| 1. |
- Bögl, Hans Peter, 1969-
(author)
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Atypical femoral fractures: Another brick in the wall : On aspects of healing, treatment strategies and surveillance
- 2021
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Doctoral thesis (other academic/artistic)abstract
- Atypical femoral fractures are stress fractures of the femoral subtrochanteric and diaphyseal region. It is a common notion that these fractures heal poorly, if at all. In this thesis we show that patients with atypical femoral fractures have a good capacity to generate bone and therefore heal fractures. In daily practice, these patients have a higher risk for reoperation when compared with patients with a normal femoral fracture. However, this risk is less likely to be dependent on the type of fracture than other factors such as age, gender, comorbidities and survival. Using an implant that protects the fragile proximal femur, the risk for reoperations can be attenuated dramatically. An intramedullary nail with fixation of the femoral neck protects the femur from subsequent hip fractures – the most common complication in elderly patients with any type of femoral shaft fracture.Atypical femoral fractures are difficult to identify in the population. Erroneous diagnosis coding, poor reporting of adverse drug reactions and low accuracy of radiology reports make the identification and surveillance a difficult task. The Swedish Fracture Register has provided the option to register this special fracture since 2015. With its physician-based registration process, it enables researchers and treating physicians to identify and follow these rare fractures longitudinally.
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| 2. |
- Bratengeier, Cornelia, 1983-
(author)
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Mechanisms of mechanically induced Osteoclastogenesis : in a novel in vitro model for bone implant loosening
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Total joint arthroplasty is the primary intervention in the treatment of end-stage osteoarthritis. Despite the high success rate, in some patients, the replacement will fail during their lifetime requiring a revision of the implant. These revisions are strenuous for the patient and costly for health care. Joint replacement at a younger age, in combination with a more active lifestyle, increases the need for an early revision of the joint prosthesis. The main reason for revision surgeries is aseptic loosening, a condition where the prosthesis is loosening due to bone degradation at the peri-prosthetic interface in the absence of infections. The most well-established pathological mechanism for aseptic loosening is related to wear particles, generated from different parts of the prosthesis that will trigger bone degradation and bone loss. In addition, early micromotions of the prosthesis and resulting local pressurized fluid flow in the peri-prosthetic interface (supraphysiological loading) have also been identified as a cause for aseptic loosening. However, it remains unknown what cells are the primary responders to supraphysiological loading, and what underlying physical, cellular and molecular mechanism that triggers osteoclast differentiation and osteolysis.In this thesis, we intended to shed light on three currently unknown aspects of mechanical loading-induced peri-prosthetic osteolysis, leading to aseptic loosening of orthopedic prostheses: (1)Which cells are the primary responder to supraphysiological loading? (2)What characteristics of the mechanical stimulus induce an osteo-protective or osteo-destructive response? (3)Which cellular mechano-sensing mechanisms are involved in an osteo-destructive response?We successfully implemented supraphysiological mechanical loading, mimicking the periprosthetic pressurized fluid flow around a loosening implant, in an in vitro model for bone implant loosening. Using this model, we uncovered the involvement of mesenchymal stem cells and myeloid progenitor cells (monocytes) in mechanical loading-induced peri-prosthetic osteolysis. Applying supraphysiological loading on cells from patients undergoing primary hip arthroplasty, successfully validated the in vitro model for the use of cells of human origin. We further identified in murine myeloid progenitor cells that a combination of high loading amplitude (3.0±0.2Pa), prolonged active loading duration per cycle (duty cycle 22%-50%), and rapid alterations in minimum/maximum values of the loading profile (square wave) is necessary to induce an osteo-destructive response. Further, the loading-induced ATP release and subsequent activation of the P2X7 receptor was essential for the release of soluble factors modulating osteoclastogenesis.In conclusion, we expect that the proposed new in vitro model is a helpful tool to further advance the knowledge in aseptic loosening, by uncovering the mechanoresponsive cellular mechanism to supraphysiological mechanical loading. The identification of the respondent cells in mechanical loading-induced prosthetic loosening gives the opportunity to deliver targeted treatment strategies. Furthermore, identifying the physical parameters that define the shift towards an osteo-destructive response emphasizes the importance of the prosthetic design and surgical technique to reduce mechanical loading-induced bone degradation around a prosthesis.
