liu.seSearch for publications in DiVA
Change search
Refine search result
1234 1 - 50 of 196
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the 'Create feeds' function.
  • 1.
    Abtahi, Jahan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Tengvall, Pentti
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology. Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden.
    Aspenberg, Per
    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.
    Bisphosphonate coating might improve fixation of dental implants in the maxilla: A pilot study2010In: International Journal of Oral and Maxillofacial Surgery, ISSN 0901-5027, E-ISSN 1399-0020, Vol. 39, no 7, 673-677 p.Article in journal (Refereed)
    Abstract [en]

    This pilot study evaluates the clinical stability of bisphosphonate-coated dental implants placed using a two-stage surgical procedure in five patients. Each patient received seven regular Branemark implants, one of which was coated with bisphosphonate in a fibrinogen matrix. The coated implant was inserted where the bone was expected to have the least favourable quality. The level of the marginal bone around each implant was measured by intraoral periapical radiographs and implant stability was recorded using resonance frequency measurements. Frequency values (ISQ) were obtained peroperatively before flap closure and after 6 months at abutment connection. At abutment connection the bisphosphonate-coated implants were removed en bloc in two patients for histological examination. An animal experiment had previously confirmed that gamma-sterilization did not reduce bioactivity of the bisphosphonate coating. In each patient, the bisphosphonate-coated implant showed the largest improvement in ISQ level of all implants. Their values at the start tended to be lower, and the absolute value at 6 months did not differ. No complications occurred with the coated implants. Histology showed no abnormalities. Improvement in ISQ values was an expected effect of the bisphosphonate coating, but could be due to the choice of insertion site. This finding warrants a randomized blinded study.

  • 2.
    Adolfsson, Lars
    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.
    Arthroscopic synovectomy in wrist arthritis2005In: Hand Clinics, ISSN 0749-0712, E-ISSN 1558-1969, Vol. 21, no 4, 527-530 p.Article, review/survey (Refereed)
    Abstract [en]

    Arthroscopic synovectomy is a safe outpatient procedure with minimal postoperative morbidity. In patients who have rheumatoid arthritis and possibly also in patients who have JRA, SLE, and postinfectious arthritis, a long period of increased comfort and improved function can be anticipated. The procedure may be considered in post-traumatic cases with joint contracture and as an adjunct to other measures for certain osteoarthritic disorders. In patients who have septic arthritis with insufficient clinical improvement after systemic antibiotics and lavage, arthroscopic synovectomy seems advantageous. © 2005 Elsevier Inc. All rights reserved.

  • 3.
    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, 395-399 p.Article 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.

  • 4.
    Adolfsson, Lars
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Open vs. arthroscopic synovectomy of the wrist2006In: Excerpta Medica: International Congress Series, ISSN 0531-5131, E-ISSN 1873-6157, Vol. 1295, 56-62 p.Article in journal (Refereed)
    Abstract [en]

    Synovectomy may be considered for the treatment of chronic wrist arthritis. The indications for wrist synovectomy are, however, not clearly defined. Open synovectomy has been reported to provide good pain relief for a relatively long time but can be associated with loss of mobility. Arthroscopic synovectomy seems equally reliable in terms of symptom reduction and no adverse effects have been reported. © 2006 Elsevier B.V. All rights reserved.

  • 5.
    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, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Hammer, R.
    Orthopaedic Surgery, Central Hospital, SE-291 85 Kristianstad, Sweden.
    Elbow hemiarthroplasty for acute reconstruction of intraarticular distal humerus fractures: A preliminary report involving 4 patients2006In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 77, no 5, 785-787 p.Article in journal (Refereed)
    Abstract [en]

    We treated 4 female patients (mean age 80) with complex intraarticular acute fracture of the distal humerus with a Kudo humeral component, i.e. a hemiarthroplasty. All fractures were considered impossible to treat with open reduction and internal fixation. At mean 10 (3-14) months, 3 patients had an excellent result and 1 a good result according to the Mayo elbow performance score. We conclude that a hemiarthroplasty may be a valuable alternative in eldery patients with complex fractures of the distal humerus. Copyright© Taylor & Francis 2006.

  • 6.
    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, 451-455 p.Article 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.

  • 7.
    Agholme, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Wnt signaling and metaphyseal bone healing2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis relates to some new aspects on the regulation of bone healing. In the last few years, Wnt-signaling has been shown to play a central role in bone biology. As well as being involved in bone maintenance and repair, Wnt-signaling has been presented as one of the key pathways through which bone responds to mechanical load. Two secreted extracellular inhibitors of Wnt-signaling, sclerostin and dickkopf-1 are potent negative regulators of bone formation.

    Using a rat fracture model we investigated how metaphyseal bone healing is influenced by changes in Wnt-signaling.

    Antibodies were used to suppress levels of sclerostin and dickkopf-1, and thereby increase Wnt-signaling. Primarily, we investigated if those antibody treatments lead to improved bone healing. Also, we investigated if the response was coupled to the loading conditions of the bone.

    Our findings suggest that suppression of either sclerostin or dickkopf-1 leads to increased bone formation and improved bone healing. Apart from just having an effect on healing, the treatment also improved bone formation in other parts of the skeleton. Depending on the loading conditions, the effects were different. Dickkopf-1 appeared to have a stronger effect on bone volume density in unloaded bone, implying a role mainly in mechano-transduction, while sclerostin had similar effect in both loaded and unloaded bone. To confirm these findings, we studied how the expression of several Wnt-related genes changed due to trauma and unloading in metaphyseal bone. We found that trauma led to upregulation of most of the genes with the largest effect seen in the unloaded bone. In untraumatized bone, there was mainly an effect on the sclerostin gene.

    In conclusion, antibodies against sclerostin and dickkopf-1 appear to be able to improve metaphyseal bone healing. There appear to be some differences in how the effect of the two antibodies manifests itself, especially if the loading conditions of the bone are altered. These findings suggest a potential for clinical use to shorten fracture healing time.

    List of papers
    1. Sclerostin Antibody Treatment Enhances Metaphyseal Bone Healing in Rats
    Open this publication in new window or tab >>Sclerostin Antibody Treatment Enhances Metaphyseal Bone Healing in Rats
    Show others...
    2010 (English)In: JOURNAL OF BONE AND MINERAL RESEARCH, ISSN 0884-0431, Vol. 25, no 11, 2412-2418 p.Article in journal (Refereed) Published
    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

    Place, publisher, year, edition, pages
    American Society for Bone and Mineral Research, 2010
    Keyword
    bone formation;implants;bone repair;sclerostin;antibody
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-62733 (URN)10.1002/jbmr.135 (DOI)000284133500016 ()20499342 (PubMedID)
    Available from: 2010-12-03 Created: 2010-12-03 Last updated: 2011-10-10
    2. The effects of Dickkopf-1 antibody on metaphyseal bone and implant fixation under different loading conditions
    Open this publication in new window or tab >>The effects of Dickkopf-1 antibody on metaphyseal bone and implant fixation under different loading conditions
    2011 (English)In: BONE, ISSN 8756-3282, Vol. 48, no 5, 988-996 p.Article in journal (Refereed) Published
    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.

    Place, publisher, year, edition, pages
    Elsevier Science B.V., Amsterdam., 2011
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-68352 (URN)10.1016/j.bone.2011.02.008 (DOI)000289879900005 ()
    Note
    Original Publication: Fredrik Agholme, Hanna Isaksson, Stuart Kuhstoss and Per Aspenberg, The effects of Dickkopf-1 antibody on metaphyseal bone and implant fixation under different loading conditions, 2011, BONE, (48), 5, 988-996. http://dx.doi.org/10.1016/j.bone.2011.02.008 Copyright: Elsevier Science B.V., Amsterdam. http://www.elsevier.com/ Available from: 2011-05-20 Created: 2011-05-20 Last updated: 2011-10-10
    3. Anti-sclerostin antibody and mechanical loading appear to influence metaphyseal bone independently in rats
    Open this publication in new window or tab >>Anti-sclerostin antibody and mechanical loading appear to influence metaphyseal bone independently in rats
    Show others...
    2011 (English)In: Acta Orthopaedica, ISSN 1745-3674, Vol. 82, no 5, 628-632 p.Article in journal (Refereed) Published
    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.

