Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Success of total hip replacements is well reported however, failures as a result of wear processes and the biological response to these products continue to challenge the orthopaedic community. Lately, corrosion of metal surfaces as well as wear particles have seen particular interest with elevated blood cobalt levels widely reported in patients receiving metal-on-metal (MoM) hip replacements. Some instances have also reported this in patients with metal-on-polyethylene (MoP) components and these corrosion products are believed to contribute to hypersensitivity reactions reported. This thesis considers wear and cobalt release in MoP and MoM hip bearings tested under standard and challenging hip simulator conditions and includes an exploration of novel bearing coatings to reduce cobalt release. The incorporation of silver into these coatings may be sufficient to produce an antibacterial response, reducing the risk of mid-term infections, another reported cause of failure. Polyethylene wear was low under standard and clinically relevant adverse conditions in 28mm and 52 mm diameter MoP bearings (less than 35 mm3/mc). Cobalt release was measurable in 28 mm diameter MoP bearings (51 ppb/mc) with higher levels produced in large 52 mm diameters (123 ppb/mc), the first time this has been reported, although cobalt release was substantially less than that observed in MoM bearings (6909 ppb/mc). Alumina abrasives introduced in the lubricant substantially damaged MoP bearings, increasing the cobalt release to 70,690 ppb after 1 mc, greater than found after edge loaded MoM bearings (19,240 ppb). The removal of these particles still produced elevated cobalt levels compared to standard conditions and increased polyethylene wear to 435 mm3/mc. A chromium nitride (CrN) coating in MoP bearings was resistant to this abrasive damage showing no delamination in the coating, with negligible cobalt released after 7.04 mc (153 ppb) and maintained a polyethylene wear rate below 20 mm3/mc. Silver CrN coatings on both bearing surfaces of MoM components prevented cobalt release under standard conditions, with silver release after 0.17 mc up to 3,720 ppb in high silver surface coatings, although the wear was relatively high (5.24 mm3/mc). A silver CrN coating with a low concentration of silver at the surface reduced wear and was resistant to 5 mc of edge loading. It generated 241 ppb of cobalt and maintained comparable steady state wear rates (0.65 mm3/mc) to the uncoated metal while releasing 18,786 ppb silver which may be sufficient to be an effective anti-microbial agent. These coatings may provide potential clinical benefits in MoP and MoM bearings by reducing both wear and cobalt release in ideal and adverse conditions. There may also be beneficial wear products in the form of silver, although further testing of optimised coatings is required.

Intra-articular fractures (IAFs) often lead to poor outcomes, despite surgeons’ best efforts at reconstructing the fractured articular surface. The objective of articular fracture reduction is to improve joint congruity thereby lower articular contact pressure and minimize the risk of post-traumatic osteoarthritis (PTOA). Surgical fracture reductions performed using less invasive approaches (i.e., percutaneously) rely heavily upon C-arm fluoroscopy to judge articular surface congruity. Based on varied outcomes, it appears that the use of 2D imaging alone for this purpose may prove inadequate. Despite this, there has been little investigation into novel metrics for assessment of reduction quality. This work first explores seven methods for assessment of reduction quality (3 2D, 3 3D, and one biomechanical). The results indicate that metrics which take 3D measurement or joint biomechanics into account when characterizing reduction quality are more strongly correlated with PTOA development. A computer assisted surgery system, which provides up-to-date 3D fracture geometry and contact stress distributions intra-operatively, was developed. Its utility was explored in a series of ten cadaveric tibial plafond fracture reductions, where contact stresses and contact areas were compared in surgeries with vs. without biomechanical guidance. The use of biomechanical guidance caused an increase in surgical time and fluoroscopy usage (39% and 17%, respectively). However, it facilitated decreases in the mean and maximum contact stress by 0.7 and 1.5 MPa, respectively. Contact areas engaged at known deleterious levels (contact stress > 4.5 MPa) were also 44% lower in cases which used guidance. The findings of this work suggest that enhanced visualization of a fracture intra-operatively may facilitate improved long-term outcomes. Further development and study of this system is warranted.

