Dissertations / Theses on the topic 'Bone fracture treatment'

Introduction Non-union (NU) is a fracture that will not unite. With over one million fractures per annum in the UK long bone non-union has serious social and economical implications. There is little epidemiological data available specifically looking at this NU patient cohort. Studies that are bone specific quote rates of non-union as a proportion of their study group but there is no data quantifying the incidence of NU in the population or per fracture. Studies have highlighted risk factors associated with atrophic non-union including age, diabetes, non-steroidals, and cigarette smoking. There is scientific interest regarding how best to classify non-unions and the role of biological agents in treating them. Aims • To quantify the incidence of non-union in a large population and calculate the risk of non-union per fracture according to age, sex and anatomical distribution. • To assess the causes contributing to non-union and outcomes of treatment in a non-union cohort and validate a new non-union scoring system. • To test the treatment potential of a novel molecule (monobutyrin) and a growth factor in a small animal model of non-union. Method • Using the ICD-10 data from the Scottish population as collected by NHS Scotland the incidence of non-union and fractures were calculated. • A cohort of 100 non-union patients were studied for risk factors associated with their non-union, treatment outcome and to assess a new NU classification system. • A rat model of tibial non-union was used to assess the potential of monobutyrin and BMP-2 in treating non-union in an animal model. Results • Fracture non-union is very rarely found in children (1 in 500 fractures) and occurs in up to 1 in 50 adult fractures. Non-union of a fracture has a significantly higher risk in young adults than the elderly by about 3 fold. Osteoporosis may not be a risk for non-union. The tibia and clavicle are the sites with the greatest potential for fracture non-union. • Non-union is multifactorial in two out of three patients. Biomechanical stability, patient host factors and infection must all be considered in every patient. Occult or unexpected recurrent infection is present in up to 10% of patients. When all factors are considered in treatment the outcome is 95% successful with 88% requiring 2 or less procedures to heal the non-union and only a minority requiring adjuvant graft or biological agents. The proposed new classification system is complex and did not clearly identify those patients who would require adjuvant treatment (eg bone grafting or BMP) or those likely to have unsuccessful non-union treatment. • Monobutyrin and BMP-2 when tested on the small animal non-union model did not improve the success rate of union. Conclusions Non-union affects approximately 1000 people per year in Scotland, this figure is not as high as 5-10% of all fractures. It is associated with fractures in young adults and of the clavicle and tibia, treatment can have a very high success rate without the need for adjuvant biological polytherapy when all contributing factors are considered and managed appropriately. A new non-union classification needs to incorporate the multifactorial aspects of non-union without being too complex to use in everyday clinical situations.

Abstract Hip fracture is a trauma with serious consequences, especially in the elderly. Etiological factors should be known better than nowadays to recognize the individuals at high risk. Also, the treatment of displaced femoral neck fractures has been controversial, and the factors leading to a functional outcome are not known well. The true impact of deep infection on the outcome after hip fracture surgery has also been insufficiently examined. The thesis is based on two etiological studies. In the first study, the geometrical parameters of the upper femur and pelvis in postmenopausal women with hip fracture were (n=70) compared to age-adjusted controls (n=40). Measurements were made from position-standardized and calibrated pelvic plain x-rays. The differences between the two different types of hip fracture, femoral neck fractures (n=46) and trochanteric fractures (n=24) were also defined. High femoral neck/shaft angle (NSA), thin femoral cortices, low femoral shaft diameter (FSD) and trochanter width and the pelvic dimensions associate strongly with the hip fracture risk in postmenopausal women. Greater NSA, smallest outer pelvic diameter and acetabular width, narrower FSD and smaller femoral neck/shaft cortex ratio were associated with femoral neck fracture rather than trochanteric fracture in postmenopausal women. In the second study, lifetime factors, some bone metabolism markers and bone mineral density were analyzed from postmenopausal women (n=74; 49 with femoral neck fracture, 25 with trochanteric fracture) and age-adjusted controls (n=40). Impaired functional ability, use of loop diuretics, antidiabetic, antidepressant and neuroleptic drugs, some concurrent diseases, such as stroke, diabetes, malignancy, cardiovascular diseases, low bone mineral density of the upper femur, low serum calcium, low serum 25-hydroxyvitamin D and high serum calcitonin, seem to be related to the risk of hip fracture, while low bone mineral density and low serum calcitonin are related to the trochanteric type of fracture in postmenopausal women. The treatment of displaced femoral fractures included two prospective case-control studies, and the first of these involved a comparison (357 matched pairs) of patients with osteosynthesis (OS) with two pins in Lund and patients with uncemented hemiarthroplasty (HA) in Oulu. The patients treated with OS had 4 months after fracture better ambulatory capacity, used walking aids less often and had less pain than the patients treated with HA. The other comparison (84 matched pairs) was made between OS with three screws and uncemented HA, and it revealed no significant differences between HA and OS in the short-term functional outcome. Both studies revealed a higher re-operation rate in OS patients than uncemented HA patients. The case-control study with 29 matched pairs showed that deep infection after a hip fracture operation impairs the short-term functional outcome and slightly increases mortality, with an attributable mortality rate of 10 %. In conclusion, this thesis suggests that the geometry of the upper femur and pelvis, the aforesaid lifetime factors, the aforesaid metabolism markers and bone mineral density are associated with the etiopathology and type of hip fracture in postmenopausal women. The short-term functional outcome was better in OS patients treated with two pins compared to uncemented HA, but the higher re-operation rate should be considered among the OS patients. Deep infection is a serious complication of hip fracture surgery, which impairs function and increases mortality.

Bone defects and fracture non-unions remain a substantial challenge for clinicians due to a high occurrence of delayed union or non-union requiring surgical intervention. The current grafting procedures used to treat these injuries have many limitations and further long-term complications associated with them. This has resulted in research efforts to identify graft substitution therapies that are able to repair and replace tissue function. Many of these tissue engineered products include the use of growth factors to induce cell differentiation, migration, proliferation, and/or matrix production. However, current growth factor delivery methods are limited by poor retention of growth factors upon implantation resulting in low bioactivity. These limiting factors lead to the use of high doses and frequent injections, putting the patients at risk for adverse effects. The goal of this work was to develop and evaluate the efficacy of BMP-2 delivery systems to improve bone regeneration. We examined two approaches for delivery of BMP-2 in this work. First, we evaluated the use of a self-assembling lipid microtube system for the sustained delivery of BMP-2. We determined that sustained delivery of BMP-2 from the lipid microtube system was able to enhance osteogenic differentiation compared to empty microtubes, however did not demonstrate a significant advantage compared to a bolus BMP-2 dose in vitro. Second, we developed and assessed the functionality of an affinity-based system to sequester BMP-2 at the implant site and retain bioactivity by incorporating heparin within a collagen matrix. Incorporation of heparin in the collagen matrix improved BMP-2 retention and bioactivity, thus enhancing cell-mediated mineralized matrix deposition in vitro. Lastly, the affinity-based BMP-2 delivery system was evaluated in a challenging in vivo bone repair model. Delivery of pre-bound BMP-2 and heparin in a collagen matrix resulted in new bone formation with mechanical properties not significantly different to those of intact bone. Whereas delivery of BMP-2 in collagen or collagen/heparin matrices had similar volumes of regenerated mineralized tissue but resulted in mechanical properties significantly less than intact bone properties. The work presented in this thesis aimed to address parameters currently preventing optimal performance of protein therapies including stability, duration of exposure, and localization at the treatment site. We were able to demonstrate that sustained delivery of BMP-2 from lipid microtubes was able to induce osteogenic differentiation, although this sustained delivery approach was not significantly advantageous over a bolus dose. Additionally, we demonstrated that the affinity-based system was able to improve BMP-2 retention within the scaffold and in vitro activity. However, in vivo implantation of this system demonstrated that only delivery of pre-complexed BMP-2 and heparin resulted in regeneration of bone with mechanical properties not significantly different from intact bone. These results indicate that delivery of BMP-2 and heparin may be an advantageous strategy for clinically challenging bone defects.

[Truncated abstract] Renewed interest in the fixation of fractures using plates has been stimulated by an improved understanding of the biology of fracture healing and a drive towards minimally invasive surgery. This has led to a change in the way we use plates nowadays and the way in which we build the bone-plate construct, as well as the development of new implants better suited to these techniques. As a result of this, we have now the potential to safely expand the indications for plate fixation especially in the management of fractures in osteopenic bone. This thesis provides scientific evidence allowing for better formulation of the optimum way to use the modern plating systems in the clinical setting. Biological fracture repair with conventional plates, in terms of a less rigid construct to enhance fracture healing, is becoming increasingly popular. By omitting screws the construct becomes more flexible with a risk of fixation failure. It was the aim of the first paper to investigate in an experimental model the construct strength of different conventional plate lengths and number / position of the screws, and if an oblique screw at the plate end could increase the fixation strength. Our data suggest that the plate length is the most important factor in withstanding forces in cantilever bending. Longer plates with an equal number of screws require greater peak loads to failure than short plates with more screws. Furthermore, an oblique screw at the plate end produces an increased strength of fixation in all different test setups. However, the difference is more significant in shorter plates and in constructs with no screw omission adjacent to the fracture site. ... Following cyclic loading, however, locking plates can better retain fracture reduction compared to compression plates. On the other hand, under torsional load the compression plate appears to be biomechanical superior to the locking system. In supracondylar comminuted femur fractures, combining the two principles results in less plastic deformation, and a higher load to failure compared to their single application. The last two papers examine the behaviour of locking plates in osteopenic bone. In cadaveric intra-articular calcaneal fractures, the locking plate showed a significantly lower irreversible deformation during cyclic loading and a significantly higher load to failure. In dorsal and volar fixed angle distal radius constructs in a cadaveric model, all constructs showed adequate stability with minimal deformation on fatigue testing under physiological conditions in good bone quality. In osteoporotic bone, however, dorsal fixed angle constructs are stiffer and stronger than volar constructs. The addition of a styloid plate to a volar plate does not significantly improve stability.

