Research 2013

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
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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
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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
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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
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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
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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.
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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.
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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
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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.
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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
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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
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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
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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.
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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.
[email protected], [email protected], [email protected]
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Arthroplasty
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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.
[email protected]
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.
[email protected]
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back
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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.
[email protected], [email protected], [email protected],
[email protected], [email protected], [email protected]
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.
[email protected], [email protected], [email protected],
[email protected], [email protected]
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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.
[email protected]
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.
[email protected], [email protected] 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.
[email protected], [email protected], [email protected],
[email protected]
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.
[email protected] , [email protected], [email protected]
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.
[email protected]
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.
[email protected]
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.
[email protected]
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.
[email protected]
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.
[email protected]
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.
[email protected], [email protected], [email protected],
[email protected], [email protected]
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.
[email protected]
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.
[email protected]
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.
[email protected]
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.
[email protected]
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.
[email protected]u.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.
[email protected]
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.
[email protected], [email protected],
[email protected], [email protected]
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.
[email protected], [email protected]
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.
[email protected], [email protected]
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.
[email protected],se, [email protected]kane.se, [email protected]
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.
[email protected]
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.
[email protected]
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.
[email protected], [email protected]
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.
Juréus J, Lindstrand A, Geijer M, Robertsson O, Tägil M. The natural course of spontaneous
osteonecrosis of the knee (SPONK). Acta Orthopaedica 2013; 2013; 84(4): 410-4.
Jöud A, Stjerna J, Malmström EM, Westergren H, Petersson IF, Englund M. Healthcare
consultation and sick leave before and after neck injury: a cohort study with matched
population-based references. BMJ Open. 2013 Aug 30;3(8):e003172. doi: 10.1136/
bmjopen-2013-003172.
Karlsson M, Dahan R, Magnusson H, Nyquist F, Rosengren B. Soccer and gender effect on
groin pain. German Journal of Sports Medicine [Epub 2013 Nov 5].
Karlsson M, Magnusson H, vonSchewelow T, Rosengren B. Prevention of falls in the elderly
– a review. Osteoporosis International 2013 Mar;24(3):747-62.
Karlsson M, vonSchewelow T, Karlsson C, Cöster M, Rosengren B. Prevention of fall in
elderly – a review. Scandinavian Journal of Public Health 2013;41 (5):442 – 454.
Karlsson M, Magnusson H, Cöster M, von Schewelov, Karlsson, Rosengren B. Patients With
Hip Osteoarthritis Have a Phenotype With High Bone Mass and Low Lean Body Mass.
Clinical Orthopaedics and Related Research (CORR) doi:10.1007/s11999-013-3395-7.
[Epub 2013 Nov 26].
Karlsson JA, Neovius M, Nilsson J-Å, Petersson IF, Bratt J, van Vollenhoven RF, Ernestam
S, Geborek P. Addition of infliximab compared with addition of sulfasalazine and
hydroxychloroquine to methotrexate in early rheumatoid arthritis: 2-year quality-of-life
results of the randomised, controlled SWEFOT trial. Annals of the Rheumatic Diseases 2013;
72: 1927-33.
Keyak JH, Sigurdsson S, Karlsdottir GS, Oskarsdottir D, Sigmarsdottir A, Kornak J, Harris
TB, Sigurdsson G, Jönsson B, Siggeirsdottir K. Effect of finite element model loading
condition on fracture risk assessment in men and women: The AGES-Reykjavik study. Bone,
2013; 57(1): 18-29.
Khayyeri H, Prendergast P, Isaksson H. Review: Corroboration of theories for
mechanoregulated stem cell differentiation. Computer Methods in Biomechanics and
Biomedical Engineering 2013.
Kiernan S, Hermann KL, Wagner P, Ryd L, Flivik G. The importance of adequate stem
anteversion for rotational stability in cemented total hip replacement: A radiostereometric
study with ten-year follow-up. Journal of Bone & Joint Surgery 2013, 95-B(1):23-30.
