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  • 1.
    Abtahi, Jahan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Henefalk, G.
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Randomised trial of bisphosphonate-coated dental implants: Radiographic follow-up after five years of loading2016In: International Journal of Oral and Maxillofacial Surgery, ISSN 0901-5027, E-ISSN 1399-0020, Vol. 45, no 12, p. 1564-1569Article in journal (Refereed)
    Abstract [en]

    The results of a randomised trial with bisphosphonate-coated dental implants have been reported previously. Each patient received one coated and one uncoated implant in a double-blind split-mouth design study. After 6 months of osseointegration, resonance frequency analysis indicated better fixation of the coated implants. Reduced marginal bone resorption was also shown. However, it was not known whether the advantage of the bisphosphonate coating would persist over time. The radiographic results at 5 years after implant installation are reported herein. A blinded investigator measured marginal resorption on fresh radiographs obtained for 14 of the 16 patients (two had died) and compared these with the post-implantation images. Non-parametric statistics were used. All implants functioned well. The median marginal bone loss for control implants was found to be 0.70 mm, which is less than usually reported in the literature. The bisphosphonate-coated implants showed even less resorption (median 0.20 mm). The median difference within each pair of implants after 5 years of use was 0.34 mm (95% confidence interval 0.00-0.75 mm; P = 0.04). The present data suggest that bisphosphonate-coated implants enable prolonged preservation of the marginal bone.

  • 2.
    Abtahi, Jahan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Henefalk, Gustav
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Impact of a zoledronate coating on early post-surgical implant stability and marginal bone resorption in the maxilla-A split-mouth randomized clinical trial.2019In: Clinical Oral Implants Research, ISSN 0905-7161, E-ISSN 1600-0501, Vol. 30, no 1, p. 49-58Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The objective of this clinical study was to evaluate the effect of a bisphosphonate coating on a titanium implant on the implant stability quotient (ISQ) and the radiographic marginal bone levels at implants during early healing (2-8 weeks).

    MATERIALS AND METHODS: In a randomized double-blind trial with internal controls, 16 patients received a dental implant coated with zoledronate and one uncoated implant as a control. The coated and uncoated implants which were visually indistinguishable were bone level titanium implants with a moderately rough surface and a microthreaded neck. ISQ values were obtained at insertion and at 2, 4, 6, and 8 weeks. Radiographs were obtained at insertion and at 8 weeks. The primary outcome was the difference in ISQ values between the coated implants and the control implants at 4 and 6 weeks, corrected for insertion values. The secondary outcome was loss of marginal bone level from insertion to 8 weeks.

    RESULTS: Implant stability quotient values remained largely constant over the 8 weeks, and there was no significant difference between coated and uncoated implants at any time point. There was 0.12 (SD 0.10) mm marginal bone loss at the control implants and 0.04 (SD 0.08) mm at the coated implants. The difference was 0.17 mm; SD 0.14; p < 0.006). On blind qualitative scoring, 13 of the 15 control implants and two of 15 coated implants showed small marginal bone defects (p = 0.003).

    CONCLUSIONS: There were no statistically significant differences observed in ISQ values between the coated and uncoated implants during the early healing. There was less marginal bone loss at the coated implants.

  • 3.
    Adolfsson, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Editorial Material: Is surgery for the subacromial pain syndrome ever indicated? in ACTA ORTHOPAEDICA, vol 86, issue 6, pp 639-6402015In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 86, no 6, p. 639-640Article in journal (Other academic)
    Abstract [en]

    n/a

  • 4.
    Adolfsson, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Post-traumatic stiff elbow2018In: EFORT open reviews, ISSN 2058-5241, Vol. 3, no 5, p. 210-216Article, review/survey (Refereed)
    Abstract [en]

    Post-traumatic and post-operative stiffness of the elbow joint is relatively common and may in pronounced cases markedly interfere with normal upper extremity function.Soft-tissue contractures and heterotopic bone formation are two major causes of limited movement.Extensive recent research has elucidated many of the pathways contributing to these conditions, but the exact mechanisms are still unknown.In the early phase of soft-tissue contractures conservative treatment may be valuable, but in longstanding cases operative treatment is often necessary.Several different options are available depending on the severity of the condition and the underlying offending structures. Surgical treatment may allow significant gains in movement but rarely complete restoration, and complications are not uncommon.The following presentation reviews the recent literature on pathomechanisms and treatment alternatives. Cite this article: EFORT Open Rev 2018;3 DOI: 10.1302/2058-5241.3.170062.

  • 5.
    Adolfsson, Lars
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Nestorson, Jens
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Scheer, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Extensive soft tissue lesions in redislocated after simple elbow dislocations2017In: Journal of shoulder and elbow surgery, ISSN 1058-2746, E-ISSN 1532-6500, Vol. 26, no 7, p. 1294-1297Article in journal (Refereed)
    Abstract [en]

    Background: The majority of simple elbow dislocations (no associated fractures) can be treated nonoperatively with a short period of immobilization followed by guided aftercare. This case series describes the soft tissue injuries in a rare subset of patients in whom the elbow redislocated despite adequate immobilization. Methods: During a 6-year period, 8 patients were identified. They were all treated with reduction and casting in 90 degrees of flexion or more. At 1 week of follow-up, redislocation had occurred in all patients and open soft tissue repair was performed. The injuries were documented and the patients were followed up clinically and with radiographs. Results: Extensive soft tissue injuries, including both collateral ligament injuries and muscle origin avulsions from either or both sides, were found in all patients. The functional result at follow-up was satisfactory in all patients. Conclusion: Vast soft tissue injuries including both collateral ligaments and muscle origins should be expected in the event of early severe instability of a dislocated elbow joint. (C) 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. All rights reserved.

  • 6.
    Amirhosseini, Mehdi
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Andersson, Göran
    Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Fahlgren, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Mechanical instability and titanium particles induce similar transcriptomic changes in a rat model for periprosthetic osteolysis and aseptic loosening2017In: Bone Reports, ISSN 2352-1872, Vol. 7, p. 17-25Article in journal (Refereed)
    Abstract [en]

    Wear debris particles released from prosthetic bearing surfaces and mechanical instability of implants are two main causes of periprosthetic osteolysis. While particle-induced loosening has been studied extensively, mechanisms through which mechanical factors lead to implant loosening have been less investigated. This study compares the transcriptional profiles associated with osteolysis in a rat model for aseptic loosening, induced by either mechanical instability or titanium particles. Rats were exposed to mechanical instability or titanium particles. After 15 min, 3, 48 or 120 h from start of the stimulation, gene expression changes in periprosthetic bone tissue was determined by microarray analysis. Microarray data were analyzed by PANTHER Gene List Analysis tool and Ingenuity Pathway Analysis (IPA). Both types of osteolytic stimulation led to gene regulation in comparison to unstimulated controls after 3, 48 or 120 h. However, when mechanical instability was compared to titanium particles, no gene showed a statistically significant difference (fold change = ± 1.5 and adjusted p-value = 0.05) at any time point. There was a remarkable similarity in numbers and functional classification of regulated genes. Pathway analysis showed several inflammatory pathways activated by both stimuli, including Acute Phase Response signaling, IL-6 signaling and Oncostatin M signaling. Quantitative PCR confirmed the changes in expression of key genes involved in osteolysis observed by global transcriptomics. Inflammatory mediators including interleukin (IL)-6, IL-1ß, chemokine (C-C motif) ligand (CCL)2, prostaglandin-endoperoxide synthase (Ptgs)2 and leukemia inhibitory factor (LIF) showed strong upregulation, as assessed by both microarray and qPCR. By investigating genome-wide expression changes we show that, despite the different nature of mechanical implant instability and titanium particles, osteolysis seems to be induced through similar biological and signaling pathways in this rat model for aseptic loosening. Pathways associated to the innate inflammatory response appear to be a major driver for osteolysis. Our findings implicate early restriction of inflammation to be critical to prevent or mitigate osteolysis and aseptic loosening of orthopedic implants.

  • 7.
    Ardern, Clare
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. School of Allied Health, La Trobe University, Melbourne, Australia.
    Österberg, Annika
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Tagesson, Sofi
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Gauffin, Håkan
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Webster, Kate E.
    La Trobe University, Australia.
    Kvist, Joanna
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Satisfaction With Knee Function After Primary Anterior Cruciate Ligament Reconstruction Is Associated With Self-Efficacy, Quality of Life, and Returning to the Preinjury Physical Activity2016In: Arthroscopy: The Journal of Arthroscopy And Related, ISSN 0749-8063, E-ISSN 1526-3231, Vol. 32, no 8, p. 1631-1638Article in journal (Refereed)
    Abstract [en]

    Purpose: To assess whether patient-reported outcomes (psychological factors, appraisals of knee function, and physical activity participation) were associated with satisfaction with knee function after anterior cruciate ligament (ACL) reconstruction. Methods: Participants who were aged 18 to 45 years and a minimum 12 months post primary ACL reconstruction completed a questionnaire battery evaluating knee self-efficacy, knee-related quality of life, self-reported function, and physical activity participation. Participants responses to the question "If you were to spend the rest of your life with your knee just the way it has been in the last week, would you feel.... (7-point ordinal scale; 1 = happy, 7 = unhappy)" were categorized as satisfied, mostly satisfied, or dissatisfied and used as the primary outcome. Ordinal regression was used to examine associations between independent variables and the primary outcome. Results: A total of 177 participants were included at an average of 3 years after primary ACL reconstruction. At follow-up, 44% reported they would be satisfied, 28% mostly satisfied, and 28% dissatisfied with the outcome of ACL reconstruction. There were significant differences in psychological responses and appraisal of knee function between the 3 groups (P = .001), and significantly more people in the satisfied group had returned to their preinjury activity (58%) than in the mostly satisfied (28%) and dissatisfied (26%) groups (P = .001). Multivariable analysis demonstrated that the odds of being satisfied increased by a factor of 3 with higher self-efficacy, greater knee-related quality of life, and returning to the preinjury activity. Conclusions: People who had returned to their preinjury physical activity and who reported higher knee-related self-efficacy and quality of life were more likely to be satisfied with the outcome of ACL reconstruction.

