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

The COVID-19 pandemic has led to unprecedented times worldwide. From lockdowns to masks now being part of our everyday routine, to the halting of elective surgeries, the virus has touched everyone and every part of our personal and professional lives. Perhaps, now more than ever, our ability to adapt, change and persevere is critical to our survival. This year's closed meeting of The Knee Society demonstrated exactly those characteristics. When it became evident that an in-person meeting would not be feasible, The Knee Society leadership, under the direction of President John Callaghan, MD and Program Chair Craig Della Valle, MD created a unique and engaging meeting held on September 10–12, 2020. Special recognition should be given to Olga Foley and Cynthia Garcia at The Knee Society for their flexibility and creativeness in putting together a world-class flawless virtual program. The Bone & Joint Journal is very pleased to partner with The Knee Society to once again publish the proceedings of the closed meeting of the Knee Society. The Knee Society is a United States based society of highly selected members who have shown leadership in education and research in knee surgery. It invites up to 15% international members; this includes some of the key opinion leaders in knee surgery from outside the USA. Each year, the top research papers from The Knee Society meeting will be published and made available to the wider orthopaedic community in The Bone & Joint Journal. The first such proceedings were published in BJJ in 2019. International dissemination should help to fulfil the mission and vision of the Knee Society of advancing the care of patients with knee disorders through leadership, education and research. The quality of dissemination that The Bone & Joint Journal provides should enhance the profile of this work and allow a larger body of surgeons, associated healthcare professionals and patients to benefit from the expertise of the members of The Knee Society. The meeting is one of the highlights of the annual academic calendar for knee surgeons. With nearly every member in attendance virtually throughout the 3 days, the top research papers from the membership were presented and discussed in a virtual format that allowed for lively interaction and discussion. There are 75 abstracts presented. More selective proceedings with full papers will be available after a robust peer review process in 2021, both online and in The Bone & Joint Journal. The meeting commenced with the first group of scientific papers focused on Periprosthetic Joint Infection. Dr Berry and colleagues from the Mayo Clinic further help to clarify the issue of serology and aspirate results to diagnose TKA PJI in the acute postoperative setting. 177 TKA's had an aspiration within 12 weeks and 22 were proven to have PJI. Their results demonstrated that acute PJI after TKA should be suspected within 6 weeks if CRP is ≥81 mg/L, synovial WBCs are ≥8500 cells/μL, and/or synovial neutrophils≥86%. Between 6– 12 weeks, concerning thresholds include a CRP ≥ 32 mg/L, synovial WBC ≥7450, and synovial neutrophils ≥ 84%. While historically the results of a DAIR procedure for PJI have been variable, Tom Fehring's study showed promise with the local delivery of vancomycin through the Intraosseous route improved early results. New member Simon Young contrasted the efficacy of the DAIR procedure when comparing early infections to late acute hematogenous PJI. DAIR failed in 63% of late hematogenous PJIs (implant age>1 year) compared to 36% of early (<1year) PJIs. Dr Masri demonstrated in a small group of patients that those with well-functioning articulating spacers can retain their spacers for over 12 months with no difference in infection from those that had a formal two stage exchange. The mental toll of PJI was demonstrated in a longitudinal study by Doug Dennis, where patient being treated with 2 stage exchange had 4x higher rates of depression compared to patient undergoing aseptic revision. The second session focused on both postoperative issues with regards to anticoagulation and manipulation. Steven Haas demonstrated high complication rates with utilization of anticoagulation for treatment of postoperative pulmonary embolism with modern therapeutic anticoagulation (warfarin, enoxaparin, Xa inhibitors) with the Xa inhibitors demonstrating lower complication rates. Two papers focused on the topic of manipulation. Mark Pagnano presented data on timing of manipulation under anesthesia up to even past 12 months. While gains were modest, a subset of patients did achieve substantial gains in ROM > 20degrees even after 3 months post op. Dr Westrich's study demonstrated no difference in MUA outcomes with either IV sedation or neuraxial anesthesia although the length of stay was shorter in the IV sedation group. Several studies in Session II focused on kinematics and femoral component position. Dr Li's in vivo kinematic study during weightbearing flexion and gait demonstrated that several knees rotated with a lateral pivot motion and not all knees can be described with a single motion character. Dr Mayman and his group utilized a computational knee model to demonstrate that