Highly comminuted intra-articular fractures are complex and difficult injuries to treat. Once emergent care is rendered, the definitive treatment objective is to restore the original anatomy while minimizing surgically induced trauma. Operations that use limited or percutaneous approaches help preserve tissue vitality, but reduced visibility makes reconstruction more difficult. A pre-operative plan of how comminuted fragments would best be re-positioned to restore anatomy helps in executing a successful reduction. The objective of this work was to create new virtual fracture reconstruction technologies that would deliver that information for a clinical series of severe intra-articular fractures. As a step toward clinical application, algorithmic development benefits from the availability of more precise and controlled data. Therefore, this work first developed 3D puzzle solving methods in a surrogate platform not confounded by various in vivo complexities. Typical tibial plafond fracture fragmentation/dispersal patterns were generated with five identical replicas of human distal tibia anatomy that were machined from blocks of high-density polyetherurethane foam (bone fragmentation surrogate). Replicas were fractured using an instrumented drop tower and pre- and post-fracture geometries were obtained using laser scans and CT. A semi-automatic virtual reconstruction computer program aligned fragment native surfaces to a pre-fracture template. After effective reconstruction algorithms were created for the surrogate tibias, the next aim was to develop new algorithms that would accommodate confounding biologic factors and puzzle solve clinical fracture cases. First, a novel image analysis technique was developed to segment bone geometries from pre- and post-surgical reduction CT scans using a modified 3D watershed segmentation algorithm. Next, 3D puzzle solving algorithms were advanced to obtain fracture reconstructions in a series of highly comminuted tibial plafond fracture cases. Each tibia was methodically reconstructed by matching fragment native (periosteal and articular) surfaces to an intact template that was created from a mirror image of the healthy contralateral limb. Virtual reconstructions obtained for ten tibial plafond fracture cases had average alignment errors of 0.39±0.5 mm. These novel 3D puzzle solving methods are a significant advancement toward improving treatment by providing a powerful new tool for planning the surgical reconstruction of comminuted articular fractures.

Articular fracture reduction is a complex surgical task that requires surgeons to be competent at multiple surgical skills to successfully complete. The list of skills needed includes the ability to use fluoroscopic images to build a 3D mental model of the fracture during reconstruction, the proper handling and use of surgical instruments, how to manipulate the fracture fragment into a reduced configuration with minimal hand motion, proper k-wire placement, and the preservation of surrounding soft tissues. Current training methodology is based on an apprenticeship model. The resident learns by watching a senior surgeon, and then preforms the procedure on live patients under the guidance of the senior surgeon to gain competence. This endangers the patient and does not provide the best outcome for either patient or resident. The work presented in this thesis is the early development of an articular fracture reduction simulator, the subsequent use of the simulator in the training of orthopaedic residents, and assessment of the improvement of residents after practice on the simulator. To date, the simulator has been tested on four different groups of residents,3 different groups from the University of Iowa and one group from the University of Minnesota. Considerable effort has been made to validate the improvement seen in resident performance through objective means. The Objective Structured Assessment of Technical Skills (OSATS) is a global rating score and procedural checklist that has been previously validated to objectively measure surgical skill. Other assessment metrics include hand motion capture to count the number of discrete actions and measure distance traveled during the surgical procedure, fluoroscopic usage and radiation exposure, articular `step-off', the surface deviation from an intact or ideal reconstruction, and contact stress exposure. The results indicate that the goals for the simulator have been met, that the simulator provides a means of training orthopaedic residents, assessing improvement, decreased the cost of training, and improved patient safety. The simulator is not without limitations including sample size, and radiation exposure. The task being trained is complex and can be broken down into basic subtasks that could be trained individually. Even with flaws, the simulator is an improvement over current training methods and is an excellent first step toward creating a surgical skills curriculum to comply with new mandates from orthopaedic surgery's governing bodies.

