Browsing by Subject "osteoarthritis"

Now showing 1 - 6 of 6
  • Thumbnail Image
    Item
    Analgesic prescribing trends in a national sample of older veterans with osteoarthritis: 2012-2017
    (Wolters Kluwer, 2019-06) Trentalange, Mark; Runels, Tessa; Bean, Andrew; Kerns, Robert D.; Bair, Matthew J.; Brody, Abraham A.; Brandt, Cynthia A.; Hwang, Ula; Medicine, School of Medicine
    Few investigations examine patterns of opioid and nonopioid analgesic prescribing and concurrent pain intensity ratings before and after institution of safer prescribing programs such as the October 2013 Veterans Health Administration system-wide Opioid Safety Initiative (OSI) implementation. We conducted a quasi-experimental pre–post observational study of all older U.S. veterans (≥50 years old) with osteoarthritis of the knee or hip. All associated outpatient analgesic prescriptions and outpatient pain intensity ratings from January 1, 2012 to December 31, 2016, were analyzed with segmented regression of interrupted time series. Standardized monthly rates for each analgesic class (total, opioid, nonsteroidal anti-inflammatory drug, acetaminophen, and other study analgesics) were analyzed with segmented negative binomial regression models with overall slope, step, and slope change. Similarly, segmented linear regression was used to analyze pain intensity ratings and percentage of those reporting pain. All models were additionally adjusted for age, sex, and race. Before OSI implementation, total analgesic prescriptions showed a steady rise, abruptly decreasing to a flat trajectory after OSI implementation. This trend was primarily due to a decrease in opioid prescribing after OSI. Total prescribing after OSI implementation was partially compensated by continuing increased prescribing of other study analgesics as well as a significant rise in acetaminophen prescriptions (post-OSI). No changes in nonsteroidal anti-inflammatory drug prescribing were seen. A small rise in the percentage of those reporting pain but not mean pain intensity ratings continued over the study period with no changes associated with OSI. Changes in analgesic prescribing trends were not paralleled by changes in reported pain intensity for older veterans with osteoarthritis.
  • Thumbnail Image
    Item
    Application of quantitative analysis in treatment of osteoporosis and osteoarthritis
    (2013-11-08) Chen, Andy Bowei; Yokota, Hiroki, 1955-; Na, Sungsoo; Schild, John H.
    As our population ages, treating bone and joint ailments is becoming increasingly important. Both osteoporosis, a bone disease characterized by a decreased density of mineral in bone, and osteoarthritis, a joint disease characterized by the degeneration of cartilage on the ends of bones, are major causes of decreased movement ability and increased pain. To combat these diseases, many treatments are offered, including drugs and exercise, and much biomedical research is being conducted. However, how can we get the most out of the research we perform and the treatment we do have? One approach is through computational analysis and mathematical modeling. In this thesis, quantitative methods of analysis are applied in different ways to two systems: osteoporosis and osteoarthritis. A mouse model simulating osteoporosis is treated with salubrinal and knee loading. The bone and cell data is used to formulate a system of differential equations to model the response of bone to each treatment. Using Particle Swarm Optimization, optimal treatment regimens are found, including a consideration of budgetary constraints. Additionally, an in vitro model of osteoarthritis in chondrocytes receives RNA silencing of Lrp5. Microarray analysis of gene expression is used to further elucidate the mode of regulation of ADAMTS5, an aggrecanase associated with cartilage degradation, by Lrp5, including the development of a mathematical model. The math model of osteoporosis reveals a quick response to salubrinal and a delayed but substantial response to knee loading. Consideration of cost effectiveness showed that as budgetary constraints increased, treatment did not start until later. The quantitative analysis of ADAMTS5 regulation suggested the involvement of IL1B and p38 MAPK. This research demonstrates the application of quantitative methods to further the usefulness of biomedical and biomolecular research into treatment and signaling pathways. Further work using these techniques can help uncover a bigger picture of osteoarthritis's mode of action and ideal treatment regimens for osteoporosis.
