Research 2013 DEPT. OF ORTHOPEDICS | LUND UNIVERSITY, SKÅNE UNIVERSITY HOSPITAL RESEARCH – scientific strategy and publications 2013 at the DEPARTMENT OF ORTHOPEDICS LUND UNIVERSITY SKÅNE UNIVERSITY HOSPITAL 2 Department of Orthopedics, Faculty of Medicine, Lund University, Box 117, SE-221 00 Lund, Sweden. www.lu.se Layout: Anna-Mi Wendel, The Department of Orthopedics at Skåne University Hospital Research 2013 is available in pdf at www.skane.se/sus/ortopeden Printed by Media-Tryck, Lund 2014 Photo cover: Roger Lundholm 3 Content The Department of Orthopedics at Skåne University Hospital Magnus Eneroth...............................................................................................................6 Descriptions of Research Activities and Strategic Research Aspects Leif Dahlberg, Kristina Åkesson......................................................................................9 Sponsors..........................................................................................................................12 Awards, Prizes and Dissertations 2013..........................................................................13 Projects Arthroplasty Joint Arthroplasty in the Hip and Knee – fixation, function and survival Gunnar Flivik...................................................................................................................15 Tailored treatment of hip fracture – minimising complications and optimising functional outcome Cecilia Rogmark..............................................................................................................16 Soft tissue biomechanics in hip disease and following hip surgery Hans Wingstrand................................................................................................................17 Back Lumbar pain and sciatica – diagnostics, RSA, treatment and long-term outcome Björn Strömqvist.............................................................................................................18 Biomaterials Biomaterials and Biomechanics Unit Liz Tanner.........................................................................................................................19 Experimental orthopedics Experimental orthopedics Magnus Tägil..................................................................................................................20 Foot & Ankle Foot & Ankle: Clinical, radiographic and patient-reported outcome of surgical treatment Åke Carlsson...................................................................................................................21 4 Minor amputations in diabetic patients and factors related to outcome Hedvig Örneholm...........................................................................................................23 Infection Deep infection after knee arthroplasty Anna Stefánsdóttir.........................................................................................................24 Musculoskeletal epidemiology Musculoskeletal epidemiology with focus on osteoarthritis Martin Englund...............................................................................................................25 Health services use and work disability in patients with musculoskeletal disorders Ingemar F Petersson.......................................................................................................27 The Swedish Knee Arthroplasty Register (SKAR) Otto Robertsson.............................................................................................................28 Epidemiology of Fractures Björn Rosengren.............................................................................................................29 Osteoarthritis Determining mechanisms in osteoarthritis to enable proper diagnosis, treatment and prevention Leif Dahlberg..................................................................................................................30 Musculoskeletal epidemiology with focus on osteoarthritis Martin Englund...............................................................................................................25 From joint injury to osteoarthritis -molecular markers and structural changes André Struglics................................................................................................................31 Joint preserving surgery for knee osteoarthritis Annette W-Dahl.................................................................................................................32 Osteoporosis Risk Factors for Osteoporosis, Falls and Fractures with Special Reference to Physical Activity Magnus Karlsson............................................................................................................33 Effect of gene-environment interactions on bone phenotypes Fiona McGuigan.............................................................................................................34 Tailored treatment of hip fracture – minimising complications and optimising functional outcome Cecilia Rogmark..............................................................................................................16 5 Frailty, falls and fractures in the elderly, especially hip fractures Karl-Göran Thorngren...................................................................................................35 Regulation of skeletal integrity: Genetic variation, risk factors and fracture Kristina Åkesson.............................................................................................................37 Treatment of distal radial fractures Magnus Tägil..................................................................................................................38 Pediatric Orthopedics Prevention of hip dislocation and musculoskeletal deformities in children with cerebral palsy Gunnar Hägglund..........................................................................................................39 Radiostereometric analysis of skeletal growth in children Henrik Lauge-Pedersen.................................................................................................40 Molecular imaging of the hip – exploring the path from DDH to OA Carl-Johan Tiderius.........................................................................................................41 Soft tissue biomechanics in hip disease and following hip surgery Hans Wingstrand.................................................................................................................17 Rheumatoid Arthritis Orthopedic surgery on rheumatoid patients Anna Stefánsdóttir.........................................................................................................43 Sports Medicine Knee injury & Osteoarthritis – outcomes, relation and treatment alternatives Richard Frobell................................................................................................................44 Knee function and development of knee osteoarthritis in ACL injured patients Paul Neuman..................................................................................................................45 Tumors Sarcoma Research Fredrik Vult von Steyern and Anders Rydholm............................................................46 Scientific papers 2013...............................................................................................47 6 The Department of Orthopedics at Skåne University Hospital The Department of Orthopedics at Skane University Hospital consists of three units: Lund, Malmö and an elective procedures site in Trelleborg. The unit in Malmö was founded in 1911 and the one in Lund in 1914. These were the first two orthopedic departments in Sweden. In Lund and Malmö, a complete orthopedic elective and emergency service is present, including spine, tumour and pediatric units. In Trelleborg, elective orthopedic procedures with special focus on hip and knee arthroplasties, shoulder surgery, foot- and ankle surgery and sports medicine are performed. The Department of Orthopedics has access to 152 beds, 16 operating rooms, complete technology, 85 orthopedic surgeons (incl. 25 residents) and 500 other staff. Annually we perform about 11 000 surgeries, 53 500 outpatient visits, 32 000 A/E visits, 34 500 other visits (nurse, physiotherapy). The total turnover is about SEK 655 M (EUR 73 M). The Department has achieved a world reputation from its many years of research as well as continuous clinical experience, supported by being a World Health Organisation Collaborating Centre for Evidence-Based Health Care in Musculoskeletal Disorders since 2007 and one of only sixteen members worldwide of the prestigious International Society of Orthopaedic Centres (ISOC). Our physicians and other staff work in an integrated and cooperative group practice that strives to provide the highest quality and most cost-effective care for 130 000 patients annually. For nearly a century, the Department of Orthopedics in both Lund and Malmö has been involved in advances to alleviate suffering from musculoskeletal disorders. Problems identified in the clinic are taken to the laboratory bench for study, and the results are then translated back into clinical practice. Lund University is Sweden’s strongest comprehensive research university; in recent years it has been awarded more research funding than any other Swedish full-scale higher education institution. In an independent review “RQ-08” of the quality of all research at Lund University, the Department of Orthopedics in Lund was ranked as outstanding, and in Malmö as excellent. 7 Currently, 250 investigators, including 10 professors (4 full professorships), 4 visiting professors, 25 associate professors and 49 PhD students employed by the Department of Orthopedics or closely linked to it, with nearly SEK 40 million in annual funding, are doing research and performing clinical trials in virtually every aspect of musculoskeletal pathology. Each year, about 5 doctoral dissertations are defended and over 150 peer-reviewed scientific papers are published. In 2004, the Faculty of Medicine started a new research area, Tissues in Motion, in which the Department of Orthopedics is an active partner. The WHO´s European office in Copenhagen, Denmark started a Health Evidence Network (HEN) , which aims to disseminate information to decision-makers regarding well-executed studies. The Department of Orthopedics is an active partner. The Department of Orthopedics started RC Syd, a national register centre in charge of 25 national quality registers (today RC Syd has developed into Epidemiology and Register Centre South, ERC Syd, Lund, Sweden). ERC Syd also now includes former EpiCentrum which is a regional centre of excellence for studies in musculoskeletal research including epidemiology. The Department of Orthopedics is still responsible for five national orthopedic quality registers. LUMSI (Lund University Musculoskeletal Institute) was formed in 2010 by the Department of Orthopedics thanks to financial support from Region Skåne. This group includes orthopedics, rheumatology, hand surgery, pain, rehab and preclinical activities. The aim is to collaborate across borders within Research & Education. The group is led by the the Department of Orthopedics. In 2013, Arthroplastywatch was started by the Department of Orthopedics. It is a unique meeting place for information on joint implants. Data are collected around the clock through our specially developed search routines. The data are examined in several steps of medical and statistical expertise. Arthroplastywatch has been developed as an information project during 20112012 with the purpose of collecting data on arthroplasty safety issues from a wide range of information sources on the Internet and disseminating this in one single, publicly accessible, channel. The Department of Orthopedics is represented in a variety of specialist associations in Swedish Orthopedics, in several cases, as chair, and is represented in the Swedish Orthopaedic Society Board. The editor of Acta Orthopaedica is a consultant at the Department of Orthopedics. 