    Place, publisher, year, edition, pages
    Taylor and Francis, 2011
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-71284 (URN)10.3109/17453674.2011.625539 (DOI)
    Available from: 2011-10-10 Created: 2011-10-10 Last updated: 2014-10-17Bibliographically approved
    4. Wnt gene expression during metaphyseal bone healing under different load conditions
    Open this publication in new window or tab >>Wnt gene expression during metaphyseal bone healing under different load conditions
    (English)Manuscript (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.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-71285 (URN)
    Available from: 2011-10-10 Created: 2011-10-10 Last updated: 2011-10-10Bibliographically approved
  • 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, 743-752 p.Article 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.
    Andersson, Therese
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Tengvall, Pentti
    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, Orthopaedic Centre, Department of Orthopaedics Linköping.
    A win for bisphosphonates? Comparison between local bisphosphonate release and hydroxyapatite coating for screw fixation in rats in BONE, vol 46, issue , pp S67-S672010In: BONE, Elsevier Science B.V., Amsterdam. , 2010, Vol. 46, S67-S67 p.Conference paper (Refereed)
    Abstract [en]

    n/a

  • 10.
    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, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Experimental results of combining bisphosphonates with allograft in a rat model2009In: Journal of Bone and Joint Surgery - Series B, ISSN 0301-620X, Vol. 91, no 5, 670-675 p.Article in journal (Refereed)
    Abstract [en]

    Soaking bone grafts in a bisphosphonate solution before implantation can prevent their resorption and increase the local bone density in rats and humans. However, recent studies suggest that pre-treatment of allografts with bisphosphonate can prevent bone ingrowth into impaction grafts. We tested the hypothesis that excessive amounts of bisphosphonate would also cause a negative response in less dense grafts. We used a model where nonimpacted metaphyseal bone grafts were randomised into three groups with either no bisphosphonate, alendronate followed by rinsing, and alendronate without subsequent rinsing, and inserted into bone chambers in rats. The specimens were evaluated histologically at one week, and by histomorphometry and radiology at four weeks. At four weeks, both bisphosphonate groups showed an increase in the total bone content, increased newly formed bone, and higher radiodensity than the controls. In spite of being implanted in a chamber with a limited opportunity to diffuse, even an excessive amount of bisphosphonate improved the outcome. We suggest that the negative results seen by others could be due to the combination of densely compacted bone and a bisphosphonate. We suggest that bisphosphonates are likely to have a negative influence where resorption is a prerequisite to create space for new bone ingrowth.

  • 11.
    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, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Reduced serum serotonin impairs metaphyseal repair in rats in BONE, vol 46, issue , pp S67-S672010In: BONE, Elsevier Science B.V., Amsterdam. , 2010, Vol. 46, S67-S67 p.Conference paper (Refereed)
    Abstract [en]

    n/a

  • 12.
    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, 125-130 p.Article 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.

  • 13.
    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, 988-996 p.Article 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.

  • 14.
    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, 628-632 p.Article 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.

  • 15.
    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, 2412-2418 p.Article 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

  • 16.
    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.

  • 17.
    Akerstedt, Anita
    et al.
    Child and Youth Habilitat, Eksjo, Sweden .
    Risto, Olof
    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.
    Ödman, Pia
    Linköping University, Department of Medicine and Health Sciences, Physiotherapy. Linköping University, Faculty of Health Sciences.
    Öberg, Birgitta
    Linköping University, Department of Medicine and Health Sciences, Physiotherapy. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Public Health Sciences.
    Evaluation of single event multilevel surgery and rehabilitation in children and youth with cerebral palsy - A 2-year follow-up study2010In: DISABILITY AND REHABILITATION, ISSN 0963-8288, Vol. 32, no 7, 530-539 p.Article in journal (Refereed)
    Abstract [en]

    Method. A prospective single-subject study with AB design and 2-year follow-up, included 11 children between 8 and 18 years old with CP, Gross Motor Function Classification System I-III. Visual analyses were used to present physical function with Physical Cost Index (PCI). Descriptive statistics were used to present number of children with a clinically important change in Gross Motor Function Measure (GMFM), self-reported walking ability, and HRQOL with child health questionnaire (CHQ). Results. PCI showed a trend of lower energy cost during gait in six children and GMFM was unchanged for 10 children and improved for one child. Walking ability was improved in 10 children. Gait distance increased in all 11. Both physical and psychosocial dimensions of CHQ improved in six of nine (two missing data). Expectations of outcomes were fulfilled in seven and partly fulfilled in four. Satisfaction with care was fulfilled in 10 of 11. Conclusion. Self-reported walking ability improved after multilevel surgery and intensive rehabilitation. This result was partly supported by lower energy cost and improved HRQOL. Expectations and satisfaction were fulfilled for the majority of children.

  • 18.
    Andersson, Therese
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Agholme, Fredrik
    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, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Tengvall, Pentti
    Gothenburg University.
    Surface immobilized zoledronate improves screw fixation in rat bone: A new method for the coating of metal implants2010In: JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE, ISSN 0957-4530, Vol. 21, no 11, 3029-3037 p.Article in journal (Refereed)
    Abstract [en]

    Previous studies show that surface immobilized bisphosphonates improve the fixation of stainless steel screws in rat tibia after 2-8 weeks of implantation. We report here about the immobilization of a potent bisphosphonate, zoledronate, to crosslinked fibrinogen by the use of another technique, i.e. ethyl-dimethyl-aminopropylcarbodiimide (EDC)/imidazole immobilization. Bone fixation of zoledronate-coated screws was compared to screws coated with crosslinked fibrinogen only and ditto with EDC/N-hydroxy-succinimide immobilized pamidronate. Fixation in rat tibia was evaluated by a pull-out test at either 2 or 6 weeks after implantation. Both bisphosphonate coatings increased the pull-out force at both time points, and zoledronate showed a significantly higher pull-out force than pamidronate. To further evaluate the new coating technique we also performed a morphometric study, focusing on the area surrounding the implant. The zoledronate coating resulted in an increased bone density around the screws compared to controls. No pronounced increase was seen around the pamidronate coated screws. Together, the results demonstrate the possibility of obtaining a significant local therapeutic effect with minute amounts of surface immobilized zoledronate.

  • 19.
    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, 274-279 p.Article 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.

  • 20.
    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, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Tissue memory in healing tendons: short loading episodes stimulate healing2009In: JOURNAL OF APPLIED PHYSIOLOGY, ISSN 8750-7587, Vol. 107, no 2, 417-421 p.Article in journal (Refereed)
    Abstract [en]

    Intact tendons adapt slowly to changes in mechanical loading, whereas in healing tendons the effect of mechanical loading or its absence is dramatic. The longevity of the response to a single loading episode is, however, unknown. We hypothesized that the tissue has a "memory" of loading episodes and that therefore short loadings are sufficient to elicit improved healing. The Achilles tendon of 70 female rats was transected and unloaded by tail suspension for 12 days (suspension started on day 2 after surgery). Each day, the rats were let down from suspension for short daily training episodes according to different regimes: 15 min of cage activity or treadmill running for 15, 30, 60, or 2 x 15 min. Rats with transected Achilles tendons and full-time cage activity served as controls. The results demonstrated that full-time cage activity increased the peak force over three times compared with unloading. Short daily loading episodes (treadmill running) increased the peak force about half as much as full-time activity. Prolongation of treadmill running above 15 min or dividing the daily training in two separate episodes had minimal further effect. This mechanical stimulation increased the cross-sectional area but had no effect on the mechanical properties of the repair tissue. The findings indicate that once the tissue had received information from a certain loading type and level, this is "memorized" and leads to a response lasting many hours. This suggests that patients might be allowed early short loading episodes following, e. g., an Achilles tendon rupture for a better outcome.

  • 21.
    Aspenberg, Per
    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.
    Bisphosphonates and implants2009In: Acta orthopaedica, ISSN 1745-3682, Vol. 80, no 1, 119-123 p.Article in journal (Refereed)
  • 22.
    Aspenberg, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Drugs and fracture repair2005In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 76, no 6, 741-748 p.Article, review/survey (Refereed)
    Abstract [en]

    [No abstract available]

  • 23.
    Aspenberg, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Impaction bone grafting2001In: Acta Orthopaedica Scandinavica, ISSN 0001-6470, Vol. 72, no 6, 662-663 p.Other (Other academic)
  • 24.
    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, 122-122 p.Article in journal (Other academic)
    Abstract [en]

    n/a

  • 25.
    Aspenberg, Per
    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.
    Overtreatment of cruciate ligament injuries2010In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 81, no 5, 524-525 p.Article in journal (Other academic)
    Abstract [en]

    n/a

  • 26.
    Aspenberg, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Response: Cox inhibitors and bone healing2003Other (Other academic)
  • 27.
    Aspenberg, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Stimulation of tendon repair: Mechanical loading, GDFs and platelets. a mini-review2007In: International Orthopaedics, ISSN 0341-2695, E-ISSN 1432-5195, Vol. 31, no 6, 783-789 p.Article, review/survey (Refereed)
    Abstract [en]

    The repair of subcutaneous tendon ruptures can be stimulated by a single application of one of several growth factors [e.g. platelet-derived growth factor (PDGF), transforming growth factor (TGF)-beta, insulin-like growth factor (IGF)-1, vascular endothelial growth factor (VEGF), bone morphogenetic proteins (BMPs) like growth differentiation factor (GDF)-5, -6, -7] or by a thrombocyte concentrate (PRP). The response to these measures is dependent on the mechanical microenvironment, which is crucial for repair. So far, almost all research has been limited to rodent models, mostly using the rat Achilles tendon. Ruptured human Achilles tendons appear to be mechanically loaded in spite of immobilisation. This suggests that the mechanical microenvironment might be favourable for the clinical use of growth factors or platelets for this indication. New methods to quantitate human Achilles tendon repair have been developed. © 2007 Springer-Verlag.

