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  • 1.
    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.

  • 2.
    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.

  • 3.
    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]

  • 4.
    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

  • 5.
    Bernhardsson, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Dietrich, Franciele
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Tätting, Love
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Eliasson, Pernilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Depletion of cytotoxic (CD8+) T cells impairs implant fixation in rat cancellous bone2019In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 37, no 4, p. 805-811Article in journal (Refereed)
    Abstract [en]

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

  • 6.
    Fahlgren, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Bratengeier, Cornelia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Semeins, Cornelis M.
    Univ Amsterdam, Netherlands; Vrije Univ Amsterdam, Netherlands.
    Klein-Nulend, Jenneke
    Univ Amsterdam, Netherlands; Vrije Univ Amsterdam, Netherlands.
    Bakker, Astrid D.
    Univ Amsterdam, Netherlands; Vrije Univ Amsterdam, Netherlands.
    Supraphysiological loading induces osteocyte-mediated osteoclastogenesis in a novel in vitro model for bone implant loosening2018In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 36, no 5, p. 1425-1434Article in journal (Refereed)
    Abstract [en]

    We aimed to develop an in vitro model for bone implant loosening, allowing analysis of biophysical and biological parameters contributing to mechanical instability-induced osteoclast differentiation and peri-implant bone loss. MLO-Y4-osteocytes were mechanically stimulated for 1h by fluid shear stress using regimes simulating: (i) supraphysiological loading in the peri-prosthetic interface (2.9 +/- 2.9Pa, 1Hz, square wave); (ii) physiologic loading in the cortical bone (0.7 +/- 0.7Pa, 5Hz, sinusoidal wave); and (iii) stress shielding. Cellular morphological parameters, membrane-bound RANKL expression, gene expression influencing osteoclast differentiation, nitric oxide release and caspase 3/7-activity were determined. Either Mouse bone marrow cells were cultured on top of loaded osteocytes or osteocyte-conditioned medium was added to bone marrow cells. Osteoclast differentiation was assessed after 6 days. We found that osteocytes subjected to supraphysiological loading showed similar morphology and caspase 3/7-activity compared to simulated physiological loading or stress shielding. Supraphysiological stimulation of osteocytes enhanced osteoclast differentiation by 1.9-fold compared to physiological loading when cell-to-cell contact was permitted. In addition, it enhanced the number of osteoclasts using conditioned medium by 1.7-fold, membrane-bound RANKL by 3.3-fold, and nitric oxide production by 3.2-fold. The stimulatory effect of supraphysiological loading on membrane-bound RANKL and nitric oxide production was higher than that achieved by stress shielding. In conclusion, the in vitro model developed recapitulated the catabolic biological situation in the peri-prosthetic interface during instability that is associated with osteoclast differentiation and enhanced RANKL expression. The model thus provides a platform for pre-clinical testing of pharmacological interventions with potential to stop instability-induced bone implant loosening. (c) 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1425-1434, 2018.

  • 7. Forslund, C
    et al.
    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.
    CDMP-2 induces bone or tendon-like tissue depending on mechanical stimulation2002In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 20, no 6, p. 1170-1174Article in journal (Refereed)
    Abstract [en]

    Cartilage derived morphogenetic proteins (CDMPs, also known as growth and differentiation factors, GDFs) are a subgroup of the bone morphogenetic protein (BMP) gene family. As most BMPs, they are known to induce cartilage or bone formation when implanted subcutaneously or intramuscularly on an appropriate carrier. However, similar implantation experiments with CDMPs have also reported the formation of a tendon-like tissue, without any cartilage or bone. A solution to this apparent contradiction might be offered by the mechanical tissue differentiation theory, suggesting that tissue differentiation depends on the mechanical environment. This study analyzes the response to CDMP-2 implants at different sites and under different loading conditions in the rat. Collagen sponges carrying CDMP-2 were implanted subcutaneously, intramuscularly or inside a freshly created defect in the achilles tendon. Large amounts of bone were induced subcutaneously, smaller amounts intramuscularly, and in the tendons, only small amounts of bone or cartilage were seen in few animals. Thus, the amount of bone appeared inversely related to the degree of mechanical stimulus. To confirm this, CDMP was also injected into tendon defects that were either loaded or partially unloaded. All the unloaded tendons showed bone induction after one CDMP-2 injection, whereas only 4 of 10 loaded ones showed any cartilage or bone (p = 0.0005). Single injections of a similar dose of CDMP-2 have previously been shown to augment tendon repair by increasing the size of the tendon callus. This study suggests that the response to CDMP-2 is dependent on the mechanical situation at the site where it is applied. ⌐ 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.