Orientador: Sheila Canevese Rahal
Resumo: O presente estudo visou avaliar temporalmente a formação e a qualidade da membrana induzida de Masquelet, tendo por modelo uma falha óssea segmentar induzida no rádio de galinhas. Foram utilizadas 16 galinhas saudáveis, com um ano de idade e massa corpórea média de 1,45 kg. Sob anestesia geral inalatória, foi induzido defeito segmentar de 1,5 cm no rádio esquerdo, o qual foi preenchido com cimento ósseo na fase pastosa. Os defeitos foram avaliados por meio de exames radiográficos e ultrassonográficos, imediatamente após o procedimento cirúrgico e aos sete, 15, 21 e 30 dias de pós-operatório. Para a avaliação histológica das membranas induzidas, uma ave foi submetida à eutanásia aos sete dias (estudo piloto) de pós-operatório e cinco aves aos 15, 21 e 30 dias de pós-operatório. No exame radiográfico do pós-operatório imediato foi possível verificar a presença do cimento ocupando a falha óssea segmentar, como uma massa radiopaca, com variações de intensidade. Com 30 dias de pós-operatório já foi evidente a presença de nova formação óssea partindo de ambas as extremidades fraturadas. Pelo exame ultrassonográfico, as membranas mostraram a maior formação de vascularização aos 30 dias de pós-operatório. Pela avaliação histológica a membrana aos sete e 15 dias de pós-operatório tinha três zonas distintas, porém aos 15 dias havia presença de neovascularização, fibras colágenas organizadas e diminuição de células inflamatórias. Aos 21 dias após a cirurgia houve uma perda de delimitaçã... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: This study aimed to evaluate the formation and quality of the induced membrane in Masquelet's technique, using a segmental bone defect induced in the chicken’s radius. Sixteen healthy domestic chickens, 1 year old and weighing 1.45 kg were used. Under general anesthesia, a 1.5-cm segmental bone defect was induced in the left radius, which was filled with bone cement during its pasty polymerization phase. The bone defects were evaluated by plain X-rays and ultrasounds, immediately after surgery and at seven, 15, 21 and 30 days postoperatively. One bird was euthanized at 7 days after surgery (pilot study), and five birds were euthanized at 15, 21 and 30 days postoperatively for histological evaluation of the induced membranes. Immediate postoperative radiographic examination showed the presence of cement that occupied the segmental bone defect, as a radiopaque mass, with intensity variations. Thirty days after surgery the presence of new bone formation at the fractured extremities was evident. Ultrasound evaluation showed that the induced-membrane had the highest rate of vascularization at 30 days post-surgery. Histologically, the induced-membrane had three distinct zones at 7 and at 15 days postoperatively, but day 15 had neovascularization, organized collagen fibers and reduced of inflammatory cells. At 21 days after surgery, the zones were less defined and there was cartilage and bone metaplastic areas. At 30 days postoperative diffuse mineralization of the membrane was obse... (Complete abstract click electronic access below)
Mestre

Diabetes is a chronic and debilitating disease that affects nearly half a billion people worldwide with the vast majority of diabetics suffering from Type 2 diabetes mellitus (T2DM), a disease characterized by insulin insensitivity that often requires pharmacotherapy to effectively maintain target blood sugar levels. The thiazolidinedione (TZD) class of drugs consists of oral hypoglycaemic agents used alone or in combination with other antidiabetic drugs to treat T2DM. The drugs within this class, which include rosiglitazone and pioglitazone, were originally heralded as providing novel first and second-line treatment of T2DM with glycaemic control and physiological effects comparable to, and in some cases, better than, first-line treatments such as metformin. However, over time they have also been associated with adverse cardiovascular, osteological, and carcinogenic effects in some, but not all clinical trials, observational studies, and meta-analyses. Given the conflicting evidence to date on the safety of TZD drugs, their role in the treatment of T2DM continues to be debated and epidemiological gaps remain. The objectives of this doctoral research are fourfold: 1) to conduct an in-depth review of the epidemiology of TZD pharmacotherapy including pharmacokinetics and modes of action, the results of previous studies investigating health risks and benefits associated with TZD treatment, and new and future uses for this class of drugs; 2) to determine whether diabetic patients treated with TZDs are at increased risk of adverse cardiovascular outcomes; 3) to assess whether TZD pharmacotherapy is associated with an increased risk of bone fractures and whether risks differ depending on fracture site and patient sex; and, 4) to investigate associations between TZD use and risk of bladder cancer. Specific research questions were investigated using nested case-control analyses designed to capture incident users of antidiabetic drugs and electronic health data from Cerner Health Facts®, an electronic medical record database that stores time-stamped patient records from more than 480 contributing hospitals throughout the United States. Findings from this work are reported in a series of manuscripts, including a published review paper. Key findings include: 1) TZD use was associated with an increased risk of incident myocardial infarction and congestive heart failure compared to never use of TZD drugs with a trend towards a potential early treatment effect within the first year of exposure to pioglitazone; 2) TZD use was associated with an increased risk of closed bone fractures among Type 2 diabetics with use of pioglitazone or rosiglitazone associated with an increased risk across multiple fracture sites in women, but only rosiglitazone use in men and only at peripheral fracture sites; 3) use of either pioglitazone or rosiglitazone were associated with an increased risk of incident bladder cancer compared to never users, however, a low number of bladder cancer cases resulted in underpowered analyses; and, 4) insulin use in a hospital setting may replace a patient's normal course of antidiabetic therapy which, when combined with other potential sources of bias in traditional nested case-control studies using hospital-based data, may lead to overestimation or underestimation of adverse health risks associated with non-insulin antidiabetic therapies. Although these findings warrant replication, the results of the research contained within this dissertation suggest that caution should be exercised when prescribing diabetic patients TZD drugs if they have cardiovascular, osteological, or carcinogenic risk factors. Additional pharmacovigilance studies should also continue to strive to better understand the health risks related to TZD therapy, especially as new therapeutic roles for TZDs in the prevention and treatment of some cancers, inflammatory diseases, and other conditions in non-diabetic populations are being explored.

Osteoporosis is a significant healthcare issue due to the increasing elderly population. Bisphosphonates are used to treat osteoporosis by reducing the rate of resorption, increasing bone mineral density (BMD) and thereby reducing fracture risk. Long-term bisphosphonate treatment, however, has been associated with low-energy fractures. Bone microdamage may provide a partial explanation for one of the mechanisms responsible for these fractures since it has been shown to reduce bone toughness, fracture resistance, and bone strength. The goal of this study was to quantify the changes in bone microdamage parameters with the duration of bisphosphonate treatment. This study selected, stained, and histomorphometrically analyzed 40 iliac crest bone biopsies from controls and female patients with osteoporosis treated with bisphosphonates for varying durations (up to 12 years). All subjects were matched for age and low turnover. The results showed that microcrack density and microcrack surface density were significantly greater in patients who took bisphosphonates for at least 5 years compared to those who took bisphosphonates for less than 5 years or not at all. These results reveal novel, clinically relevant information linking microdamage accumulation to long-term bisphosphonate treatment without influences from age or turnover.

Projeto de Graduação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Licenciada em Fisioterapia
Objetivo: Estabelecer uma relação entre a tríada feminina com as lesões músculo-esqueléticas nas atletas femininas. Metodologia: pesquisa computorizada nas bases de dados PubMed, Google scholar e Scielo para identificar estudos que analisassem as relações entre a tríade e a ocorrência de lesões nas jovens desportistas seguindo os critérios de inclusão definidos para o estudo. Foi realizada a análise de qualidade com recurso à escala Critical Appraisal Skills Programme (CASP) Resultados: Da análise metodológica obteve-se um score médio de 10/14 Nesta revisão foram incluídos 8 artigos envolvendo 833 atletas, com uma idade média de 19,3 anos. As atletas com distúrbio menstrual têm uma tendência para terem um risco acrescido de contrair lesões, com uma maior prevalência de lesões traumáticas. Os distúrbios alimentares e redução da DMO também se encontram relacionados com a ocorrência de lesões músculo-esqueléticas em atletas femininas. Conclusão: Dos artigos mencionados, podemos concluir que os distúrbios da tríade parecem representar um risco para as atletas femininas, aumentando o número de lesões músculo-esqueléticas durante a época desportiva. No entanto, identificamos as possíveis medidas preventivas e o papel do fisioterapeuta relativamente a este problema com o intuito de diminuir a prevalência desta síndrome em equipas desportivas.
Objective: To establish a relationship between female triad and musculoskeletal injuries in female athletes. Methodology: Computerized research in the PubMed, Google scholar and Scielo databases to identify studies that analyzed the relationships between the triad and the occurrence of injuries in young sportswomen following the inclusion criteria defined for the study. Quality analysis was performed using the Critical Appraisal Skills Program scale (CASP). Results: From the methodological analysis, an average score of 10/14 was obtained. In this review, 8 articles were included involving 833 athletes, with a mean age of 19,3 years old. Athletes with menstrual disorders have a tendency to have an increased risk of contracting injuries, with a higher prevalence of traumatic injuries. Eating disorders and BMD reduction are also related to the occurrence of musculoskeletal injuries in female athletes. Conclusion: From the mentioned articles, we can conclude that the triad disorders seem to represent a risk for the female athletes, increasing the number of musculoskeletal injuries during the sporting season. However, we identified the possible preventive measures and the role of the physiotherapist in relation to this problem in order to reduce the prevalence of this syndrome in sports teams.
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INTRODUÇÃO: As fraturas da extremidade proximal do úmero são frequentes, com incidência crescente no idoso e com impacto na qualidade de vida e na função do ombro. Para os casos com desvio, a placa bloqueada é o método mais utilizado de osteossíntese. Bons resultados clínicos são obtidos tanto com a placa bloqueada como com a haste intramedular bloqueada. O objetivo do estudo foi a comparação desses métodos no tratamento das fraturas da extremidade proximal do úmero quanto aos resultados clínicos, radiográficos e à taxa de complicações. MÉTODOS: Nesse estudo clínico prospectivo e randomizado, 72 pacientes com fraturas desviadas da extremidade proximal do úmero, classificadas como em 2 ou 3 partes de Neer, foram alocados para receberem osteossíntese com placa bloqueada (36 pacientes - Grupo Placa) ou haste intramedular bloqueada (36 pacientes - Grupo Haste). Os desfechos clínicos foram avaliados aos 3, 6 e 12 meses e incluíram as escalas de Constant e Murley, Universidade da Califórnia em Los Angeles modificada (UCLA), escala visual analógica de dor (EVA) e o questionário \"Disability of Arm, Shoulder and Hand\"(DASH) e a amplitude de movimento passiva. Os desfechos radiográficos consistiram na avaliação da consolidação e do ângulo cabeça-diáfise. As complicações foram avaliadas até os 12 meses e incluíram a avaliação do manguito rotador pela ultrassonografia. O desfecho primário do estudo foi a avaliação pela escala de Constant e Murley, aos 12 meses de pós-operatório. RESULTADOS: Sessenta e cinco pacientes completaram 12 meses de seguimento, sendo 32 no Grupo Haste e 33 no Grupo Placa. A escala de Constant aos 12 meses foi de 70,3 pontos para o Grupo Haste e de 71,5 pontos para o Grupo Placa (p = 0,750). A escala de Constant Relativa Individual foi de 81% para o Grupo Haste e de 85% para o Grupo Placa (p = 0,400). Também não houve diferença entre os grupos aos 3 e 6 meses para a escala de Constant. A escala EVA e o questionário DASH também não apresentaram diferença aos 3, 6 e 12 meses, assim como os resultados radiográficos. A escala UCLA apresentou diferença de 4,0 pontos aos 3 meses, com melhores resultados para o Grupo Haste (p = 0,005), mas sem diferença significante aos 6 e 12 meses. A amplitude de movimento apresentou diferença de 2,1 pontos favorável ao Grupo Haste para a rotação medial aos 6 meses (p = 0,042), sem diferença para os demais planos de movimento nos diferentes momentos de avaliação. Foram registradas 38 complicações, sendo 28 no Grupo Haste e 10 no Grupo Placa, com diferença estatística (p = 0,001). As complicações ocorreram em 18 pacientes, sendo 11 (34%) do Grupo Haste e sete (21%) do Grupo Placa, sem diferença estatística (p = 0,137). CONCLUSÕES: A osteossíntese das fraturas da extremidade proximal do úmero com placa bloqueada ou haste intramedular bloqueada produziram resultados clínicos e radiográficos semelhantes. A fixação com haste intramedular bloqueada apresentou maior taxa de complicações e reoperações
INTRODUCTION: Fractures of the proximal humerus are common, with an increasing incidence in the elderly and with a high impact on quality of life and shoulder function. For displaced fractures, the locking plate is the most used method of osteosynthesis. Studies have shown good clinical results with the use of locking plates, but also with the fixation with locking intramedullary nail. The aim of this study was to compare the clinical outcomes, radiographic results and the complications between these two methods in patients with displaced proximal humerus fractures. METHODS: In this prospective, randomized clinical trial, 72 patients with displaced fractures of the proximal humerus, classified as Neer 2- or 3-part, were randomly assigned to receive osteosynthesis with either locking plate (36 patients - Plate Group) or locking intramedullary nail (36 patients - Nail Group). The clinical outcomes were evaluated at 3, 6 and 12 months and included the Constant and Murley, University of California at Los Angeles (UCLA) and Disability of Arm, Shoulder and Hand (DASH) scores, visual analog scale (VAS) and the passive range of motion. Radiographic findings (consolidation and head shaft angle) and complications, which included the evaluation of rotator cuff by ultrasound, were also evaluated. The primary outcome was the Constant and Murley score at 12 months. RESULTS: Sixty-five patients completed 12 months of follow-up, 32 in the Nail Group and 33 in the Plate Group. The mean Constant score at 12 months was 70.3 points for the Nail Group and 71.5 points for the Plate Group (p = 0.750) and the mean Relative Constant score was 81% for the Nail Group and 85% points for the Plate Group (p = 0.400). There was also no difference at 3 and 6 months for the Constant score. VAS, DASH and radiographic findings also did not differ at 3, 6 and 12 months. Range of motion showed a 2.1 points difference in favor of the Nail Group for medial rotation at 6 months (p = 0.042), with no difference for the other motions at 3, 6 and 12 months. The UCLA score presented a difference of 4.0 points at 3 months, with better results for the Nail Group (p = 0.005), but no significant difference at 6 and 12 months. Thirty-eight complications were recorded, 28 in the Nail Group and 10 in the Plate Group, with significant difference (p = 0.001). Complications occurred in 18 patients, 11 (34%) of the Nail Group and seven (21%) of the Plate Group, with no significant difference (p = 0.137). CONCLUSIONS: Locking plates and locking intramedullary nail yielded similar clinical and radiographic results. Locking intramedullary nail fixation has a higher risk for complications and reoperations