  • 8.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Apropå! En arrogant organisation2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114Article in journal (Other academic)
    Abstract [en]

    n/a

  • 9.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Atypical fractures, a biased perspective2016In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 47, no 1, p. S28-S30Article in journal (Refereed)
    Abstract [en]

    When stress fractures started to show up in the femurs of elderly ladies, it was soon evident that bisphosphonate use lay behind, and the absolute risk increase due to bisphosphonate use was reasonably well estimated already in 2008. Thereafter followed a period of confusion: the term atypical fracture was introduced, with a definition so vague that the true stress fractures tended to disappear in a cloud of ambiguity. This cast doubt on the association with bisphosphonates. The association was then re-established by large epidemiological studies based on radiographic adjudication. Atypical fractures are largely caused by bisphosphonates. With a correct indication, bisphosphonates prevent many more fractures than they cause, at least during the first years of use. With an incorrect indication they are likely to cause more harm than good. (C) 2016 Elsevier Ltd. All rights reserved.

  • 10.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Beslut att operera kopplat till ortopeders attityder till kirurgi2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, no 41Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 11.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Editorial Material: ACADEMIC AUTHORSHIP How I was nearly duped into "authoring" a fake paper in BMJ-BRITISH MEDICAL JOURNAL, vol 351, issue h6605, pp2015In: BMJ-BRITISH MEDICAL JOURNAL, ISSN 1756-1833, Vol. 351, no h6605Article in journal (Other academic)
    Abstract [en]

    n/a

  • 12.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Editorial Material: Why do we operate proximal humeral fractures?2015In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 86, no 3, p. 279-279Article in journal (Other academic)
  • 13.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Placeboeffekten är övervärderad: »Återgång till medelvärdet« kan förklara förbättring efter skenbehandling – men misstolkas ofta2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114Article in journal (Refereed)
  • 14.
    Aspenberg, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Malouf, Jorge
    Hospital San Pablo, Spain.
    Tarantino, Umberto
    University of Roma Tor Vergata, Italy.
    Garcia-Hernandez, Pedro A.
    University Hospital, Mexico.
    Corradini, Costantino
    University of Milan, Italy.
    Overgaard, Soren
    Odense University Hospital, Denmark; University of Southern Denmark, Denmark.
    Stepan, Jan J.
    Charles University of Prague, Czech Republic; Charles University of Prague, Czech Republic.
    Borris, Lars
    University Hospital, Denmark.
    Lespessailles, Eric
    CHR Orleans, France; University of Orleans, France.
    Frihagen, Frede
    Oslo University Hospital, Norway.
    Papavasiliou, Kyriakos
    Aristotle University of Thessaloniki, Greece.
    Petto, Helmut
    Eli Lilly, Austria.
    Ramon Caeiro, Jose
    University of Santiago de Compostela, Spain.
    Marin, Fernando
    Eli Lilly Research Centre, England.
    Effects of Teriparatide Compared with Risedronate on Recovery After Pertrochanteric Hip Fracture Results of a Randomized, Active-Controlled, Double-Blind Clinical Trial at 26 Weeks2016In: Journal of Bone and Joint Surgery. American volume, ISSN 0021-9355, E-ISSN 1535-1386, Vol. 98, no 22Article in journal (Refereed)
    Abstract [en]

    Background: Osteoporosis drugs might affect fracture-healing. We therefore studied the effects of teriparatide in comparison with risedronate on recovery after pertrochanteric hip fractures. Methods: The study was a randomized, multicenter, active-controlled, 78-week trial comparing teriparatide (20 mg/day) with risedronate (35 mg/week) initiated within 2 weeks after fixation of a low-trauma pertrochanteric hip fracture (AO/OTA 31-A1 or 31-A2). The main inclusion criteria were a bone mineral density T-score of amp;lt;=-22.0 and 25-OH-vitamin D of amp;gt;= 9.2 ng/mL. During the first 26 weeks, patients received study medication with oral or injectable placebo plus calcium and vitamin D in a double-blinded fashion. Secondary (Timed Up-and-Go [TUG] test, hip pain, Short Form [SF]-36 health status, and safety) and exploratory (radiographic outcomes and ability to walk) 26-week end points are reported. Results: Of the 224 patients who were randomized, 171 (86 teriparatide, 85 risedronate) were included in the analysis. The mean age was 77 +/- 8 years, 77% were female, and 26% had a prior history of low-trauma fracture. The teriparatide group completed the TUG test in a shorter time at 6, 12, 18, and 26 weeks (differences of 25.7, -4.4, -3.1, and -3.1 seconds, respectively; p = 0.021 for the overall difference). They also reported less pain on a visual analog scale immediately after the TUG test at 12 and 18 weeks (adjusted absolute differences of 10.6 and 11.9 mm, respectively; p amp;lt; 0.05). There were no significant between-group differences in the SF-36 score, Charnley hip pain score, ability to walk, or use of walking aids during follow-up. Radiographic healing at 6, 12, and 26 weeks, mechanical failure of the implant (teriparatide, 7; risedronate, 8), loss of reduction (teriparatide, 2; risedronate, 4), and nonunion (0 cases) were not significantly different. Mild hypercalcemia and hyperuricemia were more frequent with teriparatide. Conclusions: Teriparatide was associated with less pain and a shorter time to complete the TUG test between 6 and 26 weeks compared with risedronate. Other fracture-recovery outcomes were similar. The results should be interpreted with caution as these were secondary end points.

  • 15.
    Aspenberg, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Michaëlsson, Karl
    Uppsala, Sweden.
    Rydholm, Anders
    Lund, Sweden.
    Svensson, Olle
    Umeå, Sweden.
    Artrosskolan: evidensen måste stärkas2018In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115Article in journal (Other academic)
  • 16.
    Aspenberg, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Schepull, Torsten
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Substantial creep in healing human Achilles tendons: A pilot study2015In: MLTJ Muscles, Ligaments and Tendons Journal, ISSN 2240-4554, Vol. 5, no 3, p. 151-155Article in journal (Other academic)
    Abstract [en]

    Background: healing after rupture of the Achilles tendon can be described in terms of mechanical properties of the new-formed tissue, constituting the tendon callus. In previous human studies, the elastic modulus and the density remained almost constant during 3 months after mobilization started, and then improved up to one year. So far, time-dependent deformation of the healing human tendon has not been reported.

    Methods: in a series of 16 patients, operated with Achilles tendon suture, we implanted tantalum beads into the tendon and measured the distance between them repeatedly during 3 min of constant loading, using an ordinary image intensifier. The patients unloaded their leg for 30 min before the test. To avoid bias, all images were investigated in a randomized and blinded order.

    Results: total strain during 3 min of constant loading at 7 weeks post injury amounted to 5%, and at 19 weeks to 3%. About half of the strain, after the loading was applied, occurred during the second and third min. Considerable strain also occurred just before loading, when the patient was told that a load would be applied, but before this was actually done.

    Conclusion: the measurements were crude, and this study should be seen as a pilot. Still, viscoelastic properties seem to dominate the mechanical behavior the healing Achilles tendon from start of mobilization to 19 weeks, at least when tested after 30 min rest. This deserves further studies with more precise methods.

  • 17.
    Bernhardsson, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Abaloparatide versus teriparatide: a head to head comparison of effects on fracture healing in mouse models2018In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 89, no 6, p. 674-677Article in journal (Refereed)
    Abstract [en]

    Background and purpose - Teriparatide accelerates fracture healing in animals and probably in man. Abaloparatide is a new drug with similar although not identical effects on the teriparatide receptor. Given at 4 times the teriparatide dose in a human osteoporosis trial, abaloparatide increased bone density more than teriparatide, and both reduced fracture risk. We investigated in mice whether abaloparatide stimulates fracture healing, and if it does so with the suggested dose effect relation (4:1). Patients and methods - In a validated mouse model for metaphyseal healing (burr hole with screw pull-out), 96 mice were randomly allocated to 11 groups: control (saline), teriparatide or abaloparatide, where teriparatide and abaloparatide were given at 5 different doses each. In a femoral shaft osteotomy model, 24 mice were randomly allocated to 3 groups: control (saline), teriparatide (15 mu g/kg) or abaloparatide (60 mu g/kg). Each treatment was given daily via subcutaneous injections. Results were evaluated by mechanical testing and microCT. Results - In the metaphyseal model, a dose-dependent increase in screw pull-out force could be seen. In a linear regression analysis (r = 0.78) each increase in ln(dose) by 1 (regardless of drug type) was associated with an increase in pull-out force by 1.50 N (SE 0.18) (p amp;lt; 0.001). Changing drug from teriparatide to abaloparatide increased the force by 1.41 N (SE 0.60; p = 0.02). In the diaphyseal model, the callus density was 23% (SD 10), 38% (SD 10), and 47% (SD 2) for control, for teriparatide and abaloparatide respectively. Both drugs were significantly different from controls (p = 0.001 and p = 0.008), but not from each other. Interpretation - Both drugs improve fracture healing, but in these mouse models, the potency per mu g of abaloparatide seems only 2.5 times that of teriparatide, rather than the 4:1 relation chosen in the clinical abaloparatide-teriparatide comparison trial.

