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  • 1.
    Abtahi, Jahan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Agholme, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Prevention of osteonecrosis of the jaw by mucoperiosteal coverage in a rat model2013In: International Journal of Oral and Maxillofacial Surgery, ISSN 0901-5027, E-ISSN 1399-0020, Vol. 42, no 5, p. 632-636Article in journal (Refereed)
    Abstract [en]

    There is evidence for a link between the use of systemic bisphosphonates and osteonecrosis of the jaw (ONJ). This condition has the appearance of chronic osteomyelitis, and antibiotics prevent the development of ONJ in animal models. Clinically, ONJ can sometimes be successfully treated by mucoperiosteal coverage. If ONJ is indeed primarily caused by bacterial infection, immediate coverage of the extraction alveolus might reduce the risk of ONJ development in risk patients. Therefore, we studied whether immediate mucoperiosteal coverage after tooth extraction could prevent ONJ development in a rat model. Thirty rats were randomly allocated to three groups of 10. Group I (controls): extraction, no drug treatment; Group II (non-coverage): extraction, dexamethasone plus alendronate; Group III (coverage): dexamethasone plus alendronate, plus coverage by a mucoperiosteal flap. Rats were examined for macroscopic ONJ-like wounds after 2 weeks. All animals in the non-coverage group developed large ONJ-like changes. The coverage and control groups showed an intact overlying mucosa in all rats. Findings were confirmed with histology. Bisphosphonates and dexamethasone caused ONJ-like lesions after tooth extraction in a rat model. This was prevented by immediate mucoperiosteal coverage. The risk of ONJ in patients using bisphosphonates might be reduced by mucoperiosteal coverage after tooth extraction.

  • 2.
    Abtahi, Jahan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Agholme, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Bisphosphonate-induced osteonecrosis of the jaw in a rat model arises first after the bone has become exposed. No primary necrosis in unexposed bone2012In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 41, no 6, p. 494-499Article in journal (Refereed)
    Abstract [en]

    J Oral Pathol Med (2012) 41: 494499 Background: Bisphosphonate-related osteonecrosis of the jaw was first described to start with sterile osteocyte death, similar to osteonecrosis in other parts of the skeleton. The typical chronic osteomyelitis was thought to develop when the dead bone was exposed to the oral cavity. An alternative explanation would be that the chronic osteomyelitis is a result of a bisphosphonate-related inability of infected bony lesions to heal. We tested the hypothesis that primary osteocyte death is not necessary for the development of jaw osteonecrosis. Material and methods: Forty rats were randomly allocated to four groups of 10. All animals underwent unilateral molar extraction and received the following drug treatments: Group I, controls with no drug treatment; Group II, 200 mu g/kg per day alendronate; Groups III and IV, 200 mu g/kg per day alendronate and 1 mg/kg of dexamethasone. All rats were euthanized after 14 days. Presence of osteonecrosis was determined by clinical and histological observations for groups IIII. For group IV, osteocyte viability at the contralateral uninjured site was examined using lactate dehydrogenase histochemistry (LDH). Results: All animals in the alendronate plus dexamethasone groups developed large ONJ-like lesions. Lactate dehydrogenase staining showed viable osteocytes in the contralateral jaw with no tooth extraction. No signs of osteonecosis were seen in the other groups. Conclusion: Bisphosphonates and dexamethasone caused no osteocyte death in uninjured bone, but large ONJ-like lesions after tooth extraction. Osteonecrosis of the jaw appears to arise first after the bone has been exposed. Possibly, bisphosphonates hamper the necessary resorption of bone that has become altered because of infection.

  • 3.
    Abtahi, Jahan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Agholme, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Effect of Local vs. Systemic Bisphosphonate Delivery on Dental Implant Fixation in a Model of Osteonecrosis of the Jaw2013In: Journal of Dental Research, ISSN 0022-0345, E-ISSN 1544-0591, Vol. 92, no 3, p. 279-283Article in journal (Refereed)
    Abstract [en]

    Locally applied bisphosphonates may improve the fixation of metal implants in bone. However, systemic bisphosphonate treatment is associated with a risk of osteonecrosis of the jaw (ONJ). We hypothesized that local delivery of bisphosphonate from the implant surface improves the fixation of dental implants without complications in a setting where systemic treatment induces ONJ. Forty rats were randomly allocated to 4 groups of 10. All groups received a titanium implant inserted in an extraction socket. Group I received the implants only. Group II received dexamethasone (0.5 mg/kg). Group III received dexamethasone as above plus alendronate (200 µg/kg). Group IV received zoledronate-coated implants and dexamethasone as above. The animals were sacrificed 2 weeks after tooth extraction. All 10 animals with systemic alendronate treatment developed large ONJ-like changes, while all with local treatment were completely healed. Implant removal torque was higher for the bisphosphonate-coated implants compared with the other groups (p < 0.03 for each comparison). Micro-computed tomography of the maxilla showed more bone loss in the systemic alendronate group compared with groups receiving local treatment (p = 0.001). Local bisphosphonate treatment appears to improve implant fixation in a setting where systemic treatment caused ONJ.

  • 4.
    Abtahi, Jahan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Tengvall, Pentti
    Gothenburg University.
    Aspenberg, Per
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    A bisphosphonate-coating improves the fixation of metal implants in human bone. A randomized trial of dental implants2012In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, no 5, p. 1148-1151Article in journal (Refereed)
    Abstract [en]

    Many surgical procedures use metal implants in bone. The clinical results depend on the strength of the bone holding these implants. Our objective was to show that a drug released from the implant surface can improve parameters reflecting the quality or amount of this bone. Sixteen patients received paired dental titanium implants in the maxilla, in a randomized, double-blinded fashion. One implant in each pair was coated with a thin fibrinogen layer containing 2 bisphosphonates. The other implant was untreated. Fixation was evaluated by measurement of resonance frequency (implant stability quotient; ISQ) serving as a proxy for stiffness of the implant-bone construct. Increase in ISQ at 6 months of follow-up was the primary variable. None of the patients had any complications. The resonance frequency increased 6.9 ISQ units more for the coated implants (p = 0.0001; Cohens d = 1.3). The average difference in increase in ISQ and the effect size, suggested a clinically relevant improvement. X-ray showed less bone resorption at the margin of the implant both at 2 months (p = 0.012) and at 6 months (p = 0.012). In conclusion, a thin, bisphosphonate-eluting fibrinogen coating might improve the fixation of metal implants in human bone. This might lead to new possibilities for orthopedic surgery in osteoporotic bone and for dental implants.

  • 5.
    Adolfsson, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Arthroscopic Synovectomy of the Wrist2011In: Hand Clinics, ISSN 0749-0712, E-ISSN 1558-1969, Vol. 27, no 3, p. 395-399Article in journal (Refereed)
    Abstract [en]

    Arthroscopic synovectomy is safe and reliable, with mild postoperative morbidity. The rationale of a surgical synovectomy is to excise inflamed synovium and thereby, remove as much effusion and inflammatory substrate as possible. In most cases, arthroscopic synovectomy is performed as an outpatient procedure. The technique has also been used for other diagnoses causing wrist arthritis, but very few results have been reported and the indications remain to be defined. In rheumatoid arthritis (RA), juvenile chronic arthritis (JCA), systemic lupus erythematosus (SLE), and post-infectious monoarthritis, a long period of increased comfort and improved function can be anticipated.

