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  • 151.
    Sandberg, Olof
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Glucocorticoids inhibit shaft fracture healing but not metaphyseal bone regeneration under stable mechanical conditions2015In: BONE and JOINT RESEARCH, ISSN 2046-3758, Vol. 4, no 10, p. 170-175Article in journal (Refereed)
    Abstract [en]

    Objectives Healing in cancellous metaphyseal bone might be different from midshaft fracture healing due to different access to mesenchymal stem cells, and because metaphyseal bone often heals without a cartilaginous phase. Inflammation plays an important role in the healing of a shaft fracture, but if metaphyseal injury is different, it is important to clarify if the role of inflammation is also different. The biology of fracture healing is also influenced by the degree of mechanical stability. It is unclear if inflammation interacts with stability-related factors.

    Methods We investigated the role of inflammation in three different models: a metaphyseal screw pull-out, a shaft fracture with unstable nailing (IM-nail) and a stable external fixation (ExFix) model. For each, half of the animals received dexamethasone to reduce inflammation, and half received control injections. Mechanical and morphometric evaluation was used.

    Results As expected, dexamethasone had a strong inhibitory effect on the healing of unstable, but also stable, shaft fractures. In contrast, dexamethasone tended to increase the mechanical strength of metaphyseal bone regenerated under stable conditions.

    Conclusions It seems that dexamethasone has different effects on metaphyseal and diaphyseal bone healing. This could be explained by the different role of inflammation at different sites of injury.

  • 152.
    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

  • 153.
    Sandberg, Olof
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Dånmark, Ida
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Eliasson, Pernilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Influence of a lower leg brace on traction force in healthy and ruptured Achilles tendons2015In: MLTJ Muscles, Ligaments and Tendons Journal, ISSN 2240-4554, Vol. 5, no 2, p. 63-67Article in journal (Other academic)
    Abstract [en]

    Background: we investigated how ruptured Achilles tendons are loaded in a brace. There is an ongoing discussion whether patients should be recommended to bear weight on the injuredlimb. However, little is known about the effects of bracing on tensional loading of the healing Achilles tendon: it is uncertain if load-bearing actually stresses the Achilles tendon inside a brace.

    Methods: we measured plantar flexion moment inside the brace, in order to estimate tensional loading of the tendon, by use of an insole with pressure transducers.

    Results: after wearing the brace for 1 hour, young healthy individuals reduced their maximum flexion moment during gait by half. Patients with Achilles tendon rupture showed no measurable flexion moment during gait with the brace, 4 or 7 weeks after injury. Only when specifically instructed, they could produce a considerable plantar flexion moment. We noted that gait speed with the brace at 4 weeks correlated with a heel-raise functional test at 1 year: the higher the spontaneous gait speed, the less the functional difference between the injured and the uninjured leg (r2=0.68; p=0.002).

    Conclusion: the correlation with gait speed suggests that the patients’ general physical aptness has an impact on the end result.

  • 154.
    Sandberg, Olof
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Eliasson, Pernilla T
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine.
    Andersson, Therese
    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, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Etanercept does not impair healing in rat models of tendon or metaphyseal bone injury2012In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 83, no 3, p. 305-310Article in journal (Refereed)
    Abstract [en]

    Background and purpose Should blockade of TNF-alpha be avoided after orthopedic surgery? Healing of injuries in soft tissues and bone starts with a brief inflammatory phase. Modulation of inflammatory signaling might therefore interfere with healing. For example, Cox inhibitors impair healing in animal models of tendon, ligament, and bone injury, as well as in fracture patients. TNF-alpha is expressed locally at increased levels during early healing of these tissues. We therefore investigated whether blocking of TNF-alpha with etanercept influences the healing process in established rat models of injury of tendons and metaphyseal bone. less thanbrgreater than less thanbrgreater thanMethods Rats were injected with etanercept, 3.5 mg/kg 3 times a week. Healing of transected Achilles tendons and bone healing around screws implanted in the tibial metaphysis were estimated by mechanical testing. Tendons were allowed to heal either with or without mechanical loading. Ectopic bone induction following intramuscular BMP-2 implants has previously been shown to be stimulated by etanercept in rodents. This was now tested as a positive control. less thanbrgreater than less thanbrgreater thanResults Tendon peak force after 10 days was not significantly influenced by etanercept. Changes exceeding 29% could be excluded with 95% confidence. Likewise, screw pull-out force was not significantly influenced. More than 25% decrease or 18% increase could be excluded with 95% confidence. However, etanercept treatment increased the amount of bone induced by intramuscular BMP-2 implants, as estimated by blind histological scoring. less thanbrgreater than less thanbrgreater thanInterpretation Etanercept does not appear to impair tendon or metaphyseal bone healing to any substantial degree.

  • 155.
    Sandberg, Olof
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Macias, Brandon R
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. University of California, San Diego, USA.
    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.
    Low dose PTH improves metaphyseal bone healing more when muscles are paralyzed2014In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 63, p. 15-19Article in journal (Refereed)
    Abstract [en]

    Stimulation of bone formation by PTH is related to mechanosensitivity. The response to PTH treatment in intact bone could therefore be blunted by unloading. We studied the effects of mechanical loading on the response to PTH treatment in bone healing. Most fractures occur in the metaphyses, therefor we used a model for metaphyseal bone injury. One hind leg of 20 male SD rats was unloaded via intramuscular botulinum toxin injections. Two weeks later, the proximal unloaded tibia had lost 78% of its trabecular contents. At this time-point, the rats received bilateral proximal tibiae screw implants. Ten of the 20 rats were given daily injections of 5 μg/kg PTH (1-34). After two weeks of healing, screw fixation was measured by pull-out, and microCT of the distal femur cancellous compartment was performed. Pull-out force provided an estimate for cancellous bone formation after trauma. PTH more than doubled the pull-out force in the unloaded limbs (from 14 to 30 N), but increased it by less than half in the loaded ones (from 30 to 44 N). In relative terms, PTH had a stronger effect on pull-out force in unloaded bone than in loaded bone (p=0.03). The results suggest that PTH treatment for stimulation of bone healing does not require simultaneous mechanical stimulation.

  • 156.
    Schepull, Thorsten
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics.
    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.
    Early, controlled tension improves the material properties of healing human Achilles tendons after rupture: a randomized trial2013Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Weight-bearing in a fixed brace after acute Achilles tendon rupture does not necessarily lead to mechanical tension in the tendon. Early motion has a positive effect on the clinical outcome, but it is not clear if this is due to effects on tendon strength or to unspecific effects. The aim of this study was to examine if tensional loading leads to improvement of the mechanical properties of the healing, human Achilles tendon.

    Hypothesis: The elastic modulus of the tendon callus is increased by early tensional loading.

    Study Design: Randomized controlled trial; level of evidence: 2.

    Methods: Thirty-five patients with an acute Achilles tendon rupture were recruited consecutively. They were operated with a single suture, and received metal markers in the distal and proximal part of the tendon. After surgery, patients were randomized to either cast immobilization for 7 weeks or tensional loading. The latter group wore a cast for 2 weeks, and then a removable foam walker boot for 5 weeks. They were instructed to remove the boot twice daily and push a special training pedal to produce a predetermined, gradually increasing tensional load on the healing tendon. At 7, 19 and 52 weeks postoperatively, patients were investigated with Roentgen Stereophotogrammetric Analysis (RSA) under different loading conditions, and computed tomography (CT). The collected data allowed calculation of modulus of elasticity. At 52 weeks, we also examined clinical outcome, using the Achilles tendon Total Rupture Score (ATRS) and a heel-raise index.

    Results: The elastic modulus at 19 and 52 weeks was higher in the tensional loading group. There was no significant difference in ATRS or heel-raise index at 52 weeks. As in previous studies, there was a significant correlation between the modulus at 7 weeks and the heel-raise index at 52 weeks. There was moderate tendon elongation.

    Conclusion: Early tensional loading improves the mechanical properties of the healing Achilles tendon.

  • 157.
    Schepull, Thorsten
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Early Controlled Tension Improves the Material Properties of Healing Human Achilles Tendons After Ruptures: A Randomized Trial2013In: American Journal of Sports Medicine, ISSN 0363-5465, E-ISSN 1552-3365, Vol. 41, no 11, p. 2550-2557Article in journal (Refereed)
    Abstract [en]

    Background: Weightbearing in a fixed brace after acute Achilles tendon ruptures does not necessarily lead to mechanical tension in the tendon. Early motion has a positive effect on the clinical outcome, but it is not clear if this is because of effects on tendon strength or unspecific effects. The aim of this study was to examine if tensional loading leads to an improvement in the mechanical properties of the healing Achilles tendon. Hypothesis: The elastic modulus of the tendon callus is increased by early tensional loading. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: Thirty-five patients with an acute Achilles tendon rupture were recruited consecutively. They underwent surgery with a single suture and received metal markers in the distal and proximal parts of the tendon. After surgery, the patients were randomized to either cast immobilization for 7 weeks or tensional loading. The latter group wore a cast for 2 weeks and then a removable foam walker boot for 5 weeks. They were instructed to remove the boot twice daily and push a special training pedal to produce a predetermined, gradually increasing tensional load on the healing tendon. At 7, 19, and 52 weeks postoperatively, the patients were investigated with roentgen stereophotogrammetric analysis under different loading conditions and computed tomography. The collected data allowed calculation of the modulus of elasticity. At 52 weeks, the clinical outcome was also examined using the Achilles tendon Total Rupture Score (ATRS) and the heel-raise index. Results: The elastic modulus at 19 and 52 weeks was higher in the tensional loading group. There was no significant difference in the ATRS or heel-raise index at 52 weeks. As in previous studies, there was a significant correlation between the modulus at 7 weeks and the heel-raise index at 52 weeks. There were no signs of tendon elongation. Conclusion: Early tensional loading improves the mechanical properties of the healing Achilles tendon.