INTRODUÇÃO: As fraturas do terço médio da clavícula representam 80% das fraturas claviculares e seu tratamento é motivo de discussão na literatura ortopédica. Estudos prévios relativos ao tratamento cirúrgico têm demonstrado bons resultados clínicos com o uso das placas de reconstrução ou a fixação intramedular elástica estável com hastes flexíveis de titânio. O objetivo deste estudo foi a comparação desses métodos no tratamento das fraturas do terço médio da clavícula, quanto aos resultados funcionais, parâmetros radiográficos, dor pós-operatória, taxa de satisfação e taxa de complicações. MÉTODOS: Neste ensaio clínico comparativo, prospectivo e randomizado, 59 pacientes com fratura desviada do terço médio da clavícula foram alocados aleatoriamente para receberem osteossíntese com placa de reconstrução (33 pacientes - grupo Placa) ou haste flexível de titânio (26 pacientes - grupo Haste). O desfecho primário do estudo foi a avaliação funcional pelo escore DASH aos 6 meses de pós-operatório. Os desfechos secundários foram: o escore DASH aos 12 meses; o escore de Constant- Murley aos 6 e 12 meses; o tempo de consolidação da fratura; o encurtamento residual; o nível de dor pela escala visual analógica no 1º pósoperatório; a taxa de pacientes satisfeitos e a taxa de complicações. RESULTADOS: Cinquenta e quatro pacientes completaram o seguimento, sendo 29 do grupo Placa e 25 do grupo Haste. O escore DASH médio aos 6 meses foi de 9,9 pontos no grupo Placa e 8,5 no grupo Haste, sem diferença estatisticamente significante (p = 0,329). Da mesma forma, não houve diferenças significantes no escore DASH aos 12 meses ou no escore de Constant aos 6 e 12 meses. O tempo de consolidação foi equivalente entre os grupos (p = 0,352), enquanto o encurtamento residual foi maior no grupo Placa, com significância estatística (p = 0,032), mas sem relevância clínica (0,4 cm). Os resultados da escala visual analógica para dor no 1º pósoperatório e a taxa de pacientes satisfeitos foram similares entre os grupos. O grupo Placa apresentou mais casos com angulação do implante (11 casos) do que o grupo Haste (um caso) (p = 0,003), enquanto o grupo Haste foi mais associado à dor relacionada ao implante (10 casos), em comparação ao grupo Placa (4 casos) (p = 0,035). Não houve diferenças significantes entre os grupos quanto às complicações maiores, incluindo falha do implante, infecção pós-operatória, pseudoartrose e reoperação. CONCLUSÕES: A osteossíntese das fraturas desviadas do terço médio da clavícula com placa de reconstrução ou haste flexível de titânio produzem resultados semelhantes quanto aos escores funcionais, tempo de consolidação, dor pós-operatória, satisfação dos pacientes e complicações maiores. As placas de reconstrução são mais suscetíveis à angulação do implante, enquanto as hastes flexíveis de titânio causam mais dor relacionada ao implante
INTRODUCTION: Midshaft clavicle fractures represent 80% of all clavicular fractures, and their treatment is controversial in the literature. Previous studies have shown good clinical results in patients with midshaft clavicular fractures treated with reconstruction plate fixation or elastic stable intramedullary nailing (ESIN). The objective of this study was to compare these methods in terms of functional results, radiographic parameters, postoperative pain, satisfaction rates and complication rates. METHODS: In this prospective, randomized, controlled trial, 59 patients with displaced midshaft clavicular fractures were randomly assigned to receive either reconstruction plate (33 patients - Plate group) or ESIN fixation (26 patients - ESIN group). The primary outcome was the DASH score at 6 months. The secondary outcomes were the following: DASH score at 12 months; Constant-Murley scores at 6 and 12 months; time to fracture union; residual shortening; visual analog scale for pain on the first post-operative day; percentage of satisfied patients; and complications rates. RESULTS: Fifty-four patients completed the follow-up, 29 in the Plante group and 25 in the ESIN group. The mean DASH score at 6 months was 9.9 in the plate group and 8.5 in the ESIN group, with no significant difference (p = 0.329). Similarly, there were no differences in the DASH score at 12 months or the Constant-Murley scores at 6 and 12 months. The time to union was equivalent between the groups (p = 0.352), whereas the residual shortening was significantly greater in the plate group (p = 0.032) but was not clinically relevant (0.4 cm). The visual analog scale scores for pain and the percentage of satisfied patients were similar between the groups. Implant bending was significantly more common in the plate group (eleven patients) than in the ESIN group (one patient) (p = 0.003), whereas hardware-related pain was more frequent in the ESIN group (10 patients vs. 4 patients) (p = 0.035). There were no differences in terms of major complications, including implant failure, postoperative infection, nonunion and reoperation. CONCLUSIONS: Reconstruction plates and ESIN yielded similar results in terms of functional results, time to union, post-operative pain, patient satisfaction and major complications in patients with displaced midshaft clavicular fractures. Reconstruction plates are more susceptible to implant bending, whereas ESIN causes more hardwarerelated pain

Cell-based therapies have potential for tissue regeneration but poor delivery methods lead to low viability or dispersal of cells from target sites, limiting clinical utility. Here, we developed a degradable and injectable hydrogel to deliver stem cells for bone regeneration. Alginate microbeads <200µm are injectable, persist at implantation sites and contain viable cells, but do not readily degrade in-vivo. We hypothesized that controlled release of rat adipose-derived stem cells (ASCs) from alginate microbeads can be achieved by incorporating alginate-lyase in the hydrogel. Microbeads were formed using high electrostatic potential. Controlled degradation was achieved through direct combination of alginate-lyase and alginate at 4°C. Results showed that microbead degradation and cell release depended on the alginate-lyase to alginate ratio. Viability of released cells ranged from 87% on day 2 to 71% on day 12. Monolayer cultures of released ASCs grown in osteogenic medium produced higher levels of osteocalcin and similar levels of other soluble factors as ASCs that were neither previously encapsulated nor exposed to alginate-lyase. Bmp2, Fgf2, and Vegfa mRNA in released cells were also increased. Thus, this delivery system allows for controlled release of viable cells and can modulate their downstream osteogenic factor production.