54
Kobelt G. Health economic evaluation: why? When? How? Expert Expert Review of
Neurotherapeutics 2013 Dec;13(12 Suppl):33-7. doi: 10.1586/14737175.2013.865872.
Kobrina Y, Rieppo L, Saarakkala S, Pulkkinen HJ, Tiitu V, Valonen P, Kiviranta I, Jurevlin JS,
Isaksson H. Cluster analysis of infrared spectra can differentiate intact and repaired articular
cartilage. Osteoarthritis Cartilage 2013, 21(3):462-469.
Koller DL, Zheng HF, Karasik D, Yerges-Armstrong L, Liu CT, McGuigan FE, Kemp JP,
Giroux S, Lai D, Edenberg HJ, Peacock M, Czerwinski S, McMahon G, St Pourcain B,
Timpson NJ, Lawlo DA, Evans DM, Towne B, Blangero J, Carless M, Kammerer C, KieL
DP, and Foroud T. Meta-analysis of Genome-wide Studies identifies Wnt16 and ESR1 SNPs
associated with bone mineral density in Premenopausal Women. Journal of Bone and Mineral
Research, 2013 Mar;28(3):547-58
Kristensen LE, Englund M, Neovius M, Askling J, Jacobsson LTH, Petersson IF. Long-term
work disability in patients with psoriatic arthritis treated with anti-tumour necrosis factor: a
population-based regional Swedish cohort study. Annals of the Rheumatic Diseases 2013; 72:
1675-9.
Larsson S, Lohmander S, Struglics S. An ARGS-aggrecan assay for analysis in blood and
synovial fluid. Osteoarthritis and Cartilage 2013; Dec. 18.
Lauge Pedersen H, Hägglund G. Eight plates should not be used for treating leg length
discrepancy. Journal of Children’s Orthopaedics 2013;7:285-288.
Lauge-Pedersen H. In process citation. Läkartidningen 2013, 110 (15):748-750.
Lazarinis S, Lidgren L, Stefánsdóttir A, W-Dahl A. Consensus document on prosthetic joint
infections. Acta Orthopaedica 2013; 84(6): 507-8.
Lazarinis S, Lidgren L, Stefánsdóttir A, W-Dahl A. Perioperative Antibiotics. Workgroup3.
In: Proceedings of the International Consensus Meeting on Periprosthetic Joint Infecion.
Chairs: Javad Parvizi, MD, FRCS, Thorsten Gehrke, MD. ISBN: 978-1-57400-147-1,
pp29-82, 2013.
Leonardsson O, Rolfson O, Hommel A, Garellick G, Åkesson K, Rogmark C. Patientreported outcome after displaced femoral neck fracture. A national survey of 4467 patients.
Journal of Bone and Joint Surgery, American Volume 2013; 95-A: 1693-9.
Lewerin C, Nilsson-Ehle H, Jacobsson S, Karlsson M, Ohlsson C, Mellström C.
Holotranscobalamin is not influenced by decreased renal function in elderly men: the MrOS
Sweden study. The MrOs study. Annals of Clinical Biochemistry.2013 Nov;50(Pt 6):585-94.
55
Ley CJ, Ekman S, Dahlberg LE, Björnsdóttir S, Hansson K. Evaluation of osteochondral
sample collection guided by computed tomography and magnetic resonance imaging for
early detection of osteoarthritis in centrodistal joints of young Icelandic horses. AJVR,
2013;74(6):874-87.
Leonardsson O, Rolfson O, Hommel A, Garellick G, Åkesson K, Rogmark C.
Patient-reported Outcome after Displaced Femoral Neck Fracture. A National Survey of
4,467 Patients. Journal of Bone and Joint Surgery, American Volume, 2013
Sep 18;95(18):1693-1699
Lewerin C, Nilsson-Ehle H, Jacobsson S, Johansson H, Sundh V, Karlsson M, Ljunggren Ö,
Lorentzon M, Kanis J, Cummings S, Ohlsson C, Mellström D. Low holotranscobalamin and
cobalamins predict incident fractures in elderly men – The MrOS Sweden. Osteoporosis Int.
[Epub 2013 Oct 16].
