Fusion of electronic health records and radiographic images for a multimodal deep learning prediction model of atypical femur fractures.

Atypical femur fractures (AFF) represent a very rare type of fracture that can be difficult to discriminate radiologically from normal femur fractures (NFF). AFFs are associated with drugs that are administered to prevent osteoporosis-related fragility fractures, which are highly prevalent in the elderly population. Given that these fractures are rare and the radiologic changes are subtle currently only 7% of AFFs are correctly identified, which hinders adequate treatment for most patients with AFF. Deep learning models could be trained to classify automatically a fracture as AFF or NFF, thereby assisting radiologists in detecting these rare fractures. Historically, for this classification task, only imaging data have been used, using convolutional neural networks (CNN) or vision transformers applied to radiographs. However, to mimic situations in which all available data are used to arrive at a diagnosis, we adopted an approach of deep learning that is based on the integration of image data and tabular data (from electronic health records) for 159 patients with AFF and 914 patients with NFF. We hypothesized that the combinatorial data, compiled from all the radiology departments of 72 hospitals in Sweden and the Swedish National Patient Register, would improve classification accuracy, as compared to using only one modality. At the patient level, the area under the ROC curve (AUC) increased from 0.966 to 0.987 when using the integrated set of imaging data and seven pre-selected variables, as compared to only using imaging data. More importantly, the sensitivity increased from 0.796 to 0.903. We found a greater impact of data fusion when only a randomly selected subset of available images was used to make the image and tabular data more balanced for each patient. The AUC then increased from 0.949 to 0.984, and the sensitivity increased from 0.727 to 0.849. These AUC improvements are not large, mainly because of the already excellent performance of the CNN (AUC of 0.966) when only images are used. However, the improvement is clinically highly relevant considering the importance of accuracy in medical diagnostics. We expect an even greater effect when imaging data from a clinical workflow, comprising a more diverse set of diagnostic images, are used.

Improved visualization of the bone-implant interface and osseointegration in ex vivo acetabular cup implants using photon-counting detector CT.

BACKGROUND: Successful osseointegration of joint replacement implants is required for long-term implant survival. Accurate assessment of osseointegration could enable clinical discrimination of failed implants from other sources of pain avoiding unnecessary surgeries. Photon-counting detector computed tomography (PCD-CT) provides improvements in image resolution compared to conventional energy-integrating detector CT (EID-CT), possibly allowing better visualization of bone-implant-interfaces and osseointegration. The aim of this study was to assess the quality of visualization of bone-implant-interfaces and osseointegration in acetabular cup implants, using PCD-CT compared with EID-CT. METHODS: Two acetabular implants (one cemented, one uncemented) retrieved during revision surgery were scanned using PCD-CT and EID-CT at equal radiation dose. Images were reconstructed using different reconstruction kernels and iterative strengths. Delineation of the bone-implant and bone-cement-interface as an indicator of osseointegration was scored subjectively for image quality by four radiologists on a Likert scale and assessed quantitatively. RESULTS: Delineation of bone-implant and bone-cement-interfaces was better with PCD-CT compared with EID-CT (p ≤ 0.030). The highest ratings were given for PCD-CT at sharper kernels for the cemented cup (PCD-CT, median 5, interquartile range 4.25-5.00 versus EID-CT, 3, 2.00-3.75, p < 0.001) and the uncemented cup (5, 4.00-5.00 versus 2, 2-2, respectively, p < 0.001). The bone-implant-interface was 35-42% sharper and the bone-cement-interface was 28-43% sharper with PCD-CT compared with EID-CT, depending on the reconstruction kernel. CONCLUSIONS: PCD-CT might enable a more accurate assessment of osseointegration of orthopedic joint replacement implants. KEY POINTS: • The bone-implant interface ex vivo showed superior visualization using photon-counting detector computed tomography (PCD-CT) compared to energy-integrating detector computed tomography. • Harder reconstruction kernels in PCD-CT provide sharper images with lower noise levels. • These improvements in imaging might make it possible to visualize osseointegration in vivo.

Autologous Bone Graft From the Ipsilateral Distal Femur in Tibial Condyle Fractures.