Abstract There are previous reports of an increasing incidence of children’s forearm fractures in the last few decades. Their surgical treatment is evolving. The present study was aimed at determining the incidence and background of these fractures and their treatment. It was also aimed to analyse the short- and long-term outcomes. A comprehensive population-based study (N=168) among 86,000 children in Oulu University Hospital District over a decade (2000–2009) was performed to analyse the incidence of middle-third forearm fractures. Further data (N=291) covering 1997–2009 was achieved in order to study monthly variation and backgrounds of all both-bone forearm fractures in the distal, middle or proximal thirds. An age- and sex-matched case-control study (N=94) at Vaasa Central Hospital District in 1995–1999 with approximately 11 years of follow-up was performed to evaluate long-term morbidity. The relationship between summer weather and outdoor fractures was based on daily weather readings of all summer days (N=1989) in 1997–2009. There was a 4.4-fold increase in middle-third shaft fractures in the last decade (2000–2009) and a 3.1-fold increase in all forearm shaft fractures (proximal, middle and distal) in 1997–2009. The increase in the middle-shaft fractures was still accelerating towards the end of the study period. Trampolining was increasing as a reason for the injuries. At the end of the study every third fracture was caused by a trampoline injury. The fractures caused by other recreational activities increased absolutely, but they were stable in relation to trampoline injuries. There was a clear monthly variation in fracture incidence. During the long study time, August was repeatedly the most usual month for the fractures. School terms and summer holidays did not explain the varying fracture risk. The incidence of the fractures was 50% higher in dry vs. rainy days in summer. Temperature and wind speed did not affect fracture risk. Not only were the number of children’s forearm shaft fractures increasing, but also their operative treatment in 1997–2009. The increase was mostly connected to elastic stable intramedullary nailing (ESIN), the incidence of which changed from 10% to 30% during the study period, compared with other types of treatment. Non-operative treatment showed poor short-term outcome in the form of worsening alignment and a relatively great need of re-operations. Operative treatment showed excellent primary results. In the long run, the outcome of non-operative treatment was excellent
Tiivistelmä Lasten kyynärvarren diafyysimurtumat ovat lisääntyneet viimeisten vuosikymmenten aikana. Samalla niiden kirurginen hoito on muuttunut. Tämän tutkimuksen tavoitteena oli selvittää murtumien ilmaantuvuutta ja murtumien taustalla olevia tekijöitä sekä hoidon kehittymistä. Tavoitteena oli myös tutkia lyhyt- ja pitkäaikaisia hoitotuloksia. Ilmaantuvuuden määrittämiseksi kerättiin väestöpohjainen aineisto (N=168) kaikista niistä lapsista (<16-v.), jotka ovat olleet hoidossa Oulun yliopistollisessa sairaalassa kyynärvarren keskialueen murtuman vuoksi 2000–2009. Taustatekijöiden selvittämiseksi aineisto laajennettiin koskemaan kaikkia kyynärvarren kahden luun murtumia (proksimaaliset, keskialueen ja distaaliset murtumat) 1997–2009 (N=291). Pitkäaikaistuloksia arvioitiin tapaus-verrokkitutkimuksella (N=94), jonka potilasaineiston muodostivat Vaasan keskussairaalassa vuosina 1995–1999 hoidetut lapsipotilaat. Ikä- ja sukupuolivakioidut vertailutapaukset poimittiin väestörekisteristä. Kesäsään ja ulkona tapahtuvien murtumien välisen yhteyden tutkimiseksi kerättiin säätila-aineisto kaikilta vuosien 1997–2009 kesäpäiviltä (N=1989). Lasten kyynärvarren keskidiafyysin murtumat lisääntyivät 4,4-kertaisesti vuosikymmenessä (2000–2009) ja kaikki diafyysimurtumat lisääntyivät 3,1-kertaisesti (1997–2009). Keskidiafyysimurtumien ilmaantuvuus kasvoi kiihtyvästi. Trampoliini aiheutti yksinään joka kolmannen murtuman, ja trampoliinimurtumien ilmaantuvuus kasvoi tutkimusaikana. Muut tapaturmatyypit pysyivät vakioisina. Murtumien ilmaantuvuus vaihteli kuukausittain, mutta 13 vuoden seurantajaksolla ne olivat selvästi yleisimpiä elokuussa. Koululaisten kesäloma ei vaikuttanut murtumariskiin. Murtumat olivat 50 % yleisempiä kuivalla säällä kuin sadesäällä. Lämpötila tai tuulennopeus eivät vaikuttaneet murtumien ilmaantuvuuteen. Lasten kyynärvarsimurtumien operatiivinen hoito lisääntyi. Joustavien ydinnaulojen käyttö kasvoi 10 %:sta 30 %:iin suhteessa muihin hoitomuotoihin. Kajoavan hoidon lyhytaikaiset tulokset olivat erinomaiset. Kajoamattoman hoidon tulokset olivat heikot, ja hoitoon liittyi paljon asennon huonontumista ja myöhempää leikkaustarvetta, erityisesti asennon korjaamista. Pitkän ajan seurannassa kajoamattoman hoidon tulokset olivat kuitenkin erinomaiset
Sammanfattning Barns underarmsfrakturer har ökat under de senaste årtiondena och deras behandling är under förändring. Syftet med den här forskningen var att undersöka underarmsfrakturer: förekommande, bakgrund och behandling. Meningen var också att bedöma resultat av olika frakturbehandlingar på kort och lång sikt. Totalt 168 barn undersöktes. De behandlades på Uleåborgs universitetssjukhus åren 2000–2009 p.g.a. en underarmsfraktur i mellersta tredjedelen av skaft. Därtill inkluderades 291 barn med en underarmsfraktur i hela skaftet åren 1997–2009. En fall-kontroll–undersökning innehöll 47 barn med en underarmsfraktur i Vasa centralsjukhus åren 1996–1999 samt en köns- och ålders standardiserad kontroll grupp med 47 medlemmar (N=47). Relationen mellan sommarväderlek och frakturer som skedde utomhus analyserades på basis av uppgifter om väderleken på alla sommardagarna åren 1997–2009 (N=1989). Frakturer i den mellersta underarmen ökade 4,4-faldigt och accelererande på ett årtionde (2000–2009) och alla skaftfrakturer 3,1-faldigt (1997–2009). Trampolinen tillfogade var tredje av dessa frakturer och således ökade trampolinens betydelse. Jämfört med trampolinen höll sig andra bakgrundsfaktorer stadiga. Det fanns en klar variation i förekommande av frakturer mellan månaderna. Mest förekom frakturer i augusti. Skolperioden eller sommarlovet påverkade inte risken för frakturer. Uppehållsväder ökade risken 1,5-faldigt jämfört med regniga dagar. Temperaturen eller vinden hade ingen effekt på frakturer. Operativa kirurgiska behandlingar ökade i stället för ej-operativa behandlingar åren 1997–2009. Ökningen berodde mest på tilltagande bruk av flexibla märgspikar, vilket ökade från 10 % till 30 % jämfört med andra behandlingsmetoder. Ej-operativ vård visade gott om komplikationer under den korta uppföljningen. Operativ vård var framgångsrik på kort sikt. Däremot visade ej-operativ behandling utmärkta resultat efter den långa uppföljningen

A Osteogênese Imperfeita (OI) é uma doença genética do tecido conjuntivo caracterizada por fragilidade óssea e susceptibilidade à fratura sob mínimo ou nenhum trauma. O objetivo deste trabalho foi estudar características clínicas e moleculares de crianças e adultos com Osteogênese Imperfeita e analisar o efeito do tratamento medicamentoso com bifosfonados em relação aos biomarcadores metabólicos e ósseos em pacientes adultos. Esta tese se dividiu em dois capítulos onde 1) foi realizado um estudo retrospectivo sobre as características clínicas no momento do diagnóstico de OI, com ênfase nas características clínicas, especialmente em relação às fraturas ósseas; 2) avaliação clínica e análise da mutação c.-14C>T no gene IFITM5 foi estuda em uma população com características sugestivas de OI tipo V; e 3) estudo retrospectivo em adultos com OI divididos em 2 grupos tratados com bifosfonados e não tratados. Em relação ao tratamento com bifosfonados foram avaliados os seguintes parâmetros: tipo de droga e duração do tratamento, valores de biomarcadores metabólicos e ósseos por um período de 5 anos, incidência de fraturas num de período de 5 ou 10 anos e densidade mineral óssea da coluna lombar, quadril total e colo femural no início e no final do tratamento. Nossos resultados mostraram que 1) no momento do diagnósico de OI características como escleras azuladas, dentinogênese imperfeita, ossos wormianos e fraturas de membros inferiores e superiores podem ser observadas. Pacientes com formas mais graves de OI foram diagnosticados mais precocemente quando comparados com pacientes com formas leves. Nenhuma criança com OI apresentou fraturas posteromediais das costelas, fratura de escápula ou lesões metafisárias. Essas informações associadas a história da saúde da criança são relevantes para a realização do diagnóstico diferencial. 2) OI tipo V correspondeu a 4% dos casos de OI atendidos no Centro de Referência para OI do HCPA. Indivíduos com OI V associada a mutação c.-14C> T no gene IFITM5 apresentaram características clínicas distintas como formação de calo hiperplásico, calcificação das membranas interósseas, deslocamento da cabeça radial e deformidade de coluna, porém a expressão da doença é variável. 3) Observamos que o tratamento de adultos com OI a longo prazo não foi associado com redução na incidência das fraturas e não se refletiu de forma significativa nos níveis de biomarcadores metabólicos e ósseos, porém houve uma melhora significativa na densidade mineral óssea da coluna lombar associada à terapia. Por ser uma doença rara com prevalência variável e ampla variabilidade fenotípica e genotípica, estudos clínicos e moleculares bem como estudos sobre o efeito do tratamento medicamentoso são imprescindíveis, contribuindo no melhor entendimento da doença, aconselhamento genético acurado e propiciando melhores estratégias de prevenção e tratamento para esta população.
Osteogenesis Imperfecta (OI) is a genetic connective tissue disease characterized by bone fragility and susceptibility to fracture under minimal or no trauma. The aim of this study was to evaluate clinical and molecular features of children and adults with OI and analyze the effect of the drug treatment with bisphosphonates in regarding to metabolic and bone biomarkers in adult patients. This thesis was divided by two chapters: 1) a retrospective study was performed where the clinical characteristic at the moment of diagnosis of OI, the clinical characteristics specially related to bone fractures was evaluated; 2) clinical evaluation and mutation analysis of c.-14C>T in the IFITM5gene was studied in a population with clinical charcteristics suggestive of OI type V; and 3) retrospective study in adults with OI divided in two groups treated with biphosphonates and not treated. Bisphosphonate treatment was evaluated according to the parameters: type of drug and duration of treatment, metabolic and bone biomarkers values for a period of 5 years, incidence of fractures in a period of 5 or 10 years and bone mineral density of the lumbar spine, total hip and femoral neck at baseline and at the end of treatment. Our results showed that 1) at the time of OI diagnosis features such as bluish slerae, dentinogenis imperfecta, wormian bones, and fractures of upper and lower limbs can be observed. Patients with more severe forms of OI were diagnosed earlier when compared with patients with mild forms. No OI children presented posteromedial fractures of the ribs, scapula fracture or metaphyseal lesions. This information associated with the child's health history are relevant for carrying out the differential diagnosis. This information is relevant for carrying out the differential diagnosis. 2) OI type V corresponds to 4% of OI cases at the Reference Center for OI at HCPA. Subjects with OI V associated to the mutation c.-14C> T in the IFITM5 gene presented distinctives clinical features as hyperplastic callus formation, calcification of interosseous membranes, dislocation of the radial head and spinal deformity, but the expression of the disease is variable. 3) We observed that long-term treatment with bisphosphonates (BP) for adults with OI was not associated with reduced incidence of fractures and was not reflected significantly in the levels of metabolic and bone biomarkers, but there was a significant improvement in bone mineral density of the lumbar spine associated to the therapy. Because it is a rare disease with a prevalence variable and wide phenotypic and genotypic variability, clinical and molecular studies and studies of the effect of drug treatment are essential, contributing to the better understanding of the disease, accurate genetic counseling and providing better strategies for prevention and treatment for this population.

