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Bone & Joint Research
Vol. 13, Issue 4 | Pages 149 - 156
4 Apr 2024
Rajamäki A Lehtovirta L Niemeläinen M Reito A Parkkinen J Peräniemi S Vepsäläinen J Eskelinen A

Aims. Metal particles detached from metal-on-metal hip prostheses (MoM-THA) have been shown to cause inflammation and destruction of tissues. To further explore this, we investigated the histopathology (aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) score) and metal concentrations of the periprosthetic tissues obtained from patients who underwent revision knee arthroplasty. We also aimed to investigate whether accumulated metal debris was associated with ALVAL-type reactions in the synovium. Methods. Periprosthetic metal concentrations in the synovia and histopathological samples were analyzed from 230 patients from our institution from October 2016 to December 2019. An ordinal regression model was calculated to investigate the effect of the accumulated metals on the histopathological reaction of the synovia. Results. Median metal concentrations were as follows: cobalt: 0.69 μg/g (interquartile range (IQR) 0.10 to 6.10); chromium: 1.1 μg/g (IQR 0.27 to 4.10); and titanium: 1.6 μg/g (IQR 0.90 to 4.07). Moderate ALVAL scores were found in 30% (n = 39) of the revised knees. There were ten patients with an ALVAL score of 6 or more who were revised for suspected periprosthetic joint infection (PJI), aseptic loosening, or osteolysis. R2 varied between 0.269 and 0.369 for the ordinal regression models. The most important variables were model type, indication for revision, and cobalt and chromium in the ordinal regression models. Conclusion. We found that metal particles released from the knee prosthesis can accumulate in the periprosthetic tissues. Several patients revised for suspected culture-negative PJI had features of an ALVAL reaction, which is a novel finding. Therefore, ALVAL-type reactions can also be found around knee prostheses, but they are mostly mild and less common than those found around metal-on-metal prostheses. Cite this article: Bone Joint Res 2024;13(4):149–156


Bone & Joint Open
Vol. 5, Issue 3 | Pages 174 - 183
6 Mar 2024
Omran K Waren D Schwarzkopf R

Aims. Total hip arthroplasty (THA) is a common procedure to address pain and enhance function in hip disorders such as osteoarthritis. Despite its success, postoperative patient recovery exhibits considerable heterogeneity. This study aimed to investigate whether patients follow distinct pain trajectories following THA and identify the patient characteristics linked to suboptimal trajectories. Methods. This retrospective cohort study analyzed THA patients at a large academic centre (NYU Langone Orthopedic Hospital, New York, USA) from January 2018 to January 2023, who completed the Patient-Reported Outcomes Measurement Information System (PROMIS) pain intensity questionnaires, collected preoperatively at one-, three-, six-, 12-, and 24-month follow-up times. Growth mixture modelling (GMM) was used to model the trajectories. Optimal model fit was determined by Bayesian information criterion (BIC), Vuong-Lo-Mendell-Rubin likelihood ratio test (VLMR-LRT), posterior probabilities, and entropy values. Association between trajectory groups and patient characteristics were measured by multinomial logistic regression using the three-step approach. Results. Among the 1,249 patients, a piecewise GMM model revealed three distinct pain trajectory groups: 56 patients (4.5%) in group 1; 1,144 patients (91.6%) in group 2; and 49 patients (3.9%) in group 3. Patients in group 2 experienced swift recovery post-THA and minimal preoperative pain. In contrast, groups 1 and 3 initiated with pronounced preoperative pain; however, only group 3 exhibited persistent long-term pain. Multinomial regression indicated African Americans were exceedingly likely to follow trajectory groups 1 (odds ratio (OR) 2.73) and 3 (OR 3.18). Additionally, odds of membership to group 3 increased by 12% for each BMI unit rise, by 19% for each added postoperative day, and by over four if discharged to rehabilitation services (OR 4.07). Conclusion. This study identified three distinct pain trajectories following THA, highlighting the role of individual patient factors in postoperative recovery. This emphasizes the importance of preoperatively addressing modifiable risk factors associated with suboptimal pain trajectories, particularly in at-risk patients. Cite this article: Bone Jt Open 2024;5(3):174–183


The Bone & Joint Journal
Vol. 106-B, Issue 5 Supple B | Pages 74 - 81
1 May 2024
Callary SA Broekhuis D Barends J Ramasamy B Nelissen RGHH Solomon LB Kaptein BL