  • 158.
    Schepull, Thorsten
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    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.
    Healing of human Achilles tendon ruptures: Radiodensity reflects mechanical properties2015In: Knee Surgery, Sports Traumatology, Arthroscopy, ISSN 0942-2056, E-ISSN 1433-7347, Vol. 23, no 3, p. 884-889Article in journal (Refereed)
    Abstract [en]

    Purpose

    This study tests the idea of using radiodensity from computed tomography to quantitatively evaluate the healing of ruptured Achilles tendons.

    Methods

    The radiodensity of the healing tendons in sixty-five patients who were treated for Achilles tendon rupture was measured. The hypothesis was that density would correlate with an estimate for e-modulus, derived from strain, measured by radiostereometry with different mechanical loadings.

    Results

    Radiodensity 7 weeks after injury was decreased to 67 % (SD 11) of the contralateral, uninjured tendon. There was no improvement in radiodensity from 7 to 19 weeks, whereas at 1 year, it had increased to 106 % (SD 7). Only 2 of 52 measured values at 1 year were lower than the highest value at 19 weeks, i.e. there was minimal overlap. The variation in radiodensity could explain 80 % of the variation in e-modulus, but radiodensity correlated only weakly with e-modulus at each time point separately. At 1 year, both radiodensity and e-modulus correlated with functional results, although weakly.

    Conclusions

    From 19 weeks onwards, radiodensity appears to reflect mechanical properties of the tendon and might to some extent predict the final outcome. Radiodensity at 7 weeks is difficult to interpret, probably because it reflects both callus and damaged tissues.

    Level of evidence

    Prospective, diagnostic study, Level II.

  • 159.
    Schepull, Thorsten
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics.
    Kvist, Joanna
    Linköping University, Department of Medical and Health Sciences, Physiotherapy. Linköping University, Faculty of Health Sciences.
    Norrman, Hanna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics.
    Trinks, Marie
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics.
    Berlin, Gösta
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    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.
    Autologous Platelets Have No Effect on the Healing of Human Achilles Tendon Ruptures A Randomized Single-Blind Study2011In: AMERICAN JOURNAL OF SPORTS MEDICINE, ISSN 0363-5465, Vol. 39, no 1, p. 38-47Article in journal (Refereed)
    Abstract [en]

    Background: Animal studies have shown that local application of platelet-rich plasma (PRP) stimulates tendon repair. Preliminary results from a retrospective case series have shown faster return to sports. Hypothesis: Autologous PRP stimulates healing of acute Achilles tendon ruptures. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: Thirty patients were recruited consecutively. During surgery, tantalum beads were implanted in the Achilles tendon proximal and distal to the rupture. Before skin suture, randomization was performed, and 16 patients were injected with 10 mL PRP (10 times higher platelet concentration than peripheral blood) whereas 14 were not. With 3-dimensional radiographs (roentgen stereophotogrammetric analysis; RSA), the distance between the beads was measured at 7, 19, and 52 weeks while the patient resisted different dorsal flexion moments over the ankle joint, thereby estimating tendon strain per load. An estimate of elasticity modulus was calculated using callus dimensions from computed tomography. At 1 year, functional outcome was evaluated, including the heel raise index and Achilles Tendon Total Rupture Score. The primary effect variables were elasticity modulus at 7 weeks and heel raise index at 1 year. Results: The mechanical variables showed a large degree of variation between patients that could not be explained by measuring error. No significant group differences in elasticity modulus could be shown. There was no significant difference in heel raise index. The Achilles Tendon Total Rupture Score was lower in the PRP group, suggesting a detrimental effect. There was a correlation between the elasticity modulus at 7 and 19 weeks and the heel raise index at 52 weeks. Conclusion: The results suggest that PRP is not useful for treatment of Achilles tendon ruptures. The variation in elasticity modulus provides biologically relevant information, although it is unclear how early biomechanics is connected to late clinical results.

  • 160.
    Schepull, Torsten
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion.
    Kvist, Joanna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Physiotherapy.
    Andersson, Christer A
    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.
    Aspenberg, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Mechanical properties during healing of Achilles tendon ruptures to predict final outcome: A pilot Roentgen stereophotogrammetric analysis in 10 patients2007In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 8Article in journal (Refereed)
    Abstract [en]

    Background. There are presently few methods described for in vivo monitoring of the mechanics of healing human tendon ruptures, and no methods for prediction of clinical outcome. We tested if Roentgen stereophotogrammetric analysis (RSA) can be used to follow the restoration of mechanical properties during healing of ruptured Achilles tendons, and if early measurements can predict clinical results. Methods. Achilles tendon repair was studied with RSA in 10 patients with a total rupture. Tantalum beads were implanted in conjunction with surgical repair. The patients were evaluated at 6, 12 and 18 weeks, and after 1 year. RSA was performed with two different mechanical loadings, and the strain induced by increasing load was measured. The transverse area was determined by ultrasound. CT scan at 12 weeks confirmed that the tantalum beads were located within the tendons. Functional testing was done after 1 year. A heel raise index was chosen as primary clinical outcome variable. Results. The strain was median 0.90, 0.32 and 0.14 percent per 100 N tendon force at 6 weeks, 18 weeks and one year respectively. The error of measurement was 0.04 percent units at 18 weeks. There was a large variation between patients, which appears to reflect biological variation. From 6 to 18 weeks, there was a negative correlation between increase in transverse area and increase in material properties, suggesting that healing is regulated at the organ level, to maximize stiffness. Modulus of elasticity during this time correlated with a heel raise index at one year (Rho = 0.76, p = 0.02). Conclusion. We conclude that the RSA method might have potential for comparing different treatments of Achilles tendon ruptures. © 2007 Schepull et al, licensee BioMed Central Ltd.

  • 161.
    Schepull, Torsten
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Kvist, Joanna
    Linköping University, Department of Medical and Health Sciences, Physiotherapy. 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.
    Early E-modulus of healing Achilles tendons correlates with late function: Similar results with or without surgery2012In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 22, no 1, p. 18-23Article in journal (Refereed)
    Abstract [en]

    Non-operative treatment of Achilles tendon ruptures is associated with an increased risk of rerupture. We hypothesized that this is due to inferior mechanical properties during an early phase of healing, and performed a randomized trial, using a new method to measure the mechanical properties. Tantalum markers were inserted in the tendon stumps, and tendon strain at different loadings was measured by stereo-radiography (Roentgen stereophotogrammetric analysis) at 3, 7 and 19 weeks and 18 months after injury. Thirty patients were randomized to operative or non-operative treatment. The primary out-come variable was an estimate for the modulus of elasticity at 7 weeks. Strain per force, cross-sectional area and tendon elongation were also measured. The functional outcome variable was the heel-raise index after 18 months. There was no difference in the mean modulus of elasticity or other mechanical or functional variables between operative and non-operative treatments at any time-point, but strain per force at 7 and 19 weeks had a significantly larger variation in the non-operative group. This group, therefore, might contain more outliers with poor healing. The modulus of elasticity at 7 weeks correlated with the heel-raise index after 18 months in both treatment groups (r2=0.75; P=0.0001). This correlation is an intriguing finding.

  • 162.
    Schilcher, Jörg
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Atypical fracture of the femur in a patient using denosumab - a case report2014In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 85, no 1, p. 6-7Article in journal (Other academic)
  • 163.
    Schilcher, Jörg
    et al.
    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.
    Incidence of stress fractures of the femoral shaft in women treated with bisphosphonate2009In: ACTA ORTHOPAEDICA, ISSN 1745-3674, Vol. 80, no 4, p. 413-415Article in journal (Refereed)
    Abstract [en]

    Background Recent case reports have identified an association between long-term bisphosphonate treatment and stress fractures of the femoral shaft. The risk of such fractures in bisphosphonate users has not been determined. Methods We identified women over 55 years of age with the specific fracture pattern by searching the operation registry of the hospitals in 2 healthcare districts. Prevalence of bisphosphonate treatment was provided by a Swedish national registry covering all drugs delivered to all individuals since 2005. Results The number of women on bisphosphonate treatment was 3,087. Of these, 5 had femoral stress fractures. They had been taking bisphosphonates for 3.5 to 8.5 years. The incidence density for a patient on bisphosphonate was 1/1,000 per year (95% CI: 0.3-2). In the remaining 88,869 women who were not taking bisphosphonates, there were 3 stress fractures. Thus, their risk (without correction for inhomogeneity in age distribution) was 46 times less (95% CI: 11-200). Interpretation These results are rough estimations based on a comparatively small material. Still, a treatment-associated incidence density of 1/1,000 is acceptable, considering that bisphosphonate treatment is likely to reduce the incidence density of any fracture by 1511,000 according to a large randomized trial (Black et al. 1996).