The use of injectable biomaterials is growing as the demands for minimally invasive procedures, and more easily applicable implants become higher, but their availability is still limited due to the difficulties associated to their design. Each year, more than 700,000 vertebral compression fractures (VCF’s) are reported in the US and 500,000 VCF’s in Europe due to primary osteoporosis only. VCF’s can compromise the delicacy of the spinal canal and also cause back pain, which affects the patient’s quality of life. Vertebroplasty was developed in the 80’s, and has proven to be a safe minimally invasive procedure that can, quickly and sustainably, relieve the pain in patients experiencing VCF’s. However, biomaterials for vertebroplasty still have limitations. For instance, ceramic bone cements are difficult to distinguish from the bone using X-ray techniques. On the other hand, acrylic bone cements may cause adjacent vertebral fractures (AVF’s). Large clinical studies have indicated that 12 to 20% vertebroplasty recipients developed subsequent vertebral fractures, and that 41 to 67% of these, were AVF’s. This may be attributed to the load shifting and increased pressure on the adjacent endplates reached after vertebroplasty with stiff cements. The primary aim of this thesis was to develop better injectable biomaterials for spinal applications, particularly, bone cements for vertebroplasty. Water-soluble radiopacifiers were first investigated to enhance the radiopacity of resorbable ceramic cements. Additionally, different strategies to produce materials that mechanically comply with the surrounding tissues (low-modulus bone cements) were investigated. When a suitable low-modulus cement was produced, its performance was evaluated in both bovine bone, and human vertebra ex vivo models. In summary, strontium halides showed potential as water-soluble radiocontrast agents and could be used in resorbable calcium phosphates and other types of resorbable biomaterials. Conversely, linoleic acid-modified (low-modulus) cements appeared to be a promising alternative to currently available high-modulus cements. It was also shown that the influence of the cement properties on the strength and stiffness of a single vertebra depend upon the initial bone volume fraction, and that at low bone volume fractions, the initial mechanical properties of the vertebroplasty cement become more relevant. Finally, it was shown that vertebroplasty with low-modulus cements is biomechanically safe, and could become a recommended minimally invasive therapy in selected cases, especially for patients suffering from vertebral compression fractures due to osteoporosis.

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O uso de materiais produzidos a partir de osso bovino tem sido proposto na confecção de implantes como pinos, placas e parafusos, por promoverem as mesmas funções de um enxerto ósseo, ou seja, serem osteoindutores e osteocondutores. Entretanto, aspectos estruturais e mecânicos devem ser estudados previamente ao uso in vivo de implantes de osso. Portanto, o objetivo desse estudo foi avaliar o comportamento mecânico, por meio do ensaio mecânico de flexão, de placas produzidas a partir osso cortical bovino, no reparo de fratura de tíbia de coelhos ex vivo. Para tal, 26 placas foram confeccionadas a partir de osso cortical bovino e conservadas em solução de sal a 150%. Foram utilizados três grupos para estudo: grupo GP (n=10), composto pelas placas ósseas; grupo GTP (n=16), tíbias de coelhos osteotomizadas e estabilizadas com placas ósseas e quatro parafusos; grupo GT (n=10), tíbias intactas. No ensaio biomecânico de flexão em três pontos, verificou-se a tensão máxima, deflexão máxima e rigidez. Os resultados foram submetidos ao teste de Kruskal-Wallis (p<0,05) e ao teste de Dunn. Comparando GT com o GTP, observou-se redução de 80% na tensão máxima. Também se notou redução de 87% na tensão máxima ao comparar GP com o GTP. Verificou-se que a placa de osso bovino possuiu maior tensão máxima que a tíbia do coelho. Houve redução a 52% na rigidez do GTP em relação ao GT. Não observou-se diferença significativa nesta propriedade entre GPT e GP. Observou-se diferença significativa entre os três grupos com relação à deflexão máxima, onde notou-se aumento de 100% e 30% nos grupos GTP e GP, respectivamente, em relação ao GT. Pode-se concluir que placas ósseas, no reparo de fratura de tíbia de coelhos ex vivo obtiveram propriedades mecânicas inferiores, quando comparada à tíbia intacta.

Bibliography: leaves 216-231. Examines the sliding capability of external fixators under load and describes the development and testing of an external fixator capable of providing axial cyclic motion to a fracture site while a patient is walking.

Chow, Dick Ho Kiu.
Thesis (M.Phil.)--Chinese University of Hong Kong, 2010.
Includes bibliographical references (leaves 93-103).
Abstracts in English and Chinese.
Abstract --- p.ii
Publications --- p.vii
Acknowledgement --- p.viii
Table of Contents --- p.x
List of Figures --- p.xiv
List of Tables --- p.xv
List of Abbreviations --- p.xvii
Chapter 1 --- Introduction --- p.1
Chapter 1.1 --- Bone and its Cellular Components --- p.1
Chapter 1.1.1 --- Cellular Components of Bone --- p.1
Chapter 1.1.2 --- Macroscopic Structure --- p.4
Chapter 1.1.3 --- Microscopic Structure --- p.4
Chapter 1.2 --- Fracture Healing --- p.5
Chapter 1.2.1 --- Inflammation --- p.6
Chapter 1.2.2 --- Soft Callus Formation --- p.6
Chapter 1.2.3 --- Hard Callus Formation --- p.7
Chapter 1.2.4 --- Bone Remodeling --- p.7
Chapter 1.3 --- Low Magnitude High Frequency Vibration (LMHFV) Stimulation --- p.7
Chapter 1.3.1 --- Mechanical Stimulation --- p.10
Chapter 1.3.2 --- Effect of LMHFV on Bone --- p.12
Chapter 1.4 --- Osteoporosis and Osteoporotic Fractures --- p.16
Chapter 1.4.1 --- Epidemiology of Osteoporotic Fracture --- p.17
Chapter 1.4.2 --- Pathophysiology --- p.17
Chapter 1.4.3 --- Osteoporotic Fracture Healing --- p.20
Chapter 1.5 --- Bisphosphonate --- p.23
Chapter 1.5.1 --- Background --- p.23
Chapter 1.5.2 --- Mechanism of Action --- p.24
Chapter 1.5.3 --- U sage of Bisphosphonate --- p.25
Chapter 1.5.4 --- Bisphosphonate Effects on Fracture Healing --- p.27
Chapter 1.6 --- Hypothesis --- p.27
Chapter 1.7 --- Study Plan --- p.28
Chapter 1.7.1 --- Objectives --- p.28
Chapter 2 --- Method --- p.29
Chapter 2.1 --- Ovariectomized Rat Femoral Fracture Model --- p.29
Chapter 2.1.1 --- Ovariectomized Rat Model. --- p.29
Chapter 2.1.2 --- Closed Femoral Fracture --- p.31
Chapter 2.2 --- Study Design --- p.32
Chapter 2.3 --- LMHFV Treatment Protocol --- p.32
Chapter 2.4 --- Bisphosphonate Treatment Protocol --- p.35
Chapter 2.4.1 --- Pharmacological Parameters --- p.35
Chapter 2.4.2 --- Ibandronate Injection Solution Preparation --- p.37
Chapter 2.4.3 --- Injection --- p.37
Chapter 2.5 --- Fluorochrome Labeling --- p.38
Chapter 2.5.1 --- Fluorochrome Preparation --- p.38
Chapter 2.5.2 --- Injection --- p.38
Chapter 2.6 --- Assessments --- p.39
Chapter 2.6.1 --- Radiographic Analysis --- p.39
Chapter 2.6.2 --- uCT Analysis --- p.40
Chapter 2.6.3 --- Undecalcified Histology --- p.43
Chapter 2.6.4 --- ELISA Analysis on Bone Markers --- p.47
Chapter 2.7 --- Statistical Analysis --- p.50
Chapter 3 --- Results --- p.51
Chapter 3.1 --- Radiographic Analysis --- p.52
Chapter 3.1.1 --- Callus Bridging Rate --- p.52
Chapter 3.1.2 --- Callus Width and Area --- p.52
Chapter 3.2 --- uCT Analysis --- p.55
Chapter 3.3 --- Histomorphometric Analysis --- p.61
Chapter 3.3.1 --- Bone Mineralization Rate --- p.61
Chapter 3.4 --- Bone Markers Analysis --- p.64
Chapter 3.4.1 --- Osteocalcin --- p.64
Chapter 3.4.2 --- TRAP5b --- p.64
Chapter 3.4.3 --- Summary --- p.67
Chapter 4 --- Discussion --- p.69
Chapter 4.1 --- LMHFV Enhanced Bone Remodeling --- p.69
Chapter 4.1.1 --- LMHFV Reversed Bis Inhibition on Bone Remodeling --- p.70
Chapter 4.1.2 --- LMHFV Effect on Osteoclastic Resorption During Bone Re-modeling --- p.71
Chapter 4.2 --- Enhanced Fracture Healing by LMHFV --- p.72
Chapter 4.2.1 --- Acceleration of Fracture Healing by LMHFV --- p.72
Chapter 4.2.2 --- LMHFV Inhibits Osteoclast Activity in the Early Phase of Healing --- p.73
Chapter 4.2.3 --- LMHFV Stimulates Osteoblast Activity in the Early Phase of Healing --- p.74
Chapter 4.3 --- Bis Delays Fracture Healing --- p.75
Chapter 4.4 --- Experimental Design --- p.78
Chapter 4.4.1 --- Inhibition Study --- p.78
Chapter 4.4.2 --- Bisphosphonate Injection Protocol --- p.79
Chapter 4.4.3 --- Individual Analysis of Bone Formation and Resorption . --- p.81
Chapter 4.5 --- Clinical Implications --- p.84
Chapter 4.5.1 --- LMHFV Enhanced Remodeling --- p.84
Chapter 4.5.2 --- Bisphosphonate Delayed Remodeling --- p.85
Chapter 4.6 --- Limitations --- p.85
Chapter 4.6.1 --- Measurement of Bone Resorption --- p.85
Chapter 4.6.2 --- Osteoporotic Fracture Model --- p.86
Chapter 4.6.3 --- Inhibition of Bone Remodeling --- p.87
Chapter 4.7 --- Future Studies --- p.88
Chapter 4.7.1 --- LMHFV Effect on Osteoclast in vitro --- p.88
Chapter 4.7.2 --- Biomechanics of Fracture Callus --- p.89
Chapter 4.7.3 --- LMHFV Effect on Leptin- Adrenergic Pathway --- p.89
Chapter 5 --- Conclusion --- p.91
Bibliography --- p.93