8 The current president of ISPO, the International Society of Prosthetics and Orthotics is affiliated with the Department of Orthopedics as a register holder of the Swedish national amputee register. ISPO aims to improve the quality of life for persons who may benefit from prosthetic, orthotic, mobility and assistive devices. Research as well as education of future doctors and other students within healthcare professions is a significant part of the activities. We are especially pleased to have an education unit, and our own training laboratory, which together with the Practicum Clinical Skills Centre at the hospital, can provide practical treatment. Magnus Eneroth MD, PhD, Associate Professor Head of Department of Orthopedics Skane University Hospital Sweden 9 Descriptions of Research Activities and Strategic Research Aspects Department of Orthopedics Clinical Sciences Lund and Malmö The major part of the health care consumption in musculoskeletal disorders is caused by fractures, joint diseases (osteoarthritis and rheumatoid arthritis), back problems, injuries and tumors. In the most recent WHO report on health presented in 2012, musculoskeletal conditions were identified as the second leading cause of disability globally. This is reflected in the research activities within the Academic Department in Lund and Malmö. Research on joint disease and its consequences spans from basic genetic and biochemical investigations to applied projects which monitor in national quality registers the treatment of patients with osteoarthritis to outcome of arthroplasty and includes the following: Development of methods for diagnosis and monitoring of early-stage osteoarthritis through MRI, patient administered outcome scores, radiography, arthroscopy, and analysis of cartilage biomarkers as well as investigation of disease mechanisms; Epidemiology and risk factors for osteoarthritis following joint injuries; Improvement of diagnostic and reconstructive techniques after knee ligament injury; Improve and develop techniques for joint replacement in the rheumatoid joint; Identification underlying causes for joint implant loosening in hip and knee and investigate patterns of knee joint implant failure. Research on osteoporosis, fragility fractures and its consequences spans from basic genetic and biochemical investigations to applied projects in large populationbased cohorts and nationwide register monitor the development and outcome of fragility fractures and includes the following: Studies on the genetic background of reduced bone strength; Studies on the pathophysiology of reduced bone strength and interventions to evaluate if bone strength can be improved; Epidemiology and risk factors for osteoporosis and fragility fractures through cohorts and registers; Improvement of diagnostic procedures and prophylactic interventions for fragility fractures; leading the international best practice evaluation of secondary prevention www.iofbonehealth.org/capture-fracture. Development of techniques for treatments of fragility fractures, fracture healing, and rehabilitation; Estimates on the burden of fracture in economic terms as well as health care utilization. 10 Biomaterial, bone and matrix biology research includes studies on bone induction and its stimulation by human recombinant growth factors and new synthetic bone substitutes and peptides for fracture repair. It also includes studies on tendon and cartilage repair. Research on lumbar back pain and sciatica aims to optimize patient information, surgical methods, postoperative treatment and utilization of hospital resources. Research on different methods of treatment for gangrene of the lower extremity caused by diabetes is evaluated with regard to quality of life, cost, etc. Research on orthopedic oncology evaluates diagnostic procedures, surgical techniques and prognostic classification of soft tissue tumors. Surgical treatment of skeletal metastases is studied concerning technique and outcome. Research in hand surgery includes evaluation and treatment of ligament injuries in distal radius fractures in young patients. Research in pediatric orthopedics targets early identification, monitoring and treatment of congenital disorders of the hip, gait and function analysis in children with cerebral palsy and pathophysiology in Perthes’ disease. The research is closely dependent on collaboration with the clinical department of Orthopedics, with most investigators holding positions as orthopedic surgeons or associated specialties. Furthermore, the infrastructure includes modern laboratory space and imaging facilities at the Clinical and Biomedical Research Centres in Malmö and Lund and Skåne University Hospital. Currently, about 30 graduate students mostly physicians are working on their Ph.D. thesis within the Department. Our research has been successful in obtaining regional, national and international grants with also young researchers receiving positions from the Swedish Research Council. A major 4-year EU grant of 2 million Euro on implementation research has been completed through Professor Anthony Woolf, at present Visiting Professor at our department, with our department as one of the major partners in the consortium. Website: www.eumusc.net. In 2010 a collaborative initiative was taken and a musculoskeletal science institute (LUMSI) was formed in 2010 with a broad representation from different fields including inflammatory diseases as well as basic research. Website: www.lumsi.se LOAD (Lund University network for OsteoArthritis research and Development) was established in November 2010 with the aim to gain new knowledge of the relationship between factors related to OA by applying a unique combination of methodologies available within the network. The network consists of senior 11 researchers in orthopedics, radiology, medical radiation physics, physical therapy, biochemistry, epidemiology and biomechanics that have collaborative projects and joint research grants. Scheduled meetings occur on a monthly basis as well as a yearly conference. These research projects thus involve the whole staff at the Department of Orthopedics in Lund and Malmö. For a complete listing of participants in each project, please contact the primary investigator. For further information you may also visit our websites at: www.med.lu.se/klinvetlund/ortopedi www.med.lu.se/klinvetmalmo/osteoporosforskning This report was edited by: ProfessorProfessor Leif Dahlberg Kristina Åkesson LundMalmö 12 Sponsors Alfred Österlund Foundation, Anders Otto Svärds och Ulrika Eklunds Stiftelse, Astra Zeneca, Center for Athletic Research, Centocor, Crafoordska Stiftelsen (Crafoord Foundation), Erik och Angelica Sparres Stiftelse, EULAR (European League against Rheumatism), European Community, Faculty of Medicine at Lund University, Federation of Swedish County Councils, GlaxoSmith Kline, Greta and Johan Kock Foundations, Heraeus, Herman Järnhardts Foundation, King Gustaf V 80-year Birthday Foundation, Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, Landshövding Per Westlings Minnesfond, Linnea and Josef Carlsson Foundation, Lund University, Maggie Stephens Stiftelse, Magn. Bergvalls Stiftelse, National Board of Health and Welfare in Sweden, Pfizer, Påhlsson Foundation, Region Skåne, Skåne University Hospital, SKL (Swedish Association of Local Authorities and Regions), Sports Research Council, Stiftelsen Ann-Mari och Ragnar Hemborgs Minnesfond, Stiftelsen för bistånd åt rörelsehindrade I Skåne, Stiftelsen Konsul Thure Carlssons Minne, Stiftelsen Skobranschens Utvecklingsfond, Svenska Läkaresällskapet, Swedish National Center for Research in Sports, Swedish Research Council, Swedish Rheumatism Association, Swedish Social Insurance Agency, Swedish Society of Medicine, Thelma Zoéga Foundation, Tore Nilssons Stiftelse för Medicinsk Forskning, Åke Wibergs Stiftelse 13 Awards, Prizes and Dissertations 2013 AWARDS AND PRIZES David Buchebner received the Plenary Poster Award från American Society of Bone and Mineral Research (ASBMR) 2013. Gunnar Hägglund has received the award Ehrensmedalje from the Pediatric Orthopaedic Association of Germany, Austria and Switzerland (Vereinigung für Kinderorthopädie, VKO). The award was received for Gunnar Hägglunds research in pediatric orthopedics and for his development of surveillance programs and quality registers for children with cerebral palsy. Marcus Landgren received EFORT Free Paper Award (bronze) at the 14th EFORT Congress in Istanbul june 2013 for the following paper: M. Landgren, P. Kopylov, A. Abramo, M. Tägil. The Subjective Outcome of Distal Radius Fractures as Measured by DASH Over a Ten-Year Period 2002-2011. Ante Mrkonjic received an Top 5 poster award at the 68th ASSH Annual Meeting, in september 2013 for: Mrkonjic A, Lindau T, Geijer M, Tägil M. Arthroscopically diagnosed SL ligament injuries in distal radial fractures. A 13-15-year clinical and radiographical follow-up. Björn Strömqvist, Peter Fritzell, Olle Hägg, Bo Jönsson and Bengt Sandén received the “North American Spine Society’s (NASS) Best Paper Award” 2013 for the abstract “Bench-marking the outcome of lumbar spine surgery using a spine register data base”. Karl-Göran Thorngren, M.D., Ph.D., FRCS(Ed) was appointed Honorary Member of the Hungarian Orthopedic Association in June 2013. 14 DISSERTATIONS 2013 Mattias Callréus: Peak Bone Mass, Lifestyle Factors and Birth Weight. Department of Orthopedics, Clinical Sciences, Malmö, Lund University 2013 Zana Hawezi: In vivo Sub-regional dGEMRIC Analysis and Contrast Distribution in Clinical Studies of Human Knee Cartilage. Department of Orthopedics, Clinical Sciences, Malmö, Lund University 2013 Anna Jöud: Back and neck pain: Patterns in healthcare consultations. Department of Orthopedics, Clinical Sciences, Lund, Lund University 2013 Bjarne Löfgren: Effect of Physical Activity on Bone, Muscle and Fracture Risk during Growth. Department of Orthopedics, Clinical Sciences, Malmö, Lund University 2013 Ola Svejme: Risk factors for bone fragility and fracture in post-menopausal women. Department of Orthopedics, Clinical Sciences, Malmö, Lund University 2013 Emelie Styring: Clinical and Biological Patterns in Soft Tissue Sarcoma. Department of Orthopedics, Clinical Sciences, Lund, Lund University 2013 Simon Timpka: Muscle Strength and Physical Education. Epidemiological studies of factors in adolescence and their association with later morbidity. Department of Orthopedics, Clinical Sciences, Lund, Lund University 2013 Magnus Tveit: Exercise in Youth and Long-Term Effects on Bone and Joints. Department of Orthopedics, Clinical Sciences, Malmö, Lund University 2013 Arthroplasty Joint Arthroplasty in the Hip and Knee – fixation, function and survival Gunnar Flivik Group members: Abdulemir Ali, Ola Belfrage, Uldis Kesteris, Sverrir Kiernan, Martin Sundberg, Erik Weber Background: Total joint arthroplasty, both in the hip and knee, is a successful procedure with generally good results. Developments have been fast and indications for surgery have gradually widened, with younger patients being considered for surgery as results have been improving. However, late aseptic loosening as well as wear remains a problem, and sometimes early loosening occurs without an obvious reason. The consequence of component loosening and the ensuing bone loss is often a major challenge in revision surgery. Projects: In a range of ongoing investigations we are studying different factors involved in the fixation and function of the prosthesis components. We are evaluating surgically relevant factors such as different operative techniques, pain treatment regimes, bone preparation models, types of bone cement and different prosthesis designs, both cemented and uncemented. We are also exploring the importance of anatomic restoration and how to optimize the biomechanical conditions. Another area of ongoing study is the role for bisphosphonates in joint arthroplasty. In many of these studies we use RSA (RadioStereometric Analysis) which is a radiographical method by which the 3D-micromotion of the implant in its bone bed can be followed with a very high degree of accuracy. This is the most exact method there is when it comes to measuring migration and wear patterns of prosthesis components. In the studies we have also access to evaluation with gait analysis, peroperative navigation tools and 3D-templating. Our groups of patients are also being followed up with strictly clinical and conventionally radiological examination methods as well as a comprehensive package of questionnaires, covering both general health and disease specific questions. Furthermore, we carry out complementary biomechanical in vitro laboratory studies. Concurrently with the continuous data we contribute to both the National Hip and Knee Registers we are also following up our own hospital’s material of patients with primary as well as revision hip and knee prostheses. Aim: Our aim is to evaluate and improve factors of importance for optimal implant function and survival, and not least patient satisfaction and pain relief. Significance: With success for our studies we can contribute to even better joint function and life quality for patients with hip and/or knee prostheses. We can also decrease the need for re-operations, which are often complex, costly and for the patient trying surgery. gunnar.flivik@med.lu.se, uldis.kesteris@med.lu.se, martin.sundberg@med.lu.se 15 Arthroplasty 16 Tailored treatment of hip fracture – minimising complications and optimising functional outcome Cecilia Rogmark Group members: Ammar Al-Jobory, Susanne Hansson, Olof Leonardsson, Sebastian Rönnquist Background: A hip fracture is a potential treat to an old individual’s life and independency. The injury is common, and costly to society. In spite of numerous studies leading to improvements within particular issues, the clinical pathway is suboptimal, with unsatisfactory patient reported outcome regarding pain, function and quality of life. Project and preliminary results: Our scientific achievements so far have e.g. lead to a new national treatment rationale for femoral neck fractures; internal fixation with a failure rate of nearly 50 % has changed to hip arthroplasty, after which only 5 % suffers failure. This project is a continuum, aiming at develop suitable treatment of hip fracture in different patient groups via clinical trials, and observational studies based on the Swedish Hip Arthroplasty Register. • Which is the true incidence of complications after hip fracture related arthroplasty? • Are register data reliable regarding surgical outcome? • Which are the risk factors for complication after arthroplasty? • Which type of hip arthroplasty leads to best results? • Are patients satisfied with modern hip fracture treatment, or if no so, what can be improved? Aim: To give recommendations regarding best treatment and rehabilitation of hip fracture for individuals of different ages and with different functional