Lidgren L, Alriksson-Schmidt A, Ranstam J. ArthroplastyWatch--beyond borders, beyond
compliance. BMJ (Clinical Research ed.), 2013, Feb 19, 346, f1013.
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. The Journal of Arthroplasty. 2013 Dec 16. pii: S0883-5403(13)00711-0. doi:
10.1016/j.arth.2013.09.030. [Epub ahead of print].
Lind L, Elmståhl S, Bergman E, Englund E, Lindberg E, Michaelsson K, Nilsson PM,
Sundstrom J. EpiHealth: a large population-based cohort study for investigation of
gene-lifestyle interactions in the pathogenesis of common diseases. European Journal of
Epidemiology 2013, 28(2): 189-197
Lohmander S, Roos H, Roos E, Ranstam J, Frobell R. Authors’ response to editorial by Levy
and colleagues on treating ACL injuries in young moderately active adults. BMJ (Clinical
Research ed.) 2013, 346, April,10, f2082.
Löfgren B, Daly R, Nilsson J-Å, Dencker M, Karlsson M. An Increase in School-Based
Physical Education Increases Muscle Strength in Children. Medicine & Science in Sports &
Exercise 2013;May;45(5):997-1003.
Malo M, Rohrbach D, Isaksson H, Töyräs J, Jurvelin JS, Tamminen IS, Kröger H, Raum K.
Longitudinal elastic properties and porosity of cortical bone tissue vary with age in human
proximal femur. Bone 2013, 53(2):451-458.
Mathavan N, Bosemark P, Isaksson H, Tägil M. Investigating the synergistic efficacy of BMP7 and Zoledronate on bone allografts using an open rat osteotomy model. Bone. 2013 Jul 8.
pii: S8756-3282(13)00249-4. doi: 10.1016/j.bone.2013.06.030. [Epub ahead of print]
56
Meesters J, Hagel S, Klokkerud M, Stovgaard I, Bremander A, Grotle M, Hørslev-Petersen K,
Petersson IF, Hagen KB, Pont W, Vlieland TV. Goal-setting in multidisciplinary team care for
patients with rheumatoid arthritis: an international multi-center evaluation of the contents
using the International Classification of Functioning, Disability and Health as a reference.
Journal of Rehabilitation Medicine 2013;45(9):888-99. doi: 10.2340/16501977-1191.
Mellström D, Haghsheno M, Behre CJ, Damber JE, Johansson H, Karlsson M, Ljunggren Ö,
Peeker R; Barrett-Connor E, Waern E, Sundh V, Smith U, Ohlsson C, Hammarsten J. Low
25-OH Vitamin D level is associated with benign prostatic hyperplasia. Journal of Urology
2013 Feb 8. doi:pii: S0022-5347(13)00252-8.
Misko TP, Radabaugh MR, Highkin M, Abrams M, Friese O, Gallavan R, Bramson C, Hellio
Le Graverand M, Lohmander LS, Roman D. Characterization of nitrotyrosine as a biomarker
for arthritis and joint injury. Osteoarthritis Cartilage 2013, 21(1):151-156.
Mohajeri A, Tayebwa J, Collin A, Nilsson J, Magnusson L, von Steyern FV, Brosjö O,
Domanski HA, Larsson O, Sciot R, Debiec-Rychter M, Hornick JL, Mandahl N, Nord
KH, Mertens F. Comprehensive genetic analysis identifies a pathognomonic NAB2/STAT6
fusion gene, nonrandom secondary genomic imbalances, and a characteristic gene expression
profile in solitary fibrous tumor. Genes Chromosomes Cancer. 2013 Jun 12. doi: 10.1002/
gcc.22083. [Epub ahead of print]
Moayyeri A, Kaptoge S, Mellström D, Ljunggren Ö, Karlsson M, Ohlsson C, Åkesson K,
MgGuigan F, Reeves J et al. Genetic determinants of heel bone properties: Genome-wide
association meta-analysis and replication in the GEFOS/GENOMOS consortium. Human
Molecular Genetics [Epub ahead of print 2013]
Neuman P, Owman H, Müller G, Englund M, Tiderius CJ, Dahlberg LE. Knee cartilage
assessment with MRI (dGEMRIC) and subjective knee function in ACL injured copers: a
cohort study with a 20 year follow-up 2014 Jan;22(1):84-90. doi: 10.1016/j. ca.2013.10.006.