  • 164.
    Schilcher, Jörg
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Bernhardsson, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Chronic anterior tibial stress fractures in athletes: No crack but intense remodelling2019In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Delayed healing of anterior tibial stress fractures in athletes is related to high tensional forces acting across a putative fracture gap. These forces lead to crack propagation and create strains that exceed tissue differentiation thresholds for new bone to form in the gap. The "dreaded black line" is a radiographic hallmark sign of stress fractures considered to represent a transverse fracture gap. However, whether a fracture gap truly exists at the microscopic level remains unclear. The aim of this study was to describe the area of the "dreaded black line" microscopically and to identify signs of delayed healing.

    METHODS: Between 2011 and 2016 we included seven athletes with chronic anterior mid-shaft tibial stress fractures. The fracture site was excised as a cylindrical biopsy. The biopsy was evaluated with micro-CT and histology. The formation of new bone in the defect was evaluated radiographically.

    RESULTS: The "dreaded black line" seen on preoperative radiographs in all patients could not be seen on the microscopic level. Instead, the area of the putative crack showed widened resorption cavities, lined with active osteoblasts, and surrounded by immature bone. This area of intense remodelling seemed to create a false impression of a fracture line on radiographs. Complete cortical continuity was restored at the biopsy site at median eight months (range six to 13 months).

    CONCLUSION: Tibial stress fractures in athletes normally show no fracture defect, but a region of increased remodelling. The healing process is already ongoing but seems mechanically insufficient. 

    The full text will be freely available from 2020-05-18 11:04
  • 165.
    Schilcher, Jörg
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Koeppen, Veronika
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Michaelsson, Karl
    Uppsala University, Sweden.
    Risk of Atypical Femoral Fracture during and after Bisphosphonate Use2014In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 371, no 10, p. 974-976Article in journal (Other academic)
    Abstract [en]

    n/a

  • 166.
    Schilcher, Jörg
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Koeppen, Veronika
    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.
    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.
    Michaelsson, Karl
    Uppsala University, Sweden; Uppsala University, Sweden.
    Risk of atypical femoral fracture during and after bisphosphonate use Full report of a nationwide study2015In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 86, no 1, p. 100-107Article in journal (Refereed)
    Abstract [en]

    Background and purpose - Use of bisphosphonates in women is associated with higher risk of atypical femoral fractures. The risk in terms of timing of use and type of bisphosphonate, and in men, remains unclear. Patients and methods - We reviewed radiographs of 5,342 Swedish women and men aged 55 years or more who had had a fracture of the femoral shaft in the 3-year period 2008-2010 (97% of those eligible), and found 172 patients with atypical fractures (93% of them women). We obtained data on medication and comorbidity. The risk of atypical fracture associated with bisphosphonate use was estimated in a nationwide cohort analysis. In addition, we performed a case-control analysis with comparison to 952 patients with ordinary shaft fractures. A short report of the findings has recently been presented (Schilcher et al. 2014a). Here we provide full details. Results - The age-adjusted relative risk (RR) of atypical fracture associated with bisphosphonate use was 55 (95% CI: 39-79) in women and 54 (CI: 15-192) in men. In bisphosphonate users, women had a 3-fold higher risk than men ( RR = 3.1, CI: 1.1-8.4). Alendronate users had higher risk than risedronate users (RR = 1.9, CI: 1.1-3.3). The RR after 4 years or more of use reached 126 (CI: 55-288), with a corresponding absolute risk of 11 (CI: 7-14) fractures per 10,000 person-years of use. The risk decreased by 70% per year since last use. Interpretation - Women have a higher risk of atypical femoral fracture than men. The type of bisphosphonate used may affect risk estimates and the risk decreases rapidly after cessation.

  • 167.
    Schilcher, Jörg
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Koeppen, Veronika
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Ranstam, Jonas
    Lund University, Sweden .
    Skripitz, Ralf
    University Hospital Rostock, Germany .
    Michaelsson, Karl
    Uppsala University, Sweden .
    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.
    Atypical femoral fractures are a separate entity, characterized by highly specific radiographic features. A comparison of 59 cases and 218 controls2013In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 52, no 1, p. 389-392Article in journal (Refereed)
    Abstract [en]

    Background: Estimations of the risk of bisphosphonate associated atypical femoral fractures vary between different population-based studies, from considerable to neglectable. A possible explanation for these discrepancies could be different definitions of atypical fractures. We aimed to identify specific radiographic fracture characteristics associated with bisphosphonate use. less thanbrgreater than less thanbrgreater thanMethods: In a previous nationwide study, 59 atypical and 218 ordinary fractures were diagnosed. The atypical fractures were defined by their stress-type fracture pattern. All fractures were now re-assessed by a physician in training, without information about bisphosphonate use. The fracture angle (0-180 degrees) was measured. Presence of local lateral cortical thickening (a callus reaction), more than 2 fragments, or a medial spike was noted. The reader then made a judgment whether the fracture appeared as an atypical fracture based on the ASBMR criteria. less thanbrgreater than less thanbrgreater thanResults: Frequency distribution analysis of the fracture angle showed a distinct subgroup, comprising 25% of all 277 fractures, with a mean of 89 and SD of 10 degrees. Forty-two of 57 patients in this subgroup used bisphosphonates, whereas only 27 of 213 others did (specificity 0.93; 95% CI 0.88-0.96). Presence of a callus reaction had also a high specificity for bisphosphonate use (0.96; 95% CI 0.92-0.98). The ASBMR criteria had a lower specificity, increasing the number of atypical fractures without bisphosphonate use from 13 to 31. This led to a decrease in age-adjusted relative risk associated with bisphosphonate use from 47 (95% CI 26-87) to 19 (95% CI 12-29). less thanbrgreater than less thanbrgreater thanInterpretation: Stress fractures of the femoral shaft are a specific entity, which is easily diagnosed on radiographs and strongly related to bisphosphonate use. Differences in diagnostic criteria may partially explain the large differences in relative risk between different population-based studies.

  • 168.
    Schilcher, Jörg
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics.
    Michaelsson, Karl
    Uppsala University.
    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.
    Bisphosphonate Use and Atypical Fractures of the Femoral Shaft2011In: NEW ENGLAND JOURNAL OF MEDICINE, ISSN 0028-4793, Vol. 364, no 18, p. 1728-1737Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Studies show conflicting results regarding the possible excess risk of atypical fractures of the femoral shaft associated with bisphosphonate use. METHODS In Sweden, 12,777 women 55 years of age or older sustained a fracture of the femur in 2008. We reviewed radiographs of 1234 of the 1271 women who had a subtrochanteric or shaft fracture and identified 59 patients with atypical fractures. Data on medications and coexisting conditions were obtained from national registries. The relative and absolute risk of atypical fractures associated with bisphosphonate use was estimated by means of a nationwide cohort analysis. The 59 case patients were also compared with 263 control patients who had ordinary subtrochanteric or shaft fractures. RESULTS The age-adjusted relative risk of atypical fracture was 47.3 (95% confidence interval [CI], 25.6 to 87.3) in the cohort analysis. The increase in absolute risk was 5 cases per 10,000 patient-years (95% CI, 4 to 7). A total of 78% of the case patients and 10% of the controls had received bisphosphonates, corresponding to a multivariable-adjusted odds ratio of 33.3 (95% CI, 14.3 to 77.8). The risk was independent of coexisting conditions and of concurrent use of other drugs with known effects on bone. The duration of use influenced the risk (odds ratio per 100 daily doses, 1.3; 95% CI, 1.1 to 1.6). After drug withdrawal, the risk diminished by 70% per year since the last use (odds ratio, 0.28; 95% CI, 0.21 to 0.38). CONCLUSIONS These population-based nationwide analyses may be reassuring for patients who receive bisphosphonates. Although there was a high prevalence of current bisphosphonate use among patients with atypical fractures, the absolute risk was small.

  • 169.
    Schilcher, Jörg
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Michaelsson, Karl
    Uppsala University.
    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: Bisphosphonates and Atypical Femoral Shaft Fractures REPLY2011In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 365, no 4, p. 377-377Article in journal (Other academic)
    Abstract [en]

    n/a

  • 170.
    Schilcher, Jörg
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Isaksson, Hanna
    Lund University, Sweden.
    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.
    Histology of 8 atypical femoral fractures2014In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 85, no 3, p. 280-286Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE:

    The pathophysiology behind bisphosphonate-associated atypical femoral fractures remains unclear. Histological findings at the fracture site itself may provide clues.