  • 18.
    Bernhardsson, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Osteoblast precursors and inflammatory cells arrive simultaneously to sites of a trabecular-bone injury2018In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 89, no 4, p. 457-461Article in journal (Refereed)
    Abstract [en]

    Background and purpose - Fracture healing in the shaft is usually described as a sequence of events, starting with inflammation, which triggers mesenchymal tissue formation in successive steps. Most clinical fractures engage cancellous bone. We here describe fracture healing in cancellous bone, focusing on the timing of inflammatory and mesenchymal cell type appearance at the site of injury. Material and methods - Rats received a proximal tibial drill hole, A subgroup received clodronate-containing liposomes before or after surgery. The tibiae were analyzed with micro-CT and immunohistochemistry 1 to 7 days after injury. Results - Granulocytes (myeloperoxidase) appeared in moderate numbers within the hole at day 1 and then gradually disappeared. Macrophage expression (CD68) was seen on day 1, increased until day 3, and then decreased. Mesenchymal cells (vimentin) had already accumulated in the periphery of the hole on day 1. Mesenchymal cells dominated in the entire lesion on day 3, now producing extracellular matrix. A modest number of preosteoblasts (RUNX2) were seen on day 1 and peaked on day 4. Osteoid was seen on day 4 in the traumatized region, with a distinct border to the uninjured surrounding marrow. Clodronate liposomes given before the injury reduced the volume of bone formation at day 7, but no reduction in macrophage numbers could be detected. Interpretation - The typical sequence of events in shaft fractures was not seen. Mesenchymal cells appeared simultaneously with granulocyte and macrophage arrival. Clodronate liposomes, known to reduce macrophage numbers, seemed to be associated with the delineation of the volume of tissue to be replaced by bone.

  • 19.
    Bernhardsson, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Dietrich, Franciele
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Tätting, Love
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Eliasson, Pernilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Depletion of cytotoxic (CD8+) T cells impairs implant fixation in rat cancellous bone2019In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 37, no 4, p. 805-811Article in journal (Refereed)
    Abstract [en]

    As cytotoxic (CD8(+)) T cells seem to impair shaft fracture healing, we hypothesized that depletion of CD8(+) cells would instead improve healing of cancellous bone. Additionally, we also tested if CD8-depletion would influence the healing of ruptured Achilles tendons. Rats received a single injection of either anti-CD8 antibodies or saline and put through surgery 24 h later. Three different surgical interventions were performed as follows: (1) a drill hole in the proximal tibia with microCT (BV/TV) to assess bone formation; (2) a screw in the proximal tibia with mechanical evaluation (pull-out force) to assess fracture healing; (3) Achilles tendon transection with mechanical evaluation (force-at-failure) to assess tendon healing. Furthermore, CD8-depletion was confirmed with flow cytometry on peripheral blood. Flow cytometric analysis confirmed depletion of CD8(+) cells (p amp;lt; 0.001). Contrary to our hypothesis, depletion of CD8(+) cells reduced the implant pull-out force by 19% (p amp;lt; 0.05) and stiffness by 34% (p amp;lt; 0.01), although the bone formation in the drill holes was the same as in the controls. Tendon healing was unaffected by CD8-depletion. Our results suggest that CD8(+) cells have an important part in cancellous bone healing.

  • 20.
    Bernhardsson, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Anti-RANKL treatment improves screw fixation in cancellous bone in rats2015In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 46, no 6, p. 990-995Article in journal (Refereed)
    Abstract [en]

    Bisphosphonates improve implant fixation in randomised clinical trials of knee prostheses, hip prostheses and dental implants. However, a limited amount of bone resorption is required for bisphosphonates to exert an effect. Anti-RANKL treatment does not have this limitation, and we therefore tested whether if they might be more effective for improvement of implant fixation. This is of interest, as anti-RANKL treatment with denosumab is now in common clinical use. Male SD rats received a stain-less steel screw in the right proximal tibia and a drill hole in the left (n = 42). They were randomised to subcutaneous injections of either alendronate (20 mu g/kg/day), alendronate (200 mu g/kg/day), osteoprotegerin with an Fc tag (OPG-Fc; 8 mg/kg, twice weekly), or saline control. After 4 weeks, the fixation of the steel screw was measured by pull-out test. The tibia with the drill hole was evaluated with mu CT. OPG-Fc increased the pull-out force compared to saline controls by 153% (p less than 0.001). There was no significant difference between OPG-Fc and the alendronate groups. OPG-Fc increased the bone density (BV/TV) in the previous drill hole compared to controls 7-fold (p less than 0.001). This increase was higher than with any alendronate dose (p less than 0.001). OPG-Fc increased the bone density of the L5 vertebral body, but there was no significant difference between OPG-Fc and alendronate. Our results suggest that screw fixation in cancellous bone can be dramatically improved by an antiRANKL agent. The effect was comparable to very high bisphosphonate doses. Screw insertion in cancellous bone elicits a metaphyseal fracture healing response, and our findings might be relevant not only for implant fixation, but also for fracture healing in cancellous bone.

  • 21.
    Bernhardsson, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Experimental models for cancellous bone healing in the rat Comparison of drill holes and implanted screws2015In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 86, no 6, p. 745-750Article in journal (Refereed)
    Abstract [en]

    Background and purpose - Cancellous bone appears to heal by mechanisms different from shaft fracture healing. There is a paucity of animal models for fractures in cancellous bone, especially with mechanical evaluation. One proposed model consists of a screw in the proximal tibia of rodents, evaluated by pull-out testing. We evaluated this model in rats by comparing it to the healing of empty drill holes, in order to explain its relevance for fracture healing in cancellous bone. To determine the sensitivity to external influences, we also compared the response to drugs that influence bone healing. Methods - Mechanical fixation of the screws was measured by pull-out test and related to the density of the new bone formed around similar, but radiolucent, PMMA screws. The pull-out force was also related to the bone density in drill holes at various time points, as measured by microCT. Results - The initial bone formation was similar in drill holes and around the screw, and appeared to be reflected by the pull-out force. Both models responded similarly to alendronate or teriparatide (PTH). Later, the models became different as the bone that initially filled the drill hole was resorbed to restore the bone marrow cavity, whereas on the implant surface a thin layer of bone remained, making it change gradually from a trauma-related model to an implant fixation model. Interpretation - The similar initial bone formation in the different models suggests that pull-out testing in the screw model is relevant for assessment of metaphyseal bone healing. The subsequent remodeling would not be of clinical relevance in either model.

  • 22.
    Bernhardsson, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Ressner, Marcus
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Koziorowski, Jacek
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences.
    Malmqvist, Jonas
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Shining dead bone-cause for cautious interpretation of [F-18]NaF PET scans2018In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 89, no 1, p. 124-127Article in journal (Refereed)
    Abstract [en]

    Background and purpose — [18F]Fluoride ([18F]NaF) PET scan is frequently used for estimation of bone healing rate and extent in cases of bone allografting and fracture healing. Some authors claim that [18F]NaF uptake is a measure of osteoblastic activity, calcium metabolism, or bone turnover. Based on the known affinity of fluoride to hydroxyapatite, we challenged this view.

    Methods — 10 male rats received crushed, frozen allogeneic cortical bone fragments in a pouch in the abdominal wall on the right side, and hydroxyapatite granules on left side. [18F]NaF was injected intravenously after 7 days. 60 minutes later, the rats were killed and [18F]NaF uptake was visualized in a PET/CT scanner. Specimens were retrieved for micro CT and histology.

    Results — MicroCT and histology showed no signs of new bone at the implant sites. Still, the implants showed a very high [18F]NaF uptake, on a par with the most actively growing and remodeling sites around the knee joint.