  • 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, 511-512 p.Article in journal (Other academic)
    Abstract [en]

    n/a

  • 29.
    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.
    Agholme, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Fahlgren, Anna
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Magnusson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Chemistry.
    Targeting RANKL for reduction of bone loss around unstable implants: OPG-Fc compared to alendronate in a model for mechanically induced loosening2011In: BONE, ISSN 8756-3282, Vol. 48, no 2, 225-230 p.Article in journal (Refereed)
    Abstract [en]

    Orthopedic joint prostheses may loosen because of localized bone resorption. Despite initial optimism, there are no reports showing that bisphosphonates can stop the progression of prosthetic loosening once it has begun. This might be due to the strong resorptive stimulus, which continuously recruits new osteoclasts. Therefore, we hypothesized that a treatment targeting osteoclast recruitment would be more efficacious than a treatment reducing osteoclast activity. We used a previously described rat model for instability-induced bone resorption, and compared OPG-Fc with alendronate at a clinically relevant or an extreme dose. A titanium plate was osseointegrated at the rat tibial surface. Instability was simulated by a piston, moving perpendicularly to the bone surface. Piston movement induced bone loss via hydrostatic pressure or fluid flow. Rats were randomized to 5 groups (total n = 56), of which 4 were subjected to instability and one was stable. The unstable groups were injected with either high-dose OPG-Fc (10 mg/kg, twice weekly), a high dose of alendronate (20 mu g /kg/day), an extreme dose of alendronate (200 mu g/kg/day) or saline. Significant protection against resorption could only be shown for OPG-Fc and the extreme alendronate dose. Both alendronate doses reduced serum levels of tartrate-resistant acid phosphatase isoform 5b to a similar extent, demonstrating that the lower dose was able to reduce resorption in the normally remodeling skeleton, although not in the osteolytic lesions caused by instability. Osteoclast numbers in the lesion were increased by the lower bisphosphonate dose and reduced by OPG-Fc. The results suggest the possibility of targeting osteoclast recruitment via the RANKL system in patients with impending prosthetic loosening.

  • 30.
    Aspenberg, Per
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Astrand, J
    Linkoping Univ Hosp, Dept Orthoped, SE-58185 Linkoping, Sweden.
    Bone allografts pretreated with a bisphosphonate do not resorb2002In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 30, no 3, B1- p.Conference paper (Other academic)
  • 31.
    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, 404-414 p.Article 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.

  • 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.
    Johansson, Torsten
    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.
    Teriparatide improves early callus formation in distal radial fractures2010In: ACTA ORTHOPAEDICA, ISSN 1745-3674, Vol. 81, no 2, 236-238 p.Article in journal (Refereed)
    Abstract [en]

    Methods One third of the patients of the international trial were treated at Linkoping University Hospital. The multicenter trial did not evaluate early callus formation. We therefore made a blinded qualitative scoring of the callus at 5 weeks in our 27 patients. Callus formation was arbitrarily classified as rich, intermediate, or poor. Results 9 patients were classified as rich (none had received placebo, 3 low-dose teriparatide, and 6 high-dose teriparatide). 9 patients were classified as intermediate (1 had received placebo, 5 low-dose, and 3 high-dose). 9 patients were classified as poor (7 had received placebo, 1 low-dose, and 1 high-dose) (p andlt; 0.001). Interpretation This is a post hoc subgroup analysis of an outcome variable, which was not in the official protocol. The results must therefore be interpreted with caution. However, in combination with the results of the larger trial, the data suggest that radiographic quality at an early time point might be a sensitive variable, perhaps better than time to cortical continuity. Moreover, teriparatide appeared to improve early callus formation in distal radial fractures.

  • 33.
    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.
    Schilcher, Jörg
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Fahlgren, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Histology of an undisplaced femoral fatigue fracture in association with bisphosphonate treatment2010In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 81, no 4, 460-462 p.Article in journal (Refereed)
    Abstract [en]

    n/a

  • 34.
    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.
    Virchenko, Olga
    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.
    Platelet concentrate injection improves Achilles tendon repair in rats2004In: Acta Orthopaedica Scandinavica, ISSN 1745-3674, Vol. 75, no 1, 93-99 p.Article in journal (Refereed)
    Abstract [en]

    Background:Blood platelets release a cocktail of growth factors when activated, some of which are thought to initiate and stimulate repair.

    Experiment and findings: We studied whether a platelet concentrate injection would improve Achilles tendon repair in an established rat model. The Achilles tendon was transected and a 3 mm segment removed. After 6h, a platelet concentrate was injected percutaneously into the hematoma. This increased tendon callus strength and stiffness by about 30 % after 1 week, which persisted for as long as 3 weeks after the injection. At this time, the mechanical testing indicated an improvement in material characteristics - i.e., greater maturation of the tendon callus. This was confirmed by blinded histological scoring.

    Interpretation: Platelet concentrate may prove useful for the treatment of Achilles tendon ruptures.

  • 35.
    Aspenberg, Per
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Wagner, Philippe
    Swedish National Competence Center for Musculoskeletal Disorders Lund University Hospital.
    Nilsson, Kjell G.
    Department of Orthopedics Umeå University Hospital.
    Ranstam, Jonas
    Swedish National Competence Center for Musculoskeletal Disorders Lund University Hospital.
    Fixed or loose? Dichotomy in RSA data for cemented cups2008In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 79, no 4, 467-473 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Roentgen stereometric analysis (RSA) cannot discern whether a single prosthesis is fixed or migrating below the detection level. Samples of patients usually show migration values that appear to be continuously distributed. Is there such continuity, or is there a dichotomy between stable and migrating prostheses? The hypothesis of a dichotomy has, to our knowledge, not been tested. We present an exploratory evaluation of such a dichotomy using a mixture distribution algorithm. METHODS: We analyzed the migration (as determined by RSA) of 147 cemented acetabular cups of 7 different designs by using a new set of algorithms for frequency distribution analysis called Rmix. RESULTS: We first analyzed a migration vector, regardless of direction. After 2 years there was a significant dichotomy between 2 lognormal subgroups within the sample. Although some types of cups were over-represented in one of the subgroups, neither cup design, sex, nor operating department could explain the dichotomy into two groups, which appears to reflect the existence of two basically different types of behavior of the cups. We next analyzed the migration along the 3 axes in space, and found a similar dichotomy. During the second year, around 80% of the patients belonged to a distinct, normally distributed subgroup with a mean not different from 0 mm and a small variation. The remainder differed significantly from this subgroup and showed migration. INTERPRETATION: There is a dichotomy in migration pattern. During the second postoperative year, most cups belonged to a subpopulation that appeared stable. The remainder is probably at risk of loosening. For a single type of prosthesis, the relative size of the stable subgroup may be a good index of the expected performance. The possibility of detecting subgroups within a seemingly continuous sample might be useful in many fields of medicine.

  • 36.
    Aspenberg, Per
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Wermelin, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine .
    Tengwall, Pentti
    Laboratory of Applied Physics, Department of Physics, Chemistry and Biology Linköping University.
    Fahlgren, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine .
    Additive effects of PTH and bisphosphonates on the bone healing response to metaphyseal implants in rats2008In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 79, no 1, 111-115 p.Article in journal (Refereed)
    Abstract [en]

     BACKGROUND: When PTH is used to increase the amount of bone in osteoporotic patients, combination with bisphosphonates is known to attenuate the response. This might be explained by the reduced number of remodeling sites after bisphosphonate treatment, which reduces the number of cells able to respond to PTH. However, in a repair situation after trauma, a large number of osteoblasts reside in the wound site. If their activity is no longer coupled to osteoclasts, decreased resorption by bisphosphonates and stimulation of osteoblastic activity by PTH should both (independently) increase bone formation. Thus, we hypothesized that in contrast to the case in osteoporosis treatment, PTH and bisphosphonates have an additive effect in situations involving bone regeneration. MATERIAL AND METHODS: Stainless steel screws, either coated with biphosphonates or uncoated, were inserted in 46 rat tibias. This normally elicits a bone repair response, leading to a gradual increase in the strength of screw fixation. Half of the rats also received daily injections of teriparatide (PTH). Thus, there were 4 groups: control, bisphosphonate, PTH, and bisphosphonate plus PTH. Pull-out force and energy were measured after 2 weeks. RESULTS: The combined treatment had the strongest effect. It doubled the pull-out force and tripled the pull-out energy, compared to untreated controls. Also, bisphosphonate or PTH alone increased the pull-out force and energy, although less. No treatment cross-dependency was observed. INTERPRETATION: Because bisphosphonates mainly influence osteoclasts, and intermittent administration of PTH mainly influences osteoblasts, our findings indicate that to a large extent these cells work without coupling in this model. It appears that bisphosphonates are unlikely to attenuate the response to PTH during the formation of new bone.