    PATIENTS AND METHODS:

    Between 2008 and 2013, we collected bone biopsies including the fracture line from 4 complete and 4 incomplete atypical femoral fractures. 7 female patients reported continuous bisphosphonate use for 10 years on average. 1 patient was a man who was not using bisphosphonates. Dual-energy X-ray absorptiometry of the hip and spine showed no osteoporosis in 6 cases. The bone biopsies were evaluated by micro-computed tomography, infrared spectroscopy, and qualitative histology.

    RESULTS:

    Incomplete fractures involved the whole cortical thickness and showed a continuous gap with a mean width of 180 µm. The gap contained amorphous material and was devoid of living cells. In contrast, the adjacent bone contained living cells, including active osteoclasts. The fracture surfaces sometimes consisted of woven bone, which may have formed in localized defects caused by surface fragmentation or resorption.

    INTERPRETATION:

    Atypical femoral fractures show signs of attempted healing at the fracture site. The narrow width of the fracture gap and its necrotic contents are compatible with the idea that micromotion prevents healing because it leads to strains within the fracture gap that preclude cell survival.

  • 171.
    Schilcher, Jörg
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Sen Howe, Tet
    Singapore Gen Hospital, Singapore.
    Ai Png, Meng
    Singapore Gen Hospital, Singapore.
    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.
    Koh, Joyce S. B.
    Singapore Gen Hospital, Singapore.
    Atypical Fractures are Mainly Subtrochanteric in Singapore and Diaphyseal in Sweden: A Cross-Sectional Study2015In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 30, no 11, p. 2127-2132Article in journal (Refereed)
    Abstract [en]

    We have previously noted a dichotomy in the location of atypical fractures along the femoral shaft in Swedish patients, and a mainly subtrochanteric location of atypical fractures in descriptions of patients from Singapore. These unexpected differences were now investigated by testing the following hypotheses in a cross-sectional study: first, that there is a dichotomy also in Singapore; second, that the relation between subtrochanteric and diaphyseal location is different between the two countries; third, that the location is related to femoral bow. The previously published Swedish sample (n = 151) was re-measured, and a new Singaporean sample (n = 75) was established. Both samples were based on radiographic classification of all femoral fractures in women above 55 years of age. The distance between the fracture line and the lesser trochanter was measured. Femoral bow was classified as present or absent on frontal radiographs. Frequency distribution of the measured distances was analyzed using the Bayesian information criterion to choose the best description of the observed variable distribution in terms of a compilation of normally distributed subgroups. The analysis showed a clear dichotomy of the fracture location: either subtrochanteric or diaphyseal. Subtrochanteric fractures comprised 48% of all fractures in Singapore, and 17% in Sweden (p = 0.0001). In Singapore, femoral bow was associated with more fractures in the diaphyseal subgroup (p = 0.0001). This was not seen in Sweden. A dichotomous location of atypical fractures was confirmed, because it was found also in Singapore. The fractures showed a different localization pattern in the two countries. This difference may be linked to anatomical variations, but might also be related to cultural differences between the two populations that influence physical activity. (c) 2015 American Society for Bone and Mineral Research

  • 172.
    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.

  • 173. 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.

  • 174. Siebrecht, Maikel A.N.
    et al.
    De Rooij, Philippe P.
    Arm, Douglas M.
    Olsson, Martin L.
    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.
    Platelet concentrate increases bone ingrowth into porous hydroxyapatite2002In: Orthopedics, ISSN 0147-7447, E-ISSN 1938-2367, Vol. 25, no 2, p. 169-172Article in journal (Refereed)
    Abstract [en]

    Platelets contain growth factors that are believed to stimulate early fracture repair. Autologous platelets can be sequestered, concentrated, and mixed with thrombin to yield a so-called autologous growth factor gel, which might enhance bone repair or bone graft incorporation. The effect of this platelet concentrate on total tissue and bone ingrowth into porous coralline hydroxyapatite was studied in a bone chamber rat model. Chambers with the platelet concentrate showed a significant increase in bone and total tissue ingrowth distance compared to untreated controls, indicating a platelet concentrate might enhance the clinical performance of porous hydroxyapatite in bone replacement.

  • 175.
    Skoglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    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.
    Locally applied Simvastatin Improves Fracture Healing in Mice2007In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 8, no 98Article in journal (Refereed)
    Abstract [en]

    Background: HMG-CoA reductase inhibitors, statins, are widely prescribed to lower cholesterol. High doses of orally administered simvastatin has previously been shown to improve fracture healing in a mouse femur fracture model. In this study, simvastatin was administered either subcutaneously or directly to the fracture area, with the goal of stimulating fracture repair at acceptable doses.

    Methods: Femur fractures were produced in 70 mature male Balb-C mice and stabilized with marrow-nailing. Three experiments were performed. Firstly, 20 mice received subcutaneous injections of either simvastatin (20 mg) or vehicle. Secondly, 30 mice were divided into three groups of 10 mice receiving continuous subcutaneous delivery of the vehicle substance, the vehicle with 5 mg or with 10 mg of simvastatin per kg bodyweight per day. Finally, in 20 mice, a silicone tube was led from an osmotic mini-pump to the fracture area. In this way, 10 mice received an approximate local dose of simvastatin of 0.1 mg per kg per day for the duration of the experiment and 10 mice received the vehicle compound. All treatments lasted until the end of the experiment. Bilateral femurs were harvested 14 days post-operative. Biomechanical tests were performed by way of three-point bending. Data was analysed with ANOVA, Scheffé's post-hoc test and Student's unpaired t-test.

    Results: With daily simvastatin injections, no effects could be demonstrated for any of the parameters examined. Continuous systemic delivery resulted in a 160% larger force at failure. Continuous local delivery of simvastatin resulted in a 170% larger force at failure as well as a twofold larger energy uptake.

    Conclusion: This study found a dramatic positive effect on biomechanical parameters of fracture healing by simvastatin treatment directly applied to the fracture area.

  • 176.
    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.

  • 177.
    Skoglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences.
    Forslund, Carina
    Department of Orthopedics, Lund University Hospital, Lund, Sweden.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences.
    Simvastatin Improves Fracture Healing in Mice2002In: Journal of bone and mineral research, ISSN 0884-0431, Vol. 17, no 111, p. 2004-2008Article in journal (Refereed)
    Abstract [en]

    Recently, several articles have been published dealing with the anabolic effects on bone by statins. Mundy and associates discovered that several statins were able to activate the promotor of bone morphogenetic protein (BMP) 2. Additionally, oral simvastatin and lovastatin increased the cancellous bone volume in rats, presumably an effect of the increase of BMP-2. Other studies have followed, with conflicting results; some have found a positive bone metabolic effect of statins and others have not. Studies published so far have focused on osteoporosis. In this study, femur fractures were produced in 81 mature male BALB/c mice and stabilized with marrow-nailing. Forty-one mice were given a diet prepared with simvastatin, so that each mouse received an approximate dose of 120 mg/kg of body weight per day. The remaining mice received the same diet with the exception of the simvastatin. Bilateral femurs were harvested at 8, 14, and 21 days postoperatively (po), the marrow-nail was extracted, and diameters were measured. Biomechanical tests were performed on 42 mice, by way of three-point bending. Histological specimens were prepared using standard techniques. For statistical analysis, ANOVA with Scheffé’s post hoc test was used. At 8 days, the fracture callus was too soft for meaningful biomechanical testing. At 14 days, the callus of the simvastatin-treated mice had a 53% larger transverse area than controls (p = 0.001), the force required to break the bone was 63% greater (p = 0.001), and the energy uptake was increased by 150% (p = 0.0008). Stiffness and modulus of elasticity were not significantly affected. At 21 days, the fractures were histologically healed and the mechanical differences had disappeared. The contralateral unbroken bone showed a slight increase in transverse area because of the simvastatin treatment, but there was no significant effect on the force required to break the bone or on energy uptake. These results point to a new possibility in the treatment of fractures.

  • 178.
    Skoglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Holmertz, Jonas
    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.
    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.
    Systemic and Local Ibandronate Enhance Screw Fixation2004In: Journal of Orthopaedic Reserach, ISSN 0736-0266, Vol. 22, no 5, p. 1108-1113Article in journal (Refereed)
    Abstract [en]

    The trauma involved with inserting implants into bone leads to an activation of the inflammatory response and an activation of osteoclasts. In addition, apoptosis of osteocytes in the surrounding area has been implicated in further activation of osteoclasts. If the balance between resorption and bone formation shortly after implantation favours resorption, an impairment of early fixation might ensue.Because bisphosphonates inhibit resorption, this study analyses whether they can improve early fixation. Stainless steel screws (M 1.7) were inserted into the tibiae of 76 male Sprague-Dawley rats. Daily subcutaneous injections of ibandronate (3 μg) or saline were given to 20 rats. The remaining rats received ibandronate or saline directly applied into the drill hole before the screw was inserted. Tibiae were harvested at 14 days. Mechanical tests were performed on 50 tibiae. Systemically treated tibiae were tested for pull-out strength alone. Locally treated tibiae were tested for either pull-out or torque resistance. The remaining 18 tibiae were prepared for histology.Systemic ibandronate increased the pull-out force at failure by 30% (p=0.04). Local treatment increased the force at failure by 15% (p=0.02) and stiffness by 28% (p=0.01). In the removal torque measurements, local ibandronate increased the torque-moment at failure by 60% (p=0.04), and the maximum friction moment by 51% (p=0.04). Energy for turning the screw 1/4 revolution was increased by 68% (p=0.02).These results demonstrate that early remodeling events plays an important role in screw fixation, and that systemic or local bisphosphonate treatment could be an effective pharmacological path to improve early implant fixation.