Proximal humeral fractures requiring surgical stabilization remain a therapeutic challenge, and a fully functioning joint is rarely the outcome after traumatic proximal humeral fractures. A systematic review was conducted to present the current state of knowledge concerning the postoperative rehabilitation. Tree databases was searched (PubMed, PEDro and the Cochrane library), presenting 25 publications eligible for further review and assessment. The literature was evaluated using PEDro and The Swedish Council on Health Technology, SBUs, evaluation grading system GRADE. The main functional impairments were pain and reduced range of motion in the shoulder joint, and were measured by several different scoring systems for functional outcome. Reported results were contradictory and inconsistent, and current studies typically lack randomization, and independent evaluation, with a resultant inability to produce clinical conclusions. According the post-operative rehabilitation procedure, only careful conclusions can be drawn from the literature reviewed which does not focus on, emphasize or explore the physiotherapeutic interventions at any length. It was therefore not possible to compare or connect the Axelina rehabilitation regimen with the literature. The Axelina rehabilitation program of the shoulder joint, are the most commonly used regimen at the physiotherapeutic ward at Uppsala University hospital. Neither was it possible to determine if the post-operative treatment should be different according to classification of fracture or method of stabilization. The results from this systematic review suggest that the data from the published literature are inadequate for evidence-based decision making as regards the treatment and post-operative rehabilitation for complex proximal humeral fractures.

Osteoporosis is a disease characterized by low bone mineral density, deteriorated bone microstructure and increased fracture risk. About 50% of all women and 25% of all men will have an osteoporotic fracture. Given that there is no effective cure in established osteoporosis, prevention is of high importance. Bone mineral density (BMD) is accumulated during childhood and adolescence with a peak at about 20 years of age. Peak BMD has been suggested to explain at least half of the variation in BMD up to old age. Thus, to increase peak BMD could decrease the risk of later fractures. The purpose of the present thesis was to investigate the influence of physical activity, vitamins A and D, and fatty acids on peak bone mass in men. The influence of physical activity on bone accrual was studied in two cohorts. In the first cohort 46 ice hockey players, 18 badminton players and 27 controls, all 17 years of age at baseline, were followed for four years. During the follow up the badminton players gained more bone mass at the hip compared to both the ice hockey players and controls. In the second cohort the associations between physical activity and BMD were investigated in 62 female and 62 male young medical students. The estimated high impact activity per week was associated with bone mass at all sites in the male medical students (r=0.27-0.53, p<0.05). In the female cohort different estimates of physical activity were not related to bone mass at any site. In both males and females correlations between bone mass and body constitution parameters were observed. Levels of vitamin D3, vitamin D2, retinol, retinol-binding-protein-4 (RBP-4) and fatty acids were measured in 78 young men with a mean age of 22.6 years. BMD at various sites were measured using Dual-Energy X-ray absorptiometry. Levels of vitamin D3 showed a significant positive association with all BMD sites and also lean body mass (r=0.23-0.35, p<0.05). Levels of vitamin D2, however, showed a significant negative correlation with BMD of the total body (r=-0.28, p=0.01) and spine (r=-0.27, p=0.02). There was also a significant negative relationship between levels of vitamin D3 and D2 (r=-0.31, p=0.006). Concentrations of n-3 (omega-3) fatty acids showed a positive association with BMD at the total body (r=0.27, p=0.02) and spine BMD (r=0.25, p=0.02). There was also a positive association between levels of n-3 fatty acids and changes in BMD of the spine between 16 and 22 years of age (r=0.26, p=0.02). The significant associations found seemed to be related mostly to the concentration of the n-3 fatty acid docosahexaenoic acid. Levels of retinol and RBP-4 were not related to BMD but to levels of osteocalcin, which is a marker of bone formation. This association disappeared when adjusting for the influence of abdominal fat mass. In summary, the present thesis suggests that many modifiable factors may influence the accumulation of peak bone mass in males, such as physical activity, vitamins, and fatty acids. Further studies are needed to investigate whether optimizing these factors in youth may decrease the risk of osteoporosis later in life.

