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  • 1.
    Augat, Peter
    et al.
    Trauma Ctr Murnau, Inst Biomech, Murnau, Germany; Paracelsus Med Univ, Inst Biomech, Salzburg, Austria.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Plating of fractures: current treatments and complications2018In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 49, p. S1-S1Article in journal (Other academic)
  • 2. Bhandari, Mohit
    et al.
    Sprague, Sheila
    Schemitsch, Emil H.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Resolving controversies in hip fracture care: the need for large collaborative trials in hip fractures2009In: Journal of Orthopaedic Trauma, ISSN 0890-5339, E-ISSN 1531-2291, Vol. 23, no 6, p. 479-484Article in journal (Refereed)
    Abstract [en]

    Hip fractures are a significant cause of morbidity and mortality worldwide and the burden of disability associated with hip fractures globally vindicate the need for high-quality research to advance the care of patients with hip fractures. Historically, large, multi-centre randomized controlled trials have been rare in the orthopaedic trauma literature. Similar to other medical specialties, orthopaedic research is currently undergoing a paradigm shift from single centre initiatives to larger collaborative groups. This is evident with the establishment of several collaborative groups in Canada, in the United States, and in Europe, which has proven that multi-centre trials can be extremely successful in orthopaedic trauma research.Despite ever increasing literature on the topic of his fractures, the optimal treatment of hip fractures remains unknown and controversial. To resolve this controversy large multi-national collaborative randomized controlled trials are required. In 2005, the International Hip Fracture Research Collaborative was officially established following funding from the Canadian Institute of Health Research International Opportunity Program with the mandate of resolving controversies in hip fracture management. This manuscript will describe the need, the information, the organization, and the accomplishments to date of the International Hip Fracture Research Collaborative.

  • 3.
    Billström, Gry Hulsart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Piskounova, Sonya
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Gedda, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Bowden, Tim
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Improved bone formation by altering surface area of hyaluronan-based hydrogel carrier for bone morphogenetic protein-22012In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, p. S114-S114Article in journal (Other academic)
  • 4.
    Borg, T
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Larsson, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Lindsjö, U
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Percutaneous plating of distal tibial fractures. Preliminary results in 21 patients.2004In: Injury, ISSN 0020-1383, Vol. 35, no 6, p. 608-14Article in journal (Refereed)
  • 5.
    Borg, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Berg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Fugl-Meyer, Kerstin
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Health-related quality of life and life satisfaction in patients following surgically treated pelvic ring fractures: A prospective observational study with two years follow-up2010In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 41, no 4, p. 400-404Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Pelvic ring fractures caused by high-energy trauma are severe injuries with well described radiological and clinical outcomes, whereas description from the patient's perspective is less well documented. The purpose of this study was to investigate patient-reported outcome following surgical treatment of pelvic fractures using quality of life instruments. METHODS: All 54 patients (28 male/26 female, ages 16-68) with pelvic fractures referred to our institution for surgical treatment 2003-2005 were prospectively included. The most common trauma was motor vehicle accident (44%). Additional injuries were seen in 74% and in 31% the ISS was >or=16. There were 31 B and 23 C type fractures. Patients were followed for two years using two validated questionnaires, SF-36 and LiSat-11, the latter an instrument consisting of 11 questions for evaluation of satisfaction with different aspects of life. RESULTS: 45 patients could be followed according to the study protocol for two years while 2 were untraceable and 1 died from unrelated causes. Of 6 nonresponders, 5 were unable due to psychiatric disorder. At two years pelvic fracture patients scored lower than the reference population in both physical and mental domains (SF-36). Highest mean score, 68, was in the domain Social Function (norm 89) while lowest mean score, 38, was in the domain Role Physical (norm 86). The mean score closest to the normative was for general health with 61 for patients and 78 for the normative group. In LiSat-11 pelvic fracture patients scored lower than the reference population in all areas. Satisfaction with life as a whole was 31% compared with 60% in the normative group. CONCLUSIONS: Two years after surgical treatment of pelvic ring fractures, patients reported substantially lower quality of life for both physical and mental domains, when compared with a reference population, even when radiological and clinical outcomes were considered favourable.

  • 6.
    Borg, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Berg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Quality of Life After Operative Fixation of Displaced Acetabular Fractures2012In: Journal of Orthopaedic Trauma, ISSN 0890-5339, E-ISSN 1531-2291, Vol. 26, no 8, p. 445-450Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to determine quality of life (QoL) changes over time after internal fixation of acetabular fractures.

    Design: This pertains to a prospective cohort study, which was single centered.

    Setting: The study was conducted at the University Hospital.

    Patients: One hundred thirty-six patients (108 men, 28 women), age 17-83 years operated for an acetabular fracture during 2004-2008 were prospectively included and followed up for 2 years.

    Main Outcome Measures: QoL was evaluated via Short Form-36 (SF-36) and Life Satisfaction-11 at 6, 12, and 24 months. Radiographs were evaluated according to Matta at 2 years.

    Results: The most frequent fracture types were posterior wall (n31), associated anterior-posterior hemitransverse (n34), and associated both column (n29). One hundred twenty-nine patients could be assessed at 2 years, 4 did not respond, and 3 had died. The patients scored lower than norms in all 8 SF-36 domains with improvement over time for Physical Function (P < 0.0001) and Role Physical (P < 0.0001). The patients with postop reduction 0-1 mm scored better (P < 0.001-0.039) in 7 domains, all except vitality (P = 0.07), when compared with patients with residual displacement of >= 2 mm. Life satisfaction did not change with time and showed lower scores than normative in 9 of 11 items. Nineteen patients had undergone total hip replacement, and the strongest predictor was acetabular or femoral head impaction.

    Conclusions: QoL in surgically treated patients with displaced acetabular fracture keeps improving in physical SF-36 domains over a 2-year period although still lower than norms, and anatomical reduction results in better QoL outcome in most dimensions.

  • 7.
    Borg, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Carlsson, Marianne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Questionnaire to assess treatment outcomes of acetabular fractures2012In: Journal of Orthopaedic Surgery, ISSN 1022-5536, E-ISSN 2309-4990, Vol. 20, no 1, p. 55-60Article in journal (Refereed)
    Abstract [en]

    PURPOSE

    To construct a questionnaire to assess outcomes in patients who underwent internal fixation for acetabular fractures.

    METHODS

    27 female and 100 male consecutive patients (mean age, 50 years) who underwent internal fixation for acetabular fractures were included. Patients were asked to report their outcomes at months 6, 12, and 24 using a questionnaire. The initial questionnaire was constructed by an expert group. There were 11 closed questions, each came with 6 responses from ?no discomfort? to ?very severe discomfort?. Three open questions were added to cover topics that were not included. The content validity and relevance of the 11 closed questions was determined using factor analysis to determine the number of factors involved. Factorability of the correlation matrix was measured via the Bartlett test of sphericity and Kaiser-Meyer- Olkin (KMO) measure of sampling sufficiency. Factor loadings of <0.50 were considered acceptable for factor representation. Reliability in terms of internal consistency was expressed as Cronbach alpha coefficients. The responses to the 3 open questions were analysed and categorised by a single assessor.

    RESULTS

    120 (94%) of the patients completed at least one questionnaire, and 92 (72%) completed all 3 questionnaires during the follow-up period. Based on responses to the 6-month questionnaire, responses to the 11 closed questions were significantly intercorrelated (Spearman 0.17-0.80). After factor analysis and analysis of responses to open questions, the number of questions was reduced to 6 and included questions related to pain, walking, hip motion, leg numbness, sexual life, and operation scar. Reliability of the questionnaire was estimated to alpha=0.89. Criterion validity was adequate with a high correlation with the Short Form 36 (r=0.56-0.80).

    CONCLUSION

    Patients treated with acetabular fractures can be adequately assessed using the 6-item questionnaire and one global question concerning impact on activities of daily living.