SUMMARY: Fractures of the proximal tibia often require void filling to support articular fragments in combination with internal fixation. The most common techniques are iliac autograft, allograft, or synthetic bone graft substitutes.The distal femur and its large volume condyles are a source of cancellous bone graft within the surgical site of an open reduction and internal fixation procedure. We have used a minimally invasive technique to harvest bone graft from the distal femur, using a bone graft drill. We performed this investigation to determine whether our technique of using distal femoral autograft to fill bone voids when treating proximal tibial fractures with open reduction and internal fixation is effective and safe. We also sought to determine the degree to which the bone graft incorporates into the tibia during fracture healing, the degree to which the harvest site heals, and the degree of secondary joint line depression.In all 12 patients, the bone graft had sufficient volume to fill the subchondral void in the proximal tibia, all fractures had healed at follow-up, and fracture reduction was maintained in most cases. We found no pain at the harvest site during follow-up, and there were no signs of drill penetration in articular or cortical structures. Drill holes at the harvest site showed sparse amounts of newly formed bone on CT in most of its circumference in all patients.There were no pathological changes in the femoral condyles with relation to the bone grafting procedure, and 5 patients showed radiographic signs of osteoarthritis in one or more joint compartments of the knee. The results showed this technique to provide similar success as reported alternatives without major complications and we continue to use this technique of harvesting distal femoral autograft to supplement open reduction and internal fixation of selected proximal tibial fractures.

The release of osteoclast-stimulating factors on supraphysiological loading by osteoprogenitors coincides with expression of genes associated with inflammation and cytoskeletal arrangement.

Supraphysiological loading induced by unstable orthopedic implants initiates osteoclast formation, which results in bone degradation. We aimed to investigate which mechanosensitive cells in the peri-implant environment produce osteoclast-stimulating factors and how the production of these factors is stimulated by supraphysiological loading. The release of osteoclast-stimulating factors by different types of isolated bone marrow-derived hematopoietic and mesenchymal stem cells from six osteoarthritic patients was analyzed after one hour of supraphysiological loading (3.0 ± 0.2 Pa, 1 Hz) by adding their conditioned medium to osteoclast precursors. Monocytes produced factors that enhanced osteoclastogenesis by 1.6 ± 0.07-fold and mesenchymal stem cells by 1.4 ± 0.07-fold. Medium from osteoprogenitors and pre-osteoblasts enhanced osteoclastogenesis by 1.3 ± 0.09-fold and 1.4 ± 0.03-fold, respectively, where medium from four patients elicited a response and two did not. Next generation sequencing analysis of osteoprogenitors revealed that genes encoding for inflammation-related pathways and cytoskeletal rearrangements were regulated differently between responders and non-responders. Our data suggest that released osteoclast-stimulating soluble factors by progenitor cells in the bone marrow after supraphysiological loading may be related to cytoskeletal arrangement in an inflammatory environment. This connection could be relevant to better understand the aseptic loosening process of orthopedic implants.

A prophylactic subcutaneous dose of the anticoagulant tinzaparin does not influence qPCR-based assessment of circulating levels of miRNA in humans.

Circulating microRNAs (miRNAs) have become increasingly popular biomarker candidates in various diseases. However, heparin-based anticoagulants might affect the detection of target miRNAs in blood samples during quantitative polymerase chain reaction (qPCR)-based analysis of miRNAs involving RNA extraction, cDNA synthesis and the polymerase catalyzed reaction. Because low-molecular-weight heparins (LMWH) are widely used in routine healthcare, we aimed to investigate whether a prophylactic dose of the LMWH tinzaparin influences qPCR-based quantification of circulating miRNAs. A total of 30 subjects were included: 16 fracture patients with tinzaparin treatment and 14 non-fracture controls without anticoagulation therapy. To control for the effect of tinzaparin on miRNA analysis an identical concentration of synthetic miRNAs was added to plasma, isolated RNA and prepared complementary DNA (cDNA) from all samples in both groups. No significant difference was observed for cDNA synthesis or qPCR when comparing tinzaparin-treated patients with untreated controls. Among the tinzaparin-treated patients, plasma levels of six endogenous miRNAs (hsa-let-7i-5p, hsa-miR-30e-5p, hsa-miR-222-3p, hsa-miR-1-3p, hsa-miR-133a-3p, hsa-miR-133b) were measured before and one to six hours after a subcutaneous injection of tinzaparin 4500IU. No significant effect was observed for any of the investigated miRNAs. A prophylactic dose of 4500IU tinzaparin does not seem to affect cDNA synthesis or qRT-PCR-based quantification of circulating miRNAs.