Aims. The aim of this study was to compare the biomechanical models of two frequently used techniques for reconstructing severe acetabular defects with pelvic discontinuity in revision total hip arthroplasty (THA) – the Trabecular Metal Acetabular Revision System (TMARS) and custom triflange acetabular components (CTACs) – using virtual modelling. Methods. Pre- and postoperative CT scans from ten patients who underwent revision with the TMARS for a Paprosky IIIB acetabular defect with pelvic discontinuity were retrospectively collated. Computer models of a CTAC implant were designed from the preoperative CT scans of these patients. Computer models of the TMARS reconstruction were segmented from postoperative CT scans using a semi-automated method. The amount of bone removed, the implant-bone apposition that was achieved, and the restoration of the centre of rotation of the hip were compared between all the actual TMARS and the virtual CTAC implants. Results. The median amount of bone removed for TMARS reconstructions was significantly greater than for CTAC implants (9.07 cm. 3. (interquartile range (IQR) 5.86 to 21.42) vs 1.16 cm. 3. (IQR 0.42 to 3.53) (p = 0.004). There was no significant difference between the median overall implant-bone apposition between TMARS reconstructions and CTAC implants (54.8 cm. 2. (IQR 28.2 to 82.3) vs 56.6 cm. 2. (IQR 40.6 to 69.7) (p = 0.683). However, there was significantly more implant-bone apposition within the residual acetabulum (45.2 cm. 2. (IQR 28.2 to 72.4) vs 25.5 cm. 2. (IQR 12.8 to 44.1) (p = 0.001) and conversely significantly less apposition with the outer cortex of the pelvis for TMARS implants compared with CTAC reconstructions (0 cm. 2. (IQR 0 to 13.1) vs 23.2 cm. 2. (IQR 16.4 to 30.6) (p = 0.009). The mean centre of rotation of the hip of TMARS reconstructions differed by a mean of 11.1 mm (3 to 28) compared with CTAC implants. Conclusion. In using TMARS, more bone is removed, thus achieving more implant-bone apposition within the residual acetabular bone. In CTAC implants, the amount of bone removed is minimal, while the implant-bone apposition is more evenly distributed between the residual acetabulum and the outer cortex of the pelvis. The differences suggest that these implants used to treat pelvic discontinuity might achieve short- and long-term stability through different biomechanical mechanisms. Cite this article: Bone Joint J 2024;106-B(5 Supple B):74–81


Bone & Joint Research
Vol. 12, Issue 9 | Pages 590 - 597
20 Sep 2023
Uemura K Otake Y Takashima K Hamada H Imagama T Takao M Sakai T Sato Y Okada S Sugano N

Aims. This study aimed to develop and validate a fully automated system that quantifies proximal femoral bone mineral density (BMD) from CT images. Methods. The study analyzed 978 pairs of hip CT and dual-energy X-ray absorptiometry (DXA) measurements of the proximal femur (DXA-BMD) collected from three institutions. From the CT images, the femur and a calibration phantom were automatically segmented using previously trained deep-learning models. The Hounsfield units of each voxel were converted into density (mg/cm. 3. ). Then, a deep-learning model trained by manual landmark selection of 315 cases was developed to select the landmarks at the proximal femur to rotate the CT volume to the neutral position. Finally, the CT volume of the femur was projected onto the coronal plane, and the areal BMD of the proximal femur (CT-aBMD) was quantified. CT-aBMD correlated to DXA-BMD, and a receiver operating characteristic (ROC) analysis quantified the accuracy in diagnosing osteoporosis. Results. CT-aBMD was successfully measured in 976/978 hips (99.8%). A significant correlation was found between CT-aBMD and DXA-BMD (r = 0.941; p < 0.001). In the ROC analysis, the area under the curve to diagnose osteoporosis was 0.976. The diagnostic sensitivity and specificity were 88.9% and 96%, respectively, with the cutoff set at 0.625 g/cm. 2. . Conclusion. Accurate DXA-BMD measurements and diagnosis of osteoporosis were performed from CT images using the system developed herein. As the models are open-source, clinicians can use the proposed system to screen osteoporosis and determine the surgical strategy for hip surgery. Cite this article: Bone Joint Res 2023;12(9):590–597


Bone & Joint Research
Vol. 13, Issue 4 | Pages 184 - 192
18 Apr 2024
Morita A Iida Y Inaba Y Tezuka T Kobayashi N Choe H Ike H Kawakami E