  • Thumbnail Image
    Item
    Cellular senescence in aging and osteoarthritis
    (Taylor & Francis, 2016) Toh, Wei Seong; Brittberg, Mats; Farr, Jack; Foldager, Casper Bindzus; Gomoll, Andreas H.; Hui, James Hoi Po; Richardson, James B.; Roberts, Sally; Spector, Myron; Department of Orthopaedic Surgery, IU School of Medicine
    It is well accepted that age is an important contributing factor to poor cartilage repair following injury, and to the development of osteoarthritis. Cellular senescence, the loss of the ability of cells to divide, has been noted as the major factor contributing to age-related changes in cartilage homeostasis, function, and response to injury. The underlying mechanisms of cellular senescence, while not fully understood, have been associated with telomere erosion, DNA damage, oxidative stress, and inflammation. In this review, we discuss the causes and consequences of cellular senescence, and the associated biological challenges in cartilage repair. In addition, we present novel strategies for modulation of cellular senescence that may help to improve cartilage regeneration in an aging population.
  • Thumbnail Image
    Item
    Customized biomaterials to augment chondrocyte gene therapy
    (Elsevier, 2017-04) Aguilar, Izath Nizeet; Trippel, Stephen; Shi, Shuiliang; Bonassar, Lawrence J.; Orthopaedic Surgery, School of Medicine
    A persistent challenge in enhancing gene therapy is the transient availability of the target gene product. This is particularly true in tissue engineering applications. The transient exposure of cells to the product could be insufficient to promote tissue regeneration. Here we report the development of a new material engineered to have a high affinity for a therapeutic gene product. We focus on insulin-like growth factor-I (IGF-I) for its highly anabolic effects on many tissues such as spinal cord, heart, brain and cartilage. One of the ways that tissues store IGF-I is through a group of insulin like growth factor binding proteins (IGFBPs), such as IGFBP-5. We grafted the IGF-I binding peptide sequence from IGFBP-5 onto alginate in order to retain the endogenous IGF-I produced by transfected chondrocytes. This novel material bound IGF-I and released the growth factor for at least 30 days in culture. We found that this binding enhanced the biosynthesis of transfected cells up to 19-fold. These data demonstrate the coordinated engineering of cell behavior and material chemistry to greatly enhance extracellular matrix synthesis and tissue assembly, and can serve as a template for the enhanced performance of other therapeutic proteins.
  • Thumbnail Image
    Item
    Using agents that suppress bone remodeling to treat or prevent joint disease: Quo vadis?
    (2016) Burr, David B.; Anatomy and Cell Biology, School of Medicine
    Treatment of osteoarthritis (OA) with antiremodeling agents has had a mixed record of results. It is likely that remodeling suppression is only effective when used in the early phases of OA, before significant progression. Animal and human studies largely bear this out. Treatment of young mice with a RANKL inhibitor suppresses bone resorption and prevents OA progression. Likewise, bisphosphonate treatments in rodents and rabbits with induced injury or inflammatory arthritis, reduced cartilage degeneration when administered preemptively, but later administration did not. The increased prevalence of OA in women after the menopause, and presence of estrogen receptors in joint tissues, suggests that treatment with estrogens or Selective Estrogen Receptor Modulators may be effective. However, in clinical trials of knee and hip, results show decreased or increased risk for OA, or no effect. Raloxifene had positive effects in animal models, but no effect in human studies. More recent potential treatments such as strontium ranelate or cathepsin-K inhibitors may be effective, but may work directly on the cartilage rather than through their well-known effects on bone. The conclusion from these studies is that anti-remodeling agents must be administered pre-emptively or in the very early stages of disease to be effective. This means that better imaging techniques or identification of early structural changes in bone that occur before progressive cartilage destruction must be developed.
  • Thumbnail Image
    Item
    Wnt Signaling Related to Subchondral Bone Density and Cartilage Degradation in OA
    (Wiley, 2018) Burr, David B.; Utreja, Achint; Anatomy and Cell Biology, School of Medicine
    The role of subchondral bone in the progression of osteoarthritis has been controversial for nearly 50 years.(1,2) The observation that subchondral sclerosis was nearly always present in end-stage disease led to the conclusion that the increased stiffness caused by a thicker subchondral bone plate detracted from the bone's ability to attenuate the loads imposed on the joint cartilage, increasing cartilage stresses and initiating the process of joint deterioration. Because cartilage damage does not always progress to full thickness cartilage loss and OA, Radin and Rose(3) proposed that the initiation and the progression of cartilage deterioration were separate processes.