Role Of Musculoskeletal Biomechanical Factors In Cartilage Loss In Those Who Undergo Partial Medial Menisectomy.
Funder
National Health and Medical Research Council
Funding Amount
$654,530.00
Summary
The novel outcomes from our project are that we will identify whether musculoskeletal-biomechanical factors that can be modified are associated with adverse cartilage changes in a subgroup of individuals with an increased risk of developing knee OA, those who have undergone an APM. The findings of this research are timely and of major international significance as there is increasing attention being paid to preventing OA rather than merely treating the signs and symptoms. Our state-of-the-art me ....The novel outcomes from our project are that we will identify whether musculoskeletal-biomechanical factors that can be modified are associated with adverse cartilage changes in a subgroup of individuals with an increased risk of developing knee OA, those who have undergone an APM. The findings of this research are timely and of major international significance as there is increasing attention being paid to preventing OA rather than merely treating the signs and symptoms. Our state-of-the-art measure of cartilage changes will allow us to detect those at risk much sooner than traditional measures using radiographs. The measures are also leading edge internationally. We chose these specific factors to investigate as there is evidence that they can be modified with appropriate interventions. For example, static joint alignment could be modified with foot orthoses [Crenshaw, 2000 #1016], muscle weakness can be addressed with strength programs and mechanical loading across the knee could be reduced via weight loss programs or techniques to alter gait patterns. Currently, formal supervised post-operative rehabilitation is not routinely prescribed following APM because it is considered a routine procedure. If our research identifies risk factors for increased cartilage loss then we will be able to develop appropriate intervention strategies for individuals following an APM. These interventions can then be formally tested as to their effectiveness in reducing adverse cartilage changes using randomised controlled trials. In particular, this could lead to changes in current post-operative clinical practice for this patient group. Ultimately, this could reduce the risk of OA in the future and the resultant personal and societal costs of this condition.Read moreRead less
The Effect Of Weight Loss On The Risk Of Knee Osteoarthritis And Potential Modification By Biomechanical Factors
Funder
National Health and Medical Research Council
Funding Amount
$475,388.00
Summary
Osteoarthritis (OA) has the largest impact of any chronic disease on burden of disease borne in later life. This has been acknowledged by its listing as the 7th health priority in Australia. Knee OA is the most common reason for a joint replacement, thus imposing a huge financial burden to the community. Treatments which slow-prevent OA progressioning are limited and so prevention must play a key role. Obesity is the most significant, potentially modifiable risk factor for knee OA. The combinati ....Osteoarthritis (OA) has the largest impact of any chronic disease on burden of disease borne in later life. This has been acknowledged by its listing as the 7th health priority in Australia. Knee OA is the most common reason for a joint replacement, thus imposing a huge financial burden to the community. Treatments which slow-prevent OA progressioning are limited and so prevention must play a key role. Obesity is the most significant, potentially modifiable risk factor for knee OA. The combination of the current epidemic of obesity in Western countries and the aging of the population is likely to have a synergistic effect on the prevalence and incidence of knee OA. Despite the consistent relationship between obesity and OA, little work has been done on the relationship between obesity and biomechanical factors such as knee angle and muscle mass and how these may interact with obesity and weight loss in modifying the risk of knee OA. It may be that weight loss programs could be more effective at reducing the risk of OA if they are combined with programs aimed at correcting muscle weakness and malalignment. This has the potential to promote a better quality of life as people age and to reduce the economic burden of knee OA in the community.Read moreRead less
NT-3 As An Upstream And Potentially Master Regulator Promoting Bone Fracture Healing
Funder
National Health and Medical Research Council
Funding Amount
$712,857.00
Summary
There is a strong clinical need for cost-effective treatments for delayed healing or non-union bone fractures. Our recent data suggest injury site-derived neurotrophin-3 (NT-3) may be an important overall regulator of bone repair by inducing key factors involved in fracture callus formation and remodelling. This project will address roles and mechanisms of endogenous NT-3 in bone repair and the likelihood of exogenous NT-3 protein in promoting bone healing in clinically relevant fracture models.