additional distal femoral resection results in increasing levels of mid -flexion instability and cautioned against the use of additional bony resection as the first line for flexion contractures. Using computer navigation, Dr Huddleston's study nicely outlined the variability in femoral component rotation to achieve a rectangular flexion gap utilizing a gap balanced method. The third session opened the meeting on Friday morning. The focus was on unicompartmental knee arthroplasty and the increasing utilization of robotic assisted total knee arthroplasty. David Murray showed using registry data that for patient with higher comorbidities (ASA >3), UKA was safer and more cost effective than TKA while Dr Della Valle's group demonstrated overall lower average healthcare costs in UKA patients compared to TKA in the first 10 years after surgery. Dr Geller assessed UKA survivorship among 3 international registries. While survivorship varied by nation and designs, certain designs consistently had better overall performance. Dr Nunley and his group showed robotic navigation UKA significantly reduced outliers in alignment and overhang compared to manual UKA. Dr Catani's data demonstrated that full thickness cartilage loss should still be considered a requirement for UKA success even with robotic assistance. Despite a high dislocation rate of 4%, Mr Dodd demonstrated high survivorship for lateral UKA despite historical contraindications. The growing evidence for robotics TKA was demonstrated in two studies. Professor Haddad showed less soft tissue injury, reduced bone trauma and improved accuracy or rTKA compared to manual TKA while Dr Gustke single surgeon study showed his rTKA had improved forgotten joint scores and less ligament releasing required for balancing. Despite these finding, Dr Lee's study demonstrated that a robotic TKA could not guarantee excellent pain relief and other factors such a patient expectations and psychological factors play a role. Our fourth session was devoted to machine learning and smart tools and modeling. Dr Meneghini used machine learning algorithms to identify optimal alignment outcomes that correlated with patient outcomes. Several parameters such as native tibial slope, femoral sagittal position and coronal limb alignment correlated with outcomes. Along the same lines, Bozic and coauthors demonstrated that using AI algorithms incorporated with PROM's improved levels of shared decision making and patient satisfaction. Dr Lombardi demonstrated that a mobile patient engagement platform that provided smart phone-based exercise and education was comparable to traditional methods. Dr Mahfouz demonstrated the accuracy of using ultrasound to produce 3D models of the bone compared to conventional CT based strategies and Dr Mahoney showed the valued of a preop 3D model in reproducing more normal knee kinematics. The last two talks of the session focused on some of the positives of the COVID-19 pandemic, namely the embracing of telemedicine by patients and surgeons as demonstrated by Dr Slover and the increasing and far reaching educational opportunities made available to residents and fellows during the pandemic. Session five focused on risk stratification and optimization prior to TKA. Dr O'Connor demonstrated that that the implementation of an optimization program preoperatively reduced length of stay and ED visits, and Charles Nelson's study showed that risk stratification tool can lower complication rates in obese patients undergoing TKA comparable to those that are nonobese. Dr Markel's study demonstrated that those who have preoperative depression and anxiety are at higher risk of complications and readmissions after surgery and these issues should be addressed preoperatively. Interestingly, a study by Dr Callaghan demonstrated that care improvement pathways have not lowered the gap in complications for morbidly obese patients undergoing TKA, Dr Barsoum argued that the overall complication rates were low and this patient cohort had significant gains in PROMS after TKA that would not be experienced if arbitrary cutoff for limited surgery were established. The final session on Friday, Session six, had several well done and interesting studies. There continues to be mounting evidence that liposomal bupivacaine has little effect on managing post-operative pain to warrant its increased use. Bill Macaulay and colleagues showed no change in pain scores, opioid consumption and functional scores when liposomal bupivacaine was discontinued at a large academic medical center. Dr Bugbee importantly demonstrated that a supervised ambulation program reduced falls in the early postoperative period. Several paper on healthcare economics were presented. Rich Iorio showed that stratifying complexity of total joint cases between hospitals with a system can be efficient and cost savings while Dr Jiranek demonstrated in his study that complex TKAs can be identified preoperatively and are associated with prolonged operative time and cost of care and consideration should be given in future reimbursement models to a complexity modifier. Dr Springer, in their evaluation of Medicare bundled payment models, demonstrated that providers and hospitals in historical bundled models that