Aims. This study was designed to develop a model for predicting bone mineral density (BMD) loss of the femur after total hip arthroplasty (THA) using artificial intelligence (AI), and to identify factors that influence the prediction. Additionally, we virtually examined the efficacy of administration of bisphosphonate for cases with severe BMD loss based on the predictive model. Methods. The study included 538 joints that underwent primary THA. The patients were divided into groups using unsupervised time series clustering for five-year BMD loss of Gruen zone 7 postoperatively, and a machine-learning model to predict the BMD loss was developed. Additionally, the predictor for BMD loss was extracted using SHapley Additive exPlanations (SHAP). The patient-specific efficacy of bisphosphonate, which is the most important categorical predictor for BMD loss, was examined by calculating the change in predictive probability when hypothetically switching between the inclusion and exclusion of bisphosphonate. Results. Time series clustering allowed us to divide the patients into two groups, and the predictive factors were identified including patient- and operation-related factors. The area under the receiver operating characteristic (ROC) curve (AUC) for the BMD loss prediction averaged 0.734. Virtual administration of bisphosphonate showed on average 14% efficacy in preventing BMD loss of zone 7. Additionally, stem types and preoperative triglyceride (TG), creatinine (Cr), estimated glomerular filtration rate (eGFR), and creatine kinase (CK) showed significant association with the estimated patient-specific efficacy of bisphosphonate. Conclusion. Periprosthetic BMD loss after THA is predictable based on patient- and operation-related factors, and optimal prescription of bisphosphonate based on the prediction may prevent BMD loss. Cite this article: Bone Joint Res 2024;13(4):184–192


Bone & Joint Research
Vol. 12, Issue 10 | Pages 624 - 635
4 Oct 2023
Harrison CJ Plessen CY Liegl G Rodrigues JN Sabah SA Beard DJ Fischer F

Aims. To map the Oxford Knee Score (OKS) and High Activity Arthroplasty Score (HAAS) items to a common scale, and to investigate the psychometric properties of this new scale for the measurement of knee health. Methods. Patient-reported outcome measure (PROM) data measuring knee health were obtained from the NHS PROMs dataset and Total or Partial Knee Arthroplasty Trial (TOPKAT). Assumptions for common scale modelling were tested. A graded response model (fitted to OKS item responses in the NHS PROMs dataset) was used as an anchor to calibrate paired HAAS items from the TOPKAT dataset. Information curves for the combined OKS-HAAS model were plotted. Bland-Altman analysis was used to compare common scale scores derived from OKS and HAAS items. A conversion table was developed to map between HAAS, OKS, and the common scale. Results. We included 3,329 response sets from 528 patients undergoing knee arthroplasty. These generally met the assumptions of unidimensionality, monotonicity, local independence, and measurement invariance. The HAAS items provided more information than OKS items at high levels of knee health. Combining both instruments resulted in higher test-level information than either instrument alone. The mean error between common scale scores derived from the OKS and HAAS was 0.29 logits. Conclusion. The common scale allowed more precise measurement of knee health than use of either the OKS or HAAS individually. These techniques for mapping PROM instruments may be useful for the standardization of outcome reporting, and pooling results across studies that use either PROM in individual-patient meta-analysis. Cite this article: Bone Joint Res 2023;12(10):624–635


Bone & Joint Open
Vol. 4, Issue 3 | Pages 168 - 181
14 Mar 2023
Dijkstra H Oosterhoff JHF van de Kuit A IJpma FFA Schwab JH Poolman RW Sprague S Bzovsky S Bhandari M Swiontkowski M Schemitsch EH Doornberg JN Hendrickx LAM

