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  • 1.
    Schilcher, Jörg
    et al.
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Nilsson, Alva
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten.
    Andlid, Oliver
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten.
    Eklund, Anders
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för datavetenskap, Statistik och maskininlärning.
    Fusion of electronic health records and radiographic images for a multimodal deep learning prediction model of atypical femur fractures2024Ingår i: Computers in Biology and Medicine, ISSN 0010-4825, E-ISSN 1879-0534, Vol. 168, artikel-id 107704Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

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  • 2.
    Rönnerfalk, Mattias
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Velin, Lotta
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Palm, Lars
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Meunier, Andreas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Autologous Bone Graft From the Ipsilateral Distal Femur in Tibial Condyle Fractures2023Ingår i: Journal of Orthopaedic Trauma, ISSN 0890-5339, E-ISSN 1531-2291, Vol. 37, nr 9, s. E377-E381Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 3.
    Woisetschläger, Mischa
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Booij, Ronald
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Erasmus MC, Netherlands.
    Tesselaar, Erik
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Region Östergötland, Diagnostikcentrum, Medicinsk strålningsfysik.
    Oei, Edwin H. G.
    Erasmus MC, Netherlands.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Improved visualization of the bone-implant interface and osseointegration in ex vivo acetabular cup implants using photon-counting detector CT2023Ingår i: EUROPEAN RADIOLOGY EXPERIMENTAL, ISSN 2509-9280, Vol. 7, nr 1, artikel-id 19Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BackgroundSuccessful 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.MethodsTwo 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.ResultsDelineation 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.ConclusionsPCD-CT might enable a more accurate assessment of osseointegration of orthopedic joint replacement implants.

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  • 4.
    Nilsson, Abraham
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, ANOPIVA US.
    Nerhall, Anna Maria
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Dept Orthoped Eksjo, Reg Jonkoping Cty, Sweden.
    Vechetti, Ivan
    Univ Nebraska, NE USA.
    Fornander, Lotta
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Norrköping.
    Wiklund, Simon
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Dept Orthoped Eksjo, Reg Jonkoping Cty, Sweden.
    Alkner, Björn
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Dept Orthoped Eksjo, Reg Jonkoping Cty, Sweden.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    von Walden, Ferdinand
    Karolinska Inst, Sweden.
    A prophylactic subcutaneous dose of the anticoagulant tinzaparin does not influence qPCR-based assessment of circulating levels of miRNA in humans2022Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 17, nr 11, artikel-id e0277008Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

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  • 5.
    Nilsson, Abraham
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Ibounig, Thomas
    Univ Helsinki, Finland.
    Lyth, Johan
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för samhälle och hälsa. Linköpings universitet, Medicinska fakulteten.
    Alkner, Björn
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Department of Orthopaedics, Eksjö, Region Jönköping County, Jönköping, Sweden.
    von Walden, Ferdinand
    Karolinska Inst, Sweden.
    Fornander, Lotta
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Norrköping.
    Rämö, Lasse
    Univ Helsinki, Finland.
    Schmidt, Andrew
    Hennepin Healthcare, MN USA.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    BioFACTS: biomarkers of rhabdomyolysis in the diagnosis of acute compartment syndrome - protocol for a prospective multinational, multicentre study involving patients with tibial fractures2022Ingår i: BMJ Open, E-ISSN 2044-6055, Vol. 12, nr 5, artikel-id e059918Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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 perforated 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 Linkoping (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.

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  • 6.
    Rendek, Zlatica
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Bon Beckman, Leo
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten.
    Schepull, Thorsten
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    Dånmark, Ida
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Aspenberg, Per
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Eliasson, Pernilla
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Early Tensile Loading in Nonsurgically Treated Achilles Tendon Ruptures Leads to a Larger Tendon Callus and a Lower Elastic Modulus: A Randomized Controlled Trial2022Ingår i: American Journal of Sports Medicine, ISSN 0363-5465, E-ISSN 1552-3365, Vol. 50, nr 12, s. 3286-3298Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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 mm(2) in the loaded group and from 188 +/- 65.4 to 335 +/- 87.2 mm(2) 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 mm(2) versus 252 +/- 49.2 mm(2), 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).

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  • 7.
    Zheng, Nianye
    et al.
    Musculoskeletal Research Laboratory of the Department of Orthopedics and Traumatology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; Innovative Orthopedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China; Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO, USA.
    Xu, Jiankun
    Musculoskeletal Research Laboratory of the Department of Orthopedics and Traumatology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; Innovative Orthopedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China.
    Ruan, Ye Chun
    Department of Biomedical Engineering, Faculty of Engineering, Hong Kong Polytechnic University, Hong Kong, China.
    Chang, Liang
    Musculoskeletal Research Laboratory of the Department of Orthopedics and Traumatology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; Innovative Orthopedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China.
    Wang, Xinluan
    Translational Medicine R&D Center, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, PR China.
    Yao, Hao
    Musculoskeletal Research Laboratory of the Department of Orthopedics and Traumatology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; Innovative Orthopedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China.
    Wang, Jiali
    School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, PR China.
    Zhang, Ri
    Musculoskeletal Research Laboratory of the Department of Orthopedics and Traumatology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; Innovative Orthopedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China.
    Xue, Qingyun
    Department of Orthopedic Surgery, Beijing Hospital, Beijing, PR China.
    Tang, Ning
    Musculoskeletal Research Laboratory of the Department of Orthopedics and Traumatology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China.
    Ong, Tim-yun
    Musculoskeletal Research Laboratory of the Department of Orthopedics and Traumatology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    O'Keefe, Regis J.
    Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO, USA.
    Qin, Ling
    Musculoskeletal Research Laboratory of the Department of Orthopedics and Traumatology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; Innovative Orthopedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China; Translational Medicine R&D Center, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, PR China.
    Magnesium facilitates the healing of atypical femoral fractures: A single-cell transcriptomic study2022Ingår i: Materials Today, ISSN 1369-7021, E-ISSN 1873-4103, Vol. 52, s. 43-62Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Bisphosphonates (BPs)-associated atypical femoral fractures (AFFs) present with impaired fracture healing, yet the underlying mechanism is unclear, which prevents the development of effective therapy. Peripheral sensory nerve has been shown to regulate fracture healing via releasing neuropeptides. Here we show that long-term BPs pre-treatment leads to fracture non-union in rats, characterized by reduced expression of calcitonin gene-related peptide (CGRP, a predominant type of neuropeptides) and abundant fibrous tissues in the non-bridged fracture gap, mimicking clinical AFFs. By using single-cell RNA-sequencing, long-term BPs treatment was identified to promote transition of progenitor cells into a specific cluster of fibroblasts that actively deposit dense extracellular matrix (ECM) to prevent fracture callus bridging. Administration of exogenous CGRP at early stages of fracture repair, in contrast, eliminates the ECM-secreting fibroblast cluster, attenuates fibrogenesis, and facilitates callus bridging, suggesting CGRP is a promising agent to facilitate AFF healing. Accordingly, we have developed an innovative magnesium (Mg) containing hybrid intramedullary nail fixation system (Mg-IMN) to effectively rescue BPs-impaired fracture healing via elevating CGRP synthesis and release. Such device optimizes the fracture healing in BPs-pretreated rats, comparable to direct administration of CGRP. These findings address the indispensable role of CGRP in advancing the healing of AFFs and develop translational strategies to accelerate AFF healing by taking advantage of the CGRP-stimulating effect of Mg-based biodegradable orthopedic implant. The study also indicates fibrosis could be targeted by augmenting CGRP expression to accelerate fracture healing even under challenging scenarios where fibroblasts are aberrantly activated.