  • 6.
    Adolfsson, Lars
    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.
    Fractures of the Distal Humerus: Total Elbow Arthroplasty (Hemi-Arthroplasty)2014In: European Surgical Orthopaedics and Traumatology / [ed] George Bentley, Heidelberg: Springer Berlin/Heidelberg, 2014, 3, p. 1407-1422Chapter in book (Other academic)
    Abstract [en]

    This important reference textbook covers the surgical management of all major orthopaedic and traumatological conditions. The book will act as the major source of education and guidance in surgical practice for surgeons and trainees, especially those preparing for higher surgical examinations and the Board of Orthopaedics and Traumatology examinations within and beyond Europe. The emphasis throughout is on the application of current knowledge and research to technical problems, how to avoid operative problems, and how to salvage complications if they occur. The didactic text is complemented by abundant illustrations that highlight the essentials of each clinical scenario. The authors are all recognized international authorities active at congresses and workshops as well as in universities and hospitals across the world. ​

  • 7.
    Adolfsson, Lars
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Nestorson, Jens
    Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    The Kudo humeral component as primary hemiarthroplasty in distal humeral fractures2012In: Journal of shoulder and elbow surgery, ISSN 1058-2746, E-ISSN 1532-6500, Vol. 21, no 4, p. 451-455Article in journal (Refereed)
    Abstract [en]

    Background: Treatment of intra-articular fractures of the distal humerus in the elderly is challenging. In patients with very distal fractures and severe comminution, primary arthroplasty has been advocated. Recently, a few reports have described promising results of hemiarthroplasty. This study describes the medium-term results of using the Kudo humeral implant (Biomet Ltd, Bridgend, U. K.) as replacement of the distal humerus. less thanbrgreater than less thanbrgreater thanMaterial and methods: Eight women (mean age, 79 years) were treated. Follow-up was conducted at a mean of 4 years after the procedure and consisted of the Mayo Elbow Performance Score (MEPS), radiographic images, and range of motion (ROM). less thanbrgreater than less thanbrgreater thanResults: All patients had a good or excellent outcome according to the MEPS. Mean ROM was 31 degrees to 126 degrees. Radiographic signs of attrition of the ulna were observed in 3 patients but did not correlate with the functional outcome. A periprosthetic fracture occurred in 1 patient 3 years after the index operation, and ROM was unsatisfactory in 1 patient. No other complications were observed. less thanbrgreater than less thanbrgreater thanConclusion: The use of the Kudo humeral implant as a hemiarthroplasty resulted in a reasonable functional outcome in the medium-term, but the radiographic signs of attrition suggest that the implant is not recommended as a hemiprosthesis.

  • 8.
    Agholme, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Andersson, Therese
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Tengvall, P
    University of Gothenburg.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Local bisphosphonate release versus hydroxyapatite coating for stainless steel screw fixation in rat tibiae2012In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 23, no 3, p. 743-752Article in journal (Refereed)
    Abstract [en]

    Implant fixation in bone can be improved by a coating that delivers bisphosphonates locally, or by a hydroxyapatite (HA) coating. In this study, we compared these different types of coatings. For mechanical testing, 30 rats were assigned into three groups, and similar screws were implanted bilaterally in the proximal tibiae. The rats received screws that were either uncoated, coated with nano-crystalline hydroxyapatite or coated with a bisphosphonate releasing protein matrix. After 4 weeks, one screw was subjected to pull-out testing, and the contra-lateral one to torsion testing. For morphology, 30 rats were assigned to similar treatment groups, but received only one screw each. Bisphosphonates enhanced the pull-out force by 41% (P = 0.02) compared to controls, HA increased the pull-out force although not significantly. Conversely, HA increased the maximal torque by 64% (P = 0.02). Morphometry showed higher bone volume around bisphosphonate screws in comparison to HA-coated screws (P andlt; 0.001) and controls (P andlt; 0.001). The results suggest that bisphosphonates improve fixation by increasing the amount of surrounding bone, whereas HA mainly improves bone to implant attachment.

  • 9.
    Agholme, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Wnt signaling and orthopedics, an overview2011In: ACTA ORTHOPAEDICA, ISSN 1745-3674, Vol. 82, no 2, p. 125-130Article in journal (Refereed)
    Abstract [en]

    Wnt signaling is a ubiquitous system for intercellular communication, with multiple functions during development and in homeostasis of the body. It comprises several ligands, receptors, and inhibitors. Some molecules, such as sclerostin, appear to have bone-specific functions, and can be targeted by potential drugs. Now, ongoing clinical trials are testing these drugs as treatments for osteoporosis. Animal studies have also suggested that these drugs can accelerate fracture healing and implant fixation. This brief overview focuses on currently available information on the effects of manipulations of Wnt signaling on bone healing.

  • 10.
    Agholme, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Isaksson, Hanna
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Kuhstoss, Stuart
    Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, USA.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    The effects of Dickkopf-1 antibody on metaphyseal bone and implant fixation under different loading conditions2011In: BONE, ISSN 8756-3282, Vol. 48, no 5, p. 988-996Article in journal (Refereed)
    Abstract [en]

    The secreted protein Dickkopf-1 (Dkk1) is an antagonist of canonical Wnt signaling, expressed during fracture healing. It is unclear how it is involved in the mechanical control of bone maintenance. We investigated the response to administration of a Dkk1 neutralizing antibody (Dkk1-ab) in metaphyseal bone under different loading conditions, with or without trauma. In this three part experiment, 120 rats had a screw or bone chamber inserted either unilaterally or bilaterally in the proximal tibia. Mechanical (pull-out) testing, mu CT and histology were used for evaluation. The animals were injected with either 10 mg/kg Dkk1-ab or saline every 14 days for 14, 28, or 42 days. Antibody treatment increased bone formation around the screws and improved their fixation. After 28 days, the pull-out force was increased by over 100%. In cancellous bone, the bone volume fraction was increased by 50%. In some animals, one hind limb was paralyzed with Botulinum toxin A (Botox) to create a mechanically unloaded environment. This did not increase the response to antibody treatment with regard to screw fixation, but in cancellous bone, the bone volume fraction increased by 233%. Thus, the response in unloaded, untraumatized bone was proportionally larger, suggesting that Dkk1 may be up-regulated in unloaded bone. There was also an increase in thickness of the metaphyseal cortex. In bone chambers, the antibody treatment increased the bone volume fraction. The results suggest that antibodies blocking Dkk1 might be used to stimulate bone formation especially during implant fixation, fracture repair, or bone disuse. It also seems that Dkk1 is up-regulated both after metaphyseal trauma and after unloading, and that Dkk1 is involved in mechano-transduction.

  • 11.
    Agholme, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Isaksson, Hanna
    Department of Applied physics, University of Eastern Finland, Kuopio, Finland.
    Li, Xiaodong
    Metabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.
    Ke, Hua Zhu
    Metabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Anti-sclerostin antibody and mechanical loading appear to influence metaphyseal bone independently in rats2011In: Acta Orthopaedica, ISSN 1745-3674, Vol. 82, no 5, p. 628-632Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Sclerostin is produced by osteocytes and is an inhibitor of bone formation. Thus, inhibition of sclerostin by a monoclonal antibody increases bone formation and improves fracture repair. Sclerostin expression is upregulated in unloaded bone and is downregulated by loading. We wanted to determine whether an anti-sclerostin antibody would stimulate metaphyseal healing in unloaded bone in a rat model.

    Methods: 10-week-old male rats (n = 48) were divided into 4 groups, with 12 in each. In 24 rats, the right hind limb was unloaded by paralyzing the calf and thigh muscles with an injection of botulinum toxin A (Botox). 3 days later, all the animals had a steel screw inserted into the right proximal tibia. Starting 3 days after screw insertion, either anti-sclerostin antibody (Scl-Ab) or saline was given twice weekly. The other 24 rats did not receive Botox injections and they were treated with Scl-Ab or saline to serve as normal-loaded controls. Screw pull-out force was measured 4 weeks after insertion, as an indicator of the regenerative response of bone to trauma.