  • 8. Forslund, Carina
    et al.
    Rueger, David
    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.
    A comparative dose-response study of cartilage-derived morphogenetic protein (CDMP)-1, -2 and -3 for tendon healing in rats2003In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 21, no 4, p. 617-621Article in journal (Refereed)
    Abstract [en]

    Cartilage-derived morphogenetic proteins (CDMPs), belonging to the bone morphogenetic protein (BMP) family, are known to b cartilage and bone inducers as well as to induce tendon and ligament-like tissue. In this study we investigated the influence of CDMP-1, -2 or -3 at four different doses (0, 0.4, 2 and 10 ?g) on tendon healing in a rat model, as well as differences in osteogenesis between the different CDMPs and doses. In 110 rats, a 3 mm segment of the Achilles tendon was removed via a 2 mm skin incision. CDMP-1, -2 or -3 was injected into the defect 6 h postoperative. The rats were killed 8 days after operation. The tendon regenerates were tested biomechanically. There was a significant dose-related increase in strength and stiffness with all three CDMPs, but no difference between the CDMPs was found. Another 50 rats were used to compare the highest dose of the CDMPs with controls and osteogenic protein 1 (OP-1), as regards cartilage or bone formation after 4 weeks. Cartilage occurred in all groups, including the controls. Some specimens in all groups contained bone, except the controls. No difference between the CDMPs could be demonstrated. The CDMP-1, CDMP-3 and OP-1 groups contained significantly more calcium than controls. Only the CDMP-2 group and the controls contained significantly less calcium than the OP-1 group. In conclusion, the three CDMPs appeared similar as regards improvement of tendon repair and osteogenicity in this setting. ⌐ 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.

  • 9.
    Grosso, Matthew J.
    et al.
    Hospital Special Surg, NY 10021 USA; Cleveland Clin, OH 44195 USA.
    Courtland, Hayden-William
    Hospital Special Surg, NY 10021 USA.
    Yang, Xu
    Hospital Special Surg, NY 10021 USA.
    Sutherland, James P.
    Hospital Special Surg, NY 10021 USA.
    Stoner, Kirsten
    Hospital Special Surg, NY 10021 USA.
    Nguyen, Joseph
    Hospital Special Surg, NY 10021 USA.
    Fahlgren, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Hospital Special Surg, NY 10021 USA.
    Ross, F. Patrick
    Hospital Special Surg, NY 10021 USA.
    van der Meulen, Marjolein C. H.
    Hospital Special Surg, NY 10021 USA; Cornell University, NY 14853 USA.
    Bostrom, Mathias P.
    Hospital Special Surg, NY 10021 USA.
    Intermittent PTH Administration and Mechanical Loading Are Anabolic for Periprosthetic Cancellous Bone2015In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 33, no 2, p. 163-173Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to determine the individual and combined effects on periprosthetic cancellous bone of intermittent parathyroid hormone administration (iPTH) and mechanical loading at the cellular, molecular, and tissue levels. Porous titanium implants were inserted bilaterally on the cancellous bone of adult rabbits beneath a loading device attached to the distal lateral femur. The left femur received a sham loading device. The right femur was loaded daily, and half of the rabbits received daily PTH. Periprosthetic bone was evaluated up to 28 days for gene expression, histology, and mu CT analysis. Loading and iPTH increased bone mass by a combination of two mechanisms: (1) Altering cell populations in a pro-osteoblastic/anti-adipocytic direction, and (2) controlling bone turnover by modulating the RANKL-OPG ratio. At the tissue level, BV/TV increased with both loading (+53%, pless than0.05) and iPTH (+54%, pless than0.05). Combined treatment showed only small additional effects at the cellular and molecular levels that corresponded to a small additive effect on bone volume (+13% compared to iPTH alone, pgreater than0.05). This study suggests that iPTH and loading are potential therapies for enhancing periprosthetic bone formation. The elucidation of the cellular and molecular response may help further enhance the combined therapy and related targeted treatment strategies.