  • 8.
    Laszlo, Sofia
    et al.
    Uppsala Univ, Sweden.
    Nilsson, Martin
    Ostersund Hosp, Sweden.
    Pihl, Elsa
    Danderyd Hosp, Sweden.
    Mattila, Ville M.
    Tampere Univ, Finland; Univ Hosp, Finland.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Sköldenberg, Olof
    Danderyd Hosp, Sweden.
    Frihagen, Frede
    Ostfold Hosp Trust, Norway; Univ Oslo, Norway.
    Jonsson, Kenneth B.
    Uppsala Univ, Sweden.
    Proximal Hamstring Tendon Avulsions: A Survey of Orthopaedic Surgeons Current Practices in the Nordic Countries2022Ingår i: Sports Medicine - Open, ISSN 2199-1170, Vol. 8, nr 1, artikel-id 49Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

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  • 9.
    Bögl, Hans Peter
    et al.
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Department of Orthopedic Surgery, Gävle Hospital, Gävle.
    Zdolsek, Georg
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Barnisin, Lukas
    Department of Orthopedics, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Möller, Michael
    Department of Orthopedics, Sahlgrenska University Hospital, Gothenburg; Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Surveillance of atypical femoral fractures in a nationwide fracture register2022Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 93, s. 229-233Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

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  • 10.
    Bratengeier, Cornelia
    et al.
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi.
    Bakker, Astrid D.
    Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, The Netherlands.
    Liszka, Aneta
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi.
    Schilcher, Jörg
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    Fahlgren, Anna
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi.
    The release of osteoclast-stimulating factors on supraphysiological loading by osteoprogenitors coincides with expression of genes associated with inflammation and cytoskeletal arrangement2022Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 12, nr 1, artikel-id 21578Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

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  • 11.
    Meunier, Andreas
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Palm, Lars
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Aspenberg, Per
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Antiresorptive treatment and talar collapse after displaced fractures of the talar neck: a long-term follow-up of 19 patients2021Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 92, nr 4, s. 455-460Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

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  • 12.
    Zdolsek, Georg
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Chen, Yupei
    Department of Biomedical Engineering and Health Systems, Royal Institute of Technology, Sweden.
    Bögl, Hans Peter
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Department of Orthopedic Surgery, Gävle Hospital, Sweden.
    Wang, Chunliang
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Woisetschläger, Mischa
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Deep neural networks with promising diagnostic accuracy for the classification of atypical femoral fractures2021Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 92, nr 4, s. 394-400Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

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  • 13.
    Svensson, Karin
    et al.
    Department of Orthopedics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; The Swedish Hip Arthroplasty Register, Gothenburg, Sweden.
    Rolfson, Ola
    Department of Orthopedics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; The Swedish Hip Arthroplasty Register, Gothenburg, Sweden.
    Nauclér, Emma
    The Swedish Hip Arthroplasty Register, Gothenburg, Sweden.
    Lazarinis, Stergios
    Department of Orthopedics, Institute of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Sköldenberg, Olof
    Division of Orthopedics, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Johanson, Per-Erik
    Department of Orthopedics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; The Swedish Hip Arthroplasty Register, Gothenburg, Sweden.
    Mohaddes, Maziar
    Department of Orthopedics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; The Swedish Hip Arthroplasty Register, Gothenburg, Sweden.
    Kärrholm, Johan
    Department of Orthopedics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; The Swedish Hip Arthroplasty Register, Gothenburg, Sweden.
    Exchange of Modular Components Improves Success of Debridement, Antibiotics, and Implant Retention: An Observational Study of 575 Patients with Infection After Primary Total Hip Arthroplasty2020Ingår i: JB & JS open access, ISSN 2472-7245, Vol. 5, nr 4, artikel-id e20.00110Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: 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.

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  • 14.
    Perlbach, Rico
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Palm, Lars
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Mohaddes, Maziar
    Sahlgrens Acad, Sweden; Registerctr VGR, Sweden.
    Ivarsson, Ingemar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Good implant survival after acetabular revision with extensive impaction bone grafting and uncemented components2020Ingår i: The Bone & Joint Journal, ISSN 2049-4394, E-ISSN 2049-4408, Vol. 102B, nr 2, s. 198-204Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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 amp;gt; 50% of host bone contact for successful implant survival.

  • 15.
    Bögl, Hans Peter
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping. Gavle Cent Hosp, Sweden.
    Michaelsson, K.
    Uppsala Univ, Sweden.
    Zdolsek, Georg
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Hoijer, J.
    Uppsala Univ, Sweden.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Increased rate of reoperation in atypical femoral fractures is related to patient characteristics and not fracture type. A nationwide cohort study2020Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 31, nr 5, s. 951-959Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Atypical femoral fractures are burdened with a high rate of reoperation. In our nationwide analysis, the increased rate of reoperation was related to patient background characteristics, such as age and health status, rather than fracture type. Introduction Patients with atypical fractures are complex to treat and burdened with a high risk of reoperation. We hypothesized that patients with surgically treated, complete atypical fractures have a higher risk of any reoperation and reoperation related to healing complications than patients with common femoral shaft fractures but that this increase would become insignificant when adjusted for predefined characteristics. Methods A cohort of 163 patients with atypical fractures and 862 patients with common femoral shaft or subtrochanteric fractures treated from 2008 to 2010 and who had follow-up radiographs and register data available until 31 December 2014 was included. Reoperations were identified by a complementary review of radiographs and register data and were used to calculate risks for any reoperation and reoperations related to healing complications. Results Patients with atypical fractures were more likely to be reoperated for any reason, age-adjusted OR 1.76 (95% CI, 1.08 to 2.86). However, patients with common fractures had a shorter follow-up due to a threefold higher death rate. Accordingly, in a multivariable-adjusted time-to-event model, the increased risk lost statistical significance for any reoperations, cause-specific HR 1.34 (95% CI, 0.85 to 2.13), and for reoperations related to healing complications, HR 1.32 (95% CI, 0.58 to 3.0). Continued use of bisphosphonate in the first year after the fracture did not affect the reoperation rate. Conclusions Our findings suggest that the increased risk of reoperation after an atypical femur fracture is largely explained by patient characteristics and not fracture type.

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  • 16.
    Vinther Madsen, Rune
    et al.
    Hosp Special Surg, NY 10021 USA; Zealand Univ Hosp, Denmark.
    Nam, Denis
    Rush Univ, IL USA.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Dvorzhinskiy, Aleksey
    Hosp Special Surg, NY 10021 USA.
    Sutherland, James P.
    Hosp Special Surg, NY 10021 USA.
    Bostrom, F. Mathias
    Hosp Special Surg, NY 10021 USA.
    Fahlgren, Anna
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Hosp Special Surg, NY 10021 USA.
    Mechanical instability induces osteoclast differentiation independent of the presence of a fibrous tissue interface and osteocyte apoptosis in a rat model for aseptic loosening2020Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 91, nr 1, s. 115-120Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

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  • 17.
    Bögl, Hans Peter
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping. Gavle Cent Hosp, Sweden.
    Zdolsek, Georg
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Michaelsson, Karl
    Uppsala Univ, Sweden.
    Hoijer, Jonas
    Uppsala Univ, Sweden.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Reduced Risk of Reoperation Using Intramedullary Nailing with Femoral Neck Protection in Low-Energy Femoral Shaft Fractures2020Ingår i: Journal of Bone and Joint Surgery. American volume, ISSN 0021-9355, E-ISSN 1535-1386, Vol. 102, nr 17, s. 1486-1494Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

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  • 18.
    Brandt, Jonathan
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Capio Specialistvard Motala, Sweden.
    Ledin, Hakan
    Capio Specialistvard Motala, Sweden.
    Ranstam, Jonas
    Lund Univ, Sweden.
    Roos, Ewa
    Univ So Denmark, Denmark.
    Aspenberg, Per
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    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 trial2020Ingår i: BMJ Open, E-ISSN 2044-6055, Vol. 10, nr 9, artikel-id e040985Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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 Linkoping (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.