demands. Long term outcome in terms of surgical, functional and patient reported outcome are considered. Significance: The current project will further analyse implant alternatives and scrutinize the entire clinical pathway, with the ambition to secure a lasting improvement in patient reported outcome. Currently many patients fail to recover after a hip fracture, and the reason may be insufficient implementation of scientific results, unclear responsibility for rehabilitation issues – and defeatism amongst care givers and patients. cecilia.rogmark@skane.se Arthroplasty Soft tissue biomechanics in hip disease and following hip surgery Hans Wingstrand Group members: Martin Clauss, Thomas Ilchmann, Aurimas Sirka, Justinas Stucinskas, Sarunas Tarasevicius Background: This project focuses on hip joint soft tissues. Sonography, intracapsular pressure measurements, MR and CT techniques were used in this clinical project to diagnose and follow synovitis in various hip disorders and following surgery. Projects and results: In one project the soft tissue biomechanics of the hip joint capsule in and its influence on clinical symptoms, radiological findings and subsequent loosening in hip joint arthroplasties are studied. We use ultrasonography (US) as a method of examination of THA hips for signs of synovial edema/free fluid in the joint. Pain in OA hips might be of capsular/synovial origin due to its rich sensory innervation. We investigate the intracapsular pressure and the elasticity of the hip joint capsule in OA and correlated these parameters to pain and to the radiographic stage of OA. Joint dislocation remains one of the most disturbing complications after THA. We investigate the soft tissue reaction in relation to soft tissue repair, component wear in relation to aseptic loosening of the prosthetic components. In a pediatric project concerning Legg-Calve-Perthes Disease, Transient synovitis and Septic arthritis of the child´s hip scintimetric, sonographic and MR studies indicated that increased intracapsular pressure, caused by synovitis with effusion is a factor in the disturbed blood supply to the epihysis. Synovitis causes cartilage oedema and ensuing cartilage hypertrophy with a risk of joint deformation, incongruency and poor containment. Serial MRI and plain radiography was used to follow the development of the femoral head. In cases of incongruency a proximal femoral varus, derotation and extension osteotomy reduced cartilage incongruency and an improved sphericity of the femoral head. Aim: To study the significance of hip joint soft tissue pathophysiology and biomechanics in varoius hip disorders and following hip surgery. Significance: Soft tissue reactions in varoius hip disorders and after hip surgery has so far attracted little interest but have significant biomechanical, clinical and prognostical effects. Six theses have to date been defended as results of these projects focused on the soft tissues around the hip, now continued in cooperation with Dept of Orthopedics, Kaunas Medical University, Lithuania, and Dept of Orthopedics, hip section, Liestal, Switzerland. hans.wingstrand@med.lu.se 17 back 18 Lumbar pain and sciatica ­– diagnostics, RSA, treatment and long-term outcome Björn Strömqvist Group members: Paul Axelsson, Ragnar Johnsson, Bo Jönsson, Gauti Sigmundsson, Fredrik Strömqvist Background: Both on an international and national level, surgical treatment of lumbar spine disorders is performed to an increasing extent. Improved diagnostic modalities contribute to this but also a high number of new implants with variable scientific documentation. Main aim of surgical treatment is pain relief/pain reduction and functional improvement. To demonstrate the utility of new treatments, prospective long-term follow-up using multiple result parameters is required. Project and preliminary results: Prospective long-term follow-up has been performed since the 1980s and subsequently been converted into a national register, Swespine, which today is used by 90 % of departments in Sweden. Using this, all treatments can be documented regarding outcome. RSA has been utilized for demonstrating high-precision mobility patterns in various lumbar conditions as well as under normal conditions and in healing processes. An algorithm for testing new implants has been developed. Also DCRA has been added to the armamentarium Biochemical studies of cartilage markers in disc herniation in collaboration with the department of cell and molecular biology, has demonstrated the possibility to monitor events in the disc in blood tests and further studies are ongoing. Minimally invasive treatment of lumbar spine disorders has been evaluated in prospective studies, examples are ultrasound treatment for disc herniation, percutaneous treatment of disc herniation and interspinal spacer for spinal stenosis. Also bone inductive substances in conjunction with fusion have been studied in prospective randomized studies. Evaluation by functional and ADL parameters is studied in multidisciplinary projects on disc herniation surgery. Significant gender related differences in preoperative quality of life and function before disc herniation surgery have been identified and the causes are being analysed. The limited number of patients requiring fusion in conjunction with spinal stenosis surgery has been described based on register data. Aim: The overall aim is to improve patient information before surgery and patient selection for surgery, pinpointing well functioning surgical techniques and deleting non-efficient treatment modalities. A treatment algorithm is gradually being developed. Significance: The treatment program has significantly improved treatment for patients with lumbar spine problems, an important contribution on a humanitarian basis for the individual and on an economical basis for the society. bjorn.stromqvist@med.lu.se, paul.axelsson@skane.se, bo.bj.jonsson@skane.se, ragnarjohnsson@spray.se, gauti.sigmundsson@skane.se, fredrik.stromqvist@skane.se biomaterials Biomaterials and Biomechanics Unit liz tanner Group members: Gunnar Flivik, Hanna Isaksson, Magnus Tägil, Jian-Sheng Wang Since May 1997, the biomechanics and biomaterials laboratory has provided an interface for researchers with engineering and medical backgrounds, bridging the biomechanical/ biomaterial research with more biologically oriented animal models and clinical research. The facilities within the unit are: 1) a mechanical testing laboratory with biaxial (tension/compression and torsion) mechanical test machine 2) a RSA laboratory (RadioStereometric Analysis), a technique that with a very high degree of accuracy can measure the stability of artificial joints implanted into the body, furthermore we measure in 6 degrees of freedom with some different precision values for each type of measurement 3) a biomaterials production facility for ceramic bone substitute materials 4) animal model facilities for bone and bone substitutes in in vivo studies 5) a complete set of hard tissue preparation equipment: Exakt saw, diamond saw and grinding machine provide hard tissue histology investigation for a combination of mineralized bone, metal and biomaterial study 6) this laboratory is a part of a centre for Biomechanics at Lund University The general aim of the biomechanics laboratory is to use the techniques of engineering, biomaterials and biomechanical sciences together with biological and animal models to improve the repair and regeneration of tissues in the skeletal system. A clear link to clinical use and clinical trials is prioritiesed. Our mechanical machine is used for mechanical testing of new materials or bone tissue. The RSA laboratory assesses the behavior of joint implants in the body. A large number of RSA-studies are ongoing evaluating factors such as cementing technique, bone preparation, prosthesis design and fixation methods, both cemented and uncemented. We are investigating injectable bone substitute materials, that have a similar composition to bone, and which can integrate with normal tissue. We are studying how these materials can stimulate repair of tissue, through optimizing the chemical composition or the mechanical properties of the materials. We are also studying the effects of antibiotics in the material on its biomechanical and biological properties. elizabeth.tanner@glasgow.ac.uk, gunnar.flivik@med.lu.se, hanna.isaksson@bme.lth.se, magnus.tagil@med.lu.se, jian-sheng.wang@med.lu.se 19 experimental orthopedics 20 Experimental orthopedics Magnus Tägil Group members: Ola Belfrage, Per Bosemark, Hanna Isaksson, Jan Jureus, Neashan Mathavan, Mea Pelkonen, Christina Perdikouri Background: The technical implant revolution in orthopedics has changed the lives of many patients, but not all. Still there are groups of patients we cannot help. Fractures sometimes remain unhealed for years, in spite of repeated operations, using the best implants and the best bone inductive aid we have- the bone autograft- taken from the patient him/herself. Further young and old patients with malignant bone tumors have their diseased bone resected. The bone is hard to replace and amputation sometimes is the only solution. Project and preliminary results: In our project we try combinations/mixtures of bone substitutes, bone grafts and bone active drugs. We have developed own animal models using orthopedic technique and study basal bone physiological mechanisms in several rat fracture models. We evaluate the bone strength in standardized mechanical tests. We evaluate the amount of newly formed bone by microCT and histology/ histomorphometry as well as the bone quality by new beyond state of the art methods at a molecular level, using SAXS (smalll angle X-ray scattering) for tissue structure and FTIR (Fourier transformation infrared spectroscopy) for tissue composition. These latter investigations will provide pivotal knowledge regarding the mechanisms of the individual or combined drugs. We have previously shown that bisphosphonates and PTH can augment fracture healing provided sufficient blood supply is present. In open fractures with devascularized fracture ends, only BMP can induce healing. In a critical defect model we evaluate the Masquelet technique to recreate large volumes of bone. Aim:The aim of this study is to create healing and good bone quality with a mixture that is better and more osteoinductive than bone autograft- to be used in these, the most severe cases. Significance: We believe that pharmaceutical treatment of skeletal injuries will revolutionize orthopedics the same way as biologic pharmaceutical treatment has in rheumatoid patients. magnus.tagil@med.lu.se foot & ankle Foot & Ankle: Clinical, radiographic and patientreported outcome of surgical treatment Åke Carlsson Group members: Jack Besjakov, Maria Cöster, Ylva Ericsson, Ilka Kamrad, Magnus Karlsson, Håkan Magnusson, Björn Rosengren. Background: The Swedish Ankle Register (www.swedankle.se) contains data on all ankles replaced by a prosthesis since 1993, including secondary procedures and complications, and since 2008 also information on primary ankle fusions. The register serves as a basis for clinical development and research. Projects: Project 1) Validation of the foot-specific SEFAS score (Self-reported Foot & Ankle Score). The score has been validated for ankle arthrodesis,ankle replacement and disorders of the mid and forefoot. The results are published in Acta Orthopaedica 2012 and 2013. Further analyses of this questionnaire are now being undertaken. Project 2) Clinical and radiographic evaluation of the Mobility ankle prosthesis. More than 100 cases performed in Malmö are followed clinically, by radiographs and by validated questionnaires. Project 3) The prevalence of primary ankle osteoarthritis. Radiographic evaluation of ankle osteoarthritis by different projections. Project 4) Balance, walking velocity, oxygen consumption and muscle strength. Patients undergoing ankle fusion or replacement due to osteoarthritis are examined before and two years after surgery together with controls Project 5) Self-evaluated outcome and satisfaction following primary ankle replacement and fusion. Project 6) Self-evaluated outcome and satisfaction after seconday procedures following primary ankle replacement and fusion. Aim: To evaluate the clinical, radiographic and patient-reported outcomes after ankle fusion and replacement. The intention is to elucidate the treatment method of preference in relation age, sex and diagnosis. We also intend to clarify the prevalence of idiopathic osteoarthritis. Significance: The literature contains only scarce information on the functional results after ankle replacement and comparisons with results after ankle fusion are non-existing. By our studies orthopaedic surgeons and health care authorities will be guided in decision making regarding surgical treatment of osteoarthritis and other disorders of the ankle. ake.carlsson@med.lu.se, bjorn.rosengren@med.lu.se 21 22 foot & ankle This 63 year old man had his left ankle replaced by a Mobility prosthesis due to osteoarthtitis. (Picture to the right) There was no history of a previous trauma. Now, three years later, he is scheduled for replacement of his contralateral ankle. (Picture to the left) foot & ankle Minor amputations in diabetic patients and factors related to outcome Hedvig örneholm Group members: Jan Apelqvist, Magnus Eneroth, Jan Larsson Background: Around 4 % of the Swedish population has diabetes. A considerable proportion of these patients will at some point