Statins are potent inhibitors of cholesterol synthesis. Several statins are available with different molecular and pharmacokinetic properties. Simvastatin is more lipophilic than pravastatin and has a higher affinity to phospholipid membranes than atorvastatin, allowing its passive diffusion through the cell membrane. In vitro studies on bone marrow stromal cells, osteoblast-like cells, and embryonic stem cells have shown statins to have cholesterol-independent anabolic effects on bone metabolism; alas, statins were supplemented in osteogenic medium, which does not facilitate elucidation of their potential osteoinductive properties. Embryonic stem cells (ESCs), derived from the inner cell mass of the blastocyst, are unique in that they enjoy perpetual self-proliferation, are pluripotent, and are able to differentiate toward all the cellular lineages composing the body, including the osteogenic lineage. Consequently, ESCs represent a potentially potent cell source for future clinical cellular therapies of various bone diseases, even though there are several hurdles that still need to be overcome. Herein we demonstrate, for the first time to our knowledge, that simvastatin induces murine ESC (mESC) differentiation toward the osteogenic lineage in the absence of osteoinductive supplements. Specifically, we found that a simvastatin concentration in the micromolar range and higher was toxic to the cells and that an effective concentration for osteoinduction is 0.1 nM, as shown by increased alizarin red staining as well as increased osteocalcin and osetrix gene expression. These results suggest that in the future, lipophilic simvastatin may provide a novel pharmacologic agent for bone tissue engineering applications. ß

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Aims The aim of this study was to identify the effect of the manufacturing characteristics of polyethylene acetabular liners on the survival of cementless and hybrid total hip arthroplasty (THA). Methods Prospective cohort study using linked National Joint Registry (NJR) and manufacturer data. The primary endpoint was revision for aseptic loosening. Cox proportional hazard regression was the primary analytical approach. Manufacturing variables included resin type, crosslinking radiation dose, terminal sterilization method, terminal sterilization radiation dose, stabilization treatment, total radiation dose, packaging, and face asymmetry. Total radiation dose was further divided into G1 (no radiation), G2 (> 0 Mrad to < 5 Mrad), G3 (≥ 5 Mrad to < 10 Mrad), and G4 (≥ 10 Mrad). Results A total of 5,329 THAs were revised, 1,290 of which were due to aseptic loosening. Total radiation dose, face asymmetry, and stabilization treatments were found to significantly affect implant survival. G1 had the highest revision risk for any reason and for aseptic loosening and G3 and G4 the lowest. Compared with G1, the adjusted hazard ratio for G2 was 0.74 (95% confidence interval (CI) 0.64 to 0.86), G3 was 0.36 (95% CI 0.30 to 0.43), and G4 was 0.38 (95% CI 0.31 to 0.47). The cumulative incidence of revision for aseptic loosening at 12 years was 0.52 and 0.54 per 100 THAs for G3 and G4, respectively, compared with 1.95 per 100 THAs in G1. Asymmetrical liners had a lower revision risk due to aseptic loosening and reasons other than aseptic loosening compared with symmetric (flat) liners. In G3 and G4, stabilization with vitamin E and heating above melting point performed best. Conclusion Polyethylene liners with a total radiation dose of ≥ 5 Mrad, an asymmetrical liner face, and stabilization with heating above the melting point demonstrate best survival. Cite this article: Bone Joint J 2020;102-B(1):90–101

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The results indicate that far cortical locking screws can reduce the overall effective stiffness of the locking plates and increase the fracture movement while maintaining the overall strength of the PFF fixation construct. However, in unstable fractures, alternative fixation methods, for example, long stem revision might be a better option.

Level IV. Case series.

purpose. To compare the effects of different warfarin reversal protocols on surgical delay and complication rate in hip fracture patients. Methods. Records of 7 men and 17 women aged 68 to 93 (mean, 82) years who were on warfarin and underwent surgery for femoral neck fractures were reviewed. The time to surgery, complication rate, and mortality were recorded, as were the International Normalised Ratio (INR) on admission and the day of operation, as well as the dose, route, and time of administration of vitamin K for reversing the anticoagulation effect of warfarin. Patients were divided into 4 groups based on the warfarin reversal treatment. Group 1 (n=4) included patients who did not receive reversal treatment, as their admission INR was ≤1.5. Group 2 (n=6) included patients who did not receive reversal treatment even though their INR was >1.6. Group 3 (n=5) included patients who received inappropriate reversal treatment (late or low-dose oral administration). Group 4 (n=9) included patientsComparison of different warfarin reversal protocols on surgical delay and complication rate in hip fracture patients who received appropriate reversal treatment in terms of dose, route, and time of administration. results. Among the 4 groups, the mean INR was 2.2 (range, 1.3-4.6) on admission and 1.4 (range, 1.0-1.6) on the day of surgery. Group 1 was excluded from further analysis. Respectively in groups 2, 3, and 4, the mean times to surgery were 2.3, 2.6, and 1.2 days, and the complication rates were 67%, 20%, and 11%. conclusion. Early administration of intravenous vitamin K for hip fracture patients on warfarin is recommended to ensure early operative management and avoid postoperative complications.

Aims: Metaphyseal cones and sleeves are components used in revision knee arthroplasty to ensure load transfer, encourage bone on-growth and prevent stress shielding. Additive manufacturing of titanium alloy implants is a novel technique with limited clinical outcome reports in the literature. The aim of this study was to determine radiographic evidence of osseointegration and early results of a single manufacturer porous titanium metaphyseal components in the proximal tibia. Methods: We retrospectively reviewed the prospectively collected database of two institutions. Patients who underwent revision knee arthroplasty using porous titanium components by a single manufacturer were identified. Immediate post-operative and latest follow-up radiographs were independently analysed by 2 reviewers to determine metaphyseal bone contact and level of osseointegration in relevant Knee Society Radiographic Evaluation and Scoring System zones. Results: 22 patients (15 males; 7 females) with a mean age of 71 (49e92) years were included. The mean follow-up period was 14 months (2e44 months). Cones were used in 16 patients and sleeves in 6. Interobserver reliability assessment showed substantial agreement (weighted Kappa 0.71, (95% CI: 0.60, 0.81). There was significant correlation between the bone contact in the immediate postop radiograph and osseointegration at final follow-up (kendall's tau-b: 0.698, p < 0.001). Infection free prosthetic joint survival was 20/22 at final follow-up. Conclusion: Porous titanium metaphyseal components produced with additive manufacturing provided excellent osseointegration and no early clinical failures. Partial or complete contact of the cone with native bone in the immediate postoperative radiograph resulted in osseointegration in all cases.