Vitamin E-diffused highly cross-linked UHMWPE particles induce less osteolysis compared to highly cross-linked virgin UHMWPE particles in vivo.

Recent in vitro findings suggest that UHMWPE wear particles containing vitamin E (VE) may have reduced biologic activity and decreased osteolytic potential. We hypothesized that particles from VE-stabilized, radiation cross-linked UHMWPE would cause less osteolysis in a murine calvarial bone model when compared to virgin gamma irradiated cross-linked UHMWPE. Groups received equal amount of particulate debris overlaying the calvarium for 10 days. Calvarial bone was examined using high resolution micro-CT and histomorphometric analyses. There was a statistically significant difference between virgin (12.2%±8%) and VE-UHMWPE (3%±1.4%) groups in regards to bone resorption (P=0.005) and inflammatory fibrous tissue overlaying the calvaria (0.48 vs. 0.20, P<0.0001). These results suggest that VE-UHMWPE particles have reduced osteolytic potential in vivo when compared to virgin UHMWPE.

The potential role of herbal extract Wedelolactone for treating particle-induced osteolysis: an in vivo study.

BACKGROUND: Osteolysis is one of the most prevalent clinical complications affecting people who undergo total joint replacement (TJR). Wedelolactone (WDL) is a coumestan compound derived from the Wedelia chinensis plant and has been demonstrated to exhibit anti-inflammatory properties. This study aimed to investigate the oral administration of WDL as a potential treatment for particle-induced osteolysis using a well-established mice calvarial disease model. METHODS: Thirty-two C57BL/6 J mice were randomized into four groups: Sham, vehicle, osteolysis group with oral WDL treatment for 4 weeks (WDL 4w), and osteolysis group treated for 8 weeks (WDL 8w). Micro-CT was used to quantitatively analyze the bone mineral density (BMD), bone volume/tissue volume (BV/TV) and trabecular bone thickness (Tb.Th). Osteoclast numbers were also measured from histological slides by two investigators who were blind to the treatment used. RESULTS: The results from micro-CT observation showed that BMD in the WDL 8w group improved significantly over the vehicle group (p < 0.05), but there was no significant difference between WDL 4w and 8w for BV/TV and Tb.Th. Osteoclast numbers in the WDL 4w group were also lower than the vehicle group (p < 0.05), but the difference between WDL 8w and 4w groups was not significant. CONCLUSIONS: Particle-induced osteolysis is an inevitable long-term complication after TJR. The results of this animal study indicate that an oral administration of WDL can help reduce the severity of osteolysis without adverse effects.

The potential role of strontium ranelate in treating particle-induced osteolysis.

Ultra high molecular weight polyethylene (UHMWPE) wear-particle-induced osteolysis is one of the major issues affecting the long-term survival of total joint prostheses. Currently, there are no effective therapeutic options to prevent osteolysis from occurring. The aim of this study was to evaluate the role of strontium ranelate (SR) in reducing the risk of particle-induced osteolysis. Forty-eight C57BL/6J ultra-high molecular weight polyethylene (UHMWPE) particle-induced murine calvarial osteolysis models were used. The mice were randomized into four groups as: sham (Group 1), UHMWPE particles (Group 2), and SR with UHMWPE particles (Group 3 and Group 4). Groups 1 to 3 were sacrificed at two weeks and group 4 was sacrificed at the fourth week. The skulls were then analyzed with a high-resolution micro-CT. Histological evaluation was then conducted and osteoclast numbers were analyzed for comparison. Based on the micro-CT, percentage bone volume and trabecular thickness were found to be significantly higher in Group 4 than in Group 2 (p<0.001). Osteoclast numbers in SR treated groups (Group 3 and Group 4) were reduced when compared to groups that did not receive SR treatment (Group 2). These results indicated that SR treatment helps to increase bone volume percentage and trabecular thickness and also suppresses osteoclast proliferation. It is suggested that oral SR treatment could serve as an alternative therapy for preventing particle-induced osteolysis.

NF-κB decoy oligodeoxynucleotide inhibits wear particle-induced inflammation in a murine calvarial model.

Wear particles induce periprosthetic inflammation and osteolysis through activation of nuclear factor kappa B (NF-κB), which up-regulates the downstream target gene expression for proinflammatory cytokines in macrophages. It was hypothesized that direct suppression of NF-κB activity in the early phases of this disorder could be a therapeutic strategy for preventing the inflammatory response to wear particles, potentially mitigating osteolysis. NF-κB activity can be suppressed via competitive binding with double stranded NF-κB decoy oligodeoxynucleotides (ODNs) that blocks this transcription factor from binding to the promoter regions of targeted genes. In this murine calvarial study, clinically relevant polyethylene particles (PEs) with/without ODN were subcutaneously injected over the calvarial bone. In the presence of PE particles, macrophages migrated to the inflammatory site and induced tumor necrosis factor alpha (TNF-α) and receptor activator of nuclear factor kappa B ligand (RANKL) expression, resulting in an increase in the number of osteoclasts. Local injections of ODN mitigated the expression of TNF-α, RANKL, and induced the expression of two anti-inflammatory, antiresorptive cytokines: interleukin-1 receptor antagonist and osteoprotegerin. Local intervention with NF-κB decoy ODN in early cases of particle-induced inflammation in which the prosthesis is still salvageable may potentially preserve periprosthetic bone stock.