  • 179.
    Skoglund, Björn
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine.
    Larsson, L
    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.
    Bone-resorptive effects of endotoxin-contaminated high-density polyethylene particles spontaneously eliminated in vivo2002In: Journal of Bone and Joint Surgery, ISSN 0301-620X, E-ISSN 2044-5377, Vol. 84, no 5, p. 767-773Article in journal (Refereed)
    Abstract [en]

    Wear particles commonly used for experiments may carry adherent endotoxin on their surfaces, which may be responsible for the observed effects. In this study, we attached titanium plates to the tibiae of 20 rats. After osseointegration, endotoxin-contaminated or uncontaminated high-density-polyethylene (HDPE) particles were applied. Contaminated specimens showed a dramatic resorption of bone after seven days but new bone filled the site again at 21 days. Uncontaminated specimens showed no resorption. In 18 rats we implanted intramuscularly discs of ultra-high-molecular-weight polyethylene (UHMWPE) with baseline or excess contamination of endotoxin. Excess endotoxin disappeared within 24 hours and the amount of endotoxin remained at baseline level (contamination from production). Uncontaminated titanium discs did not adsorb endotoxin in vivo. The endotoxin was measured by analytical chemistry. Locally-applied endotoxin stimulated bone resorption similarly to that in experiments with wear particles. Endotoxin on the surface of implants and particles appeared to be inactivated in situ. A clean implant surface did not adsorb endotoxin. Our results suggest that endotoxin adhering to orthopaedic implants is not a major cause for concern.

  • 180.
    Skripitz, R
    et al.
    University Hospital Rostock.
    Johansson, H R
    Sinai Hospital Baltimore.
    Ulrich, S D
    Sinai Hospital Baltimore.
    Werner, A
    University Hospital Eppendorf.
    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.
    Effect of alendronate and intermittent parathyroid hormone on implant fixation in ovariectomized rats2009In: JOURNAL OF ORTHOPAEDIC SCIENCE, ISSN 0949-2658, Vol. 14, no 2, p. 138-143Article in journal (Refereed)
    Abstract [en]

    Intermittent administration of parathyroid hormone (PTH) leads to bone formation by increasing osteoblast numbers and activity levels. Animal studies have shown that intermittent PTH administration increases implant fixation in normal rats. The purpose of this study was to analyze the osseous incorporation of an implant in osteoporotic rats while treating them with intermittent PTH (1-34) or alendronate.

    A total of 36 ovariectomized (OVX) Wistar rats were randomized into three groups. Polymethylmethacrylate cement rods were implanted in one tibia in each rat. The three groups received daily PTH (60 mu g/kg body weight [BW]), alendronate (200 mu g/kg BW), or saline (0.5 ml/kg BW). A sham-ovariectomized group (n = 12) was treated with saline. After 2 weeks, the area around the implants was analyzed by histomorphometry for bone volume density (BVD) and implant bone contact. Bone mineral density (BMD) was evaluated by dual-energy X-ray absorptiometry.

    The BVD was higher in the specimens treated with PTH than in the other groups. PTH improved the BVD, BMD, and implant bone contact. Alendronate doubled the implant bone contact compared to the OVX and sham groups but did not improve BVD or BMD.

    These findings confirm that intermittent PTH enhances implant fixation in osteoporotic bone. The clinical significance of these findings is that application of intermittent PTH may be beneficial for early implant fixation in fractures, nonunions, and prosthetic replacements when bone density is decreased.

  • 181. Skripitz, Ralf
    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.
    Early effect of parathyroid hormone (1-34) on implant fixation2001In: Clinical Orthopaedics and Related Research, ISSN 0009-921X, E-ISSN 1528-1132, no 392, p. 427-432Article in journal (Refereed)
    Abstract [en]

    Intermittent systemic administration of parathyroid hormone increases bone formation by stimulating osteoblastic activity. The current study determined how parathyroid hormone (1-34) administration influences the bony fixation of stainless steel screws with time. A screw was implanted in the left tibia and a metal rod was implanted in the right tibia in 30 adult male rats that then were injected three times a week with human parathyroid hormone (1-34) at 60 ╡g/kg/injection (n = 15) or saline (n = 15). The animals were euthanized after 1, 2, or 4 weeks of treatment. Eight additional rats received only the screw and were euthanized immediately after implantation. No significant effects of parathyroid hormone on body weight change or ash weight of the femurs were seen. The degree of fixation was assessed by measuring pullout strength of the screws. The mean pullout strength immediately after implantation was 12 N. The pullout strength of the group injected with saline was 33 N after 1 week, 23 N after 2 weeks, and 41 N after 4 weeks. The pullout strength of the group injected with parathyroid hormone increased to 43 N after 1 week, 58 N after 2 weeks, and 100 N after 4 weeks. The increase at 2 and 4 weeks was statistically significant. Strength reflects the mechanical properties of the bone within the screw threads. The contralateral tibia with its metal rod was used for blinded histologic assessment. Parathyroid hormone increased the fraction of the metal surface having contract with bone without an intervening soft tissue layer from 45% to 69% after 1 week. The current results suggest that intermittent parathyroid hormone treatment can enhance early implant fixation by enhancing the density of the surrounding bone and by increasing the implant bone contact.

  • 182. Skripitz, Ralf
    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.
    Parathyroid hormone - A drug for orthopedic surgery?2004In: Acta Orthopaedica Scandinavica, ISSN 0001-6470, Vol. 75, no 6, p. 654-662Article in journal (Refereed)
    Abstract [en]

    Whereas continuous exposure to PTH results in bone resorption, administration at intermittent doses results in bone formation by increasing osteoblast number and activity. The anabolic action of PTH has also been demonstrated in clinical trials, in which PTH increased the bone mass and reduced fracture rate in patients with osteoporosis. In animal models of fracture healing and fixation of orthopedic implants, PTH increases the bone density in a dose-dependent manner, leading to faster repair and better fixation. The effect appears to be stronger on the new forming bone than on pre-existing bone. Based on these preclinical studies, we suggest that intermittent PTH treatment may also benefit fracture healing and implant fixation in patients.

  • 183. Skripitz, Ralf
    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.
    Parathyroid hormone (1-34) increases attachment of PMMA cement to bone2001In: Journal of Orthopaedic Science, ISSN 0949-2658, E-ISSN 1436-2023, Vol. 6, no 6, p. 540-544Article in journal (Refereed)
    Abstract [en]

    The attachment of an implant material to bone is related to the surface of the implanted material and the ability of the bone to form around the implant. Intermittent parathyroid (PTH) administration increases bone formation by stimulating osteoblastic activity. Little is known about the effect of PTH administration on orthopedic implant incorporation. The present study determined how PTH (1-34) administration influenced bone bonding, i.e., the bone-cement interfacial tensile strength, of vacuum-mixed polymethylmethacrylate (PMMA) bone cement (surface roughness, Ra, 4.8╡m). Bone bonding was evaluated by a detachment test. We used unloaded cement surfaces, which could be detached from the bone. Titanium plates were developed such that a cement fill was contained within a plate that was contained within a titanium holder. Thus. a flat cement surface came into contact with traumatized bone only, and the rest of the plate had no contact with tissue. After implantation of the plate in the left tibia, 20 adult male rats were injected daily with human PTH (1-34) at 60╡g/kg per injection (n = 10) or vehicle (n = 10), the animals were killed after 4 weeks. The plates were detached from the bone by a perpendicular force. PTH treatment increased the median pull-away strength (0.21MPa), compared with that in the vehicle-treated rats, (0.04MPa) (P = 0.02). The results suggest that PTH treatment may have the potential to enhance the incorporation of cemented orthopedic implants.

  • 184.
    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.

  • 185.
    Tengvall, Pentti
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics . Linköping University, The Institute of Technology.
    Skoglund, Björn
    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.
    Askendal, Agneta
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    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.
    Surface Immobilized Bisphosphonate Improves Stainless-Steel Screw Fixation in Rats2004In: Biomaterials, ISSN 0142-9612, Vol. 25, no 11, p. 2133-2138Article in journal (Refereed)
    Abstract [en]

    An increase in the mechanical fixation in bone of metallic biomaterials is considered advantageous in joint replacement and fracture surgery. Different approaches to improve fixation may be e.g. surface roughening, Ca-mineral coating or surface immobilization of growth factors or drugs. In the present work, bisphosphonate, a class of drugs that inhibit bone resorption, was immobilized onto stainless-steel screws.