in their life have foot-related problems, the most severe being ulceration, infection and gangrene. Almost half of all non-traumatic amputations in the industrialized world are performed on diabetic patients. In most studies the major (above the ankle) amputation rate only is reported. The principal aim of minor (below the ankle) amputations in these patients is to avoid major amputation in order to facilitate ambulation. Although minor amputations are performed in large numbers on diabetic patients, in most countries the incidence is unknown and little is known about the outcome. Project: We analyze factors leading to amputation and those that influence the outcome of such surgery. Can the outcome be predicted by using specific parameters? Which factors play a greater part in outcome after surgery? Trying to find the answers to these questions will hopefully lead to better treatment options for these patients. Taking the patients’ aspect into account is also important. A large proportion of these patients are elderly and have to rely on family or social services in their everyday living. How amputation affects their quality of life is also subject to our studies. Aim: The goal is to reduce the number of major and minor amputations in these patients. Significance: Reducing amputation rate is important not only for the patient but also for society in general as an amputation is associated with higher costs than if you can avoid an amputation. hedvig.orneholm@med.lu.se, jan.apelqvist@skane.se, magnus.eneroth@skane.se, jan.jl.larsson@skane.se 23 infection 24 Deep infection after knee arthroplasty Anna Stefánsdóttir Group members: Anna Holmberg, Annette W-Dahl Background: The incidence of deep infection after a primary knee arthroplasty is approximately 1,5 %. As the number of operations performed steadily increases so does even the number of patients that are affected by this serious complication. Since 1975 the Swedish Knee Arthroplasty Register (SKAR) has registered information on knee arthroplasties performed in Sweden. This large nation-wide database provides unique possibilities to study a low-frequent complication like deep infection. Project: During the last decade it has become common to treat an infected knee arthroplasty with open debridement and exchange of the tibial insert, followed by antibiotic treatment. In the medical literature it is debated which patients should be treated in this manner. Of special interest is the time interval from the signs of symptoms until debridement, and the microbiology. Information on approximately 150 cases of primary total knee arthroplasties having a first time revision due to infection with exchange of the tibial insert has been collected and is now being analyzed. Aim: To reveal the success rate of open debridement and exchange of tibial insert in infected knee arthroplasty in Sweden, and to identify possible prognostic factors for failure. Significance: Deep infection is a devastating complication that can have severe consequences for the patients and brings high costs to the health care system. The study will help orthopedic surgeons and infectious disease specialists to choose the most effective treatment for every patient. Further, health economic analysis is needed. anna.stefansdottir@med.lu.se , anna.holmberg@med.lu.se, annette.w-dahl@med.lu.se musculoskeletal epidemiology Musculoskeletal epidemiology with focus on osteoarthritis martin englund Group members: Jenny Hubertsson1,2, Anna Jöud3, Aleksandra Turkiewicz1,4, Dan Bergkvist1,5, Fan Zhang1,6, Fredrik Svensson1,6, Charlotte Bergknut7, Caddie Zhou4,7, Lotte Höjgård-Hansen8, Jaanika Kumm9, Yuri Yamamoto10,11, Alishgar Ahmad Kiadaliri12 Background: Musculoskeletal conditions are the leading causes of chronic pain and reduced quality of life in an ageing European population. The burden on society due to these conditions will rapidly increase making it an urgent matter. However, there is lack of knowledge of natural history, future disease prognoses and monitoring of treatments on population level, critical for health care planning. Osteoarthritis, a chronic degenerative joint disease causing pain and reduced joint function is specifically believed to be one of the most common causes of musculoskeletal disability in developed countries. Projects: We determine the specific roles of meniscus lesions and position in early osteoarthritis pathogenesis are as well developing an innovative bone biomarker to predict incidence and progression of the disease in collaboration with biomechanical engineers. We will accomplish our goals by analysis of large datasets including state-of-the-art repeat knee MRIs and radiographs. In our population-based epidemiologic studies of musculoskeletal diseases in a wider perspective, focusing on chronic conditions as well as fractures and other injuries, we use physician-coded steadily growing in- and outpatient health care data in southern Sweden currently encompassing 20 million person-years. Personal identifiers will be used to set up linkages, not attainable in any other way, with, e.g., data on sick-leave, diagnoses, surgical procedures, prescribed drugs and socio-economic variables. Aim: To gain novel insights on musculoskeletal diseases and injuries with focus on osteoarthritis etiology, occurrence, natural history, treatments, prediction, disease monitoring, and burden to allow for better care, decision making, resource prioritizing, and methods of prevention. Significance: With our current translational approach pushing the frontiers in our fields of research, we will provide much needed new knowledge and information to researchers and clinicians specializing in musculoskeletal conditions, and the patients. Public health professionals, politicians, and policy makers are just a few examples of other professionals who will benefit from the information the team will provide. Considering meniscal damage is present in about every third knee in middle-aged and older adults, and is the most potent risk factor for knee OA so far identified, understanding of its natural course is highly needed. In clinical practice early identification of patients at high risk is vital fore early information and potential intervention. 25 musculoskeletal epidemiology 26 The research group is cross-disciplinary and includes me as PI and epidemiologist, orthopedic surgeons6, a couple of physicians under recidency3 or specialty training5, a physiotherapist11, a political scientist2, a postdoc public health scientist3, two statisticians4, data managers/SAS analysts7, a health economist12, and a secretary8. I am currently mentoring five PhD students1 as main advisor, a postdoc radiologist9, and an international research fellow10 as well as serve as co-mentor an additional PhD student. We collaborate with Lund University postdoc researchers in several disciplines to facilitate register research, e.g., (but not limited to) Björn Rosengren, Dept of Orthopedics (fractures) and Aladdin Mohammad, Dept of Rheumatology (Giant Cell Arteritis). The group is active in the Lund University Strategic Research Area “Epidemiology for Health (EpiHealth)”, the Lund University osteoarthritis network LOAD, and the by the Faculty of Medicine officially supported creative research environment for young investigators in osteoarthritis, ReLOAD. We have a comprehensive international network of active collaborators in the fields of biomechanics, clinical epidemiology, MRI analysis methodology, orthopedics, radiology and rheumatology in Australia, Austria, Canada, Denmark, Finland, Germany, Norway, United Kingdom and USA. The group is supported by the Swedish Research Council, ALF, Crafoord Foundation and Kock Foundations. martin.englund@med.lu.se Fig. 1: Hypothetical “meniscal pathway” to the pathogenesis of knee OA. 1. Risk factors: systemic, local & environmental (knee trauma, obesity, genes, malalignment) Early Late Pain OA musculoskeletal epidemiology Health services use and work disability in patients with musculoskeletal disorders Ingemar F Petersson Group members: Birgitta Grahn, Sofia Löfvendahl, Tor Olofsson, Kjerstin Stigmar, Malin Forsbrand, Lotta Post Sennehed, Maria Sandberg Background: Every third visit to a GP as well as one third of the disease burden in sick leave practice comes from musculoskeletal disorders (MSKD:s) which cause a high degree of functional impairment, work disability and decreased quality of life for people of all ages. Project: New strategies to improve health in patients with musculoskeletal disorders are monitored and further developed by using different types of registers and electronic patient record information. This can be used for structured and continuous follow-up, evaluation and bench marking. With this program it is possible to achieve new ways for collaboration with research groups and decision makers within Sweden, Europe and other parts of the world including European programs such as the EUMUSC.NETproject and other national and international collaborations. We use registers from the Swedish National Insurance Agency (Försäkringkassan), the local health authorities of Region Skåne and national registers on occupation, income, education. We also include data from National Patient Registers (Nationella kvalitetsregister) and plan to include data from the municipality level. Aim: Aims of the program • To study the impact on Functioning, Activity and Participation due to musculoskeletal disorders on a group level for different inflammatory MSKD diagnoses • To estimate of the impact of MSKD:s and other chronic conditions on the health care system and the national social insurance system • To study the Burden of Disease and Cost of Illness due to musculoskeletal disorders on a group level for different inflammatory MSKD diagnoses • To evaluate the effect of a national rehabilitation program in Sweden on work participation and health related quality of life in patients with back pain • To evaluate in register based follow-up studies, the effects of structured interventions and work place interventions in patients with back and neck pain on work participation and health related quality of life in the Work-Up study • To study the development and implementation of guidelines for the treatment, rehabilitation and sick leave procedures for patients with inflammatory MSKD:s Significance: The program has a focus on the consequences for the individual and the society in patients with inflammatory MSKD. ingemar.petersson@med.lu.se 27 musculoskeletal epidemiology 28 The Swedish Knee Arthroplasty Register (SKAR) Otto Robertsson Group members: Kaj Knutson, Lars Lidgren, Otto Robertsson, Anna Stefánsdóttir, Martin Sundberg, Annette W-Dahl Background: Since 1975 the Swedish Knee Arthroplasty Register (SKAR) has prospectively followed patients operated on with knee arthroplasty. In the seventies there was an explosive expansion in the number of implants produced and the Swedish orthopedic surgeons realized that in this environment it would be impossible for an individual surgeon to base his choice of optimal operative treatment on his own experience, thus a national registration was started. Project: Initially, the register only gathered a minimal set of data for each primary operation containing information on identity, age, disease, treating hospital, what implant was inserted and the method of fixation. As an additional measure of outcome, self-administrated questionnaires have been sent to subsets of patients and in a pilot project selected hospitals have delivered data on patient reported outcome measures pre- and postoperatively. In 2009 the register added a number of questions to its form concerning previous surgeries, surgical methods used (tourniquet, drainage, CAS, MIS), prophylaxis (infection, thrombosis) as well as timing and in 2013 registration of tibia osteotomies was started. The registry has in the past succeeded in giving early warning about inferior techniques and implants as well as stimulating hospitals and surgeons to improve their routines. The annual report and a list of publications can be found on our website www.knee.se Aim: The original aim of the project was to detect which implants were suitable respectively unsuitable for use in patients with different types of knee destructions. Later on the register started evaluating patient satisfaction and different health measures in order to better understand the results of knee arthroplasty from the patient perspective. Further, by the new variables concerning surgical techniques and drug prophylaxis we hope to be able improve knowledge on the efficacy of the treatment. Significance: During 2013 13 410 primary arthroplasties and 856 revisions were reported in Sweden. 