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

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

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

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

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

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

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

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

  • 5.
    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, p. 673-677Article 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.

  • 6.
    Agholme, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Andersson, Therese
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Tengvall, P
    University of Gothenburg.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Local bisphosphonate release versus hydroxyapatite coating for stainless steel screw fixation in rat tibiae2012In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 23, no 3, p. 743-752Article in journal (Refereed)
    Abstract [en]

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

  • 7.
    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, p. S67-S67Conference paper (Refereed)
    Abstract [en]

    n/a

  • 8.
    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, p. 670-675Article 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.

  • 9.
    Agholme, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, 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, p. S67-S67Conference 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, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Wnt signaling and orthopedics, an overview2011In: ACTA ORTHOPAEDICA, ISSN 1745-3674, Vol. 82, no 2, p. 125-130Article in journal (Refereed)
    Abstract [en]

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

  • 11.
    Agholme, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Isaksson, Hanna
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Kuhstoss, Stuart
    Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, USA.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    The effects of Dickkopf-1 antibody on metaphyseal bone and implant fixation under different loading conditions2011In: BONE, ISSN 8756-3282, Vol. 48, no 5, p. 988-996Article in journal (Refereed)
    Abstract [en]

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

  • 12.
    Agholme, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Isaksson, Hanna
    Department of Applied physics, University of Eastern Finland, Kuopio, Finland.
    Li, Xiaodong
    Metabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.
    Ke, Hua Zhu
    Metabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Anti-sclerostin antibody and mechanical loading appear to influence metaphyseal bone independently in rats2011In: Acta Orthopaedica, ISSN 1745-3674, Vol. 82, no 5, p. 628-632Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 13.
    Agholme, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Li, Xiaodong
    Amgen Inc.
    Isaksson, Hanna
    University of Eastern Finland.
    Zhu Ke, Hua
    Amgen Inc.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Sclerostin Antibody Treatment Enhances Metaphyseal Bone Healing in Rats2010In: JOURNAL OF BONE AND MINERAL RESEARCH, ISSN 0884-0431, Vol. 25, no 11, p. 2412-2418Article in journal (Refereed)
    Abstract [en]

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

  • 14.
    Agholme, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Macias, Brandon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Hamang, Matt
    Lilly Research Labs, IN USA .
    Lucchesi, Jonathan
    Lilly Research Labs, IN USA .
    Adrian, Mary D.
    Lilly Research Labs, IN USA .
    Kuhstoss, Stuart
    Lilly Research Labs, IN USA .
    Harvey, Anita
    Lilly Research Labs, IN USA .
    Sato, Masahiko
    Lilly Research Labs, IN USA .
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Efficacy of a Sclerostin Antibody Compared to a Low Dose of PTH on Metaphyseal Bone Healing2014In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 32, no 3, p. 471-476Article in journal (Refereed)
    Abstract [en]

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

  • 15.
    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.

  • 16.
    Amirhosseini, Mehdi
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Andersson, Göran
    Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Fahlgren, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Mechanical instability and titanium particles induce similar transcriptomic changes in a rat model for periprosthetic osteolysis and aseptic loosening2017In: Bone Reports, ISSN 2352-1872, Vol. 7, p. 17-25Article in journal (Refereed)
    Abstract [en]

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

  • 17.
    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, p. 3029-3037Article 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.

  • 18.
    Andersson, Therese
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Eliasson, Pernilla
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Achilles tendon healing in rats is improved by intermittent mechanical loading during the inflammatory phase2012In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 30, no 2, p. 274-279Article in journal (Refereed)
    Abstract [en]

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

  • 19.
    Andersson, Therese
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Eliasson, Pernilla
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Growth hormone does not stimulate early healing in rat tendons2012In: International Journal of Sports Medicine, ISSN 0172-4622, E-ISSN 1439-3964, Vol. 33, no 3, p. 240-243Article in journal (Refereed)
    Abstract [en]

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

  • 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, p. 417-421Article 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.
    Andersson, Therese
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Eliasson, Pernilla
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Hammerman, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Low-level mechanical stimulation is sufficient to improve tendon healing in rats2012In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 113, no 9, p. 1398-1402Article in journal (Refereed)
    Abstract [en]

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

  • 22.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Alendronate-eluting polyglucose-lignol composite (POGLICO): A new biomaterial for fracture fixating implants2014In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 85, no 6, p. 687-690Article in journal (Refereed)
    Abstract [en]

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

  • 23.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Apropå! En arrogant organisation2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114Article in journal (Other academic)
    Abstract [en]

    n/a

  • 24.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Atypical fractures, a biased perspective2016In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 47, no 1, p. S28-S30Article in journal (Refereed)
    Abstract [en]

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

  • 25.
    Aspenberg, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Avoid cox inhibitors after skeletal surgery!2002In: Acta Orthopaedica Scandinavica, ISSN 0001-6470, Vol. 73, no 5, p. 489-490Article in journal (Refereed)
  • 26.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Benvävnad och frakturläkning2014Report (Other academic)
    Abstract [sv]