  • 37.
    Bachrach-Lindström, Margareta
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Nursing Science.
    Karlsson, Susanne
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Pettersson, Lars-Goran
    Kalmar Central Hospital.
    Johansson, Torsten
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Patients on the waiting list for total hip replacement: a 1-year follow-up study2008In: Scandinavian Journal of Caring Sciences, ISSN 0283-9318, E-ISSN 1471-6712, Vol. 22, no 4, 536-542 p.Article in journal (Refereed)
    Abstract [en]

    Patients on the waiting list for total hip replacement: a 1-year follow-up study

    Untreated osteoarthritis (OA) in the hip causes pain and reduced physical and social functioning. The aim of this study was to evaluate the effect of waiting time on health-related quality of life (HRQOL), functional condition and dependence on help at the time of surgery and during follow-up 1 year after surgery. A further aim was to elucidate possible differences between men and women. Two hundred and twenty-nine consecutively included patients with OA in the hip were interviewed when assigned to the waiting list, again 1 week prior to surgery with unilateral total hip replacement (THR), and 1 year after surgery. Health-related quality of life and function were measured using the Nottingham Health Profile, EuroQoL and the Western Ontario and McMaster Universities Osteoarthritis Index. The result showed that the average waiting time was 239 days, that 15% of the patients were operated on within 3 months, and that 21% had to wait more than 6 months. At the time of surgery, HRQOL had deteriorated significantly (p < 0.05) and the number of patients receiving support from relatives had increased from 31% to 58% during the wait. At the 1-year follow-up, both HRQOL and functional condition had improved significantly despite the wait, and the need for support from relatives had decreased to 11% (p < 0.001). In conclusion, long waiting time for THR is detrimental to patients HRQOL causing reduced functional condition, pain and increased need for support from relatives, which limit the independence in daily life.

  • 38. Bauer, HCF
    et al.
    Alvegard, TA
    Berlin, O
    Erlanson, M
    Kalén, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Lindholm, P
    Gustafson, P
    Smeland, S
    Trovik, CS
    The Scandinavian Sarcoma Group Register 1986-20012004In: Acta Orthopaedica Scandinavica, ISSN 0001-6470, Vol. 75Article in journal (Refereed)
  • 39.
    Berg, Svante
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences.
    On Total Disc Replacement2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Low back pain consumes a large part of the community’s resources dedicated to health care and sick leave. Back disorders also negatively affect the individual leading to pain suffering, decreased quality-of-life and disability. Chronic low back pain (CLBP) due to degenerative disc disease (DDD) is today often treated with fusion when conservative treatment has failed and symptoms are severe. This treatment is as successful as arthroplasty is for hip arthritis in restoring the patient’s quality of life and reducing disability. Even so, there are some problems with this treatment, one of these being recurrent CLBP from an adjacent segment (ASD) after primarily successful surgery. This has led to the development of alternative surgical treatments and devices that maintain or restore mobility, in order to reduce the risk for ASD. Of these new devices, the most frequently used are the disc prostheses used in Total Disc Replacement (TDR).

    This thesis is based on four studies comparing total disc replacement with posterior fusion. The studies are all based on a material of 152 patients with DDD in one or two segments, aged 20-55 years that were randomly treated with either posterior fusion or TDR.

    The first study concerned clinical outcome and complications. Follow-up was 100% at both one and two years. It revealed that both treatment groups had a clear benefit from treatment and that patients with TDR were better in almost all outcome scores at one-year follow-up. Fusion patients continued to improve during the second year. At two-year follow-up there was a remaining difference in favour of TDR for back pain. 73% in the TDR group and 63% in the fusion group were much better or totally pain-free (n.s.), while twice as many patients in the TDR group were totally pain free (30%) compared to the fusion group (15%).

    Time of surgery and total time in hospital were shorter in the TDR group.

    There was no difference in complications and reoperations, except that seventeen of the patients in the fusion group were re-operated for removal of their implants.

    The second study concerned sex life and sexual function. TDR is performed via an anterior approach, an approach that has been used for a long time for various procedures on the lumbar spine. A frequent complication reported in males when this approach is used is persistent retrograde ejaculation. The TDR group in this material was operated via an extra-peritoneal approach to the retroperitoneal space, and there were no cases of persistent retrograde ejaculation. There was a surprisingly high frequency of men in the fusion group reporting deterioration in ability to have an orgasm postoperatively.

    Preoperative sex life was severely hampered in the majority of patients in the entire material, but sex life underwent a marked improvement in both treatment groups by the two-year follow-up that correlated with reduction in back pain.

    The third study was on mobility in the lumbar spinal segments, where X-rays were taken in full extension and flexion prior to surgery and at two-year follow-up. Analysis of the films showed that 78% of the patients in the fusion group reached the surgical goal (non-mobility) and that 89% of the TDR patients maintained mobility.

    Preoperative disc height was lower than in a normative database in both groups, and remained lower in the fusion group, while it became higher in the TDR group. Mobility in the operated segment increased in the TDR group postoperatively. Mobility at the rest of the lumbar spine increased in both treatment groups. Mobility in adjacent segments was within the norm postoperatively, but slightly larger in the fusion group.

    In the fourth study the health economics of TDR vs Fusion was analysed. The hospital costs for the procedure were higher for patients in the fusion group compared to the TDR group, and the TDR patients were on sick-leave two months less.

    In all, these studies showed that the results in the TDR group were as good as in the fusion group. Patients are more likely to be totally pain-free when treated with TDR compared to fusion. Treatment with this new procedure seems justified in selected patients at least in the short-term perspective. Long-term follow-up is underway and results will be published in due course.

    List of papers
    1. Total disc replacement compared to lumbar fusion: a randomised controlled trial with 2-year follow-up
    Open this publication in new window or tab >>Total disc replacement compared to lumbar fusion: a randomised controlled trial with 2-year follow-up
    Show others...
    2009 (English)In: EUROPEAN SPINE JOURNAL, ISSN 0940-6719, Vol. 18, no 10, 1512-1519 p.Article in journal (Refereed) Published
    Abstract [en]

    The study design includes a prospective, randomised controlled study comparing total disc replacement (TDR) with posterior fusion. The main objective of this study is to compare TDR with lumbar spinal fusion, in terms of clinical outcome, in patients referred to a spine clinic for surgical evaluation. Fusion is effective for treating chronic low back pain (LBP), but has drawbacks, such as stiffness and possibly adjacent level degradation. Motion-preserving options have emerged, of which TDR is frequently used because of these drawbacks. How the results of TDR compare to fusion, however, is uncertain. One hundred and fifty-two patients with a mean age of 40 years (21-55) were included: 90 were women, and 80 underwent TDR. The patients had not responded to a conservative treatment programme and suffered from predominantly LBP, with varying degrees of leg pain. Diagnosis was based on clinical examination, radiographs, MRI, and in unclear cases, diagnostic injections. Outcome measures were global assessment (GA), VAS for back and leg pain, Oswestry Disability Index, SF36 and EQ5D at 1 and 2 years. Follow-up rate was 100%, at both 1 and 2 years. All outcome variables improved in both groups between preoperative and follow-up assessment. The primary outcome measure, GA, revealed that 30% in the TDR group and 15% in the fusion group were totally pain-free at 2 years (P = 0.031). TDR patients had reached maximum recovery in virtually all variables at 1 year, with significant differences compared to the fusion group. The fusion patients continued to improve and at 2 years had results similar to TDR patients apart from numbers of pain-free. Complications and reoperations were similar in both groups, but pedicle screw removal as additive surgery, was frequent in the fusion group. One year after surgery, TDR was superior to spinal fusion in clinical outcome, but this difference had diminished by 2 years, apart from (VAS for back pain and) numbers of pain-free. The long-term benefits have yet to be examined.