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  • 19.
    Wolf, Olof
    et al.
    Uppsala Univ, Sweden.
    Mukka, Sebastian
    Umea Univ, Sweden.
    Notini, Maja
    Uppsala Univ, Sweden.
    Moller, Michael
    Univ Gothenburg, Sweden.
    Hailer, Nils P.
    Uppsala Univ, Sweden.
    Mannberg, Maria
    Uppsala Univ, Sweden.
    Skoldenberg, Olof
    Karolinska Inst, Sweden.
    Kadum, Kamal
    Univ Gothenburg, Sweden.
    Mohaddes, Maziar
    Univ Gothenburg, Sweden.
    Rolfson, Ola
    Univ Gothenburg, Sweden.
    Jessen, Nicole
    Sunderby Hosp, Sweden.
    Stam, Daniel
    Hallands Hosp, Sweden.
    Aghaee, Mohammadamin
    Lidkoping Hosp, Sweden.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Nemlander, Elin
    Ljungby Hosp, Sweden.
    Study protocol: The DUALITY trial-a register-based, randomized controlled trial to investigate dual mobility cups in hip fracture patients2020Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 91, nr 5, s. 506-513Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and purpose - Physically and mentally fit patients with a displaced femoral neck fracture (FNF) are mostly treated with total hip arthroplasty (THA). Dislocation is a severe and frequent complication in this group, and dual mobility cups (DMC) were developed to reduce the risk of dislocation after THA. The DUALITY trial investigates whether the use of DMC in FNF patients treated with a THA reduces the risk of dislocation. Patients and methods - The trial is a national, multicenter, register-based, randomized controlled trial (rRCT). Patients >= 65 years with a non-pathological, displaced FNF (Type Garden 3-4/AO 31-B2 or B3) who are suitable for a THA according to local guidelines are assessed for eligibility using the web-based registration platform of the Swedish Fracture Register (SFR). 1,600 patients will be randomized 1:1 to either insertion of a DMC (intervention group) or a standard cup (control group). The study is pragmatic in that the choice of implant brands, surgical approach, and peri- and postoperative protocols follow the local routines of each participating unit. All outcome variables will be retrieved after linkage of the study cohort obtained from the SFR with the Swedish Hip Arthroplasty Register and the National Patient Register. Outcomes - The primary outcome is the occurrence of any dislocation of the index joint treated with closed or open reduction within 1 year after surgery, expressed as a relative risk when comparing groups, and a risk reduction of at least 45% is considered clinically relevant. Secondary outcomes are the relative risk of any reoperation of the index joint, periprosthetic joint infection, and mortality within 90 days and 1 year. Patient-reported outcomes and health economics are evaluated. Start of trial and estimated duration - The DUALITY trial started recruiting patients in January 2020 and will continue for approximately 5 years. Trial registration - The trial is registered at clinicaltrials.gov (NCT03909815; December 12, 2019).

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  • 20.
    Kharazmi, Mohammad
    et al.
    Uppsala Univ, Sweden.
    Michaelsson, Karl
    Uppsala Univ, Sweden.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Eriksson, Niclas
    Uppsala Univ, Sweden.
    Melhus, Hakan
    Uppsala Univ, Sweden.
    Wadelius, Mia
    Uppsala Univ, Sweden.
    Hallberg, Par
    Uppsala Univ, Sweden.
    A Genome-Wide Association Study of Bisphosphonate-Associated Atypical Femoral Fracture2019Ingår i: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 105, nr 1, s. 51-67Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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 pamp;lt;5x10(-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 pamp;lt;5.7x10(-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.

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  • 21.
    Kharazmi, Mohammad
    et al.
    Uppsala Universitet Institutionen for kirurgiska vetenskaper - Ortopedi Uppsala, Sweden Uppsala Universitet Institutionen for kirurgiska vetenskaper - Ortopedi Uppsala, Sweden.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Hallberg, Pär
    Uppsala Universitet - Uppsala, Sweden Uppsala Universitet - Uppsala, Sweden.
    Michaëlsson, Karl
    institutionen för kirurgiska vetenskaper, ortopedi, Uppsala universitet, Sweden.
    Atypisk femurfraktur en allvarlig komplikation till bisfosfonater [Bisphosphonate-associated atypical fractures of the femur: an update of the current evidence]2019Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 116Artikel, forskningsöversikt (Refereegranskat)
    Abstract [sv]

    Atypisk femurfraktur är en insufficiensfraktur starkt kopplad till bisfosfonatanvändning.Frakturen uppstår utan eller efter minimalt trauma, ofta efter en period av ljumsk- eller lårsmärta.Risken för atypisk femurfraktur kan reduceras genom att begränsa behandlingstiden med bisfosfonater.Vid inkomplett fraktur bör bisfosfonatbehandling sättas ut, och vid samtidig lårsmärta bör lårbenet märgspikas förebyggande, annars föreligger stor risk för att frakturen blir genomgående.Postoperativ frakturläkning kan vara förlängd med viss ökning av komplikationer.Ökad spridning av kunskap om nytta och biverkningar av bisfosfonatbehandling är önskvärd. Den långsiktiga nettoeffekten är just nu inte känd.

  • 22.
    Schilcher, Jörg
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Bernhardsson, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Chronic anterior tibial stress fractures in athletes: No crack but intense remodelling2019Ingår i: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 29, nr 10, s. 1521-1528Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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 preoperative 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 remodelling seemed to create a false impression of a fracture line on radiographs. Complete cortical continuity was restored at the biopsy site at median eight months (range six to 13 months).

    CONCLUSION: Tibial stress fractures in athletes normally show no fracture defect, but a region of increased remodelling. The healing process is already ongoing but seems mechanically insufficient. 

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  • 23.
    Nilsson, Abraham
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Alkner, Björn
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Department of Orthopedics, Regional Hospital Eksjö, Region Jönköping County, Sweden.
    Wetterlöv, Patrick
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Department of Orthopedics, Regional Hospital Eksjö, Region Jönköping County, Sweden.
    Wetterstad, Stefan
    Department of Orthopedics, Region Hospital Kalmar, Kalmar, Sweden.
    Palm, Lars
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Low compartment pressure and myoglobin levels in tibial fractures with suspected acute compartment syndrome.2019Ingår i: BMC Musculoskeletal Disorders, E-ISSN 1471-2474, Vol. 20, nr 1, artikel-id 15Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The intense ischemic pain of acute compartment syndrome can be difficult to discriminate from the pain related to an associated fracture. Lacking objective measures, the decision to perform fasciotomy is often only based on clinical findings and performed at a low threshold. Biomarkers of muscle cell damage might help to identify and monitor patients at risk. In patients with fractures, however, markers of muscle cell damage could be elevated because of other reasons associated with the trauma, which would make interpretation difficult. In a review of all patients who underwent emergency fasciotomy in our health care district we aimed to investigate the decision-making process and specifically the use of biomarkers in patients with and without fractures.