    Results: Unloading reduced the pull-out force. Scl-Ab treatment increased the pull-out force, with or without unloading. The response to the antibody was similar in both groups, and no statistically significant relationship was found between unloading and antibody treatment. The cancellous bone at a distance from the screw showed changes in bone volume fraction that followed the same pattern as the pull-out force.

    Interpretation: Scl-Ab increases bone formation and screwfixation to a similar degree in loaded and unloaded bone.

  • 12.
    Agholme, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Li, Xiaodong
    Amgen Inc.
    Isaksson, Hanna
    University of Eastern Finland.
    Zhu Ke, Hua
    Amgen Inc.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Sclerostin Antibody Treatment Enhances Metaphyseal Bone Healing in Rats2010In: JOURNAL OF BONE AND MINERAL RESEARCH, ISSN 0884-0431, Vol. 25, no 11, p. 2412-2418Article in journal (Refereed)
    Abstract [en]

    Sclerostin is the product of the SOST gene Loss of-function mutations in the SOST gene result in a high bone-mass phenotype demonstrating that sclerostin is a negative regulator of bone mass Primarily expressed by osteocytes in bone sclerostin is reported to bind the LRP5/6 receptor thereby antagonizing canonical Wnt signaling and negatively regulating bone formation We therefore investigated whether systemic administration of a sclerostin neutralizing antibody would increase the regeneration of traumatized metaphyseal bone in rats Young male rats had a screw inserted in the proximal tibia and were divided into six groups given 25 mg/kg of sclerostin antibody or control twice a week subcutaneously for 2 or 4 weeks In four groups, the screws were tested for pull out strength At the time of euthanasia a similar screw also was inserted in the contralateral tibia and pull-out tested immediately Sclerostin antibody significantly increased the pull out force by almost 50% compared with controls after 2 and 4 weeks Also the screws inserted at the time of euthanasia showed increased pull out force Micro-computed tomography (mu CT) of the remaining two groups showed that the antibody led to a 30% increase in bone volume fraction in a region surrounding the screw There also was a general increase in trabecular thickness in cancellous bone Thus as measured by the amount of bone and its mechanical resistance the sclerostin antibody increased bone formation during metaphyseal repair but also in untraumatized bone

  • 13.
    Agholme, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Macias, Brandon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Hamang, Matt
    Lilly Research Labs, IN USA .
    Lucchesi, Jonathan
    Lilly Research Labs, IN USA .
    Adrian, Mary D.
    Lilly Research Labs, IN USA .
    Kuhstoss, Stuart
    Lilly Research Labs, IN USA .
    Harvey, Anita
    Lilly Research Labs, IN USA .
    Sato, Masahiko
    Lilly Research Labs, IN USA .
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Efficacy of a Sclerostin Antibody Compared to a Low Dose of PTH on Metaphyseal Bone Healing2014In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 32, no 3, p. 471-476Article in journal (Refereed)
    Abstract [en]

    We compared the effect of a sclerostin antibody to that of a clinically relevant dose of parathyroid hormone (PTH) in a rat model for metaphyseal bone healing. Screws of steel or poly methyl methacrylate (PMMA) were inserted bilaterally into the proximal tibia of young male rats. During 4 weeks the animals then received injections of either phosphate buffered saline (control), sclerostin antibody (25mg/kg, twice weekly) or PTH (5 mu g/kg, daily). The healing response around the screws was then assessed by mechanical testing and X-ray microtomography (mu CT). To distinguish between effects on healing and general effects on the skeleton, other untraumatized bone sites and serum biomarkers were also assessed. After 4 weeks of treatment, PTH yielded a 48% increase in screw pull-out force compared to control (p=0.03), while the antibody had no significant effect. In contrast, the antibody increased femoral cortical and vertebral strength where PTH had no significant effect. mu CT showed only slight changes that were statistically significant for the antibody mainly at cortical sites. The results suggest that a relatively low dose of PTH stimulates metaphyseal repair (screw fixation) specifically, whereas the sclerostin antibody has wide-spread effects, mainly on cortical bone, with less influence on metaphyseal healing.

  • 14.
    Agholme, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Wnt gene expression during metaphyseal bone healing under different load conditionsManuscript (preprint) (Other academic)
    Abstract [en]

    Bone Wnt signalling has been presented as one of the key pathways through which bone responds to mechanical load. This pathway is also active during the healing process after bone trauma. Bone healing can be improved by pharmacological modulation of Wnt signalling. We investigated how the expression of several Wntrelated genes changed due to trauma and unloading in metaphyseal bone.

    20 male rats had one hind limb unloaded by intramuscular Botox injections. In half of the animals a hole was drilled bilaterally in the proximal tibia. After 7 days, a cylindrical biopsy was taken from the bone surrounding the hole and at a corresponding site in animals without trauma. The biopsies were analyzed for the mRNA expression of Wnt1, Wnt3a, Wnt4, Wnt5a, Wnt5b, Sost, Dkk1, Dkk2, Sfrp1, Sfrp4, Lrp5, Lrp6, Wisp1, Wif1 and Wnt10b.

    Trauma led to upregulation of most of the studied genes. This effect was most evident in unloaded bone, where 8 genes were upregulated, among them Wnt receptors, ligands and inhibitors. Unloading increased the expression of Sost in untraumatized bone, but did not significantly influence the other genes.

  • 15.
    Andersson, Therese
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Eliasson, Pernilla
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Achilles tendon healing in rats is improved by intermittent mechanical loading during the inflammatory phase2012In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 30, no 2, p. 274-279Article in journal (Refereed)
    Abstract [en]

    Tendons adapt to changes in mechanical loading, and numerous animal studiesshow that immobilization of a healing tendon is detrimental to the healingprocess. The present study addresses whether the effects of a few episodes ofmechanical loading are different during different phases of healing. Fifty femalerats underwent Achilles tendon transection, and their hind limbs were unloadedby tail suspension on the day after surgery. One group of 10 rats was taken downfrom suspension to walk on a treadmill for 30 minutes per day, on days 2-5 aftertransection. They were euthanized on day 8. Another group underwent similartreadmill running on days 8-11 and was euthanized on day 14. Completelyunloaded groups were euthanized on day 8 and 14. Tendon specimens were thenevaluated mechanically. The results showed that just 4 loading episodesincreased the strength of the healing tendon. This was evident irrespective of thetime-point when loading was applied (early or late). The positive effect on earlyhealing was unexpected, considering that the mechanical stimulation was appliedduring the inflammatory phase, when the calluses were small and fragile. Ahistological study of additional groups with early loading also showed someincreased bleeding in the loaded calluses. Our results indicate that a smallamount of early loading may improve the outcome of tendon healing. This couldbe of interest to clinical practice.

  • 16.
    Andersson, Therese
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Eliasson, Pernilla
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Growth hormone does not stimulate early healing in rat tendons2012In: International Journal of Sports Medicine, ISSN 0172-4622, E-ISSN 1439-3964, Vol. 33, no 3, p. 240-243Article in journal (Refereed)
    Abstract [en]

    Growth Hormone stimulates bone growth and fracture repair. It acts mainly by increasing the systemic levels of IGF-1. Local treatment with IGF-1 appears to stimulate tendon healing. We therefore hypothesized that systemic treatment with Growth Hormone would also stimulate tendon healing. Rat Achilles tendons were transected and left to heal. 4 groups were studied. Intramuscular injections of botulinum toxin A (Botox) were used to reduce loading in 2 groups. The animals were randomized to twice daily injections of Growth Hormone (n=2×10) or saline (n=2×10), and killed after 10 days. Healing was assessed by mechanical testing. Muscle paralysis induced by Botox reduced the strength of the healing tendon by two thirds. Growth Hormone increased femoral and tibial length in the unloaded, and femoral and tibial weight in the loaded group. Body weight and muscle weight were increased in both. In contrast, there was no increase in the strength of the healing tendons, regardless of mechanical loading status. An increase in peak force of the loaded healing tendons by more than 5% could be excluded with 95% confidence. In spite of its stimulatory effects on other tissues, Growth Hormone did not appear to stimulate tendon or tendon repair.