    Keyword
    Degenerative disc disease, Prospective randomised controlled trial, Total disc replacement, Spinal fusion, Patients global assessment of back pain
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-51285 (URN)10.1007/s00586-009-1047-0 (DOI)
    Available from: 2009-10-26 Created: 2009-10-26 Last updated: 2010-03-08
    2. Sex life and sexual function in men and women before and after total disc replacement compared with posterior lumbar fusion
    Open this publication in new window or tab >>Sex life and sexual function in men and women before and after total disc replacement compared with posterior lumbar fusion
    2009 (English)In: The spine journal, ISSN 1529-9430, E-ISSN 1878-1632, Vol. 9, no 12, 987-994 p.Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND CONTEXT: Sex life and sexual function maybe affected by low back pain (LBP). Sexual dysfunction after anterior lumbar fusion is reported in both men and women, but focus is mainly on impaired male biological function (retrograde ejaculation) as this may cause infertility. This has led to concern as to whether anterior surgery should be employed in men, at least in younger age groups. PURPOSE: To investigate how chronic low back pain (CLBP) of assumed discogenic origin affects sex life and sexual function in patients considered for surgical treatment, whether this is affected by surgical treatment (total disc replacement [TDR] or posterolateral fusion [PLF]/posterior lumbar interbody fusion [PLIF]), and if so, are there differences between the surgical procedures undertaken. STUDY DESIGN: A randomized controlled trial comparing TDR and instrumented lumbar spine fusion, performed either as a PLF or PLIF. PATIENT SAMPLE: One hundred fifty-two patients were included in this randomized controlled trial to compare the effect on CLBP of either TDR via an anterior retroperitoneal approach or instrumented posterior lumbar fusion, PLF or PLIF. OUTCOME MEASURES: Global assessment of back pain, back pain (visual analog scale [VAS] 0-100), function (Oswestry Disability Index [ODI] 0-100), quality of life (EQ5D [EuroQol] 0-1), and answers on specific sexual function. METHODS: Outcome was assessed using data from the Swedish Spine Register (SweSpine). In ODI, one question, ODI 8, reflects the impact of back pain on sex life. This question was analyzed separately. Patients also answered a gender-specific questionnaire preoperatively and at the 2-year follow-up to determine any sexual dysfunction regarding erection, orgasm, and ejaculation. Followup was at 1 and 2 years. RESULTS: Before surgery, 34% reported that their sex life caused some extra LBP, and an additional 30% that their sex life was severely restricted by LBP. After surgery, sex life improved in both groups, with a strong correlation to a reduction of LBP. The gender-specific questionnaire used to measure sexual function after 2 years revealed no negative effect of TDR or Fusion in men regarding erection or retrograde ejaculation. However, 26% of all men in the Fusion group, compared with 3% in the TDR group, reported postoperative deterioration in the ability to achieve orgasm, despite a reduction of LBP CONCLUSIONS: Impairment of sex life appears to be related to CLBP. An improvement in sex life after TDR or lumbar fusion was positively correlated to a reduction in LBP. Total disc replacement in this study, performed through an anterior retroperitoneal approach, was not associated with greater sexual dysfunction compared with instrumented lumbar fusion performed either as a PLF or as a PLIF. Sexual function, expressed as orgasm, deteriorated in men in the Fusion group postoperatively, in spite of this group reporting less LBP after 2 years.

    Keyword
    Sex life; Sexual dysfunction; Retrograde ejaculation; Total disc replacement; Lumbar fusion; Low back pain
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-52885 (URN)10.1016/j.spinee.2009.08.454 (DOI)
    Available from: 2010-01-13 Created: 2010-01-12 Last updated: 2017-12-12
    3. Disc height and motion patterns in the lumbar spine in patients treated with total disc replacement or fusion for discogenic back pain: Results from a randomized controlled trial
    Open this publication in new window or tab >>Disc height and motion patterns in the lumbar spine in patients treated with total disc replacement or fusion for discogenic back pain: Results from a randomized controlled trial
    2011 (English)In: The spine journal, ISSN 1529-9430, E-ISSN 1878-1632, Vol. 11, no 11, 991-998 p.Article in journal (Refereed) Published
    Abstract [en]

    Study Design. Comparison of X-ray measurements in a randomized controlled trial between instrumented posterior fusion (N=72) and total disc replacement (TDR) (N=80) for chronic low back pain assumed to be discogenic. Results were compared to clinical outcome.

    Objective. To see if surgical goals for respective treatments had been reached, if clinical outcome was related to this, and if differences in disc height and adjacent segment motion patterns between groups occurred.

    Summary of Background Data. Fusion is considered the “gold standard” in surgical treatment of degenerated disc disease, though the resulting stiffness may induce degeneration in adjacent segments. TDR aims to restore and maintain mobility by replacing a painful disc. Little is known about the degree and quality of mobility in artificial discs in vivo, and whether maintained mobility reduces stress on adjacent segments.

    Methods. Flexion-extension X-rays were analyzed pre- and two years postoperatively using Distortion Compensated Roentgen Analysis (DCRA) at treated and adjacent levels, mobility following fusion and TDR was estimated. Changes in disc height and changes in mobility patterns in adjacent segments were compared. The results were compared with clinical outcome regarding back pain.

    Results. 78% of fused patients had no mobility whereas 89% of TDR-patients were mobile, but with less than normal mobility. The fulfilment of surgical goals was not correlated to clinical outcome. Fused segments were lower and TDR-segments were higher than normal. There were minor differences, there being more translation or flexion-extension at adjacent levels in the fusion group than in the TDR group.

    Conclusions. This very accurate X-ray method (DCRA) indicates that surgical goals were reached in most patients. This however, was not correlated to outcome. Differences between the groups in postoperative disc height and motion patterns at adjacent segments may lead to differences in outcome in the long-term perspective, but this was not detectable after two years.

    Place, publisher, year, edition, pages
    Elsevier, 2011
    Keyword
    RCT, Fusion, total disc replacement, mobility, disc height, clinical outcome, DCRA, adjacent segment
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-54288 (URN)10.1016/j.spinee.2011.08.434 (DOI)000297864300001 ()
    Available from: 2010-03-08 Created: 2010-03-08 Last updated: 2017-12-12
    4. Cost effectiveness of disc prosthesis versus lumbar fusion in patients with chronic low back pain: randomized controlled trial with 2-year follow-up:  
    Open this publication in new window or tab >>Cost effectiveness of disc prosthesis versus lumbar fusion in patients with chronic low back pain: randomized controlled trial with 2-year follow-up:  
    Show others...
    2011 (English)In: European spine journal, ISSN 0940-6719, E-ISSN 1432-0932, Vol. 20, no 7, 1001-1011 p.Article in journal (Refereed) Published
    Abstract [en]

    When low back pain becomes chronic, surgery is sometimes performed. The gold standard today is lumbar fusion (FUS), using a variety of procedures. Total disc replacement (TDR) aimed at motion preservation is increasing in popularity. This randomized controlled health economic study assesses the cost-effectiveness of TDR (Charité/Prodisc/Maverick) compared with instrumented FUS (posterior lumbar fusion (PLF)/posterior lumbar interbody fusion (PLIF). Social and healthcare perspectives after two years are reported. In all, 152 patients were randomized to either TDR (n=80) or FUS (n=72). Cost to society, (total mean cost/patient, Swedish kronor=SEK, standard deviation) for TDR was SEK 599,560 (400,272), and for FUS SEK 685,919 (422,903) (ns). TDR was significantly less costly from a healthcare perspective, SEK 22,996 (43,055- -1,202). Number of days on sick leave among those who returned to work was 185 (146) in the TDR group, and 252 (189) in the FUS group (ns). Using EQ-5D, the total gain in quality adjusted life years (QALYs) over two years was 0.41 units for TDR and 0.40 units for FUS (ns). Based on EQ-5D, the incremental cost effectiveness ratio (ICER) of using TDR instead of FUS was difficult to analyze due to the “non-difference” in treatment outcome, which is why cost/QALY could not be defined. Using cost-effectiveness probabilistic analysis, the net benefit with CI) was found to be SEK 91,359 (-73,643 – 249,114) (ns).

    Conclusion: It is not possible to state whether TDR or FUS is more cost-effective after two years. Since disc replacement and lumbar fusion are based on different conceptual approaches, it is important to follow these results over time.