58 % of the primary surgeries and 55 % of the revisions were performed in women. Due to changes in the age-profile of the population in the coming years, demand is still expected to increase. The cost for revisions is substantially higher than that for primary operations, especially in infected cases. The number of revisions is affected by many factors such as unsuccessful methods or implants, where the revision rate will be higher than the average. Therefore, it is of the highest importance that the use of such methods, implants and techniques can be limited to reduce the extra cost and suffering. otto.robertsson@med.lu.se musculoskeletal epidemiology Epidemiology of Fractures Björn Rosengren Group members: Daniel Jerrhag, Anton Karlsson Background: With the anticipated changes in population size and age-structure even small changes in risk of disease can significantly alter resource demands for society. The lifetime risk of fragility fracture at age 50 years in Sweden is as high as 50 % in women and 25 % in men and more than 3 % of the Swedish national health care costs are the result of osteoporosis related diseases. The lack of current data on occurrence of overall and type-specific fracture disease makes predictions on the future number of fractures uncertain. Project and preliminary results: Our earlier work infers that hip fracture incidence has levelled off in Sweden and has since the mid-1990s been replaced by a decreasing incidence. In women this appears to be the result of cohort+period effects, with a lower incidence in those born recently than those born earlier. As no changes in prevalence of osteoporosis have been apparent in our studies, the changes in fracture incidence seem associated to other factors, probably linked to changes in society during the lifespan (from 1885 to 2011) of the examined individuals. Aim: • Improve projections of fracture burden, by defining changes in regional and nationwide fracture epidemiology during the recent 30 years including effects of age+cohort+period and medication, migration, and urbanization. • Produce algorithms to identify individuals at high risk of fracture to better target preventive strategies. • Define time trends in fracture severity (classification) and treatment protocol for common fracture types. • Make cost and resource descriptions and cost benefit-analyses for both pharmacological regimes and other interventions for different fracture types. Significance: This project will enable more accurate prediction of the future fracture burden, imperative for society and politicians to know when planning the future resources for fracture care. bjorn.rosengren@med.lu.se 29 osteoarthritis 30 Determining mechanisms in osteoarthritis to enable proper diagnosis, treatment and prevention leif dahlberg Group members: Shahrzad Hosseininia, Therese Jönsson, Henrik Owman, Ulf Sigurdsson, Jon Tjörnstrand, Ylva Ericsson, Paul Neuman, Carl Johan Tiderius Background: Osteoarthritis (OA) is a chronic degenerative joint disease, causing pain and functional impairment, which results in reduced physical and daily activities as well as decreased quality of life. It is the 11th highest global contributor to years lived with disability. The risk for developing OA is related to the individual’s cartilage quality and to risk factors such as meniscectomy, obesity, muscle weakness, major injuries and, in the hips, developmental joint anomalies. All joints can be affected but OA is most commonly seen in the knees, hips, fingers and spine. The hallmark of OA is cartilage loss, which together with joint pain defines the disease. It is a complex disease that often causes great suffering due to pain, reduced mobility and reduced quality of life. Project: We combine state-of-the-art magnetic resonance imaging technology (dGEMRIC) with molecular composition analysis to examine cartilage structure and quality. Using this approach we can identify metabolic events that will result in cartilage structural changes as well as relate the MRI signal to molecular content. In vitro, we use dGEMRIC on excised cartilage samples which are also analysed for molecular composition. In vivo, we follow patient cohorts at increased risk of developing OA longitudinally, from emergence of risk factors to radiographically diagnosed OA. The combination of advanced imaging methods and molecular indicators, applied in parallel to experimental models and patient cohorts, provides novel understanding and new means to detect the process leading to disease. Moreover, we study effects of early intervention i.e. physiotherapy to improve treatment of OA patients. Aim: The aim of our research is to get the whole picture of OA; from comprehension at molecular and structural levels, to understanding which external factors that influence progression of the disease. By determining disease mechanisms at early stages of OA, methods for proper diagnosis, treatment and, not the least, prevention of the disease can be developed. Significance: Besides causing pain and hampered physical mobility for the affected patient OA has effects in a larger context due to huge socioeconomic expenses associated with the disease. Both from a patient and a socio-economical perspective it is thus of utter importance to develop better diagnostic methods, treatment interventions and prevention programs. leif.dahlberg@med.lu.se osteoarthritis From joint injury to osteoarthritis ­– molecular markers and structural changes André Struglics Group members: Maria Hansson, Staffan Larsson, Stefan Lohmander, Per Swärd Background and significance: Osteoarthritis (OA) is a common musculoskeletal disease causing destruction of joint tissues leading to pain and disability. Little is known about disease onset and the mechanisms, and no disease modifying drug or reparative surgical intervention are available. OA affects elderly people, but middle-aged people with symptomatic OA are increasing. This increase is due to the strong linkage between joint injury and OA. Project and preliminary results: We use animal models, and body fluids from cross sectional and longitudinal patient cohorts for immunochemical assays of cytokines and joint tissue molecular markers, use MRI for analysis of joint structures, and monitor patient-reported outcomes. Preliminary data: • Explant cultures of mechanically injured bovine cartilage shows no increased release of aggrecanase and MMP generated ARGS- and FFGV-aggrecan fragments. Co-culturing the cartilage with synovium only increases the release of ARGS fragments. Combined mechanical injury of the cartilage and co-incubation with the synovium increases both ARGS and FFGV fragments. These results indicate differences in the process of activating aggrecanases and MMPs. • Synovial fluid TNF-α concentration is elevated directly after ACL injury and remains elevated over 5 years compared to knee healthy controls. Knee injuries with an osteochondral fracture have higher synovial fluid TNF-α concentrations compared to knees without fractures. This suggests that knee injuries associated with an osteochondral fracture cause joint inflammation which may contribute to the development of OA. Aim: Investigate the biological response following joint injury and the processes leading to OA. Relate molecular markers to imaging and clinical outcomes in the early phases of knee injury and OA. Validate aggrecan protein fragments as biomarkers of OA disease burden and prediction. andre.struglics@med.lu.se, maria.hansson@med.lu.se, staffan.larsson@med.lu.se, stefan.lohmander@med.lu.se, per.sward@med.lu.se 31 osteoarthritis 32 Joint preserving surgery for knee osteoarthritis Annette W-Dahl Group members: Lars Lidgren, Otto Robertsson, Martin Sundberg Background: High tibial osteotomy (HTO) is a joint preserving surgical alternative in the treatment of knee osteoarthritis (OA). From being the standard treatment for knee OA in the late 1960’s, HTO has decreased substantially and represented less than 2 % of the primary knee reconstruction surgery in Sweden in 2012. HTO is mostly performed in younger and/or physically active patients and was the most commonly used surgical alternative before 2000. However since 2000, these patients are predominantly treated with total knee arthroplasty. For HTO, there is a lack of information regarding its use and outcome as well as patient selection as compared to knee arthroplasty surgery for which there is a national registration. Project and preliminary results: In a population based study of HTO in Sweden between 1998 and 2007 the majority of patients showed to be younger than 55 years of age and most of them men. The risk of revision for HTO to be converted to a knee arthroplasty was 30 % at 10 year. The risk of revision increased by increasing age and was significant higher in women than men. In 2013 national registration of knee osteotomy’s were started using the same methods that already are used for knee arthroplasty surgery in Sweden. Aim: To gain knowledge of knee osteotomy, the reasons for surgery, surgical methods and techniques used, complications and the patient perspective on outcome. Significance: The information will allow for comparison of the joint preserving knee osteotomy and the knee arthroplasty surgery and may origin in new treatment recommendations. annette.w-dahl@med.lu.se osteoporosis Risk Factors for Osteoporosis, Falls and Fractures with Special Reference to Physical Activity Magnus Karlsson Group members: Jack Besjakov, Caroline Karlson, Magnus Dencker, Björn Rosengren PhD students: Chrstian Buttazzoni, Maria Cöster, Fredrik Detter, Mehrsa Kehrad, Jesper Fritz, Marcus Cöster, Vasileios Lempesis Background: The accrual of bone mineral at growth and the age related bone loss influence who will develop osteoporosis. But also skeletal architecture influence bone strength and muscle function determine who will fall. Thus, it is imperative to determine regulation and suitable interventions that could modify each trait and identify risk individuals for fractures. Project and preliminary results: Secular changes of fractures are followed in regional and national registers. Bone and muscle trait evaluations are done in several population-based cohorts of children, adolescents, adults and elderly now followed 10-40 years by bone scanning, neuromuscular tests, anthropometry, fall frequency and fracture registration. Data has shown that hip fracture incidence has decreased while proximal humeral fractures have increased. The total number of fractures has increased. This has necessitated recalculations for future fracture burden. Daily physical training at growth enhances bone mass, bone size, reduces overweight and improves school performance. The benefits remain remains in adulthood. Daily physical activity should therefore be implemented in school. Clinical functional tests could identify fallers and should therefore be used in the health care. Aim: 1) study regulation and how to modify bone mass, skeletal architecture and soft tissues during growth and ageing; 2) evaluate risk factors and prognostic factors for osteoporosis, fall and fractures; 3) evaluate if benefits achieved by interventions remains in a long term perspective; 4) follow fracture epidemiology to improve projections for the future. Significance: Our studies increase the understanding of the pathophysiology of osteoporosis, improve our ability to target risk individuals and identify beneficial intervention strategies. magnus.karlsson@med.lu.se 33 osteoporosis 34 Effect of gene-environment interactions on bone phenotypes Fiona McGuigan Group members: Gaurav Garg, Maria Herlin, Lisa Jansson, Kristina Åkesson Background: Osteoporosis is a complex multifactorial disease regulated by genetic and environmental factors. The influence of genetic factors affects all aspects of the osteoporotic phenotype. However, osteoporosis is a polygenic condition and each gene confers a relatively small effect. Although our genetic makeup is unchanging, genes do not act uniformly throughout life, but respond to changes in internal or external triggers and environmental factors. Projects: In addition to the comprehensive studies of genes related to bone phenotypes I lead as senior researcher in Professor Åkesson’s group, I have several independent research projects. One project involves how the effect of specific genes can be modified by micro-nutrients and environmental factors that we are exposed to at sub-toxic levels on a daily basis. One such gene is Pirin, the transcriptional response of which has the potential for modulation by phytoestrogens and heavy metals through novel regulatory mechanisms. A second project revolves around a gene identified in a knockout mouse model, which affects both metabolism and bone in mice lacking the gene for an accessory protein involved in an important signaling pathway. The aim is to study the association between this gene and bone and body composition in young and elderly women to identify age-related regulatory effects. Aim: To explore the effects of genetic variation and gene-environment interactions on bone and body composition parameters. Significance: In terms of health and economic benefits, discovery of genes and gene-environment interactions affecting bone mass and fracture could lead to earlier diagnosis of osteoporosis. Exploring factors influencing bone activity at the cellular level also introduces the possibility of identifying novel targets for pharmacological treatment. fiona.mcguigan@med.lu.se osteoporosis Frailty, falls and fractures in the elderly, especially hip fractures Karl-Göran Thorngren Group members: Ami Hommel, Per Ola Norrman, Emma Turesson, Hans Wingstrand Background: Patients with hip fractures constitute one of the most resource consuming groups in health care. They consume one fourth of all bed days in orthopedic departments in Sweden. We have pioneered a treatment program with fracture repair (osteosynthesis), immediate direct weight bearing, and continued walking rehabilitation in the patient´s own home. During the last decades the risk of hip fracture has doubled in persons above 80 years of age and the total number of elderly in the population is increasing. We must therefore continue the improvement in the overall care, operation techniques and rehabilitation of the hip fracture patients, as well as in the prevention. Project: The