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| 3. |
- Linderbäck, Paula, 1980-
(author)
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Improved titanium and steel implants : Studies on bisphosphonate, strontium and surface treatments
- 2011
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Doctoral thesis (other academic/artistic)abstract
- Purpose: The general aim of this thesis was to increase the understanding of biomaterial surface modifications and local delivery of osteoporosis drugs for bone integration. We therefore (i) characterised and investigated model surface coatings for controlled drug delivery in a rat tibia screw model (ii) elucidated the effect of surface treatment for activation of complement system in vitro.Materials and methods: Bisphosphonate was immobilised directly to implant surfaces by two methods. In the first method, bisphosphonate was bound via a crosslinked fibrinogen layer to titanium surfaces. In the second method, stainless steel screws were first dip coated in a TiO2 solgel, and thereafter incubated in simulated body fluid (SBF). The so prepared thin calcium phosphate layer on titania bound then bisphosphonate directly with high affinity. The drug release kinetics was determined in vitro by 14C marked alendronate that was quantified with scintillation techniques. The screws were inserted in the metaphysis of rat tibia and the mechanical fixation monitored by screw pullout measurements after 2 or 4 weeks of implantation. In order to compare two different osteoporosis drugs, bisphosphonate and strontium ranelate, stainless steel and PMMA screws were inserted in the tibial metaphysis of rat for 4 and 8 weeks. Bisphosphonate was then delivered subcutaneously and strontium ranelate orally during the whole implantation period. The mechanical fixation was analysed by pullout force measurements, and bone architecture studied by micro-computed tomography (μCT). The immune complement activation on sol-gel- and smooth titanium surfaces was analysed in human blood plasma before and after annealing of titanium at 100-500ºC or upon UVO-treatment for up to 96 hours.Results: Bisphosphonate coated screws enhanced the screw pull out force after 2 weeks of implantation by more than 30% (fibrinogen coating) and by 93% after 4 weeks (sol-gel derived TiO2 coating). Systemically administered bisphosphonate enhanced the mechanical screw fixation after 4 weeks by more than 96% and after 8 weeks by more than 55% as compared to strontium ranelate treated animals (p = 0.00). Strontium ranelate treatment did not show significant improvement of screw pullout force after 4 and 8 weeks, compared to control. The immune complement surface deposition from blood plasma vanished irreversibly after Ti heat treatment at 250-300 ºC during 30 minutes or after UVO exposure for 24 hours or longer. Tentatively, changes in surface water/hydroxyl binding upon heat- and UVO treatments were observed by XPS and infrared spectroscopy.Conclusions: The results show that fixation at short implantation time (weeks) of orthopaedic implant can be enhanced by immobilised bisphosphonate on stainless steel or titanium implants. Systemic delivery of strontium ranelate showed no significant effect on implant fixation in rat tibia, and we hypothesise therefore that strontium ranelate will not become a power tool to increase the early implant fixation, but may be beneficial at longer times. Heat annealing or UVO-treatment of titanium surfaces change the surface hydroxylation, leading to decreased immune complement deposition from blood plasma.