    METHODS: In the southeast health care region of Sweden 79 patients (60 men) with fractures (median age 26 years) and 42 patients (34 men) without associated fractures (median age 44 years) were treated with emergency fasciotomy of the lower leg between 2007 and 2016. Differences in clinical findings, p-myoglobin and p-creatine phosphokinase as well as pressure measurements were investigated.

    RESULTS: P-myoglobin was analyzed preoperatively in 20% of all cases and p-creatine phosphokinase in 8%. Preoperative levels of p-myoglobin were lower in patients with fractures (median 1065 μg/L, range 200-3700 μg/L) compared with those without fractures (median 7450 μg/L, range 29-31,000 μg/L), p < 0.05. Preoperative intracompartmental pressure was lower in the fracture group (median 45 mmHg, range 25-90 mmHg) compared with those without fractures (median 83 mmHg, range 18-130 mmHg), p < 0.05.

    CONCLUSIONS: Biomarkers are seldom used in the context of acute fasciotomy of the lower leg. Contrary to our expectations, preoperative levels of p-myoglobin and intracompartmental pressures were lower in fracture patients. These findings support differences in the underlying pathomechanism between the groups and indicate that biomarkers of muscle cell necrosis might play a more important role in the diagnosis of acute compartment syndrome than previously thought.

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  • 24.
    Pihl, Elsa
    et al.
    Karolinska Inst, Sweden.
    Kristoffersen, Malfrid Holen
    Haukeland Hosp, Norway.
    Rosenlund, Anne-Mari
    Oslo Univ Hosp, Norway.
    Laszlo, Sofia
    Uppsala Univ Hosp, Sweden.
    Berglof, Mida
    Karolinska Inst, Sweden.
    Ribom, Eva
    Uppsala Univ Hosp, Sweden.
    Eriksson, Karl
    Karolinska Inst, Sweden.
    Frihagen, Frede
    Oslo Univ Hosp, Norway.
    Mattila, Ville M.
    Tampere Univ Hosp, Finland.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Eklund, Martin
    Karolinska Inst, Sweden.
    Snellman, Greta
    Uppsala Univ Hosp, Sweden.
    Skorpil, Mikael
    Karolinska Inst, Sweden.
    Skoldenberg, Olof
    Karolinska Inst, Sweden.
    Hedbeck, Carl Johan
    Karolinska Inst, Sweden.
    Jonsson, Kenneth
    Uppsala Univ Hosp, Sweden.
    The proximal hamstring avulsion clinical trial (PHACT)-a randomised controlled non-inferiority trial of operative versus non-operative treatment of proximal hamstrings avulsions: study protocol2019Ingår i: BMJ Open, E-ISSN 2044-6055, Vol. 9, nr 9, artikel-id e031607Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

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  • 25.
    Kharazmi, Mohammad
    et al.
    Section of Orthopaedics, Department of Surgical Sciences, Uppsala University, 751 85, Uppsala, Sweden. kharazmi.mohammad@gmail.com; Department of Oral and Maxillofacial Surgery, Västmanland Hospital, Västerås, Sweden. kharazmi.mohammad@gmail.com.
    Michaëlsson, Karl
    Section of Orthopaedics, Department of Surgical Sciences, Uppsala University, 751 85, Uppsala, Sweden.
    Hallberg, Pär
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Lateral fixation: an alternative surgical approach in the prevention of complete atypical femoral fractures2018Ingår i: European Journal of Orthopaedic Surgery & Traumatology, ISSN 1633-8065, E-ISSN 1432-1068, Vol. 28, nr 2, s. 299-304Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Little evidence is available on how to treat incomplete atypical fractures of the femur. When surgery is chosen, intramedullary nailing is the most common invasive technique. However, this approach is adopted from the treatment of other types of ordinary femoral fracture and does not aim to prevent the impending complete fracture by interrupting the mechanism underlying the pathology. We suggest a different surgical approach that intends to counteract the underlying biomechanical conditions leading to a complete atypical fracture and thus could be better suited in selected cases. Here, we share an alternative surgical approach and present two cases treated accordingly.

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  • 26.
    Bernhardsson, Magnus
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Tätting, Love
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Sandberg, Olof
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Marrow compartment contribution to cortical defect healing2018Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 89, nr 1, s. 119-123Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and purpose - Healing of shaft fractures is commonly described as regards external callus. We wanted to clarify the role of the bone marrow compartment in the healing of stable shaft fractures. Patients and methods - A longitudinal furrow was milled along the longitudinal axis of the femoral shaft in mice. The exposed bone marrow under the furrow was scooped out. The mice were then randomized to no further treatment, or to receiving 2 silicone plugs in the medullary canal distal and proximal to the defect. The plugs isolated the remaining marrow from contact with the defect. Results were studied with histology and flow cytometry. Results - Without silicone plugs, the marrow defect was filled with new bone marrow-like tissue by day 5, and new bone was seen already on day 10. The new bone was seen only at the level of the cortical injury, where it seemed to form simultaneously in the entire region of the removed cortex. The new bone seemed not to invade the marrow compartment, and there was a sharp edge between new bone and marrow. The regenerated marrow was similar to uninjured marrow, but contained considerably more cells. In the specimens with plugs, the marrow compartment was either filled with loose scar tissue, or empty, and there was only minimal bone formation, mainly located around the edges of the cortical injury. Interpretation - Marrow regeneration in the defect seemed to be a prerequisite for normal cortical healing. Shaft fracture treatment should perhaps pay more attention to the local bone marrow.

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  • 27.
    Schilcher, Jörg
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Palm, Lars
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Ivarsson, Ingemar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Local bisphosphonate reduces migration and formation of radiolucent lines adjacent to cemented acetabular components2017Ingår i: The Bone & Joint Journal, ISSN 2049-4394, E-ISSN 2049-4408, Vol. 99B, nr 3, s. 317-324Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims Post-operative migration of cemented acetabular components as measured by radiostereometric analysis (RSA) has a strong predictive power for late, aseptic loosening. Also, radiolucent lines predict late loosening. Migration has been reduced by systemic bisphosphonate treatment in randomised trials of hip and knee arthroplasty. Used as a local treatment, a higher local dose of bisphosphonate can be achieved without systemic exposure. We wished to see if this principle could be applied usefully in total hip arthroplasty (THA). Patients and Methods In this randomised placebo-controlled, double-blinded trial with 60 participants, we compressed gauze soaked in bisphosphonate solution (ibandronate) or saline against the acetabular bone bed immediately before cementing the acetabular component. RSA, classification of radiolucent lines, the Harris Hip Score (HHS) and the Western Ontario McMasters Universities Osteoarthritis Index (WOMAC) were carried out at three-, six-, 12-, and 24-month follow-up. Results Migration of the cemented acetabular component relative to the pelvis was reduced by movement almost half in the ibandronate group, when measured as maximum total point or as movement of the femoral head (p = 0.001 and 0.004, respectively). Radiolucent lines after one year were classified as absent, partial or complete, and correlated with treatment (rho 0.37; p = 0.004). Only three of 30 patients in the ibandronate group had complete lines, compared with 13 of 28 in the placebo group (p = 0.002). There were no significant effects on HHS or WOMAC score. Conclusion Considering the power of RSA to predict loosening of cemented acetabular components, and the likelihood that radiolucent lines indicate risk of loosening, these data suggest that local treatment with a bisphosphonate can reduce the risk of late aseptic loosening.

