The principal aim of this thesis was to develop and implement a standardised protocol for the fractal analysis of cancellous bone architecture. Cancellous bone structure from different skeletal sites in groups of osteoporotic, osteoarthritic and normal individuals was analysed. The results of fractal analysis were explained in the context of conventional bone histomorphometry and a priori knowledge to advance the understanding of cancellous bone architecture. There has been much effort devoted to the pursuit of descriptors of cancellous bone complexity. The aim of these endeavours has been to develop morphological descriptors of bone quality that explain the functional properties of the cancellous bone structure for age-related changes, the effect of disease processes or the effect of therapeutic agents on the diseased skeleton. The fractal analysis of the complexity of cancellous bone architecture promises to be an exciting addition to existing analytical techniques. The establishment of a standardised methodology for the fractal analysis of cancellous bone encompassed many components. Knowledge of the stereological and histomorphometric principles that are employed in currently available techniques enabled a comprehensive examination of the factors that effect the measurement of the fractal dimensions. The methodology presented in this thesis has been optimised specifically for measuring sectional fractal dimensions in histological sections of cancellous bone. The sectional fractal dimensions show that, over three ranges of scale, cancellous bone is effectively fractal at multiple sites in the normal skeleton. The three sectional fractal dimensions describe different morphological compartments of the cancellous bone structure. Fractal 1 describes the surface texture of the trabeculae, fractal 2 describes the shape or form of individual trabeculae and fractal 3 describes the spatial arrangement or overall architecture of the cancellous bone. This thesis reports that in the normal skeleton there are differences between skeletal sites for the fractal dimensions, which are dependent on the functional properties of the skeletal sites. Fractal 2 and fractal 3 for subchondral cancellous bone is greater than vertebral body and iliac crest cancellous bone, which indicates greater morphological complexity. Also, fractal 2 and fractal 3 in subchondral cancellous bone show an age-related decrease, which suggests that the cancellous bone structure becomes less complex with age. This interostotic variability in response to ageing is indicative of the heterogeneity in functional properties of cancellous bone in the skeleton. In this thesis, fractal analysis has been shown to detect morphological differences in the cancellous bone between normals, osteoporotics and osteoarthritics in the compressive and tensile trabeculae of the femoral head and the iliac crest. These data have provided new insights into the mechanisms of change to cancellous bone structure in ageing and in disease. Age-related changes in the structural parameters of cancellous bone are seen at all the skeletal sites in the normals but are only present in the compressive trabeculae of the femoral head in the osteoporotics and not at all in the osteoarthritics. These observations indicate that these disease processes are associated with an uncoupling of the control mechanisms that affect cancellous bone structural complexity. In the normals, the fractal dimensions only show age-related change in the tensile trabeculae of the femoral head, suggesting that fractal analysis is not suitable for detecting the age-related changes that are quantified by the structural parameters of cancellous bone in these study groups but the fractal dimensions detect underlying cancellous bone complexity independent of age. For the osteoporotics, fractal 1 is the same at all skeletal sites. This suggests that the relative levels of remodeling activity are the same for both normals and osteoporotics. Fractal 2 for both the compressive and tensile trabeculae in the femur is significantly lower for the osteoporotics than the normals but in the iliac crest, fractal 2 is the same. This implies that in the femoral head the osteoporotics have trabeculae that are significantly less complex in shape than the normals. This phenomenon is not seen in the iliac crest, which is usually the site of diagnostic biopsy. Therefore, biopsies for diagnosis of osteoporosis may not show changes in cancellous bone structural complexity that are evident in disease affected sites. The structural parameters of cancellous bone show that osteoporotics lose whole trabeculae due to perforation of trabeculae, through decreased Tb.N and increased Tb.Sp. This leads to less interconnection between trabeculae, loss of branching and more rounded trabeculae, hence the trabeculae are less complex in shape. For fractal 3, in compressive and tensile regions of the femur the osteoporotics are significantly lower than the normals and in the iliac crest the osteoporotics are the same as the normals. This indicates that in the femoral head the spatial arrangement of the trabeculae within the cancellous structure of the osteoporotics is less complex. The structural parameters of cancellous bone show that there is loss of whole trabeculae, which is associated with increased spatial separation between the trabeculae as bone is lost. For the osteoarthritics, fractal 1 is the same as the normals at all skeletal sites. Fractal 2 for the compressive trabeculae in the femoral head is significantly higher for the osteoarthritics than the normals but in the tensile trabeculae of the femoral head and the iliac crest fractal 2 for the osteoarthritics is the same as the normals. This implies that in the compressive trabeculae of the femoral head the osteoarthritics have trabeculae that are significantly more complex in shape than the normals. The structural parameters of cancellous bone show that the compressive trabeculae of the femoral head are thicker, more numerous and less widely separated with greater BV/TV than the normals. This leads to greater interconnectivity between trabeculae and more complex branching, hence the trabeculae are more complex in shape. For fractal 3, in the compressive and tensile regions of the femoral head the osteoarthritics and the normals are the same but in the iliac crest the osteoarthritics are lower than the normals. This indicates that the spatial arrangement of the trabeculae within the cancellous structure of the osteoarthritics does not change in response to the disease process in subchondral cancellous bone adjacent to the articular lesion but in the iliac crest the spatial arrangement of the trabeculae in osteoarthritics is less complex in shape. The structural parameters of cancellous bone show that BV/TV is increased in the compressive and tensile trabeculae of the femoral head but not in the iliac crest of the osteoarthritics. This indicates that the spatial complexity of the trabecular arrangement within the cancellous structure of osteoarthritics changes independently of changes in cancellous bone structure detected by the structural parameters of cancellous bone. The sectional fractal dimensions have detected differences in morphological complexity between the normals and disease groups and between the skeletal sites. These novel data have been obtained using an innovative technique that is not dependent on assumptions based on conceptual models of cancellous bone structure. A priori knowledge of bone biology is utilised to enable the fractal analysis to measure specific morphological entities within the cancellous bone structure. The fractal dimensions have identified changes in the morphological complexity of specific components of the cancellous structure, which are not identified by existing model-based morphometric techniques. This has enabled new understanding of how change to cancellous bone structure occurs as a result of a disease process. Fractal analysis is a novel tool that will prove useful for the study of changes in cancellous bone structure due to disease and to study the use of therapies to alter or maintain the quality of cancellous bone architecture. / Thesis (Ph.D.)--Medical School, 2002.