  • 10.
    Harding, A.K.
    et al.
    Department of Orthopedics, Lund University Hospital, SE-221 85 Lund, Sweden.
    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.
    Kataoka, M.
    Department of Orthopedics, Lund University Hospital, SE-221 85 Lund, Sweden, Department of Orthopaedic Surgery, Oita University, Oita, Japan.
    Bylski, D.
    Department of Orthopedics, Lund University Hospital, SE-221 85 Lund, Sweden.
    Tagil, M.
    Tägil, M., Department of Orthopedics, Lund University Hospital, SE-221 85 Lund, Sweden.
    Aharinejad, S.
    Aharinejad, S..
    Manipulating the anabolic and catabolic response in bone graft remodeling: Synergism by a combination of local BMP-7 and a single systemic dosis of zoledronate2008In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 26, no 9, p. 1245-1249Article in journal (Refereed)
    Abstract [en]

    Remodeling of a bone graft can be influenced both by anabolic substances, such as a bone morphogenic protein (BMP) and by anticatabolic substances, such as the bisphosphonates. BMPs are potent bone anabolic substances, but also boost catabolism and cause resorption. Bisphosphonates inhibit osteoclast function and can be used to postpone resorption. In the present study a combination of both drugs was explored in a rat bone chamber model. Cancellous bone grafts were treated with either BMP-7 or saline and placed in a bone chamber implanted in the proximal tibia. After 2 weeks, an injection of either zoledronate 0.1 mg/kg or saline was given subcutaneously. The rats were killed after 6 weeks, and bone ingrowth distance into the graft and graft resorption were measured by histomorphometry. BMP-7 significantly (p = 0.007) increased new bone ingrowth distance into the graft from 2.0 mm (SD = 0.98 mm) in the controls to 3.1 mm (SD = 0.93 mm). If bisphosphonate was not given, most of the newly formed and old graft bone was resorbed. A single injection of zoledronate significantly (p< 0.001) increased the trabecular volume/total volume to 40% (SD = 9%) compared to 14% (SD = 10%) in the nonbisphosphonate treated. In total, the net amount of bone increased by 400% when BMP-7 and zoledronate combined was compared to saline. A bone graft can be treated with BMP-7 to increase new bone formation and at the same time be protected against premature catabolism by a single dose of a bisphosphonate. This combination might be useful in various conditions in orthopedic reconstruction. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  • 11.
    Sandberg, Olof
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Bernhardsson, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Earlier effect of alendronate in mouse metaphyseal versus diaphyseal bone healing2017In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 35, no 4, p. 793-799Article in journal (Refereed)
    Abstract [en]

    Healing of injured cancellous bone is characterized by a transient stage of rapid bone formation throughout the traumatized bone volume, often followed by similarly rapid resorption. This is different from the slower diaphyseal healing via an external callus. We, therefore, hypothesized that antiresorptive treatment might have an earlier positive effect in cancellous bone healing than in diaphyseal fractures. One hundred and twenty-three male C57bl6 mice received either an internally stabilized diaphyseal osteotomy of the femur or a screw inserted into the tibial metaphysis. The mice were randomized to daily alendronate injections (200 μg/kg/day), or control injections, and killed for mechanical testing after 14, 21, or 28 days. The hypothesis was tested by a three-way Anova (time, site, and drug). The ultimate force was increased by bisphosphonate treatment in both models. There was a significant interaction between time, site, and drug (p < 0.001) so that the full positive effect of alendronate was evident in the metaphysis at 14 days, but first after 28 days in the diaphysis. While the early effect in the metaphysis might be translated into earlier healing, the late effect in the diaphysis was due to delayed remodeling of the callus, which might have less clinical importance. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

  • 12.
    Schizas, Nikos
    et al.
    Karolinska University Hospital.
    Li, Jian
    Karolinska University Hospital.
    Andersson, Therese
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Fahlgren, Anna
    Linköping University, Department of Clinical and Experimental 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.
    Ahmed, Mahmood
    Karolinska University Hospital.
    W. Ackermann, Paul
    Karolinska University Hospital.
    Compression Therapy Promotes Proliferative Repair during Rat Achilles Tendon Immobilization2010In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 28, no 7, p. 852-858Article in journal (Refereed)
    Abstract [en]

    Achilles tendon ruptures are treated with an initial period of immobilization, which obstructs the healing process partly by a reduction of blood circulation. Intermittent pneumatic compression (IPC) has been proposed to enhance tendon repair by stimulation of blood flow. We hypothesized that daily IPC treatment can counteract the deficits caused by 2 weeks of immobilization post tendon rupture. Forty-eight Sprague-Dawley SD) rats, all subjected to blunt Achilles tendon transection, were divided in three equal groups. Group A was allowed free cage activity, whereas groups B C were immobilized at the operated hindleg. Group C received daily IPC treatment. Two weeks post-rupture the rats were euthanatized and the tendons analyzed with tensile testing and histological assessments of collagen organization and collagen III-LI occurrence. Immobilization significantly reduced maximum force, energy uptake, stiffness, tendon length, transverse area, stress, organized collagen diameter and collagen III-LI occurrence by respectively 80, 75, 77, 22, 47, 65, 49, and 83% compared to free mobilization. IPC treatment improved maximum force 65%, energy 168%, organized collagen diameter 50%, tendon length 25%, and collagen III-LI occurrence 150% compared to immobilization only. The results confirm that immobilization impairs healing after tendon rupture and furthermore demonstrate that IPC-treatment can enhance proliferative tendon repair by counteracting biomechanical and morphological deficits caused by immobilization.