  • 28.
    Schilcher, Jörg
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Ivarsson, Ingemar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Perlbach, Rico
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Hälsouniversitetet.
    Palm, Lars
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    No Difference in Periprosthetic Bone Loss and Fixation Between a Standard-Length Stem and a Shorter Version in Cementless Total Hip Arthroplasty. A Randomized Controlled Trial2017Ingår i: The Journal of Arthroplasty, ISSN 0883-5403, E-ISSN 1532-8406, Vol. 32, nr 4, s. 1220-1226Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Cementless femoral stems in total hip arthroplasty provide dependable clinical and radiographic results in the treatment of osteoarthritis. Stem length might affect the preservation of proximal bone stock and stability. We hypothesized that a shorter stem decreases proximal bone loss without affecting implant stability. Methods: We randomly assigned 60 patients aged between 50 and 70 years to either a standard cementless femoral stem or a 35-mm shorter version. Patients were followed with dual-energy X-ray absorptiometry, radiostereometric analysis, Harris hip score, Western Ontario and McMaster Universities Osteoarthritis Index score, and clinical follow-up at 3, 6, 12, and 24 months. The trial is registered on ClinicalTrials. gov/. Results: After 24 months, short stems had on average 3.8% (95% confidence interval, 1.2%-8.9%) more bone loss in zone 1 compared to standard stems (P - .14). In zone 7, the bone loss was on average 6.5% (95% confidence interval, 6.6%-19.7%) higher compared to standard stems (P - .33). After 24 months, standard stems had migrated 0.93 mm (range, 0.25-4.66 mm) and short stems 0.93 mm (range, 0.17-2.96 mm; Student t-test after log transformation, P - .3). Patient-reported outcome measures were similar in both groups. One patient in the standard stem group was diagnosed with infection, one with a posterior dislocation, and one with a deep venous thrombosis. No stems were revised. Conclusion: There were no statistically significant differences in periprosthetic bone loss or fixation between the stems at 24 months. (C) 2016 Elsevier Inc. All rights reserved.

  • 29.
    Kharazmi, Mohammad
    et al.
    Uppsala University, Sweden.
    Hallberg, Par
    Uppsala University, Sweden.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping. Linköpings universitet, Medicinska fakulteten.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Michaelsson, Karl
    Uppsala University, Sweden.
    Mortality After Atypical Femoral Fractures: A Cohort Study2016Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 31, nr 3, s. 491-497Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Although osteoporotic fracture rates can be reduced by bisphosphonates, prolonged therapy is associated with higher risk of atypical femoral fractures. Ordinary fragility fractures are linked to high mortality rates. We aimed to determine whether atypical femoral fractures also confer excess mortality. Radiographs were reviewed for all patients aged 55 years who had experienced a subtrochanteric or femoral shaft fracture in Sweden in 2008 to 2010. The fractures were classified as either atypical or ordinary. Data on medication use, coexisting conditions, and date of death were obtained from national registers. We estimated multivariable-adjusted relative risks of death after atypical femoral fractures compared with ordinary subtrochanteric or femoral shaft fractures and calculated age- and sex-standardized mortality ratios (SMRs) for atypical and ordinary fractures compared with the population average. During a mean of 4 years of follow-up, 39 of 172 (23%) patients with an atypical fracture had died compared with 588 of 952 (62%) with an ordinary fracture, corresponding to a relative risk of 0.51 (95% confidence interval [CI] 0.38-0.68). The lower risk was evident in both users and nonusers of bisphosphonates. No patient with atypical fracture died in the first year after fracture. Individuals with an ordinary fracture had a higher mortality risk than the general population (SMR=1.82; 95% CI 1.69-1.99), but no excess risk was found in patients with atypical fracture (SMR=0.92; 95% CI 0.65-1.26). We conclude that in contrast to ordinary subtrochanteric and femoral shaft fractures, atypical femoral fractures are not associated with excess mortality. (c) 2015 American Society for Bone and Mineral Research.

  • 30.
    Gustafsson, Anna
    et al.
    Lund University, Sweden.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping. Linköpings universitet, Medicinska fakulteten.
    Grassi, Lorenzo
    Lund University, Sweden.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Isaksson, Hanna
    Lund University, Sweden.
    Strains caused by daily loading might be responsible for delayed healing of an incomplete atypical femoral fracture2016Ingår i: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 88, s. 125-130Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Atypical femoral fractures are insufficiency fractures in the lateral femoral diaphysis or subtrochanteric region that mainly affect older patients on bisphosphonate therapy. Delayed healing is often seen in patients with incomplete fractures (cracks), and histology of bone biopsies shows mainly necrotic material inside the crack. We hypothesized that the magnitude of the strains produced in the soft tissue inside the crack during normal walk exceeds the limit for new bone formation, and thereby inhibit healink. A patient specific finite element model was developed, based on clinical CT images and high resolution CT images of a biopsy from the crack site. Strain distributions in the femur and inside the crack were calculated for load cases representing normal walk. The models predicted large strains inside the crack, with strain levels above 10% in more than three quarters of the crack volume. According to two different tissue differentiation theories, bone would only form in less than 1-5% cif the crack volume. This can explain the impaired healing generally seen in incomplete atypical fractures. Furthermore, the microgeometry of the crack highly influenced the strain distributions. Hence, a realistic microgeometry needs to be considered when modeling the crack. Histology of the biopsy showed signs of remodeling in the bone tissue adjacent to the fracture line, while the crack itself contained mainly necrotic material and signs of healing only in portions that seemed to have been widened by resorption. In conclusion, the poor healing capacity of incomplete atypical femoral fractures can be explained by biomechanical factors, and daily low impact activities are enough to cause strain magnitudes that prohibit bone formation. (C) 2016 Elsevier Inc. All rights reserved.

  • 31.
    Schilcher, Jörg
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping. Linköpings universitet, Medicinska fakulteten.
    Scheer, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Adolfsson, Lars
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Transclavicular Osseous Sutures for the Treatment of Displaced Distal Clavicular Fractures in Children2016Ingår i: Journal of Orthopaedic Trauma, ISSN 0890-5339, E-ISSN 1531-2291, Vol. 30, nr 5, s. E181-E185Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We describe a novel surgical technique for the treatment of displaced distal clavicular fractures in children. These fractures are rare, and recommendations on treatment vary. Conservative treatment might lead to persistent deformity and limitations of function. Previous reports of surgical treatment involve fracture fixation with K-wires. This requires a routine sequential reoperation to remove the implant and has been associated with serious complications in some patients. The surgical technique described here is based on osseous sutures through the clavicular shaft and coracoclavicular ligaments and is found successful for the treatment of distal clavicular fractures in children and may also be feasible for true acromioclavicular dislocations. The main principle of the technique is a fixation of the displaced clavicle through transclavicular drill holes, against the intact inferior periosteal sleeve at the insertion of the coracoclavicular ligaments. No temporary K-wire fixation is needed. To date, we have treated 7 patients with this technique. All fractures healed uneventfully with an excellent functional result and without skeletal deformity.