  • 17.
    Andersson, Therese
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Eliasson, Pernilla
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Hammerman, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Low-level mechanical stimulation is sufficient to improve tendon healing in rats2012In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 113, no 9, p. 1398-1402Article in journal (Refereed)
    Abstract [en]

    Treatment of tendon injuries often involves immobilization. However, immobilization might not prevent mild involuntary isometric muscle contraction. The effect of weak forces on tendon healing is therefore of clinical interest. Studies of tendon healing with various methods for load reduction in rat Achilles tendon models show a consistent reduction in tendon strength by at least half, compared with voluntary cage activity. Unloading was not complete in any of these models, and the healing tendon was therefore still exposed to mild mechanical stimulation. By reducing the forces acting on the tendon even further, we now studied the effects of this mild stimulation. Rat Achilles tendons were transected and allowed to heal spontaneously under four different loading conditions: 1) normal cage activity; 2) calf muscle paralysis induced by botulinum toxin A (Botox); 3) tail suspension; 4) Botox and tail suspension, combined, to eliminate even mild stimulation. Healing was evaluated by mechanical testing after 8 days. Botox alone and suspension alone both reduced tendon callus size (transverse area), thereby impairing its strength compared with normal cage activity. The combination of Botox and suspension did not further reduce tendon callus size but drastically impaired the material properties of the tendon callus compared with each treatment alone. The peak force was only a fifth of that in the normal cage activity group. The results indicate that also the mild loading that occurs with either Botox or suspension alone stimulates tendon healing. This stimulation appears to affect mainly tissue quality, whereas stronger stimulation also increases callus size.

  • 18.
    Ardern, Clare
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Österberg, Annika
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences. Uppsala Univ, Ctr Clin Res Sormland, Eskilstuna, Sweden.
    Tagesson (Sonesson), Sofi
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Gauffin, Håkan
    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.
    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.
    The impact of psychological readiness to return to sport and recreational activities after anterior cruciate ligament reconstruction2014In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 48, no 22, p. 1613-U50Article in journal (Refereed)
    Abstract [en]

    Background This cross-sectional study aimed to examine whether appraisal of knee function, psychological and demographic factors were related to returning to the preinjury sport and recreational activity following anterior cruciate ligament (ACL) reconstruction. Method 164 participants completed a questionnaire battery at 1-7 years after primary ACL reconstruction. The battery included questionnaires evaluating knee self-efficacy, health locus of control, psychological readiness to return to sport and recreational activity, and fear of reinjury; and self-reported knee function in sport-specific tasks, knee-related quality of life and satisfaction with knee function. The primary outcome was returning to the preinjury sport or recreational activity. Results At follow-up, 40% (66/164) had returned to their preinjury activity. Those who returned had more positive psychological responses, reported better knee function in sport and recreational activities, perceived a higher knee-related quality of life and were more satisfied with their current knee function. The main reasons for not returning were not trusting the knee (28%), fear of a new injury (24%) and poor knee function (22%). Psychological readiness to return to sport and recreational activity, measured with the ACL-Return to Sport after Injury scale (was most strongly associated with returning to the preinjury activity). Age, sex and preinjury activity level were not related. Conclusions Less than 50% returned to their preinjury sport or recreational activity after ACL reconstruction. Psychological readiness to return to sport and recreation was the factor most strongly associated with returning to the preinjury activity. Including interventions aimed at improving this in postoperative rehabilitation programmes could be warranted to improve the rate of return to sport and recreational activities.

  • 19.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Alendronate-eluting polyglucose-lignol composite (POGLICO): A new biomaterial for fracture fixating implants2014In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 85, no 6, p. 687-690Article in journal (Refereed)
    Abstract [en]

    Background and purpose - Due to the known drawbacks of metal implants, new biomaterials for internal fracture fixation are attracting increasing interest, among them poly(lactic-coglucolic) acids (PLGAs) and the recently developed silk-tenoin derived materials (STDMs). In accordance with the new philosophy of bio-derived biomaterials (BIODERIBIOs), I describe a novel innovative technology for use in fracture fixation. Patients and methods - Screws (2 mm dia.) were manufactured from cylindrical bars of polyglucose-lignol composite (POGLICO) in the form of birch toothpicks from the hospital canteen, dip-coated with alendronate (1 mg/mL, n = 6) or saline (n = 6), and inserted in the proximal tibias of rats for 4 weeks. Fixation was evaluated by mechanical pullout testing. POGLICO nails were inserted in the contralateral tibia for microCT and histology. Results - All POGLICO implants remained fixed in the bone (p less than 0.001) with a mean pullout force of 37 (SD 5.5) N. MicroCT showed that the control nails were surrounded by a thin layer of new bone, while all bisphosphonate-treated implants were surrounded by a thick layer of cancellous bone. Bisphosphonates more than doubled the bone density around the nails (p = 0.004). Interpretation - POGLICO is biocompatible, remains in situ, and appears to provide a higher resistance to pullout forces than bulk silk protein. The material is light, strong, and bio-derived. BIODERIBIO-POGLICO can be sterilized by autoclaving, and has a porous surface that can serve for slow release of drugs applied by simple dip-coating, as demonstrated by the effect of the alendronate treatment. As the raw material for the screws is readily available from the toothpick industry, I believe that the possibilities for commercial development of the material for fracture fixation are promising.

  • 20.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Benvävnad och frakturläkning2014Report (Other academic)
    Abstract [sv]

    Benvävnaden är utmärkande för ryggsträngsdjuren. Innan benet fanns, hade våra maskliknande förfäder en broskliknande ryggsträng, som möjliggjorde effektiva ringlande rörelser, som gjorde att de kunde simma som en fisk, något som en mask utan ryggsträng inte kan. Hos dessa djur uppstod redan under Cambrium, för 500 miljoner år sedan, förmågan att kontrollera utfällning av hydroxylapatit i bindväv, först som primitiva tänder och - för att undvika att bli biten - hudpansar. Emalj och dentin har alltså funnits lite längre på jorden, men snart nog uppstod benet, som förstärkningar i käkarna och som hudsköldar. Det inre skelettet, ryggraden, bestod då fortfarande av brosk.

  • 21.
    Aspenberg, Per
    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.
    Bone: Silk, metal and bone: why take implants out?2014In: Nature Reviews Rheumatology, ISSN 1759-4790, E-ISSN 1759-4804, Vol. 10, no 7, p. 386-387Article in journal (Other academic)
    Abstract [en]

    Degradable screws and plates for bone surgery have been produced from silk protein. The idea is to eliminate the need to take the implant out when the bone has healed. Will they provide sufficient strength, and will they degrade without causing inflammation? And why take implants out in the first place?

  • 22.
    Aspenberg, Per
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Hur läker senor och ledband?2013Report (Other academic)
    Abstract [sv]

    Vad händer när man stukar foten? Går ledbandet av eller töjs det ut? Hur lång tid tar det innan det är läkt? Blir det fullt återställt?

    Man kan tycka att svaren på dessa frågor borde vara grundläggande kunskap bland läkare och sjukgymnaster, men så är det inte. Frågorna är bara skenbart enkla; egentligen kan vi inte svara bestämt på någon av dem. Men nu ska vi ändå försöka. I det följande kommer jag att skriva senor ibland och ledband ibland, men det mesta gäller både och. Senor kan vara olika och även så ledband. I grova drag kan vi dock dra allihop över en kam, om vi utesluter det specialfall som fingrarnas böjsenor utgör.