  • 8.
    Borg, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hernefalk, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Carlsson, Marianne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Uppsala Univ, Dept Publ Hlth & Caring Sci, Uppsala, Sweden..
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Development of a pelvic discomfort index to evaluate outcome following fixation for pelvic ring injury2015In: Journal of Orthopaedic Surgery, ISSN 1022-5536, E-ISSN 2309-4990, Vol. 23, no 2, p. 146-149Article in journal (Refereed)
    Abstract [en]

    Purpose. To develop a pelvic discomfort index (PDI) to evaluate outcome following fixation for pelvic ring injury. Methods. 29 female and 44 male consecutive patients (mean age, 36 years) underwent internal fixation for pelvic ring injury of type B1 (n=10), B2 (n=22), B3 (n=15), C1 (n=18), C2 (n=5), and C3 (n=3), based on the AO/OTA classification. At postoperative 6, 12, and 24 months, patients were asked to assess their discomfort in the pelvis using a 14-item questionnaire. Three questions were open-ended, and responses were categorised by a single assessor. The remaining 11 questions were closed-ended and had 6 ordinal options from 'no discomfort' (score=0) to' extremely severe discomfort' (score=5). The content validity and relevance of the 11 closed-ended questions was determined. The 14-item questionnaire was compared with the 36-item Short Form Health Survey (SF-36). Results. Respectively at postoperative 6, 12, and 24 months, 78%, 71%, and 71% of the patients completed the 14-item questionnaire. Based on the factor analysis and responses to the open-ended questions, the number of items was reduced to 6 including pain, walking, mobility of the hips, loss of sensation in the legs, sexual life, and operation scar. Four factors could explain 96% of the total variance. The first factor involved the first 3 items (pain, walking, and hip motion) and addressed 'pelvis', whereas 3 factors involved the remaining items and each addressed peripheral neurology, sexual life, and operation scar. A PDI was developed using these 6 items. The PDI had high internal reliability (alpha=0.89), adequate content and criterion validity, and moderate correlation with the SF-36 total score or scores of physical function, bodily pain, and general health (r=0.50-0.77). Conclusion. The PDI provides valid, specific, and relevant information to assess

  • 9.
    Borg, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Holstad, M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Quality of life in patients operated for pelvic fractures caused by suicide attempt by jumping2010In: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 99, no 3, p. 180-186Article in journal (Refereed)
    Abstract [en]

    Background and Aims: Jumping from great height is an aggressive method of suicide attempt where the frequent combination of psychiatric disorder and somatic injuries makes treatment difficult. Our aim was to evaluate survival rate and get patient-reported outcome in patients operated for a pelvic or acetabular fracture sustained when jumping from a height as a suicide attempt. Patients and Methods: During the period 2003-2004, 12 patients (11 women) of whom eight were below 30 years of age, were prospectively included. At two years HRQoL (Health-Related Quality of Life) questionnaires (SF-36 and LiSat-11) were used to describe outcome, and at four years a structured psychiatric interview SCID-I (Structured Clinical Interview for DSM-IV Axis I Disorders) was done. Results: At four years all patients were alive. One patient had made a new suicide attempt. Eight patients gave adequate reply on SF-36 and LiSat-11 at two years. In all domains patients scored lower than a norm group with the relatively lowest values in physical domains. Younger patients assessed life as better when compared with middle aged patients. Conclusions: This study showed a very low recurrence rate into suicidal behaviour in a group of jumpers and all patients were alive at four years after a suicidal attempt by jumping. The high proportion of psychiatric disorder in these patients highlights the need for a combined treatment effort between orthopaedic and psychiatric expertise.

  • 10.
    Carlsson, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Treerattrakoon, Kiatnida
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lopez, Alejandro
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Karlsson Ott, Marjam
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    In vitro and in vivo response to low-modulus PMMA-based bone cement2015In: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, article id 594284Article in journal (Refereed)
    Abstract [en]

    The high stiffness of acrylic bone cements has been hypothesized to contribute to the increased number of fractures encountered after vertebroplasty, which has led to the development of low-modulus cements. However, there is no data available on the in vivo biocompatibility of any low-modulus cement. In this study, the in vitro cytotoxicity and in vivo biocompatibility of two types of low-modulus acrylic cements, one modified with castor oil and one with linoleic acid, were evaluated using human osteoblast-like cells and a rodent model, respectively. While the in vitro cytotoxicity appeared somewhat affected by the castor oil and linoleic acid additions, no difference could be found in the in vivo response to these cements in comparison to the base, commercially available cement, in terms of histology and flow cytometry analysis of the presence of immune cells. Furthermore, the in vivo radiopacity of the cements appeared unaltered. While these results are promising, the mechanical behavior of these cements in vivo remains to be investigated.

  • 11.
    Christersson, Albert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sandén, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Clinical outcome after plaster cast fixation for 10 days versus 1 month in reduced distal radius fractures: A prospective randomized study2018In: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 107, no 1, p. 82-90Article in journal (Refereed)
    Abstract [en]

    Introduction: this study aimed to evaluate clinical results after plaster cast fixation for 10 days versus 1 month of moderately displaced and reduced distal radius fractures.Material and Methods: in a prospective randomized study, 109 patients with moderately displaced and conservatively treated distal radius fractures (age ≥50 years) were randomized 10 days after reduction to either removal of the plaster cast and immediate mobilization (active group) or to continued plaster cast fixation for another 3 weeks (control group). Grip strength, pincer strength, range of motion, and pain were assessed at 1, 4, and 12 months after reduction. Clinical outcome was evaluated using three functional assessment scores at 12 months.Results: treatment failed in 3/54 (6%) patients in the active group. one of these patients had the plaster cast reinstituted because of feelings of instability. the fractures in the other two patients displaced severely after mobilization and were therefore treated surgically. for the remaining 51 patients in the active group, the range of wrist motion was slightly better at 1 month compared with the controls, but there were no differences in grip or pincer strength or pain at the 1-month follow-up. there were no differences between the active and control group in any outcome at 4 or 12 months, including functional assessment scores at 12 months.Conclusion: treatment with mobilization 10 days after reduction of moderately displaced distal radius fractures resulted in a few treatment failures compared with none among controls. the only functional benefit for the remaining patients was a small and transient increase in range of motion at the 1-month follow-up. plaster cast removal 10 days after reduction in moderately displaced distal radius fractures is therefore not recommended.

  • 12.
    Christersson, Albert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Presurgical localization of infected avascular bone segments in chronic complicated posttraumatic osteomyelitis in the lower extremity using dual-tracer PET/CT.2018In: EJNMMI Research, ISSN 2191-219X, E-ISSN 2191-219X, Vol. 8, article id 65Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Localizing and removing the infected sequestrum in long-standing trauma-related chronic osteomyelitis remains a clinical challenge. PET/CT with 18F-fluorodeoxyglucose (FDG-PET) has a high sensitivity for chronic osteomyelitis and 18F-sodium-fluoride PET/CT (NaF-PET) has a high specificity for identifying non-viable bone. Combining both, high signal on FDG-PET in the bone without signal on NaF-PET could potentially guide surgery to become more precise with curative intent. Eight patients with long-standing (average 22 years) posttraumatic (n = 7) or postoperative (n = 1) chronic osteomyelitis in the lower extremity and with multiple futile attempts for curative surgery were recruited in this prospective pilot study. FDG-PET and NaF-PET were performed within a week in between using standard scanning protocols. The most likely location of the culprit sequestrum was identified and was surgically removed. Based on perioperative tissue cultures, antibiotics were given for 6-8 months. Dual-tracer (FDG- and NaF-PET/CT) was performed again after 12 months to rule out persisting signs of infection.

    RESULTS: A likely culprit sequestrum could preoperatively be identified by dual-tracer PET in all eight cases and in four cases an additional sequestrum was identified at a location with no clinical sign of infection. The infected necrotic tissue was removed during surgery. Follow-up dual-tracer PET revealed no signs of persistent infection. All patients recovered with no clinical signs of recurrence for a follow-up of mean 4.5 (SD 1.3) years.

    CONCLUSIONS: Dual-tracer PET/CT with FDG and NaF allows successful precise surgery with curative intent in patients with long-standing complicated posttraumatic chronic osteomyelitis with severely deranged anatomy.

  • 13.
    Christersson, Albert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Östlund, Bengt
    Nyköping Hosp, Dept Orthoped, S-61185 Nyköping, Sweden.
    Sandén, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Radiographic results after plaster cast fixation for 10 days versus 1 month in reduced distal radius fractures: a prospective randomised study2016In: Journal of Orthopaedic Surgery and Research, ISSN 1749-799X, E-ISSN 1749-799X, Vol. 11, article id 145Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The aim of this study was to examine whether reduced distal radius fractures can be treated with early mobilisation without affecting the radiographic results.