    The screws were first roughened and coated with immobilized and cross-linked fibrinogen. Subsequently, an N-bisphosphonate, pamidronate, was immobilized onto fibrinogen, and another N-bisphosphonate, ibandronate, adsorbed on top of this. The so coated screws were inserted into the tibiae of eight male Sprague-Dawley rats. Another eight rats received screws prepared in the same way, but without the bisphosphonate coating. Pullout strength tests were performed after 2 weeks of implantation.

    The results showed a 28% (p=0.0009) higher pullout force and 90% increased pullout energy for the bisphosphonate coated screws, and support the idea that surface immobilized bisphosphonates can be used to improve biomaterials fixation in bone.

  • 186.
    Toksvig-Larsen, Soren
    et al.
    Department of Orthopedics, Hässleholm Hospital, Hässleholm, and Department of Orthopedics, Clinical Sciences, Lund University , Lund.
    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.
    Bisphosphonate-coated external fixation pins appear similar to hydroxyapatite-coated pins in the tibial metaphysis and to uncoated pins in the shaft: a randomized trial2013In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 84, no 3, p. 314-318Article in journal (Refereed)
    Abstract [en]

    Background and purpose External fixation pins tend to loosen with time, especially from cancellous bone. A coating that releases a bisphosphonate has been shown to improve the fixation of dental implants in humans. We now tested a bisphosphonate coating on steel pins for external fixation. The primary hypothesis was that coated pins would be better fixed in the diaphysis.

    Methods 20 patients with medial knee osteoarthritis underwent proximal tibial correction osteotomy with hemicallotasis. They received a pair of pins (Orthofix) in the tibial shaft, one bisphosphonate-coated and one uncoated. Another pair of pins was inserted in the metaphysis, near the joint. This pair was a bisphosphonate-coated pin and an HA-coated pin. All pins were inserted according to a random list. The pins were removed after the osteotomy had healed (8–15 weeks), and extraction torque served as the predetermined main outcome variable.

    Results No pins showed clinical signs of loosening. Removal torque for the shaft pins was 6.6 Nm (SD 2.2) for the bisphosphonate and 6.0 Nm (SD 2.5) for the uncoated (difference = 0.5, 95% CI: –0.03 to 1.3). Removal torque for the metaphyseal pins was 4.4 Nm (SD 1.3) for the bisphosphonate-coated and 4.2 Nm (SD 1.6) for the HA-coated (difference = 0.2, 95% CI: –0.5 to 1.0).

    Interpretation We could not show any improved cortical fixation, but the metaphyseal findings are striking. In a previous study on 19 patients with a similar layout, HA-coated and uncoated pins were compared. In the metaphysis, all 19 uncoated pins loosened before removal. It was concluded that uncoated pins could not be used in the metaphyseal region. The present results suggest that a bisphosphonate coating enables metaphyseal fixation similar to that of hydroxyapatite coatings, with no difference from uncoated pins in cortical bone.

  • 187. Tägil, Magnus
    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.
    Åstrand, Jörgen
    Systemic zoledronate precoating of a bone graft reduces bone resorption during remodeling2006In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 77, no 1, p. 23-26Article in journal (Refereed)
    Abstract [en]

    Background: Cartilage degeneration often occurs after osteosynthesis of a devascularized intermediary fragment in a joint fracture, in mosaicplasty or in whole-joint toe-to-finger transplantation. Hypothetically, the degeneration is secondary to a collapse of the transferred subchondral bone as it remodels during high mechanical load. Bisphosphonates are used to reduce resorption of necrotic bone. We tested a systemic pretreatment before harvesting the graft in order to protect the bone and cartilage against collapse and secondary arthrosis. Methods: Rats were given one zoledronate injection and bone grafts were harvested. The grafts were frozen, thawed and placed into bone chambers, and implanted into another batch of rats. Graft resorption and new bone formation was measured by histomorphometric analysis and compared with untreated grafts. Results: In the remodeled area of the controls, the graft was almost totally resorbed and replaced by bone marrow. In the zoledronate-treated specimens, the graft remained and the graft trabeculas were lined with new bone. By histomorphometry, the total amount of bone (graft plus new bone) within the remodeled area was 16% in the zoledronate-treated grafts and 5% in the controls (p = 0.003). Interpretation: A bone graft can be pretreated with bisphosphonate and remain protected against resorption once implanted again. Copyright© Taylor & Francis 2006. all rights reserved.

  • 188. Tägil, Magnus
    et al.
    Jeppsson, Charlotte
    Wang, Jian-Sheng
    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.
    No augmentation of morselized and impacted bone graft by OP-1 in a weight-bearing model2003In: Acta Orthopaedica Scandinavica, ISSN 0001-6470, Vol. 74, no 6, p. 742-748Article in journal (Refereed)
    Abstract [en]

    Introduction: Impacted morselized bone allograft is thought to be remodeled to a great extent We have previously shown that load-bearing increases the remodeling of impacted morselized bone allografts in a rabbit knee prosthesis model. Bone Morphogenic Proteins (BMPs) also stimulate bone formation and bone allograft remodeling. In this study, our aim was to determine whether it was possible to increase further the remodeling of impacted morselized bone allografts by combining load-bearing with a BMP. Experiment: A solution of Osteogenic Protein-1 (OP-1, also called BMP-7) was added to freeze-dried bone allograft chips before impaction grafting in our rabbit knee prosthesis model. 23 skeletally mature rabbits received an uncemented tibial knee prosthetic component inserted into a bed of impacted morselized bone allograft. 12 rabbits were given OP-1-treated allograft (50 ╡g OP-1 per gram allograft), and 11 rabbits vehicle-treated allograft. Each rabbit received mean 0.53 g graft. The rabbits were killed after 3 or 6 weeks and the grafted region was examined by histomorphometric assessment of the volume fraction of newly formed bone and remaining graft Results and interpretation: We found that OP-1 did not increase the bone density (graft plus new bone) to any substantial extent. However, we can not exclude that this might be due to a carrier problem, since the OP-1 was added as a solution directly to the dry graft.

  • 189. Tägil, Magnus
    et al.
    Åstrand, Jörgen
    Westman, Lars
    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.
    Alendronate prevents collapse in mechanically loaded osteochondral grafts: A bone chamber study in rats2004In: Acta Orthopaedica Scandinavica, ISSN 0001-6470, Vol. 75, no 6, p. 756-761Article in journal (Refereed)
    Abstract [en]

    Background: Subchondral bone necrosis is important in osteonecrosis, Mb Kienboeck, intraarticular fractures or osteochondral grafting. As revascularization follows, bone resorption may lead to collapse in load bearing areas during the remodeling. Bisphosphonates are potent osteoclast inhibitors. Our hypothesis was that local bisphosphonate treatment of an osteochondral graft, in a high load environment, would protect the subchondral bone from collapse and maintain the joint architecture during remodeling. To investigate this, we used a rat bone chamber model to subject a necrotic osteochondral graft to a large mechanical load during remodeling. Method: Cylindrical osteochondral grafts were taken from the patellar groove of rats, one end of the cylinder being the joint surface. The grafts were frozen, thawed and treated with alendronate. The length of the cylinder was measured and the grafts were placed in the chambers, which were inserted into the proximal tibia of rats. The chambers were left to heal in for two weeks to allow establishment of a vascular supply, and then the transplanted osteochondral plugs were mechanically loaded for 4 weeks, once a day with 10 cycles of 2 MPa pressure at 0.16 Hz. Results: At harvest, the graft length had decreased during remodeling in 5 of the 6 untreated controls, but only in 2 out of 8 alendronate-treated rats (p = 0.05). Histologically, the bone graft in the non-treated controls was resorbed in the remodeled part of the graft, whereas in the alendronate-treated rats a dense trabecular bone was found consisting of both new bone and graft. Interpretation: Local treatment of the graft with bisphosphonate diminishes the risk of collapse during revascularization and bone remodeling in a mechanically loaded osteochondral graft. This could be useful in a variety of situations when bone remodeling occurs after a necrosis close to a joint, either spontaneously after osteonecrosis or a fracture, or after surgical procedures such as mosaic-plasty or other osteochondral grafting.

