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Integrin complexes facilitate cell communication, playing a role in ligament homeostasis. ITGB2 rs2230528 (C/T) wasimplicated in anteriorcruciate ligament rupture (ACL) risk in a South African cohort. Identifying biologically significant DNA signatures in the predisposition to ACL rupture risk remains important towards understanding mechanisms of ACL ruptures. ITGB2 is essential for the activation of important biological pathways regulated by structural components such as collagens and biomechanical components such as vasculo-endothelial growth factors. This study tested the association of (i) ITGB2 rs2230528 and (ii) allele-allele combinations of ITGB2’s network partners (COL5A1 rs12722 C/T, VEGFA rs699947 C/A and VEGFA rs2010963 G/C) with ACL rupture risk. The genetic study was conducted in a combined cohort [n=1279: uninjured controls (CON), n=548; ACL ruptures (ACL), n=731; subgroup with non-contact mechanism of ACL ruptures (NON, n=425)] recruited from Australia, Poland, Sweden and South Africa. The combined cohort, rs2230528 TT (best fit model) was significantly over-represented in the ACL (p=8.00×10⁻⁸; OR:3.21; 95% CI:2.10–4.89, AIC=1549) and NON (p=1.59×10⁻⁶; OR:3.11; 95% CI:1.97–4.91, AIC=1191) groups compared to CON. ITGB2 rs2230528-COL5A1 rs12722-VEGFA rs699947-VEGFA rs2010963, the C-C-A-G and C-T-C-G combinations were significantly associated with reduced ACL risk. This study provided additional evidence highlighting ITGB2 as potentially being associated with ACL ruptures even though the gene-gene combinations had a small effect size. Integrins containing the b2 subunit together with its key extracellular matrix components (type V collagen and VEGFA) are potential therapeutic targets for ACL ruptures and potentially other connective tissue-related conditions.

Background and purpose: The design and coating of uncemented joint implants impact bone ingrowth and thereby the stability of the implant. This prospective randomized clinical trial aimed to compare early migration of two uncemented, similarly shaped femoral stems with either calcium phosphate or hydroxyapatite coating.

Patients and methods: 93 patients (102 hips) were randomized to either an intervention calcium phosphate or a conventional hydroxyapatite-coated stem. Migration measurements were performed postoperatively, and at 6 weeks, 3, 12 months, and 2 and 5 years after operation, and analyzed with radiostereometric analysis.

Results: There were no significant differences in migration between the two stems from postoperative to 5-year follow-up. With 6 weeks follow-up as baseline, the calcium phosphate coated stem showed a tendency towards migrating less with a maximum total point motion up to 2 years of 0.84 mm (0.68 to 1.00 95% CI) compared to the hydroxyapatite-coated stem which migrated 1.25 mm (0.99 to 1.52 95% CI) (P = 0.010).

Conclusions: Our data show that the calcium phosphate-coated stem is a safe implant in terms of ingrowth stability, and with migration patterns comparable to a hydroxyapatite-coated stem.

Background and purpose — Sonication fluid cultures have been proposed as a complementary diagnostic method to intraoperative tissue culture sampling for the diagnosis of periprosthetic joint infection (PJI). We evaluated whether sonication provides additional clinically relevant information in the diagnosis of PJI in hip revision.

Methods — Episodes of hip revision performed between January 2007 and December 2016 were assigned retrospectively to the European Bone and Joint Infection Society (EBJIS) definition of periprosthetic joint infection: infection unlikely, infection likely, and infection confirmed. The inclusion criteria were a minimum of 2 perioperative tissue cultures collected at the index procedure and sonication performed on a removed implant. The results of the tissue cultures were compared with the results of the implant sonication fluid cultures (SFCs).

Results — 288 hip revision episodes in 250 patients fulfilled the inclusion criteria and were analyzed. The “infection unlikely” group included 203 episodes (178 patients), the “infection likely” group included 5 episodes (5 patients), and the “infection confirmed” group included 80 episodes (67 patients). SFC delivered additional clinical information in 15/288: 6 of 203 episodes in the “infection unlikely” group, 2 of 5 episodes in the “infection likely” group, and 7 of 80 in the “infection confirmed” group. Coagulase-negative staphylococci and Staphylococcus aureus were the dominant bacterial species in both the SFC and tissue cultures.

Conclusion — In addition to tissue cultures, sonication fluid cultures optimized the microbiological yield in 15 out of 288 hip revision episodes.

Background: Uncemented trabecular metal (TM) monoblock tibial components in total knee arthroplasty (TKA) have shown excellent clinical results for up to 10 years. However, these studies were performed in highly specialized units, with few surgeons and often excluding knees with secondary osteoarthritis (OA), severe malalignments and previous surgery. The purpose of this study was to investigate implant survivorship and clinical and radiological outcome of the uncemented TM high-flex posterior stabilized (PS) monoblock tibial component in routine clinical practice.