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

  • 27.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Beslut att operera kopplat till ortopeders attityder till kirurgi2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, no 41Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 28.
    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, p. 119-123Article in journal (Refereed)
  • 29.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Black holes in bone - irresistible attractors of foreign materials?2009In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 80, no 1, p. 2-3Article in journal (Other academic)
  • 30.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Bone: Silk, metal and bone: why take implants out?2014In: Nature Reviews Rheumatology, ISSN 1759-4790, E-ISSN 1759-4804, Vol. 10, no 7, p. 386-387Article in journal (Other academic)
    Abstract [en]

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

  • 31.
    Aspenberg, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Don´t administer NSAID after bone surgery2002In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 99, no 22, p. 2554-2554Article in journal (Other (popular science, discussion, etc.))
  • 32.
    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, p. 741-748Article, review/survey (Refereed)
    Abstract [en]

    [No abstract available]

  • 33.
    Aspenberg, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Editorial: Bisphosphonate-induced fractures: Nature strikes back?2008In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 79, no 4, p. 459-460Article in journal (Other academic)
  • 34.
    Aspenberg, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Editorial: Is inflammation harmless to loaded tendons?2007In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 102, no 1, p. 3-4Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 35.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Editorial Material: ACADEMIC AUTHORSHIP How I was nearly duped into "authoring" a fake paper in BMJ-BRITISH MEDICAL JOURNAL, vol 351, issue h6605, pp2015In: BMJ-BRITISH MEDICAL JOURNAL, ISSN 1756-1833, Vol. 351, no h6605Article in journal (Other academic)
    Abstract [en]

    n/a

  • 36.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Editorial Material: Why do we operate proximal humeral fractures?2015In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 86, no 3, p. 279-279Article in journal (Other academic)
  • 37.
    Aspenberg, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Editorial: Osteonecrosis of the jaw: What do bisphosphonates do?2006In: Expert Opinion on Drug Safety, ISSN 1474-0338, E-ISSN 1744-764X, Vol. 5, no 6, p. 743-745Article in journal (Other academic)
    Abstract [en]

    Osteonecrosis of the jaw is a new disease, partly caused by bisphosphonates. It is commonly assumed that the bisphosphonates somehow cause cell death (osteocyte necrosis) within the jawbone, which makes it prone to chronic infection. In this article, an alternative pathogenetic theory is suggested, based on the normal effect of bisphosphonates. According to the new theory, the bone is alive until it is injured and infected, and the reduced resorptive ability due to bisphosphonates hinders the formation of a fresh bone surface for re-establishment of bone cell coverage. The theories are compared, based on the recent, very scarce literature. None of them can be completely refuted, but the demonstration of living osteocytes within the lesion and the number of necessary assumptions speak against the theory of a primary, bisphosphonate-induced necrosis.

  • 38.
    Aspenberg, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Editorial: Osteonecrosis: what does it mean? One condition partly caused by bisphosphonates - or another one, preferably treated with them?2006In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 77, no 5, p. 693-694Article in journal (Other academic)
  • 39.
    Aspenberg, Per
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Hur läker senor och ledband?2013Report (Other academic)
    Abstract [sv]

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

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

  • 40.
    Aspenberg, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Impact bone grafting2001In: Acta Orthopaedica Scandinavica, ISSN 0001-6470, Vol. 72, p. 661-663Article in journal (Refereed)
  • 41.
    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, p. 662-663Other (Other academic)
  • 42.
    Aspenberg, Per
    Linköping University, Department of Neuroscience and Locomotion. Linköping University, Faculty of Health Sciences.
    Letter: "Differential inhibition of fracture healing by non-selective and cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs" (multiple letters)2004In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 22, no 3, p. 684-685Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 43.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Letter: Overtreatment of cruciate ligament injuries2011In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 82, no 1, p. 122-122Article in journal (Other academic)
    Abstract [en]

    n/a

  • 44.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Letter: Platelet concentrates and achilles tendon healing2013In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 31, no 9, p. 1500-1500Article in journal (Other academic)
    Abstract [en]

    n/a

  • 45.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Mythbusting in Orthopedics challenges our desire for meaning2014In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 85, no 6, p. 547-547Article in journal (Other academic)
  • 46.
    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, p. 524-525Article in journal (Other academic)
    Abstract [en]

    n/a

  • 47.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Parathyroid hormone and fracture healing2013In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 84, no 1, p. 4-6Article in journal (Refereed)
    Abstract [en]

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

  • 48.
    Aspenberg, Per
    Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Pharmacological treatment of osteonecrosis2006In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 77, no 2, p. 175-176Article in journal (Other academic)
    Abstract [en]

      

  • 49.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Placeboeffekten är övervärderad: »Återgång till medelvärdet« kan förklara förbättring efter skenbehandling – men misstolkas ofta2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114Article in journal (Refereed)
  • 50.
    Aspenberg, Per
    Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Postoperative Cox inhibitors and late prosthetic loosening--suspicion increases!2005In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 76, no 6, p. 733-734Article in journal (Other academic)
12345 1 - 50 of 203
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