    METHODS: In a prospective randomised study, 109 patients (mean age 65.8 (range 50-92)) with moderately displaced distal radius fractures were treated with closed reduction and plaster cast fixation for about 10 days (range 8-13 days) followed by randomisation to one of two groups: early mobilisation (n = 54, active group) or continued plaster cast fixation for another 3 weeks (n = 55, control group).

    RESULTS: For three patients in the active group (6%), treatment proved unsuccessful because of severe displacement of the fracture (n = 2) or perceived instability (n = 1). From 10 days to 1 month, i.e. the only period when the treatment differed between the two groups, the active group displaced significantly more in dorsal angulation (4.5°, p < 0.001), radial angulation (2.0°, p < 0.001) and axial compression (0.5 mm, p = 0.01) compared with the control group. However, during the entire study period (i.e. from admission to 12 months), the active group displaced significantly more than the controls only in radial angulation (3.2°, p = 0.002) and axial compression (0.7 mm, p = 0.02).

    CONCLUSIONS: Early mobilisation 10 days after reduction of moderately displaced distal radius fractures resulted in both an increased number of treatment failures and increased displacement in radial angulation and axial compression as compared with the control group. Mobilisation 10 days after reduction cannot be recommended for the routine treatment of reduced distal radius fractures.

    TRIAL REGISTRATION: ClinicalTrail.gov, NCT02798614 . Retrospectively registered 16 June 2016.

  • 14.
    Christersson, Albert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Nysjö, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Malmberg, Filip
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sintorn, Ida-Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Nyström, Ingela
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Comparison of 2D radiography and a semi-automatic CT-based 3D method for measuring change in dorsal angulation over time in distal radius fractures2016In: Skeletal Radiology, ISSN 0364-2348, E-ISSN 1432-2161, Vol. 45, no 6, p. 763-769Article in journal (Refereed)
    Abstract [en]

    Objective The aim of the present study was to compare the reliability and agreement between a computer tomography-based method (CT) and digitalised 2D radiographs (XR) when measuring change in dorsal angulation over time in distal radius fractures. Materials and methods Radiographs from 33 distal radius fractures treated with external fixation were retrospectively analysed. All fractures had been examined using both XR and CT at six times over 6 months postoperatively. The changes in dorsal angulation between the first reference images and the following examinations in every patient were calculated from 133 follow-up measurements by two assessors and repeated at two different time points. The measurements were analysed using Bland-Altman plots, comparing intra- and inter-observer agreement within and between XR and CT. Results The mean differences in intra- and inter-observer measurements for XR, CT, and between XR and CT were close to zero, implying equal validity. The average intra- and inter-observer limits of agreement for XR, CT, and between XR and CT were +/- 4.4 degrees, +/- 1.9 degrees and +/- 6.8 degrees respectively. Conclusions For scientific purpose, the reliability of XR seems unacceptably low when measuring changes in dorsal angulation in distal radius fractures, whereas the reliability for the semi-automatic CT-based method was higher and is therefore preferable when a more precise method is requested.

  • 15.
    Christersson, Albert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sandén, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Prospective randomized feasibility trial to assess the use of rhPDGF-BB in treatment of distal radius fractures2015In: Journal of Orthopaedic Surgery and Research, ISSN 1749-799X, E-ISSN 1749-799X, Vol. 10, article id 37Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Recombinant human platelet-derived growth factor BB (rhPDGF-BB) combined with an osteoconductive scaffold (β-TCP) has been demonstrated to increase bone formation, but rhPDGF-BB has not been studied in human fractures. The purpose of this study was to evaluate the safety and potential use of locally administered rhPDGF-BB/β-TCP (Augment®) in acute wrist fractures.

    METHODS: Forty patients with unstable distal radial fracture were randomized to closed reduction and external fixation alone (n = 20) or combined with injection of rhPDGF-BB/β-TCP (Augment®) into the fracture (n = 20). All patients were followed for 24 weeks. Outcome was based on adverse events, fracture displacement on radiographs, fracture healing, range of motion, grip strength, pain, and the disability of the arm, shoulder and hand (DASH) score.

    RESULTS: There were no serious adverse events in the study, but the pin tract infection rate was significantly lower in the Augment® group. There was no difference between the groups in fracture healing time, based on number of healed cortices or fracture displacement. The Augment® group had an early temporary significant decrease in wrist flexion, but no difference in range of motion at 24 weeks. There were no differences between the two treatment groups for any other outcome variables.

    CONCLUSION: rhPDGF-BB/β-TCP (Augment®) is safe and convenient for local administration into wrist fractures. In this pilot study, we could not detect any reduced healing time in the Augment® group although potential efficacy should be addressed in larger studies.

    CLINICAL TRIAL REGISTRATION NUMBER: The clinical trial registration number for the study protocol is BMPI-2014-02-E.

  • 16. Ekström, Wilhelmina
    et al.
    Karlsson-Thur, Charlotte
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ragnarsson, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Alberts, Karl-Akke
    Functional outcome in treatment of unstable trochanteric and subtrochanteric fractures with the proximal femoral nail and the Medoff sliding plate2007In: Journal of Orthopaedic Trauma, ISSN 0890-5339, E-ISSN 1531-2291, Vol. 21, no 1, p. 18-25Article in journal (Refereed)
    Abstract [en]

    Objective: To compare outcome between the proximal femoral nail (PFN) and the Medoff sliding plate (MSP) in patients with unstable trochanteric or subtrochanteric fractures.

    Methods: This was a consecutive prospective randomized clinical study. In all, 203 patients admitted to two university hospitals with an unstable trochanteric or a subtrochanteric fracture type were included. Surgery was performed with a short intramedullary nail or a dual-sliding plate device. Follow up visits occurred at 6 weeks, 4 months, and 12 months. Functional outcome was measured by walking ability, rising from a chair, curb test, and additional assessments of abductor strength, pain, living conditions, and complications.

    Results: The ability to walk 15 m at 6 weeks was significantly better in the PFN group compared to the MSP group with an odds ratio 2.2 (P = 0.04, 95% confidence limits 1.03-4.67). No statistical difference in walking ability could be found between trochanteric and subtrochanteric fractures. The major complication rate (8% in the PFN group and 4% in the MSP group) did not differ statistically (P = 0.50) but reoperations were more frequent in the PFN group (9%) compared to the MSP group (1%; P < 0.02).

    Conclusions: There were no major differences in functional outcome or major complications between the treatment groups. Reasons other than the operated fracture seem to be equally important in determining the long-term functional ability of the patients in our study. An advantage with the MSP was the lower reoperation rate.

  • 17. Giannoudis, P V
    et al.
    Chris Arts, J J
    Schmidmaier, G
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    What should be the characteristics of the ideal bone graft substitute?2011In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 42, no Suppl 2, p. S1-S2Article in journal (Refereed)
  • 18.
    Grandfield, Kathryn
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Ericson, Fredric
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Sanden, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Johansson, Carina
    School of health and medical sciences, Örebro University.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Botton, Gianluigi
    Dept of Materials Science and Engineering, McMaster University, Hamilton, Ontario, Kanada.
    Palmquist, Anders
    Dept of Biomaterials, Sahlgrenska Academy at University of Gothenburg.
    Thomsen, Peter
    Dept of Biomaterials, Sahlgrenska Academy at University of Gothenburg.
    Håkan, Engqvist
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Ultrastructural characterization of the hydroxyapatite-coated pedicle screw and human bone interface2012In: International Journal of Nano and Biomaterials, ISSN 1752-8941, Vol. 4, no 1, p. 1-11Article in journal (Refereed)
  • 19.
    Gunnarsson, Anna-Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Gunningberg, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Jonsson, Kenneth B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Cranberry juice concentrate does not significantly decrease the incidence of acquired bacteriuria in female hip-fracture patients receiving urine catheter: a double-blind randomised trial2017In: Clinical Interventions in Aging, ISSN 1176-9092, E-ISSN 1178-1998, Vol. 12, p. 137-143Article in journal (Refereed)
    Abstract [en]

    Background

    Urinary tract infection (UTI) is a common complication among patients with hip fractures. Receiving an indwelling urinary catheter is a risk factor for developing UTIs. Treatment of symptomatic UTIs with antibiotics is expensive and can result in the development of antimicrobial resistance. Cranberries (lat. Vaccinium macrocarpon Ait.)  are thought to prevent UTI. There is no previous research on this potential effect in patients with hip fracture who receive urinary catheters.