Early Tensile Loading in Nonsurgically Treated Achilles Tendon Ruptures Leads to a Larger Tendon Callus and a Lower Elastic Modulus: A Randomized Controlled Trial.

BACKGROUND: Early tensile loading improves material properties of healing Achilles tendon ruptures in animal models and in surgically treated human ruptures. However, the effect of such rehabilitation in patients who are nonsurgically treated remains unknown. HYPOTHESIS: In nonsurgically treated Achilles tendon ruptures, early tensile loading would lead to higher elastic modulus 19 weeks after the injury compared with controls. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: Between October 2015 and November 2018, a total of 40 nonsurgically treated patients with acute Achilles tendon rupture were randomized to an early tensile loading (loaded group) or control group. Tantalum bead markers were inserted percutaneously into the tendon stumps 2 weeks after the injury to allow high-precision measurements of callus deformation under mechanical testing. The loaded group used a training pedal twice daily to produce a gradual increase in tensile load during the following 5 weeks. Both groups were allowed full weightbearing in an ankle orthosis and unloaded range of motion exercises. Patients were followed clinically and via roentgen stereophotogrammetric analysis and computed tomography at 7, 19, and 52 weeks after the injury. RESULTS: The mean ± standard deviation elastic modulus at 19 weeks was 95.6 ± 38.2 MPa in the loaded group and 108 ± 45.2 MPa in controls (P = .37). The elastic modulus increased in both groups, although it was lower in the loaded group at all time points. Tendon cross-sectional area increased from 7 weeks to 19 weeks, from 231 ± 99.5 to 388 ± 142 mm2 in the loaded group and from 188 ± 65.4 to 335 ± 87.2 mm2 in controls (P < .001 for the effect of time). Cross-sectional area for the loaded group versus controls at 52 weeks was 302 ± 62.4 mm2 versus 252 ± 49.2 mm2, respectively (P = .03). Gap elongation was 7.35 ± 13.9 mm in the loaded group versus 2.86 ± 5.52 mm in controls (P = .27). CONCLUSION: Early tensile loading in nonsurgically treated Achilles tendon ruptures did not lead to higher elastic modulus in the healing tendon but altered the structural properties of the tendon via an increased tendon thickness. REGISTRATION: NCT0280575 (ClinicalTrials.gov identifier).

BioFACTS: biomarkers of rhabdomyolysis in the diagnosis of acute compartment syndrome - protocol for a prospective multinational, multicentre study involving patients with tibial fractures.

INTRODUCTION: The ischaemic pain of acute compartment syndrome (ACS) can be difficult to discriminate from the pain linked to an associated fracture. Lacking objective measures, the decision to perform fasciotomy is based on clinical findings and performed at a low level of suspicion. Biomarkers of muscle cell damage may help to identify and monitor patients at risk, similar to current routines for patients with acute myocardial infarction. This study will test the hypothesis that biomarkers of muscle cell damage can predict ACS in patients with tibial fractures. METHODS AND ANALYSIS: Patients aged 15-65 years who have suffered a tibial fracture will be included. Plasma (P)-myoglobin and P-creatine phosphokinase will be analysed at 6-hourly intervals after admission to the hospital (for 48 hours) and-if applicable-after surgical fixation or fasciotomy (for 24 hours). In addition, if ACS is suspected at any other point in time, blood samples will be collected at 6-hourly intervals. An independent expert panel will assess the study data and will classify those patients who had undergone fasciotomy into those with ACS and those without ACS. All primary comparisons will be performed between fracture patients with and without ACS. The area under the receiver operator characteristics curves will be used to identify the success of the biomarkers in discriminating between fracture patients who develop ACS and those who do not. Logistic regression analyses will be used to assess the discriminative abilities of the biomarkers to predict ACS corrected for prespecified covariates. ETHICS AND DISSEMINATION: The study has been approved by the Regional Ethical Review Boards in Linköping (2017/514-31) and Helsinki/Uusimaa (HUS/2500/2000). The BioFACTS study will be reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology recommendations. TRIAL REGISTRATION NUMBER: NCT04674592.