    Place, publisher, year, edition, pages
    Springer, 2011
    Keyword
    Disc prosthesis; Lumbar fusion; Cost-effectiveness; Cost-utility; Health economic evaluation
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-54289 (URN)10.1007/s00586-010-1607-3 (DOI)000292746500002 ()
    Available from: 2010-03-08 Created: 2010-03-08 Last updated: 2017-12-12
  • 40.
    Berg, Svante
    et al.
    Lowenstromska Hosp, Stockholm Spine Ctr, SE-19489 Stockholm, Sweden.
    Fritzell, Peter
    Falun Cent Hosp, Dept Orthoped Surg, S-79182 Falun, Sweden.
    Tropp, Hans
    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.
    Sex life and sexual function in men and women before and after total disc replacement compared with posterior lumbar fusion2009In: The spine journal, ISSN 1529-9430, E-ISSN 1878-1632, Vol. 9, no 12, 987-994 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND CONTEXT: Sex life and sexual function maybe affected by low back pain (LBP). Sexual dysfunction after anterior lumbar fusion is reported in both men and women, but focus is mainly on impaired male biological function (retrograde ejaculation) as this may cause infertility. This has led to concern as to whether anterior surgery should be employed in men, at least in younger age groups. PURPOSE: To investigate how chronic low back pain (CLBP) of assumed discogenic origin affects sex life and sexual function in patients considered for surgical treatment, whether this is affected by surgical treatment (total disc replacement [TDR] or posterolateral fusion [PLF]/posterior lumbar interbody fusion [PLIF]), and if so, are there differences between the surgical procedures undertaken. STUDY DESIGN: A randomized controlled trial comparing TDR and instrumented lumbar spine fusion, performed either as a PLF or PLIF. PATIENT SAMPLE: One hundred fifty-two patients were included in this randomized controlled trial to compare the effect on CLBP of either TDR via an anterior retroperitoneal approach or instrumented posterior lumbar fusion, PLF or PLIF. OUTCOME MEASURES: Global assessment of back pain, back pain (visual analog scale [VAS] 0-100), function (Oswestry Disability Index [ODI] 0-100), quality of life (EQ5D [EuroQol] 0-1), and answers on specific sexual function. METHODS: Outcome was assessed using data from the Swedish Spine Register (SweSpine). In ODI, one question, ODI 8, reflects the impact of back pain on sex life. This question was analyzed separately. Patients also answered a gender-specific questionnaire preoperatively and at the 2-year follow-up to determine any sexual dysfunction regarding erection, orgasm, and ejaculation. Followup was at 1 and 2 years. RESULTS: Before surgery, 34% reported that their sex life caused some extra LBP, and an additional 30% that their sex life was severely restricted by LBP. After surgery, sex life improved in both groups, with a strong correlation to a reduction of LBP. The gender-specific questionnaire used to measure sexual function after 2 years revealed no negative effect of TDR or Fusion in men regarding erection or retrograde ejaculation. However, 26% of all men in the Fusion group, compared with 3% in the TDR group, reported postoperative deterioration in the ability to achieve orgasm, despite a reduction of LBP CONCLUSIONS: Impairment of sex life appears to be related to CLBP. An improvement in sex life after TDR or lumbar fusion was positively correlated to a reduction in LBP. Total disc replacement in this study, performed through an anterior retroperitoneal approach, was not associated with greater sexual dysfunction compared with instrumented lumbar fusion performed either as a PLF or as a PLIF. Sexual function, expressed as orgasm, deteriorated in men in the Fusion group postoperatively, in spite of this group reporting less LBP after 2 years.

  • 41.
    Berg, Svante
    et al.
    Lowenstromska Hospital.
    Tropp, Hans
    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.
    Leivseth, Gunnar
    Institute Of Clinical Neuroscience,Norwegian University of Science and Technology, Trondheim, Norway.
    Disc height and motion patterns in the lumbar spine in patients treated with total disc replacement or fusion for discogenic back pain: Results from a randomized controlled trial2011In: The spine journal, ISSN 1529-9430, E-ISSN 1878-1632, Vol. 11, no 11, 991-998 p.Article in journal (Refereed)
    Abstract [en]

    Study Design. Comparison of X-ray measurements in a randomized controlled trial between instrumented posterior fusion (N=72) and total disc replacement (TDR) (N=80) for chronic low back pain assumed to be discogenic. Results were compared to clinical outcome.

    Objective. To see if surgical goals for respective treatments had been reached, if clinical outcome was related to this, and if differences in disc height and adjacent segment motion patterns between groups occurred.

    Summary of Background Data. Fusion is considered the “gold standard” in surgical treatment of degenerated disc disease, though the resulting stiffness may induce degeneration in adjacent segments. TDR aims to restore and maintain mobility by replacing a painful disc. Little is known about the degree and quality of mobility in artificial discs in vivo, and whether maintained mobility reduces stress on adjacent segments.

    Methods. Flexion-extension X-rays were analyzed pre- and two years postoperatively using Distortion Compensated Roentgen Analysis (DCRA) at treated and adjacent levels, mobility following fusion and TDR was estimated. Changes in disc height and changes in mobility patterns in adjacent segments were compared. The results were compared with clinical outcome regarding back pain.

    Results. 78% of fused patients had no mobility whereas 89% of TDR-patients were mobile, but with less than normal mobility. The fulfilment of surgical goals was not correlated to clinical outcome. Fused segments were lower and TDR-segments were higher than normal. There were minor differences, there being more translation or flexion-extension at adjacent levels in the fusion group than in the TDR group.

    Conclusions. This very accurate X-ray method (DCRA) indicates that surgical goals were reached in most patients. This however, was not correlated to outcome. Differences between the groups in postoperative disc height and motion patterns at adjacent segments may lead to differences in outcome in the long-term perspective, but this was not detectable after two years.

  • 42.
    Berg, Svante
    et al.
    Lowenstromska Hospital.
    Tullberg, Tycho
    Lowenstromska Hospital.
    Branth, Bjoern
    Lowenstromska Hospital.
    Olerud, Claes
    Lowenstromska Hospital.
    Tropp, Hans
    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.
    Total disc replacement compared to lumbar fusion: a randomised controlled trial with 2-year follow-up2009In: EUROPEAN SPINE JOURNAL, ISSN 0940-6719, Vol. 18, no 10, 1512-1519 p.Article in journal (Refereed)
    Abstract [en]

    The study design includes a prospective, randomised controlled study comparing total disc replacement (TDR) with posterior fusion. The main objective of this study is to compare TDR with lumbar spinal fusion, in terms of clinical outcome, in patients referred to a spine clinic for surgical evaluation. Fusion is effective for treating chronic low back pain (LBP), but has drawbacks, such as stiffness and possibly adjacent level degradation. Motion-preserving options have emerged, of which TDR is frequently used because of these drawbacks. How the results of TDR compare to fusion, however, is uncertain. One hundred and fifty-two patients with a mean age of 40 years (21-55) were included: 90 were women, and 80 underwent TDR. The patients had not responded to a conservative treatment programme and suffered from predominantly LBP, with varying degrees of leg pain. Diagnosis was based on clinical examination, radiographs, MRI, and in unclear cases, diagnostic injections. Outcome measures were global assessment (GA), VAS for back and leg pain, Oswestry Disability Index, SF36 and EQ5D at 1 and 2 years. Follow-up rate was 100%, at both 1 and 2 years. All outcome variables improved in both groups between preoperative and follow-up assessment. The primary outcome measure, GA, revealed that 30% in the TDR group and 15% in the fusion group were totally pain-free at 2 years (P = 0.031). TDR patients had reached maximum recovery in virtually all variables at 1 year, with significant differences compared to the fusion group. The fusion patients continued to improve and at 2 years had results similar to TDR patients apart from numbers of pain-free. Complications and reoperations were similar in both groups, but pedicle screw removal as additive surgery, was frequent in the fusion group. One year after surgery, TDR was superior to spinal fusion in clinical outcome, but this difference had diminished by 2 years, apart from (VAS for back pain and) numbers of pain-free. The long-term benefits have yet to be examined.

  • 43.
    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, 187-192 p.Article 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.

  • 44.
    Björnsson, Hanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Norlin, Rolf
    Örebro University Hospital.
    Knutsson, Anders
    Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping.
    Adolfsson, Lars
    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.
    Fewer rotator cuff tears fifteen years after arthroscopic subacromial decompression2010In: Journal of shoulder and elbow surgery, ISSN 1058-2746, E-ISSN 1532-6500, Vol. 19, no 1, 111-115 p.Article in journal (Refereed)
    Abstract [en]

    Background: A successful clinical result is reported in 75% to 85% of impingement patients after arthroscopic subacromial decompression. The result is maintained over time, but few studies have investigated the integrity of the rotator cuff in these patients. Materials and methods: Using ultrasonography, we examined the integrity of the rotator cuff in 70 patients 15 years after arthroscopic subacromial decompression. All patients had an intact rotator cuff at the index procedure. Results: Tendons were still intact in 57 patients (82%), 10 (14%) had partial-thickness tears, and 3 (4%) had full-thickness tears. Discussion: The total number of 18% tears (partial and full thickness) in this study, including patients clinically diagnosed with subacromial impingement at a mean age of 60 years, is unexpectedly low compared with 40% degenerative tears reported in asymptomatic adults of the same age. Conclusion: Arthroscopic subacromial decompression seems to reduce the prevalence of rotator cuff tears in impingement patients. This appears attributable to elimination of extrinsic factors such as mechanical wear and bursitis. The potential effect of surgery on intrinsic cuff degeneration is unknown, but intrinsic factors may explain tears still developing despite decompression.