research project contains epidemiological, prognostic, preventive and technical as well as rehabilitation and economical aspects of the hip fracture treatment. The project further contains optimized patient care including rapid handling to operation, prevention of infection and pressure ulcers, pain management and improved nutrition. It includes the nationwide quality register RIKSHÖFT (www.rikshoft.se). In a European Commision project called Standardized Audit of Hip Fractures in Europe (SAHFE), the Swedish national registration has spread internationally widely also outside Europe. Techniques used are : epidemiology, balance testing, patient inquires, skeletal scintimetry, bone densitometry, histology, MRI, CT, x-ray, ultrasound, pressure measurement. The project parts are listed below: • Fracture epidemiology, background factors, screening and prevention of sarcopenia, osteoporosis and falls. • Comparison of osteoporosis treatments • Comparison of operation methods • Investigation of femoral head blood circulation and vitality after femoral neck fracture, osteonecrosis • Acute fast track treatment from hip fracture to operation and rapid rehabilitation • Nutrition, pain relief and prevention of pressure ulcers and cognitive impairment in hip fracture patients • Bone transplantation, bone substitutes and healing improvement • Nationwide registration of quality in treatment of all Swedish patients with hip fractures and international comparisons 35 osteoporosis 36 Fig. 1 RIKSHÖFT 1988-90 100 90 Åter till ursprung 80 70 60 50 40 30 20 10 0 0 5 10 15 20 Medelvårdtid 25 30 Fig. 2 Fig. 1 and Fig. 2 show the relation between the mean hospitalization time in days and the percentage of the patients who could directly be discharged from the acute treating department to their original form of living. Each dot is a Swedish hospital. The resource consumption has obviously decreased considerably when year 2011 is compared with the period from the end of the 1980ies. Aim: To optimize the health of the hip fracture patients and help them to regain the same functional level as before the fracture, if possible improve further. Significance: The optimal treatment of this large and increasing group of elderly patients has great importance both for the individual and the society with its limited resources for health care. karl-goran.thorngren@med.lu.se osteoporosis Regulation of skeletal integrity: Genetic variation, risk factors and fracture kristina åkesson Group members: Anna-Karin Abelson, David Buchebner, Lisa Egund, My von Friesendorff, Gaurav Garg, Maria Herlin, Anna Holmberg, Lisa Jansson, Holger Luthman, Linnea Malmgren, Fiona McGuigan Background: Osteoporosis is a major public health concern, causing over 70 000 fragility fractures each year in Sweden, inflicting enormous costs on health care system and suffering on the patient. The current difficulty to offer patients an optimal treatment calls for further research on underlying mechanisms to find better intervention options. The pathogenesis of fragility fractures is complex, including environment, biomechanics, hormones, cellular regulatory mechanisms and genetics, the latter accounting for < 80 % of skeletal variance. We integrate basic and clinical research to evaluate in parallel the different aspects of this multifaceted interaction. Project: Our overall objective is to identify and evaluate internal and external risk factors for osteoporosis and fracture, as well as opportunities to influence these factors and ultimately contribute to better bone health and reduced risk of fragility fractures. We currently focus on delineating interactions between bone and skeletal muscle, adipose tissue, glucose metabolism, and inflammation. Of particular interest is our recent finding on the role of inflammatory genes and bone loss in elderly women, suggesting that low grade inflammation is involved in osteoporosis development with advancing age. In addition, we performed a genome-wide association study in our cohort of 75-year-old women, the results will provide further insight in to etiological pathways for fracture susceptibility. Aim: Our general aims are to: 1) Define external and internal risk factors for bone strength and fracture from young adults to the very elderly; 2) Identify genetic determinants influencing bone mass, bone loss and fracture at different ages; 3) Investigate underlying mechanisms influencing bone cell activity in humans and in animal models; 4) Evaluate and target clinical interventions based on evidence from research studies. Significance: By combining clinical, genetic and molecular studies, we contribute to a better understanding of the underlying mechanisms of osteoporosis and fragility fractures, which in the longer term can be used to achieve a personalized treatment for patients of various ages. Our results are implemented in the clinic, where they contribute to improved prediction and monitoring of fragility fracture risk. kristina.akesson@med.lu.se 37 osteoporosis 38 Treatment of distal radial fractures Magnus Tägil Group members: Antonio Abramo, Anna Kajsa Harding, Philippe Kopylov, Marcus Landgren, Ante Mrkonjic Background: The distal radial fracture is the most common fracture in the emergency clinic. The majority of the patients return to an almost normal function but about 10-15 % has substantial functional impairments at one year. The next years we intend to focus our research on these patients. Project and preliminary results: To determine the outcome and morbidity of the fracture in the population and validate the present treatment flow-chart, all distal radial fractures in Lund are followed prospectively. Since 2002, a subjective functional outcome score (DASH) is distributed to all patients, approximately 450 a year, at three and twelve months and the outcome is registered prospectively. The ten year register data was presented by PhD student Marcus Landgren at the EFORT meeting in 2013. Prospective studies and randomized series are added to the registration system. A randomized study is finished and under evaluation comparing the common volar plate to the best option in our previous study the fragment specific plates. Artificial bone substitutes have been tested in distal radial fractures. A follow up of a cohort with wrist fracture patients from the 90s having concomitant ligament injuries is investigated by Ante Mrkonjic in a PhD project. The next studies will focus on: 1) Propose better surgical solutions to the fractures that are very comminuted and intraarticular; 2) Improve the rehab training after distal radius fractures introducing a warning system for the PTs and occupational therapists in the primary care; 3) Identify and intervene early in patients with a history or ongoing pain problems at the time of the fracture; 4) Develop mobile health and internet based patient education and communication systems. Aim: To design a treatment protocol eliminating inferior results (DASH > 30) after a distal radius fracture. Significance: The proposed project will provide much needed evidence on the treatment of the most frequent but most often neglected fracture. Our proposed project will map the long term (>1 year) sequels of a DRF and in RCTs determine if the rising frequency of distal surgery is justified by superior results compared to older methods. magnus.tagil@med.lu.se pediatric orthopedics Prevention of hip dislocation and musculoskeletal deformities in children with cerebral palsy Gunnar Hägglund Group members: Henrik Lauge-Pedersen, Måns Persson Bunke, Elisabet Rodby Bousquet Background: CPUP, a cerebral palsy register and a health care programme for children with CP, was established in Southern Sweden in 1994 as a joint project between the pediatric orthopedics and the child rehabilitation units. The background was that we saw that a number of children with CP had developed hip dislocation and severe contractures. Project: The basis of CPUP is to identify all children with CP and offer them participation in the programme. CPUP includes a standardized follow-up of each child in terms of an assessment form. The children are assessed 1-2 times a year. The form includes information on the child’s gross and fine motor function, range of joint motion, use of orthoses and treatment. The programme also includes a standardised radiographic follow-up of the children’s hips and spine. All reports are administered via Internet. In 2005, a 10-year follow up showed that hip dislocation is preventable and also that there was a decrease in the number of children that developed severe contractures, windswept deformity and scoliosis. In 2005, CPUP received funding as a National Quality Register. Since 2007 all counties in Sweden have joined CPUP. CPUP became a National Quality Register in Norway in 2009, and in Denmark in 2013. It is also used on Island, Scotland and New South Wales. Since 2011 adults with CP are included in CPUP. This total population followed prospectively is used for several research projects. Aim: The aims are to: 1) prevent hip dislocation and severe contractures; 2) gain knowledge about CP; 3) improve the co-operation between the various professionals with respect to people with CP. Significance: This is a unique total population of people with CP followed prospectively in a standardised way. It has been used in three PhD-theses, it is used in four PhDprojects and more than 30 scientific papers based on the material has been published. gunnar.hagglund@med.lu.se, henriklaugepedersen@gmail.com, mans.persson-bunke@skane.se, elisabet.rodby_bousquet@med.lu.se 39 pediatric orthopedics 40 Radiostereometric analysis of skeletal growth in children Henrik Lauge-Pedersen Group members: Gunnar Hägglund Background: RSA(Radiostereometric analysis) as developed by Göran Selvik 1974 has been used extensively for orthopedic and radiographic research. The radiostereometric technique can be used to determine the three-dimensional dynamics of one skeletal structure relative another and therefore we found it suitable for investigating physeal growth. RSA permits accurate determination of longitudinal growth and rotational movements over short periods of time. This makes it possible to detect an incomplete physiodesis at a very early stage, and, if necessary, do a repeat operation before an angular deformity or inaccurate correction of LLD is of any clinical importance Project and preliminary results: After establishing the accuracy of the method on the first 10 children and following another 40 children closely with this technique, we now perform RSA on all physiodesis as a routine follow – up postoperatively and at 12 and 15 weeks postoperatively. Leg Length Discrepancy: Children with LLD are treated with percutaneous physiodesis and followed with RSA. The time perspective from physiodesis to physeal arrest is evaluated in relation to age and gender. A prospective study using eight plates instead of percutaneous physiodesis is carried out with the potential possibility of this method to be reversible and making correction of LLD a very accurate procedure. Extreme tall stature: Girls with predicted height >187cm (+3sd) and boys >200cm were earlier on occasionally treated with hormones by the paediatricians to reduce height at skeletal maturity. In corporation with the paediatricians we now treat some of these children with knee physiodesis and follow them with RSA. Fractures: Physeal fractures can result in partial or complete arrest of the physis leading to asymmetrical growth or growth arrest. Aim: To develope new methods for reversible treatment of LLD. To evaluate knee physiodesis as treatment for extreme tall staure. To improve RSA as a clinical tool for monitoring Physiodesis and fractures in relation to physes. Significance: To accomplish reversible physiodesis in patients with LLD would largely improve final results. Physiodesis is probably a much safer and more reliable method for treating extreme tall stature. Introducing RSA as a tool for follow up after physiodesis has made this procedure much safer. henrik.lauge-pedersen@med.lu.se, gunnar.hagglund@med.lu.se pediatric orthopedics Molecular imaging of the hip ­– exploring the path from DDH to OA Carl-Johan Tiderius Group members: Henrik Düppe, Daniel Wenger Background: In Malmö, screening for developmental dysplasia of the hip (DDH) has been in use since 1956. There is a general assumption that DDH in infancy is related to hip dysplasia in adulthood, but the link is far from understood. Hip dysplasia, characterized by a steep acetabulum with undercoverage of the femoral head, is a major cause of osteoarthritis (OA). In order to detect early signs of OA, sensitive diagnostic tools are needed. Delayed Gadolinium-Enhanced MRI of Cartilage (dGEMRIC) is a non-invasive technique to study joint cartilage integrity, in particular the cartilage glycosaminoglycan (GAG) content. The method has been developed by our group since the late 1990’s. In dGEMRIC, the negatively charged contrast medium (Gd-DTPA2-) is given intravenously and distributes in the cartilage in an inverse relationship to the amount of negatively charged GAGs, which are lost early in OA. Because Gd-DTPA2- shortens the longitudinal relaxation time (T1), T1 in the presence of Gd-DTPA2- (usually referred to as the dGEMRIC index) correlates to the cartilage GAG content. Figure 1: Hips with neonatal dislocation had a higher mean acetabular index than control hips in spite of early treatment. 