Proximal Hamstring Tendon Avulsions: A Survey of Orthopaedic Surgeons' Current Practices in the Nordic Countries.

BACKGROUND AND PURPOSE: Evidence guiding the decision on whether to treat proximal hamstring tendon avulsions (PHA) operatively or non-operatively is very limited. The aim of this study was to identify the current practices and the rationale behind PHA treatment decisions in the Nordic countries. METHODS: A survey was sent to orthopaedic surgeons in Sweden, Norway, Finland and Denmark. The study population consisted of responding surgeons with exposure to surgical treatment of PHA (n = 125). The questions covered surgeon and unit characteristics, and surgeons' understanding of the evidence for treatment, and they explored which patient and injury factors influence treatment allocation. RESULTS: Although some surgeons indicated a preference for one of the treatments, 84% stated that the treatment decision was based on patient and injury-related factors. Severe obesity, drug abuse, a sedentary lifestyle, age > 60 years and delayed diagnosis (> 6 weeks) were considered contraindications to surgical treatment. Also, there was agreement that patients expressing a preference for non-operative treatment should not be operated. Complete avulsions with tendon dislocation ≥ 2-3 cm on MRI were relative indications for surgical treatment. The majority of surgeons did not believe that operatively treated patients did better than non-operatively treated patients and experienced that patients, generally, were satisfied with the treatment result, regardless of the type of treatment. Most surgeons had experienced significant complications to operative treatment. CONCLUSION: Current practices varied among different units, and despite the lack of evidence for their prognostic value, several factors were inconsistently being used as decision modifiers when selecting patients for surgical treatment.

Surveillance of atypical femoral fractures in a nationwide fracture register.

Background and purpose - To continuously assess the incidence of atypical femoral fractures (AFFs) in the population is important, to allow the evaluation of the risks and benefits associated with osteoporosis treatment. Therefore, we investigated the possibility to use the Swedish Fracture Register (SFR) as a surveillance tool for AFFs in the population and to explore means of improvement. Patients and methods - All AFF registrations in the SFR from January 1, 2015 to December 31, 2018 were enrolled in the study. For these patients, radiographs were obtained and combined with radiographs from 176 patients with normal femoral fractures, to form the study cohort. All images were reviewed and classified into AFFs or normal femur fractures by 2 experts in the field (gold-standard classification) and 1 orthopedic resident educated on the specific radiographic features of AFF (educated-user classification). Furthermore, we estimated the incidence rate of AFFs in the population captured by the register through comparison with a previous cohort and calculated the positive predictive value (PPV) and, where possible, the inter-observer agreement (Cohen's kappa) between the different classifications. Results - Of the 178 available patients with AFF in the SFR, 104 patients were classified as AFF using the goldstandard classification, and 89 using the educated-user classification. The PPV increased from 0.58 in the SFR classification to 0.93 in the educated-user classification. The interobserver agreement between the gold-standard classification and the educated-user classification was 0.81. Interpretation - With a positive predictive value of 0.58 the Swedish Fracture Register outperforms radiology reports and reports to the Swedish Medical Products Agency on adverse drug reactions as a diagnostic tool to identify atypical femoral fractures.

Antiresorptive treatment and talar collapse after displaced fractures of the talar neck: a long-term follow-up of 19 patients.

Background and purpose - Displaced fractures of the talar neck are associated with a high risk of structural collapse. In this observational analysis we hypothesized that pharmacological inhibition of osteoclast function might reduce the risk of structural collapse through a reduction in bone resorption during revascularization of the injured bone.Patients and methods - Between 2002 and 2014 we treated 19 patients with displaced fractures of the talar neck with open reduction and internal fixation. Of these, 16 patients were available for final follow-up between January and November 2017 (median 12 years, IQR 7-13). Among these, 6 patients with Hawkins type 3 fractures and 2 patients with Hawkins type 2b fractures received postoperative antiresorptive treatment (7 alendronate, 1 denosumab) for 6 to 12 months. The remaining 8 patients received no antiresorptive treatment. The self-reported foot and ankle score (SEFAS) was available in all patients and 15 patients had undergone computed tomography (CT) at final follow-up, which allowed evaluation of structural collapse of the talar dome and signs of post-traumatic osteoarthritis.Results - The risk for partial collapse of the talar dome was equal in the 2 groups (3 in each group) and post-traumatic arthritis was observed in all patients. The SEFAS in patients with antiresorptive treatment was lower, at 21 points (95% CI 15-26), compared with those without treatment, 29 points (CI 22-35).Interpretation - Following a displaced fracture of the talar neck, we found no effect of antiresorptive therapy on the rate of talar collapse, post-traumatic osteoarthritis, and patient-reported outcomes.