Bone fracture, particularly that occurring in osteoporotic conditions, has become a major health issue. Fracture healing is a well-orchestrated regenerative process, the enhancement of which has been one of the major goals in fracture management. Low-magnitude high-frequency vibration (LMHFV) is osteogenic for intact bone and beneficial for limb blood circulation, which implies a potential of enhancement for fracture healing. Three parts of the experiments were conducted in this study to test the hypothesis that LMHFV would accelerate fracture healing by promoting chondrogenesis, endochondral ossification, and remodeling in both normal and osteoporotic bones.
Part I study. Three-month-old female SD rats underwent closed femoral fracture and were randomized into either vibration group (VG-I, 35Hz, 0.3g, 20min/day, 5days/week) or sham-treated control group (CG-I). Femora were harvested at 1, 2 and 4 weeks for micro-CT analysis, histomorphometry, and mechanical testing. Part II study. Osteoporotic model was established in nine-month-old SD rats after three months of inducement following ovariectomy. Similar grouping (VG-II and CG-II) and treatment regimes were performed after fracture, with the femora harvested at 2, 4 and 8 weeks for assessments like those in the Part I study. Part III study. After fracture, 3-month-old female SD rats were grouped (VG-III and CG-III) and treated as in the Part I study. At 1, 2 and 4 weeks, femora were collected for gene quantification (Col-1, Col-2, BMP-2, VEGF, and TGF-beta1) using real-time PCR. Type I and II collagens were located immunochemically in histological sections.
Results of the Part I and II studies demonstrated that LMHFV promoted callus formation (together with chondrogenesis), mineralization (endochondral ossification), and remodeling, which led to faster healing and better mechanical outcomes in both normal and osteoporotic fractures. In molecular level, the effect of LMHFV was reflected by the stimulation of chondrogenesis and osteogenesis related matrix collagen formation and growth factor expression. The molecular data echo Part I and II findings well. This study proved that LMHFV accelerated fracture healing by promoting chondrogenesis, endochondral ossification, and remodeling in both normal and osteoporotic bones, and indicated great potential of its future clinical application on fracture healing.
Shi, Hongfei.
Adviser: Kwok-Sui Leung.
Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3422.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2008.
Includes bibliographical references (leaves 180-201).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstracts in English and Chinese.
School code: 1307.

Or Pui Ching.
Thesis submitted in: December 1999.
Thesis (M.Phil.)--Chinese University of Hong Kong, 2000.
Includes bibliographical references (leaves 174-201).
Abstracts in English and Chinese.
acknowledgement --- p.i
abstract (english version) --- p.ii
abstract (chinese version) --- p.vii
table of contents --- p.xi
abbreviations --- p.xvi
list of tables --- p.xviii
list of figures --- p.xxii
Chapter chapter 1. --- introduction --- p.1
Chapter chapter 2. --- literature review --- p.3
Chapter 2.1. --- Bone structure --- p.3
Chapter 2.1.1. --- Composition --- p.3
Chapter 2.1.2. --- Cortical and Trabecular bone --- p.3
Chapter 2.2. --- Bone Remodeling --- p.4
Chapter 2.3. --- Bone Mass --- p.5
Chapter 2.3.1. --- Peak Bone Mass --- p.5
Chapter 2.3.1.1. --- Racial and Genetic Factors --- p.5
Chapter 2.3.1.2. --- Gonadal Factors --- p.6
Chapter 2.3.1.3. --- Nutrition Factors --- p.6
Chapter 2.3.1.4. --- Exercise and Physical Activity --- p.7
Chapter 2.3.2. --- Bone Loss --- p.7
Chapter 2.3.2.1. --- Determinants of Osteoporotic Bone Loss --- p.7
Chapter 2.3.2.2. --- Estrogen Deficiency --- p.8
Chapter 2.3.2.3. --- Dietary Calcium deficiency and Vitamin D deficiency --- p.8
Chapter 2.3.2.4. --- Physical Activity --- p.9
Chapter 2.3.2.5. --- Alcoholism and Smoking --- p.9
Chapter 2.3.2.6. --- Disease-specific Osteoporosis --- p.9
Chapter 2.3.2.7. --- Drug-induced Osteoporosis --- p.10
Chapter 2.3.3. --- Bone Mass and Fracture Risk --- p.11
Chapter 2.4. --- Clinical Presentation of Osteoporosis --- p.12
Chapter 2.4.1. --- Vertebral Fractures --- p.12
Chapter 2.4.1.1. --- Radiological Aspects of Vertebral Fracture --- p.13
Chapter 2.4.1.1.1. --- Changes in Trabecular Pattern --- p.13
Chapter 2.4.1.1.2. --- Changes in Shape of the Vertebral bodies --- p.13
Chapter 2.4.1.1.3. --- Changes of Intervertebral Discs --- p.14
Chapter 2.4.1.2. --- Back Pain --- p.15
Chapter 2.4.2. --- Hip Fractures --- p.15
Chapter 2.4.3. --- Quality of Life --- p.16
Chapter 2.5. --- Treatment of Established Osteoporosis --- p.18
Chapter 2.5.1. --- Pain Relief --- p.18
Chapter 2.5.2. --- Drug Therapy --- p.19
Chapter 2.5.2.1. --- Calcium Supplement --- p.19
Chapter 2.5.2.2. --- Vitamin D --- p.20
Chapter 2.5.2.3. --- Estrogen --- p.21
Chapter 2.5.2.4. --- Fluorides --- p.22
Chapter 2.5.2.5. --- Calcitonin --- p.23
Chapter 2.5.2.6. --- Bisphosphonates --- p.24
Chapter 2.5.2.6.1. --- Physicochemical effects --- p.27
Chapter 2.5.2.6.2. --- Mechanisms --- p.27
Chapter 2.5.2.6.3. --- Therapeutic Use --- p.27
Chapter 2.5.2.6.4. --- Side effects --- p.29
Chapter 2.5.2.6.5. --- Alendronate --- p.30
Chapter 2.5.2.7. --- Summary of drug treatment --- p.33
Chapter 2.6. --- Diagnostic Methods of Osteoporosis --- p.40
Chapter 2.6.1. --- Biochemical Markers of Bone Metabolism in Osteoporosis --- p.40
Chapter 2.6.1.1. --- Bone Formation Markers --- p.41
Chapter 2.6.1.1.1. --- Bone-specific Alkaline Phosphatase (bALP) --- p.41
Chapter 2.6.1.2. --- Bone Resorption Markers --- p.42
Chapter 2.6.1.2.1. --- Deoxypyridinoline (Dpd) --- p.43
Chapter 2.6.2. --- Bone Densitometry --- p.45
Chapter 2.6.2.1. --- Dual Energy X-ray Absorptiometry (DEXA) --- p.45
Chapter 2.6.2.2. --- Peripheral Quatitative Computed Tomography (pQCT) --- p.47
Chapter 2.6.2.3. --- Quantitative Ultrasound (QUS) --- p.48
Chapter 2.6.3. --- Summary of Diagnostic Methods --- p.49
Chapter chapter 3. --- methodology --- p.50
Chapter 3.1. --- Study on Vertebral Structures --- p.51
Chapter 3.1.1. --- Procedures --- p.51
Chapter 3.1.2. --- Data analysis --- p.53
Chapter 3.2. --- Alendronate Treatment --- p.54
Chapter 3.2.1. --- Subject Selection --- p.54
Chapter 3.2.2. --- Study design and drug administration --- p.55
Chapter 3.2.3. --- Bone Densitometry --- p.56
Chapter 3.2.3.1. --- Dual Energy X-ray absorptiometry --- p.56
Chapter 3.2.3.2. --- Peripheral Quantitative Computed Tomography (pQCT) --- p.58
Chapter 3.2.4. --- Biochemical Markers --- p.63
Chapter 3.2.4.1. --- Bone formation marker --- p.63
Chapter 3.2.4.2. --- Bone resorption marker --- p.64
Chapter 3.2.5. --- Quality of Life --- p.65
Chapter 3.2.6. --- New fracture assessment --- p.66
Chapter 3.2.7. --- Statistical analysis --- p.67
Chapter 3.3. --- Proximal femur fracture study --- p.68
Chapter 3.3.1. --- Subject and study design --- p.69
Chapter 3.3.2. --- Statistical analysis --- p.70
Chapter chapter 4. --- results of study on vertebral structures --- p.71
Chapter 4.1. --- Results of morphological change of vertebral bodes in osteoporotic patients --- p.71
Chapter 4.2. --- Morphological changes of intervertebral discs --- p.71
Chapter 4.3. --- Correlation between morphological changes of vertebrae and bulging ratio --- p.72
Chapter chapter 5. --- results of alendronate study --- p.76
Chapter 5.1. --- Baseline measurement --- p.76
Chapter 5.1.1. --- Demographic characteristics --- p.76
Chapter 5.1.2. --- Reasons for admission --- p.77
Chapter 5.1.3. --- Social support --- p.77
Chapter 5.1.4. --- Number of vertebral fracture(s) --- p.78
Chapter 5.1.5. --- BMD measurement (Baseline) --- p.79
Chapter 5.1.5.1. --- BMD of Lumbar spine and Hip (measured by DEXA) --- p.79
Chapter 5.1.5.2. --- BMD of distal tibia and radius measured by pQCT --- p.80
Chapter 5.1.6. --- Biochemical Markers (Bone formation and resorption) --- p.86
Chapter 5.2. --- After treatment --- p.88
Chapter 5.2.1. --- Bone mineral density measurement (measured by DEXA) --- p.90
Chapter 5.2.1.1. --- Lumbar spine --- p.90
Chapter 5.2.1.2. --- Femoral Neck --- p.93
Chapter 5.2.1.3. --- Trochanter --- p.95
Chapter 5.2.1.4. --- Ward's Triangle --- p.98
Chapter 5.2.1.5. --- Summary --- p.101
Chapter 5.2.2. --- Bone Mineral Density measured by pQCT --- p.103
Chapter 5.2.2.1. --- Distal Radius (Program 1) --- p.103
Chapter 5.2.2.1.1. --- BMD change of D50 --- p.103
Chapter 5.2.2.1.2. --- BMD changes of D100 --- p.106
Chapter 5.2.2.1.3. --- BMD change of P100 --- p.108
Chapter 5.2.2.2. --- Distal Radius (Program 2) --- p.111
Chapter 5.2.2.2.1. --- BMD change of pure trabecular bone --- p.112
Chapter 5.2.2.2.2. --- BMD changes of pure cortical bone --- p.114
Chapter 5.2.2.3. --- Distal Tibia (Program 1) --- p.118
Chapter 5.2.2.3.1. --- BMD changes of D50 --- p.118
Chapter 5.2.2.3.2. --- BMD changes of D100 --- p.121
Chapter 5.2.2.3.3. --- BMD changes of P100 --- p.124
Chapter 5.2.2.4. --- Distal Tibia (Program 2) --- p.128
Chapter 5.2.2.4.1. --- BMD changes of pure trabecular bone --- p.128
Chapter 5.2.2.4.2. --- BMD changes of pure cortical bone --- p.131
Chapter 5.2.3. --- Bone turnover --- p.135
Chapter 5.2.3.1. --- Bone Resorption Marker (urinary Deoxypyridinoline) --- p.135
Chapter 5.2.3.2. --- Bone Formation Marker (Bone Specific Alkaline Phosphatase) --- p.137
Chapter 5.2.4. --- Quality of Life (QOL) --- p.139
Chapter 5.2.5. --- Oswestry Disability Index (ODI) --- p.139
Chapter 5.2.6. --- Pain --- p.141
Chapter 5.2.6.1. --- Pain frequency --- p.141
Chapter 5.2.6.2. --- Night Pain --- p.142
Chapter 5.2.6.3. --- Administration of pain relief drugs --- p.143
Chapter 5.2.7. --- Activity of daily living --- p.144
Chapter 5.2.8. --- Prevention of new vertebral fracture(s) --- p.146
Chapter 5.2.9. --- Safety and Tolerability --- p.147
Chapter chapter 6. --- results on proximal femoral fractures study --- p.149
Chapter 6.1. --- Epidemiological study on proximal femoral fractures --- p.149
Chapter 6.2. --- The role of ultrasound equipment in the assessment osteoporosis in patients with proximal femoral fractures --- p.154
Chapter 6.3. --- Summary --- p.155
Chapter chapter 7. --- discussion --- p.156
Chapter 7.1. --- The study on vertebral structures --- p.156
Chapter 7.1.1. --- Changes in Shape of Vertebral Bodies --- p.156
Chapter 7.1.2. --- Changes of Interevertbral Discs --- p.157
Chapter 7.2. --- Alendronate treatment on Chinese elderly women with Osteoporotic vertebral fracture --- p.158
Chapter 7.2.1. --- The Effect of Alendronate on BMD of Lumbar Spine --- p.159
Chapter 7.2.2. --- The Effects of Alendronate on BMD of Proximal Femur --- p.159
Chapter 7.2.3. --- The Effects of Alendronate on the BMD of Trabecular and Cortical Bone in the Distal Radius and Distal Tibia --- p.160
Chapter 7.2.4. --- The Effects of Calcium Supplementation in the study --- p.162
Chapter 7.2.5. --- The Effect of alendronate on Biochemical Turnover --- p.162
Chapter 7.2.6. --- The Efficacy of Alendronate on Prevention of New Fractures --- p.163
Chapter 7.2.7. --- The Effect of Alendronate on Quality of Life --- p.164
Chapter 7.2.8. --- Adverse Effects of Alendronate --- p.165
Chapter 7.3. --- Proximal Femur Fracture Study --- p.165
Chapter chapter 8. --- conclusion --- p.168
bibliography --- p.174
epilogue --- p.202
appendix --- p.xxv