Growth factor delivery may be useful to accelerate the rate of tendon healing. We studied Platelet Concentrate, which in effect can be regarded as a cocktail of growth factors relevant for tendon healing. In a rat Achilles tendon transection model, one postoperative injection of Platelet Concentrate resulted in increased strength even 3 weeks later. Mechanical stimulation improves the repair of ruptured tendons. We studied the effects of platelets upon Achilles tendon regenerates in rats 3, 5 and 14 days after transection, either unloaded or mechanically stimulated. At 14 days, physical activity and platelets increased repair independently. Unloading decreased the mechanical properties of the repair tissue to less than half of normal. Moreover, the platelets had no effect without loading. Thrombin, which we used for platelet activation, improved healing of the rat Achilles tendon by itself. Conversely, continuous inhibition of thrombin by low molecular weight heparin (LMWH) inhibited tendon repair. However, intermittent inhibition, similar to clinical thromboprophylaxis, had no effect on tendon healing. Cartilage Derived Morphogenetic Protein-2 (CDMP-2) can improve tendon healing in loaded defect models. We now studied unloaded repair in a rabbit patellar tendon model. Two hours postoperative, the rabbits received CDMP-2 injected into the haematoma. The healing tendon became 65 % stronger than controls. We then studied Achilles tendon healing with CDMP-2 injections in sheep, to get a bigger animal model. There was an unexpectedly high variation of repair in these animals, and the study turned out to be underpowered. Spontaneous ruptures in humans have a more variable geometry than in our sheep model, so humans can also be expected to vary a lot in mechanical characteristics of Achilles tendon repair. This accentuates the importance of individualized rehabilitation programs. In conclusion, both platelet concentrate and CDMP-2 injections might be of interest for clinical use as a complement to surgical or conservative treatment of tendon ruptures. Platelet treatment for tendon ruptures should probably be combined with early physiotherapy.

Tendinopathies are painful tendon conditions of presumably multifactorial genesis. In tendinosis, as in Achilles tendinosis, there is apart from pain also morphological changes which are described as degenerative with no signs of inflammation. The exact mechanisms behind these conditions are still, to a large extent, unknown. Pain, being the foremost impairing symptom, leads us to the hypothesis that nerves are deeply involved in the symptoms and processes of Achilles tendinosis. Locally produced nerve signal substances may also be involved in the processes. Knowledge of the innervation patterns within the tendon and knowledge on a possible local nerve signal substance production are therefore of utmost importance. There is a lack of information on these aspects. The specific aims of this thesis were 1) to investigate the innervation patterns regarding general, sensory, cholinergic and sympathetic innervations, and 2) to examine for the possible occurrence of a production of nerve signal substances and a presence of receptors related to these in the tendon cells, the tenocytes. Painfree normal and tendinosis Achilles tendons were examined. Immunohistochemistry, using antibodies against the general nerve marker PGP9.5, the synthesizing enzymes for acetylcholine (choline acetyltransferase; ChAT), and catecholamines (tyrosine hydroxylase; TH), the vesicular acetylcholine transporter (VAChT), neuropeptide Y (NPY), substance P and calcitonin gene-related peptide, was applied. Immunohistochemistry was also used for the delineation of muscarinic (M2R), adrenergic (α1-AR) and NPY-ergic (Y1 and Y2) receptors. To detect mRNA for TH and ChAT, in situ hybridization was used. In normal Achilles tendons, as well as in the tendinosis tendons, there was a very scanty innervation within the tendon tissue proper, the main general, sensory and sympathetic innervations being found in the paratendinous loose connective tissue. Interestingly, the tenocytes showed immunoreactions for ChAT, VAChT, TH, M2R, α1-AR and Y1R. The reactions were clearly more observable in tendons of tendinosis patients than in those of controls. The tenocytes of tendinosis patients also displayed mRNA reactions for ChAT and TH. Nevertheless, all tenocytes in the tendinosis specimens did not show these reactions. Immunoreactions for α1-AR, M2R and Y1R were also seen for blood vessel walls. The present thesis shows that there is a very limited innervation within tendon tissue proper, whilst there is a substantial innervation in the paratendinous loose connective tissue. It also gives evidence for an occurrence of production of catecholamines and acetylcholine in tenocytes, especially for tendinosis tendons. Furthermore, that ACh, catecholamines and NPY can have effects on these, as well as on blood vessels, via the receptors observed. The observations suggest that Achilles tendon tissue, whilst containing a very scarce innervation, exhibits autocrine/paracrine cholinergic/catecholaminergic/NPY-ergic effects that are upregulated in tendinosis. These findings are of great importance as the results of such effects may mimic processes that are known to occur in tendinosis. That includes effects related to proliferation and angiogenesis, and blood vessel and collagen regulating effects. In conclusion, within the Achilles tendon there is a very scarce innervation, whilst there appears to be a marked local production of nerve signal substances in Achilles tendinosis, namely in the tenocytes, the cells also harbouring receptors for these substances. The observations give a new insight into how the tendon tissue of the Achilles tendon is influenced by signal substances and may give options for new treatments of Achilles tendinosis.