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| 4. |
- Schilcher, Jörg, 1978-
(author)
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Epidemiology, Radiology and Histology of Atypical Femoral Fractures : Development of understanding
- 2013
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In: Acta Orthopaedica. - Linköping : Linköping University Electronic Press. - 1745-3674 .- 1745-3682. ; 84:S352, s. 1-26
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Doctoral thesis (other academic/artistic)abstract
- Bisphosphonates have been used successfully in the prevention of osteoporosis-related fractures for over two decades. Only recently an association between bisphosphonate use and femoral insufficiency fractures – atypical femoral fractures – has been found.Bone remodeling is necessary to maintain a healthy skeleton. With age this process can get out of balance and bone resorption can outweigh formation of new bone. This can lead to osteoporosis and fractures that occur after minor trauma. Almost half of all women 50 years of age or older will suffer an osteoporosis related fracture during their remaining life. Bisphosphonates inhibit bone resorption, and after some years of treatment an increase in bone mass can be noted. This increase in bone mass can reduce fracture risk by as much as half. However, bisphosphonate use seems associated with the development of femoral insufficiency fractures, so called atypical femoral fractures. This thesis aimed to estimate the risk of atypical femoral fractures in the population and its association with bisphosphonate use. It also describes the radiographic and histologic features of these fractures in order to improve our understanding of the pathophysiological background.Study 1) All women 55 years of age and older, who had sustained a femoral shaft fracture during 2008, were identified through the Swedish National Patient Register. Radiographs of 1234 women were reviewed, and 59 patients with atypical fractures and 263 control patients with common femoral shaft fractures were identified. Atypical femoral fractures were defined by their stress fracture-like appearance. In a cohort analysis, we estimated an age-adjusted relative risk of 47 for bisphosphonate users to suffer an atypical femoral fracture compared to non-users. A total of 78% of the patients with an atypical fracture and 10% of the controls had received bisphosphonates, corresponding to a multivariable-adjusted odds ratio of 33. The risk was independent of coexisting conditions and of concurrent use of other drugs with known effects on bone. These results indicate that bisphosphonate use is strongly associated with atypical femoral fractures. The absolute risk is low and benefits of treatment will outweigh the risks.Study 2) A transverse fracture line and a small but visible callus reaction are well established radiographic features of stress fractures. Radiographs from 59 atypical fracture patients and 218 control patients from Study 1 were re-reviewed to measure fracture angles and to detect callus reactions. The majority of the patients with a transverse fracture angle used bisphosphonates. Fracture angle and callus reaction had a high specificity to detect bisphosphonate treatment. When an oblique fracture line was chosen to define atypical femoral fractures in the cohort from Study 1, the association of atypical femoral fractures to bisphosphonate use became attenuated. Therefore, a correct case definition of atypical femoral fractures is necessary for adequate risk calculations.Study 3) Bone biopsies from 8 patients with atypical femoral fractures were obtained during surgical fixation. The histological analysis of the fracture site itself showed a thin fracture line running perpendicular to the long axis of the femur. Despite ongoing remodeling in the bone adjacent to the fracture gap, no healing occurred within the gap itself. Necrotic material in the gap suggests that strains within the gap might prohibit ingrowth of cells necessary for healing. This mechanism of inhibited healing might share similarities with that of stress fractures in athletes. Although it is highly likely that bisphosphonates play a causative role, the pathogenesis of these fractures is still unclear. It may involve a reduced capacity for targeted remodeling.
