Introduction. Initial post-operative implant instability leads to impaired osseointegration, one of the most common reasons for aseptic loosening and revision surgery. In this study, we developed a novel murine model of implant instability and demonstrated the anabolic effect of immediate and delayed intermittent Parathyroid Hormone (iPTH) treatment in the setting of instability-induced osseointegration failure. Methods. 3D-printed titanium implants were inserted in an oversized drill-hole in the tibia of C57Bl/6 mice (n=54). After implantation, the mice were randomly divided in 3 treatment groups (control: PBS-vehicle; iPTH; delayed iPTH). Radiographic analysis was performed to confirm signs of implant loosening. Peri-implant tissue formation was assessed through histology. Osseointegration was assessed through µCT and biomechanical pullout testing. Results. Immediate iPTH treatment reduced radiolucencies and induced a distinct pedestal sign distal to the implant stem (white arrow Fig 1A). The PBS treated mice had fibrous tissue implant encapsulation, whereas new mineralized tissue and no fibrous tissue was observed with immediate iPTH treatment (Fig 1E). Delayed iPTH treatment was also able to exhibit significant peri-implant bone mineralization, osteoblasts, angiogenesis, and a reduction of fibrous tissue (Fig 2A-B). iPTH treatment increased the force required to pull out the implant significantly from 8.41 ± 8.15N in the PBS group to 21.49 ± 10.45N and 23.68 ± 8.99N, in the immediate and delayed iPTH treatment groups, respectively (Fig 2D). PBS vehicle resulted in a bone volume/trabecular volume (BV/TV) of 0.23 ± 0.03, while immediate and delayed iPTH treatment increased BV/TV significantly to 0.46 ± 0.07 and 0.34 ± 0.10, respectively (Fig 2E). Conclusion. Immediate iPTH treatment prevents peri-implant fibrous tissue formation and enhances peri-implant bone formation in our murine model of mechanical instability. Delayed iPTH treatment was able to resolve the peri-implant fibrous tissue and stimulate bone formation. This study potentially addresses a leading cause of aseptic loosening by demonstrating that initial implant instability can be rescued by iPTH even with delayed start of treatment. For any figures or tables, please contact authors directly

Aims. It is increasingly appreciated that coordinated regulation of angiogenesis and osteogenesis is needed for bone formation. How this regulation is achieved during peri-implant bone healing, such as osseointegration, is largely unclear. This study examined the relationship between angiogenesis and osteogenesis in a unique model of osseointegration of a mouse tibial implant by pharmacologically blocking the vascular endothelial growth factor (VEGF) pathway. Materials and Methods. An implant was inserted into the right tibia of 16-week-old female C57BL/6 mice (n = 38). Mice received anti-VEGF receptor-1 (VEGFR-1) antibody (25 mg/kg) and VEGF receptor-2 (VEGFR-2) antibody (25 mg/kg; n = 19) or an isotype control antibody (n = 19). Flow cytometric (n = 4/group) and immunofluorescent (n = 3/group) analyses were performed at two weeks post-implantation to detect the distribution and density of CD31. hi. EMCN. hi. endothelium. RNA sequencing analysis was performed using sorted CD31. hi. EMCN. hi. endothelial cells (n = 2/group). Osteoblast lineage cells expressing osterix (OSX) and osteopontin (OPN) were also detected with immunofluorescence. Mechanical pull-out testing (n = 12/group) was used at four weeks post-implantation to determine the strength of the bone-implant interface. After pull-out testing, the tissue attached to the implant surface was harvested. Whole mount immunofluorescent staining of OSX and OPN was performed to determine the amount of osteoblast lineage cells. Results. Flow cytometry revealed that anti-VEGFR treatment decreased CD31. hi. EMCN. hi. vascular endothelium in the peri-implant bone versus controls at two weeks post-implantation. This was confirmed by the decrease of CD31 and endomucin (EMCN) double-positive cells detected with immunofluorescence. In addition, treated mice had more OPN-positive cells in both peri-implant bone and tissue on the implant surface at two weeks and four weeks, respectively. More OSX-positive cells were present in peri-implant bone at two weeks. More importantly, anti-VEGFR treatment decreased the maximum load of pull-out testing compared with the control. Conclusion. VEGF pathway controls the coupling of angiogenesis and osteogenesis in orthopaedic implant osseointegration by affecting the formation of CD31. hi. EMCN. hi. endothelium. Cite this article: Bone Joint J 2019;101-B(7 Supple C):108–114

Aims

Periprosthetic joint infection (PJI) occurs in approximately 1% to 2% of total knee arthroplasties (TKA) presenting multiple challenges, such as difficulty in diagnosis, technical complexity, and financial costs. Two-stage exchange is the gold standard for treating PJI but emerging evidence suggests 'two-in-one' single-stage revision as an alternative, delivering comparable outcomes, reduced morbidity, and cost-effectiveness. This study investigates five-year results of modified single-stage revision for treatment of PJI following TKA with bone loss.