became efficient were penalized in the new model, forcing many groups to drop out and return to a fee for service model. Ron Delanois important work showed that social determinants can have a major negative impact on outcomes following TKA. Our final day on Saturday opened with Session seven, and several interesting paper on metal ions/debris in TKA. Dr Whitesides simulator study showed the absence of scratches and material loss in a ceramic TKA compared with Co-Cr TKA and suggested an advantage to this material in patients with metal sensitivity. Conversely, in a histological study of failed TKA, perivascular lymphocytic infiltration was not associated with worse clinical outcomes or differences in revision in a series of 617 aseptic revisions, 19% of which had PVLI found on histology. The Mayo group and Dr Trousdale however, noted that serum metal ion levels can be helpful in identifying implant failure in a group of revision TKAs, especially those with metallic junctions. Dr Dalury demonstrated nicely that use of maximally conforming inserts did not have a negative effect on implant loosening in a series of 76 revision TKA's at an average follow up of 7 years, while Kevin Garvin and his group showed no difference in end of stem pain between cemented and cementless stems in revision TKA. The final two studies in the session by Bolognesi and Peters respectively showed that metaphyseal cones continue to demonstrate excelled survivorship in rTKA setting despite extensive bone loss. Session eight was highlighted by a large series of revision reported by new member Dr Schwarzkopf, who showed that revision TKA done by high volume surgeons demonstrated better outcomes and lower revision rates compared to surgeon who did less than 18 rTKA's per year. Dr Maniar importantly showed that preoperatively, patients with high activity level and low pain and indicated by a high preop forgotten joint score did poorly following TKA while David Ayers nicely demonstrated that KOOS scores that assess specific postoperative outcomes can predict patient dissatisfaction after TKA. The final paper in this session by Max Courtney showed that the majority of surgical cancellations are due to medical issues, yet a minority of these undergo any intervention specifically for that condition, but they resulted in a delay of 5 months. The first two studies of Session nine focused on polyethylene thickness. Dr Backstein demonstrated no difference in KSS scores, change in ROM and aseptic revision rates based on polyethylene thickness in a series of 195 TKA's. An interesting lab study by Dr Tim Wright showed a surprising consistency in liner thickness choice among varying levels of surgeon experience that did not correlate with applied forces or gap stability estimates. Two studies looked specifically at the issue of tibial loosening and implant design. Nam and colleagues were not able to demonstrate concerning findings for increasing tibial loosening in a tibial baseplate with a shortened tibial keel at short term follow up, while Lachiewicz demonstrated a 19% revision or revision pending rate in 223 cemented fixed bearing ATTUNE TKA at a mean of 30 months. Our final session of the meeting, began with encouraging news, that despite only currently capturing about 40% of TJA's done in the US, the American Joint Replacement Registry data is representative of data in other representative US databases. An interesting study presented by Robert Barrack looked at bone remodeling in the proximal tibia after cemented and cementless TKA of two different designs. No significant difference was noted among the groups with the exception of the cemented thicker cobalt chrome tray which demonstrated significantly more bone mineral density loss. Along the same lines, a study out of Dr Bostrom's lab demonstrated treatment of a murine tibial model with iPTH prevents fibrous tissue formation and enhances bone formation in cementless implants. New Member Jamie Howard showed no difference in implant migration and kinematics of a single radius cementless design using either a measured resection or gap balancing technique and Dr Cushner show no difference in blood loss with cemented or cementless TKA with the use of TKA. The final two studies looked at staging and bilateral TKA's. Peter Sharkey showed that simultaneous TKA's were associated with higher complication compared to staged TKA and that staged TKA with less than a 90-day interval was not associated with higher risk. However, Mark Figgie showed that patients undergoing simultaneous TKA compared to staged TKA, missed 17 fewer days of work. In spite of the virtual nature of the meeting, there were some outstanding scientific interactions and the material presented will continue to generate debate and to guide the direction of knee arthroplasty as we move forwards

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.

Objectives

Lower limb muscle power is thought to influence outcome following total knee replacement (TKR). Post-operative deficits in muscle strength are commonly reported, although not explained. We hypothesised that post-operative recovery of lower limb muscle power would be influenced by the number of satellite cells in the quadriceps muscle at time of surgery.