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| 5. |
- Wermelin, Karin, 1977-
(author)
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Surface bound bisphosphonate for implant fixation in bone
- 2008
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Doctoral thesis (other academic/artistic)abstract
- During the surgical preparation of bone, prior to insertion of an implant, bone will be traumatized which leads to local resorption. Consequently, early implant fixation might be reduced. Impaired early fixation, as evidenced by radiostereometry, has been associated with increased risk of late loosening. Bisphosphonates are known to inhibit bone resorption by osteoclasts and have shown to increase implant fixation when administered systemically or locally directly at the bone prior to implant insertion.A method to bind bisphosphonates directly to the implant was developed. Stainless steel screws were coated with crosslinked fibrinogen, serving as an anchor for bisphosphonate attachment. The screws were inserted in the tibial metaphysis in rats and implant fixation was analyzed with pullout measurements. Bisphosphonate coated screws turned out to have 28 % higher pullout force at 2 weeks compared to control screws with the fibrinogen coating only. The next experiment was designed to measure at what stage in the healing process the strongest bisphosphonate effect was gained. Bisphosphonate coated screws were expected to reduce the resorption of the traumatized bone. However, no decreased fixation was found in the control group. Instead, the fixation increased with time, and so did the effect of the bisphosphonates. At 8 weeks, the pullout force was twice as high for screws with bisphosphonate compared to control screws. By histology at 8 weeks, a bone envelope was found around bisphosphonate coated screws but absent around control screws. Thus, the anti catabolic action of the bisphosphonate resulted in an increased amount of bone surrounding the bisphosphonate screws.Titanium is generally considered to be better fixated in bone compared to stainless steel. The coating technique was found to be applicable on titanium as well, again with improved fixation.A majority of fractures occur in osteoporotic bone. Despite the relatively low amount of bisphosphonates at the screws, the bisphosphonate coating improved implant fixation at 2 weeks also in rats made osteoporotic by ovariectomy.In conclusion, bisphosphonates bound to titanium or stainless steel screws coated with fibrinogen increased fixation in bone, in rats. These results suggest that the bisphosphonate and fibrinogen coating might improve the fixation of screw shaped implants and possibly also arthroplasties, in humans.
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| 6. |
- Abtahi, Jahan, 1965-
(author)
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Bisphosphonates and implants in the jaw bone
- 2013
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Doctoral thesis (other academic/artistic)abstract
- Insertion of metal implants in bone is one of the commonest of all surgical procedures. The success of these operations is dependent on the fixation of the implants, which, in turn, depends on the strength of the bone that holds them. If the quality of the bone holding the implant could be improved locally, surgical procedures would become simpler and rehabilitation would become faster. Bisphosphonates are anti-resorptive drugs that act specifically on osteoclasts, thereby maintaining bone density and strength. Once released from the surface of a coated implant, bisphosphonates reduce osteoclast activity, thereby changing the balance of bone turnover in favor of bone formation, leading to a net gain in local bone density. During the last decades, the effects of bisphosphonate treatment on the stability of implants have been tested in several clinical and animal studies, but not in human jaws. This may be because it has been suggested that there is a link between the use of bisphosphonates (especially those given intravenously) and a condition called osteonecrosis of the jaw (ONJ). The pathophysiology and treatment of ONJ is controversial. The difficulty in treating ONJ has highlighted the importance of prevention.The overall aim of the present thesis was to evaluate the effect of local and systemic use of bisphosphonates on bone tissue. Could a thin, bisphosphonate-eluting fibrinogen coating improve the fixation of metal implants in the human jaw? Would it be possible to reproduce ONJ and prevent the development of this condition in an animal model?In two clinical studies, a total number of 96 implants were inserted in 21 patients. In a randomized trial with a paired design, one implant in each pair was coated with a thin fibrinogen layer containing two bisphosphonates (pamidronate and ibandronate). The bisphosphonate-coated implants showed better stability as measured by resonancefrequency analysis. Radiographic intraoral films also showed less bone loss. Three animal models were developed. In a study comparing local and systemic effects of bisphosphonates, zoledronate-coated screws inserted in rats showed better fixation in spite of a drug treatment that is known to induce ONJ-like lesions when given systemically. In another rat model, ONJ-like lesions were reproducibly induced at sites of tooth extraction whereas there were no signs of bone cell death in uninjured sites. Finally, rat experiments showed that the development of ONJ-like lesions after tooth extraction could be prevented by early mucoperiosteal coverage.In conclusion, a thin, bisphosphonate-eluting fibrinogen coating can improve the fixation of dental implants in human bone. This may lead to new possibilities in orthopaedic surgery and dentistry. The pathophysiology of ONJ is strongly linked to bone exposure in combination with drugs that reduce resorption.