Epub 2013 Nov 1.
Nilsson M, Sundh D, Ohlsson C, Karlsson M, Mellström D, Lorentzon M. Exercise During
Growth and Young Adulthood is Independently Associated with Cortical Bone Size and
Strength in Old Swedish Men. Journal of Bone and Mineral Research. [Epub ahead of print
2013].
Nilsson G, Eneroth M, Ekdahl C. The Swedish version of OMAS is a reliable and valid
outcome measure for patients with ankle fractures. BMC Musculoskeletal Disorder 2013,
Mars 25, 14:109.
Nilsson M, Zheng MH, Tägil M. The composite of hydroxyapatite and calcium sulphate: a
review of preclinical evaluation and clinical applications. Expert Reviews 2013; 675-84. doi.
10.1586/17434440.2013.827529.
57
Nord KH, Nilsson J, Arbajian E, Vult von Steyern F, Brosjö O, Cleton-Jansen AM, Szuhai
K, Hogendoorn PC. Recurrent chromosome 22 deletions in osteoblastoma affect inhibitors
of the Wnt/beta-catenin signaling pathway. PLOS One. 2013 Nov 13;8(11):e80725. doi:
10.1371/journal.pone.0080725.
Norman P, Iyengar S, Svensson I, Flivik G. Fatigue Fracture in Dual Modular Revision Total
Hip Arthroplasty Stems: Failure Analysis and Computed Tomography Diagnostics in Two
Cases. Journal of Arthroplasty, 2013, Oct 11
Oei L, Estrada K, Duncan E, Karlsson M, Ljunggren Ö, Mellström D, Ohlsson C, Ralston
S, Kiel D, Rivadeneira F et al. Genome-wide Association Study for Radiographic Vertebral
Fractures: a potential role for the 16q24 BMD locus versus lessons learned from challenging
phenotype definition. Bone 2013 Oct 25. pii: S8756-3282(13)00425-0. doi: 10.1016/j.
bone.2013.10.015.
Oiestad BE, Osterås N, Frobell R, Grotle M, Brøgger H, Risberg MA.,Efficacy of strength
and aerobic exercise on patient‐reported outcomes and structural changes in patients with
knee osteoarthritis: study protocol for a randomized controlled trial. BMC Musculoskeletal
Disorders 2013 Sep 12;14(1):266
Olerud F, Olsson C, Flivik G. Comparison of refobacin bone cement and Palacos with
Gentamicin in total hip arthroplasty: an RSA study with two years follow-up. Hip
international: the journal of clinical and experimental research on hip pathology and therapy
2013; Sep 20.
Olofsson TO, Petersson IF, Eriksson JK, Englund M, Simard, JF, Nilsson JÅ, Geborek P,
Jacobsson LT, Askling J, Neovius M. Predictors of work disability during the first 3 years
after diagnosis in a national rheumatoid arthritis inception cohort. Annals of the Rheumatic
Diseases 2013, Mars 21.
Paradowski PT, Lohmander LS, Englund M. The association between metacarpal ratio,
radiographic hand and knee osteoarthritis and its progression after meniscectomy.
Osteoarthritis Cartilage 2013; 21(8): 1053-7.
Paternoster L, Lorentzon M, Lehtimäki T, Eriksson J, Kähönen M, Raitakari O, Laaksonen
M, Mikkilä V, Viikari J, Lyytikäinen L-P, Mellström D, Ljunggren Ö, Karlsson M, Kemp J,
Sayers A, Nethander M, Evans D, Vandenput L, Tobias J, Ohlsson C. Genetic determinants
of trabecular and cortical volumetric bone mineral densities and bone microstructure. PLOS
Genetics 2013; Feb;9(2):e1003247.doi:10.1371/journal.pgen.1003247.