Deep neural networks with promising diagnostic accuracy for the classification of atypical femoral fractures.

Background and purpose - A correct diagnosis is essential for the appropriate treatment of patients with atypical femoral fractures (AFFs). The diagnostic accuracy of radiographs with standard radiology reports is very poor. We derived a diagnostic algorithm that uses deep neural networks to enable clinicians to discriminate AFFs from normal femur fractures (NFFs) on conventional radiographs.Patients and methods - We entered 433 radiographs from 149 patients with complete AFF and 549 radiographs from 224 patients with NFF into a convolutional neural network (CNN) that acts as a core classifier in an automated pathway and a manual intervention pathway (manual improvement of image orientation). We tested several deep neural network structures (i.e., VGG19, InceptionV3, and ResNet) to identify the network with the highest diagnostic accuracy for distinguishing AFF from NFF. We applied a transfer learning technique and used 5-fold cross-validation and class activation mapping to evaluate the diagnostic accuracy.Results - In the automated pathway, ResNet50 had the highest diagnostic accuracy, with a mean of 91% (SD 1.3), as compared with 83% (SD 1.6) for VGG19, and 89% (SD 2.5) for InceptionV3. The corresponding accuracy levels for the intervention pathway were 94% (SD 2.0), 92% (2.7), and 93% (3.7), respectively. With regards to sensitivity and specificity, ResNet outperformed the other networks with a mean AUC (area under the curve) value of 0.94 (SD 0.01) and surpassed the accuracy of clinical diagnostics.Interpretation - Artificial intelligence systems show excellent diagnostic accuracies for the rare fracture type of AFF in an experimental setting.

Exchange of Modular Components Improves Success of Debridement, Antibiotics, and Implant Retention: An Observational Study of 575 Patients with Infection After Primary Total Hip Arthroplasty.

Debridement, antibiotics, and implant retention (DAIR) is a surgical treatment for periprosthetic joint infection (PJI). DAIR is a desirable treatment option from an economic and patient perspective, if successful. The aim of this observational study was to compare the rates of success, defined as no additional reoperations due to PJI, between DAIR with exchange of modular components and DAIR without exchange in patients who had first-time PJI after primary total hip arthroplasty (THA). METHODS: Patients with PJI at the site of a primary THA who were treated with DAIR in Sweden between January 1, 2009, and December 31, 2016, were identified in the Swedish Hip Arthroplasty Register. Supplementary questionnaires were sent to orthopaedic departments for additional variables of interest related to PJI. The primary end point was another reoperation due to PJI within 2 years after the first-time DAIR. DAIR with exchange was compared with DAIR without exchange using Kaplan-Meier survival analysis and Cox regression analysis. RESULTS: A total of 575 patients treated with DAIR for a first-time PJI at the site of a primary THA were analyzed; 364 underwent component exchange and 211 did not. The exchange of components was associated with a lower rate of reoperations due to PJI after DAIR (28.0%) compared with non-exchange (44.1%). The Kaplan-Meier implant survival estimate for exchange was 71.4% (95% confidence interval [CI] = 66.9% to 76.3%) compared with 55.5% (95% CI = 49.1% to 62.7%) for non-exchange. With the analysis adjusted for confounders, DAIR with exchange was associated with a significantly decreased risk of another reoperation due to PJI compared with non-exchange (hazard ratio [HR] = 0.51 [95% CI = 0.38 to 0.68]). CONCLUSIONS: In patients with a first-time PJI at the site of a primary THA, DAIR with exchange of modular components was superior to non-exchange DAIR. Surgeons should strive to exchange components when they perform DAIR, but there is a need to further identify how DAIR best should be practiced and which patients benefit from it. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Single postoperative infusion of zoledronic acid to improve patient-reported outcome after hip or knee replacement: study protocol for a randomised, controlled, double-blinded clinical trial.