Aims. To develop prediction models using machine-learning (ML) algorithms for 90-day and one-year mortality prediction in femoral neck fracture (FNF) patients aged 50 years or older based on the Hip fracture Evaluation with Alternatives of Total Hip arthroplasty versus Hemiarthroplasty (HEALTH) and Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trials. Methods. This study included 2,388 patients from the HEALTH and FAITH trials, with 90-day and one-year mortality proportions of 3.0% (71/2,388) and 6.4% (153/2,388), respectively. The mean age was 75.9 years (SD 10.8) and 65.9% of patients (1,574/2,388) were female. The algorithms included patient and injury characteristics. Six algorithms were developed, internally validated and evaluated across discrimination (c-statistic; discriminative ability between those with risk of mortality and those without), calibration (observed outcome compared to the predicted probability), and the Brier score (composite of discrimination and calibration). Results. The developed algorithms distinguished between patients at high and low risk for 90-day and one-year mortality. The penalized logistic regression algorithm had the best performance metrics for both 90-day (c-statistic 0.80, calibration slope 0.95, calibration intercept -0.06, and Brier score 0.039) and one-year (c-statistic 0.76, calibration slope 0.86, calibration intercept -0.20, and Brier score 0.074) mortality prediction in the hold-out set. Conclusion. Using high-quality data, the ML-based prediction models accurately predicted 90-day and one-year mortality in patients aged 50 years or older with a FNF. The final models must be externally validated to assess generalizability to other populations, and prospectively evaluated in the process of shared decision-making. Cite this article: Bone Jt Open 2023;4(3):168–181


The Bone & Joint Journal
Vol. 106-B, Issue 10 | Pages 1111 - 1117
1 Oct 2024
Makaram NS Becher H Oag E Heinz NR McCann CJ Mackenzie SP Robinson CM

Aims. The risk factors for recurrent instability (RI) following a primary traumatic anterior shoulder dislocation (PTASD) remain unclear. In this study, we aimed to determine the rate of RI in a large cohort of patients managed nonoperatively after PTASD and to develop a clinical prediction model. Methods. A total of 1,293 patients with PTASD managed nonoperatively were identified from a trauma database (mean age 23.3 years (15 to 35); 14.3% female). We assessed the prevalence of RI, and used multivariate regression modelling to evaluate which demographic- and injury-related factors were independently predictive for its occurrence. Results. The overall rate of RI at a mean follow-up of 34.4 months (SD 47.0) was 62.8% (n = 812), with 81.0% (n = 658) experiencing their first recurrence within two years of PTASD. The median time for recurrence was 9.8 months (IQR 3.9 to 19.4). Independent predictors increasing risk of RI included male sex (p < 0.001), younger age at PTASD (p < 0.001), participation in contact sport (p < 0.001), and the presence of a bony Bankart (BB) lesion (p = 0.028). Greater tuberosity fracture (GTF) was protective (p < 0.001). However, the discriminative ability of the resulting predictive model for two-year risk of RI was poor (area under the curve (AUC) 0.672). A subset analysis excluding identifiable radiological predictors of BB and GTF worsened the predictive ability (AUC 0.646). Conclusion. This study clarifies the prevalence and risk factors for RI following PTASD in a large, unselected patient cohort. Although these data permitted the development of a predictive tool for RI, its discriminative ability was poor. Predicting RI remains challenging, and as-yet-undetermined risk factors may be important in determining the risk. Cite this article: Bone Joint J 2024;106-B(10):1111–1117


Bone & Joint 360
Vol. 13, Issue 3 | Pages 18 - 20
3 Jun 2024

The June 2024 Hip & Pelvis Roundup. 360. looks at: Machine learning did not outperform conventional competing risk modelling to predict revision arthroplasty; Unravelling the risks: incidence and reoperation rates for femoral fractures post-total hip arthroplasty; Spinal versus general anaesthesia for hip arthroscopy: a COVID-19 pandemic- and opioid epidemic-driven study; Development and validation of a deep-learning model to predict total hip arthroplasty on radiographs; Ambulatory centres lead in same-day hip and knee arthroplasty success; Exploring the impact of smokeless tobacco on total hip arthroplasty outcomes: a deeper dive into postoperative complications


The Bone & Joint Journal
Vol. 105-B, Issue 6 | Pages 587 - 589
1 Jun 2023
Kunze KN Jang SJ Fullerton MA Vigdorchik JM Haddad FS

The OpenAI chatbot ChatGPT is an artificial intelligence (AI) application that uses state-of-the-art language processing AI. It can perform a vast number of tasks, from writing poetry and explaining complex quantum mechanics, to translating language and writing research articles with a human-like understanding and legitimacy. Since its initial release to the public in November 2022, ChatGPT has garnered considerable attention due to its ability to mimic the patterns of human language, and it has attracted billion-dollar investments from Microsoft and PricewaterhouseCoopers. The scope of ChatGPT and other large language models appears infinite, but there are several important limitations. This editorial provides an introduction to the basic functionality of ChatGPT and other large language models, their current applications and limitations, and the associated implications for clinical practice and research. Cite this article: Bone Joint J 2023;105-B(6):587–589