  • 190.
    van der Donk, S
    et al.
    Univ Nijmegen, Med Ctr, Dept Orthoped, Orthoped Res Lab, NL-6500 HB Nijmegen, Netherlands Univ Lund Hosp, Dept Orthoped, S-22185 Lund, Sweden Linkoping Univ Hosp, Dept Orthoped, S-58185 Linkoping, Sweden.
    Buma, P
    Univ Nijmegen, Med Ctr, Dept Orthoped, Orthoped Res Lab, NL-6500 HB Nijmegen, Netherlands Univ Lund Hosp, Dept Orthoped, S-22185 Lund, Sweden Linkoping Univ Hosp, Dept Orthoped, S-58185 Linkoping, 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.
    Schreurs, BW
    Univ Nijmegen, Med Ctr, Dept Orthoped, Orthoped Res Lab, NL-6500 HB Nijmegen, Netherlands Univ Lund Hosp, Dept Orthoped, S-22185 Lund, Sweden Linkoping Univ Hosp, Dept Orthoped, S-58185 Linkoping, Sweden.
    Similarity of bone ingrowth in rats and goats: A bone chamber study2001In: Laboratory animal science (Chicago), ISSN 0023-6764, Vol. 51, no 4, p. 336-340Article in journal (Refereed)
    Abstract [en]

    Bone ingrowth has been studied extensively in rats by use of bone chambers. However, it is not known whether results in small animals, with respect to bone ingrowth processes, are similar in large animals, in which more realistic models are often used. Since the metabolic rate in small animals is, in general, higher than that in larger species, we hypothesized that bone ingrowth in chambers develops more rapidly in small animals. Therefore, identical bone chambers were placed in the tibias of rats and goats. After 6 and 12 weeks, histologic and histomorphometric examinations were carried out to measure bone and tissue ingrowth distances. Bone ingrowth was higher in both species at 12, compared with 6 weeks (P < 0.01). Tissue ingrowth in general (including soft tissue) was less in rats than in goats at both time periods (P < 0.001). However, bone ingrowth did not differ between species. Thus, when differences in size of an osseous defect are corrected for, there seems to be only little influence of differences in body size.

  • 191. van der Donk, S
    et al.
    Weernink, T
    Buma, P
    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.
    Slooff, TJJH
    Schreurs, BW
    Rinsing morselized allografts improves bone and tissue ingrowth2003In: Clinical Orthopaedics and Related Research, ISSN 0009-921X, E-ISSN 1528-1132, no 408, p. 302-310Article in journal (Refereed)
    Abstract [en]

    Bone defects in revision hip surgery can be reconstructed with impacted morselized bone grafts. Rinsing these trabecular allografts may enhance graft incorporation by washing out immunogenic factors present in blood, marrow, and fat. However, it has been proposed that impaction of the graft releases biologically active factors, which can provide sufficient activity to stimulate new bone formation. Rinsing before impaction could enhance bone allograft incorporation, but rinsing after impaction could diminish the incorporation process of impacted bone graft. To study the effect of rinsing and impaction of morselized bone grafts on bone ingrowth, a bone chamber study was done in goats. Autografts and allografts were divided into three treatment groups: (A) impacted, (B) rinsed and impacted, and (C) rinsed, impacted, rinsed, and impacted again. Ten goats received three bone chambers in each proximal tibia. The chambers were filled with either allograft or autograft, yielding six different implants per goat. After 6 weeks, histologic analyses were done and bone and tissue ingrowth were measured. New bone and total tissue ingrowth were higher in autografts than in allografts, especially in the non-rinsed group. With rinsing, total tissue ingrowth increased in the allograft group to approach that of autografts. Rinsing after impaction did not additionally alter bone ingrowth. The current findings show that incorporation of allografts can be improved by rinsing the grafts before impaction.

  • 192.
    Virchenko, Olena
    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.
    How can one platelet injection after tendon injury lead to a stronger tendon after 4 weeks?: Interplay between early regeneration and mechanical stimulation2006In: Acta Orthopaedica, ISSN 1745-3674, Vol. 77, no 5, p. 806-812Article in journal (Refereed)
    Abstract [en]

    Background Mechanical stimulation improves the repair of ruptured tendons. Injection of a platelet concentrate (platelet-rich plasma, PRP) can also improve repair in several animal models. In a rat Achilles tendon transection model, 1 postoperative injection resulted in increased strength after 4 weeks. Considering the short half-lives of factors released by platelets, this very late effect calls for an explanation.

    Methods We studied the effects of platelets on Achilles tendon regenerates in rats 3, 5 and 14 days after transection. The tendons were either unloaded by Botulinum toxin A (Botox) injections into the calf muscles, or mechanically stimulated in activity cages. No Botox injections and ordinary cages, respectively, served as controls. Repair was evaluated by tensile testing.

    Results At 14 days, unloading (with Botox) abolished any effect of the platelets and reduced the mechanical properties of the repair tissue to less than half of normal. Thus, some mechanical stimulation is a prerequisite for the effect of platelets at 14 days. Without Botox, both activity and platelets increased repair independently of each other. However, at 3 and 5 days, platelets improved the mechanical properties in Botox-treated rats.

    Interpretation Platelets influence only the early phases of regeneration, but this allows mechanical stimulation to start driving neo-tendon development at an earlier time point, which kept it constantly ahead of the controls.

  • 193.
    Virchenko, Olena
    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.
    Fahlgren, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine.
    Rundgren, Mats
    Department of Physiology and Pharmacology Karolinska Institutet, Stockholm.
    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.
    Early Achilles tendon healing in sheep2008In: Archives of Orthopaedic and Trauma Surgery, ISSN 0936-8051, E-ISSN 1434-3916, Vol. 128, no 9, p. 1001-1006Article in journal (Refereed)
    Abstract [en]

    Introduction: The biomechanics of early tendon healing is important for designing post-injury training, but this has not been described in an animal model, similar to humans in size. We measured elastic and viscoelastic properties of a tendon regenerate in sheep, in a study designed to see the effects of exogenously applying the growth and differentiation factor CDMP-2. This is the first description of early tendon healing in sheep Achilles tendons. Materials and methods: Twenty female sheep underwent Achilles tendon transection without suturing or immobilization. Two hours after the operation, 100 μg of CDMP-2 or placebo was injected into the hematoma. The sheep were slaughtered after 3 weeks, and tendon regenerates tested for viscoelastic properties by cyclical loading, before a destructive tensile test. Thereafter, all specimens were examined by high resolution computerized tomography (CT), and histology. Results: The tendon regenerate formed a sleeve, around the tendon stumps. Failure occurred between the regenerate sleeve and the tendon stumps. There was an unexpectedly large variation in force at failure. In the CDMP-2 group, force correlated with regenerate transverse area, but not in the controls. Thus, the variation in maximum stress was smaller in the CDMP-2 group (P = 0.009). Although the force at failure was only a tenth of normal, the capacity to store elastic energy was already near normal (hysteresis 16%). The mean transverse area, force at failure and stiffness were all about 30% larger in the CDMP-2 group, but this was not significant. There were no signs of bone or cartilage formation on CT or histology. Conclusions: Results are compatible with a positive effect of CDMP-2, but the power was too low to demonstrate any such effect. Considering that spontaneous ruptures in humans are likely to have a more variable geometry than in this model, humans can also be expected to vary a lot in early mechanical characteristics. This emphasizes the importance of individualized rehabilitation programs. The low hysteresis suggests that the energy storing capacity is rather easy for the tissues to develop, possibly it is harder to create appropriate energy dissipation, in order to avoid re-rupture. © Springer-Verlag 2008.

  • 194.
    Virchenko, Olena
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences.
    Grenegård, Magnus
    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.
    Independent and additive stimulation of tendon repair by thrombin and platelets2006In: Acta Orthopaedica, ISSN 1745-3674, Vol. 77, no 6, p. 960-966Article in journal (Refereed)
    Abstract [en]

    Background Platelet concentrate application with added thrombin improves Achilles tendon repair in the rat. Upon tissue injury, platelets are activated by thrombin, which has many biological properties in common with growth factors. We wanted to differentiate the effect of platelets from that of thrombin.

    Methods The Achilles tendon was transected in 50 rats. Platelet gel was prepared from the blood of 10 other rats. The rats were given either platelet gel with active or neutralized thrombin implanted into the defect during the operation, or a local injection 6h postoperatively with 50 μL of either platelet concentrate, thrombin or saline. The rats were killed after 14 days and the tendons were mechanically tested.

    Results Compared to saline, platelet gel caused a 42% increase in force at failure, a 90% increase in energy, and a 61% increase in ultimate stress. Platelet gel with neutralized thrombin caused a 22% increase in force at failure, and energy and stress were less elevated. Injected platelet concentrate caused a 24% increase in force at failure, and thrombin caused a 10% increase. These effects and the differences between treatments were statistically significant.

    Interpretation Platelets and thrombin had independent and additive stimulatory effects on tendon repair. The clinical relevance is so far unknown.

  • 195.
    Virchenko, Olena
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. 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.
    Low Molecular Weight Heparin impairs tendon repair2008In: Journal of Bone and Joint Surgery, ISSN 0301-620X, E-ISSN 2044-5377, Vol. 90-B, no 3, p. 388-392Article in journal (Refereed)
    Abstract [en]

    Thrombin has many biological properties similar to those of growth factors. In a previous study, we showed that thrombin improves healing of the rat tendo Achillis. Low molecular weight heparin (LMWH) inhibits the activity and the generation of thrombin. We therefore considered that LMWH at a thromboprophylactic dose might inhibit tendon repair.