Chung, Shu Lu.
Thesis (M.Phil.)--Chinese University of Hong Kong, 2008.
Includes bibliographical references (leaves 109-118).
Abstracts in English and Chinese.
Abstract --- p.i-iv
中文摘要 --- p.v-vii
Publications --- p.viii
Acknowledgements --- p.ix
List of Abbreviations --- p.x-xi
Index for Figures --- p.xii-xiv
Index for Tables --- p.xv
Table of Contents --- p.xvi-xix
Chapter Session 1: --- Introduction --- p.1
Chapter 1.1 --- Biology of fracture healing process --- p.2
Chapter 1.1.1 --- Stage of inflammation --- p.2-3
Chapter 1.1.2 --- Stage of soft callus formation --- p.3-4
Chapter 1.1.3 --- Stage of hard callus formation --- p.4-5
Chapter 1.1.4 --- Stage of bone remodeling --- p.5
Chapter 1.2 --- Conventional treatments and its limitations --- p.5-6
Chapter 1.3 --- Biological treatments in accelerating fracture healing process --- p.6-7
Chapter 1.4 --- Biophysical treatments in accelerating fracture healing process --- p.7-8
Chapter 1.4.1 --- Electromagnetic fields --- p.8-9
Chapter 1.4.2 --- Shockwave --- p.9
Chapter 1.4.3 --- Low intensity pulsed ultrasound --- p.9-11
Chapter 1.5 --- Properties of ultrasound --- p.11
Chapter 1.5.1 --- Ultrasound signals --- p.11-12
Chapter 1.5.2 --- Attenuation of ultrasound --- p.12-14
Chapter 1.5.3 --- Modes of ultrasound wave propagation --- p.14-15
Chapter 1.5.4 --- Reflection and critical angle --- p.15-18
Chapter 1.6 --- Insights from previous studies --- p.18-19
Chapter 1.7 --- Hypothesis --- p.19
Chapter 1.8 --- Study plan --- p.20
Chapter 1.9 --- Objectives --- p.20
Chapter Session 2: --- Materials and Methodology --- p.25
Chapter 2.1 --- Materials --- p.26
Chapter 2.2. --- Closed femoral fracture rat model --- p.26
Chapter 2.2.1 --- Operation procedures --- p.26-27
Chapter 2.3 --- Groupings --- p.27
Chapter 2.4 --- Low Iintensity Pulsed Ultrasound treatment --- p.28
Chapter 2.4.1 --- Incident angles determination --- p.28
Chapter 2.4.2 --- LIPUS devices --- p.29
Chapter 2.4.2 --- Set up of standardized platform --- p.29-30
Chapter 2.4.4 --- Treatment procedure --- p.30
Chapter 2.5 --- Radiographic analysis --- p.31
Chapter 2.6 --- Micro-Computed Tomography --- p.32
Chapter 2.6.1 --- Micro-Computed Tomography scanning --- p.32
Chapter 2.6.2 --- Micro-Computed Tomography analysis --- p.32-33
Chapter 2.7 --- Histology --- p.34
Chapter 2.7.1 --- Sample preparation --- p.34
Chapter 2.7.2 --- Histomorphometrical analysis --- p.34-35
Chapter 2.8 --- Mechanical Testing --- p.35
Chapter 2.9 --- Statistical analysis --- p.35
Chapter Session 3: --- Results --- p.48
Chapter 3.1 --- Radiographic analysis --- p.49
Chapter 3.1.1 --- Qualitative analysis - Callus bridging rate --- p.49
Chapter 3.1.2 --- Quantitative analysis - Callus area and callus width --- p.49-50
Chapter 3.2 --- Micro-computed tomography analysis --- p.50
Chapter 3.2.1 --- Qualitative analysis - 3D reconstructed images --- p.50-51
Chapter 3.2.2 --- Quantitative analysis - Bone volume of callus --- p.51
Chapter 3.2.3 --- Quantitative analysis - Bone mineral density and bone mineral content --- p.51-52
Chapter 3.3 --- Biomechanical test --- p.52-53
Chapter 3.4 --- Histomorphological analysis --- p.53
Chapter 3.4.1 --- Qualitative analysis --- p.53
Chapter 3.4.2 --- Quantitative analysis --- p.53-54
Chapter Session 4: --- Discussion --- p.85-87
Chapter 4.1 --- Enhancement effects of LIPUS at different incident angles --- p.88
Chapter 4.1.1 --- LIPUS transmitted at 350 accelerated the fracture healing process --- p.88
Chapter 4.1.1.1 --- Callus bridging and callus mineralization --- p.88-89
Chapter 4.1.1.2 --- Dose dependent effects of LIPUS -Maximization of ultrasound energy --- p.89-90
Chapter 4.1.2 --- LIPUS transmitted at 35° enhanced the restoration of mechanical properties in fracture healing process --- p.90
Chapter 4.1.2.1 --- Biomechanical properties --- p.90-91
Chapter 4.1.2.2 --- Bone mineral density and bone mineral content --- p.91-92
Chapter 4.1.2.3 --- Highly mineralized callus area and volume --- p.92-93
Chapter 4.2 --- 35° may be the critical angle for further enhancing fracture healing --- p.93
Chapter 4.2.1 --- LIPUS transmitted at 35° may be the first critical angle in this study --- p.93-95
Chapter 4.2.2 --- Effects of different incident angles --- p.95-96
Chapter 4.3 --- Mechanism of LIPUS at different incident angles on fracture healing process --- p.96
Chapter 4.3.1 --- Endochondral ossification --- p.96-99
Chapter 4.4 --- Advantages in using LIPUS transmitted at critical angle --- p.99
Chapter 4.5 --- Limitations of the study --- p.100
Chapter 4.5.1 --- Animal model --- p.100
Chapter 4.5.2 --- Treatment sites of LIPUS transmitted at different incident angles --- p.100
Chapter 4.5.3 --- Types of fracture --- p.101
Chapter Session 5: --- Conclusions --- p.102-104
Chapter Session 6: --- Future Studies --- p.105
Chapter 6.1 --- Protocol and regime of LIPUS transmitted at different angles --- p.106
Chapter 6.2 --- Periosteum-stripped fracture model --- p.106-107
Chapter 6.3 --- Molecular mechanism of LIPUS transmitted at different incident angles --- p.107-108
Bibliography --- p.109-118
Appendix I --- p.119