Petersson IF, Strömbeck B, Andersen L, Cimmino M, Greiff R, Loza E, Sciré C, Stamm
T, Stoffer M, Uhlig T, Woolf AD, Vliet Vlieland TP; the eumusc.net-working group.
Development of healthcare quality indicators for rheumatoid arthritis in Europe: the
eumusc.net project. Annals of the Rheumatic Diseases 2013 Aug 19. doi: 10.1136/
annrheumdis-2013-203765. [Epub ahead of print]
58
Ranstam J. The importance of clear language. Acta Orthopaedica 2013; 84(5): 443.
Ratasvuori M, Wedin R, Keller J, Nottrott M, Zaikova O, Bergh P, Kalen A, Nilsson J,
Jonsson H, Laitinen M. Insight opinion to surgically treated metastatic bone disease:
Scandinavian Sarcoma Group Skeletal Metastasis Registry report of 1195 operated skeletal
metastasis. Surgical Oncology. 2013; 22(2):132-8.
Rezaei H, Saevarsdottir S, Geborek G, Petersson I,F, van Vollenhoven RF, Forslind K.
Evaluation of hand bone loss by digital X-ray radiogrammetry as a complement to clinical
and radiographic assessment in early rheumatoid arthritis: results from the SWEFOT trial.
BMC Musculoskeletal Disorders 2013, 14:79.
Ricciardi BF, Bostrom MP, Lidgren L, Ranstam J, Merollini K, W-Dahl A. Prevention of
Surgical Site Infection in Total Joint Arthroplasty: An International Tertiary Care Center
Survey. Hospital for Special Surgery. HSSJ, DOI 10.1007/s11420-013-9369-1. Published on
line: 03 December 2013.
Riordan EA, Frobell RB, Roemer FW, Hunter DJ. The Health and Structural Consequences
of Acute Knee Injuries Involving Rupture of the Anterior Cruciate Ligament. Rheumatic
Disease Clinics of North America 2013, 39(1):107-122.
Robb JE, Hägglund G. Hip surveillance and management of the displaced hip in cerebral
palsy. Journal of Children’s Orthopaedics 2013;7:407-413.
Rodby-Bousquet E, Czuba T, Hägglund G, Westbom L. Postural asymmetries in young
adults with cerebral palsy. Developmental Medicine and Child Neurology 2013;55:100910015.
Roemer FW, Felson DT, Tianzhong Y, Niu J, Crema MD, Englund M, Nevitt MC, Zhang
Y, Lynch JA, El Khoury GY. The association between meniscal damage of the posterior horns
and localized posterior synovitis detected on T1-weighted contrast-enhanced MRI-The
MOST study. Seminars in Arthritis and Rheumatism 2013; 42(6): 573-81.
Roos EM, Juhl CB, Lohmander LS. Expert panels: can they be trusted? Arthroscopy.
2013;29(7):1127-8. doi: 10.1016/j.arthro.2013.05.016.
Rosengren B, Karlsson C, Cöster M, vonSchewelow T, Magnusson H, ,Karlsson M. Training
and bone – from health to injury. Danish Journal of Sports Medicine 2013;3(17):16-20.
Rosengren B, Karlsson M. My mother was saved from hip fracture by treatment for
osteoporosis but will I be? – Implications on risk-estimates from successful osteoporosis
treatment. Osteoporosis International 2013;Feb;24(2):739.
59
Rosengren B, Ribom E, Nilsson JA, Mallmin H, Ljunggren Ö, Ohlsson C, Mellström
D, Lorentzon M, Stefanick M, Lapidus J, Leung PC, Kwok T, Orwoll E, Karlsson M.
International and ethnic variability of falls in older men. Scandinavian Journal of Public
Health doi: 10.1177/1403494813510789. [Epub 2013 Nov 20].
Schilcher J, Koeppen V, Ranstam J, Skripitz R, Michaelsson, K, Aspenberg P. Atypical
femoral fractures are a separate entity, characterized by highly specific radiographic features. A
comparison of 59 cases and 218 controls. Bone 2013, 52(1):389-392.