Bone & Joint Research
Vol. 11, Issue 11 | Pages 826 - 834
17 Nov 2022
Kawai T Nishitani K Okuzu Y Goto K Kuroda Y Kuriyama S Nakamura S Matsuda S

Aims. The preventive effects of bisphosphonates on articular cartilage in non-arthritic joints are unclear. This study aimed to investigate the effects of oral bisphosphonates on the rate of joint space narrowing in the non-arthritic hip. Methods. We retrospectively reviewed standing whole-leg radiographs from patients who underwent knee arthroplasties from 2012 to 2020 at our institute. Patients with previous hip surgery, Kellgren–Lawrence grade ≥ II hip osteoarthritis, hip dysplasia, or rheumatoid arthritis were excluded. The rate of hip joint space narrowing was measured in 398 patients (796 hips), and the effects of the use of bisphosphonates were examined using the multivariate regression model and the propensity score matching (1:2) model. Results. A total of 45 of 398 (11.3%) eligible patients were taking an oral bisphosphonate at the time of knee surgery, with a mean age of 75.8 years (SD 6.2) in bisphosphonate users and 75.7 years (SD 6.8) in non-users. The mean joint space narrowing rate was 0.04 mm/year (SD 0.11) in bisphosphonate users and 0.12 mm/year (SD 0.25) in non-users (p < 0.001). In the multivariate model, age (standardized coefficient = 0.0867, p = 0.016) and the use of a bisphosphonate (standardized coefficient = −0.182, p < 0.001) were associated with the joint space narrowing rate. After successfully matching 43 bisphosphonate users and 86 non-users, the joint narrowing rate was smaller in bisphosphonate users (p < 0.001). Conclusion. The use of bisphosphonates is associated with decreased joint degeneration in non-arthritic hips after knee arthroplasty. Bisphosphonates slow joint degeneration, thus maintaining the thickness of joint cartilage in the normal joint or during the early phase of osteoarthritis. Cite this article: Bone Joint Res 2022;11(11):826–834


Bone & Joint Research
Vol. 12, Issue 8 | Pages 504 - 511
23 Aug 2023
Wang C Liu S Chang C

Aims. This study aimed to establish the optimal fixation methods for calcaneal tuberosity avulsion fractures with different fragment thicknesses in a porcine model. Methods. A total of 36 porcine calcanea were sawed to create simple avulsion fractures with three different fragment thicknesses (5, 10, and 15 mm). They were randomly fixed with either two suture anchors or one headless screw. Load-to-failure and cyclic loading tension tests were performed for the biomechanical analysis. Results. This biomechanical study predicts that headless screw fixation is a better option if fragment thickness is over 15 mm in terms of the comparable peak failure load to suture anchor fixation (headless screw: 432.55 N (SD 62.25); suture anchor: 446.58 N (SD 84.97)), and less fracture fragment displacement after cyclic loading (headless screw: 3.94 N (SD 1.76); suture anchor: 8.68 N (SD 1.84)). Given that the fragment thickness is less than 10 mm, suture anchor fixation is a safer option. Conclusion. Fracture fragment thickness helps in making the decision of either using headless screw or suture anchor fixation in treating calcaneal tuberosity avulsion fracture, based on the regression models of our study. Cite this article: Bone Joint Res 2023;12(8):504–511


Bone & Joint Research
Vol. 13, Issue 8 | Pages 383 - 391
2 Aug 2024
Mannala GK Rupp M Walter N Youf R Bärtl S Riool M Alt V

Aims. Bacteriophages infect, replicate inside bacteria, and are released from the host through lysis. Here, we evaluate the effects of repetitive doses of the Staphylococcus aureus phage 191219 and gentamicin against haematogenous and early-stage biofilm implant-related infections in Galleria mellonella. Methods. For the haematogenous infection, G. mellonella larvae were implanted with a Kirschner wire (K-wire), infected with S. aureus, and subsequently phages and/or gentamicin were administered. For the early-stage biofilm implant infection, the K-wires were pre-incubated with S. aureus suspension before implantation. After 24 hours, the larvae received phages and/or gentamicin. In both models, the larvae also received daily doses of phages and/or gentamicin for up to five days. The effect was determined by survival analysis for five days and quantitative culture of bacteria after two days of repetitive doses. Results. In the haematogenous infection, a single combined dose of phages and gentamicin, and repetitive injections with gentamicin or in combination with phages, resulted in significantly improved survival rates. In the early-stage biofilm infection, only repetitive combined administration of phages and gentamicin led to a significantly increased survival. Additionally, a significant reduction in number of bacteria was observed in the larvae after receiving repetitive doses of phages and/or gentamicin in both infection models. Conclusion. Based on our results, a single dose of the combination of phages and gentamicin is sufficient to prevent a haematogenous S. aureus implant-related infection, whereas gentamicin needs to be administered daily for the same effect. To treat early-stage S. aureus implant-related infection, repetitive doses of the combination of phages and gentamicin are required. Cite this article: Bone Joint Res 2024;13(8):383–391