Aim. The overall aims of this study were to develop a tailor-made educational intervention and to examine its effectiveness on short- and longer-term outcomes among Chinese patients with traumatic limb fractures who had undergone surgery.
Background. Fracture limb and undergoing surgery is the common problem after injury. It is the most common source of pain and anxiety and research continues to demonstrate a high prevalence of unrelieved pain in injured patients who have undergone surgery. Patient's belief in pain is the major barrier in pain management. Strategies directed to have appropriate educational interventions are urgently needed to improve patient outcomes for those suffering acute pain after surgery for traumatic limb fracture.
Conclusion. The C-BEI was effective in terms of reducing the pain barrier, providing post-operative pain relief, reducing anxiety, and improving sleep satisfaction in patients with fractured limbs during their first week of hospitalization after surgery. This study has generated evidence supporting the use of a C-BEI in acute pain management.
Method. The study was conducted in the orthopaedic wards of two regional hospitals in Hong Kong and comprised two phases. In phase one, qualitative interviews were conducted with twenty-six Chinese patients who had traumatic limb fractures and were undergoing surgery regarding their experiences of and beliefs about pain management. Ten orthopaedic nurses were also interviewed about their perceived pain management practices and the barriers that prevented better pain control among patients. The findings from these qualitative interviews were used to develop a cognitive behavioural approach educational intervention (C-BEI). C-BEI was used to enhance knowledge of pain, modify their beliefs about pain management and promote positive coping thoughts and behaviour. The C-BEI consisted of two sessions. The first was a 30-minute session comprised a combination of patient education and breathing relaxation exercise and conducted at T0 (1 day before surgery). A 30-minute reinforcement session was conducted at day 7 after surgery (T3).
Results. A total of 125 participants completed the study, with 62 in the experimental group and 63 in the control group. The participants were homogenous in terms of demographic data (P > 0.05) and baseline clinical characteristics (p > 0.05). The short-term outcomes (from T0 to T3) for the participants in the experimental group were a statistically significant with lower pain barrier (p = .003), lower level of pain (p = .003), lower level of anxiety (p < .001), and better sleep satisfaction (p = .001) than the control group. The experimental group had a significantly higher frequency of analgesic use at T2 (p < .001) and better self-efficacy in pain management at T3 (p = .011) than the control group. There were no statistically significant differences in the total length of stay in hospital, although the mean length of stay was shorter in the experimental group than in the control group (8.1 day VS 10.1 days). For longer-term effects, the C-BEI was effective at the post-operative stage in anxiety reduction ( p = .002) and sleep satisfaction improvement (p = .002). There were no statistically significant differences for the VAS pain level, GSE scores, physical health summary component (PCS) and mental health summary component (MCS) of the SF36 between two groups over three months, although the experimental group had better scores in the mental health dimension. Findings of the process evaluation showed that most participants perceived the C-BEI as effective in enhancing their knowledge on pain management and the use of analgesics, and helping them to cope with pain, the could sleep better and regain self-control.
The main study was conducted in phase II which consisted of outcomes and process evaluation. A quasi-experimental design of two groups' pre-test and post-test between subjects was employed for the outcomes evaluation. All participants in the experimental group received the C-BEI and usual care, whereas those in the control group received usual care only. The short-term outcomes were treated as primary outcomes and evaluated in terms of the participants' pain barrier score, pain level (Visual Analogue Pain Scale: VAS, anxiety level (State-Trait Anxiety Inventory:STAI), sleep satisfaction, self-efficacy in pain management (General Self Efficacy Scale: GSE), and frequency of analgesic use. All of which were measured at T0, T1 (day 2), T2 (day 4), and T3 (day 7) after surgery. The total length of stay in hospital of the two groups was also compared. Longer-term outcomes were further evaluated over three months at T4 (1 month) and T5 (3 months), and included the VAS pain level, STAI, sleep satisfaction, GSE and health-related quality of life (SF36).The intention-to-treat method was adopted. The process evaluation involved a qualitative study using telephone interviews.
Wong, Mi Ling, Eliza.
Adviser: Sally Chan.
Source: Dissertation Abstracts International, Volume: 71-01, Section: B, page: 0231.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2009.
Includes bibliographical references (leaves 256-278).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstracts in English and Chinese.

Sun, Minghui.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2011.
Includes bibliographical references (leaves 125-159).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstract also in Chinese.

碩士
長庚大學
醫療機電工程研究所
101
Interochanteric fractures associated with severe osteoporosis and comminution remain a considerable challenge to orthopedic surgeon. The standard treatment of these fractures is by osteosynthesis with a dynamic hip screw (DHS). However, in unstable intertrochanteric fractures, complications of cut-out and excessive sliding of the lag screw occurred frequently. Another device frequently used to treat these unstable intertrochanteric fractures is the use of a intramedullary nail. Although PMMA bone cement has been widely applied as a secondary fixation to facilitate fracture stability, there has been few biomechanical studies regarding the significance of bone cement in unstable fracture patterns with osteoporotic bone, therefore this study was conducted to compare the biomechanical behavior between a PMMA cemented DHS and an intramedullary device in treatment of interochanteric fractures associated with severe osteoporosis. Methods: Both finite element analysis (FEA) and In vitro experiment were conducted in current study. For FEA study, CT images obtained from standardized composite femur was used to create 3-D finite element model simulating unstable interochanteric fracture. The solid model and finite element model of DHS and intramedullary device were created by actual measurement. Loading condition simulating single leg stance was performed. Femora with three different degree of density (normal, osteoporotic and augmented with cemented) were compared. For experiment study, postoperative stability for femora with unstable interochanteric fracture treated with DHS and intramedullary device were compared. Results: The results of finite element analysis indicated that, for femur treated with DHS, the maximal femoral head displacement for normal, osteoporotic and cemented femur were 7.143 mm, 8.714 mm and 6.889 mm, respectively; whereas for femur implanted with intramedullary device, the maximal femoral head displacement for normal, osteoporotic and cemented femur were 1.869 mm, 2.207 mm and 1.859 mm, respectively. Regardless of DHS or intramedullary device, unstable interochanteric fractures associated with severe osteoporosis exhibited the highest femoral head displacement. In addition, the maximal von Mises stress of DHS device for normal, osteoporotic and cemented femur were 2,112 MPa, 2,006 MPa and 2,084 MPa, respectively; whereas for femur implanted with intramedullary device, the maximal von Mises stress of intramedullary device for normal, osteoporotic and cemented femur were 1,444, 1,452, and 1,616 MPa, respectively. Regardless of DHS or intramedullary device, the application of bone cement increases the von Mises stress of fixation device. Furthermore, the results of in vito experiment indicated, under 2000 N compressive loading, the vertical displacement of femoral head for femora implanted with DHS and intramedullary device are 11.3 mm and 4.6 mm, respectively Conclusion: The intramedullary device may be suitable to treat unstable interochanteric fractures associated with severe osteoporosis due to the lower displacement and stresses. DHS treated femur exhibits a higher risk of screw cut-out. The application of bone cement reduces the risk of screw cut-out, however, it increases the risk of implant damage.

Indiana University-Purdue University Indianapolis (IUPUI)
An excess of bone resorption over bone formation leads to osteoporosis, resulting in a reduction of bone mass and an increase in the risk of bone fracture. Anabolic and anti-resorptive drugs are currently available for treatment, however, none of these drugs are able to both promote osteoblastogenesis and reduce osteoclastogenesis. This thesis focused on the role of eukaryotic translation initiation factor 2 alpha (eIF2alpha), which regulates efficiency of translational initiation. The elevation of phosphorylated eIF2alpha was reported to stimulate osteoblastogenesis, but its effects on osteoclastogenesis have not been well understood. Using synthetic chemical agents such as salubrinal and guanabenz that are known to inhibit the de-phosphorylation of eIF2alpha, the role of phosphorylation of eIF2alpha in osteoclastogenesis was investigated in this thesis. The questions addressed herein were: Does the elevation of phosphorylated eIF2alpha (p-eIF2alpha) by salubrinal and guanabenz alter osteoclastogenesis? If so, what regulatory mechanism mediates the process? It was hypothesized that p-eIF2alpha could attenuate the development of osteoclast by regulating the transcription factor(s) amd microRNA(s) involved in osteoclastogenesis. To test this hypothesis, we conducted in vitro and in silico analysis of the responses of RAW 264.7 pre-osteoclast cells to salubrinal and guanabenz. First, the in vitro results revealed that the elevated level of phosphorylated eIF2alpha inhibited the proliferation, differentiation, and maturation of RAW264.7 cells and downregulated the expression of NFATc1, a master transcription factor of osteoclastogenesis. Silencing eIF2alpha by RNA interference suppressed the downregulation of NFATc1, suggesting the involvement of eIF2alpha in regulation of NFATc1. Second, the in silico results using genome-wide expression data and custom-made Matlab programs predicted a set of stimulatory and inhibitory regulator genes as well as microRNAs, which were potentially involved in the regulation of NFATc1. RNA interference experiments indicated that the genes such as Zfyve21 and Ddit4 were primary candidates as an inhibitor of NFATc1. In summary, the results showed that the elevation of p-eIF2alpha by salubrinal and guanabenz leads to attenuation of osteoclastogenesis through the downregulation of NFATc1. The regulatory mechanism is mediated by eIF2alpha signaling, but other signaling pathways are likely to be involved. Together with the previous data showing the stimulatory role of p-eIF2alpha in osteoblastogenesis, the results herein suggest that eIF2alpha-mediated signaling could provide a novel therapeutic target for treatment of osteoporosis by promoting bone formation and reducing bone resorption.

A traumatologia é uma das patologias mais frequentes da área maxilo e crânio facial. Este trabalho tem como objecto o estudo das fracturas condilares, a classificação delas e o tratamento conservador e médico-cirurgico, através da utilização de vários tipos de placas de fixação (rétas, trapezoidais, a lambda ou y, e a grelha). Para a realização desta revisão foram consultados vários textos e artigos científicos sobre o argumento, utilizando as seguintes palavras-chave: “fraturas condilares”, “fraturas subcondilares”, “tratamento cirurgico das fraturas condilares”, “placas de titânio”, “osteosíntese”, “placa lambda”, “placa trapezoidal”, “placas 3D”.
Condyle’s trauma in the last few years has been the subject of numerous studies and clinical tries. This job has, as its goal, the study of condylar fractures, their classification and its medical and surgical treatment, through the most current techniques. To do this research many texts and scientific articles concerning this topic have been consulted, using these keywords: “condylar fractures”, “subcondylar fractures”, “surgical treatment of condylar fractures”, “titanium plates”, “bone synthesis”, “lambda plate”, “trapezoidal plate”, “3D plates”.