    Interpretation — [18F]NaF binds with high affinity to dead bone and calcium phosphate materials. Hence, an [18F]NaF PET/CT scan does not allow for sound conclusions about new bone ingrowth into bone allograft, healing activity in long bone shaft fractures with necrotic fragments, or remodeling around calcium phosphate coated prostheses

  • 23.
    Bernhardsson, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Tätting, Love
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Schilcher, Jörg
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Marrow compartment contribution to cortical defect healing2018In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 89, no 1, p. 119-123Article in journal (Refereed)
    Abstract [en]

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

  • 24.
    Björnsson Hallgren, Hanna C
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Adolfsson, Lars E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Johansson, Kajsa
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Öberg, Birgitta
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Petersson, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Holmgren, Theresa M
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Specific exercises for subacromial pain: Good results maintained for 5 years2017In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 88, no 6, p. 600-605Article in journal (Refereed)
    Abstract [en]

    Background and purpose — We have previously shown that specific exercises reduced the need for surgery in subacromial painpatients at 1-year follow-up. We have now investigated whetherthis result was maintained after 5 years and compared the outcomesof surgery and non-surgical treatment.Patients and methods — 97 patients were included in the previouslyreported randomized study of patients on a waiting list forsurgery. These patients were randomized to specifi c or unspecifi cexercises. After 3 months of exercises the patients were asked ifthey still wanted surgery and this was also assessed at the present5-year follow-up. The 1-year assessment included Constant–Murley score, DASH, VAS at night, rest and activity, EQ-5D, andEQ-VAS. All these outcome assessments were repeated after 5years in 91 of the patients.Results — At the 5-year follow-up more patients in the specifi cexercise group had declined surgery, 33 of 47 as compared with16 of 44 (p = 0.001) in the unspecifi c exercise group. The meanConstant–Murley score continued to improve between the 1- and5-year follow-ups in both surgically and non-surgically treatedgroups. On a group level there was no clinically relevant changebetween 1 and 5 years in any of the other outcome measuresregardless of treatment.Interpretation — This 5-year follow-up of a previously publishedrandomized controlled trial found that specifi c exercisesreduced the need for surgery in patients with subacromial pain.Patients not responding to specifi c exercises may achieve similargood results with surgery. These fi ndings emphasize that a specifi cexercise program may serve as a selection tool for surgery.

  • 25.
    Blomgran, Parmis
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    A possible link between loading, inflammation and healing: Immune cell populations during tendon healing in the rat2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 29824Article in journal (Refereed)
    Abstract [en]

    Loading influences tendon healing, and so does inflammation. We hypothesized that the two are connected. 48 rats underwent Achilles tendon transection. Half of the rats received Botox injections into calf muscles to reduce mechanical loading. Cells from the regenerating tissue were analyzed by flow cytometry. In the loaded group, the regenerating tissue contained 83% leukocytes (CD45(+)) day 1, and 23% day 10. The M1/M2 macrophage ratio (CCR7/CD206) peaked at day 3, while T helper (CD3(+)CD4(+)) and T-reg cells (CD25(+) Foxp3(+)) increased over time. With Botox, markers associated with down-regulation of inflammation were more common day 5 (CD163, CD206, CD25, Foxp3), and M1 or M2 macrophages and T-reg cells were virtually absent day 10, while still present with full loading. The primary variable, CCR7/CD206 ratio day 5, was higher with full loading (p = 0.001) and the T-reg cell fraction was lower (p amp;lt; 0.001). Free cage activity loading is known to increase size and strength of the tendon in this model compared to Botox. Loading now appeared to delay the switch to an M2 type of inflammation with more T-reg cells. It seems a prolonged M1 phase due to loading might make the tendon regenerate bigger.

  • 26.
    Blomgran, Parmis
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Cox-2 inhibition and the composition of inflammatory cell populations during early and mid-time tendon healing2017In: Muscles, ligaments and Tendons journal, ISSN 2240-4554, Vol. 7, no 2, p. 223-229Article in journal (Refereed)
    Abstract [en]

    Background: During early tendon healing, the cells within the regenerating tissue are, to a large part, inflammatory leukocytes (CD45+). In a rat Achilles tendon healing model, the inflammation resolves between 5 and 10 days. In the same model, Cox inhibitors (NSAIDs) impair healing when given during the first 5 days, but have a positive effect if given later. We tested the hypothesis that a Cox inhibitor would exert these effects by influencing inflammation, and thereby the composition of the inflammatory cell subpopulations.Methods: Achilles tendon transection was performed in 44 animals. Animals were randomized to either parecoxib or saline injections. Healing was evaluated by mechanical testing day 7 after surgery and by flow cytometry day 3 and 10.Results: Cross-sectional area, peak force and stiffness were reduced by parecoxib 31, 33, and 25% respectively (p=0.005, p=0.002, and p=0.005). By flow cytometry, there was a strong effect of time (p<0.001) on virtually all inflammatory cell subpopulations (CD45, CD11b, CD68, CCR7, CD163, CD206, CD3, CD4), but no significant effect of parecoxib at any time point.Conclusion: The results suggest that the negative effects of Cox inhibitors on tendon healing might be exerted mainly via mechanisms not directly related to inflammatory cells.

  • 27.
    Blomgran, Parmis
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Hammerman, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Systemic corticosteroids improve tendon healing when given after the early inflammatory phase2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 12468Article in journal (Refereed)
    Abstract [en]

    Inflammation initiates tendon healing and then normally resolves more or less completely. Unresolved inflammation might disturb the remodeling process. We hypothesized that suppression of inflammation during the early remodeling phase by systemic dexamethasone treatment can improve healing. 36 rats underwent Achilles tendon transection and were randomized to dexamethasone or saline on days 0-4 after surgery (early inflammatory phase), and euthanasia day 7. Another 54 rats received injections days 5-9 (early remodeling phase) and were euthanized day 12 for mechanical, histological and flow cytometric evaluation. Dexamethasone treatment days 0-4 reduced the cross-sectional area, peak force and stiffness by day 7 to less than half (p amp;lt; 0.001 for all), while material properties (peak stress and elastic modulus) were not significantly affected. In contrast, dexamethasone treatment days 5-9 increased peak force by 39% (p = 0.002) and stiffness by 58% (p amp;lt; 0.001). The cross-sectional area was reduced by 42% (p amp;lt; 0.001). Peak stress and elastic modulus were more than doubled (p amp;lt; 0.001 for both). Semi-quantitative histology at day 12 showed that late dexamethasone treatment improved collagen alignment, and flow cytometry revealed reduced numbers of CD8a(+) cytotoxic T cells in the tendon callus. These results suggest that downregulation of lingering inflammation during the early remodeling phase can improve healing.

  • 28.
    Bogl, H. P.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Schilcher, J.
    Gavle Central Hospital, Sweden.
    Undisturbed local bone formation capacity in patients with atypical femoral fractures: a case series2017In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 28, no 8, p. 2439-2444Article in journal (Refereed)
    Abstract [en]

    We excised the fracture site in 8 patients with incomplete atypical femoral fractures by drilling an 11-mmdiameter hole. New bone formation could be seen in the hole within a normal time frame. Delayed healing of these fractures might be unrelated to an impaired capacity to form bone. Introduction Incomplete atypical femoral fractures (undisplaced cracks) heal slowly or not at all, and often progress to a complete fracture with minimal trauma. The impaired healing has been attributed to an impaired biologic healing capacity related to bisphosphonate use, or, alternatively, to the mechanical environment within the fracture crack. This study aimed to investigate the capacity for bone formation after resection of the fracture site. Methods Between 2008 and 2014, we recruited eight patients with incomplete atypical femoral fractures. All used oral bisphosphonates before the fracture for on average 8 years (range 4 to 15) and complained of thigh pain. The fractures were stabilized with reamed cephalomedullary nails. During surgery, the fracture site in the lateral cortex was resected with a cylindrical drill (diameter 11.5 mm). The cylindrical cortical defect allowed radiographic evaluation of new bone formation, and the patients were followed clinically and radiologically for 24 months (range 15 to 92). Results After 3 months, newly formed bone could be seen in the cortical defects in all patients. After 13-26 months, the previous defects showed continuous cortical bone. At final follow-up, all patients reported full recovery of pre-surgical complaints. No complications occurred and no reoperations were performed. Conclusions New bone formation occurred within a time frame that appears normal for healing of cortical bone defects. This suggests that the capacity to form new bone is intact.

  • 29.
    Brink, Rob C.
    et al.
    Department of Orthopaedic Surgery, G05.228, University Medical Center Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands..
    Vavruch, Ludvig
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Schlösser, Tom P. C.
    Department of Orthopaedic Surgery, G05.228, University Medical Center Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands..
    Abul-Kasim, Kasim
    Division of Neuroradiology, Diagnostic Centre for Imaging and Functional Medicine, Faculty of Medicine, Lund University, Skåne University Hospital, Malmö, Sweden..
    Ohlin, Acke
    Department of Orthopaedic Surgery, Faculty of Medicine, Lund University, Skåne University Hospital, Malmö, Sweden..
    Tropp, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Castelein, René M.
    Department of Orthopaedic Surgery, G05.228, University Medical Center Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands. r.m.castelein@umcutrecht.nl..
    Vrtovec, Tomaž
    Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia..
    Three-dimensional pelvic incidence is much higher in (thoraco)lumbar scoliosis than in controls2019In: European spine journal, ISSN 0940-6719, E-ISSN 1432-0932, Vol. 28, no 3, p. 544-550Article in journal (Refereed)
    Abstract [en]

    Purpose

    The pelvic incidence (PI) is used to describe the sagittal spino-pelvic alignment. In previous studies, radiographs were used, leading to less accuracy in establishing the three-dimensional (3D) spino-pelvic parameters. The purpose of this study is to analyze the differences in the 3D sagittal spino-pelvic alignment in adolescent idiopathic scoliosis (AIS) subjects and non-scoliotic controls.