Shi J, Browne M, Strickland M, Flivik G, Taylor M. Sensitivity analysis of a cemented hip
stem to implant position and cement mantle thickness. Computer Methods in Biomechanics
and Biomedical Engineering. 2013 Feb 13. [Epub ahead of print]
Sigmundsson FG, Jönsson B, Strömqvist B. The impact of pain on function and health
related quality of life in lumbar spinal stenosis: A register study of 14821 patients. Spine
2013; 38(15): E937-45.
Sigmundsson FG, Jönsson B, Strömqvist B. Preoperative pain pattern predicts surgical
outcome more than type of surgery in patients with central spinal stenosis without
concomitant spondylolisthesis: A register study of 9,051 patients. Spine 2013; Oct 29. [Epub
ahead of print]
Stefansdottir A, Johansson Å, Lidgren L, Wagner P, W-Dahl A. Bacterial colonization
and resistance patterns in 133 patients undergoing a primary hip- or knee replacement in
Southern Sweden. Acta Orthopaedica 2013, 84(1): 87-91.
Stigmar K, Petersson IF, Jöud A, Grahn BE. Promoting work ability in a structured national
rehabilitation program in patients with musculoskeletal disorders: outcomes and predictors in
a prospective cohort study. BMC Musculoskeletal Disorder 2013, Feb 6, 14:57.
Stoffer MA, Smolen JS, Woolf A, Ambrozic A, Bosworth A, Carmona L, Fialka-Moser
V, Loza E, Olejnik P, Petersson IF, Uhlig T, Stamm TA; the eumusc.net-working group.
Development of patient-centred standards of care for rheumatoid arthritis in Europe:
the eumusc.net project. Annals of the Rheumatic Diseases 2013 Aug 6. doi: 10.1136/
annrheumdis-2013-203743. [Epub ahead of print]
Strömqvist B, Berg S, Gerdhem P, Johnsson R, Möller A, Sahlstrand T, Ahmed Soliman
A, Tullberg T. X-Stop versus decompressive surgery for lumbar neurogenic intermittent
claudication: A randomized controlled trial with 2 years follow-up. Spine 2013, 38(17):
1436-42.
Strömqvist B, Fritzell P, Hägg O, Jönsson B, Sandén B. Swedish Society of Spinal Surgeons.
Swespine: the Swedish spine register: The 2012 report. European Spine Journal 2013, 22
(4):953-974.
60
Stucinskas J, Clauss M, Tarasevicius S, Wingstrand H, Ilchmann T. Dynamics of femoral
bone remodelling in well fixed total hip arthroplasty. A 20-year follow-up of 20 hips. Hip
International 2013 Nov 7:0. doi: 10.5301/hipint.5000097. [Epub ahead of print]
Svejme O, Ahlborg HG, Nilsson JA, Karlsson M. Low BMD is an independent predictor of
fracture and early menopause of mortality in post-menopausal women – A 34-year prospective
study. Maturitas 2013;74(1013):341-345.
Svejme O, Ahlborg H, Karlsson M. Physical activiy reduces bone loss in the distal forearm in
postmenopausal women – a 25-year prospective study. Scandinavian Journal of Medicine &
Science in Sports doi: 10.1111/j.1600-0838.2012.01504.x. [Epub ahead of print 2012 Jul 30]
Swärd P, Fridén T, Boegård T, Kostogiannis I, Neuman P, Roos H. Association between varus
alignment and post-traumatic osteoarthritis after anterior cruciate ligament injury. Knee Surgery,
Sports Traumatology, Arthroscopy 2013 Sep;21(9):2040-7.
Tamminen IS, Yli-Kyyny T, Isaksson H, Turunen MJ, Tong S, Jurvelin JS, Kröger H. Incidence
and bone biopsy findings of atypical femoral fractures. Journal of Bone and Mineral Metabolism
2013; 31(5): 585-94.
Tarasevicius S, Robertsson O, Dobozinskas P, Wingstrand H. A comparison of outcomes and
dislocation rates using dual articulation cups and THA for intracapsular femoral neck fractures.