  • 23.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Letter: Overtreatment of cruciate ligament injuries2011In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 82, no 1, p. 122-122Article in journal (Other academic)
    Abstract [en]

    n/a

  • 24.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Letter: Platelet concentrates and achilles tendon healing2013In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 31, no 9, p. 1500-1500Article in journal (Other academic)
    Abstract [en]

    n/a

  • 25.
    Aspenberg, Per
    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.
    Mythbusting in Orthopedics challenges our desire for meaning2014In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 85, no 6, p. 547-547Article in journal (Other academic)
  • 26.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Parathyroid hormone and fracture healing2013In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 84, no 1, p. 4-6Article in journal (Refereed)
    Abstract [en]

    This annotation describes some early rat studies which conclude that parathyroid hormone (PTH) has more dramatic stimulatory effects on bone repair than on untraumatized bone. It also suggests, based on the effects of PTH on osteoblasts, that it is more likely to accelerate normal fracture healing than to prevent nonunion. The only 2 controlled clinical trials that have been published are critically discussed. Although both are encouraging and appear to show acceleration of normal fracture healing, they have methodological shortcomings that preclude definitive conclusions.

  • 27.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Special Review: Accelerating fracture repair in humans: a reading of old experiments and recent clinical trials2013In: BoneKEy reports, ISSN 2047-6396, Vol. 2, no 244Article, review/survey (Refereed)
    Abstract [en]

    Based on their mode of action and preclinical data, one would expect bisphosphonates to improve the healing of fractures in cancellous bone, and bone morphogenetic proteins (BMPs) to reduce the risk of non-union in severe shaft fractures. Parathyreoid hormone (PTH) can be expected to accelerate fracture healing in general. The clinical data in support of this is meager. Stimulation of cancellous bone healing and strength by bisphosphonates has been inadvertently shown in the context of implant fixation, but not convincingly in fractures per se. The clinical BMP literature is confusing, and the chance of ever demonstrating reduced numbers of non-union are small, due to power issues. Still, acceleration of 'normal' healing may be possible, but largely remains to show. For PTH, the two available clinical trials both show accelerated healing, but none of them is flawless, and there is a need for better studies.

  • 28.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Under-reported complications related to BMP use in spine surgery2011In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 82, no 5, p. 511-512Article in journal (Other academic)
    Abstract [en]

    n/a

  • 29.
    Aspenberg, Per
    et al.
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Abtahi, Jahan
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    A bisphosphonate-coating improves the fixation of metal implants in human bone. A randomized trial with internal controls in BONE, vol 50, issue , pp S56-S562012In: BONE, Elsevier , 2012, Vol. 50, p. S56-S56Conference paper (Refereed)
    Abstract [en]

    n/a

  • 30.
    Aspenberg, Per
    et al.
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Abtahi, Jahan
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Agholme, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Bisphosphonate-induced osteonecrosis of the jaw in a rat model arises first after the bone has become exposed. no primary necrosis in unexposed bone in BONE, vol 50, issue , pp S173-S1732012In: BONE, Elsevier , 2012, Vol. 50, p. S173-S173Conference paper (Refereed)
    Abstract [en]

    n/a

  • 31.
    Aspenberg, Per
    et al.
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Abtahi, Jahan
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Agholme, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Dental implants in a rat model: Bisphosphonate coating improved fixation while systemic treatment caused osteonecrosis in BONE, vol 50, issue , pp S173-S1742012In: BONE, Elsevier , 2012, Vol. 50, p. S173-S174Conference paper (Refereed)
    Abstract [en]

    n/a

  • 32.
    Aspenberg, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Genant, Harry K
    University of California San Francisco.
    Johansson, Torsten
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    See, Kyoungah
    Eli Lilly and Co.
    Krohn, Kelly
    Eli Lilly and Co.
    Garcia-Hernandez, Pedro A
    Hospital University Nuevo Leon.
    Recknor, Christopher P
    United Osteoporosis Centre, Gainesville, FL USA .
    Einhorn, Thomas A
    Boston University.
    Dalsky, Gail P
    Eli Lilly and Co.
    Mitlak, Bruce H
    Eli Lilly and Co.
    Fierlinger, Anke
    Synarc Inc, San Francisco, CA USA .
    Lakshmanan, Mark C
    Eli Lilly and Co.
    Teriparatide for Acceleration of Fracture Repair in Humans: A Prospective, Randomized, Double-Blind Study of 102 Postmenopausal Women With Distal Radial Fractures2010In: JOURNAL OF BONE AND MINERAL RESEARCH, ISSN 0884-0431, Vol. 25, no 2, p. 404-414Article in journal (Refereed)
    Abstract [en]

    Animal experiments show a dramatic improvement in skeletal repair by teriparatide. We tested the hypothesis that recombinant teriparatide, at the 20 mu g dose normally used for osteoporosis treatment or higher, would accelerate fracture repair in humans. Postmenopausal women (45 to 85 years of age) who had sustained a dorsally angulated distal radial fracture in need of closed reduction but no surgery were randomly assigned to 8 weeks of once-daily injections of placebo (n = 34) or teriparatide 20 mu g (n = 34) or teriparatide 40 mu g (n = 34) within 10 days of fracture. Hypotheses were tested sequentially, beginning with the teriparaticle 40 mu g versus placebo comparison, using a gatekeeping strategy. The estimated median time from fracture to first radiographic evidence of complete cortical bridging in three of four cortices was 9.1, 7.4, and 8.8 weeks for placebo and teriparaticle 20 1 and 40 mu g, respectively (overall p = .015). There was no significant difference between the teriparaticle 40 mu g versus placebo groups (p = .523). In post hoc analyses, there was no significant difference between teriparaticle 40 1 versus 20 mu g (p = .053); however, the time to healing was shorter in teriparaticle 20 mu g than placebo (p = .006). The primary hypothesis that teriparatide 40 jug would shorten the time to cortical bridging was not supported. The shortened time to healing for teriparaticle 20 mu g compared with placebo still may suggest that fracture repair can be accelerated by teriparaticle, but this result should be interpreted with caution and warrants further study.

  • 33.
    Aspenberg, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Distal radial fractures heal by direct woven bone formation2013In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 84, no 3, p. 297-300Article in journal (Refereed)
    Abstract [en]

    Background Descriptions of fracture healing almost exclusively deal with shaft fractures and they often emphasize endochondral bone formation. In reality, most fractures occur in metaphyseal cancellous bone. Apart from a study of vertebral fractures, we have not found any histological description of cancellous bone healing in humans.

    Patients and methods We studied histological biopsies from the central part of 12 distal radial fractures obtained during surgery 6–28 days after the injury, using routine hematoxylin and eosin staining.

    Results New bone formation was seen in 6 cases. It was always in the form of fetal-like, disorganized woven bone. It seldom had contact with old trabeculae and appeared to have formed directly in the marrow. Cartilage was scarce or absent. The samples without bone formation showed only necrosis, scar, or old cancellous bone.

    Interpretation The histology suggests that cells in the midst of the marrow respond to the trauma by direct formation of bone, independently of trabecular surfaces.