    Methods

    Thirty-seven female AIS patients that underwent preoperative supine low-dose computed tomography imaging of the spine, hips and pelvis as part of their general workup were included and compared to 44 non-scoliotic age-matched female controls. A previously validated computerized method was used to measure the PI in 3D, as the angle between the line orthogonal to the inclination of the sacral endplate and the line connecting the center of the sacral endplate with the hip axis.

    Results

    The PI was on average 46.8° ± 12.4° in AIS patients and 41.3° ± 11.4° in controls (p = 0.025), with a higher PI in Lenke type 5 curves (50.6° ± 16.2°) as compared to controls (p = 0.042), whereas the Lenke type 1 curves (45.9° ± 12.2°) did not differ from controls (p = 0.141).

    Conclusion

    Lenke type 5 curves show a significantly higher PI than controls, whereas the Lenke type 1 curves did not differ from controls. This suggests a role of pelvic morphology and spino-pelvic alignment in the pathogenesis of idiopathic scoliosis. Further longitudinal studies should explore the exact role of the PI in the initiation and progression of different AIS types.

  • 30.
    Carlfjord, Siw
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsing-Strid, Emma
    University Health Care Research Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Johansson, Kajsa
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Holmgren, Theresa
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Öberg, Birgitta
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Practitioner experiences from the structured implementation of evidence-based practice in primary care physiotherapy: A qualitative study2019In: Journal of Evaluation In Clinical Practice, ISSN 1356-1294, E-ISSN 1365-2753, Vol. 25, no 4, p. 622-629Article in journal (Refereed)
    Abstract [en]

    Rationale, Aims, and Objectives

    To provide best available care, the practitioners in primary health care (PHC) must have adequate knowledge about effective interventions. The implementation of such interventions is challenging. A structured implementation strategy developed by researchers at Linköping University, Sweden, was used for the implementation of an evidence‐based assessment and treatment programme for patients with subacromial pain among physiotherapists in PHC. To further develop strategies for implementation of evidence‐based practices, it was deemed important to study the implementation from the practitioners' perspective. The aim of this study was to explore the practitioners' experiences from the implementation.

    Methods

    A qualitative design with focus group discussions was applied. The implementation in terms of perceptions of process and outcome was evaluated by focus group discussions with, in total, 16 physiotherapists in the target group. Data were analysed using the method qualitative content analysis.

    Results

    The components of the strategy were viewed positively, and the applicability and evidence base behind the programme were appreciated. The programme was perceived to be adopted, and the practitioners described a changed behaviour and increased confidence in handling patients with subacromial pain. Both patient‐ and provider‐related challenges to the implementation were mentioned.

    Conclusions

    The practitioners' experiences from the implementation were mainly positive. A strategy with collaboration between academy and practice, and with education and implementation teams as facilitators, resulted in changes in practice. Critical voices concerned interprofessional collaboration and that the programme was focused explicitly on the shoulder, not including other components of physical function.

  • 31.
    Dietrich, Franciele
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Minist Educ Brazil, Brazil; Pontificia University of Catolica Rio Grande Sul PUCRS, Brazil.
    Hammerman, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Parmis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Tätting, Love
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Faccin Bampi, Vinicius
    Pontificia University of Catolica Rio Grande Sul PUCRS, Brazil.
    Braga Silva, Jefferson
    Pontificia University of Catolica Rio Grande Sul PUCRS, Brazil.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Correction: Effect of platelet-rich plasma on rat Achilles tendon healing is related to microbiota (vol 15, pg 1, 2017)2017In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 88, no 4, p. 463-463Article in journal (Other academic)
    Abstract [en]

    n/a

  • 32.
    Dietrich, Franciele
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. CAPES Fdn, Brazil; Pontificia University of Catolica Rio Grande do Sul PUCRS, Brazil.
    Hammerman, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Parmis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Tätting, Love
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Faccin Bampi, Vinicius
    Pontificia University of Catolica Rio Grande do Sul PUCRS, Brazil.
    Braga Silva, Jefferson
    Pontificia University of Catolica Rio Grande do Sul PUCRS, Brazil.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Effect of platelet-rich plasma on rat Achilles tendon healing is related to microbiota2017In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 88, no 4, p. 416-421Article in journal (Refereed)
    Abstract [en]

    Background and purpose - In 3 papers in Acta Orthopaedica 10 years ago, we described that platelet-rich plasma (PRP) improves tendon healing in a rat Achilles transection model. Later, we found that microtrauma has similar effects, probably acting via inflammation. This raised the suspicion that the effect ascribed to growth factors within PRP could instead be due to unspecific influences on inflammation. While testing this hypothesis, we noted that the effect seemed to be related to the microbiota. Material and methods - We tried to reproduce our old findings with local injection of PRP 6h after tendon transection, followed by mechanical testing after 11 days. This failed. After fruitless variations in PRP production protocols, leukocyte concentration, and physical activity, we finally tried rats carrying potentially pathogenic bacteria. In all, 242 rats were used. Results - In 4 consecutive experiments on pathogen-free rats, no effect of PRP on healing was found. In contrast, apparently healthy rats carrying Staphylococcus aureus showed increased strength of the healing tendon after PRP treatment. These rats had higher levels of cytotoxic T-cells in their spleens. Interpretation - The failure to reproduce older experiments in clean rats was striking, and the difference in response between these and Staphylococcus-carrying rats suggests that the PRP effect is dependent on the immune status. PRP functions may be more complex than just the release of growth factors. Extrapolation from our previous findings with PRP to the situation in humans therefore becomes even more uncertain.1

  • 33.
    Dietrich-Zagonel, Franciele
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Hammerman, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Tätting, Love
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Dietrich, Fabricia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Kozak Ljunggren, Monika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Parmis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Eliasson, Pernilla T.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Stimulation of Tendon Healing With Delayed Dexamethasone Treatment Is Modified by the Microbiome2018In: American Journal of Sports Medicine, ISSN 0363-5465, E-ISSN 1552-3365, Vol. 46, no 13, p. 3281-3287Article in journal (Refereed)
    Abstract [en]

    Background:

    The immune system reflects the microbiome (microbiota). Modulation of the immune system during early tendon remodeling by dexamethasone treatment can improve rat Achilles tendon healing. The authors tested whether changes in the microbiota could influence the effect of dexamethasone treatment.

    Hypothesis:

    A change in microbiome would influence the response to dexamethasone on regenerate remodeling, specifically tendon material properties (peak stress).

    Study Design:

    Controlled laboratory study.

    Methods:

    Specific opportunist and pathogen-free female rats were housed separately (n = 41) or together with specific pathogen-free rats carrying opportunistic microbes such as Staphylococcus aureus (n = 41). After 6 weeks, all co-housed rats appeared healthy but now carried S aureus. Changes in the gut bacterial flora were tested by API and RapID biochemical tests. All rats (clean and contaminated) underwent Achilles tendon transection under aseptic conditions. Flow cytometry was performed 8 days postoperatively on tendon tissue. Sixty rats received subcutaneous dexamethasone or saline injections on days 5 through 9 after transection. The tendons were tested mechanically on day 12. The predetermined primary outcome was the interaction between contamination and dexamethasone regarding peak stress, tested by 2-way analysis of variance.

    Results:

    Dexamethasone increased peak stress in all groups but more in contaminated rats (105%) than in clean rats (53%) (interaction, P = .018). A similar interaction was found for an estimate of elastic modulus (P = .021). Furthermore, dexamethasone treatment reduced transverse area but had small effects on peak force and stiffness. In rats treated with saline only, contamination reduced peak stress by 16% (P = .04) and elastic modulus by 35% (P = .004). Contamination led to changes in the gut bacterial flora and higher levels of T cells (CD3+CD4+) in the healing tendon (P < .05).

    Conclusion:

    Changes in the microbiome influence tendon healing and enhance the positive effects of dexamethasone treatment during the early remodeling phase of tendon healing.

    Clinical Relevance:

    The positive effect of dexamethasone on early tendon remodeling in rats is strikingly strong. If similar effects could be shown in humans, immune modulation by a few days of systemic corticosteroids, or more specific compounds, could open new approaches to rehabilitation after tendon injury.

  • 34.
    Djerf, K
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Edholm, P
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Hedbrant, Johan
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, Faculty of Science & Engineering.
    A simplified roentgen stereophotogrammetric method. Analysis of small movements between the prosthetic stem and the femur after total hip replacement.1987In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 28, no 5, p. 603-606Article in journal (Refereed)
    Abstract [en]

    A simplified roentgen stereophotogrammetric method is described. It is based on the use of a 50 mm thick reference plate consisting of a carbon-fibre-reinforced polyester box. The patient is placed directly on this box, which makes the methods less cumbersome and more suitable for routine use. The method has been tested in a model experiment designed for detecting small movements between femur and prosthesis at an early stage after total hip replacement. The head and two hemispheres on the prosthesis and three small tantalum balls inserted in the femur serve as reference points. The model experiment now reported shows that the method has acceptable precision.