INTRODUCTION: In Sweden, roughly 3000 patients are reoperated each year due to pain and loss of function related to a loosened hip or knee prosthesis. These reoperations are strenuous for the patient, technically demanding and costly for the healthcare system. Any such reoperation that can be prevented would be of great benefit. Bisphosphonates are drugs that inhibit osteoclast function. Several clinical trials suggest that bisphosphonates lead to improved implant fixation and one small study even indicates better functional outcome. Furthermore, in epidemiological studies, bisphosphonates have been shown to decrease the rate of revision for aseptic loosening by half. Thus, there are several indirect indications that bisphosphonates could improve patient-reported outcome, but no firm evidence. METHODS AND ANALYSIS: This is a pragmatic randomised, placebo-controlled, double-blinded, academic clinical trial of a single postoperative dose of zoledronic acid, in patients younger than 80 years undergoing primary total hip or knee replacement for osteoarthritis. Participants will be recruited from two orthopaedic departments. All surgeries will be performed, and study drugs given at Motala Hospital, Sweden. The primary endpoint is to investigate between-group differences in the Hip dysfunction and Osteoarthritis Outcome Score and the Knee injury and Osteoarthritis Outcome Score at 3-year follow-up. Secondary outcomes will be investigated at 1 year, 3 years and 6 years, and stratified for hip and knee implants. These secondary endpoints are supportive, exploratory or explanatory. A total of 1000 patients will be included in the study. ETHICS AND DISSEMINATION: The study has been approved by the Regional Ethical Review Board in Linköping (DNR 2015/286-31). The study will be reported in accordance with the Consolidated Standards of Reporting Trials statement for pharmacological trials. The results will be submitted for publication in peer-reviewed academic journals and disseminated to patient organisations and the media. TRIAL REGISTRATION NUMBER: EudraCT: No 2015-001200-55; Pre-results.

Reduced Risk of Reoperation Using Intramedullary Nailing with Femoral Neck Protection in Low-Energy Femoral Shaft Fractures.

BACKGROUND: In Sweden, approximately 1 in 4 women who are ≥50 years of age will sustain a hip fracture. Patients treated for a femoral shaft fracture are likely to have an even higher risk. We hypothesized that intramedullary nails protecting the femoral neck reduce the risk of subsequent hip fracture and allow the patient to avoid a challenging reoperation. METHODS: Between 2008 and 2010, 5,475 fractures of the femoral shaft, in patients who were ≥55 years of age, were registered in a national registry in Sweden. Of these patients, 897 fulfilled the inclusion criteria. We used radiographs and register data to identify the reasons for and the types of reoperation that occurred between the index surgical procedure and December 31, 2014. The categories of implants were determined through a review of radiographs as intramedullary nails with and without femoral neck protection. Reoperations related to peri-implant fractures (including hip fractures) were analyzed as a subgroup of all major reoperations. Multivariable-adjusted, cause-specific hazard ratios (HRs) were calculated to compare the risk of reoperation between cases with nails with and without femoral neck protection. RESULTS: Among the 897 patients, a total of 82 reoperations were performed. In 640 patients who were treated with intramedullary nails with femoral neck protection, there were 7 peri-implant fractures (no hip fractures) and 27 major reoperations. Among the 257 patients who were treated with intramedullary nails without femoral neck protection, 14 peri-implant hip fractures and 24 major reoperations were identified. Patients who received nails with femoral neck protection had a lower hazard for any peri-implant fracture (multivariable-adjusted cause-specific HR, 0.19 [95% confidence interval (CI), 0.07 to 0.5]) and major reoperation (multivariable-adjusted cause-specific HR, 0.51 [95% CI, 0.28 to 0.92]). CONCLUSIONS: Intramedullary nails with femoral neck protection in the treatment of low-energy femoral shaft fractures prevent secondary hip fractures and decrease the overall risk of reoperation for 4 to 6 years postoperatively. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Good implant survival after acetabular revision with extensive impaction bone grafting and uncemented components.

