigated in periprosthetic osteolysis. We co-cultured osteoblast-like cells with increasing concentrations of metallic (Co-35Ni-20Cr-10Mo and Co-28Cr-6Mo) and Co-ions simulating wear debris. Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to quantify gene and protein expression of CXCR4. The expression of tumor necrosis factor-alpha (TNF-α) and the effects of AMD3100 (bicyclam) on both CXCR4 and TNF-α expression among these cells was investigated. RT-PCR showed an increase in CXCR4 mRNA (7.5-fold for MG63 and 4.0-fold for SaOs-2 cells) among cells co-cultured with metal alloy particles. Western blotting showed a time-dependent increase in protein expression of CXCR4. The attempted blockade of CXCR4 by its known competitive receptor agonist AMD3100 led to a significant inhibition TNF-α mRNA expression. Immunohistochemistry showed CXCR4 positivity among patients with failed metal-on-metal hip replacements and radiographic evidence of osteolysis. Our data collectively suggest that the CXCR4 chemokine is upregulated in a dose- and time-dependent manner in the presence of metallic wear debris.

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Bone homeostasis, the balance of bone formation and resorption is affected by numerous influences, such as, hormones, inflammation, mechanical load, and external stimuli. The transforming growth factor-beta (TGF-β), which exists in three isoforms in humans, is a major factor in the maintenance of this balance by regulating osteoblast and osteoclast maturation, development, and function. In artificial joint replacements, release of particles or ions from arthroplasties may exert local effects on the periprosthetic tissue and modulate the expression of bone specific genes and functions. Therefore, the influence of cobalt (II) and chromium (III) ions on the expression levels of the three TGF-β isoforms in human osteosarcoma cell lines MG63 and SaOs-2 was analyzed and the impact on mineralization was studied. The osteosarcoma cell lines expressed all three TGF-β isoforms, with TGF-β1 being the most abundant isoform. A dose dependent reduction of all TGF-β isoforms by Co ions was observed, the strongest effect was found on TGF-β2. The effect was lesser pronounced in SaOs-2 cells. However, the Cr ions had no significant effect on the expression of all TGF-β isoforms. In contrast, Co ions in a concentration range of 50-250 µM did not impair the mineralization, but Cr exerted a strong inhibitory effect on the mineralization in a dose dependent fashion. These data suggest that the influence of cobalt ions on bone homeostasis may in part result from the inhibitory effect on the transcription of the bone regulating cytokines TGF-β1-3 whereas the chromium ions affect the process of mineralization. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2105-2115, 2018.

Large-diameter metal-on-metal (MoM) bearings evolved from the success of hip resurfacing. These implants were used in revision surgery in cases with well-fixed acetabular cups but loose or failed femoral stems, to avoid cup revision. Early data showed low rates of dislocation and potentially low wear profiles due to better fluid film lubrication. The risk of impingement was also thought to be low due to the increased head-neck ratio. Subsequently large-diameter MoM heads gained popularity in primary hip replacement. Recent data has emerged on the unacceptably high revision rates among patients with large-diameter MoM total hip arthroplasties (THAs), high blood levels of metal ions, and adverse tissue reactions. The head-neck (cone-taper) modular interface probably represents the weak link in large metal heads that have been used on conventional tapers. Increased torque of the large head, micromotion, and instability at the cone-taper interface, synergistic interactions between corrosion and wear, edge loading, low clearance, and psoas impingement are the likely causes for early failure of these prostheses.