    Aim

    To investigate whether cranberry capsules given pre- and postoperatively are useful in preventing hospital-acquired UTIs in female patients with hip fracture and urinary catheter.

    Design

    Randomised, placebo-controlled double-blind trial.

    Method

    Female patients, age 60 years and older, with hip fracture were recruited (n=227). The patients were randomised to receive cranberry (n=113) or placebo (n=114) capsules daily, from admission to the ward, until five days postoperatively. Urine cultures were obtained at admission and at five and 14 days postoperatively. In addition, EQ-5D assessments were performed and patients were screened for UTI symptoms.

    Result

    There was no difference between the groups in the proportion of patients with postoperative positive urine cultures. When excluding patients with positive cultures at admission, patients with antibiotic treatment during follow-up, and patients that did not adhere to the protocol, there was a trend towards a protective effect of cranberry treatment against hospital-acquired UTIs ; e.g. 36% (n=33) in the control group vs. 22%  (n=41) in cranberry group (p=0.17) at 5 days postoperatively.

    Conclusion

    Cranberry concentrate does not seem to have an effect in preventing UTI in female patients with hip fracture and indwelling urinary catheter.

     

  • 20.
    Gunnarsson, Anna-Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Education in Nursing.
    Åkerfeldt, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Gunningberg, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Increased energy intake in hip fracture patients affects nutritional biochemical markers2012In: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 101, no 3, p. 204-210Article in journal (Refereed)
    Abstract [en]

    Background and Aims: We have previously shown that nutritional guidelines decreased the incidence of pressure ulcers in hip fracture patients. In the present study, we evaluate whether the nutritional biochemical markers S-IGF-1 (Insulin-like Growth Factor 1), S-Transthyretin and S-Albumin are affected by patients' energy intake, and whether the markers are useful as predictors of postoperative complications. Material and Methods: Quasi-experimental design, with one intervention and one control group, as well as pre- and post-study measurements. Eighty-eight hip fracture patients were included: 42 in the control group and 46 in the intervention group. The control group received regular nutritional support pre- and postoperatively, while the intervention group received nutritional support that followed new, improved clinical guidelines from admission to five days postoperatively. S-Albumin, S-Transthyretin, C-Reactive Protein (S-CRP) and S-IGF-1 were analysed at admission and five days postoperatively as well as complications like pressure ulcer and infection. Results: The intervention group had a significantly higher energy intake; for example, 1636 kcal versus 852 kcal postoperative day 1. S-IGF-1 levels decreased significantly in the control group, while no decrease in the intervention group. S-Albumin and S-Transthyretin decreased and S-CRP increased significantly in both groups, indicating that those markers were not affected short-term by a high-energy intake. There was no correlation between short-term postoperative complications and S-IGF-1, S-Transthyretin or S-Albumin at admission. Conclusion: The results of our study showed that S-IGF-1 can be used as a short-term nutritional biochemical marker, as it was affected by a five-day high-energy regimen. However, neither S-IGF-1, S-Transthyretin or S-Albumin were useful in predicting postoperative complications within five days postoperatively.

  • 21. Gutleb, Arno C.
    et al.
    Arvidsson, Dan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Örberg, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Skaare, Janneche Utne
    Aleksandersen, Mona
    Ropstad, Erik
    Lind, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Effects on bone tissue in ewes (Ovies aries) and their foetuses exposed to PCB 118 and PCB 1532010In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 192, no 2, p. 126-133Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to investigate whether low levels of mono-ortho PCB 118 and di-ortho PCB 153, affect bone composition and strength in ewes (Dala breed) and their foetuses following exposure starting at conception and ending a week before expected delivery. In male foetuses, trabecular bone mineral content at the metaphysis was almost 30% lower in the PCB 118 (49mug/kg body wt/day) group compared to the control group (corn oil) (ANCOVA, P<0.05). In female foetuses of the PCB 153 (98mug/kg body wt/day) group trabecular cross-sectional area at the metaphysis was 19% smaller than in the controls (ANCOVA, P<0.05). At the diaphysis a smaller marrow cavity area (up to 24% reduction) was observed in female and male foetuses exposed to PCB 153 compared with controls (ANCOVA, P<0.05). There were also significant differences at the mid diaphyseal measure point between the PCB 153 and the control group females (ANCOVA, P<0.05). Cortical and total bone mineral density, cortical thickness were significantly higher, endosteal circumference shorter and marrow cavity significantly smaller in the PCB 153 group (ANCOVA, P<0.05). In conclusion there were gender dependent effects on bone tissue and cortical bone was more affected than trabecular bone.

  • 22.
    Hedin, H
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Borgquist, Lars
    Larsson, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    A cost analysis of three methods of treating femoral shaft fractures in children: a comparison of traction in hospital, traction in hospital/home and external fixation.2004In: Acta Orthop Scand, ISSN 0001-6470, Vol. 75, no 3, p. 241-8Article in journal (Refereed)
  • 23.
    Hedin, H
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences. Ortopedi.
    Larsson, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Technique and considerations when using external fixation as a standard treatment of femoral fractures in children.2004In: Injury, ISSN 0020-1383, Vol. 35, no 12, p. 1255-63Article in journal (Refereed)
  • 24.
    Hellström, Hans-Olov
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Larsson, Sune
    No association between the biomechanical properties and the aluminium content of boneManuscript (Other academic)
  • 25.
    Henriques, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Cunningham, Bryan
    Olerud, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Shimamoto, Norimichi
    Lee, Guy
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    McAfee, Paul
    Biomechanical comparison of five different atlantoaxial posterior fixation techhniques2000In: Spine, ISSN 0362-2436, E-ISSN 1528-1159, Vol. 25, no 22, p. 2877-2883Article in journal (Refereed)
    Abstract [en]

    STUDY DESIGN:

    Five different reconstructions of the atlantoaxial complex were biomechanically compared in vitro in a nondestructive test.

    OBJECTIVES:

    To determine whether non-bone graft-dependent one-point fixation affords stability levels equivalent to three-point reconstructions.

    SUMMARY OF BACKGROUND DATA:

    Previous investigations have demonstrated that three-point fixation, using bilateral transarticular screws in combination with posterior wiring, provide the most effective resistance to minimize motion around C1-C2. However, placement of transarticular screws is technically demanding. Posterior wiring techniques affording one-point fixation have failure rates of approximately 15%, with failure considered to be secondary to structural bone graft failures. One-point, non-bone graft-dependent fixations have not been tested.

    METHODS:

    Eight human cervical specimens, C0-C3 were loaded nondestructively. Unconstrained three-dimensional segmental motion was measured. The reconstructions tested were two one-point fixations, one two-point fixation, and two three-point fixations.

    RESULTS:

    Under axial rotation two and three-point reconstructions provided better stiffness than the one-point reconstructions (P < 0.05). During flexion-extension, higher stiffness levels were observed in one- and three-point fixations when compared with the intact spine (P < 0.05). In lateral bending no significant differences were observed among the six groups, although the trend was that reconstructions including transarticular screws provided greater stability than one-point fixations.