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| 7. |
- Eliasson, Pernilla
(author)
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Response to mechanical loading in healing tendons
- 2011
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Doctoral thesis (other academic/artistic)abstract
- Ruptured tendons heal faster if they are exposed to mechanical loading. Loading creates deformation of the extracellular matrix and cells, which give rise to intracellular signalling, increased gene expression and protein synthesis. The effects of loading have been extensively studied in vitro, and in intact tendons in vivo. However, the response to loading in healing tendons is less known.The general aim of this thesis was to understand more about the response to mechanical loading during tendon healing. The specific aims were to find out how short daily loading episodes could influence tendon healing, and to understand more about genes involved in tendon healing.The studies were performed using rat models. Unloading of healing tendons resulted in a weaker callus tissue. This could be reversed to some extent by short daily loading episodes. Loading induced more matrix production, making the tendons thicker and stronger, but there was no improvement in the material properties of the matrix. Lengthening is one potential adversity with early loading, during tendon healing in patients. This was also seen with continuous loading in the rat models. However, short loading episodes did not result in any lengthening, not even when loading was applied during the inflammatory phase of healing. It also appeared as loading once daily was enough to make healing tendons stronger, while loading twice daily with 8 hours interval did not give any additional effect. The strongest gene expression response to one loading episode was seen after 3 hours. The gene expression changes persisted 12 hours after the loading episode but had disappeared by 24 hours. Loading appeared to regulate genes involved in inflammation, wound healing and coagulation, angiogenesis, and production of reactive oxygen species. Inflammation-associated genes were regulated both by continuous loading and by one short loading episode. Inflammation is an important part of the healing response, but too much can be harmful. Loading might therefore have a role in fine-tuning the inflammatory response during healing.In conclusion, these studies show that short daily loading episodes during early tendon healing could potentially be beneficial for rehabilitation. Loading might have a role in regulating the inflammatory response during healing.
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| 8. |
- Lindgren, Christer
(author)
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On healing of titanium implants in biphasic calcium phosphate
- 2012
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Doctoral thesis (other academic/artistic)abstract
- Background: Previously, autogenous bone was considered the gold standard for grafting procedures in implant surgery. Today, the use of bone graft substitutes is an alternative for sinus lift procedures. Nevertheless, only a few bone substitutes are well documented and can be recommended as an alternative to autogenous bone grafts. Both deproteinized bovine bone (DBB) and tricalcium phosphate (TCP) are materials that are frequently used and well documented. During the last years a novel biphasic calcium phosphate (BCP) has been introduced to the market. Until now only a few studies have been published.Aims: Studies I, II, III and IV. The overall aim of the present thesis was to evaluate a new biphasic calcium phosphate for bone augmentation of the maxillary sinus. Deproteinized bovine bone was used as a control.Study V. The aim of this in vitro study was to evaluate the response of human osteoblast-like cells (HOB) to nano-crystalline-diamond-particle-modified (nDP-modified) and un-modified (control) deproteinized bovine bone (DBB) and biphasic calcium phosphate (BCP) scaffolds.Materials and Methods: Studies I, II, III and IV. The studies were based on 11 patients (six women, five men) with a mean age of 67 years (range; 50 to 79 years). All patients showed severe maxillary resorption with less than 5mm of residual alveolar bone in the floor of the maxillary sinus, which excluded conventional implant treatment. Twenty-two maxillary sinuses were augmented with BCP on one side and with DBB acting as a control at the contralateral side. Simultaneously with the augmentation procedure 22 microimplants were placed inside the augmented materials. After 8 months of graft healing the microimplants and a surrounding bone core were retrieved for histomorphometrical analysis (Paper I) and for energy dispersive spectroscopy (Paper II). After retrieval of the microimplants, 