"January 2003" / Errata slip inserted inside front cover. / Includes bibliographical references (leaves 282-313) / xxx, 313 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Pathology, 2003

With increasing rates of obesity, research has begun to focus of co-morbidities of obesity such as osteoarthritis. The majority of existing research has focused on older adults as the group most likely to suffer from osteoarthritis. The purpose of this study was to determine if overweight and obese young adults exhibit biomechanical risk factors for knee osteoarthritis, and to determine if young adults with biomechanical risk factors of osteoarthritis can modify these with instruction. This purpose was divided into two separate studies. Study 1: Thirty adults between 18-35 years old were recruited into three groups according to body mass index: normal, overweight, and obese. Participants walked through the lab while we collected 3-d kinematic and kinetic data. Overweight and obese young adults walked with similar gait compared to normal weight young adults. Study 2: Nine young adults between 18-35 years were recruited who walked with stiff-knee gait. Baseline measures of gait were collected in the form of 3-d kinematics and kinetics as participants walked through the laboratory. They then completed the gait instruction program which consisted of four blocks of training. Each block included ten single steps where the participant was provided feedback, followed by 100 practice steps around the laboratory. Participants were successful in increasing sagittal plane kinematics and kinetics of interest in the study. Conclusion: Identifying individuals who had biomechanical risk factors of osteoarthritis according to body mass index was not possible. According to the results of our study, obese and overweight young adults are not at increased risk of osteoarthritis compared to normal weight young adults. Individuals who may be at increased risk due to stiff-knee gait were able to improve their gait following instruction.

Thesis (Ph.D.)--University of Delaware, 2006. / Principal faculty advisor: Lynn Snyder-Mackler, Dept. of Physical Therapy. Includes bibliographical references.