  • 13. Seebach, C
    et al.
    Skripitz, R
    Andréasson, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care.
    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.
    Intermittent parathyroid hormone (1-34) enhances mechanical strength and density of new bone after distraction osteogenesis in rats2004In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 22, no 3, p. 472-478Article in journal (Refereed)
    Abstract [en]

    Distraction osteogenesis is used both for leg lengthening and for bone transportation in the treatment of fractures and nonunions. The main problem with this method is that the time until full recovery may be up to a year, partly because of the time needed for the new formed bone to consolidate and become strong enough for weight bearing. We have studied whether intermittent parathyroid hormone (PTH(1-34)) could accelerate the consolidation of new formed bone after distraction osteogenesis in rats. Forty-seven, 3-months-old mate Sprague-Dawley rats underwent lengthening of the right femur using an external fixator. After a middiaphyseal osteotomy and a 7-day latency period, the callus was distracted during 10 days, with a distraction rate of 0.25 mm twice a day. The consolidation time was either 20 days or 40 days after distraction was completed. A dose of 60 mug of human PTH(1-34)/kg body weight/injection or vehicle was given every second day beginning 30 days before the rats were killed. Both femura of each rat were subjected to mechanical testing and dual-energy X-ray absorptiometry. Blinded histological examination was done for the distracted femura. In the 20 days consolidation experiment, PTH(1-34) increased ultimate load (56%), stiffness (117%), total regenerate callus volume (58%), callus BMC (24%) and histologic bone density (35%) compared to untreated distraction osteogenesis specimens. In the 40 days consolidation experiment, PTH(1-34) increased ultimate load (54%), stiffness (55%), callus BMC (33%) and histologic bone density (23%) compared to untreated distraction osteogenesis specimens. Total regenerate callus volume was unchanged. The contralateral femur also became stronger, stiffer and denser under PTH(1-34) treatment, but to a lesser degree. PTH(1-34) might become useful to shorten the consolidation time after distraction osteogenesis in humans. (C) 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.

  • 14.
    Skoglund, Björn
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine.
    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.
    PMMA particles and pressure - A study of the osteolytic properties of two agents proposed to cause prosthetic loosening2003In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 21, no 2, p. 196-201Article in journal (Refereed)
    Abstract [en]

    Amongst the wear debris particles implicated in the particle hypothesis for prosthetic loosening are polymethylmethacrylate (PMMA), and particularly PMMA with barium sulphate contrast agent. Another suggested cause for loosening is hydrostatic pressure. PMMA particles were combined with hydrostatic pressure in a study to investigate whether there could be a synergistic or additive effect between these two factors. Titanium plates were fastened onto tibiae of 59 rats. After osseointegration, PMMA particles with barium sulphate were administered to the bone-implant interface. Further, PMMA particles were introduced into a previously published model for hydrostatic pressure induced osteolysis. There was measurable resorption in response to the PMMA particles but no additive or synergistic effect from introducing particles to the pressure model, and the effect of pressure was far greater than that of particles. These results suggest that, whereas particles can be shown to elicit an osteolytic response, the much less studied osteolytic effects of pressure could be far more important. ⌐ 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.

  • 15.
    Skripitz, Ralf
    et al.
    Orthopaedic Department, University Hospital Eppendorf, Hamburg, Germany.
    Böhling, Silvia
    Orthopaedic Department, University Hospital Eppendorf, Hamburg, Germany.
    Rüther, Wolfgang
    Orthopaedic Department, University Hospital Eppendorf, Hamburg, Germany.
    Aspenberg, Per
    Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Stimulation of implant fixation by parathyroid hormone (1-34)-A histomorphometric comparison of PMMA cement and stainless steel.2005In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 23, no 6, p. 1266-70Article in journal (Refereed)
    Abstract [en]