62 conventional implants were placed and left to heal for 8 weeks before rehabilitation with fixed prosthetic constructions. The conventional implants were evaluated clinically at baseline, after 1- and 3 years of loading (Papers III and IV). After 3 years of graft healing 18 biopsies were harvested from 9 patients for histomorphometrical analysis (Paper IV).Computerized tomography (CT) of the maxillary sinuses was performed after 3 years of graft healing to allow examination of the recipient sites.Study V. Nano-crystalline-diamond particle-modification of DBB and BCP particles was carried out through different steps of preparation including grinding and ultrasonic techniques. Scanning electron microscopy (SEM) was carried out after 24 hours and 3 days. Real time-polymerase chain reaction (PCR) was carried out after 3 days, 1 week and 2 weeks of incubation. The following osteoblast differentiation markers were analyzed: alkaline phosphatase (ALP), osteocalcin (OC), bone morphogenetic protein type 2 (BMP-2) and integrin alpha 10 (ITGA 10).Results: In paper I, the results revealed a similar degree of bone formation and bone-to-implant contact around sandblasted and acid-etched microimplants placed in sinuses augmented with BCP or DBB. No obvious signs of resorption of the BCP and DBB particles were noticed. There was a significantly higher amount of DBB particles in contact with newly formed bone compared to BCP (p=.007).In paper II, the median Ca/P ratios (atomic %), determined from >200 discreet sites within residual graft particles and adjacent bone were analysed. The difference between the median values for BCP and DBB and for BCP-augmented bone compared with DBB-augmented bone were statistical significant (p=.028 in each case). The reduction in Ca/P ratio for BCP over the healing period is consistent with the dissolution of β-TCP and reprecipitation on the surface of calcium-deficient hydroxyapatite.In paper III, the results revealed that no implant placed in residual bone was lost, one implant placed in BCP was lost after 3 months of functional loading due to infection, and one implant placed in DBB was lost only a few weeks after insertion due to lack of initial instability. The overall implant survival rate was 96.8%. Success rates for implants placed in BCP and DBB were 91.7% and 95.7% respectively. No significant differences in marginal bone loss were found around implants placed in BCP, DBB or residual bone respectively.In paper IV, it was shown that after 36 months (range; 36 to 37 months) of functional loading the overall implant survival rate was 96.8%. Success rates for implants placed in BCP, DBB and residual bone were 91.7%, 95.7% and 86.7% respectively. No significant difference was found between implants placed in BCP, DBB and residual bone. The corresponding histological evaluation after 3 years of graft healing showed BCP particles under different levels of dissolution. Dissolution was mostly observed on the edges of the BCP particles but in some cases the entire particle was dissolving. In contrast, DBB particles showed no signs of resorption. The percentage of graft particles in contact with newly formed bone was not significantly different after 3 years of healing for BCP and DBB.In paper V, cellular responses were evaluated in terms of attachment and differentiation. SEM after 24 hours and 3 days of incubation disclosed similar cell attachment and spreading for nDP-modified and non-modified DBB and BCP particles. Real-time PCR revealed significant up-regulation of mRNA expression of ALP and OC and by HOB grown on nDP-modified DBB and BCP-particles after 1 and 2 weeks compared to non-modified particles. A significant down-regulation of BMP-2 on nDP-modified DBB and a significant up-regulation of BMP-2 on DP-modified BCP was disclosed for HOB in relation to un-modified particles. Cell adhesion marker ITGA 10 showed significant down-regulation in the mRNA level for both nDP-modified groups after 2 weeks of incubation (mDP-BCP (p<.01) and nDP-DBB (p<.05) compared to the non-modified materials.Conclusion: It is concluded that BCP can be used for maxillary floor augmentation and later placement of dental implants producing equal results to those for DBB. Nevertheless, the initial HA/β-TCP ratio in BCP might not be optimized for cell adhesion, which can affect the early healing phase. Furthermore, the results indicate that BCP is not optimized for gene expression in its present form and that nDP-modified BCP enhances the osteoblast phenotype suggesting that these scaffolds are appropriate cell carriers, superior to non-modified BCP particles. Surface modification of bone substitutes is a new interesting field in bone tissue engineering (BTE). Nevertheless, it´s still unclear if the modification will have any clinical impact.