41 pediatric orthopedics 42 Project and preliminary results: In a first radiographic evaluation of 246 children at age 1 year, the acetabular index (a measure of hip dysplasia) was significantly higher in neonatally dislocated hips than in stable hips (see figure). This indicates that a dislocatable hip does not normalize within one year, despite adequate diagnosis and treatment. Future studies will include examination of adult patients who were dysplastic at the 1-year radiographic control to evaluate any persisting radiographic abnormalities and early degenerative cartilage changes. The follow-up will include dGEMRIC, radiographic measures and clinical scores. Aim: The purpose of this project is a longitudinal follow-up of patients who were diagnosed with hip dislocation neonatally. Since early treatment has lowered the rate of late presenting DDH by factor 10, the patients diagnosed early probably constitute the majority of DDH patients. There is one Norwegian study indicating that even such patients have a more than doubled risk of later total hip replacement. However, they are a much less studied group than the more serious (but less common) late diagnosed DDH patients. Significance: OA is the most common joint disease with an economical burden for society that is second only to cardiovascular diseases. Hip dysplasia is a major cause of early hip OA. DDH is generally associated with hip dysplasia but very little is known about the longitudinal relationship. Our research group has a unique possibility to address this issue due to the DDH register since 1956, including radiographs, and a new sensitive method to detect early cartilage changes, dGEMRIC. carljohan.tiderius@skane.se, daniel.wenger@med.lu.se rheumatoid arthritis Orthopedic surgery on rheumatoid patients Anna Stefánsdóttir Group members: Johan Lindahl, Urban Rydholm Background: Despite improvements in the medical treatment of rheumatoid disorders, that have reduced the need for rheumatoid surgery, there are still many rheumatoid specific orthopedic problems to be addressed. The new biological antirheumatic drugs modulate the immune system, but it is still unclear if their use affects the incidence of infection in conjunction with orthopedic surgery. Project: a) Since 2006 patients receiving biological antirheumatic drugs have not paused their medication when undergoing orthopedic surgery at the rheumatoid unit of the department of orthopedics at Skåne University hospital. In a current study the incidence of deep infection after primary hip and knee arthroplasty among rheumatoid patients is to be revealed. b) The rheumatoid patient often has to undergo an arthrodesis of the subtalar joints. In the case of concomitant ankle disease ankle prosthesis can provide maintained movement and thereby improved function. A multi-center pilot study on a new ankle prosthesis is ongoing. c) Still, the survival of ankle prosthesis is inferior to hip- and knee prosthesis and there is a need for reliable methods for converting a prosthetic ankle joint to a fusion. Techniques are being developed and evaluated. Aim: a) To provide information on the safety of performing surgery with ongoing treatment with biological antirheumatic drugs. b) To contribute to the development of a better ankle prosthesis. c) To improve and evaluate the methods used to convert an ankle prosthesis to a fusion. Significance: Better understanding of the effect of anti-rheumatic medication in conjunction with surgery will increase patient safety. Improvements in surgical methods will give better results and decreased need for reoperations. anna.stefansdottir@med.lu,se, johan.lindahl@skane.se, urban.rydholm@med.lu.se 43 sports medicine 44 Knee injury & Osteoarthritis – outcomes, relation and treatment alternatives richard frobell Group members: Anders Hansson, Anders Isacsson, Ola Olsson Background: OA is the most common reason for musculoskeletal disability in the western world and accounts for a large proportion of the global disease burden. Little is known about the pathogenesis and there is currently no disease modifying treatment available. Knee injuries often occur in sports. The most severe knee injury is the anterior cruciate ligament (ACL) tear, resulting in instability and decreased activity level in the short term and increasing the risk knee osteoarthritis (OA) in the longer term. Meniscus tear is another example of knee injury where an increased risk of subsequent OA have been determined but for other types of knee trauma diagnoses (such as patellar dislocations and contusions), a corresponding increased risk is still to be determined. Projects: We focus our research on knee injuries: 1) The KANON-trial, a randomized controlled trial comparing the effect of surgical and non-surgical treatment strategies after ACL injury in young active adults. After two and five years, we could not identify differences in clinical outcome or the frequency of radiographic OA (5 years). We continue to follow this cohort over 10 and 15 years. 2) The Acute Knee injury Project (AKP), a prospective cohort study of more than 1 300 patients with acute knee injury. All patients received treatment in the normal clinical setting and a 5-7 year follow up is planned. 3) The EDEMA-cohort, a cohort of approximately 100 individuals with acute hemarthrosis where synovial fluid was aspirated within 25 days of injury and where MRI was performed within a week of aspiration. 4) The MOHAK-trial, an ongoing trial including patients with acute knee injury. Hemarthrosis is aspirated at the time of clinical assessment; serum samples and patient reported outcomes are collected at the same time. MRI is routinely performed within one week of injury. Aim: The general aim of our research is to identify injury related factors with possible relation to the long term outcome after injury. We cover the traumatic response of injury from a biology- (serum and synovial fluid samples), structural- (imaging) and patient perspective (patient reported outcomes) to identify early markers of OA and to identify targets of therapy to reduce the risk of OA development. Significance: Osteoarthritis is not primarily a lethal disease, but it causes severe pain, disability, and reduced quality of life for several hundred millions of people worldwide. With the increased number of aging people, a cure for this disease is urgently needed. richard.frobell@med.lu.se sports medicine Knee function and development of knee osteoarthritis in ACL injured patients Paul Neuman Background: Anterior cruciate ligament (ACL) injuries are common among young athletes involved in sports with knee pivoting and cutting movements. ACL injuries are functionally disabling with knee joint instability predisposing the knee to subsequent injuries and in the long-term to the early onset of osteoarthritis (OA). Risk factors for subsequent knee OA are clearly multifactorial. It has been estimated that OA develops in approximately 0-90 % of patients with ACL tears 10-20 years after the injury and so far there are no studies that prove that ACL reconstruction can minimize the future development of knee OA. According to the literature meniscal injuries and meniscectomies are well documented risk factors for the development of knee OA after ACL injury. ACL reconstruction, cartilage lesions together with bone marrow lesions, obesity, knee joint laxity, loss of knee motion, decreased muscle strength and inferior neuromuscular function need further documentation. Project and preliminary results: We evaluate ACL injured patients activity level, subjective knee function with self-administered questionnaires like the Knee Osteoarthritis Outcome Score (KOOS), knee function evaluated with manual examination, knee radiography, contrast-enhanced MRI (dGEMRIC) and biomarkers from synovial fluid and serum after the acute injury and at follow-up during 20 years. We show that ACL injured patients treated with early neuromuscular knee rehabilitation and activity modification without primary ACL reconstruction have a much lower prevalence of radiographic knee OA 16 years after injury than presented in the literature before. We also show that a concomitant meniscus injury treated with partial meniscectomy is the strongest risk factor for development of radiographic knee OA. ACL injured patients, ACL reconstructed or not, have an inferior knee cartilage quality compared with controls according to indirect measurement of cartilage content of glycosaminoglycan (GAG) by dGEMRIC, both 3 weeks and 2 years after the injury. The general decrease in cartilage quality in ACL-injured patients compared with references provide evidence for structural matrix GAG changes that seem more pronounced if a concomitant meniscal injury is present. The fact that post-traumatic OA commonly develops in ACL-injured patients, in particularly those with meniscectomy, suggests that decreased GAG content discerned by dGEMRIC may be an early biomarker for OA. Aim: To study ACL injured cohorts in an ongoing effort to characterize patients with a good or an inferior outcome, and to find risk factors for development of knee OA. Significance: Our results have direct clinical implications in counseling the ACL injured patient about different treatment options. paul.neuman@skane.se 45 tumors 46 Sarcoma Research Fredrik Vult von Steyern and Anders Rydholm Group members: Ana Carneiro2, Henryk Domanski3, Jacob Engellau2, Mats Jönsson2, Fredrik Mertens4, Mef Nilbert2, Pehr Rissler3, Emelie Styring1 Background: Soft tissue sarcoma is a heterogenous group of tumours with some 50 histopathologic types. Two thirds of the tumours are highly malignant and one third of the patients die because of metastatic disease. Novel prognostic tools, treatment-predictive markers and development of targeted therapies are needed for improved survival. The management of soft tissue sarcoma patients in southern Sweden is since long centralized to the Sarcoma Group in Lund. A large data base on tumour characteristics, treatment and outcome and a tissue bank comprising close to 1000 patients have been created. Project and preliminary results: We have recently 1) Validated the prognostic importance of invasive growth pattern, which is now included in the high-risk criteria in the Scandinavian Sarcoma Group prognostic SING system. 2) Described the changing clinical presentation of angiosarcoma after breast cancer treatment, reported results indicating that surgical excision of all irradiated skin and extrathoracic soft tissue may improve prognosis in secondary angiosarcoma and identified differences in gene expression patterns between primary and secoondary angiosarcomas. 3) Demonstrated that simple guidelines combined with an open access tumour clinic are efficient for referral and centralisation of soft tissue sarcomas. 4) Achieved data showing that among small (≤ 5 cm) soft tissue sarcomas, which in general have a good prognosis, tumours with high risk of metastasis can be identified by the presence of tumour necrosis and vascular invasion. Aim: We apply a translational approach to study genetic and molecular profiles, validate gene/protein expression patterns in large clinical materials, link novel markers to prognosis, and apply the findings for refined diagnostics and prognostics in soft tissue sarcomas. The projects are carried out in collaboration between the Departments of Orthopedics1, Oncology2, Pathology3 and Clinical Genetics4. International collaborations include groups in Scandinavia within the Scandinavian Sarcoma Group and The Netherlands. Significance: Soft tissue sarcomas are rare tumours where the majority are of high malignancy grade. There are many different histotypes with different genetic aberrations and clinical behaviour. Adjuvant, and sometimes neoadjuvant, treatment (chemotherapy and radiotherapy) is considered when the tumour is regarded as a ”high-risk tumour”. However, the effect of chemotherapy is uncertain and different histotypes are more or less prone to respond to such treatment. Better and more precise diagnostics and prognostics is needed in order to improve survival and outcome for patients with soft tissue sarcomas. fredrik.vult_von_steyern@med.lu.se, anders.rydholm@med.lu.se 47 Scientific papers 2013 Department of Orthopedics, Lund University This list includes original papers, review papers and book chapters (but not abstracts) authored by members of the staff and printed in 2013. Alriksson-Schmidt A, Thibadeau JK, Swanson ME , Marcus D, Carris KL, Siffel C, Ward E. The Natural History of Spina Bifida in Children Pilot Project. JMIR Research Protocols 2013 Jan 25;2(1):e2. Andersson ML, Svensson B, Petersson IF, Hafström I, Albertsson K, Forslind K, Heinegård D, Saxne T. Early increase in serum-COMP is associated with joint damage progression over the first five years in patients with rheumatoid arthritis. BMC Musculoskeletal Disorders 2013 Aug 2;14:229. doi: 10.1186/1471-2474-14-229. Andréasson K, Saxne T, Bergknut C, Hesselstrand R, Englund M. Prevalence and incidence of systemic sclerosis in southern Sweden: population-based data with case ascertainment using the 1980 ARA criteria and the proposed ACR-EULAR classification criteria. Annals of the Rheumatic Diseases 2013 Jul 29. doi: 10.1136/annrheumdis-2013-203618. [Epub ahead of print] Arbajian E, Magnusson L, Mertens F, Domanski HA, Vult von Steyern F, Nord KH. A novel GTF2I/NCOA2 fusion gene emphasizes the role of NCOA2 in soft tissue angiofibroma development. Genes Chromosomes Cancer. 