Methods: A retrospective study of 339 knees (282 patients) operated with the implant in routine clinical practice at two hospitals on patients aged 60 years or younger between 2007 and 2015. The operations were performed by 12 surgeons and there were no specific contraindications for use of the implant. Follow up ended in 2020. The status of the implant of deceased patients at death and those not attending follow up was checked with the Swedish Knee Arthroplasty Register. Clinical follow up consisted of clinical investigation, PROMs, and knee X-ray.

Results: Follow up was mean (range) 8.5 (5–13.8) years, and the 8-year survival rate was 0.98 (standard error 0.007). Five patients five knees) were deceased, five knees were revised (none due to aseptic loosening), and 16 patients did not attend the clinical follow up. Forty-four percent of the knees had secondary OA and 45% had had previous operations. 93% were satisfied or very satisfied with the operation and forgotten joint score (FJS) was median (interquartile range) 81 (44–94). Radiographic analysis revealed bone in close contact with the tibial tray and pegs in most cases, and in only 2% of the knees were potential radiolucent lines found.

Conclusion: The results indicate that this uncemented implant performs excellently in routine clinical practice and also in younger patients with secondary OA or previous knee operations.

BACKGROUND AND PURPOSE: The aim of this prospective, randomised and controlled study was to evaluate the wear and fixation properties of a new cemented highly cross-linked all-polyethylene (HXLPE) cup in comparison with a conventional cemented ultra-high molecular weight polyethylene (ConvPE) cup using radiostereometric analysis (RSA).

PATIENTS AND METHODS: A total of 58 patients (58 hips) with primary osteoarthritis (OA) were enrolled in a randomised controlled trial to receive either a ConvPE cup (control) or HXLPE cup (intervention) with identical geometry. The subjects were randomised in a 1:1 ratio. The primary endpoint was proximal wear measured as femoral head penetration into the cup, secondary outcomes were 3D-wear and annual proximal wear from 1 to 5 years. Cup fixation was measured as movement of the cup in relation to the acetabular bone with proximal migration being the primary outcome measure, 3D-migration and change in inclination as secondary outcomes. The patients were followed for 5 years with RSA performed postoperatively, at 3, 12, 24, and 60 months.

RESULTS: The HXLPE displayed a lower median proximal femoral head penetration compared to ConvPE, with a median difference at 2 years of -0.07 mm (95% CI, -0.10 to -0.04 mm), and -0.19 mm (95% CI, -0.27 to -0.15 mm) at 5 years. Annual proximal wear between 1 and 5 years was 0.03 mm/year for HXLPE and 0.06 mm/year for ConvPE (mean difference 0.05 mm, [95% CI, 0.03-0.07 mm]). Proximal migration, 3D migration and change in inclination was numerically slightly higher for HXLPE, albeit not statistically significant.

CONCLUSIONS: Compared to ConvPE, the HXLPE cup displayed significantly lower polyethylene wear. Cup migration was not statistically significant different.

CLINICALTRIALS.GOV IDENTIFIER: NCT04322799.

Polymorphisms in VEGFA and KDR encoding proteins have been associated with anterior cruciate ligament (ACL) injury risk. We leveraged a collective sample from Sweden, Poland, and Australia to investigate the association of functional polymorphisms in VEGFA and KDR with susceptibility to ACL injury risk. Using a case–control genetic association approach, polymorphisms in VEGFA and KDR were genotyped and haplotypes inferred from 765 controls, and 912 cases clinically diagnosed with ACL rupture. For VEGFA, there was a significant overrepresentation of the rs2010963 CC genotype (p = 0.0001, false discovery rate [FDR]: p = 0.001, odds ratio [OR]: 2.16, 95% confidence interval [CI]: 1.47–3.19) in the combined ACL group (18%) compared to the combined control group (11%). The VEGFA (rs699947 C/A, rs1570360 G/A, rs2010963 G/C) A-A-G haplotype was significantly (p = 0.010, OR: 0.85, 95% CI: 0.69–1.05) underrepresented in the combined ACL group (23%) compared to the combined control group (28%). In addition, the A-G-G construct was significantly (p = 0.036, OR: 0.81, 95% CI: 0.64–1.02) underrepresented in the combined ACL group (12%) compared to the combined CON group (16%). Our findings support the association of the VEGFA rs2010963 CC genotype with increased risk and (ii) the VEGFA A-A-G haplotype with a reduced risk, and are in alignment with the a priori hypothesis. Collectively identifying a genetic interval within VEGFA to be implicated in ACL risk modulation and highlight further the importance of vascular regulation in ligament biology.