The Bone & Joint Journal
Vol. 106-B, Issue 10 | Pages 1165 - 1175
1 Oct 2024
Frost Teilmann J Petersen ET Thillemann TM Hemmingsen CK Olsen Kipp J Falstie-Jensen T Stilling M

Aims. The aim of this study was to evaluate the kinematics of the elbow following increasing length of the radius with implantation of radial head arthroplasties (RHAs) using dynamic radiostereometry (dRSA). Methods. Eight human donor arms were examined by dRSA during motor-controlled flexion and extension of the elbow with the forearm in an unloaded neutral position, and in pronation and supination with and without a 10 N valgus or varus load, respectively. The elbows were examined before and after RHA with stem lengths of anatomical size, + 2 mm, and + 4 mm. The ligaments were maintained intact by using a step-cut lateral humeral epicondylar osteotomy, allowing the RHAs to be repeatedly exchanged. Bone models were obtained from CT scans, and specialized software was used to match these models with the dRSA recordings. The flexion kinematics of the elbow were described using anatomical coordinate systems to define translations and rotations with six degrees of freedom. Results. The greatest kinematic changes in the elbows were seen with the longest, + 4 mm, implant, which imposed a mean joint distraction of 2.8 mm in the radiohumeral joint and of 1.1 mm in the ulnohumeral joint, an increased mean varus angle of up to 2.4° for both the radius and the ulna, a mean shift of the radius of 2.0 mm in the ulnar direction, and a mean shift of the ulna of 1.0 mm posteriorly. Conclusion. The kinematics of the elbow deviated increasingly from those of the native joint with a 2 mm to a 4 mm lengthening of the radius. This confirms the importance of restoring the natural length of the radius when undertaking RHA. Cite this article: Bone Joint J 2024;106-B(10):1165–1175


Bone & Joint Research
Vol. 12, Issue 1 | Pages 58 - 71
17 Jan 2023
Dagneaux L Limberg AK Owen AR Bettencourt JW Dudakovic A Bayram B Gades NM Sanchez-Sotelo J Berry DJ van Wijnen A Morrey ME Abdel MP

Aims. As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA). Methods. Experimental knees were immobilized for either four weeks (72 mice) or eight weeks (72 mice), followed by a remobilization period of zero weeks (24 mice), two weeks (24 mice), or four weeks (24 mice) after suture removal. Half of the experimental knees also received an intra-articular injury. Biomechanical data were collected to measure passive extension angle (PEA). Histological data measuring area and thickness of posterior and anterior knee capsules were collected from knee sections. Results. Experimental knees immobilized for four weeks demonstrated mean PEAs of 141°, 72°, and 79° after zero, two, and four weeks of remobilization (n = 6 per group), respectively. Experimental knees demonstrated reduced PEAs after two weeks (p < 0.001) and four weeks (p < 0.0001) of remobilization compared to controls. Following eight weeks of immobilization, experimental knees exhibited mean PEAs of 82°, 73°, and 72° after zero, two, and four weeks of remobilization, respectively. Histological analysis demonstrated no cartilage degeneration. Similar trends in biomechanical and histological properties were observed when intra-articular violation was introduced. Conclusion. This study established a novel mouse model of robust knee contracture without evidence of OA. This was appreciated consistently after eight weeks of immobilization and was irrespective of length of remobilization. As such, this arthrofibrotic model provides opportunities to investigate molecular pathways and therapeutic strategies. Cite this article: Bone Joint Res 2023;12(1):58–71


Bone & Joint Research
Vol. 13, Issue 1 | Pages 28 - 39
10 Jan 2024
Toya M Kushioka J Shen H Utsunomiya T Hirata H Tsubosaka M Gao Q Chow SK Zhang N Goodman SB