2013 Mar;52(3):330-1 Atroshi I, Flondell M, Hofer M, Ranstam J. Methylprednisolone injections for the carpal tunnel syndrome: a randomized, placebo-controlled trial. Annals of Internal Medicine 2013 Sep 3;159(5):309-17. Bhat S, Lidgren L, Kumar A. In vitro neo-cartilage formation on a three-dimensional composite polymeric cryogel matrix. Macromolecular Bioscience 2013 Jul;13(7):827-37 Bloecker K, Guermazi A, Wirth W, Benichou O, Kwoh CK, Hunter DJ, Englund M, Resch H, Eckstein F. Tibial coverage, meniscus position, size and damage in knees discordant for joint space narrowing – data from the Osteoarthritis Initiative. Osteoarthritis Cartilage 2013, 21(3):419-427. Bosemark P, Isaksson H, McDonald MM, Little DG, Tägil M. Augmentation of autologous bone graft by a combination of bone morphogenic protein and bisphosphonate increased both callus volume and strength. Acta Orthopaedica 2013, 84 (1):106-111. 48 Brogren E, Wagner P, Petranek M, Atroshi A. Distal Radius Malunion Increases Risk of Persistent Disability 2 Years After Fracture: A Prospective Cohort Study. Clinical Orthopaedics and Related Research 2013, 471(5):1691-1697. Buttazzoni C, Rosengren EB, Tveit M, Landin L, Nilsson J-Å, Karlsson M. Does a Childhood Fracture Predicts Low Bone Mass In Young Adulthood – A 27-Year Prospective Controlled Study. Journal of Bone and Mineral Research 2013 Feb;28(2):351-9. Buttazzoni C, Rosengren B, Tveit M, Landin L, Nilsson J-Å, Karlsson M. A Pediatric Bone Mass Scan has Low Ability to Predict the Level of Bone Mass in Adulthood – A 28-Year Prospective Observational Study in 214 Children. Calcified Tissue International. [Epub ahead of print 2013 Oct 8]. Callréus M, McGuigan F, Åkesson K. Adverse Effects of Smoking on Peak Bone Mass May Be Attenuated by Higher Body Mass Index in Young Female Smokers. Calcified Tissue International 2013;93;517-25 Callréus M, McGuigan F, Åkesson K. Birth Weight is More Important for Peak Bone Mineral Content than for Bone Density: The PEAK-25 Study of 1,061 Young Adult Women. Osteoporosis International 2013 Apr;24(4):1347-55. Callréus M, McGuigan F, Åkesson K . Country-specific young-adult DXA reference data are warranted for T-score calculations in women: Data from the PEAK-25 cohort. Journal of Clinical Densitometry 2013.03.008. [Epub ahead of print] Carstens A, Kirberger RM, Velleman M, Dahlberg LE, Fletcher L, Lammentausta E. Feasibility for mapping cartilage t1 relaxation times in the distal metacarpus3/metatarsus3 of thoroughbred racehorses using delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC): normal cadaver study. Veterinary Radiology & Ultrasound. 2013;54(4):365-72. Carstens A, Kirberger RM, Dahlberg LE, Prozesky L, Fletcher L, Lammentausta E. Validation of delayed gadolinium-enhanced magnetic resonance imaging of cartilage and t2 mapping for quantifying distal metacarpus/metatarsus cartilage thickness in thoroughbred racehorses. Veterinary Radiology & Ultrasound. 2013;54(2):139-48. Chandran M, Akesson K. Secondary fracture prevention: plucking the low hanging fruit. Annals Academy of Medicine Singapore. 2013 Oct;42(10):541-4. Chockalingam PS, Glasson SS, Lohmander S. Tenascin-C levels in synovial fluid are elevated after injury to the human and canine joint and correlate with markers of inflammation and matrix degradation. Osteoarthritis Cartilage 2013, 21(2):339-345. 49 Cosman F, Ruffing J, Zion M, Uhorchak J, Ralston S, Tendy S, McGuigan F, Lindsay R, Nieves J. Determinants of Stress Fracture Risk in United States Military Academy Cadets. Bone 2013 Aug;55(2):359-66. Chounti A, Hägglund G, Wagner P, Westbom L. Sex differences in cerebral palsy difference and functional ability: a total population study. Acta Paediatrica 2013: 102(7): 712-7. Cotofana S, Wyman BT, Benichou O, Dreher D, Nevitt M, Gardiner J, Wirth W, Hitzl W, Kwoh CK, Eckstein F. Relationship between knee pain and the presence, location, size and phenotype of femorotibial denuded areas of subchondral bone as visualized by MRI. Osteoarthritis and Cartilage, 2013, 21, 9, 1214-22. Cöster M, Magnusson H, Brudin L, Rosengren B, Karlsson M. Bone mass and anthropometry in patients with osteoarthritis of the foot and ankle. Foot and Ankle Surgery [Epub 2013 Nov 10]. Cöster M, Bremander A, Rosengren B, Magnusson H, Carlsson Å, Karlsson M. Validity, Reliability and Responsiveness of the Self-reported Foot and Ankle Score (SEFAS) in Patients with Forefoot, Hindfoot and Ankle Disorders. Acta Orthopaedica doi: 10.3109/17453674.2014.889979. [Epub ahead of print]. Daly R, Alwis G, Rosengren B, Ahlborg H, Sernbo I, Karlsson M. Gender specific age-related changes in bone density, muscle strength and functional performance in the elderly: a-10 year prospective population-based study. BMC Geriatrics 2013 Jul6;13(1):71. Dencker M, Tanha T, Wollmer P, Karlsson M, Andersen LB, Thorsson O. Tracking of physical activity with accelerometers over a two-years time period. Longitudinal findings of physical activity patterns in young children. Journal of Physical Activity & Health 2013;10(2):241-248. Dencker M, Wollmer P, Karlsson M, Andersen LB, Thorsson O. Aerobic capacity related to cardiac size in young children. The Journal of Sports Medicine and Physical Fitness 2013;Feb;53(1):42-7. Dencker M, Wollmer P, Karlsson M, Andersen LB, Thorsson O. Aerobic capacity related to cardiac size in young children. The Journal of Sports Medicine and Physical Fitness. 2013 Feb;53(1):42-7. Dencker M, Wollmer P, Karlsson M, Andersen LB, Thorsson O. Cardiac size related to aerobic capacity in young children. The Journal of Sports Medicine and Physical Fitness 2013;53(1):42-7. Detter F, Rosengren B, Dencker M, Nilsson J-Å, Karlsson M. A 5-Year Exercise Program in Pre- and Peri-Pubertal Children Improves Bone Mass and Bone Size without Affecting Fracture Risk. Calcified Tissue International 2013;Apr;92(4):385-93. 50 Detter F, Rosengren BE, Dencker M, Lorentzon M, Nilsson JA, Karlsson M. A Six-Year Exercise Program Improves Skeletal Traits without Affecting Fracture Risk – a Prospective Controlled Study in 2621 Children. Journal of Bone and Mineral Research. [Epub ahead of print 2013] Dunbar MJ, Richardson G, Robertsson O. I can’t get no satisfaction after my total knee replacement: rhymes and reasons. Bone & Joint Journal 2013 Nov;95-B(11 Suppl A):148-52. Review Elgzyri T, Larsson J, Thörne J, Eriksson KF, Apelqvist J. Outcome of ischemic foot ulcer in diabetic patients who had no invasive vascular intervention. European Journal of Vascular and Endovascular Surgery. 2013 Jul;46(1):110-7. doi: 10.1016/j.ejvs.2013.04.013. Epub 2013 May 1. Ericsson I, Karlsson M. Motor skills and school performance in children with daily physical education in school – a 9-year intervention study. Scandinavian Journal of Medicine and Science in Sports doi: 10.1111/j.1600-0838.2012.01458. [Epub 2013 Apr 9]. Eriksson A, Movérare-Skrtic S, Ljunggren Ö, Karlsson M, Mellström D, Ohlsson C. High Sensitive CRP is an independent risk factor for all fractures and vertebral fractrues in elderly men: The MrOS Sweden Study. Journal of Bone and Mineral Research. doi: 10.1002/ jbmr.2037. [Epub ahead of print 2013 Oct 20] Ericsson Y, Roos E, Frobell R. Lower extremity performance following ACL rehabilitation in the KANON-trial: impact of reconstruction and predictive value at 2 and 5 years. British Journal of Sports Medicine 2013; 47(15): 980-5. Eriksson JK1, Neovius M, Bratt J, Petersson IF, van Vollenhoven RF, Geborek P, Ernestam S. Biological vs. conventional combination treatment and work loss in early rheumatoid arthritis: a randomized trial. JAMA Internal Medicine 2013 Aug 12;173(15):1407-14. doi: 10.1001/jamainternmed.2013.7801 Exarchou S, Johnel-Redlund I, Karlsson M, Mellström D, Ohlsson C, Turesson C, Kristensen LE, Jacobsson LT. The prevalence of moderate to severe radiographically verified sacroiliitis and the correlation with health status in elderly Swedish men – The MrOS Study. BMC Musculoskeletal Disorders 2013 Dec 13;14(1):352.doi: 10.1186/1471-2474-14-352. Felson DT, Niu J, Gross KD, Englund M, Sharma L, Cooke TD, Guermazi A, Roemer FW, Segal N, Goggins JM. Valgus malalignment is a risk factor for lateral knee osteoarthritis incidence and progression findings from the Multicenter Osteoarthritis Study and the osteoarthritis initiative. Arthritis Rheumatology 2013, 65(2):355-362. Fernandes L, Hagen KB, Bijlsma JW, Andreassen O, Christensen P, Conaghan PG, Doherty 51 M, Geenen R, Hammond A, Kjeken I, Lohmander LS, Lund H, Mallen CD, Nava T, Oliver S, Pavelka K, Pitsillidou I, da Silva JA, de la Torre J, Zanoli G, Vliet Vlieland TP; European League Against Rheumatism (EULAR). EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis. Annals of the Rheumatic Diseases. 2013 Jul;72(7):1125-35. doi: 10.1136/annrheumdis-2012-202745. Epub 2013 Apr 17. Frobell R, Roos HP, Roos EM, Roemer FW, Ranstam J, Lohmander LS. Treatment for acute anterior cruciate ligament tear: five year outcome of randomised trial. BMJ (Clinical Research ed.) 2013, 346, f232. Frobell RB, Roos HP, Roos EM, Roemer FW, Ranstam J, Lohmander LS. Republished research: Treatment for acute anterior cruciate ligament tear: five year outcome of randomised trial. British Journal of Sports Medicine 2013, Apr, 47(6):373. Frobell R, Börjesson M. Welcome to the Swedish theme issue: putting exercise into sports medicine. British Journal of Sports Medicine. 2013 Oct;47(15):935-6. Ghanei I, Rosengren B., Hasserius R, Mellström D, Ohlsson C, Ljunggren Ö, Karlsson M. The prevalence and severity of low back pain and associated symptoms in 3009 old men. European Spine Journal. [Epub ahead of print 2013 Dec 27.] Grauers A, Danielsson A, Karlsson M, Ohlin A, Gerdhem P. Family history and its association to curve size and treatment in 1463 patients with idiopathic scoliosis. European Spine Journal 2013 Nov;22(11):2421-6. Gudbergsen H, Lohmander LS, Jones G, Christensen R, Bartels EM, Danneskiold-Samsoe B Bliddal H, Boesen M.Correlations between radiographic assessments and MRI features of knee osteoarthritis – a cross-sectional study. Osteoarthritis Cartilage 2013, 21(4):535-543 Guermazi A, Hayashi D, Jarraya M, Roemer FW, Zhang Y, Niu J, Crema MD, Englund M, Lynch JA, Nevitt MC. Medial Posterior Meniscal Root Tears Are Associated with Development or Worsening of Medial Tibiofemoral Cartilage Damage: The Multicenter Osteoarthritis Study. Radiology 2013, May 21. Hagel S, Petersson IF, Bremander A, Lindqvist E, Bergknut C, Englund M. Trends in the first decade of 21st century healthcare utilisation in a rheumatoid arthritis cohort compared with the general population. Annals of the Rheumatic Diseases. 2013 Jul;72(7):1212-6. doi: 10.1136/annrheumdis-2012-202571. Epub 2012 Dec 8. Haglund E, Bremander A, Bergman S, Jacobsson L, Petersson I. Work productivity in a population-based cohort of patients with spondyloarthritis. Rheumatology 2013; 52(9): 1708-14. 52 Hansen E, Belden K, Silibovsky R, Vogt M, Arnold WV, Bicanic G, Bini SA, Catani F, Chen J, Ghazavi MT, Godefroy KM, Holham P, Hosseinzadeh H, Kim KI, Kirketerp-Møller K, Lidgren L, Lin JH, Lonner JH, Moore CC, Papagelopoulos P, Poultsides L, Randall RL, Roslund B, Saleh K, Salmon JV, Schwarz EM, Stuyck J, Dahl AW, Yamada K. Perioperative Antibiotics. Journal of Arthroplasty. 2013 Dec 16. pii: S0883-5403(13)00711-0. doi: 10.1016/j.arth.2013.09.030. [Epub ahead of print].304. Hansén Nord K, Macchia G, Tayebwa J, Nilsson J, Vult von Steyern F, Brosjö O, Mandahl N, Mertens F. Integrative Genome and Transcriptome Analyses Reveal Two Distinct Types of Ring Chromosome in Soft Tissue Sarcomas. Human molecular genetics 2013; Sep 26. Hare KB1, Lohmander LS, Christensen R, Roos EM. Arthroscopic partial meniscectomy in middle-aged patients with mild or no knee osteoarthritis: a protocol for a double-blind, randomized sham-controlled multi-centre trial. BMC Musculoskeletal Disorder 2013 Feb 25;14:71. doi: 10.1186/1471-2474-14-71. Harsten A, Kehlet H, Toksvig-Larsen S. Recovery after total intravenous general anaesthesia or spinal anaesthesia for total knee arthroplasty: a randomized trial. British journal of anaesthesia 2013, May 21. Hessle L, Stordalen GA, Wenglén C, Petzold C, Tanner KE, Brorson SH, Baekkevold ES, Önnerfjord P, Reinholt FP, Heinegård D. The Skeletal Phenotype of Chondroadherin Deficient Mice, PLOS One, Vol. 8(6), paper e63080. doi:10.1371/journal.pone.0063080, 2013. Hosseininia S, Lindberg LR, Dahlberg LE. Cartilage collagen damage in hip osteoarthritis similar to that seen in knee osteoarthritis; a case-control study of relationship between collagen, glycosaminoglycan and cartilage swelling. BMC Musculoskeletal Disorder 2013;14(1):1-7. Hubertsson J, Petersson IF, Thorstensson CA, Englund M. Risk of sick leave and disability pension in working-age women and men with knee osteoarthritis. Annals of the Rheumatic Diseases 2013; 72: 401-5. Hägglund G. Positive development with follow up program for children with cerebral palsy. In Process Citation. Läkartidningen 2013, 110(15):765-766. Hägglund M, Atroshi I, Wagner P, Walden M. Superior compliance with a neuromuscular training programme is associated with fewer ACL injuries and fewer acute knee injuries in female adolescent football players: secondary analysis of an RCT. British Journal of Sports Medicine, 2013; 47(15): 974-9. Julkunen P, Wilson W, Isaksson H, Jurevlin J´S, Herzog W, Korhonen RK. A review of the combination of experimental measurements and fibril-reinforced modeling for investigation 53 of articular cartilage and chondrocyte response to loading. Computational and Mathematical Methods in Medicine 2013. 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