  • 34.
    Aspenberg, Per
    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.
    Schilcher, Jörg
    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.
    Atypical femoral fractures, bisphosphonates, and mechanical stress2014In: Current osteoporosis reports, ISSN 1544-1873, Vol. 12, no 2, p. 189-193Article in journal (Refereed)
    Abstract [en]

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

  • 35.
    Aspenberg, Per
    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.
    Schilcher, Jörg
    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.
    Stressfrakturer: hjulaxlar och idrottskarriärer brister2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 36, p. 1436-1439Article in journal (Refereed)
    Abstract [en]

    Stress fractures are caused by material fatigue. Microcracks appear normally in bone, and are dealt with by remodeling, specifically targeting areas of microdamage. Inhibition of targeted remodeling can allow microcracks to grow and form fractures. Intensive athletic training can lead to an increased microcrack formation rate, which exceeds what can be balanced by remodeling. Stress fractures often heal poorly, possibly because they are so thin: normal deformation of the bone during loading has been shown to lead to strains within thin cracks that are incompatible with cell survival. If the patient can't reduce loading sufficiently to allow healing, surgical stabilization will therefore be required. If the crack is transformed into a larger defect, e.g. by drilling a hole, strains will be reduced and healing facilitated by a simple procedure.

  • 36.
    Björnsson Hallgren, Hanna Cecilia
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Eliasson, Pernilla T
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Adolfsson, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Elevated plasma levels of TIMP-1 in patients with rotator cuff tear2012In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 83, no 5, p. 523-528Article in journal (Refereed)
    Abstract [en]

    Background and purpose:Extracellular matrix remodelling is altered in rotator cuff tears,16partly due to altered expression of matrix metalloproteinases (MMPs) and their inhibitors. It is unclear if this altered expression can be traced as changes in plasma protein levels.

    The purposes were to measure the plasma level of MMPs and their tissue inhibitors (TIMPs) inpatients with rotator cuff tears and to relate changes in the pattern of MMP and TIMP levels with the extent of the rotator cuff tear.

    Methods: Blood samples were collected from 17 patients, median 61 (range 39-77) years, with sonographically verified rotator cuff tears (partial- or full-thickness). These were compared with 16 gender and age matched control persons with sonographically intact rotator cuffs. Plasma levels of MMPs and TIMPs were measured simultaneously using Luminex technology and ELISA.

    Results: The plasma level of TIMP-1 was elevated in patients with rotator cuff tears, especially in those with full-thickness tears. The levels of TIMP-1, TIMP-3 and MMP-9 were higher in patients with full-thickness tears compared to those with partial-thickness tears, but only TIMP-1 was different from controls.

    Interpretation: The observed elevation of TIMP-1 in plasma might reflect local pathological processes in or around the rotator cuff, or a genetic predisposition in these patients. That levels of TIMP-1 and certain MMP´s was found to differ between partial and full thickness tears may reflect the extent of the lesion or different aetiology and pathomechanisms.

  • 37.
    Björnsson Hallgren, Hanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Holmgren, Theresa
    Linköping University, Department of Medical and Health Sciences, Physiotherapy. Linköping University, Faculty of Health Sciences.
    Öberg, Birgitta
    Linköping University, Department of Medical and Health Sciences, Physiotherapy. Linköping University, Faculty of Health Sciences.
    Johansson, Kajsa
    Linköping University, Department of Medical and Health Sciences, Physiotherapy. Linköping University, Faculty of Health Sciences.
    Adolfsson, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    A specific exercise strategy for patients with subacromial pain significantly reduced the need for surgery: one-year results of a randomised controlled studyManuscript (preprint) (Other academic)
    Abstract [en]

    Background: A specific exercise strategy focusing on eccentric exercises, for treating sbacromial pain has in a previous study been found effective at three-month followup.

    The aim of the present study was to investigate if the positive short-term results were maintained after one year. A further aim was to examine if baseline clinical score, rotator cuff status and radiological findings influenced the choice of surgery.

    Methods: 97 patients on the waiting-list for arthroscopic subacromial decompression were in the first study randomized to a three-month specific exercise strategy or unspecific exercises (controls). Patients were examined with radiology, ultrasound and assessed with clinical scores: primary Constant-Murley score. After three months of exercises the patients were asked if they still wanted surgery and this option was available until the one-year follow-up. All patients were re-assessed with clinical scores one year after inclusion or one year after surgical intervention and the number of patients that had chosen surgery in each group was compared. The baseline Constant-Murley score and the status of subacromial structures were analyzed in relation to patient's choice of surgery.

    Results: The positive short-term effect (improved shoulder function and pain) of the specific exercises was maintained after one-year. Compared to the three-month followup all patients had improved significantly (p < 0.0001) in Constant-Murley score. The number of patients that had chosen surgery in the control exercise group (63%) was significantly larger (p < 0.0001) than in the specific exercise group (24%). Patients that had chosen surgery had a significantly lower baseline Constant-Murley score and significantly more often a full-thickness tear. Patients with partial-thickness tears did not differ from those with intact cuff tendons.

    Conclusions: The positive short-term outcomes after specific exercises were maintained after one year and reduced the need of surgery significantly more than the unspecific control exercises. Patients with low baseline clinical score and/or a full-thickness tear significantly more often chose surgery.

    Level of evidence: I, Randomized controlled trail according to Consort statement.

  • 38.
    Björnsson Hallgren, Hanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Holmgren, Theresa
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Öberg, Birgitta
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Johansson, Kajsa
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Adolfsson, Lars
    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.
    A specific exercise strategy reduced the need for surgery in subacromial pain patients2014In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 48, no 19, p. 1431-1436Article in journal (Refereed)
    Abstract [en]

    Background and purpose A programme based on eccentric exercises for treating subacromial pain was in a previous study found effective at 3-month follow-up. The purposes of the present study were to investigate whether the results were maintained after 1 year and whether the baseline Constant-Murley score, rotator cuff status and radiological findings influenced the outcome. Patients and methods 97 patients on the waiting list for arthroscopic subacromial decompression had been randomised to a specific exercise programme or unspecific exercises (controls). After 3 months of exercises, the patients were asked whether they still wanted surgery and this option was available until a 1-year follow-up. 1 year after inclusion or 1 year after surgery, the number of patients who decided to have surgery in each group was compared. The choice of surgery was related to the baseline Constant-Murley score, ultrasound and radiographs taken at inclusion. Results All patients had improved significantly (pless than0.0001) in the Constant-Murley score at the 1-year follow-up. Significantly more patients in the control group decided to have surgery (63%) than those in the specific exercise group (24%; pless than0.0001). Patients who decided to have surgery had a significantly lower baseline Constant-Murley score and more often a full-thickness tear. Patients with partial tears did not differ from those with intact tendons. Interpretation The positive short-term results of specific exercises were maintained after 1 year, and this exercise strategy reduces the need for surgery. Full-thickness tear and a low baseline Constant-Murley score appear to be a predictive marker for a less good outcome.

  • 39.
    Björnsson, Hanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Norlin, Rolf
    Orebro University Hospital.
    Johansson, Kajsa
    Linköping University, Department of Medical and Health Sciences, Physiotherapy. Linköping University, Faculty of Health Sciences.
    Adolfsson, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    The influence of age, delay of repair, and tendon involvement in acute rotator cuff tears Structural and clinical outcomes after repair of 42 shoulders2011In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 82, no 2, p. 187-192Article in journal (Refereed)
    Abstract [en]

    Background and purpose Few authors have considered the outcome after acute traumatic rotator cuff tears in previously asymptomatic patients. We investigated whether delay of surgery, age at repair, and the number of cuff tendons involved affect the structural and clinical outcome. Patients and methods 42 patients with pseudoparalysis after trauma and no previous history of shoulder symptoms were included. A full-thickness tear in at least 1 of the rotator cuff tendons was diagnosed in all patients. Mean time to surgery was 38 (6-91) days. Follow-up at a mean of 39 (12-108) months after surgery included ultrasound, plain radiographs, Constant-Murley score, DASH score, and western Ontario rotator cuff (WORC) score. Results At follow-up, 4 patients had a full-thickness tear and 9 had a partial-thickness tear in the repaired shoulder. No correlation between the structural or clinical outcome and the time to repair within 3 months was found. The patients with a tendon defect at follow-up had a statistically significantly lower Constant-Murley score and WORC index in the injured shoulder and were significantly older than those with intact tendons. The outcomes were similar irrespective of the number of tendons repaired. Interpretation A delay of 3 months to repair had no effect on outcome. The patients with cuff defects at follow-up were older and they had a worse clinical outcome. Multi-tendon injury did not generate worse outcomes than single-tendon tears at follow-up.

