Aims Aseptic loosening is a leading cause of uncemented arthroplasty failure, often accompanied by fibrotic tissue at the bone-implant interface. A biological target, neutrophil extracellular traps (NETs), was investigated as a crucial connection between the innate immune system’s response to injury, fibrotic tissue development, and proper bone healing. Prevalence of NETs in peri-implant fibrotic tissue from aseptic loosening patients was assessed. A murine model of osseointegration failure was used to test the hypothesis that inhibition (through Pad4-/- mice that display defects in peptidyl arginine deiminase 4 (PAD4), an essential protein required for NETs) or resolution (via DNase 1 treatment, an enzyme that degrades the cytotoxic DNA matrix) of NETs can prevent osseointegration failure and formation of peri-implant fibrotic tissue. Methods Patient peri-implant fibrotic tissue was analyzed for NETs biomarkers. To enhance osseointegration in loose implant conditions, an innate immune system pathway (NETs) was either inhibited ( Pad4-/- mice) or resolved with a pharmacological agent (DNase 1) in a murine model of osseointegration failure. Results NETs biomarkers were identified in peri-implant fibrotic tissue collected from aseptic loosening patients and at the bone-implant interface in a murine model of osseointegration failure. Inhibition ( Pad4-/- ) or resolution (DNase 1) of NETs improved osseointegration and reduced fibrotic tissue despite loose implant conditions in mice. Conclusion This study identifies a biological target (NETs) for potential noninvasive treatments of aseptic loosening by discovering a novel connection between the innate immune system and post-injury bone remodelling caused by implant loosening. By inhibiting or resolving NETs in an osseointegration failure murine model, fibrotic tissue encapsulation around an implant is reduced and osseointegration is enhanced, despite loose implant conditions. Cite this article: Bone Joint J 2021;103-B(7 Supple B):135–144.
Background and purpose: Elective total hip replacement (THR) was halted in our institution during the COVID-19 surge in March 2020. Afterwards, elective THR volume increased with emphasis on fast-track protocols, early discharge, and post-discharge virtual care. We compare early outcomes during this “return-to-normal period” with those of a matched pre-pandemic cohort.Patients and methods: We identified 757 patients undergoing THR from June to August 2020, who were matched 1:1 with a control cohort from June to August 2019. Length of stay (LOS) for the study cohort was lower than the control cohort (31 vs. 45 hours; p < 0.001). The time to first postoperative physical therapy (PT) was shorter in the study cohort (370 vs. 425 minutes; p < 0.001). More patients were discharged home in the study cohort (99% vs. 94%; p < 0.001). Study patients utilized telehealth office and rehabilitation services 14 times more frequently (39% vs. 2.8%; p < 0.001). Outcomes included post-discharge 90-day unscheduled office visits, emergency room (ER) visits, complications, readmissions, and PROMs (HOOS JR, and VR-12 mental/physical). Mann–Whitney U and chi-square tests were used for group comparisons.Results: Rates of 90-day unscheduled outpatient visits (5.0% vs. 7.3%), ER visits (5.0% vs. 4.8%), hospital readmissions (4.0% vs. 2.8%), complications (0.04% vs. 0.03%), and 3-month PROMs were similar between cohorts. There was no 90-day mortality.Interpretation: A reduction in LOS and increased telehealth use for office and rehabilitation visits did not adversely influence 90-day clinical outcomes and PROMs. Our findings lend further support for the utilization of fast-track arthroplasty with augmentation of postoperative care delivery using telemedicine.
Aims To develop an early implant instability murine model and explore the use of intermittent parathyroid hormone (iPTH) treatment for initially unstable implants. Methods 3D-printed titanium implants were inserted into an oversized drill-hole in the tibiae of C57Bl/6 mice (n = 54). After implantation, the mice were randomly divided into three treatment groups (phosphate buffered saline (PBS)-control, iPTH, and delayed iPTH). Radiological analysis, micro-CT (µCT), and biomechanical pull-out testing were performed to assess implant loosening, bone formation, and osseointegration. Peri-implant tissue formation and cellular composition were evaluated by histology. Results iPTH reduced radiological signs of loosening and led to an increase in peri-implant bone formation over the course of four weeks (timepoints: one week, two weeks, and four weeks). Observational histological analysis shows that iPTH prohibits the progression of fibrosis. Delaying iPTH treatment until after onset of peri-implant fibrosis still resulted in enhanced osseointegration and implant stability. Despite initial instability, iPTH increased the mean pull-out strength of the implant from 8.41 N (SD 8.15) in the PBS-control group to 21.49 N (SD 10.45) and 23.68 N (SD 8.99) in the immediate and delayed iPTH groups, respectively. Immediate and delayed iPTH increased mean peri-implant bone volume fraction (BV/TV) to 0.46 (SD 0.07) and 0.34 (SD 0.10), respectively, compared to PBS-control mean BV/TV of 0.23 (SD 0.03) (PBS-control vs immediate iPTH, p < 0.001; PBS-control vs delayed iPTH, p = 0.048; immediate iPTH vs delayed iPTH, p = 0.111). Conclusion iPTH treatment mediated successful osseointegration and increased bone mechanical strength, despite initial implant instability. Clinically, this suggests that initially unstable implants may be osseointegrated with iPTH treatment. Cite this article: Bone Joint Res 2022;11(5):260–269.
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