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| 9. |
- Lundin, Anna-Carin
(author)
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Tendinosis in Trigger Finger
- 2017
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Doctoral thesis (other academic/artistic)abstract
- Trigger finger is one of the most common hand conditions, with a prevalence of almost 3%. The aetiology remains unclear even though many causes have been suggested. The prevailing paradigm is that the pathogenesis of trigger finger is ascribed to primary changes in the first fibrous condensation of the tendon sheath (A1-pulley). Several studies have investigated pathology in the pulley, but few have investigated the tendon. The general aim of this thesis was to find out if there is pathology in the trigger finger tendon and to define it.We first looked at trigger finger tendon biopsies in a light microscope, and found that they were histologically different from healthy tendons. They showed signs of micro-ruptures, collagen degradation, increased amounts of ground substance, both hyper- and hypo-cellular areas, round active cell nuclei and absence of inflammatory cells, all similar to tendinosis. The histological picture was further assessed by using a scoring system for Achilles tendinosis. The trigger finger tendons scored high, suggesting a similar histopathology.Next, we performed a quantitative real-time polymerase chain reaction (qPCR) on trigger finger tendons. We assessed the mRNA expression of 10 genes, which have been described to be differently expressed in Achilles tendinosis (collagen 1 and 3, versican, decorin, biglycan, aggrecan, MMP-2, MMP-3, ADAMTS-5, and TIMP-3). The overall expression pattern agreed with previous studies on Achilles tendinosis, suggesting that the cellular function in trigger finger tendons is disturbed in a similar way as in Achilles tendinosis.Recent experimental and observational research has suggested potential side effects of statin treatment on tendons, but firm evidence was lacking. We performed an epidemiological study on two large population-based cohorts. Statin use was found to increase the risk of both trigger finger and tendinosis in the shoulder and Achilles tendons, especially among men. This suggests a similar pathology in trigger finger and tendinosis.We have also studied the time to treatment effect after a single injection of glucocorticoid in trigger finger. Our results suggest that 60-80% of patients can expect resolution of the triggering within 14 days, and half of them within seven days. This result allows correct information to be given to the patient and proper planning of follow-ups.In conclusion, the pathology in trigger finger tendons is similar to tendinosis in other tendons.
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| 10. |
- Meunier, Andreas, 1964-
(author)
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Cyclooxygenase-2 inhibitors and knee prosthesis surgery
- 2008
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Doctoral thesis (other academic/artistic)abstract
- Adverse effects of cyclooxygenase (COX) inhibitors on bone healing have previously been demonstrated in diaphyseal fracture models in animals. In spite of that, they are widely used as postoperative analgesics in orthopaedic surgery. After joint replacement, a bone repair process starts at the interface between bone and cement. If this process is disturbed, the prosthesis may never become rigidly fixed to the bone, leading to migration and with time loosening.This thesis investigates the effects of a selective COX-2 inhibitor (parecoxib or celecoxib) on bone healing in metaphyseal bone in a rat model and on knee prosthesis migration after total knee replacement, as measured with radiostereometric analysis. Blood loss, postoperative recovery, and the 2-year subjective outcome, were also measured. In addition, a hemoglobin dilution method for blood loss estimation, used in this thesis, was evaluated.In the first study, pull-out force of a screw inserted in metaphyseal bone of the tibia in rats was only marginally decreased by parecoxib after 7 days but not after 14 days. In the second and third study, celecoxib treatment resulted in less pain postoperatively in conjunction with total knee replacement (TKR), but no effects were seen on blood loss, range of motion, subjective outcome, or prosthesis migration after 2 years.Comparing the true blood loss of blood donors with the blood loss estimated by the hemoglobin dilution method, this method was found to underestimate the true blood loss. It is therefore not suitable for calculation of the absolute blood loss volume, but may be used for a rough estimate.In summary, celecoxib and presumably other cyclooxygenase inhibitors seems not likely to increase the risk of prosthesis loosening.
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