AIMS: This single-centre observational study aimed to describe the results of extensive bone impaction grafting of the whole acetabular cavity in combination with an uncemented component in acetabular revisions performed in a standardized manner since 1993. METHODS: Between 1993 and 2013, 370 patients with a median age of 72 years (interquartile range (IQR) 63 to 79 years) underwent acetabular revision surgery. Of these, 229 were more than ten years following surgery and 137 were more than 15 years. All revisions were performed with extensive use of morcellized allograft firmly impacted into the entire acetabular cavity, followed by insertion of an uncemented component with supplementary screw fixation. All types of reoperation were captured using review of radiographs and medical charts, combined with data from the local surgical register and the Swedish Hip Arthroplasty Register. RESULTS: Among patients with possible follow-up of ten and 15 years, 152 and 72 patients remained alive without revision of the acetabular component. The number of deaths was 61 and 50, respectively. Of those who died, six patients in each group had a reoperation performed before death. The number of patients with a reoperation was 22 for those with ten-year follow-up and 21 for those with 15 years of follow-up. The Kaplan-Meier implant survival rate for aseptic loosening among all 370 patients in the cohort was 96.3% (95% confidence interval (CI) 94.1 to 98.5) after ten years and 92.8% (95% CI 89.2 to 96.6) after 15 years. CONCLUSION: Extensive bone impaction grafting combined with uncemented revision components appears to be a reliable method with favourable long-term survival. This technique offers the advantage of bone stock restoration and disputes the long-standing perception that uncemented components require > 50% of host bone contact for successful implant survival. Cite this article: Bone Joint J 2020;102-B(2):198-204.

Mechanical instability induces osteoclast differentiation independent of the presence of a fibrous tissue interface and osteocyte apoptosis in a rat model for aseptic loosening.

Background and purpose - Insufficient initial fixation or early micromotion of an implant is associated with a thin layer of fibrous tissue at the peri-implant interface. It is unknown if bone loss is induced by the fibrous tissue interface acting as an active biological membrane, or as a membrane that will produce supraphysiologic fluid flow conditions during gait, which activates the mechanosensitive osteocytes to mediate osteoclast differentiation. We investigated whether mechanically induced osteolysis is dependent on the fibrous tissue interface as a biologically active scaffold, or if it merely acts as a conduit for fluid flow, affecting the mechanosensitive osteocytes in the peri-prosthetic bone.Methods - Using a rat model of mechanically instability-induced aseptic loosening, we assessed whether the induction of osteoclast differentiation was dependent on the presence of a peri-implant fibrous interface. We analyzed the amount of osteoclast differentiation, osteocyte apoptosis, pro-resorptive cytokine expression and bone loss using immunohistochemistry, mRNA expression and micro-CT.Results - Osteoclast differentiation and bone loss were induced by mechanical instability but were not affected by the presence of the fibrous tissue membrane or associated with osteocyte apoptosis. There was no increased mRNA expression of any of the cytokines in the fibrous tissue membrane compared with the peri-implant bone.Interpretation - Our data show that the fibrous tissue membrane in the interface plays a minor role in inducing bone loss. This indicates that the peri-implant bone adjacent to loose bone implants might play an important role for osteoclast differentiation.

[Bisphosphonate-associated atypical fractures of the femur: an update of the current evidence]. / Atypisk femurfraktur en allvarlig komplikation till bisfosfonater - En uppdatering av evidensläget.

Atypical fracture of the femur is a well-documented adverse reaction to antiresorptive treatment with bisphosphonates. Although there has been significant gain of knowledge during the past decade, the pathogenesis of this type of fracture is still poorly understood. We present an update on the evidence in regard to epidemiology, pathophysiology, and management of atypical fractures.

The proximal hamstring avulsion clinical trial (PHACT)-a randomised controlled non-inferiority trial of operative versus non-operative treatment of proximal hamstrings avulsions: study protocol.