Hip International 2013 Jan-Feb;23(1):22-6. doi: 10.5301/HIP.2013.10632.
Tenne M, McGuigan F, Besjakov J, Gerdhem P, Åkesson K. Degenerative Changes at the
Lumbar Spine – Implications for Bone Mineral Density Measurement in Elderly Women.
Osteoporos International. 2013;24:1419-28
Thorlund JB, Christensen R, Nissen N, Jørgensen U, Schjerning J, Pørneki JC, Englund
M, Lohmander LS. Knee Arthroscopy Cohort Southern Denmark (KACS): protocol
for a prospective cohort study. BMJ Open. 2013 Oct 14;3(10):e003399. doi: 10.1136/
bmjopen-2013-003399.
Timberg P, Lång K, Nyström M, Holmqvist K, Wagner P, Förnvik D, Tingberg A, Zackrisson
S. Investigation of viewing procedures for interpretation of breast tomosynthesis image volumes:
a detection-task study with eye tracking. European Radiology 2013, Apr, 23(4):997-1005
Timpka S, Petersson IF, Zhou C, Englund M. Muscle strength in adolescent men and future
musculoskeletal pain: a cohort study with 17 years of follow-up. BMJ Open. 2013 May 28;3(5).
pii: e002656. doi: 10.1136/bmjopen-2013-002656.
Toksvig-Larsen S, Aspenberg P. Bisphosphonate-coated external fixation pins appear similar
to hydroxyapatite-coated pins in the tibial metaphysis and to uncoated pins in the shaft. Acta
Orthopaedica 2013, 84(3):314-8.
61
Tveit M, Rosengren B, Nyquist F, Nilsson J-Å, Karlsson M. Former Male Elite Athletes
Have Lower Incidence of Fragility Fractures than Expected. Medicine & Science in Sports &
Exercise 2013 Mar;45(3):405-10.
Tveit M, Rosengren B, Nilsson JA, Ahlborg H, Karlsson M. Bone mass following physical
activity in young years: a mean 39-year prospective controlled study in men. Osteoporosis
International 2013;Apr; 24(4):1389-97.
Tägil M, Geijer M, Abramo A, Kopylov P. Ten years’ experience with a pyrocarbon prosthesis
replacing the proximal interphalangeal joint. A prospective clinical and radiographic
follow-up. Journal of Hand Surgery, Eur Vol, 2013, Mars 5.
Uddenfeldt Wort U1, Nordmark E, Wagner P, Düppe H, Westbom L. Fractures in children
with cerebral palsy: a total population study. Developmental Medicine & Child Neurology.
2013;55(9):821-6. doi: 10.1111/dmcn.12178. Epub 2013 Jun 11.
Vandenput L, Nilsson M, Tivesten Å, Ryberg H, Mellström D, Karlsson M, Ljunggren Ö,
Labrie F, Orwoll E, O’Neill T, Pye S; Wu F, Vanderschueren D, Ohlsson C. Comparisons
of immunoassay and mass spectrometry measurements of serum estradiol levels and their
influence on clinical association studies in men. The Journal of Clinical Endocrinology and
Metabolism 2013:2013 Jun; 98(6):E1097-102.
Van Meirhaeghe J, Bastian L, Boonen S, Ranstam J, Tillman JB, Wardlaw D. A randomized
trial of balloon kyphoplasty and non-surgical management for treating acute vertebral
compression fractures: Vertebral body kyphosis correction and surgical parameters. Spine
2013, Mar 5.
van Tiel J, Bron EE, Tiderius CJ, Bos PK, Reijman M, Klein S, Verhaar JA, Krestin GP,
Weinans H, Kotek G, Oei EH. Reproducibility of 3D delayed gadolinium enhanced MRI
of cartilage (dGEMRIC) of the knee at 3.0 T in patients with early stage osteoarthritis.
European Radiology 2013;23(2):496-504. doi: 10.1007/s00330-012-2616-x.
Epub 2012 Aug 11.