  • 45. Bottner, F
    et al.
    Zawadsky, M
    Su, EP
    Bostrom, M
    Palm, Lars
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Ryd, Leif
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine .
    Sculco, TP
    Implant migration after early weightbearing in cementless hip replacement2005In: Clinical Orthopaedics and Related Research, ISSN 0009-921X, E-ISSN 1528-1132, no 436, 132-137 p.Article in journal (Refereed)
    Abstract [en]

    Twenty-nine patients (five women and 24 men) with an average age of 47 years (range, 24-59 years) had 37 total hip arthroplasties using a hydroxyapatite-coated double-wedge press-fit femoral component. All patients had a Type A bone quality. Patients were either mobilized with weightbearing as tolerated or toe-touch weightbearing for 6 weeks postoperatively. After 6 weeks all patients were advanced to weightbearing as tolerated. Radiostereometric analysis radiographs were taken at 3 days, 6 weeks, and 6 months postoperatively to measure migration of the femoral component. Radiostereometric analysis revealed no difference in stem migration between the two groups as defined by maximal total point migration. There was a difference in the vertical (proximal-distal) migration within the first 6 weeks between groups (0.81 mm versus 0.13 mm), but not afterwards (0.17 mm versus 0.18 mm). Continuous migration after 6 weeks was observed in three patients from each group. There was no loosening in either group within a 2-year followup. Weightbearing as tolerated is recommended for young patients with excellent bone quality after cementless total hip arthroplasty with a double-wedge press-fit femoral component. Level of Evidence: Diagnostic study, Level I (testing of previously developed diagnostic criteria in series of consecutive patients-with previously applied reference gold standard). See the Guidelines for Authors for a complete description of levels of evidence.

  • 46.
    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.

  • 47.
    Eliasson, Pernilla
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Response to mechanical loading in healing tendons2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Ruptured tendons heal faster if they are exposed to mechanical loading. Loading creates deformation of the extracellular matrix and cells, which give rise to intracellular signalling, increased gene expression and protein synthesis. The effects of loading have been extensively studied in vitro, and in intact tendons in vivo. However, the response to loading in healing tendons is less known.

    The general aim of this thesis was to understand more about the response to mechanical loading during tendon healing. The specific aims were to find out how short daily loading episodes could influence tendon healing, and to understand more about genes involved in tendon healing.

    The studies were performed using rat models. Unloading of healing tendons resulted in a weaker callus tissue. This could be reversed to some extent by short daily loading episodes. Loading induced more matrix production, making the tendons thicker and stronger, but there was no improvement in the material properties of the matrix. Lengthening is one potential adversity with early loading, during tendon healing in patients. This was also seen with continuous loading in the rat models. However, short loading episodes did not result in any lengthening, not even when loading was applied during the inflammatory phase of healing. It also appeared as loading once daily was enough to make healing tendons stronger, while loading twice daily with 8 hours interval did not give any additional effect. The strongest gene expression response to one loading episode was seen after 3 hours. The gene expression changes persisted 12 hours after the loading episode but had disappeared by 24 hours. Loading appeared to regulate genes involved in inflammation, wound healing and coagulation, angiogenesis, and production of reactive oxygen species. Inflammation-associated genes were regulated both by continuous loading and by one short loading episode. Inflammation is an important part of the healing response, but too much can be harmful. Loading might therefore have a role in fine-tuning the inflammatory response during healing.

    In conclusion, these studies show that short daily loading episodes during early tendon healing could potentially be beneficial for rehabilitation. Loading might have a role in regulating the inflammatory response during healing.

    List of papers
    1. Tissue memory in healing tendons: short loading episodes stimulate healing
    Open this publication in new window or tab >>Tissue memory in healing tendons: short loading episodes stimulate healing
    2009 (English)In: JOURNAL OF APPLIED PHYSIOLOGY, ISSN 8750-7587, Vol. 107, no 2, 417-421 p.Article in journal (Refereed) Published
    Abstract [en]

    Intact tendons adapt slowly to changes in mechanical loading, whereas in healing tendons the effect of mechanical loading or its absence is dramatic. The longevity of the response to a single loading episode is, however, unknown. We hypothesized that the tissue has a "memory" of loading episodes and that therefore short loadings are sufficient to elicit improved healing. The Achilles tendon of 70 female rats was transected and unloaded by tail suspension for 12 days (suspension started on day 2 after surgery). Each day, the rats were let down from suspension for short daily training episodes according to different regimes: 15 min of cage activity or treadmill running for 15, 30, 60, or 2 x 15 min. Rats with transected Achilles tendons and full-time cage activity served as controls. The results demonstrated that full-time cage activity increased the peak force over three times compared with unloading. Short daily loading episodes (treadmill running) increased the peak force about half as much as full-time activity. Prolongation of treadmill running above 15 min or dividing the daily training in two separate episodes had minimal further effect. This mechanical stimulation increased the cross-sectional area but had no effect on the mechanical properties of the repair tissue. The findings indicate that once the tissue had received information from a certain loading type and level, this is "memorized" and leads to a response lasting many hours. This suggests that patients might be allowed early short loading episodes following, e. g., an Achilles tendon rupture for a better outcome.

    Keyword
    hindlimb suspension, immobilization, Achilles tendon, tendon healing, mechanical stimulation
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-19914 (URN)10.1152/japplphysiol.00414.2009 (DOI)
    Available from: 2009-08-14 Created: 2009-08-14 Last updated: 2012-03-27
    2. Achilles tendon healing in rats is improved by intermittent mechanical loading during the inflammatory phase
    Open this publication in new window or tab >>Achilles tendon healing in rats is improved by intermittent mechanical loading during the inflammatory phase
    2012 (English)In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 30, no 2, 274-279 p.Article in journal (Refereed) Published
    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.

    Place, publisher, year, edition, pages
    Wiley Online Library, 2012
    Keyword
    Early loading, tail-suspension, unloading, mechanical testing, cell differentiation
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-70772 (URN)10.1002/jor.21511 (DOI)000298581200016 ()
    Note

    funding agencies|Swedish National Centre for Research in Sports||Swedish Research Council| VR 2009-6725 |Ostergotland County Council||

    Available from: 2011-09-16 Created: 2011-09-16 Last updated: 2017-12-08Bibliographically approved
    3. Rat Achilles tendon healing: mechanical loading and gene expression
    Open this publication in new window or tab >>Rat Achilles tendon healing: mechanical loading and gene expression
    2009 (English)In: JOURNAL OF APPLIED PHYSIOLOGY, ISSN 8750-7587, Vol. 107, no 2, 399-407 p.Article in journal (Refereed) Published
    Abstract [en]

    Injured tendons require mechanical tension for optimal healing, but it is unclear which genes are upregulated and responsible for this effect. We unloaded one Achilles tendon in rats by Botox injections in the calf muscles. The tendon was then transected and left to heal. We studied mechanical properties of the tendon calluses, as well as mRNA expression, and compared them with loaded controls. Tendon calluses were studied 3, 8, 14, and 21 days after transection. Intact tendons were studied similarly for comparison. Altogether 110 rats were used. The genes were chosen for proteins marking inflammation, growth, extracellular matrix, and tendon specificity. In intact tendons, procollagen III and tenascin-C were more expressed in loaded than unloaded tendons, but none of the other genes was affected. In healing tendons, loading status had small effects on the selected genes. However, TNF-alpha transforming growth factor-beta 1, and procollagens I and III were less expressed in loaded callus tissue at day 3. At day 8 procollagens I and III, lysyl oxidase, and scleraxis had a lower expression in loaded calluses. However, by days 14 and 21, procollagen I, cartilage oligomeric matrix protein, tenascin-C, tenomodulin, and scleraxis were all more expressed in loaded calluses. In healing tendons, the transverse area was larger in loaded samples, but material properties were unaffected, or even impaired. Thus mechanical loading is important for growth of the callus but not its mechanical quality. The main effect of loading during healing might thereby be sought among growth stimulators. In the late phase of healing, tendon-specific genes (scleraxis and tenomodulin) were upregulated with loading, and the healing tissue might to some extent represent a regenerate rather than a scar.