  • 35.
    Forsberg, Daniel
    et al.
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Sectra AB, Linköping, Sweden.
    Lindblom, Maria
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Quick, Petter
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Gauffin, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Quantitative analysis of the patellofemoral motion pattern using semi-automatic processing of 4D CT data2016In: International Journal of Computer Assisted Radiology and Surgery, ISSN 1861-6410, E-ISSN 1861-6429, Vol. 11, no 9, p. 1731-1741Article in journal (Refereed)
    Abstract [en]

    To present a semi-automatic method with minimal user interaction for quantitative analysis of the patellofemoral motion pattern. 4D CT data capturing the patellofemoral motion pattern of a continuous flexion and extension were collected for five patients prone to patellar luxation both pre- and post-surgically. For the proposed method, an observer would place landmarks in a single 3D volume, which then are automatically propagated to the other volumes in a time sequence. From the landmarks in each volume, the measures patellar displacement, patellar tilt and angle between femur and tibia were computed. Evaluation of the observer variability showed the proposed semi-automatic method to be favorable over a fully manual counterpart, with an observer variability of approximately 1.5 for the angle between femur and tibia, 1.5 mm for the patellar displacement, and 4.0-5.0 for the patellar tilt. The proposed method showed that surgery reduced the patellar displacement and tilt at maximum extension with approximately 10-15 mm and 15-20 for three patients but with less evident differences for two of the patients. A semi-automatic method suitable for quantification of the patellofemoral motion pattern as captured by 4D CT data has been presented. Its observer variability is on par with that of other methods but with the distinct advantage to support continuous motions during the image acquisition.

  • 36.
    Fältström, Anne
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Kvist, Joanna
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Division of Physiotherapy, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Gauffin, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Hägglund, Martin
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Football Research Group, Linköping University, Linköping, Sweden.
    Female Soccer Players With Anterior Cruciate Ligament Reconstruction Have a Higher Risk of New Knee Injuries and Quit Soccer to a Higher Degree Than Knee-Healthy Controls2019In: American Journal of Sports Medicine, ISSN 0363-5465, E-ISSN 1552-3365, Vol. 47, no 1, p. 31-40Article in journal (Refereed)
    Abstract [en]

    Background:

    Many patients with anterior cruciate ligament (ACL) reconstruction who return to sport suffer new ACL injuries or quit sports soon after returning.

    Purpose:

    To prospectively follow a cohort of female soccer players with primary unilateral ACL reconstruction and matched knee-healthy controls from the same soccer teams to compare (1) the rate of new traumatic and nontraumatic knee injuries and other injuries, (2) the proportion of players who quit soccer, and (3) player-reported activity level and satisfaction with activity level and knee function.

    Study Design:

    Cohort study; Level of evidence, 2.

    Methods:

    A total of 117 active female soccer players (mean ± SD age, 19.9 ± 2.5 years) 18.9 ± 8.7 months after ACL reconstruction and 119 knee-healthy female soccer players (19.5 ± 2.5 years) matched from the same teams were prospectively followed for 2 years for new knee injuries, other injuries, soccer playing level, activity level according to the Tegner Activity Scale, and satisfaction with activity level and knee function.

    Results:

    Players with ACL reconstruction had a higher rate of new ACL injuries (n = 29 vs 8; 19 vs 4 per 100 player years; rate ratio [RR], 4.82; 95% CI, 2.20-10.54; P < .001), other traumatic knee injuries (29 vs 16 per 100 player years; RR, 1.84; 95% CI, 1.16-2.93; P < .01), and nontraumatic knee injuries (33 vs 9 per 100 player years; RR, 3.62; 95% CI, 2.11-6.21; P < .001) as compared with controls. There was no difference in the rate of other (not knee) injuries (43 vs 48 per 100 player years; RR, 0.90; 95% CI, 0.65-1.23; P = .494). During the 2-year follow-up, 72 (62%) players with ACL reconstruction quit soccer, as opposed to 43 (36%) controls (P = .001). The median Tegner Activity Scale score decreased in both groups (P < .001) but more for the ACL-reconstructed group (P < .015).

    Conclusion:

    Female soccer players with ACL reconstruction had nearly a 5-fold-higher rate of new ACL injuries and a 2- to 4-fold-higher rate of other new knee injuries, quit soccer to a higher degree, and reduced their activity level to a greater extent as compared with knee-healthy controls.

  • 37.
    Gauffin, Håkan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Tagesson (Sonesson), Sofi
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Activity and Health.
    Meunier, Andreas
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology.
    Magnusson, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Kvist, Joanna
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Knee Arthroscopic Surgery in Middle-Aged Patients With Meniscal Symptoms A 3-Year Follow-up of a Prospective, Randomized Study2017In: American Journal of Sports Medicine, ISSN 0363-5465, E-ISSN 1552-3365, Vol. 45, no 9, p. 2077-2084Article in journal (Refereed)
    Abstract [en]

    Background: The optimal treatment for middle-aged patients with knee pain and meniscal lesions has been extensively debated. Most previous studies have revealed only short-term beneficial results of knee arthroscopic surgery. The authors have previously shown a positive benefit of knee arthroscopic surgery and an exercise program after 1 year when compared with an exercise program alone. Purpose: To evaluate if knee arthroscopic surgery combined with an exercise program provided an additional long-term benefit after 3 years compared with an exercise program alone in middle-aged patients with meniscal symptoms. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Of 179 eligible patients, aged 45 to 64 years, 150 were randomized to (1) a 3-month exercise program (nonsurgery group) or (2) the same as group 1 plus knee arthroscopic surgery within 4 weeks (surgery group). The primary outcome was the change in the Knee Injury and Osteoarthritis Outcome Score (KOOS) subscore of pain between baseline and the 3-year follow-up. Results from the 1-year follow-up have been published previously. Results: Both treatment groups improved significantly in the KOOS pain subscore at 3 years follow-up in the intention-to-treat and as-treated analyses (P amp;lt; .001). The between-group difference for the change in the KOOS pain subscore between baseline and the 3-year follow-up was no longer statistically significant, neither in the intention-to-treat analysis (7.6 points; 95% CI, -0.6 to 15.9; P = .068) nor in the as-treated analysis (5.3 points; 95% CI, -3.1 to 13.8; P = .216). The factorial analysis of the effect of the intervention and age, onset of pain, and mechanical symptoms indicated that older patients improved more, regardless of treatment, and surgery may be more beneficial for patients without mechanical symptoms (as-treated analysis). The effect of the predictive factors on the KOOS pain subscore was uncertain because of the small sample size in the subgroup analyses. Conclusion: The benefit of knee arthroscopic surgery, seen at 1 year in middle-aged patients with meniscal symptoms, was diminished at 3 years and was no longer statistically significant.

  • 38.
    Gustafsson, Anna
    et al.
    Lund University, Sweden.
    Schilcher, Jörg
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Grassi, Lorenzo
    Lund University, Sweden.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Isaksson, Hanna
    Lund University, Sweden.
    Strains caused by daily loading might be responsible for delayed healing of an incomplete atypical femoral fracture2016In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 88, p. 125-130Article in journal (Refereed)
    Abstract [en]

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

  • 39.
    Hammerman, Malin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Parmis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Dansac, Arie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Eliasson, Pernilla T.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Different gene response to mechanical loading during early and late phases of rat Achilles tendon healing2017In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 123, no 4, p. 800-815Article in journal (Refereed)
    Abstract [en]

    Mechanical loading stimulates tendon healing both when applied in the inflammatory phase and in the early remodeling phase of the process, although not necessarily via the same mechanisms. We investigated the gene response to mechanical loading in these two phases of tendon healing. The right Achilles tendon in rats was transected, and the hindlimbs were unloaded by tail suspension. The rats were exposed to 5 min of treadmill running 3 or 14 days after tendon transection. Thereafter, they were resuspended for 15 min or 3 h until euthanasia. The controls were suspended continuously. Gene analysis was first performed by microarray analysis followed by quantitative RTPCR on selected genes, focusing on inflammation. Fifteen minutes after loading, the most important genes seemed to be the transcription factors EGR1 and C-FOS, regardless of healing phase. These transcription factors might promote tendon cell proliferation and differentiation, stimulate collagen production, and regulate inflammation. Three hours after loading on day 3, inflammation was strongly affected. Seven inflammation-related genes were upregulated according to PCR: CCL20, CCL7, IL-6, NFIL3, PTX3, SOCS1, and TLR2. These genes can be connected to macrophages, T cells, and recruitment of leukocytes. According to Ingenuity Pathway Analysis, the recruitment of leukocytes was increased by loading on day 3, which also was confirmed by histology. This inflammation-related gene response was not seen on day 14. Our results suggest that the immediate gene response after mechanical loading is similar in the early and late phases of healing but the late gene response is different. NEW amp; NOTEWORTHY This study investigates the direct effect of mechanical loading on gene expression during different healing phases in tendon healing. One isolated episode of mechanical loading was studied in otherwise unloaded healing tendons. This enabled us to study a time sequence, i.e., which genes were the first ones to be regulated after the loading episode.