    Whereas continuous exposure to PTH results in bone resorption, PTH administration at intermittent doses results in bone formation by increasing osteoblast number and activity. PTH leads to faster fracture repair and better fixation of orthopaedic implants in animal models. The present study evaluates if PTH is able to increase the contact surface between bone and implant and whether the effect of PTH is dependent on implant material characteristics. The implants were made as rods, either of stainless steel or Palacos R bone-cement. The steel rods had a surface roughness of R(a) 0.1 microm and the cement rods R(a) 2.2 microm. In 40 adult male rats, one cement rod was inserted in the left tibia and one steel rod in the right tibia. After implantation, the rats were divided into groups by random. One group was injected three times a week with human PTH (1-34) at a dose of 60 microg/kg BW/injection. The second group was injected with the vehicle only. Both groups were then divided into groups for 2 and 4 weeks time till tibial harvest. The tibial segments around the hole of the rods were then prepared by standard histological techniques. The linear tissue surfaces, that had been in contact with the surface of the rod, were analyzed in a blind fashion. PTH increased the bone contact fraction compared with the vehicle in the steel group from 7.4 (SD 7.6) to 21.1 (SD 10.7) % after 2 weeks and from 9.8 (SD 8.1) to 47.1 (SD 13.3) % after 4 weeks. In the cement group PTH increased the contact index again compared with the vehicle from 7.8 (SD 10.2) to 53.6 (SD 26.3) % already after 2 weeks and from 14.3 (SD 15) to 65.6 (SD 15.7) % after 4 weeks. The bone trabeculae adjacent to the implant had become fewer and thicker after the treatment with PTH (1-34), with an increase of the bone mass in the area next to the bone-implant-interface. The earlier onset of PTH effects in the rougher cement group suggests that intermittent PTH treatment might lead to an increased micro-interlock between implant and bone, and might therefore be considered as a possible drug to enhance incorporation of orthopedic implants.

  • 16.
    Tillander, Bo
    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.
    Franzen, L.
    Franzén, L., Department of Pathology, University Hospital of Örebro, S-701 85 Örebro, Sweden.
    Norlin, Rolf
    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.
    Fibronectin, MMP-1 and histologic changes in rotator cuff disease2002In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 20, no 6, p. 1358-1364Article in journal (Refereed)
    Abstract [en]

    This study was designed to investigate human surgical specimens from patients with impingement (n = 16), ruptured supraspinatus tendons (n = 7), frozen shoulder (n = 2) and controls (n = 9) with respect to histological changes and the presence of fibronectin and Matrix metalloprotease-1 (MMP-1). The biopsy of the middle part of the supraspinatus tendons was analyzed microscopically after staining with hematoxyline eosin, Van Giesons hematoxyline and Phospho Tungstic Acid Hematoxyline for visualization of fibrin. Immunofluorescent stainings for fibronectin and MMP-1 were performed. Histology and immunofluorescence were assessed blindly. Necrotic tendinous tissue and fibrin were found only in some specimens from ruptures. The staining for fibronectin was significantly increased among patients with a rupture. MMP-1 was, however, only infrequently found in specimens from patients with impingement and ruptures. Fibrosis and thinning of fascicles seemed to be a more non-specific finding, appearing in control, impingement and rupture specimens. In conclusion, necrotic tendinous tissue, fibrin and fibronectin appear to be signs of tendon degeneration, whereas fibrosis and thinning of fascicles were found also in controls. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.

  • 17.
    Åstrand, Jörgen
    et al.
    Lunds Universitet.
    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.
    Topical, single dose bisphosphonate treatment reduced bone resorption in a rat model for prosthetic loosening2004In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 22, no 2, p. 244-249Article in journal (Refereed)
    Abstract [en]

    Fluid pressure, instability or particles have been suggested to cause peri-prosthetic bone resorption. High intracapsular pressures have been reported in hip joints with loose prosthetic components, and oscillating fluid pressure has been shown to cause dramatic bone resorption in animal models. Resorption can be reduced by systemic bisphosphonate treatment in rat models with oscillating fluid pressure, but this has required higher doses than needed to inhibit normal remodelling. Bisphosphonates have high affinity to bone mineral. Topical application of the drug is therefore feasible. We used a previously described rat model where oscillating fluid pressure causes bone resorption. Before pressurization, a 1 mg/ml solution of alendronate was applied onto the bone surface for 1 min, after which excess bisphosphonate was rinsed away. Bone resorption was measured on histological slides as soft tissue area at the interface. Rats treated with topical alendronate had soft tissue areas reduced by half. Topical bisphosphonate treatment before cementing a joint implant could possibly reduce the risk of later loosening.

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