    Transection of the tendo Achillis was carried out in 86 rats and the healing tested mechanically. Low molecular weight heparin (dalateparin) was either injected a few minutes before the operation and then given continuously with an osmotic mini pump for seven days, or given as one injection before the operation. In another experiment ,we gave LMWH or a placebo by injection twice daily. The anti-factor Xa activity was analysed.

    Continuous treatment with LMWH impaired tendon healing. After seven days, this treatment caused a 33% reduction in force at failure, a 20% reduction in stiffness and a 67% reduction in energy uptake. However, if injected twice daily, LMWH had no effect on tendon healing. Anti-factor Xa activity was increased by LMWH treatment, but was normal between intermittent injections.

    Low molecular weight heparin delays tendon repair if given continuously, but not if injected intermittently, probably because the anti-factor Xa activity between injections returns to normal, allowing sufficient thrombin stimulation for repair. These findings indicate the need for caution in the assessment of long-acting thrombin and factor Xa inhibitors.

  • 196.
    Virchenko, Olena
    et al.
    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.
    Skoglund, Björn
    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.
    Parecoxib impairs early tendon repair but improves later remodeling2004In: American Journal of Sports Medicine, ISSN 0363-5465, E-ISSN 1552-3365, Vol. 32, no 7, p. 1743-1747Article in journal (Refereed)
    Abstract [en]

    Background: Cyclooxygenase-2 inhibitors inhibit bone repair. Hypothesis: Cyclooxygenase inhibitors might also have a negative effect on early tendon repair, although a positive effect on late tendon repair previously has been shown. Study Design: Controlled laboratory study. Methods: Achilles tendon transection was performed on 80 rats. Sixty rats were given daily intramuscular injections of either parecoxib (6.4 mg/kg body weight) or saline for the first 5 days after surgery and sacrificed either at 8 or 14 days. The remaining 20 rats were given intramuscular parecoxib or saline injections from day 6 until sacrifice at 14 days. Results: At 8 days, early parecoxib treatment caused a 27% decrease in force at failure (P = .007), a 25% decrease in maximum stress (P = .01), and a 31 % decrease in energy uptake (P = .05). Stiffness and transverse area were not significantly affected. At 14 days, early parecoxib treatment caused a decrease in stiffness (P = .004). In contrast to early treatment, late parecoxib treatment caused a 16% decrease in cross-sectional area (P = .03) and a 29% increase in maximum stress (P = .04). Conclusions: During early tendon repair, a cyclooxygenase-2 inhibitor had a detrimental effect. During remodelling, however, inflammation appears to have a negative influence, and cyclooxygenase-2 inhibitors might be of value. Clinical Relevance: The results suggest that cyclooxygenase-2 inhibitors should be used with care in the early period after tendon injury.

  • 197.
    Virchenko, Olena
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences.
    Skoglund, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences.
    Fahlgren, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences.
    CDMP-2 injection improves early tendon healing in a rabbit model for surgical repair2005In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, Vol. 15, no 4, p. 260-264Article in journal (Refereed)
    Abstract [en]

    This study examines the hypothesis that cartilage-derived morphogenic protein-2 (CDMP-2) can improve tendon healing after surgical repair. We have previously found improved tendon healing by applying CDMP-2 in models for conservative treatment with mechanically loaded Achilles tendon defects in rats and rabbits. In this study, the patellar tendon was unloaded by patello- tibial cerclage and cut transversely in 40 rabbits. Two hours post-operative, the rabbits received a dose of 20 μg of CDMP-2 or vehicle injected into the hematoma. Specimens were harvested after 14 and 28 days and evaluated by biomechanical testing, radiography and histology. At 14 days, CDMP-2 caused a 65% increase in force at failure, a 50% increase in ultimate stress and a 57% increase in stiffness, as compared with controls. There was no effect on callus size. At 28 days, no differences between the treatment groups could be demonstrated. No bone or cartilage was found in any tendon or regenerated tissue at any time point. Thus, early tendon repair can be stimulated by CDMP-2 in an unloaded model. These results suggest that CDMP-2 might be of interest for clinical use as a complement to surgical treatment of tendon ruptures.

  • 198.
    Wermelin, Karin
    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.
    Linderbäck Stenfors, Paula
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Tengvall, Pentti
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Bisphosphonate coating on titanium screws increases mechanical fixation in rat tibia after two weeks2008In: Journal of Biomedical Materials Research. Part A, ISSN 1549-3296, E-ISSN 1552-4965, Vol. 86A, no 1, p. 220-227Article in journal (Refereed)
    Abstract [en]

    Recently published data indicate that immobilized N-bisphosphonate enhances the pullout force and energy uptake of implanted stainless steel screws at 2 weeks in rat tibia. This study compares titanium screws with and without a bisphosphonate coating in the same animal model. The screws were first coated with an 100-nm thick crosslinked fibrinogen film. Pamidronate was subsequently immobilized into this film via EDC/NHS-activated carboxyl groups within the fibrinogen matrix, and finally another N-bisphosphonate, ibandronate, was physically adsorbed. The release kinetics of immobilized 14C-alendronate was measured in buffer up to 724 h and showed a 60% release within 8 h. Mechanical tests demonstrated a 32% (p = 0.04) and 48% (p = 0.02) larger pullout force and energy until failure after 2 weeks of implantation, compared to uncoated titanium screws. A control study with physically adsorbed pamidronate showed no effect on mechanical fixation, probably due to a too small adsorbed amount. We conclude that the fixation of titanium implants in bone can be improved by fibrinogen matrix-bound bisphosphonates.

  • 199.
    Wermelin, Karin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences.
    Suska, F.
    Department of Biomaterials, Inst. of Surgical Sciences, Sahlgrenska Academy at Göteborg University, Box 412, SE-405 30 Göteborg, Sweden.
    Tengvall, Pentti
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics . Linköping University, The Institute of Technology.
    Thomsen, P.
    Department of Biomaterials, Inst. of Surgical Sciences, Sahlgrenska Academy at Göteborg University, Box 412, SE-405 30 Göteborg, 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.
    Stainless steel screws coated with bisphosphonates gave stronger fixation and more surrounding bone. Histomorphometry in rats2008In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 42, no 2, p. 365-371Article in journal (Refereed)
    Abstract [en]

    Coating of stainless steel screws with bisphosphonate in a fibrinogen matrix leads to an enhancement of the pullout strength 2 weeks after insertion in rat tibiae. This effect then increases over time until at least 8 weeks. The pullout force reflects the mechanical properties of the bone within the threads, which acts as a screw nut. The aim of the present study was to find descriptive and morphometric histological correlates to the increased pullout strength. Because the bisphosphonates are applied via the implant surface, we also measured bone to implant contact and how far away from the surface any effects could be seen.

    Stainless steel screws underwent one of three treatments: uncoated control, controls coated with a layer of cross-linked fibrinogen, or screws further modified with bisphosphonates covalently linked and physically adsorbed to the fibrinogen layer. At 1 (n = 33) and 8 (n = 27) weeks, bone to implant contact and bone area density in the threads were measured, as well as bone area density at 250 and 500 μm from the outer edge of the threads. Additionally, removal torque for each screw treatment was measured at 2 weeks (n = 28).

    At 8 weeks, the part of the bisphosphonate screw that was located in the marrow cavity had become surrounded with bone, whereas there was almost no bone surrounding the controls. The bone area density in the threads along the entire bisphosphonate screw was increased by 40% compared with uncoated controls, and at 250 μm distance it was more than doubled. At 1 week, coated screws had less implant–bone contact, but at 8 weeks there was no difference between uncoated and bisphosphonate-coated screws. The bisphosphonate screws had 50% increased removal torque at 2 weeks compared to uncoated screws. Howship's lacunae and osteoclasts were found near the screws with bisphosphonates at 8 weeks, suggesting that some bone remodeling took place near the implant, in spite of the presence of bisphosphonates.

  • 200.
    Wermelin, Karin
    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.
    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 bisphosphonate coating improves the bony fixation of stainless steel screws in ovariectomized rats2008Article in journal (Refereed)
    Abstract [en]

    Background: Bisphosphonate coatings improve the fixation of implants in bone. Stainless steels screws inserted in the rat tibia become encapsulated by new bone if they are coated with bisphosphonates in a crosslinked fibrinogen matrix. Thereby, the coating leads to a gradual increase in pull-out force. We now investigate if this bisphosphonate coating is capable to improve the mechanical fixation also in osteoporotic bone.

    Methods: Stainless steel screws were coated with a thin crosslinked fibrinogen matrix. With EDC/NHS coupling technique, pamidronate was bound to carboxylic groups and ibandronate was adsorbed in the fibrinogen matrix. Uncoated stainless steel screws and bisphosphonatecoated screws were inserted bilaterally in the proximal tibia in 10 ovariectomized and 10 sham operated rats. At 2 weeks pull-out force and energy was measured.

    Results: In the ovariectomized rats, pull-out force was 53 % higher for bisphosphonate coated screws compared to control screws. Energy was 44 % higher. The sham operated rats showed a higher variation, and no effect of the coating was found.

    Conclusion: The coating was sufficient to improve fixation in ovariectomized rats

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