  • 40.
    Bäck, Karolina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Wahlström, Ola
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Kjölhede, Preben
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Gasslander, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Differential expression of insulin and IGF-I receptors in human tissuesManuscript (preprint) (Other academic)
    Abstract [en]

    Insulin and IGF-I are related peptides with similar structure. They both signal via their cognate receptors, the insulin receptor (IR) and the insulin-like growth factor (IGF)-I receptor (IGF-IR).

    Our aim was to simultaneously measure the amount of insulin and IGF-I receptors in different human tissues and also the IR-A and IR-B isoforms to study tissue specific expression

    Renal artery intima-media, myometrium, skeletal muscle or liver tissue samples were obtained from patients undergoing surgery. IR, IGF-IR, IR-A and IR-B gene expression was investigated with real-time RT-PCR and expression of IR and IGF-IR protein was examined by Western blot and ELISA.

    Renal arteries and myometrium expressed the IGF-IR gene to a higher extent than the IR gene, liver expressed more IR than IGF-IR and skeletal muscle expressed almost equal amounts of both receptors. IR-B was the most abundant isoform in all tissues. With Western blot we could detect IR in skeletal muscle, liver and myometrium. With ELISA we found that, normalized to total protein, the highest levels of IGF-IR were found in renal arteries and myometrium and low levels in skeletal muscle and liver. The highest levels of IR were found in liver.

    In conclusion there is a large variation in the quantity and ratio of insulin receptors and IGF-I receptors expressed in different tissues, the extremes being arterial intima media with predominantly IGF-I receptors and liver with predominantly insulin receptors. This suggests that differential expression of insulin and IGF-I receptors is a key mechanism in regulation of growth and metabolism.

  • 41.
    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.

  • 42.
    Eliasson, Pernilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Andersson, Therese
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Influence of a single loading episode on gene expression in healing rat Achilles tendons2012In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 112, no 2, p. 279-288Article in journal (Refereed)
    Abstract [en]

    Mechanical loading stimulates tendon healing via mechanisms that are largely unknown. Genes will be differently regulated in loaded healing tendons, compared to unloaded, just because of the fact that healing processes have been changed. In order to avoid such secondary effects and study the effect of loading per se, we therefore studied the gene expression response shortly after a single loading episode in otherwise unloaded healing tendons.

    The Achilles tendon was transected in 30 tail suspended rats. The animals were let down from the suspension to load their tendons on a treadmill for 30 min once, 5 days after tendon transection. Gene expression was studied by Affymetrix microarray before, and 3, 12, 24 and 48 h after loading. The strongest response in gene expression was seen 3 hours after loading, when 150 genes were up- or down-regulated (fold change≥ 2, p≤0.05). 12 hours after loading, only 3 genes were up-regulated, while 38 were down-regulated. Less than 7 genes were regulated after 24 and 48 hours. Genes involved in the inflammatory response were strongly regulated at 3 and 12 hours after loading; this included up-regulation of iNOS, PGE synthase, and IL-1β. Also genes involved in wound healing/coagulation, angiogenesis and production of reactive oxygen species were strongly regulated by loading. Microarray results were confirmed for 14 selected genes in a repeat experiment (N=30 rats) using real-time PCR. It was also confirmed that a single loading episode on day 5 increased the strength of the healing tendon on day 12. The fact that there were hardly any regulated genes 24 h after loading suggests that optimal stimulation of healing requires a mechanical loading stimulus every day.

  • 43.
    Eliasson, Pernilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Andersson, Therese
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Hammerman, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Primary gene response to mechanical loading in healing rat Achilles tendons2013In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 114, no 11, p. 1519-1526Article in journal (Refereed)
    Abstract [en]

    Loading can stimulate tendon healing. In healing rat Achilles tendons, we have found more than 150 genes upregulated or downregulated 3 h after one loading episode. We hypothesized that these changes were preceded by a smaller number of regulatory genes and thus performed a microarray 15 min after a short loading episode, to capture the primary response to loading. We transected the Achilles tendon of 54 rats and allowed them to heal. The hind limbs were unloaded by tail-suspension during the entire experiment, except during the loading episode. The healing tendon tissue was analyzed by mechanical testing, microarray, and quantitative real-time polymerase chain reaction (qRT-PCR). Mechanical testing showed that 5 min of loading each day for 4 days created stronger tissue. The microarray analysis after one loading episode identified 15 regulated genes. Ten genes were analyzed in a repeat experiment with new rats using qRT-PCR. This confirmed the increased expression of four genes: early growth response 2 (Egr2), c-Fos, FosB, and regulation of G protein signaling 1 (Rgs1). The other genes were unaltered. We also analyzed the expression of early growth response 1 (Egr1), which is often coregulated with c-Fos or Egr2, and found that this was also increased after loading. Egr1, Egr2, c-Fos, and FosB are transcription factors that can be triggered by numerous stimuli. However, Egr1 and Egr2 are necessary for normal tendon development, and can induce ectopic expression of tendon markers. The five regulated genes appear to constitute a general activation machinery. The further development of gene regulation might depend on the tissue context.

  • 44.
    Fahlgren, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Johansson, Lars
    Linköping University, Department of Management and Engineering, Mechanics. Linköping University, The Institute of Technology.
    Edlund, Ulf
    Linköping University, Department of Management and Engineering, Mechanics. Linköping University, The Institute of Technology.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Direct ex vivo measurement of the fluid permeability of loose scar tissue2012In: Acta of Bioengineering and Biomechanics, ISSN 1509-409X, Vol. 14, no 2, p. 47-51Article in journal (Refereed)
    Abstract [en]

    Fluid flow is important in many biomechanical models, but there is a lack of experimental data that quantifies soft tissue permeability. We measured the tissue permeability in fibrous soft tissue, using a novel technique to obtain specimens by allowing soft tissue to grow into coralline hydroxyapatite scaffoldings implanted between the abdominal muscle layers of rats.

  • 45.
    Forsberg, Daniel
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Lundström, Claes
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, The Institute of Technology.
    Andersson, Mats
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Vavruch, Ludvig
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Tropp, Hans
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Knutsson, Hans
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Health Sciences.
    Fully automatic measurements of axial vertebral rotation for assessment of spinal deformity in idiopathic scoliosis2013In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 58, no 6, p. 1775-1787Article in journal (Refereed)
    Abstract [en]

    Reliable measurements of spinal deformities in idiopathic scoliosis are vital, since they are used for assessing the degree of scoliosis, deciding upon treatment and monitoring the progression of the disease. However, commonly used two dimensional methods (e.g. the Cobb angle) do not fully capture the three dimensional deformity at hand in scoliosis, of which axial vertebral rotation (AVR) is considered to be of great importance. There are manual methods for measuring the AVR, but they are often time-consuming and related with a high intra- and inter-observer variability. In this paper, we present a fully automatic method for estimating the AVR in images from computed tomography. The proposed method is evaluated on four scoliotic patients with 17 vertebrae each and compared with manual measurements performed by three observers using the standard method by Aaro-Dahlborn. The comparison shows that the difference in measured AVR between automatic and manual measurements are on the same level as the inter-observer difference. This is further supported by a high intraclass correlation coefficient (0.971-0.979), obtained when comparing the automatic measurements with the manual measurements of each observer. Hence, the provided results and the computational performance, only requiring approximately 10 to 15 s for processing an entire volume, demonstrate the potential clinical value of the proposed method.