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  • 32.
    Schilcher, Jörg
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping. Linköpings universitet, Medicinska fakulteten.
    Sen Howe, Tet
    Singapore Gen Hospital, Singapore.
    Ai Png, Meng
    Singapore Gen Hospital, Singapore.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Koh, Joyce S. B.
    Singapore Gen Hospital, Singapore.
    Atypical Fractures are Mainly Subtrochanteric in Singapore and Diaphyseal in Sweden: A Cross-Sectional Study2015Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 30, nr 11, s. 2127-2132Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We have previously noted a dichotomy in the location of atypical fractures along the femoral shaft in Swedish patients, and a mainly subtrochanteric location of atypical fractures in descriptions of patients from Singapore. These unexpected differences were now investigated by testing the following hypotheses in a cross-sectional study: first, that there is a dichotomy also in Singapore; second, that the relation between subtrochanteric and diaphyseal location is different between the two countries; third, that the location is related to femoral bow. The previously published Swedish sample (n = 151) was re-measured, and a new Singaporean sample (n = 75) was established. Both samples were based on radiographic classification of all femoral fractures in women above 55 years of age. The distance between the fracture line and the lesser trochanter was measured. Femoral bow was classified as present or absent on frontal radiographs. Frequency distribution of the measured distances was analyzed using the Bayesian information criterion to choose the best description of the observed variable distribution in terms of a compilation of normally distributed subgroups. The analysis showed a clear dichotomy of the fracture location: either subtrochanteric or diaphyseal. Subtrochanteric fractures comprised 48% of all fractures in Singapore, and 17% in Sweden (p = 0.0001). In Singapore, femoral bow was associated with more fractures in the diaphyseal subgroup (p = 0.0001). This was not seen in Sweden. A dichotomous location of atypical fractures was confirmed, because it was found also in Singapore. The fractures showed a different localization pattern in the two countries. This difference may be linked to anatomical variations, but might also be related to cultural differences between the two populations that influence physical activity. (c) 2015 American Society for Bone and Mineral Research

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  • 33.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping. Linköpings universitet, Medicinska fakulteten.
    High revision rate but good healing capacity of atypical femoral fractures. A comparison with common shaft fractures2015Ingår i: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 46, nr 12, s. 2468-2473Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Healing of complete, atypical femoral fractures is thought to be impaired, but the evidence is weak and appears to be based on the delayed healing observed in patients with incomplete atypical fractures. Time until fracture healing is difficult to assess, therefore we compared the reoperation rates between women with complete atypical femoral fractures and common femoral shaft fractures. Methods: We searched the orthopaedic surgical registry in Ostergotland County for patients with subtrochanteric and femoral shaft fractures (ICD-10 diagnosis codes S72.2, S72.3 and M84.3F) between January 1st 2007 and December 31st 2013. Out of 895 patients with surgically treated femoral shaft fractures, 511 were women 50 years of age or older. Among these we identified 24 women with atypical femoral shaft fractures, and 71 with common shaft fractures. Results: Reoperations were performed in 6 and 5 patients, respectively, odds ratio 4.4 (95% CI 1.2 to 16.1). However, 5 reoperations in the atypical fracture group could not be ascribed to poor healing. In 3 patients the reoperation was due to a new fracture proximal to a standard intramedullary nail. In 2 patients the distal locking screws were removed due to callus formation that was deemed incomplete 5 months post-operatively. The one patient with poor healing showed faint callus formation at 5 months when the fracture was dynamised and callus remained sparse at 11 months. Among patients with common shaft fractures, 2 reoperations were performed to remove loose screws, 2 because of peri-implant fractures and 1 reoperation due to infection. Discussion: Reoperation rates in patients with complete atypical femoral fractures are higher than in patients with common shaft fractures. The main reason for failure was peri-implant fragility fractures which might be prevented with the use of cephalomedullary nails at the index surgery. Fracture healing however, seems generally good. A watchful waiting approach is advocated in patients with fractures that appear to heal slowly. (C) 2015 Elsevier Ltd. All rights reserved.

  • 34.
    Schilcher, Jörg
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Koeppen, Veronika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Michaelsson, Karl
    Uppsala University, Sweden; Uppsala University, Sweden.
    Risk of atypical femoral fracture during and after bisphosphonate use Full report of a nationwide study2015Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 86, nr 1, s. 100-107Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and purpose - Use of bisphosphonates in women is associated with higher risk of atypical femoral fractures. The risk in terms of timing of use and type of bisphosphonate, and in men, remains unclear. Patients and methods - We reviewed radiographs of 5,342 Swedish women and men aged 55 years or more who had had a fracture of the femoral shaft in the 3-year period 2008-2010 (97% of those eligible), and found 172 patients with atypical fractures (93% of them women). We obtained data on medication and comorbidity. The risk of atypical fracture associated with bisphosphonate use was estimated in a nationwide cohort analysis. In addition, we performed a case-control analysis with comparison to 952 patients with ordinary shaft fractures. A short report of the findings has recently been presented (Schilcher et al. 2014a). Here we provide full details. Results - The age-adjusted relative risk (RR) of atypical fracture associated with bisphosphonate use was 55 (95% CI: 39-79) in women and 54 (CI: 15-192) in men. In bisphosphonate users, women had a 3-fold higher risk than men ( RR = 3.1, CI: 1.1-8.4). Alendronate users had higher risk than risedronate users (RR = 1.9, CI: 1.1-3.3). The RR after 4 years or more of use reached 126 (CI: 55-288), with a corresponding absolute risk of 11 (CI: 7-14) fractures per 10,000 person-years of use. The risk decreased by 70% per year since last use. Interpretation - Women have a higher risk of atypical femoral fracture than men. The type of bisphosphonate used may affect risk estimates and the risk decreases rapidly after cessation.

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  • 35.
    Aspenberg, Per
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Atypical femoral fractures, bisphosphonates, and mechanical stress2014Ingår i: Current osteoporosis reports, ISSN 1544-1873, Vol. 12, nr 2, s. 189-193Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Atypical fractures are stress fractures occurring in the femoral shaft and closely related to bisphosphonate use. We here discuss their radiographic definition and different putative etiologies, apart from mechanical stress. Long time reduction of skeletal remodeling because of bisphosphonate use is thought to allow time for the bone to deteriorate mechanically, resulting in reduced toughness. However, the risk of atypical fracture diminishes rapidly after cessation of treatment, which suggests more acute effects of bisphosphonate use. Microdamage normally accumulates at areas of high stress. Possibly, ongoing bisphosphonate use reduces the ability to resorb and replace areas of microdamage by targeted remodeling. This could lead to crack propagation beyond a point of no return, ending in macroscopic stress fracture.

  • 36.
    Schilcher, Jörg
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Atypical fracture of the femur in a patient using denosumab - a case report2014Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 85, nr 1, s. 6-7Artikel i tidskrift (Övrigt vetenskapligt)
  • 37.
    Schilcher, Jörg
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Sandberg, Olof
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Isaksson, Hanna
    Lund University, Sweden.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Histology of 8 atypical femoral fractures2014Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 85, nr 3, s. 280-286Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND PURPOSE:

    The pathophysiology behind bisphosphonate-associated atypical femoral fractures remains unclear. Histological findings at the fracture site itself may provide clues.