Aims. Transcription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that sex differences affect the response to NF-κB treatment during chronic inflammation in bone. This study investigated the therapeutic effects of NF-κB decoy oligodeoxynucleotides (ODN) during chronic inflammation in male and female mice. Methods. We used a murine model of chronic inflammation induced by continuous intramedullary delivery of lipopolysaccharide-contaminated polyethylene particles (cPE) using an osmotic pump. Specimens were evaluated using micro-CT and histomorphometric analyses. Sex-specific osteogenic and osteoclastic differentiation potentials were also investigated in vitro, including alkaline phosphatase, Alizarin Red, tartrate-resistant acid phosphatase staining, and gene expression using reverse transcription polymerase chain reaction (RT-PCR). Results. Local delivery of NF-κB decoy ODN in vivo increased osteogenesis in males, but not females, in the presence of chronic inflammation induced by cPE. Bone resorption activity was decreased in both sexes. In vitro osteogenic and osteoclastic differentiation assays during inflammatory conditions did not reveal differences among the groups. Receptor activator of nuclear factor kappa Β ligand (Rankl) gene expression by osteoblasts was significantly decreased only in males when treated with ODN. Conclusion. We demonstrated that NF-κB decoy ODN increased osteogenesis in male mice and decreased bone resorption activity in both sexes in preclinical models of chronic inflammation. NF-κB signalling could be a therapeutic target for chronic inflammatory diseases involving bone, especially in males. Cite this article: Bone Joint Res 2024;13(1):28–39


Bone & Joint Research
Vol. 11, Issue 10 | Pages 700 - 714
4 Oct 2022
Li J Cheung W Chow SK Ip M Leung SYS Wong RMY

Aims. Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models. Methods. Literature research was performed on PubMed and Embase databases. Keywords used for search criteria were “bone AND biofilm”. Information on the species of the animal model, bacterial strain, evaluation of biofilm and bone infection, complications, key findings on observations, prevention, and treatment of biofilm were extracted. Results. A total of 43 studies were included. Animal models used included fracture-related infections (ten studies), periprosthetic joint infections (five studies), spinal infections (three studies), other implant-associated infections, and osteomyelitis. The most common bacteria were Staphylococcus species. Biofilm was most often observed with scanning electron microscopy. The natural history of biofilm revealed that the process of bacteria attachment, proliferation, maturation, and dispersal would take 14 days. For systemic mono-antibiotic therapy, only two of six studies using vancomycin reported significant biofilm reduction, and none reported eradication. Ten studies showed that combined systemic and topical antibiotics are needed to achieve higher biofilm reduction or eradication, and the effect is decreased with delayed treatment. Overall, 13 studies showed promising therapeutic potential with surface coating and antibiotic loading techniques. Conclusion. Combined topical and systemic application of antimicrobial agents effectively reduces biofilm at early stages. Future studies with sustained release of antimicrobial and biofilm-dispersing agents tailored to specific pathogens are warranted to achieve biofilm eradication. Cite this article: Bone Joint Res 2022;11(10):700–714


Bone & Joint Research
Vol. 13, Issue 7 | Pages 332 - 341
5 Jul 2024
Wang T Yang C Li G Wang Y Ji B Chen Y Zhou H Cao L

Aims. Although low-intensity pulsed ultrasound (LIPUS) combined with disinfectants has been shown to effectively eliminate portions of biofilm in vitro, its efficacy in vivo remains uncertain. Our objective was to assess the antibiofilm potential and safety of LIPUS combined with 0.35% povidone-iodine (PI) in a rat debridement, antibiotics, and implant retention (DAIR) model of periprosthetic joint infection (PJI). Methods. A total of 56 male Sprague-Dawley rats were established in acute PJI models by intra-articular injection of bacteria. The rats were divided into four groups: a Control group, a 0.35% PI group, a LIPUS and saline group, and a LIPUS and 0.35% PI group. All rats underwent DAIR, except for Control, which underwent a sham procedure. General status, serum biochemical markers, weightbearing analysis, radiographs, micro-CT analysis, scanning electron microscopy of the prostheses, microbiological analysis, macroscope, and histopathology evaluation were performed 14 days after DAIR. Results. The group with LIPUS and 0.35% PI exhibited decreased levels of serum biochemical markers, improved weightbearing scores, reduced reactive bone changes, absence of viable bacteria, and decreased inflammation compared to the Control group. Despite the greater antibiofilm activity observed in the PI group compared to the LIPUS and saline group, none of the monotherapies were successful in preventing reactive bone changes or eliminating the infection. Conclusion. In the rat model of PJI treated with DAIR, LIPUS combined with 0.35% PI demonstrated stronger antibiofilm potential than monotherapy, without impairing any local soft-tissue. Cite this article: Bone Joint Res 2024;13(7):332–341