A Prospective Study To Identify The Mechanical Causes And Methods For Early Detection Of Knee Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Knee osteoarthritis is a great cost to society, financially and in quality of life. Anti-inflammatory drugs are commonly used to treat the symptoms, but many people receive joint replacements to stop pain and improve function. We need to prevent osteoarthritis, but the causes for this common disease are largely unknown. Animal studies have shown two particular mechanical factors that cause osteoarthritis, which are seen in the walking and running, or gait, patterns of some people. We call these ....Knee osteoarthritis is a great cost to society, financially and in quality of life. Anti-inflammatory drugs are commonly used to treat the symptoms, but many people receive joint replacements to stop pain and improve function. We need to prevent osteoarthritis, but the causes for this common disease are largely unknown. Animal studies have shown two particular mechanical factors that cause osteoarthritis, which are seen in the walking and running, or gait, patterns of some people. We call these pathological gait patterns as they impose larger-than-normal forces on the knee's articular surfaces. We measure these knee forces with our new computer knee model coupled with data that we measure in a gait analysis laboratory. These forces may cause knee osteoarthritis in humans, but this is still unknown. Currently there is no simple medical test to detect the early onset of knee osteoarthritis. The bones in the knee are one of the first structures to show osteoarthritic changes. Using our new computerised analysis of high definition X-ray of the knee we can identify subtle differences in the knee due to osteoarthritis. This will be compared with changes to joint assessed using MRI. Osteoarthritis develops slowly in normal people, so to study progression of knee osteoarthritis we need a human population that has a higher risk of developing the disease. Partial meniscectomy in the knee is a common surgery performed to improve knee function in those who have suffered a knee meniscus injury. However, partial meniscectomy patients have a high risk of developing knee osteoarthritis. Therefore, using partial meniscectomy patients we are investigating if pathological gait patterns cause knee osteoarthritis, measuring the development of the disease with our new X-ray methods. With the gait analysis methods we can also identify the movements that characterise these pathological gait patterns so we can formulate rehabilitation programmes to help prevent knee osteoarthritis.Read moreRead less
Roles Of Injury-induced Inflammatory Response In Regulating Bony Repair At Injured Growth Plate Cartilage
Funder
National Health and Medical Research Council
Funding Amount
$366,301.00
Summary
Children's growth plate cartilage is responsible for bone lengthening. Due to popularity of sports and play, trauma-induced growth plate damage and subsequently bone growth defects are common in children, with up to 30% of growth plate injury cases resulting in growth abnormality, for which the present surgical correction is highly invasive and not fully effective. Although we know that the growth plate injury-induced bone growth defects result from bony repair of the injured growth cartilage, w ....Children's growth plate cartilage is responsible for bone lengthening. Due to popularity of sports and play, trauma-induced growth plate damage and subsequently bone growth defects are common in children, with up to 30% of growth plate injury cases resulting in growth abnormality, for which the present surgical correction is highly invasive and not fully effective. Although we know that the growth plate injury-induced bone growth defects result from bony repair of the injured growth cartilage, we largely don't understand why and how this bony repair occurs. Understanding mechanisms for this faulty bony repair of injured growth plate will be critical prior to effective biological treatments can be developed. Recently, using an injury model in young rats, we found that bony tissue formation at injured growth plate is preceded sequentially by inflammatory, fibrogenic, chondrogenic and osteogenic responses. The inflammatory response is an initial event and our recent studies suggest that inflammatory response recruits inflammatory cells and produces important molecules that could significantly influence subsequent fibrogenic, chondrogenic and osteogenic events leading to the bony repair of the injured growth plate cartilage. The current proposal further addresses roles of the inflammatory response and the molecular pathways of this response in regulating downstream bony repair events. This project will generate novel understanding on the faulty bony repair of injured growth plate, and will provide valuable information for developing cost-effective and simple therapeutic intervention that aims to prevent bony repair and to enhance cartilage regeneration of the injured growth plate in children.Read moreRead less
We will seek to address an important clinical problem in orthpaedics, namely the bone loss that commonly occurs around joint replacement prostheses. Termed peri-prosthetic osteolysis (PO), this bone loss can result in the loosening and ultimate failure and need for revision of the artificial joint components. PO is thought to be caused by the body's reaction to wear particles generated from the articulating surface of the prosthesis. However, it has not previously been possible to accurately exp ....We will seek to address an important clinical problem in orthpaedics, namely the bone loss that commonly occurs around joint replacement prostheses. Termed peri-prosthetic osteolysis (PO), this bone loss can result in the loosening and ultimate failure and need for revision of the artificial joint components. PO is thought to be caused by the body's reaction to wear particles generated from the articulating surface of the prosthesis. However, it has not previously been possible to accurately explore the relationship between prothesis wear and PO, or the progression of PO, because of a lack of techniques to image and measure the volume of PO around metal prosthesis components. We have developed a means to accurately and reproducibly measure the volume of bone loss, using CT, and will do so longitudinally in joint replacement patients to obtain the first information about the progression of PO. New computer based methods will be used concurrently to relate prosthesis wear and migration parameters to PO. Patients who come to surgery for replacement of failed prostheses will be investigated further by analysis of the tissues involved in the bone loss around prostheses. Basic science experiments will seek to understand the underlying causes of PO and the findings will be important in interpreting the clinical results. An animal model will be used to seek approaches to inhibiting the pathological response to wear particles. The significance of these studies is that they will lead to improved outcomes for joint replacement patients, increasing the interval to revision surgery, which is both extremely costly and brings an attendant morbidity and mortality.Read moreRead less