Väänänen SP, Yavari SA, Weinans H, Zadpoor AA, Jurvelin JS, Isaksson H. Repeatability of
digital image correlation for measurement of surface strains in composite long bones. Journal
of Biomechanics 2013; 46(11): 1928-32.
Walther C, Nilsson J, Vult von Steyern F, Wiebe T, Bauer HC, Nord KH, Gisselsson
D, Domanski HA, Mandahl N, Mertens F. Cytogenetic and single nucleotide
polymorphism array findings in soft tissue tumors in infants. Cancer Genet. 2013 JulAug;206(7-8):299-303. doi: 10.1016/j.cancergen.2013.06.004. Epub 2013 Aug 12.
Wenger D, Düppe H, Tiderius C-J. Acetabular dysplasia at the age of 1 year in children with
neonatal instability of the hip. A cohort study of 243 infants. Acta Orthopaedica
2013; 84(5): 483-8.
62
Wenger A, Wirth W, Hudelmaier M, Noebauer-Huhmann I, Trattnig S, Bloecker K,
Frobell RB, Kwoh CK, Eckstein F, Englund M. Meniscus body position, size, and shape in
persons with and persons without radiographic knee osteoarthritis: quantitative analyses of
knee magnetic resonance images from the osteoarthritis initiative. Arthritis Rheumatology.
2013;65(7):1804-11. doi: 10.1002/art.37947
Westerberg P-A, Tivesten Å, Karlsson M, Mellström D, Orwoll E, Ohlsson C, Larsson T,
Linde T, Ljunggren Ö. Fibroblast Growth Factor 23, mineral metabolism and mortality
among elderly men (MrOs Sweden). BMC Nephrology 2013;14(1):85.
Zampelis V, Tägil M, Lidgren L, Isaksson H, Atroshi I, Wang J-S. The effect of a biphasic
injectable bone substitute on the interface strength in a rabbit knee prosthesis model. Journal
of Orthopaedic Surgery and Research 2013; 8:25.
Åkesson K, Marsh D, Mitchell PJ, McLellan AR, Stenmark J, Pierroz DD, Kyer C, Cooper
C and the IOF Fracture Working Group. Position paper. Capture the Fracture: A Best
Practice Framework and Global Campaign to Break the Fragility Fracture Cycle. Osteoporosis
International 2013(8):2135-52 (peer-reviewed)
Åkesson K, Mitchell P. Capture the Fracture. A global campaign to break the fragility fracture
cycle. International Osteoporosis Foundation 2013.
Åkesson K, Tenne M, Gerdhem P, Luthman H, McGuigan F. Variation in the PTH2R gene
is associated with age-related degenerative changes in the lumbar spine. Journal of Bone &
Mineral Metabolism. 2013 Dec 31. [Epub ahead of print]
Øiestad BE, Østerås N, Frobell R, Grotle M, Brøgger H, Risberg MA. Efficacy of strength
and aerobic exercise on patient-reported outcomes and structural changes in patients with
knee osteoarthritis: study protocol for a randomized controlled trial. BMC Musculoskeletal
Disorder 2013 Sep 12;14:266. doi: 10.1186/1471-2474-14-266.
63
Annual Reports
CPUP årsrapport 2013. Red. Hägglund G. ISBN978-91-980722-0-4
Det svenska fotledsregistret, årsrapport 2012, ansvarig utgiv.: Åke Carlsson, ISSN: 2001-6697
Ledord. Ortopedi Reumatologi. Sydsvenska medicinhistoriska sällskapets årsskrift 2013. Ny
serie nr 7 Temaredaktör Lidgren L och Saxne T. Huvudredaktör Persson BEB.
RIKSHÖFT, årsrapport 2012, ISBN 978-91-980722-1-1
Strömqvist B, Fritzell P, Hägg O, Jönsson B. Svensk Ryggkirurgisk Förening. Uppföljning av
ländryggskirurgi i Sverige. Årsrapport 2012. 63 s. 2013. ISBN 978-91-980722-3-5.
The Swedish Knee Arthroplasty Register Annual Report 2013. Robertsson O, W-Dahl A,
Lidgren L, Sundberg M. ISBN 978-91-979924-9-7
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