INTRODUCTION: The treatment of proximal hamstring avulsions is controversial. While several trials have investigated the outcome for patients treated surgically, there is today no prospective trial comparing operative treatment with non-operative treatment. This protocol describes the design for the proximal hamstring avulsion clinical trial (PHACT)-the first randomised controlled trial of operative versus non-operative treatment for proximal hamstring avulsions. METHODS AND ANALYSIS: PHACT is a multicentre randomised controlled trial conducted across Sweden, Norway and Finland. Eligible patients (60 participants/treatment arm) with a proximal hamstring avulsion of at least two of three tendons will be randomised to either operative or non-operative treatment. Participants allocated to surgery will undergo reinsertion of the tendons with suture anchors. The rehabilitation programme will be the same for both treatment groups. When patient or surgeon equipoise for treatment alternatives cannot be reached and randomisation therefore is not possible, patients will be invited to participate in a parallel observational non-randomised cohort. The primary outcome will be the patient-reported outcome measure Perth hamstring assessment tool at 24 months. Secondary outcomes include the Lower Extremity Functional Score, physical performance and muscle strength tests, patient satisfaction and MR imaging. Data analysis will be blinded and intention-to-treat analysis will be preformed. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Ethical Committee of Uppsala University (DNR: 2017-170) and by the Norwegian ethical board (REC: 2017/1911). The study will be conducted in agreement with the Helsinki declaration. The findings will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT03311997.

Chronic anterior tibial stress fractures in athletes: No crack but intense remodeling.

PURPOSE: Delayed healing of anterior tibial stress fractures in athletes is related to high tensional forces acting across a putative fracture gap. These forces lead to crack propagation and create strains that exceed tissue differentiation thresholds for new bone to form in the gap. The "dreaded black line" is a radiographic hallmark sign of stress fractures considered to represent a transverse fracture gap. However, whether a fracture gap truly exists at the microscopic level remains unclear. The aim of this study was to describe the area of the "dreaded black line" microscopically and to identify signs of delayed healing. METHODS: Between 2011 and 2016, we included seven athletes with chronic anterior mid-shaft tibial stress fractures. The fracture site was excised as a cylindrical biopsy. The biopsy was evaluated with micro-CT and histology. The formation of new bone in the defect was evaluated radiographically. RESULTS: The "dreaded black line" seen on pre-operative radiographs in all patients could not be seen on the microscopic level. Instead, the area of the putative crack showed widened resorption cavities, lined with active osteoblasts, and surrounded by immature bone. This area of intense remodeling seemed to create a false impression of a fracture line on radiographs. Complete cortical continuity was restored at the biopsy site at median 8 months (range 6-13 months). CONCLUSION: Tibial stress fractures in athletes normally show no fracture defect, but a region of increased remodeling. The healing process is already ongoing but seems mechanically insufficient.

A Genome-Wide Association Study of Bisphosphonate-Associated Atypical Femoral Fracture.

Atypical femoral fracture is a well-documented adverse reaction to bisphosphonates. It is strongly related to duration of bisphosphonate use, and the risk declines rapidly after drug withdrawal. The mechanism behind bisphosphonate-associated atypical femoral fracture is unclear, but a genetic predisposition has been suggested. With the aim to identify common genetic variants that could be used for preemptive genetic testing, we performed a genome-wide association study. Cases were recruited mainly through reports of adverse drug reactions sent to the Swedish Medical Products Agency on a nation-wide basis. We compared atypical femoral fracture cases (n = 51) with population-based controls (n = 4891), and to reduce the possibility of confounding by indication, we also compared with bisphosphonate-treated controls without a current diagnosis of cancer (n = 324). The total number of single-nucleotide polymorphisms after imputation was 7,585,874. A genome-wide significance threshold of p < 5 × 10-8 was used to correct for multiple testing. In addition, we performed candidate gene analyses for a panel of 29 genes previously implicated in atypical femoral fractures (significance threshold of p < 5.7 × 10-6). Compared with population controls, bisphosphonate-associated atypical femoral fracture was associated with four isolated, uncommon single-nucleotide polymorphisms. When cases were compared with bisphosphonate-treated controls, no statistically significant genome-wide association remained. We conclude that the detected associations were either false positives or related to the underlying disease, i.e., treatment indication. Furthermore, there was no significant association with single-nucleotide polymorphisms in the 29 candidate genes. In conclusion, this study found no evidence of a common genetic predisposition for bisphosphonate-associated atypical femoral fracture. Further studies of larger sample size to identify possible weakly associated genetic traits, as well as whole exome or whole-genome sequencing studies to identify possible rare genetic variation conferring a risk are warranted.