<p>This scientific paper is about the changes in the skeleton caused by the diseases osteoarthritis and osteoporosis. Six males and one female from Banken 1, S:ta Gertrud  and S:t Hans in Visby were chosen for an osteological analysis. All individuals are adults and dates back to the middle ages. One male suffered from both osteoporosis and osteoarthritis and one female and three males suffered from osteoarthritis. One male might have been in the beginning faze of osteoarthritis, and one male shows no sign of any of the diseases. In addition to osteoarthritis and osteoporosis, some of the individuals suffer from other pathological conditions. Some of the bones from most of the individuals were x-rayed at Visby hospital, to see if medical technique could show some additional information to the osteological analysis. The x-rays were interpreted by doctor Staffan Jennerholm from Visby hospital, but other doctors have also participated. The x-rays confirmed results from the osteological analysis in most cases, although it showed new information in several cases. Some bones from three individuals were taken to Roland Alvarssons` Doctor Practice in Visby to measure the bone density, to check if any of the individuals had osteoporosis. The result confirmed that one male had osteoporosis, as expected from the osteological analysis.</p> / Noen steder i oppgaven står det "osteoartrithis", men det skal stå "osteoarthritis"

The first objective of my work was to use the ank/ank (progressive ankylosis) mutant mice, which have a deficiency in inorganic pyrophosphate transport, to address the role of Ank in joint ankylosis. I observed the presence of hypertrophic chondrocytes in the uncalcified ank/ank mice articular cartilage. This novel phenotype is likely due to a dysregulation of chondrocyte maturation as these chondrocytes expressed hypertrophic chondrocyte markers (collagen type X and tissue non-specific alkaline phosphatase). I also showed by immunohistochemical staining that beta-catenin expression was upregulated and localized in the nuclei of articular ank/ank chondrocytes, suggesting activation of Wnt/beta-catenin signaling in these chondrocytes. The second objective was to use ank/ank mice as an informative model for understanding ankylosis mechanisms in human ankylosing spondylitis (AS) patients, as WNT/beta-catenin signaling plays an important role in ankylosis in AS patients. We attempted rescue of joint ankylosis in ank/ank mice by gene transfer of noggin, an antagonist of BMP signaling. Paradoxically, noggin-treated ank/ank mice had accelerated ankylosis, as evidenced by joint pathology and IHC staining of beta-catenin showed more intense signals in the spinal chondrocytes of the treated mice. As noggin and sclerostin (an antagonist of beta-catenin signaling) form a mutually inhibitory complex, we hypothesize that the formation of this complex results in relieving suppression of both beta-catenin and BMP signaling, leading to more severe ankylosis in ank/ank mice. By quantitative molecular imaging, I have demonstrated that ankylosis in these mutant mice developed simultaneously in distal and axial joint, instead of being a centripetal process. In summary, I have made three original observations in the ank/ank mice: the hypertrophic chondrocyte phenotype; activation of beta-catenin signaling and the simultaneous development of ankylosis in distal and axial joints. These mutant mice serve as valuable model for pre-clinical studies which enable modeling and testing of novel anti-ankylosis treatments.

Osteoarthritis is a disease that causes decreases in hand function in the elderly adult and can lead to full disability of the hand. There is no clear cause of osteoarthritis of the hand, although injury and overuse can contribute to development of the disease. Traditional treatments include splinting, paraffin therapy, medications and, in severe cases, joint replacement. Nontraditional therapies include mobility training, therapeutic touch, acupuncture and exercise. The purpose of this study was to explore the non-traditional treatment of hand-strengthening exercise as a way to improve hand function. Specifically, this study evaluated the effects of an eightweek hand exercise program utilizing Hand Exercisers and FlexBars on hand grip strength and dexterity in 13 elderly women aged 70-85 (M=80.4, SD= +/- 4.25) who showed signs and symptoms of hand osteoarthritis, which are pain, stiffness and swelling.. Participants were evaluated before and after the exercise intervention for grip strength, pinch strength, range of motion of the trapeziometacarpal, metacarpophalangeal, interphalangeal and wrist joints, and were timed on a hand dexterity test that involved putting on and buttoning a shirt with ten 3/8th inch buttons. A repeated measures ANOVA was the mode of data analysis. Hand strength significantly improved (p<0.05), as both grip (19%) and pinch (26%) strength showed improvements. In range of motion testing, palmar flexion (12%), interphalangeal flexion (46%), metacarpophalangeal flexion (39%) and wrist extension (11%) showed significant improvements while palmar abduction (12%) and wrist flexion (8%) did not. Hand dexterity also improved as evidenced by a 24% decrease in the amount of time to button a shirt. Pain, stiffness and disability, as measured by the AUSCAN, also decreased significantly, with a 17.3% decrease in means. The results indicate that hand exercise programs can be used to increase hand function while decreasing the signs and symptoms in patients with hand osteoarthritis. / Thesis (M.Ed.)--Wichita State University, College of Education, Dept. of Kinesiology and Sport Studies. / "July 2006." / Includes bibliographic references (leaves 33-37).