  • 46.
    Gauffin, Håkan
    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.
    Tagesson (Sonesson), Sofi
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Meunier, Andreas
    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.
    Magnusson, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Kvist, Joanna
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Knee arthroscopic surgery is beneficial to middle-aged patients with meniscal symptoms: a prospective, randomised, single-blinded study2014In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 22, no 11, p. 1808-1816Article in journal (Refereed)
    Abstract [en]

    Objective: There is no evidence that a knee arthroscopy is more beneficial to middle-aged patients with meniscal symptoms compared to other treatments. This randomised controlled trial aimed to determine whether an arthroscopic intervention combined with a structured exercise programme would provide more benefit than a structured exercise programme alone for middle-aged patients with meniscal symptoms that have undergone physiotherapy. Method: 150 out of 179 eligible patients, aged 45 to 64 (mean: 54 +/- 5), symptom duration more than 3 months and standing X-ray with Ahlback grade 0, were randomised to: (1) a physiotherapy appointment within 2 weeks of inclusion that included instructions for a 3-month exercise programme (non-surgery group); or (2) the same as (1) plus, within 4 weeks of inclusion, knee arthroscopy for resection of any significant meniscal injuries (surgery group). The primary outcome was change in pain at 12 months, assessed with the Knee Injury and Osteoarthritis Outcome Score (KOOSPAIN). Results: In the Intention-To-Treat analysis, pain at 12 months was significantly lower in the surgery than in the non-surgery group. The change in KOOSPAIN was significantly larger in the surgery than in the non-surgery group (between-group difference was 10.6 points of change; 95% CI: 3.4 to 17.7, P = 0.004). The As-Treated analysis results were consistent with the Intention-To-Treat analysis results. Conclusion: Middle-aged patients with meniscal symptoms may benefit from arthroscopic surgery in addition to a structured exercise programme. Patients age or symptom history (i.e., mechanical symptoms or acute onset of symptoms) didnt affect the outcome.

  • 47.
    Hammerman, Malin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Eliasson, Pernilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Microtrauma stimulates rat Achilles tendon healing via an early gene expression pattern similar to mechanical loading2014In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 116, no 1, p. 54-60Article in journal (Refereed)
    Abstract [en]

    Mechanical loading increases the strength of healing tendons, but also induces small localized bleedings. Therefore, it is unclear if increased strength after loading is a response to mechanotransduction or microtrauma. We have previously found only five genes to be up-regulated 15 min after a single loading episode, of them four were transcription factors. These genes are followed by hundreds of genes after 3 h, many of them involved in inflammation. We now compared healing in mechanically unloaded tendons with or without added microtrauma induced by needling of the healing tissue. Nineteen rats received Botox into the calf muscle to reduce loading, and the Achilles tendon was transected. Ten rats were randomized to needling days 2-5. Mechanical testing on day 8 showed increased strength by 45% in the needling group. Next, another 24 rats were similarly unloaded, and 16 randomized to needling on day 5 after transection. Nineteen characteristic genes, known to be regulated by loading in this model, were analyzed by qRT-PCR. Four of these genes were regulated 15 min after needling. Three of them (Egr1, c-Fos, Rgs1) were among the five regulated genes after loading in a previous study. Sixteen of the 19 genes were regulated after 3 h, in the same way as after loading. In conclusion, needling increased strength, and there was a striking similarity between the gene expression response to needling and mechanical loading. This suggests that the response to loading in early tendon healing can, at least in part, be a response to microtrauma.

  • 48.
    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.

  • 49.
    Holmgren, Theresa
    et al.
    Linköping University, Department of Medical and Health Sciences, Physiotherapy. Linköping University, Faculty of Health Sciences.
    Björnsson Hallgren, Hanna
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Öberg, Birgitta
    Linköping University, Department of Medical and Health Sciences, Physiotherapy. Linköping University, Faculty of Health Sciences.
    Adolfsson, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Johansson, Kajsa
    Linköping University, Department of Medical and Health Sciences, Physiotherapy. Linköping University, Faculty of Health Sciences.
    Effect of specific exercise strategy on need for surgery in patients with subacromial impingement syndrome: randomised controlled study2012In: BMJ. British Medical Journal (International Ed.), ISSN 0959-8146, E-ISSN 0959-535X, Vol. 344, p. e787-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate if a specific exercise strategy, targeting the rotator cuff and scapula stabilisers, improves shoulder function and pain more than unspecific exercises in patients with subacromial impingement syndrome, thereby decreasing the need for arthroscopic subacromial decompression.

    DESIGN: Randomised, participant and single assessor blinded, controlled study.

    SETTING: Department of orthopaedics in a Swedish university hospital.

    PARTICIPANTS: 102 patients with long standing (over six months) persistent subacromial impingement syndrome in whom earlier conservative treatment had failed, recruited through orthopaedic specialists.

    INTERVENTIONS: The specific exercise strategy consisted of strengthening eccentric exercises for the rotator cuff and concentric/eccentric exercises for the scapula stabilisers in combination with manual mobilisation. The control exercise programme consisted of unspecific movement exercises for the neck and shoulder. Patients in both groups received five to six individual guided treatment sessions during 12 weeks. In between these supervised sessions the participants performed home exercises once or twice a day for 12 weeks.

    MAIN OUTCOME MEASURES: The primary outcome was the Constant-Murley shoulder assessment score evaluating shoulder function and pain. Secondary outcomes were patients' global impression of change because of treatment and decision regarding surgery.

    RESULTS: Most (97, 95%) participants completed the 12 week study. There was a significantly greater improvement in the Constant-Murley score in the specific exercise group than in the control exercise group (24 points (95% confidence interval 19 to 28.0) v 9 points (5 to 13); mean difference between group: 15 points (8.5 to 20.6)). Significantly more patients in the specific exercise group reported successful outcome (defined as large improvement or recovered) in the patients' global assessment of change because of treatment: 69% (35/51) v 24% (11/46); odds ratio 7.6, 3.1 to 18.9; P<0.001. A significantly lower proportion of patients in the specific exercise group subsequently chose to undergo surgery: 20% (10/51) v 63% (29/46); odds ratio 7.7, 3.1 to 19.4; P<0.001).

    CONCLUSION: A specific exercise strategy, focusing on strengthening eccentric exercises for the rotator cuff and concentric/eccentric exercises for the scapula stabilisers, is effective in reducing pain and improving shoulder function in patients with persistent subacromial impingement syndrome. By extension, this exercise strategy reduces the need for arthroscopic subacromial decompression within the three month timeframe used in the study.

    TRIAL REGISTRATION: Clinical trials NCT01037673.

  • 50.
    Holmgren, Theresa
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Björnsson Hallgren, Hanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, 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 Health Sciences.
    Adolfsson, Lars
    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.
    Johansson, Kajsa
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Republished research: Effect of specific exercise strategy on need for surgery in patients with subacromial impingement syndrome: randomised controlled study2014In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 48, no 19, p. 1456-1457Article in journal (Other academic)
    Abstract [en]

    STUDY QUESTION Can a specific exercise strategy improve shoulder function and pain in patients with subacromial impingement syndrome, thereby decreasing the need for arthroscopic subacromial decompression? SUMMARY ANSWER Compared with a control exercise group, patients in the specific exercise group had significantly greater improvements in shoulder function and pain and fewer patients needed surgery at the three month assessment. WHAT IS KNOWN AND WHAT THIS PAPER ADDS Different exercise programmes are used as first line treatment in patients with subacromial impingement syndrome, but conclusive evidence to support the efficacy for these programmes is lacking. This specific exercise strategy proved effective in improving shoulder function and pain in patients in whom earlier conservative treatment had failed.

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