  • 40.
    Hammerman, Malin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Blomgran, Parmis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Ramstedt, Sandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Linköping University, Faculty of Health Sciences.
    COX-2 inhibition impairs mechanical stimulation of early tendon healing in rats by reducing the response to microdamage2015In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 119, no 5, p. 534-540Article in journal (Refereed)
    Abstract [en]

    Early tendon healing can be stimulated by mechanical loading and inhibited by cyclooxygenase (COX) inhibitors (nonsteroidal anti-inflammatory drugs). Therefore, we investigated if impairment of tendon healing by a COX-2 inhibitor (parecoxib) is related to loading. Because loading might infer microdamage, which also stimulates healing, we also investigated if this effect is inhibited by parecoxib. The Achilles tendon was transected in 114 rats. Three degrees of loading were used: full loading, partial unloading, and unloading (no unloading, Botox injections in the plantar flexor muscles, or Botox in combination with tail suspension). For each loading condition, the rats received either parecoxib or saline. In a second experiment, rats were unloaded with Botox, and the tendon was subjected to microdamage by needling combined with either saline or parecoxib. Mechanical testing day 7 showed that there was a significant interaction between loading and parecoxib for peak force at failure (P less than 0.01). However, logarithmic values showed no significant interaction, meaning that we could not exclude that the inhibitory effect of parecoxib was proportionate to the degree of loading. Microbleeding was common in the healing tissue, suggesting that loading caused microdamage. Needling increased peak force at failure (P less than 0.01), and this effect of microdamage was almost abolished by parecoxib (P less than 0.01). Taken together, this suggests that COX-2 inhibition impairs the positive effects of mechanical loading during tendon healing, mainly by reducing the response to microdamage.

  • 41.
    Hammerman, Malin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Dietrich, Franciele
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Parmis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Eliasson, Pernilla T.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Different mechanisms activated by mild versus strong loading in rat Achilles tendon healing2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 7, article id e0201211Article in journal (Refereed)
    Abstract [en]

    Background Mechanical loading stimulates Achilles tendon healing. However, various degrees of loading appear to have different effects on the mechanical properties of the healing tendon, and strong loading might create microdamage in the tissue. This suggests that different mechanisms might be activated depending on the magnitude of loading. The aim of this study was to investigate these mechanisms further. Methods Female rats had their right Achilles tendon cut transversely and divided into three groups: 1) unloading (calf muscle paralysis by Botox injections, combined with joint fixation by a steel-orthosis), 2) mild loading (Botox only), 3) strong loading (free cage activity). Gene expression was analyzed by PCR, 5 days post-injury, and mechanical testing 8 days post-injury. The occurrence of microdamage was analyzed 3, 5, or 14 days post-injury, by measuring leakage of injected fluorescence-labelled albumin in the healing tendon tissue. Results Peak force, peak stress, and elastic modulus of the healing tendons gradually improved with increased loading as well as the expression of extracellular matrix genes. In contrast, only strong loading increased transverse area and affected inflammation genes. Strong loading led to higher fluorescence (as a sign of microdamage) compared to mild loading at 3 and 5 days post-injury, but not at 14 days. Discussion Our results show that strong loading improves both the quality and quantity of the healing tendon, while mild loading only improves the quality. Strong loading also induces microdamage and alters the inflammatory response. This suggests that mild loading exert its effect via mechanotransduction mechanisms, while strong loading exert its effect both via mechanotransduction and the creation of microdamage. Conclusion In conclusion, mild loading is enough to increase the quality of the healing tendon without inducing microdamage and alter the inflammation in the tissue. This supports the general conception that early mobilization of a ruptured tendon in patients is advantageous.

  • 42.
    Jarvinen, T. L. N.
    et al.
    University of Helsinki, Finland; University of Helsinki, Finland.
    Michaelsson, K.
    Uppsala University, Sweden.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Sievanen, H.
    UKK Institute Health Promot Research, Finland.
    Osteoporosis: the emperor has no clothes2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 277, no 6, p. 662-673Article in journal (Refereed)
    Abstract [en]

    Current prevention strategies for low-trauma fractures amongst older persons depend on the notions that fractures are mainly caused by osteoporosis (pathophysiology), that patients at high risk can be identified (screening) and that the risk is amenable to bone-targeted pharmacotherapy (treatment). However, all these three notions can be disputed. PathophysiologyMost fracture patients have fallen, but actually do not have osteoporosis. A high likelihood of falling, in turn, is attributable to an ageing-related decline in physical functioning and general frailty. ScreeningCurrently available fracture risk prediction strategies including bone densitometry and multifactorial prediction tools are unable to identify a large proportion of patients who will sustain a fracture, whereas many of those with a high fracture risk score will not sustain a fracture. TreatmentThe evidence for the viability of bone-targeted pharmacotherapy in preventing hip fracture and other clinical fragility fractures is mainly limited to women aged 65-80years with osteoporosis, whereas the proof of hip fracture-preventing efficacy in women over 80years of age and in men at all ages is meagre or absent. Further, the antihip fracture efficacy shown in clinical trials is absent in real-life studies. Many drugs for the treatment of osteoporosis have also been associated with increased risks of serious adverse events. There are also considerable uncertainties related to the efficacy of drug therapy in preventing clinical vertebral fractures, whereas the efficacy for preventing other fractures (relative risk reductions of 20-25%) remains moderate, particularly in terms of the low absolute risk reduction in fractures with this treatment.

  • 43.
    Johansson, Torsten
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    PTH 1-34 (teriparatide) may not improve healing in proximal humerus fractures A randomized, controlled study of 40 patients2016In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 87, no 1, p. 79-82Article in journal (Refereed)
    Abstract [en]

    Background and purpose - There is solid evidence from animal experiments that parathyroid hormone (PTH) improves fracture healing. So far, only 3 papers on PTH and fracture repair in humans have been published. They suggest that PTH may enhance fracture healing, but the results do not appear to justify specific clinical recommendations. This study was carried out to determine whether teriparatide enhances fracture healing of proximal humerus fractures. Patients and methods - 40 post-menopausal women with a proximal humerus fracture were randomized to either daily injections with 20 mu g teriparatide (PTH 1-34 (Forteo)) for 4 weeks or control treatment. At randomization, the patients were asked to assess how their pain at rest and during activity (visual analog scale (VAS)) and also function (DASH score) had been prior to the fracture. At 7 weeks and again at 3 months, their current state was assessed and the tests were repeated, including radiographs. 2 radiologists performed a blind qualitative scoring of the callus at 7 weeks. Callus formation was arbitrarily classified as normal or better. Results - 39 patients completed the follow-up. The radiographic assessment showed a correct correlation, better in the teriparatide group and normal in the control group, in 21 of the 39 cases. There were no statistically significant differences in pain, in use of strong analgesics, or in function between the groups at the follow-up examinations. Interpretation - There were no radiographic signs of enhanced healing or improved clinical results in the group treated with teriparatide

  • 44.
    Johansson, Torsten
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Department Orthopaed, Sweden.
    Lindblad, Maria
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Norrköping.
    Bladh, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Josefsson, Ann
    Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Sydsjö, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Incidence of Perthes disease in children born between 1973 and 1993: A Swedish nationwide cohort study of 2.1 million individuals2017In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 88, no 1, p. 96-100Article in journal (Refereed)
    Abstract [en]

    Background and purpose - The incidence of Perthes disease as reported in the literature varies widely between and within countries. The etiology of the disease is still unknown. Both environmental and genetic factors have been suggested to play a part in either causing the disease or increasing the susceptibility of an individual. We determined the incidence of Perthes disease in Sweden and investigated possible relationships to parental socioeconomic status, ethnicity, marital status, mothers age when giving birth, parity, number of siblings, and smoking habits. Patients and methods - Six Swedish population-based registers were used, together covering all children born in Sweden from 1973 through 1993. Results - The incidence of Perthes disease in Sweden was 9.3 per 100,000 subjects. The ratio between boys and girls was 3.1:1. The educational level of the father and the mother of a child with Perthes disease was lower than in the controls. The incidence was lower when the fathers were in the highest income bracket (above the 90(th) percentile). A higher proportion of parents of Nordic lineage had children with Perthes disease than parental pairs with one or both who were not of such lineage. Interpretation - This study confirms that there is an association between the incidence of Perthes disease and the socioeconomic status of the parents.