    PATIENTS AND METHODS:

    Between 2008 and 2013, we collected bone biopsies including the fracture line from 4 complete and 4 incomplete atypical femoral fractures. 7 female patients reported continuous bisphosphonate use for 10 years on average. 1 patient was a man who was not using bisphosphonates. Dual-energy X-ray absorptiometry of the hip and spine showed no osteoporosis in 6 cases. The bone biopsies were evaluated by micro-computed tomography, infrared spectroscopy, and qualitative histology.

    RESULTS:

    Incomplete fractures involved the whole cortical thickness and showed a continuous gap with a mean width of 180 µm. The gap contained amorphous material and was devoid of living cells. In contrast, the adjacent bone contained living cells, including active osteoclasts. The fracture surfaces sometimes consisted of woven bone, which may have formed in localized defects caused by surface fragmentation or resorption.

    INTERPRETATION:

    Atypical femoral fractures show signs of attempted healing at the fracture site. The narrow width of the fracture gap and its necrotic contents are compatible with the idea that micromotion prevents healing because it leads to strains within the fracture gap that preclude cell survival.

  • 38.
    Schilcher, Jörg
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Koeppen, Veronika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Michaelsson, Karl
    Uppsala University, Sweden.
    Risk of Atypical Femoral Fracture during and after Bisphosphonate Use2014Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 371, nr 10, s. 974-976Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

  • 39.
    Aspenberg, Per
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Stressfrakturer: hjulaxlar och idrottskarriärer brister2014Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, nr 36, s. 1436-1439Artikel i tidskrift (Refereegranskat)
    Abstract [sv]

    Stressfrakturer beror på materialutmattning.

    Mikrospickor i ben uppstår normalt och balanseras genom riktad remodellering.

    Vid hämning av riktad remodellering kan mikrosprickor växa till frakturer.

    Vid intensiv träning hinner den riktade remodelleringen inte med.

    Stressfrakturer i kortikalt ben läker dåligt. Benets normala böjning vid belastning kan tänkas leda till alltför stora deformationer inuti sprickan för att läkning ska kunna ske.

    En ny experimentell behandlingsmetod minskar deformationen i sprickan genom att göra den vidare.

  • 40.
    Schilcher, Jörg
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Koeppen, Veronika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Ranstam, Jonas
    Lund University, Sweden .
    Skripitz, Ralf
    University Hospital Rostock, Germany .
    Michaelsson, Karl
    Uppsala University, Sweden .
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Atypical femoral fractures are a separate entity, characterized by highly specific radiographic features. A comparison of 59 cases and 218 controls2013Ingår i: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 52, nr 1, s. 389-392Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Estimations of the risk of bisphosphonate associated atypical femoral fractures vary between different population-based studies, from considerable to neglectable. A possible explanation for these discrepancies could be different definitions of atypical fractures. We aimed to identify specific radiographic fracture characteristics associated with bisphosphonate use. less thanbrgreater than less thanbrgreater thanMethods: In a previous nationwide study, 59 atypical and 218 ordinary fractures were diagnosed. The atypical fractures were defined by their stress-type fracture pattern. All fractures were now re-assessed by a physician in training, without information about bisphosphonate use. The fracture angle (0-180 degrees) was measured. Presence of local lateral cortical thickening (a callus reaction), more than 2 fragments, or a medial spike was noted. The reader then made a judgment whether the fracture appeared as an atypical fracture based on the ASBMR criteria. less thanbrgreater than less thanbrgreater thanResults: Frequency distribution analysis of the fracture angle showed a distinct subgroup, comprising 25% of all 277 fractures, with a mean of 89 and SD of 10 degrees. Forty-two of 57 patients in this subgroup used bisphosphonates, whereas only 27 of 213 others did (specificity 0.93; 95% CI 0.88-0.96). Presence of a callus reaction had also a high specificity for bisphosphonate use (0.96; 95% CI 0.92-0.98). The ASBMR criteria had a lower specificity, increasing the number of atypical fractures without bisphosphonate use from 13 to 31. This led to a decrease in age-adjusted relative risk associated with bisphosphonate use from 47 (95% CI 26-87) to 19 (95% CI 12-29). less thanbrgreater than less thanbrgreater thanInterpretation: Stress fractures of the femoral shaft are a specific entity, which is easily diagnosed on radiographs and strongly related to bisphosphonate use. Differences in diagnostic criteria may partially explain the large differences in relative risk between different population-based studies.

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  • 41.
    Koeppen, Veronika A
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Dichotomous location of 160 atypical femoral fractures2013Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 84, nr 6, s. 561-564Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and purpose The risk of atypical fracture of the femur is associated with bisphosphonate use. While characterizing atypical fractures from a previous nationwide study in radiographic detail, we had the impression that the fractures were located either in the subtrochanteric region or in the shaft. We determined whether there is a dichotomy in this respect. less thanbrgreater than less thanbrgreater thanPatients and methods The distance between the atypical fractures and the lesser trochanter was measured on plain radiographs from 129 of 160 patients with atypical fractures, taken from 2008 through 2010. Analysis of the distances measured showed 2 clusters, which were then analyzed with regard to bisphosphonate use and age. less thanbrgreater than less thanbrgreater thanResults The distribution of the distances would be best described as 2 clusters, with a dichotomy at 8 cm. The proximal (subtrochanteric) cluster comprised 25 patients who were generally younger (median 71 years) than the 104 patients in the cluster with shaft fractures (median 80 years). The 95% CI for the difference between medians was 4-11 years. Of the patients with subtrochanteric fractures, 18 of 25 used bisphosphonates as compared to 89 of 104 with shaft fractures. less thanbrgreater than less thanbrgreater thanInterpretation The younger age and possibly smaller proportion of bisphosphonate users in the subtrochanteric cluster may be compatible with a greater influence of mechanical stress in the underlying pathophysiology of proximal fractures.

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  • 42.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Epidemiology, radiology and histology of atypical femoral fractures Development of understanding2013Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 84, nr S352, s. 1-26Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    n/a

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  • 43. Beställ onlineKöp publikationen >>
    Schilcher, Jörg
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Epidemiology, Radiology and Histology of Atypical Femoral Fractures: Development of understanding2013Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Bisphosphonates have been used successfully in the prevention of osteoporosis-related fractures for over two decades. Only recently an association between bisphosphonate use and femoral insufficiency fractures – atypical femoral fractures – has been found.

    Bone remodeling is necessary to maintain a healthy skeleton. With age this process can get out of balance and bone resorption can outweigh formation of new bone. This can lead to osteoporosis and fractures that occur after minor trauma. Almost half of all women 50 years of age or older will suffer an osteoporosis related fracture during their remaining life. Bisphosphonates inhibit bone resorption, and after some years of treatment an increase in bone mass can be noted. This increase in bone mass can reduce fracture risk by as much as  half. However, bisphosphonate use seems associated with the development of femoral insufficiency fractures, so called atypical femoral fractures. This thesis aimed to estimate the risk of atypical femoral fractures in the population and its association with bisphosphonate use. It also describes the radiographic and histologic features of these fractures in order to improve our understanding of the pathophysiological background.

    Study 1)  All women 55 years of age and older, who had sustained a femoral shaft fracture during 2008, were identified through the Swedish National Patient Register. Radiographs of 1234 women were reviewed, and 59 patients with atypical fractures and 263 control patients with common femoral shaft fractures were identified. Atypical femoral fractures were defined by their stress fracture-like appearance. In a cohort analysis, we estimated an age-adjusted relative risk of 47 for bisphosphonate users to suffer an atypical femoral fracture compared to non-users. A total of 78% of the patients with an atypical fracture and 10% of the controls had received bisphosphonates, corresponding to a multivariable-adjusted odds ratio of 33. The risk was independent of coexisting conditions and of concurrent use of other drugs with known effects on bone. These results indicate that bisphosphonate use is strongly associated with atypical femoral fractures. The absolute risk is low and benefits of treatment will outweigh the risks.