The first objective of my work was to use the ank/ank (progressive ankylosis) mutant mice, which have a deficiency in inorganic pyrophosphate transport, to address the role of Ank in joint ankylosis. I observed the presence of hypertrophic chondrocytes in the uncalcified ank/ank mice articular cartilage. This novel phenotype is likely due to a dysregulation of chondrocyte maturation as these chondrocytes expressed hypertrophic chondrocyte markers (collagen type X and tissue non-specific alkaline phosphatase). I also showed by immunohistochemical staining that beta-catenin expression was upregulated and localized in the nuclei of articular ank/ank chondrocytes, suggesting activation of Wnt/beta-catenin signaling in these chondrocytes. The second objective was to use ank/ank mice as an informative model for understanding ankylosis mechanisms in human ankylosing spondylitis (AS) patients, as WNT/beta-catenin signaling plays an important role in ankylosis in AS patients. We attempted rescue of joint ankylosis in ank/ank mice by gene transfer of noggin, an antagonist of BMP signaling. Paradoxically, noggin-treated ank/ank mice had accelerated ankylosis, as evidenced by joint pathology and IHC staining of beta-catenin showed more intense signals in the spinal chondrocytes of the treated mice. As noggin and sclerostin (an antagonist of beta-catenin signaling) form a mutually inhibitory complex, we hypothesize that the formation of this complex results in relieving suppression of both beta-catenin and BMP signaling, leading to more severe ankylosis in ank/ank mice. By quantitative molecular imaging, I have demonstrated that ankylosis in these mutant mice developed simultaneously in distal and axial joint, instead of being a centripetal process. In summary, I have made three original observations in the ank/ank mice: the hypertrophic chondrocyte phenotype; activation of beta-catenin signaling and the simultaneous development of ankylosis in distal and axial joints. These mutant mice serve as valuable model for pre-clinical studies which enable modeling and testing of novel anti-ankylosis treatments.

One of the most poorly understood co-morbidities associated with obesity is the pathway to osteoarthritis of the knee. To implement appropriate preventative strategies, it is important to explore how obesity is a causal factor for osteoarthritis. The present research compared the kinematics and kinetics of a group of young obese, but otherwise healthy, adults to a group of young, healthy-weight adults, in an attempt to identify mechanical abnormalities at the knee during walking that may predispose the obese to osteoarthritis of the knee. Optotrak motion capture (Northern Digital Inc. Waterloo, Ontario) and a forceplate (AMTI OR6-7, Advanced Mechanical Technology Inc, Watertown, MA) were used to measure ground reaction forces and moments of 16 participants – 8 obese and 8 sex-, age- and height-matched healthy-weight – to analyze knee joint kinematics and kinetics at three walking speeds. Participants wore an accelerometer (ActiGraph GT3X, Fort Walton Beach, USA) for seven days to measure daily steps counts. Dependent t-tests were performed to determine group differences in ground reaction forces, knee angles and knee moments, as well as knee adduction moment impulse and cumulative knee adductor load (CKAL). The obese group walked at a significantly slower self-selected speed (p=0.013). While not statistically significant, the obese group did present with a more valgus mean dynamic knee alignment than the health-weight group. A significantly greater maximum abduction angle (p=0.009) and smaller minimum knee flexion angle at heel contact (p=0.001) was found in the obese group. A significant difference was found in the peak medial rotation moment in the transverse plane (p=0.003). A greater stance duration lead to a significantly greater knee adduction moment impulse (p=0.049) in the obese group. While significant group differences were not found in the steps per day, the obese group had a significantly greater CKAL (p=0.025). Obese young adults with healthy knees demonstrated a gait pattern of reduced medial knee joint compartment loading through greater knee abduction, medial knee rotation and a slower walking speed compared to matched controls. The ramifications of gait modifications on long-term musculoskeletal health remain unknown, but compensations may lead to increased risk of osteoarthritis of the knee.

Thesis (Ph. D.)--University of Missouri--Columbia, 2003. / Typescript. Vita. Includes bibliographical references.