    Keyword
    unloading, tendon healing, inflammation, extracellular matrix, mechanobiology
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-19899 (URN)10.1152/japplphysiol.91563.2008 (DOI)
    Available from: 2009-08-14 Created: 2009-08-14 Last updated: 2012-03-27
    4. Mechanical load and BMP signaling during tendon repair: A role for follistatin?
    Open this publication in new window or tab >>Mechanical load and BMP signaling during tendon repair: A role for follistatin?
    2008 (English)In: Clinical Orthopaedics and Related Research, ISSN 0009-921X, E-ISSN 1528-1132, Vol. 466, no 7, 1592-1597 p.Article in journal (Refereed) Published
    Abstract [en]

    Healing of the rat Achilles tendon is sensitive to mechanical loading, and the callus strength is reduced by 3/4 after 14 days, if loading is prevented. Exogenous GDFs stimulate tendon healing. This response is influenced by loading: without loading, cartilage and bone formation is initiated. This implies BMP signaling is crucial during tendon healing and influenced by mechanical loading. We therefore asked if mechanical loading influences the gene expression of the BMP signaling system in intact and healing tendons, and how the BMP signaling system changes during healing. The genes were four BMPs (OP-1/BMP-7, GDF-5/CDMP-1/BMP-14, GDF-6/CDMP2/BMP-13, and GDF-7/CDMP-3/BMP-12), two receptors (BMPR1b and BMPR2), and the antagonists follistatin and noggin. The Achilles tendon was transected in rats and left to heal. Half of the rats had one Achilles tendon unloaded by injection of Botox in the calf muscles. Ten tendons were analyzed before transection and for each of four time points. All genes except noggin were expressed at all points, but followed different patterns during healing. Loading strongly decreased the expression of follistatin, which could lead to increased signaling. The BMP system appears involved in tendon maintenance and healing, and may respond to mechanical loading.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-45883 (URN)10.1007/s11999-008-0253-0 (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13
    5. Myostatin in tendon maintenance and repair
    Open this publication in new window or tab >>Myostatin in tendon maintenance and repair
    Show others...
    2009 (English)In: Growth Factors, ISSN 0897-7194, E-ISSN 1029-2292, Vol. 27, no 4, 247-254 p.Article in journal (Refereed) Published
    Abstract [en]

    Myostatin, a negative regulator of muscle growth, has recently been found to be expressed in tendons. Myostatin-deficient mice have weak and brittle tendons, which suggest that myostatin could be important for tendon maintenance. Follistatin expression in the callus tissue after tendon transection is influenced by loading. We found that follistatin antagonises myostatin, but not GDF-5 or OP-1 in vitro. To study if myostatin might play a physiological role in soft tissue, we transected 64 rat Achilles tendons and studied the gene expression for myostatin and its receptors at four different time-points during healing. Intact tendons were also studied. All samples were studied with or without mechanical loading. Unloading was achieved with botulinum toxin injections in the calf muscles. The expression of the myostatin gene was more than 40 times higher in intact tendons than in the callus tissue during tendon healing. The expression of myostatin was also influenced by loading status in both intact and healing tendons. Thereafter, we measured the mechanical properties of healing tendons after local myostatin administration. This treatment increased the volume and the contraction of the callus after 8 days, but did not improve its strength. Our results indicate that myostatin plays a positive role in tendon maintenance and that exogenous protein administration stimulates proliferation and growth of early repair tissue. However, no effect on further development towards connective tissue formation was found.

    Keyword
    GDF-8; myostatin; follistatin; gene expression; mechanical loading; Achilles tendon
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-20180 (URN)10.1080/08977190903052539 (DOI)
    Available from: 2009-09-02 Created: 2009-08-31 Last updated: 2017-12-13Bibliographically approved
    6. Influence of a single loading episode on gene expression in healing rat Achilles tendons
    Open this publication in new window or tab >>Influence of a single loading episode on gene expression in healing rat Achilles tendons
    2012 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 112, no 2, 279-288 p.Article in journal (Refereed) Published
    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.

    Place, publisher, year, edition, pages
    AMER PHYSIOLOGICAL SOC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA, 2012
    Keyword
    Gene expression, tendons, healing
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-70773 (URN)10.1152/japplphysiol.00858.2011 (DOI)000299318400006 ()
    Note
    funding agencies|Board of Research at the Karolinska Institute||Research Committee at the Karolinska Hospital||Swedish Research Council| 2009-6725 |Swedish National Centre for Research in Sports||King Gustaf V and Queen Victoria Free Mason Foundation||Available from: 2011-09-16 Created: 2011-09-16 Last updated: 2017-12-08Bibliographically approved
  • 48.
    Eliasson, Pernilla
    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, 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, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Rat Achilles tendon healing: mechanical loading and gene expression2009In: JOURNAL OF APPLIED PHYSIOLOGY, ISSN 8750-7587, Vol. 107, no 2, 399-407 p.Article in journal (Refereed)
    Abstract [en]

    Injured tendons require mechanical tension for optimal healing, but it is unclear which genes are upregulated and responsible for this effect. We unloaded one Achilles tendon in rats by Botox injections in the calf muscles. The tendon was then transected and left to heal. We studied mechanical properties of the tendon calluses, as well as mRNA expression, and compared them with loaded controls. Tendon calluses were studied 3, 8, 14, and 21 days after transection. Intact tendons were studied similarly for comparison. Altogether 110 rats were used. The genes were chosen for proteins marking inflammation, growth, extracellular matrix, and tendon specificity. In intact tendons, procollagen III and tenascin-C were more expressed in loaded than unloaded tendons, but none of the other genes was affected. In healing tendons, loading status had small effects on the selected genes. However, TNF-alpha transforming growth factor-beta 1, and procollagens I and III were less expressed in loaded callus tissue at day 3. At day 8 procollagens I and III, lysyl oxidase, and scleraxis had a lower expression in loaded calluses. However, by days 14 and 21, procollagen I, cartilage oligomeric matrix protein, tenascin-C, tenomodulin, and scleraxis were all more expressed in loaded calluses. In healing tendons, the transverse area was larger in loaded samples, but material properties were unaffected, or even impaired. Thus mechanical loading is important for growth of the callus but not its mechanical quality. The main effect of loading during healing might thereby be sought among growth stimulators. In the late phase of healing, tendon-specific genes (scleraxis and tenomodulin) were upregulated with loading, and the healing tissue might to some extent represent a regenerate rather than a scar.

  • 49.
    Eliasson, Pernilla
    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, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Kulas, Jana
    Max Planck Institute.
    Seemann, Petra
    Max Planck Institute.
    Aspenberg, Per
    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.
    Myostatin in tendon maintenance and repair2009In: Growth Factors, ISSN 0897-7194, E-ISSN 1029-2292, Vol. 27, no 4, 247-254 p.Article in journal (Refereed)
    Abstract [en]

    Myostatin, a negative regulator of muscle growth, has recently been found to be expressed in tendons. Myostatin-deficient mice have weak and brittle tendons, which suggest that myostatin could be important for tendon maintenance. Follistatin expression in the callus tissue after tendon transection is influenced by loading. We found that follistatin antagonises myostatin, but not GDF-5 or OP-1 in vitro. To study if myostatin might play a physiological role in soft tissue, we transected 64 rat Achilles tendons and studied the gene expression for myostatin and its receptors at four different time-points during healing. Intact tendons were also studied. All samples were studied with or without mechanical loading. Unloading was achieved with botulinum toxin injections in the calf muscles. The expression of the myostatin gene was more than 40 times higher in intact tendons than in the callus tissue during tendon healing. The expression of myostatin was also influenced by loading status in both intact and healing tendons. Thereafter, we measured the mechanical properties of healing tendons after local myostatin administration. This treatment increased the volume and the contraction of the callus after 8 days, but did not improve its strength. Our results indicate that myostatin plays a positive role in tendon maintenance and that exogenous protein administration stimulates proliferation and growth of early repair tissue. However, no effect on further development towards connective tissue formation was found.

  • 50.
    Eliasson, Pernilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Fahlgren, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Mechanical load and BMP signaling during tendon repair: A role for follistatin?2008In: Clinical Orthopaedics and Related Research, ISSN 0009-921X, E-ISSN 1528-1132, Vol. 466, no 7, 1592-1597 p.Article in journal (Refereed)
    Abstract [en]

    Healing of the rat Achilles tendon is sensitive to mechanical loading, and the callus strength is reduced by 3/4 after 14 days, if loading is prevented. Exogenous GDFs stimulate tendon healing. This response is influenced by loading: without loading, cartilage and bone formation is initiated. This implies BMP signaling is crucial during tendon healing and influenced by mechanical loading. We therefore asked if mechanical loading influences the gene expression of the BMP signaling system in intact and healing tendons, and how the BMP signaling system changes during healing. The genes were four BMPs (OP-1/BMP-7, GDF-5/CDMP-1/BMP-14, GDF-6/CDMP2/BMP-13, and GDF-7/CDMP-3/BMP-12), two receptors (BMPR1b and BMPR2), and the antagonists follistatin and noggin. The Achilles tendon was transected in rats and left to heal. Half of the rats had one Achilles tendon unloaded by injection of Botox in the calf muscles. Ten tendons were analyzed before transection and for each of four time points. All genes except noggin were expressed at all points, but followed different patterns during healing. Loading strongly decreased the expression of follistatin, which could lead to increased signaling. The BMP system appears involved in tendon maintenance and healing, and may respond to mechanical loading.

1234 1 - 50 of 196
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf