Acta orthopaedica. Supplementum最新文献

Revision arthroplasty is a challenging aspect of the otherwise quite successful area of joint replacement surgery. The instable interaction between implant and host bone has often initiated a destructive process of inflammation and osteolysis, rendering the revision site sclerotic and with insufficient bone stock. One way of dealing with this is to build up a bed of tightly packed morselized bone graft to support the revision implant in a procedure often referred to as impaction grafting. Fresh frozen morselized femoral head allograft is the gold standard material for impaction grafting of the large defects usually involved in revision arthroplasty. The clinical outcome does not match that of primary arthroplasties. Implant subsidence is greater, implant survival shorter, and the bone graft is often not incorporated into living bone. The studies constituting this thesis have investigated ways of improving early implant fixation and bone graft incorporation. All studies used the same experimental canine model of early fixation and osseointegration of uncemented implant components inserted into a bed of impacted bone graft. Study I compared bone grafted implants where the morselized allograft was used alone or had been added rhBMP-2, the bisphosphonate pamidronate or a combination of the two. The main object was to see wether the previously observed growth factor related accelerated allograft resorption could be counteracted by the addition of an anti-catabolic drug. The study also compared HA-coated and non-coated porous Ti implants. The untreated control implants had better mechanical fixation than all other treatment groups. RhBMP-2 raised the total metabolic turnover of bone within the allograft with a net negative result on implant fixation. Pamidronate virtually blocked bone metabolism, also when combined with rhBMP-2. The HA-coated implants had more than twice as good mechanical fixation and improved osseointegration compared to the corresponding Ti implants. Study II investigated the addition of a bovine bone matrix lyophilisate (Colloss) to the allograft in three different doses. The main object was to see, whether the addition of a biological delivery device of low-dose osteogenic growth factors could provide a sufficient signal to increase the bioactivity of the bone graft without also yielding mechanical instability through increased allograft resorption. Allograft resorption increased with increased signal dose, but not to the extent that it affected implant fixation negatively at the observational time point. Mechanical implant fixation was doubled, and implant osseointegration and graft incorporation were improved. Study III compared a beta-TCP ceramic bone graft substitute (Ossaplast) with and without an osteogenic signal (Colloss E) to morselized allograft with and without the same signal. The object was to investigate, whether the addition of an osteogenic stimulus to a bio ceramic could replace biological allograft bone. Th

The typical dysplastic hip joint is characterised by maldirection of the acetabulum and femoral neck, insufficient coverage of the femoral head focally and globally and erosions of the limbus acetabuli (1). An unknown number of persons with hip dysplasia will suffer from pain in hip or groin, decreased hip function and development of osteoarthritis at a young age. The Bernese periacetabular osteotomy is performed to prevent osteoarthritis in patients with hip dysplasia and has been carried out at Aarhus University Hospital, Denmark since 1996 with more than 500 osteotomies performed. Throughout the years, research and quality improvement of the treatment has taken place and this PhD thesis is part of that process. The aims of this PhD thesis were to evaluate outcome aspects after periacetabular osteotomy in terms of I) estimating the projected loadbearing surface before and after periacetabular osteotomy, II) estimating bone density changes in the acetabulum after periacetabular osteotomy, III) developing a technique to precisely and efficiently estimate the thickness of the articular cartilage in the hip joint and IV) examining the stability of the re-orientated acetabulum after periacetabular osteotomy. In study I, we applied a stereologic method based on 3D computed tomography (CT) to estimate the projected loadbearing surface in six normal hip joints and in six dysplastic hips. The dysplastic hips were CT scanned before and after periacetabular osteotomy. We found that the average area of the projected loadbearing surface of the femoral head preoperatively was 7.4 (range 6.5-8.4) cm2 and postoperatively 11 (9.8-14.3) cm2. The area of the projected loadbearing surface was increased significantly with a mean of 49% (34-70%) postoperatively and thus comparable with the load-bearing surface in the normal control group. Double measurements were performed and the error variance of the mean was estimated to be 1.6%. The effect of overprojection, on the projected loadbearing surface was minimal. Consequently, the stereo-logic method proved to be precise and unbiased. The study indicates that this method is applicable in monitoring the loadbearing area in the hip joint of patients undergoing periacetabular osteotomy. In study II, a method based on CT and 3D design-based sampling principles was used to estimate bone density in different regions of the acetabulum. Baseline density was measured within the first seven days following periacetabular osteotomy and compared with density two years postoperatively. Double measurements were performed on three patients, and the error variance was estimated to be 0.05. Six patients with hip dysplasia scheduled for periacetabular osteotomy were consecutively included in the study. Bone density increased significantly in the anteromedial quadrant of the acetabulum as well as in the posteromedial quadrant between the two time-points. In the anterolateral quadrant bone density was unchanged following surgery, an

Distal tibial fractures are rare and difficult to treat because the bones are subcutaneous. External fixation is commonly used, but the method often results in delayed union. The aim of the present study was to find out the factors that affect fracture union in tibial pilon fractures. For this purpose, prospective data collection of tibial pilon fractures was carried out in 1998-2004, resulting in 159 fractures, of which 83 were treated with external fixation. Additionally, 23 open tibial fractures with significant > 3 cm bone defect that were treated with a staged method in 2000-2004 were retrospectively evaluated. The specific questions to be answered were: What are the risk factors for delayed union associated with two-ring hybrid external fixation? Does human recombinant BMP-7 accelerate healing? What is the role of temporary ankle-spanning external fixation? What is the healing potential of distal tibial bone loss treated with a staged method using antibiotic beads and subsequent autogenous cancellous grafting compared to other locations of the tibia? The following risk factors for delayed healing after external fixation were identified: post-reduction fracture gap of >3 mm and fixation of the associated fibula fracture. Fracture displacement could be better controlled with initial temporary external fixation than with early definitive fixation, but it had no significant effect on healing time, functional outcome or complication rate. Osteoinduction with rhBMP-7 was found to accelerate fracture healing and to shorten the sick leave. A staged method using antibiotic beads and subsequent autogenous cancellous grafting proved to be effective in the treatment of tibial bone loss. Healing potential of the bone loss in distal tibia was at least equally good as in other locations of the tibia.

Background: Gene therapy is a technique that draws on the introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Numerous growth factors and other proteins with the ability to promote the regeneration of tissues in the locomotive system have been identified, but their clinical use is often hindered by delivery problems. In principle, these problems can be overcome by delivering the relevant genes, as the therapeutic substances thereby can be persistently produced directly by local cells at the site of diseases.

Healing of articular cartilage: Articular chondrocytes are receptive to transduction using various gene delivery methods. Following genetic modification, they are capable of sustained expression of transgene products at biologically relevant levels. Our research has proved the AAV vector to be an effective tool for gene delivery to articular chondrocytes in vitro as well as in vivo. To this end, we have demonstrated that the AAV vector mediated TGFbeta1-overexpression stimulates cartilage anabolism. WEAR DEBRIS-INDUCED OSTEOLYSIS: The RANKL system may be a key therapeutic target in treatment of aseptic periprosthetic loosening. We investigated whether gene transfer of OPG using an AAV vector has protective effects against orthopaedic wear debris-induced bone loss. In osteoclastogenesis and in bone wafer resorption assays, the bioactivity of the transgene OPG was proven by depletion of osteoclastogenesis and reduced bone resorption. Using an in vivo model of debris-induced bone resorption, we demonstrated complete inhibition of osteolysis in animals receiving AAV-OPG gene therapy.

Fracture healing in relation to osteoporosis: The success of future OPG treatment of osteoporosis is highly dependent on its effects on fracture healing and remodelling. Using an in vivo fracture healing model, our studies demonstrated that AAV-OPG gene therapy did not conflict with normal bone healing, in contrast to high-dosage intravenous treatment with OPG. However, AAV-OPG therapy depressed remodelling and integration of the genuine cortical bone at the fracture line.

Structural bone allograft healing: Structural bone allografts often fracture due to their lack of osteogenic and remodelling potiential. To overcome these limitations, we utilized allografts coated with AAV-caALK2 vector that mediated in vivo gene transfer. We showed that the AAV vector was capable of transducing adjacent inflammatory cells and osteoblasts in the fracture callus and that BMP signals delivered via AAV-caALK2 coating induced bone formation directly on the cortical surface of the allograft.

Conclusion: The presented research may be seen as initial steps towards development of gene therapeutic treatment options for complex orthopaedic diseases. As such, our studies represent proof-of-principle that the rAAV vector p

Osteoarthritis (OA) presupposes the interaction of systemic and/or local factors. In hip joint OA, congenital or developmental malformation is believed to constitute an individual risk factor for premature degeneration. Hip dysplasia (HD) is such a malformation. The radiological and epidemiological studies had several aims: To critically evaluate the radiological source material of the Copenhagen Heart Study: The Osteoarthritis Substudy, consisting of 4,151 standardized, weight bearing pelvic radiographs recorded 1991-1994. To qualify or disqualify the radiological source material for further studies. To develop a comprehensible and reproducible radiographic discriminator of hip OA with as close an association to self reported hip pain as possible. To identify prevalences of hip OA and HD in a Caucasian, urban background population and investigate the influence of sex, age, physical and occupational parameters on these prevalences. To evaluate the influence of HD on hip OA development relative to other potential risk factors. To evaluate degeneration in dysplastic hips over time. To evaluate the three dimensional anatomy of HD and the distribution of degenerative features in severely dysplastic hips, and To evaluate risk factors for total hip replacement surgery. In the course of the studies we found that assessments of classic indices of HD were significantly influenced by pelvic orientation during x-ray recording and identified exclusion limits of rotation and inclination/reclination of pelvic radiographs to stay inside a measurement error of +/- 3 degrees. We found that minimum joint space width (JSW) /= 60 years of age, and HD prevalence was 4-10%, depending on the radiographic criteria applied. Age and HD were significant risk factors for hip OA development in women, and HD was found to be a significant risk factor for hip OA in men. However, only obesity was found to determine an event of hip replacement surgery. In a longitudinal study of 81 subjects and with mild or moderate hip dysplasia followed for a decade we did not document a tendency for radiological degeneration compared to 136 control subjects. In a computerized tomographic study of severely dysplastic hips we found a close relationship between insufficient anterior, acetabular containment and proximal femoral anteversion. The primary area of degeneration in dysplastic hips was in the antero-lateral quadrant of the joint.

This thesis aimed to study osteoarthritis (OA) of the knee and its subgroup with lateral wear (valgus knees). Anatomy, kinematics and kinetics (movements and moments) of the hip and knee joint and the sensitivity and specificity of diagnostic procedures were evaluated. Our hypothesis was that there are biomechanical reasons for development of either lateral or medial OA. The wear pattern of the tibial plateau and the femoral condyles was delineated in 42 patients. The diagnostic accuracy of standing knee radiographs was validated in 34 and reproducibility and validity of the Ahlbäck classification was studied in 48 patients. The Influence of working conditions or gender on the prevalence of uni or bilateral knee OA was evaluated in 990 patients from 2 hospitals (Varberg and Halmstad) operated during 1985-1994 with knee arthroplasty or proximal tibial osteotomy. For each patient, 3 age- and gender-matched controls were found. Studies of the anatomy of the hip and pelvic regions and the motions and moments in the hip and knee in medial and lateral OA were performed. The detailed kinematics of the knee during active extension in lateral OA were recorded using dynamic radiostereometry (RSA). In both medial and lateral OA the central part of the tibial plateau showed the most pronounced wear (p<0.001), followed by the anterior part in medial OA (p=0.02) and the posterior part in lateral OA (p=0.001). In medial OA the observed difference between the 2 radiographic methods was small and acceptable (median; p=0.05; 0-0.5 mm). In lateral OA there was no consistent underestimation, but larger scatter (median; p=0.04; -0.1-1.2 mm) suggesting less precise determination. The repeatability of the Ahlbäck classification for one observer was fair (kappa: medial OA: 0.15-0.65; lateral OA: 0.59-0.76), but between observers it was poor (kappa: 0.1). The validity revealed an acceptable sensitivity in both medial (67-95%) and lateral (43--86%) OA but the specificity was low (medial: 11-67%; lateral: 25-75%). Farmers (RR: 1.7; p<0.0005) and building workers (RR: 1.4; p=0.047) run increased risk to undergo surgical treatment because of OA of the knee. Unilateral disease was 3.7 times more common among men. Patients with lateral knee OA had a 14 mm wider pelvis (p=0.001) and those with medial knee OA an 11 mm higher offset (p=0.005). In the gait analysis they showed more outward rotation of the hip (p=0.001) and more inward rotation of the tibia than did patients with medial OA (p=0.001). In lateral OA, the medial femoral condyle translated 7-8 mm forward with 450 flexion whereas controls translated 4 mm less (p=0.03), without any difference of the lateral femoral condyle. Conventional radiographs do not give sufficient information for correct grading, especially in lateral OA where the scatter is high. The joint space can often be seen on radiographs despite presence of bone attrition as observed on the preparations. Increased incidence of unilateral disease in m