Destructive bone loss is a serious complication of many common inflammatory diseases. Three important examples are are, periodontal disease, rheumatoid arthritis and peri-implant osteolysis. The mechanism of osteoclast formation in these diseases is distinctly different from physiologic osteoclast formation. Despite the prevalence of these diseases until recently little is known about how bone erosion occurs However, recent advances in the understanding of these diseases has allow us to better i ....Destructive bone loss is a serious complication of many common inflammatory diseases. Three important examples are are, periodontal disease, rheumatoid arthritis and peri-implant osteolysis. The mechanism of osteoclast formation in these diseases is distinctly different from physiologic osteoclast formation. Despite the prevalence of these diseases until recently little is known about how bone erosion occurs However, recent advances in the understanding of these diseases has allow us to better investigate the mechanisms of the bone loss. Drugs to stop the loss of bone have only recently been available to patients and many new treatments are being developed. While most of these drugs are proving useful to treat osteoporosis, their suitability for the treatment of bone loss in diseases such as periodontal disease, rheumatoid arthritis and peri-implant osteolysis is largely unknown. As the way bone is lost in these inflammatory diseases quite different from osteoporosis different treatments are needed. This project aims to better understand bone loss in these diseases and identify new treatments to prevent the debilitating bone loss associated with inflammation in disease.Read moreRead less
Pathophysiology And Prevention Of Methotrexate Chemotherapy-induced Bone Growth Defects
Funder
National Health and Medical Research Council
Funding Amount
$622,598.00
Summary
Childhood chemotherapy often causes growth arrest, osteoporosis, and fractures in cancer patients and survivors. Using a rat model, this project will study how the most commonly used chemotherapy drug methotrexate causes bone growth defects and examine any protective effects of two natural-derived substances. This work will increase our knowledge on chemotherapy-induced bone growth defects, and will be useful for developing a preventative treatment.
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