  • 45.
    Kalland, Kristine
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Nykoping Hosp, Sweden.
    Aberg, Henrik
    Uppsala Univ, Sweden.
    Berggren, Anna
    Falun Cent Hosp, Sweden.
    Ullman, Michael
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Snellman, Greta
    Uppsala Univ, Sweden.
    Jonsson, Kenneth B.
    Uppsala Univ, Sweden.
    Johansson, Torsten
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Dept Orthoped, Sweden.
    Similar outcome of femoral neck fractures treated with Pinloc or Hansson Pins: 1-year data from a multicenter randomized clinical study on 439 patients2019In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682Article in journal (Refereed)
    Abstract [en]

    Background and purpose - There are few reports on the efficiency of the Hansson Pinloc System (Pinloc) for fixation of femoral neck fractures. We compare Pinloc with the commonly used Hansson Pin System in a randomized clinical trial. The primary outcome measure is non-union or avascular necrosis within 2 years. We now report fracture failures and reoperations within the first year. Patients and methods - Between May 2014 and February 2017, 439 patients were included in the study. They were above 50 years of age and treated for a femoral neck fracture at 9 orthopedic departments in Sweden. They were randomized to either Pinloc or Hansson pins. The fractures were grouped as (a) non-displaced regardless of age, (b) displaced in patients amp;lt; 70 years, or (c) amp;gt;= 70 years old, but deemed unfit to undergo arthroplasty. Follow-up with radiographs and outpatient visits were at 3 and 12 months. Failure was defined as early displacement/non-union, symptomatic segmental collapse, or deep infection. Results - 1-year mortality was 11%. Of the 325 undisplaced fractures, 12% (21/169) Pinloc and 13% (20/156) Hansson pin patients had a failure during the first year. The reoperation frequencies were 10% (16/169) and 8% (13/156) respectively. For the 75 patients 50-69 years old with displaced fractures, 11/39 failures occurred in the Pinloc group and 11/36 in the Hansson group, and 8/39 versus 9/36 patients were reoperated. Among those 39 patients amp;gt;= 70 years old, 7/21 failures occurred in the Pinloc group and 4/18 in the Hansson group. Reoperation frequencies were 4/21 for Pinloc and 3/18 for the Hansson pin patients. No statistically significant differences were found in any of the outcomes between the Pinloc and Hansson groups. Interpretation - We found no advantages with Pinloc regarding failure or reoperation frequencies in this 1-year follow-up.

  • 46.
    Kharazmi, Mohammad
    et al.
    Uppsala University, Sweden.
    Hallberg, Par
    Uppsala University, Sweden.
    Schilcher, Jörg
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Michaelsson, Karl
    Uppsala University, Sweden.
    Mortality After Atypical Femoral Fractures: A Cohort Study2016In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 31, no 3, p. 491-497Article in journal (Refereed)
    Abstract [en]

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

  • 47.
    Kharazmi, Mohammad
    et al.
    Uppsala Univ, Sweden.
    Michaelsson, Karl
    Uppsala Univ, Sweden.
    Schilcher, Jörg
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Eriksson, Niclas
    Uppsala Univ, Sweden.
    Melhus, Hakan
    Uppsala Univ, Sweden.
    Wadelius, Mia
    Uppsala Univ, Sweden.
    Hallberg, Par
    Uppsala Univ, Sweden.
    A Genome-Wide Association Study of Bisphosphonate-Associated Atypical Femoral Fracture2019In: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 105, no 1, p. 51-67Article in journal (Refereed)
    Abstract [en]

    Atypical femoral fracture is a well-documented adverse reaction to bisphosphonates. It is strongly related to duration of bisphosphonate use, and the risk declines rapidly after drug withdrawal. The mechanism behind bisphosphonate-associated atypical femoral fracture is unclear, but a genetic predisposition has been suggested. With the aim to identify common genetic variants that could be used for preemptive genetic testing, we performed a genome-wide association study. Cases were recruited mainly through reports of adverse drug reactions sent to the Swedish Medical Products Agency on a nation-wide basis. We compared atypical femoral fracture cases (n=51) with population-based controls (n=4891), and to reduce the possibility of confounding by indication, we also compared with bisphosphonate-treated controls without a current diagnosis of cancer (n=324). The total number of single-nucleotide polymorphisms after imputation was 7,585,874. A genome-wide significance threshold of pamp;lt;5x10(-8) was used to correct for multiple testing. In addition, we performed candidate gene analyses for a panel of 29 genes previously implicated in atypical femoral fractures (significance threshold of pamp;lt;5.7x10(-6)). Compared with population controls, bisphosphonate-associated atypical femoral fracture was associated with four isolated, uncommon single-nucleotide polymorphisms. When cases were compared with bisphosphonate-treated controls, no statistically significant genome-wide association remained. We conclude that the detected associations were either false positives or related to the underlying disease, i.e., treatment indication. Furthermore, there was no significant association with single-nucleotide polymorphisms in the 29 candidate genes. In conclusion, this study found no evidence of a common genetic predisposition for bisphosphonate-associated atypical femoral fracture. Further studies of larger sample size to identify possible weakly associated genetic traits, as well as whole exome or whole-genome sequencing studies to identify possible rare genetic variation conferring a risk are warranted.

  • 48.
    Kharazmi, Mohammad
    et al.
    Section of Orthopaedics, Department of Surgical Sciences, Uppsala University, 751 85, Uppsala, Sweden. kharazmi.mohammad@gmail.com; Department of Oral and Maxillofacial Surgery, Västmanland Hospital, Västerås, Sweden. kharazmi.mohammad@gmail.com.
    Michaëlsson, Karl
    Section of Orthopaedics, Department of Surgical Sciences, Uppsala University, 751 85, Uppsala, Sweden.
    Hallberg, Pär
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Schilcher, Jörg
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Lateral fixation: an alternative surgical approach in the prevention of complete atypical femoral fractures2018In: European Journal of Orthopaedic Surgery & Traumatology, ISSN 1633-8065, E-ISSN 1432-1068, Vol. 28, no 2, p. 299-304Article in journal (Refereed)
    Abstract [en]

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

  • 49.
    Khayyeri, Hanifeh
    et al.
    Lund University, Sweden.
    Blomgran, Parmis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Hammerman, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Turunen, Mikael J.
    University of Eastern Finland, Finland.
    Lowgren, Annika
    Lund University, Sweden.
    Guizar-Sicairos, Manuel
    Paul Scherrer Institute, Switzerland.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Isaksson, Hanna
    Lund University, Sweden.
    Achilles tendon compositional and structural properties are altered after unloading by botox2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 13067Article in journal (Refereed)
    Abstract [en]

    Tendon function and homeostasis rely on external loading. This study investigates the biological mechanisms behind tendon biomechanical function and how the mechanical performance is affected by reduced daily loading. The Achilles tendons of 16 weeks old female Sprague Dawley rats (n = 40) were unloaded for 5 weeks by inducing muscle paralysis with botulinum toxin injections in the right gastrocnemius and soleus muscles. The contralateral side was used as control. After harvest, the tendons underwent biomechanical testing to assess viscoelasticity (n = 30 rats) and small angle X-ray scattering to determine the structural properties of the collagen fibrils (n = 10 rats). Fourier transform infrared spectroscopy and histological staining (n = 10 rats) were performed to investigate the collagen and proteoglycan content. The results show that the stiffness increased in unloaded tendons, together with an increased collagen content. Creep and axial alignment of the collagen fibers were reduced. Stress-relaxation increased whereas hysteresis was reduced in response to unloading with botox treatment. Our findings indicate that altered matrix deposition relies on mechanical loading to reorganize the newly formed tissue, without which the viscoelastic behavior is impaired. The results demonstrate that reduced daily loading deprives tendons of their viscoelastic properties, which could increase the risk of injury.

  • 50.
    Khayyeri, Hanifeh
    et al.
    Lund University, Sweden.
    Gustafsson, Anna
    Lund University, Sweden.
    Heuijerjans, Ashley
    Eindhoven University of Technology, Netherlands.
    Matikainen, Marko K.
    Lappeenranta University of Technology, Finland.
    Julkunen, Petro
    Kuopio University Hospital, Finland; University of Eastern Finland, Finland.
    Eliasson, Pernilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Isaksson, Hanna
    Lund University, Sweden.
    A Fibre-Reinforced Poroviscoelastic Model Accurately Describes the Biomechanical Behaviour of the Rat Achilles Tendon2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 6, article id e0126869Article in journal (Refereed)
    Abstract [en]

    Background Computational models of Achilles tendons can help understanding how healthy tendons are affected by repetitive loading and how the different tissue constituents contribute to the tendons biomechanical response. However, available models of Achilles tendon are limited in their description of the hierarchical multi-structural composition of the tissue. This study hypothesised that a poroviscoelastic fibre-reinforced model, previously successful in capturing cartilage biomechanical behaviour, can depict the biomechanical behaviour of the rat Achilles tendon found experimentally. Materials and Methods We developed a new material model of the Achilles tendon, which considers the tendons main constituents namely: water, proteoglycan matrix and collagen fibres. A hyperelastic formulation of the proteoglycan matrix enabled computations of large deformations of the tendon, and collagen fibres were modelled as viscoelastic. Specimen-specific finite element models were created of 9 rat Achilles tendons from an animal experiment and simulations were carried out following a repetitive tensile loading protocol. The material model parameters were calibrated against data from the rats by minimising the root mean squared error (RMS) between experimental force data and model output. Results and Conclusions All specimen models were successfully fitted to experimental data with high accuracy (RMS 0.42-1.02). Additional simulations predicted more compliant and soft tendon behaviour at reduced strain-rates compared to higher strain-rates that produce a stiff and brittle tendon response. Stress-relaxation simulations exhibited strain-dependent stress-relaxation behaviour where larger strains produced slower relaxation rates compared to smaller strain levels. Our simulations showed that the collagen fibres in the Achilles tendon are the main load-bearing component during tensile loading, where the orientation of the collagen fibres plays an important role for the tendons viscoelastic response. In conclusion, this model can capture the repetitive loading and unloading behaviour of intact and healthy Achilles tendons, which is a critical first step towards understanding tendon homeostasis and function as this biomechanical response changes in diseased tendons.

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