    Study 2)  A transverse fracture line and a small but visible callus reaction are well established radiographic features of stress fractures. Radiographs from 59 atypical fracture patients and 218 control patients from Study 1 were re-reviewed to measure fracture angles and to detect callus reactions. The majority of the patients with a transverse fracture angle used bisphosphonates. Fracture angle and callus reaction had a high specificity to detect bisphosphonate treatment. When an oblique fracture line was chosen to define atypical femoral fractures in the cohort from Study 1, the association of atypical femoral fractures to bisphosphonate use became attenuated. Therefore, a correct case definition of atypical femoral fractures is necessary for adequate risk calculations.

    Study 3)  Bone biopsies from 8 patients with atypical femoral fractures were obtained during surgical fixation. The histological analysis of the fracture site itself showed a thin fracture line running perpendicular to the long axis of the femur. Despite ongoing remodeling in the bone adjacent to the fracture gap, no healing occurred within the gap itself. Necrotic material in the gap suggests that strains within the gap might prohibit ingrowth of cells necessary for healing. This mechanism of inhibited healing might share similarities with that of stress fractures in athletes. Although it is highly likely that bisphosphonates play a causative role, the pathogenesis of these fractures is still unclear. It may involve a reduced capacity for targeted remodeling.

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    Epidemiology, Radiology and Histology of Atypical Femoral Fractures: Development of understanding
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  • 44.
    Koeppen, V A
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Atypical fractures do not have a thicker cortex2012Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 23, nr 12, s. 2893-2896Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    An association between atypical fractures and general cortical thickness of the femoral shaft is often suggested in the literature. Our radiographic measurements of 59 atypical and 218 ordinary fractures now exclude a difference larger than 10 % in mean femoral cortical thickness (sum of lateral and medial) with 95 % confidence. less thanbrgreater than less thanbrgreater thanAn increased general cortical thickness in patients with fatigue fracture of the femoral shaft (atypical fractures) is commonly suggested. However, there are scarce data to support this. less thanbrgreater than less thanbrgreater thanIn a published nationwide Swedish study, we identified by radiographic review 59 women with an atypical fracture during 2008. The femoral cortical thickness index (thickness/femoral diameter) of these women was now compared with the 218 ordinary fractures that occurred in the same region of the femur in a case-control design. The cortical thickness index 5 cm below the lesser trochanter was the primary variable. less thanbrgreater than less thanbrgreater thanPatients with atypical fractures were younger. Without correction for age, they had a thicker cortex (i.e., higher index). However, the difference in cortical thickness disappeared after age correction. The 95 % CI excludes a group mean difference exceeding 10 % of total mean thickness. Similarly, there was no significant difference in cortical thickness between patients with or without bisphosphonate treatment or between the ipsi- and contralateral femurs in patients with an atypical fracture. less thanbrgreater than less thanbrgreater thanThe concept of a generally increased cortical thickness in patients with atypical fractures should be reconsidered.

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  • 45.
    Michaelsson, K
    et al.
    Uppsala University, Sweden .
    Schilcher, Jörg
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Letter: Comment on Compston: Pathophysiology of atypical femoral fractures and osteonecrosis of the jaw2012Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 23, nr 12, s. 2901-2902Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

  • 46.
    Schilcher, Jörg
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi.
    Michaelsson, Karl
    Uppsala University.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Bisphosphonate Use and Atypical Fractures of the Femoral Shaft2011Ingår i: NEW ENGLAND JOURNAL OF MEDICINE, ISSN 0028-4793, Vol. 364, nr 18, s. 1728-1737Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND Studies show conflicting results regarding the possible excess risk of atypical fractures of the femoral shaft associated with bisphosphonate use. METHODS In Sweden, 12,777 women 55 years of age or older sustained a fracture of the femur in 2008. We reviewed radiographs of 1234 of the 1271 women who had a subtrochanteric or shaft fracture and identified 59 patients with atypical fractures. Data on medications and coexisting conditions were obtained from national registries. The relative and absolute risk of atypical fractures associated with bisphosphonate use was estimated by means of a nationwide cohort analysis. The 59 case patients were also compared with 263 control patients who had ordinary subtrochanteric or shaft fractures. RESULTS The age-adjusted relative risk of atypical fracture was 47.3 (95% confidence interval [CI], 25.6 to 87.3) in the cohort analysis. The increase in absolute risk was 5 cases per 10,000 patient-years (95% CI, 4 to 7). A total of 78% of the case patients and 10% of the controls had received bisphosphonates, corresponding to a multivariable-adjusted odds ratio of 33.3 (95% CI, 14.3 to 77.8). The risk was independent of coexisting conditions and of concurrent use of other drugs with known effects on bone. The duration of use influenced the risk (odds ratio per 100 daily doses, 1.3; 95% CI, 1.1 to 1.6). After drug withdrawal, the risk diminished by 70% per year since the last use (odds ratio, 0.28; 95% CI, 0.21 to 0.38). CONCLUSIONS These population-based nationwide analyses may be reassuring for patients who receive bisphosphonates. Although there was a high prevalence of current bisphosphonate use among patients with atypical fractures, the absolute risk was small.

  • 47.
    Schilcher, Jörg
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Michaelsson, Karl
    Uppsala University.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Letter: Bisphosphonates and Atypical Femoral Shaft Fractures REPLY2011Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 365, nr 4, s. 377-377Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

  • 48.
    Aspenberg, Per
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Ortopedicentrum, Ortopedkliniken Linköping.
    Schilcher, Jörg
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet.
    Fahlgren, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet.
    Histology of an undisplaced femoral fatigue fracture in association with bisphosphonate treatment2010Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 81, nr 4, s. 460-462Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    n/a

  • 49.
    Schilcher, Jörg
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Ortopedicentrum, Ortopedkliniken Linköping.
    Incidence of stress fractures of the femoral shaft in women treated with bisphosphonate2009Ingår i: ACTA ORTHOPAEDICA, ISSN 1745-3674, Vol. 80, nr 4, s. 413-415Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Recent case reports have identified an association between long-term bisphosphonate treatment and stress fractures of the femoral shaft. The risk of such fractures in bisphosphonate users has not been determined. Methods We identified women over 55 years of age with the specific fracture pattern by searching the operation registry of the hospitals in 2 healthcare districts. Prevalence of bisphosphonate treatment was provided by a Swedish national registry covering all drugs delivered to all individuals since 2005. Results The number of women on bisphosphonate treatment was 3,087. Of these, 5 had femoral stress fractures. They had been taking bisphosphonates for 3.5 to 8.5 years. The incidence density for a patient on bisphosphonate was 1/1,000 per year (95% CI: 0.3-2). In the remaining 88,869 women who were not taking bisphosphonates, there were 3 stress fractures. Thus, their risk (without correction for inhomogeneity in age distribution) was 46 times less (95% CI: 11-200). Interpretation These results are rough estimations based on a comparatively small material. Still, a treatment-associated incidence density of 1/1,000 is acceptable, considering that bisphosphonate treatment is likely to reduce the incidence density of any fracture by 1511,000 according to a large randomized trial (Black et al. 1996).

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