The Bone & Joint Journal
Vol. 106-B, Issue 11 | Pages 1231 - 1239
1 Nov 2024
Tzanetis P Fluit R de Souza K Robertson S Koopman B Verdonschot N

Aims. The surgical target for optimal implant positioning in robotic-assisted total knee arthroplasty remains the subject of ongoing discussion. One of the proposed targets is to recreate the knee’s functional behaviour as per its pre-diseased state. The aim of this study was to optimize implant positioning, starting from mechanical alignment (MA), toward restoring the pre-diseased status, including ligament strain and kinematic patterns, in a patient population. Methods. We used an active appearance model-based approach to segment the preoperative CT of 21 osteoarthritic patients, which identified the osteophyte-free surfaces and estimated cartilage from the segmented bones; these geometries were used to construct patient-specific musculoskeletal models of the pre-diseased knee. Subsequently, implantations were simulated using the MA method, and a previously developed optimization technique was employed to find the optimal implant position that minimized the root mean square deviation between pre-diseased and postoperative ligament strains and kinematics. Results. There were evident biomechanical differences between the simulated patient models, but also trends that appeared reproducible at the population level. Optimizing the implant position significantly reduced the maximum observed strain root mean square deviations within the cohort from 36.5% to below 5.3% for all but the anterolateral ligament; and concomitantly reduced the kinematic deviations from 3.8 mm (SD 1.7) and 4.7° (SD 1.9°) with MA to 2.7 mm (SD 1.4) and 3.7° (SD 1.9°) relative to the pre-diseased state. To achieve this, the femoral component consistently required translational adjustments in the anterior, lateral, and proximal directions, while the tibial component required a more posterior slope and varus rotation in most cases. Conclusion. These findings confirm that MA-induced biomechanical alterations relative to the pre-diseased state can be reduced by optimizing the implant position, and may have implications to further advance pre-planning in robotic-assisted surgery in order to restore pre-diseased knee function. Cite this article: Bone Joint J 2024;106-B(11):1231–1239


The Bone & Joint Journal
Vol. 106-B, Issue 3 | Pages 256 - 261
1 Mar 2024
Goodall R Borsky K Harrison CJ Welck M Malhotra K Rodrigues JN

Aims. The Manchester-Oxford Foot Questionnaire (MOxFQ) is an anatomically specific patient-reported outcome measure (PROM) currently used to assess a wide variety of foot and ankle pathology. It consists of 16 items across three subscales measuring distinct but related traits: walking/standing ability, pain, and social interaction. It is the most used foot and ankle PROM in the UK. Initial MOxFQ validation involved analysis of 100 individuals undergoing hallux valgus surgery. This project aimed to establish whether an individual’s response to the MOxFQ varies with anatomical region of disease (measurement invariance), and to explore structural validity of the factor structure (subscale items) of the MOxFQ. Methods. This was a single-centre, prospective cohort study involving 6,637 patients (mean age 52 years (SD 17.79)) presenting with a wide range of foot and ankle pathologies between January 2013 and December 2021. To assess whether the MOxFQ responses vary by anatomical region of foot and ankle disease, we performed multigroup confirmatory factor analysis. To assess the structural validity of the subscale items, exploratory and confirmatory factor analyses were performed. Results. Measurement invariance by pathology was confirmed, suggesting the same model can be used across all foot and ankle anatomical regions. Exploratory factor analysis demonstrated a two- to three-factor model, and suggested that item 13 (inability to carry out work/everyday activities) and item 14 (inability to undertake social/recreational activities) loaded more positively onto the “walking/standing” subscale than their original “social interaction” subscale. Conclusion. This large cohort study supports the current widespread use of the MOxFQ across a broad range of foot and ankle pathologies. Our analyses found indications that could support alterations to the original factor structure (items 13 and 14 might be moved from the “social interaction” to the “walking/standing” subscale). However, this requires further work to confirm. Cite this article: Bone Joint J 2024;106-B(3):256–261