    CONCLUSION:

    The current findings substantiate the use of three-point fixation as the treatment of choice for C1-C2 instability. [l: atlantoaxial fixation, biomechanics, cervical spine, instability, spinal instrumentation, transarticular screws]

  • 26. Herlin, Maria
    et al.
    Kalantari, Fereshteh
    Stern, Natalia
    Sand, Salomon
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Viluksela, Matti
    Tuomisto, Jouni T.
    Tuomisto, Jouko
    Tuukkanen, Juha
    Jämsä, Timo
    Lind, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Håkansson, Helen
    Quantitative characterization of changes in bone geometry, mineral density and biomechanical properties in two rat strains with different Ah-receptor structures after long-term exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin2010In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 273, no 1-3, p. 1-11Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Both industrial chemicals and environmental pollutants can interfere with bone modeling and remodeling. Recently, detailed toxicological bone studies have been performed following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which exerts most of its toxic effects through the aryl hydrocarbon receptor (AhR). OBJECTIVES: The aims of the present study were to quantitatively evaluate changes in bone geometry, mineral density and biomechanical properties following long-term exposure to TCDD, and to further investigate the role of AhR in TCDD-induced bone alterations. To this end, tissue material used in the study was derived from TCDD-exposed Long-Evans (L-E) and Han/Wistar (H/W) rats, which differ markedly in sensitivity to TCDD-induced toxicity due to a strain difference in AhR structure. METHODS: Ten weeks old female L-E and H/W rats were administered TCDD s.c. once per week for 20 weeks, at doses corresponding to calculated daily doses of 0, 1, 10, 100 and 1000ngTCDD/kgbw (H/W only). Femur, tibia and vertebra from the L-E and H/W rats were analyzed by peripheral quantitative computed tomography (pQCT) and biomechanical testing at multiple sites. Dose-response modeling was performed to establish benchmark doses for the analyzed bone parameters, and to quantify strain sensitivity differences for those parameters, which were affected by TCDD exposure in both rat strains. RESULTS: Bone geometry and bone biomechanical parameters were affected by TCDD exposure, while bone mineral density parameters were less affected. The trabecular area at proximal tibia and the endocortical circumference at tibial diaphysis were the parameters that showed the highest maximal responses. Significant strain differences in response to TCDD treatment were observed, with the L-E rat being the most sensitive strain. For the parameters that were affected in both strains, the differences in sensitivity were quantified, showing the most pronounced (about 49-fold) strain difference for cross-sectional area of proximal tibia. CONCLUSION: The study provides novel information about TCDD-induced bone alterations at doses, which are of relevance from a health risk assessment point of view. In addition, the obtained results provide further support for a distinct role of the AhR in TCDD-induced bone alterations, and suggest that the benchmark dose modeling approach is appropriate for quantitative evaluation of bone toxicity parameters.

  • 27.
    Hernefalk, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Borg, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Estimating pre-traumatic quality of life in patients with surgically treated acetabular fractures and pelvic ring injuries: Does timing matter?2016In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 47, no 2, p. 389-394Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Evaluation of patient-assessed functional outcome in traumatic conditions has specific challenges. To obtain pre-traumatic data to allow for comparison during follow-up, retrospective assessments are needed. How such data is affected by posttraumatic time-point chosen for evaluation is unknown. The primary purpose of this study was to investigate how the time-point chosen for retrospective assessment of pre-traumatic quality of life (QoL) in patients with surgically treated acetabular fractures and pelvic ring injuries influenced the results. A secondary purpose was to examine the pre-traumatic QoL-profile in patients with these injuries.

    PATIENTS AND METHODS: 73 patients were included, where 50 had an acetabular fracture and 23 a pelvic ring injury. Pre-traumatic QoL was evaluated using the generic instruments SF-36 and EQ5D in conjunction with the condition-specific Pelvic Trauma Questionnaire (PTQ). Questionnaires were completed at three time points: 0, 1 and 2 months post-surgery.

    RESULTS: Number of responders were 73 patients at 0 months, 61 patients at 1 month and 53 patients at 2 months. 50 patients answered the questionnaires at all three time-points. A trend was observed with all instruments where patients estimated a better pre-traumatic status with narrower distributions when assessment was delayed. At 2 months, scores for 4 out of 8 SF-36 domains where significantly higher compared to 0 months. For EQ5D, EQ VAS improved at 1 and 2 months compared to month 0 results but no other significant differences between time-points were found. Results from the PTQ demonstrated no significant differences over time. Pre-traumatic quality of life was high and for SF-36 comparable to a population norm. A very low level of pre-existing discomfort from the pelvic region was reported through the PTQ.

    CONCLUSION: Patients with surgically treated acetabular fractures and pelvic ring injuries estimate a higher pre-traumatic functional status when assessment is carried out at 1 or 2 months post-surgery compared to perioperative measurements. The SF-36 seems to be more sensitive than the EQ5D in this respect. Pre-traumatic QoL in patients with surgically treated acetabular fractures and pelvic ring injuries is generally high and pre-existing discomfort from the pelvic region is uncommon.

  • 28.
    Hulsart Billström, Gry
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Blom, Ashley W.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Beswick, Andrew D.
    Application of scaffolds for bone regeneration strategies: Current trends and future directions2013In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 44, p. S28-S33Article in journal (Refereed)
    Abstract [en]

    Scaffolds are extensively used in surgery to replace missing bone and to achieve bony union and fusion. An ideal scaffold should not only maintain, induce, and restore biological functions where cells, extracellular matrix, and growth factors are needed, but also have the right properties with respect to degradation, cell binding, cellular uptake, non-immunogenicity, mechanical strength, and flexibility. Here we examine both the basic science behind the development of scaffolds and comprehensively and systematically review the clinical applications. 

  • 29.
    Hulsart Billström, Gry
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Selvaraju, Ramkumar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET-MRI Platform.
    Estrada, Sergio
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET-MRI Platform.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Asplund, Veronika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Bergman, Kristoffer
    TERMIRA, Stockholm, Sweden.
    Marsell, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Non-invasive tri-modal visualisation via PET/SPECT/μCT of recombinant human bone morphogenetic protein-2 retention and associated bone regeneration: A proof of concept2018In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 285, p. 178-186Article in journal (Refereed)
    Abstract [en]

    Bone morphogenetic proteins (BMP's) are vital for bone and cartilage formation, where bone morphogenetic protein-2 (BMP-2) is acknowledged as a growth factor in osteoblast differentiation. However, uncontrolled delivery may result in adverse clinical effects. In this study we investigated the possibility for longitudinal and non-invasive monitoring of implanted [125I]BMP-2 retention and its relation to ossification at the site of implantation. A unilateral critically sized femoral defect was produced in the left limb of rats while the right femur was retained intact as a paired reference control. The defect was filled with a hyaluronan hydrogel with 25% hydroxyapatite alone (carrier control; n = 2) or combined with a mixture of [125I]BMP-2 (150 μg/ml; n = 4). Bone formation was monitored using micro computed tomography (μCT) scans at 1, 3, 5, 7, 9 and 12 weeks. The retention of [125I]BMP-2 was assessed with single photon emission computed tomography (SPECT), and the bone healing process was followed with sodium fluoride (Na18F) using positron emission tomography (PET) at day 3 and at week 2, 4, and 6. A rapid burst release of [125I]BMP-2 was detected via SPECT. This was followed by a progressive increase in uptake levels of [18F]fluoride depicted by PET imaging that was confirmed as bone formation via μCT. We propose that this functional, non-invasive imaging method allows tri-modal visualisation of the release of BMP-2 and the following in vivo response. We suggest that the potential of this novel technique could be considered for preclinical evaluation of novel smart materials on bone regeneration.

  • 30.
    Hulsart-Billstrom, Gry
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Estrada, Sergio
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    BMP-2 Induced bone regeneration visualized by PET and SPECT2014In: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 8, p. 513-513Article in journal (Other academic)
  • 31.
    Hulsart-Billstrom, Gry
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Nouhi, Shirin
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Iodine-enhanced contrast applicable for microcomputed tomography2014In: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 8, p. 245-246Article in journal (Refereed)
  • 32.
    Hulsart-Billström, Gry
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Bergman, Kristoffer
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Andersson, Brittmarie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Jonsson, Kenneth B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    A uni-cortical femoral defect model in the rat: evaluation using injectable hyaluronan hydrogel as a carrier for bone morphogenetic protein-22015In: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 9, no 7, p. 799-807Article in journal (Refereed)
    Abstract [en]

    The development of biomaterial for bone regeneration requires animal models that are reliable and designed to mimic clinically relevant situations. We have previously investigated hydrogels comprised of modified hyaluronic acid and polyvinyl alcohol in models of ectopic bone formation. This hydrogel induces bone regeneration when loaded with bone morphogenetic proteins (BMPs). To allow further optimization of hydrogels, we developed a new, femoral, non-critical-sized cortical defect model. In the rat femur, we drilled standardized, elongated unilateral cortical defects that did not require stabilization and that could be created bilaterally to allow paired comparisons of biomaterials. After optimizing the defect size, subsequent stress fractures occurred in only 8% and the defect healed partially over the 40 day study period. In a time-course experiment, we treated bone defects with the previously studied hyaluronan hydrogel loaded with 10 µg hydroxyapatite and 6 µg BMP-2. The shape of the defect allowed controlled containment of the material within the defect. The defect in the right leg was left untreated, while the left defect was filled with 40 µl of the BMP hydrogel. As determined by pQCT analysis, the treated defects had a higher bone mineral content, bone area and bone density than control defects. The relative difference was greatest between the groups at 10 and 20 days and diminished as the defect healed in the untreated legs. We conclude that this animal model allows facile and rapid screening of biomaterials for bone regeneration in cortical femoral defects without requiring external fixation.

  • 33.
    Hulsart-Billström, Gry
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Bergman, Kristoffer
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Polymer Chemistry.
    Bowden, Tim
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Polymer Chemistry.
    Engstrand, Thomas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Polymer Chemistry.
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Polymer Chemistry.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    The Effect of Incubation Time of Preformed Injectable Hydrogels on Bone Formation when used as Carrier for rhBMP-22011In: TERMIS-EU 2011 Abstracts, 2011Conference paper (Refereed)
  • 34.
    Hulsart-Billström, Gry
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Carlsson, Elin
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    In vivo and in vitro performance of Sr-doped hydroxyapatite composite in the form of hollow nano-spheres2012Conference paper (Refereed)
  • 35.
    Hulsart-Billström, Gry
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Polymer Chemistry.
    Hu, Qinghong
    Centre of Biopathways and Biomaterials, Dept of Chemistry, Zhejiang University, Hangzhou, Zhejiang, China .
    Bergman, Kristoffer
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Polymer Chemistry.
    Jonsson, Kenneth B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Åberg, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Tang, Ruikang
    Centre of Biopathways and Biomaterials, Dept of Chemistry, Zhejiang University, Hangzhou, Zhejiang, China .
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Polymer Chemistry.
    Calcium phosphates compounds in conjunction with hydrogel as carrier for BMP-2: A study on ectopic bone formation in rats2011In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 7, no 8, p. 3042-3049Article in journal (Refereed)
    Abstract [en]

    Current treatment of fractures often involves the use of bone graft or bone morphogenetic proteins (BMP) to induce fracture healing, especially in patients with a compromised healing capacity. BMP has to be delivered in conjunction with a carrier. Unfortunately, there are drawbacks and limitations with current carriers, including their bovine origin which carries the risk of an immunological response. The physical properties also limit the use to open surgical procedures, as it cannot be injected. New carriers with improved properties are therefore needed. The aim of this study was to assess the ectopic bone forming capability of various calcium phosphate compounds when used in conjunction with a hydrogel as the carrier for BMP-2. Five different ceramic additives were tested, including beta-tricalcium phosphate and four types of hydroxyapatite (HAP) (nanoHAP, HAP, clods of HAP >100 mu m, and the biomimetic HAP Ostim35 (R)). The compounds were injected into the thigh muscle of rats, where it formed a gel in situ. After 4 weeks bone formation was evaluated by peripheral quantitative computed tomography and histology. The major finding was that the 20 nm nanoHAP yielded a higher bone density than the other additives (P = 0.0008, ANOVA with Tukey's multiple comparison test). We hypothesize that the higher bone density induced by nanoHAP might be due to nanocrystals of calcium phosphate acting as direct building blocks for biomineralization.

  • 36.
    Hulsart-Billström, Gry
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Jonsson, Kenneth B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Bergman, Kristoffer
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Polymer Chemistry.
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Polymer Chemistry.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    The use of a Large but not Critically Sized Fermoral Bone Defect in a Rat Model for Assesment of the Bone Forming Capacity of Various Bioactive Scaffolds2011In: TERMIS-EU 2011 Abstracts, 2011Conference paper (Refereed)
  • 37.
    Hulsart-Billström, Gry
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Piskounova, Sonya
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Gedda, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Andersson, Britt-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Bergman, Kristoffer
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Bowden, Tim
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Morphological differences in BMP-2-induced ectopic bone between solid and crushed hyaluronan hydrogel templates2013In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 24, no 5, p. 1201-1209Article in journal (Refereed)
    Abstract [en]

    The possibility to affect bone formation by using crushed versus solid hydrogels as carriers for bone morphogenetic protein 2 (BMP-2) was studied. Hydrogels, based on chemical crosslinking between hyaluronic acid and poly(vinyl alcohol) derivatives, were loaded with BMP-2 and hydroxyapatite. Crushed and solid forms of the gels were analyzed both in vitro via a release study using I-125 radioactive labeling of BMP-2, and in vivo in a subcutaneous ectopic bone model in rats. Dramatically different morphologies were observed for the ectopic bone formed in vivo in the two types of gels, even though virtually identical release profiles were observed in vitro. Solid hydrogels induced formation of a dense bone shell around non-degraded hydrogel, while crushed hydrogels demonstrated a uniform bone formation throughout the entire sample. These results suggest that by crushing the hydrogel, the construct's three-dimensional network becomes disrupted. This could expose unreacted functional groups, making the fragment's surfaces reactive and enable limited chemical fusion between the crushed hydrogel fragments, leading to similar in vitro release profiles. However, in vivo these interactions could be broken by enzymatic activity, creating a macroporous structure that allows easier cell infiltration, thus, facilitating bone formation.

  • 38.
    Hulsart-Billström, Gry
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Pankotai, Eszter
    Department of Orthopedics, Semmelweis University, Budapest, Ungern.
    Weszl, Miklos
    Department of Orthopedics, Semmelweis University, Budapest, Ungern.
    Carlsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Lacza, Zsombor
    Department of Orthopedics, Semmelweis University, Budapest, Ungern.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Bone forming potential of Sr doped hydroxyapatite hollow spheres in a rat vertebral bone defect model2012In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, no supplement 1, p. S114-Article in journal (Refereed)
  • 39.
    Hulsart-Billström, Gry
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Pankotai, Eszter
    Department of Orthopedics, Semmelweis University.
    Weszl, Miklós
    Department of Orthopedics, Semmelweis University.
    Forster-Horváth, Csaba
    Department of Orthopedics, Semmelweis University.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Lacza, Zsombor
    Department of Orthopedics, Semmelweis University.
    Osteogenic potential of Sr-doped calcium phosphate hollow spheres in vitro and in vivo2013In: Journal of Biomedical Materials Research. Part A, ISSN 1549-3296, E-ISSN 1552-4965, Vol. 101, no 8, p. 2322-2331Article in journal (Refereed)
    Abstract [en]

    Treatment of osteoporotic fractures with conventional surgical methods is associated with a high rate of complications. Intense search for new treatment options includes development of specific biomaterials aimed to be part of the surgical armamentarium. Strontium doped calcium phosphate spheres (SrCPS) is a new material that might be of interest due to the influence on osteoclast and osteoblast activity. In the present study, we successfully constructed hollow spherical SrCPS particles with a diameter of ∼700 nm and shell thickness of ∼150 nm. The Sr content was about 20 wt %. Cell viability and cytotoxicity were investigated in vitro with concentrations from 0 to 1000 μg/mL of SrCPS in medium extract in a day chase study. The in vivo biocompatibility was tested in a delayed bone-healing model in a rat vertebral defect by histology, μCT, and nanoSPECT. The SrCPS showed no toxicity in vitro with comparable cell number in all concentrations. Increased metabolism was seen in the cell viability study in cells exposed to 400 and 600 μg/mL. SPECT showed good biocompatibility with no local adverse effects and an increased osteoblast activity as compared to adjacent vertebra. SrCPS implantation induced bone formation and resulted in complete resorption and defect consolidation.

  • 40.
    Hulsart-Billström, Gry
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Yuen, Pik Kwan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Marsell, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ossipov, Dmitri
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Bisphosphonate-Linked Hyaluronic Acid Hydrogel Sequesters and Enzymatically Releases Active Bone Morphogenetic Protein-2 for Induction of Osteogenic Differentiation2013In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 14, no 9, p. 3055-3063Article in journal (Refereed)
    Abstract [en]

    Regeneration of bone by delivery of bone morphogenetic proteins (BMPs) from implantable scaffolds is a promising alternative to the existing autologous bone grafting procedures. Hydrogels are used extensively in biomaterials as delivery systems for different growth factors. However, a controlled release of the growth factors is necessary to induce bone formation, which can be accomplished by various chemical functionalities. Herein we demonstrate that functionalization of a hyaluronan (HA) hydrogel with covalently linked bisphosphonate (BP) ligands provides efficient sequestering of BMP-2 in the resulting HA-BP hydrogel. The HA-BP hydrogel was investigated in comparison with its analogue lacking BP groups (HA hydrogel). While HA hydrogel released 100% of BMP-2 over two weeks, less than 10% of BMP-2 was released from the HA-BP hydrogel for the same time. We demonstrate that the sequestered growth factor can still be released by enzymatic degradation of the HA-BP hydrogel. Most importantly, entrapment of BMP-2 in HA-BP hydrogel preserves the growth factor bioactivity, which was confirmed by induction of osteogenic differentiation of mesenchymal stem cells (MSCs) after the cells incubation with the enzymatic digest of the hydrogel. At the same time, the hydrogels degradation products were not toxic to MSCs and osteoblasts. Furthermore, BP-functionalization of HA hydrogels promotes adhesion of the cells to the surface of HA hydrogel. Altogether, the present findings indicate that covalent grafting of HA hydrogel with BP groups can alter the clinical effects of BMPs in bone tissue regeneration.

  • 41. Jensen, Per
    et al.
    Keeling, L.
    Schutz, K.
    Andersson, L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Mormede, P.
    Brändström, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Forkman, B.
    Kerje, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Fredriksson, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Ohlsson, C.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Feather pecking in chickens is genetically related to behavioural and developmental traits2005In: Physiology and Behavior, ISSN 0031-9384, E-ISSN 1873-507X, Vol. 86, no 1-2, p. 52-60Article in journal (Refereed)
    Abstract [en]

    Feather pecking (FP) is a detrimental behaviour in chickens, which is performed by only some individuals in a flock. FP was studied in 54 red junglefowl (ancestor of domestic chickens), 36 White Leghorn laying hens, and 762 birds from an F(2)-intercross between these two lines. From all F(2)-birds, growth and feed consumption were measured. Age at sexual maturity and egg production in females, and corticosterone levels in males were also measured. From 333 F(2)-birds of both sexes, and 20 parental birds, body composition with respect to bone mineral content, muscle and fat was obtained by post-mortem examinations using Dual X-Ray Absorptiometry (DXA). In femurs of the same birds, the bone density and structure were analysed using DXA and Peripheral Quantitative Computerized Tomography (pQCT), and a biomechanical analysis of bone strength was performed. Furthermore, plumage condition was determined in all birds as a measure of being exposed to feather pecking. Using 105 DNA-markers in all F(2)-birds, a genome-wide scan for Quantitative Trait Loci (QTL), associated with the behaviour in the F(2)-generation was performed. FP was at least as frequent in the red junglefowl as in the White Leghorn strain studied here, and significantly more common among females both in the parental strains and in the F(2)-generation. In the F(2)-birds, FP was phenotypically linked to early sexual maturation, fast growth, weak bones, and, in males, also high fat accumulation, indicating that feather peckers have a different resource allocation pattern. Behaviourally, F(2) feather peckers were more active in an open field test, in a novel food/novel object test, and in a restraint test, indicating that feather pecking might be genetically linked to a proactive coping strategy. Only one suggestive QTL with a low explanatory value was found on chromosome 3, showing that many genes, each with a small effect, are probably involved in the causation of feather pecking. There were significant effects of sire and dam on the risk of being a victim of feather pecking, and victims grew faster pre- and post-hatching, had lower corticosterone levels and were less active in a restraint test. Hence, a wide array of behavioural and developmental traits were genetically linked to FP.

  • 42. Kakar, Sanjeev
    et al.
    Tornetta, Paul
    Schemitsch, Emil H
    Swiontkowski, Marc F
    Koval, Kenneth
    Hanson, Beate P
    Jönsson, Anders
    Bhandari, Mohit
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Technical considerations in the operative management of femoral neck fractures in elderly patients: a multinational survey.2007In: The Journal of trauma, injury, infection, and critical care, ISSN 1079-6061, Vol. 63, no 3, p. 641-646Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To identify current opinions among orthopedic traumatologists relating to technical aspects of internal fixation and arthroplasty for patients with femoral neck fractures. METHODS: We developed and administered a survey to orthopedic surgeons who were members of the Orthopedic Trauma Association and European clinics affiliated with AO International (Davos, Switzerland). Surgeons reported preferences in specific aspects of the surgical technique for internal fixation as well as arthroplasty. Each surgeon received either a mailed package (7-page survey, a personalized cover letter, and a stamped return envelope) or an email with a link to the same survey on the Internet with an identification code. At 6 weeks, 12 weeks, and 18 weeks after the initial mailing, we remailed the questionnaire to all nonresponders. RESULTS: Of the 442 surgeons who were sent the questionnaire, 298 (68%) responded. The typical respondent was a North American aged more than 40 years, in academic practice, supervised residents, had fellowship training in trauma, and worked in a low-volume center. Among surgeons who treated displaced femoral neck fractures with arthroplasty, significant disparities existed in terms of the type of anesthesia (51% preferring general anesthesia), surgical approach (47% used posterior approach), and placement of unipolar implants (50%). Surgeons tended to agree on the use of cement fixation (69%), repairing the capsule (80%), and not using a drain postoperatively (68%). Surgeons who preferentially treated hip fractures with internal fixation tended to have a lack of consensus in terms of what constituted acceptable surgical delays (43% allowing greater than 48 hours) and which screw configuration to use, with more than half using a triangle with base inferior construct. Surgeons tended to agree on the use of closed fracture reduction techniques (69%), three cannulated screws (73%), and did not routinely perform a capsulotomy (80%) or aspirate the fracture hematoma (90%). Within both treatment groups (internal fixation and arthroplasty), surgeons tended to agree on the use of perioperative antibiotics (>92%), thromboprophylaxis (98%), and postoperative weight bearing status (>87%). CONCLUSIONS: A general lack of consensus exists among orthopedic trauma surgeons in the management of displaced femoral neck fractures. With an ever-growing emphasis upon the practice of evidence-based medicine, we have demonstrated several disparities in the technical aspects of fixation and perioperative care likely caused by a general lack of available evidence. We recommend the need for future research and large collaborative efforts.

  • 43.
    Kammerlander, Christian
    et al.
    Munich Univ Hosp LMU, Dept Trauma Surg, Nussbaumstr 20, D-80336 Munich, Germany.;Med Univ Innsbruck, Dept Trauma Surg & Sportsmed, Anichstr 35, A-6020 Innsbruck, Austria..
    Neuerburg, Carl
    Munich Univ Hosp LMU, Dept Trauma Surg, Nussbaumstr 20, D-80336 Munich, Germany..
    Verlaan, Jorrit-Jan
    Univ Med Ctr Utrecht, Dept Orthopaed, Utrecht, Netherlands..
    Schmoelz, Werner
    Med Univ Innsbruck, Dept Trauma Surg & Sportsmed, Anichstr 35, A-6020 Innsbruck, Austria..
    Miclau, Theodore
    Univ Calif San Francisco, Dept Orthopaed Surg, Orthopaed Trauma Inst, San Francisco, CA USA..
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    The use of augmentation techniques in osteoporotic fracture fixation2016In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 47, p. S36-S43Article in journal (Refereed)
    Abstract [en]

    There are an increasing number of fragility fractures, which present a surgical challenge given the reduced bone quality of underlying osteoporosis. Particularly in aged patients, there is a need for early weight bearing and mobilization to avoid further complications such as loss of function or autonomy. As an attempt to improve fracture stability and ultimate healing, the use of biomaterials for augmentation of osseous voids and fracture fixation is a promising treatment option. Augmentation techniques can be applied in various locations, and fractures of the metaphyseal regions such as proximal humerus, femur, tibia and the distal radius remain the most common areas for its use. The current review, based on the available mechanical and biological data, provides an overview of the relevant treatment options and different composites used for augmentation of osteoporotic fractures.

  • 44.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Anti-sclerostin - is there an indication?2016In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 47, p. S31-S35Article in journal (Refereed)
    Abstract [en]

    Several decades ago, a clinical condition that included severe bone overgrowth was described in a few patients in South Africa. The autosomal-recessive disease that later was named sclerosteosis was found to be caused by a mutation in the SOTS gene causing a lack of the protein sclerostin. This protein is produced by osteocytes and exerts its effect as an inhibitor of bone formation by blocking the Wnt signaling pathway. By the use of a monoclonal antibody that can block sclerostin a novel therapeutic pathway for rebuilding bone has been described. Preclinical studies have shown increased bone mass following subcutaneously administered anti-sclerostin antibody in animals with induced postmenopausal osteoporosis as well as in intact male rats and non-human primates. In a phase II study the efficacy and safety of an anti-sclerostin antibody, romosozumab, has been evaluated in 419 postmenopausal women for 12 months. 70, 140 or 210 mg was given subcutaneously monthly or every three months and compared to 70 mg of oral alendronate given once a week or 20 mu g of teriparatide subcutaneously once daily. All dose levels of romosozumab were associated with significant increase in BMD with the most pronounced gain in the group receiving 210 mg where lumbar spine BMD increased with 11.3% from baseline. The BMD for the placebo group decreased by 0.1% while the alendronate group increased 4.1% and the teriparatide increased 7.1%. Biochemical markers revealed a transitory increase in the bone formation marker P1NP while no change in the bone resorption marker beta-CTX. In comparison, teriparatide resulted in an increase for both P1NP and beta-CTX for the complete study period. Even though the rapid gain in BMD is promising when considering a treatment option for osteoporosis and other conditions with bone loss, there are so far no published studies on whether anti-sclerostin can reduce the number of fractures. Wnt signaling might also play an important role in fracture healing with substances that causes an upregulation of the Wnt pathway producing enhancement of the fracture healing process. Healing of experimental fractures in various animal models have shown improvement following subcutaneously administered anti-sclerostin antibody. While there are no published reports on the potential effect of systemically administered anti-sclerostin antibodies on fracture healing in humans.

  • 45.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Calcium phosphates: what is the evidence?2010In: Journal of Orthopaedic Trauma, ISSN 0890-5339, E-ISSN 1531-2291, Vol. 24, no Suppl.1, p. S41-S45Article in journal (Refereed)
    Abstract [en]

    A number of different calcium phosphate compounds such as calcium phosphate cements and solid beta-tricalcium phosphate products have been introduced during the last decade. The chemical composition mimics the mineral phase of bone and as a result of this likeness, the materials seem to be remodeled as for normal bone through a cell-mediated process that involves osteoclastic activity. This is a major difference when compared with, for instance, calcium sulphate compounds that after implantation dissolve irrespective of the new bone formation rate. Calcium phosphates are highly biocompatible and in addition, they act as synthetic osteoconductive scaffolds after implantation in bone. When placed adjacent to bone, osteoid is formed directly on the surface of the calcium phosphate with no soft tissue interposed. Remodeling is slow and incomplete, but by adding more and larger pores, like in ultraporous beta-tricalcium phosphate, complete or nearly complete resorption can be achieved. The indications explored so far include filling of metaphyseal fracture voids or bone cysts, a volume expander in conjunction with inductive products, and as a carrier for various growth factors and antibiotics. Calcium phosphate compounds such as calcium phosphate cement and beta-tricalcium phosphate will most certainly be part of the future armamentarium when dealing with fracture treatment. It is reasonable to believe that we have so far only seen the beginning when it comes to clinical applications.

  • 46.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Cement augmentation in fracture treatment2006In: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 95, no 2, p. 111-118Article in journal (Refereed)
    Abstract [en]

    Surgical treatment of fractures close to joints, especially in osteoporotic patients, is often associated with problems to obtain. adequate strength of the bone-implant construct as well as sufficient purchase for screws in the weak bone. One way to address this increasing problem is through the development of new metal implants specifically designed for fixation of fractures in osteopenic bone. An alternative strategy is to develop methods for augmentation of the weak bone that surrounds the metal implant. In most instances augmentation is achieved by using injectable cement to reinforce the bone. Conventional PMMA provides good strength but due to several drawbacks it has never gained general acceptance for fracture augmentation. More recently several injectable cements based on calcium-phosphate, calcium-sulphate or bioglass has been developed for augmentation of fractures in the extremities as well as for vertebral compressive fractures in the spine. On the basis of biomechanical studies and the clinical experience so far, cement augmentation will enable faster rehabilitation, as the strength of the cement makes it possible to allow full weight-bearing earlier than conventional metal implants alone. More clinical studies are needed in order to refine the surgical technique, develop cement types aimed for fracture treatment and define the most appropriate indications and limitations of augmentation for fracture repair.

    The purpose of this article is to review the possible use of augmentation as a technique in the treatment of fractures in the extremities as well as in the spine.

  • 47.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Clavicula fractures: considerations when plating2018In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 49, no suppl. 1, p. S24-S28Article in journal (Refereed)
    Abstract [en]

    The preferred treatment of clavicula midshaft fractures in adults has gone from being very conservative into surgery being frequently recommended. However, based on recent meta-analysis favorable outcome with internal fixation is not as consistent as previously reported. Probably due to a combination of indications for surgery becoming too wide and surgery being performed by a wider group of surgeons. When using plating for clavicula fractures there are several considerations to consider to improve outcome while reducing the risk for complications. Traditionally a horizontal approach along the clavicula is used as it provides good exposure. However, this incision is associated with a high risk for permanent anterior chest wall numbness that might be very disturbing for patients. A vertical incision can instead be used. Plates are traditionally placed in a superior position. An alternative can be an anterior-inferior position that allows better soft tissue coverage, less risk for hardware protrusion, longer screws can be used and the risk for damaging the underlying neurovascular bundle is reduced. Angle-stable screw-plate systems has not in a convincing way shown any benefit in clavicula fractures. In part because most patients have good bone quality where conventional screws will be sufficient.

  • 48.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Periarticular fractures around the hip and knee: fix or replace?2011In: Journal of Orthopaedic Trauma, ISSN 0890-5339, E-ISSN 1531-2291, Vol. 25, no Suppl 2, p. S90-S94Article in journal (Refereed)
    Abstract [en]

    The number of periarticular fragility fractures around the hip and knee is increasing. If surgical treatment is indicated, open reduction and internal fixation or replacement can often be viable options. In contrast to secondary replacement, the use of replacement in the acute stage might be advantageous because early rehabilitation and weightbearing can be initiated. This article describes the current literature related to internal fixation or primary replacement in periarticular fractures around the hip and knee.

  • 49.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Time to invest in a "fracture liaison nurse"!2007In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 38, no 11, p. 1225-1226Article in journal (Refereed)
  • 50.
    Larsson, Sune
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Fazzalari, Nicola L.
    Anti-osteoporosis therapy and fracture healing2014In: Archives of Orthopaedic and Trauma Surgery, ISSN 0936-8051, E-ISSN 1434-3916, Vol. 134, no 2, p. 291-297Article in journal (Refereed)
    Abstract [en]

    A number of medications are approved for treatment of osteoporosis. As mode of action usually is anti-catabolic/anti-resorptive or anabolic, it is of interest to know whether these drugs affect not only normal bone remodeling, but also fracture healing. The purpose of this paper is to give a short overview of the potential effect of various anti-osteoporotic medication on fracture healing. A narrative literature review was performed to describe the current knowledge. Anti-catabolic/anti-resorptive drugs: for bisphosphonates, the most common class of drugs in this group, experimental studies have shown a larger and stronger callus and delayed remodeling but no evidence of delayed healing. A human monoclonal antibody to RANKL is another anti-catabolic drug, with the only report to date showing enhanced healing in an animal model. Strontium ranelate is a drug where both anti-catabolic and a weak anabolic effect have been proposed, with experimental data ranging from no effect to significant increase in both callus volume and strength. Anabolic drugs: PTH has demonstrated accelerated healing of various experimental fractures and of distal radius and pelvic fractures in humans. While the exact mechanism is not fully understood, PTH results in increased recruitment and differentiation of chondrocytes and enhancement of endochondral ossification. A monoclonal antibody to block sclerostin is another potential anabolic pathway, where animal data have shown increase in bone mass and strength. The potential effect on fracture healing is yet to be studied. There are still large gaps in the understanding of the potential effect of anti-osteoporotic drugs on fracture healing, although based on present knowledge a recent or present fracture should not be considered as a contraindication to such treatment.

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