Osteoporosis-related fracture is already today a major public health problem and the number of hip fractures is expected to double to 2030. Sweden has one of the highest hip fracture incidences worldwide. This may be explained by several factors: e.g. age, genetic, climatologic, geographic and a relative vitamin D deficiency, secondary to the limited sunlight exposure especially during winter months. Intrinsic and extrinsic factors contribute to a fracture, although a prior low energy fracture is one of the strongest predictors for a subsequent one and this should be a target for secondary fracture prevention in an orthopaedic setting. Since 1993 all injured patients admitted to the emergency floor and all in-hospital fractures at Umeå University Hospital, Sweden, were registered according to the Injury Data Base, former EHLASS. There were 31,173 fracture events (one or more fractures at the same time), of which 13,931 were in patients’ ≥ 50 years old. The fracture database was co analyzed with the Northern Sweden Health and Disease Study cohort in a nested case-control study for investigations of associations between osteoporotic fracture and serum markers, lifestyle data, nutrition etc. We found that there were differences in fracture pattern depending on age and sex. Both injury mechanism and fracture site were strongly dependent of age. The most severe fragility fracture, hip fracture, had a decreasing incidence. However, the incidence curve was right-shifting leading to an increase, both in numbers and in incidence of hip fractures among the oldest female. To identify people at high risk for fractures, re-fracture patients are useful. No less than 21% of the fracture patients had suffered more than one fracture event, accounting for 38% of all fracture events. The total risk ratio for a subsequent fracture was 2.2 (2.1-2.3 95% CI). In males the highest risk for re fracture was in the age cohort 70-79 years (RR 2.7, 2.3-3.2 95% CI), in females > 90 years (RR 3.9, 3.2-4.8 95% CI). Another possible risk factor in this subarctic population is the lack of sunlight, leading to a vitamin D deficit. The overall adjusted risk of sustaining a hip fracture in this population was 2.7 (95%CI:1.3-5.4) in subjects with a serum 25 hydroxyvitamin D below 50 nmol/l. The association was, however, different according to age at baseline. Thus in subjects aged 60 years and above at baseline, the adjusted odds ratio of sustaining a hip fracture was 6.2 (1.2-32.5 95%CI) for the group of individuals with a serum 25OHD below 50 nmol/l, whereas no significant association was found in the youngest age group. In the next 30 years the ongoing demographic changes will accelerate. The World War II baby boomers will cause an age quake. We can already see signs heralding a new fracture pattern: an increasing cohort of mobile but fragile elderly, with considerable co-morbidity is now at risk for fragility fractures. In fracture patients, clinical information is sufficient to pinpoint patients with a high risk for re-fractures. It is therefore clinically important to use the information provided by the fracture event. We suggest that trauma units and primary care units should screen for risk factors and inform patients about the treatment options, and to organize fracture liaison services. This seems to be especially cost-efficient for our oldest and frailest patients. Secondary prophylaxis and follow-up treatment after cardiovascular disorders are now a matter of course worldwide, but the screening for risk factors, in order to prevent a second fracture, is often neglected. This is one of the most important issues of fracture care in the future in order to improve general health.