Introduction. Poor osseointegration of cementless implants is the leading clinical cause of implant loosening, subsidence, and replacement failure, which require costly and technically challenging revision surgery. The mechanism of osseointegration requires further elucidation. We have recently developed a novel titanium implant for the mouse tibia that maintains in vivo knee joint function and allows us to study osseointegration in an intra-articular, load-bearing environment. Vascular endothelial growth factor (VEGF) is one of the most important growth factors for regulation of vascular development and angiogenesis. It also plays critical roles in skeletal development and bone repair and regeneration. A specialized subset of vascular endothelium, CD31. hi. EMCN. hi. cells displaying high cell surface expression of CD31 and Endomucin, has been reported to promote osteoblast maturation and may be responsible for bone formation during development and fracture healing. Because of their potential role in osseointegration, the aim of this study was to use our mouse implant model to investigate the role of VEGF and CD31. hi. EMCN. hi. endothelium in osseointegration. Methods. Under an IACUC-approved protocol, the implant was inserted into the right tibia of 16-week-old female C57BL/6 mice (N = 38). The mice were then randomized into 2 groups: Control group (N=19) and Anti-VEGFR group (N=19). A cocktail of VEGFR-1 antibody (25mg/kg) and VEGFR-2 antibody (25mg/kg) was given to the mice in the Anti-VEGFR group by intraperitoneal injection every third day starting immediately after surgery until euthanasia. An equivalent amount of an isotype control antibody was given to the control group. Flow cytometric (N = 4/group) and immunofluorescencent (N = 3/group) analyses were performed at 2 weeks post-implantation to detect the distribution and density of CD31. hi. EMCN. hi. endothelium in the peri-implant bone. Pull-out testing was used at 4 weeks post-implantation to determine the strength of the bone-implant interface. Results. Flow cytometry revealed that Anti-VEGFR treatment decreased CD31. hi. EMCN. hi. vascular endothelium percentage in the peri-implant bone vs. control (p = 0.039) at 2 weeks post-implantation (Fig. 1). This was confirmed by the decrease of CD31 and EMCN double positive cells detected with immunofluorescence at the same time point (Fig. 2). More importantly, anti-VEGFR treatment decreased the maximum load of pullout testing compared with control (p = 0.042) (Fig. 3). Conclusion. VEGF is a key mediator of osseointegration and the development of CD31. hi. EMCN. hi. endothelium. This may provide a new drug target for the enhancement of osseointegration. We have also developed a system to run flow cytometric analysis and perform fluorescent staining on the limited tissue around the implant in this mouse model. This will be a powerful platform for future mechanistic studies on osseointegration. For any figures or tables, please contact authors directly

Aim. A case series with functional and radiographic outcomes, of modular endoprosthetic distal femoral replacement in complex cases of periprosthetic fracture. Method. Sixteen cases were identified of endoprosthetic replacement (EPR) from the bone and soft tissue cancer implant registry. A retrospective review was undertaken. Results. There were 11 periprosthetic fractures of total knee arthroplasty, 3 revision arthroplasty cases, and 3 cases of distal femoral fracture. Of which four were complicated by infection. AKSS scores ranged from 62-100, average 82, with 6 month minimum follow up. There were two post operative infections, both successfully treated. One femoral component required exchange for aseptic loosening at two years. Conclusion. EPR is an effective surgical procedure for complex cases with a demonstrable good functional outcome

We explored the literature surrounding whether allergy and hypersensitivity has a clinical basis for implant selection in total knee arthroplasty (TKA). In error, the terms hypersensitivity and allergy are often used synonymously. Although a relationship is present, we could not find any evidence of implant failure due to allergy. There is however increasing basic science that suggests a link between loosening and metal ion production. This is not an allergic response but is a potential problem. With a lack of evidence logically there can be no justification to use ‘hypoallergenic’ implants in patients who have pre-existing skin sensitivity to the metals used in TKA.

Cite this article: Bone Joint J 2016;98-B:437–41.

Intra-operative, peri-articular injection of local anaesthesia is an increasingly popular way of controlling pain following total knee replacement. At the same time, the problems associated with allogenic blood transfusion have led to interest in alternative methods for managing blood loss after total knee replacement, including the use of auto-transfusion of fluid from the patient’s surgical drain. It is safe to combine peri-articular infiltration with auto-transfusion from the drain. We performed a randomised clinical trial to compare the concentration of local anaesthetic in the blood and in the fluid collected in the knee drain in patients having either a peri-articular injection or a femoral nerve block. Clinically relevant concentrations of local anaesthetic were found in the fluid from the drains of patients having peri-articular injections (4.92 μg/ml (sd 3.151)). However, none of the patients having femoral nerve blockade had detectable levels. None of the patients in either group had clinically relevant concentrations of local anaesthetic in their blood after re-transfusion.

The evidence from this study suggests that it is safe to use peri-articular injection in combination with auto-transfusion of blood from peri-articular drains during knee replacement surgery.