Background and purpose - Knowing how to interpret values obtained with patient reported outcome measures (PROMs) is essential. We estimated the substantial clinical benefit (SCB) and patient acceptable symptom state (PASS) for Forgotten Joint Score 12 (FJS) and explored differences depending on methods used for the estimates. Patients and methods - The study was based on 195 knee arthroplasties (KA) performed at a university hospital. We used 1 item from the Knee injury and Osteoarthritis Outcome Score domain quality of life and satisfaction with surgery, obtained 1-year postoperatively, to assess SCB and PASS thresholds of the FJS with anchor-based methods. We used different combinations of anchor questions for SCB and PASS (satisfied, satisfied with no or mild knee difficulties, and satisfied with no knee difficulties). A novel predictive approach and receiver-operating characteristics curve were applied for the estimates.

Results - 70 and 113 KAs were available for the SCB and PASS estimates, respectively. Depending on method, SCB of the FJS (range 0-100) was 28 (95% CI 21-35) and 22 (12-45) respectively. PASS was 31 (2-39) and 20 (10-29) for satisfied patients, 40 (31-47) and 38 (32-43) for satisfied patients with no/mild difficulties, and 76 (39-80) and 64 (55-74) for satisfied patients with no difficulties. The areas under the curve ranged from 0.82 to 0.88.

Interpretation - Both the SCB and PASS thresholds varied depending on methodology. This may indicate a problem using meaningful values from other studies defining outcomes after KA. This study supports the premise of the FJS as a PROM with good discriminatory ability in patients undergoing KA.

BACKGROUND: Radiostereometric analysis (RSA) is a highly accurate tool to detect implant migration and predict loosening following total knee arthroplasty (TKA). However, little is known about the predisposing risk factors for implant migration, nor which migration profile should be considered physiological (i.e., merely part of an implant-settling phase) and which should be considered pathological (i.e., having a high probability for implant loosening). By pooling individual participant data from long-term follow-up RSA studies, we aimed to identify predisposing risk factors for tibial component loosening.

METHODS: Individual data were collected for 630 patients from 11 RSA studies. The repeated measurements were analyzed with use of a linear mixed-effects model, determining the effect of age, sex, body mass index, diagnosis, preoperative and postoperative limb alignment, and prosthesis characteristics on tibial component migration over time, taking into account the clustering of patients within studies.

RESULTS: High initial migration was found to result in early mechanical loosening in 18 cases (2.9%) and septic loosening in 2 cases (0.3%), whereas stabilization of high initial migration occurred in 17 cases (2.7%). Late loosening occurred in 13 cases (2.1%). All other 580 cases (92.1%) showed early stabilization and remained stable over time. Mixed-effects model analyses showed that for cemented prostheses, sex, diagnosis, and posterior cruciate ligament type had an effect on migration, but these differences were nonsignificant when analyzing migration from 3 months onwards. Uncemented prostheses aligned in varus showed more migration than neutrally and valgus-aligned TKAs (p = 0.031), and this difference increased over time (p < 0.001). Significantly higher migration was observed following uncemented TKA without an osseointegration-promoting surface (p < 0.001).

CONCLUSIONS: For cemented prostheses, increased migration during the first 3 postoperative months was observed for female patients, patients with rheumatoid arthritis, and patients who underwent a posterior-stabilized TKA. For uncemented prostheses, both postoperative varus alignment of the lower limb and the absence of an osseointegration-promoting surface significantly increased postoperative tibial component migration.

LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Rotator cuff tendinopathy (RCT), anterior cruciate ligament (ACL) ruptures, and carpal tunnel syndrome (CTS), are examples of chronic (RCT and CTS) and acute (ACL ruptures) musculoskeletal soft tissue injuries. These injuries are multifactorial in nature, with several identified intrinsic and extrinsic risk factors. Previous studies have implicated specific sequence variants within genes encoding structural and regulatory components of the extracellular matrix of tendons and/ligaments to predispose individuals to these injuries. An example, includes the association of sequence variants within the apoptotic regulatory gene, caspase-8 (CASP8) with other musculoskeletal injury phenotypes, such as Achilles tendinopathy. The primary aim of this study was, therefore, to investigate previously implicated DNA sequence variants within CASP8: rs3834129 (ins/del) and rs1045485 (G/C), and the rs13113 (T/A) identified using a whole exome sequencing approach, with risk of musculoskeletal injury phenotypes (RCT, ACL ruptures, and CTS) in three independent studies. In addition, the aim was to implicate a CASP8 genomic interval in the modulation of risk of RCT, ACL ruptures, or CTS. It was found that the AA genotype of CASP8 rs13113 (T/A) was independently associated with increased risk for CTS. In addition, it was found that the del-C haplotype (rs3834129-rs1045485) was significantly associated with non-contact ACL ruptures, which is in alignment with previous research findings. Collectively, the results of this study implicate the apoptosis pathway as biologically significant in the underlying pathogenesis of musculoskeletal injury phenotypes. These findings should be repeated in larger sample cohorts and across different populations.