Browsing by Subject "Renal osteodystrophy"

Now showing 1 - 4 of 4
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    Bone Quality in Chronic Kidney Disease: Definitions and Diagnostics
    (Springer, 2017-06) McNerny, Erin M.B.; Nickolas, Thomas L.; Medicine, School of Medicine
    PURPOSE OF REVIEW: In this paper, we review the epidemiology, diagnosis, and pathogenesis of fractures and renal osteodystrophy. RECENT FINDINGS: The role of bone quality in the pathogenesis of fracture susceptibility in chronic kidney disease (CKD) is beginning to be elucidated. Bone quality refers to bone material properties, such as cortical and trabecular microarchitecture, mineralization, turnover, microdamage, and collagen content and structure. Recent data has added to our understanding of the effects of CKD on alterations to bone quality, emerging data on the role of abnormal collagen structure on bone strength, the potential of non-invasive methods to inform our knowledge of bone quality, and how we can use these methods to inform strategies that protect against bone loss and fractures. However, more prospective data is required. CKD is associated with abnormal bone quality and strength which results in high fracture incidence.
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    Renal Osteodystrophy or Kidney-Induced Osteoporosis?
    (Springer, 2017-06) Moe, Sharon M.; Medicine, School of Medicine
    PURPOSE OF REVIEW: Chronic kidney disease (CKD) affects nearly 10% of the population. The incidence of fractures in population studies demonstrate an increase with worsening stages of kidney disease suggesting specific CKD related causes of fracture. RECENT FINDINGS: The increase in fractures with CKD most likely represents disordered bone quality due to the abnormal bone remodeling from renal osteodystrophy. There is also an increase in fractures with age in patients with CKD, suggesting that patients with CKD also have many fracture risk factors common to patients without known CKD. Osteoporosis is defined by the National Institutes of Health as "A skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. Bone strength reflects the integration of two main features: bone quantity and bone quality." Thus, CKD-related fractures can be considered a type of osteoporosis-where the bone quality is additionally impaired above that of age/hormonal-related osteoporosis. Perhaps using the term CKD-induced osteoporosis, similar to steroid-induced osteoporosis, will allow patients with CKD to be studied in trials investigating therapeutic agents. In this series, we will examine how CKD-induced osteoporosis may be diagnosed and treated.
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    Renal osteodystrophy: A historical review of its origins and conceptual evolution
    (Elsevier, 2022-11-24) Eknoyan, Garabed; Moe, Sharon M.; Medicine, School of Medicine
    Long considered an inert supporting framework, bone studies went neglected until the 17th century when they began as descriptive microscopic studies of structure which over time progressed into that of chemistry and physiology. It was in the mid-19th century that studies evolved into an inquisitive discipline which matured into the experimental investigation of bone in health and disease in the 20th century, and ultimately that of molecular studies now deciphering the genetic language of bone biology. These fundamental studies were catalyzed by increasing clinical interest in bone disease. The first bone disease to be identified was rickets in 1645. Its subsequent connection to albuminuric patients reported in 1883 later became renal osteodystrophy in 1942, launching studies that elucidated the functions of vitamin D and parathyroid hormone and their role in the altered calcium and phosphate metabolism of the disease. Studies in osteoporosis and renal osteodystrophy have driven most recent progress benefitting from technological advances in imaging and the precision of evaluating bone turnover, mineralization, and volume. This review exposes the progress of bone biology from a passive support structure to a dynamically regulated organ with vital homeostatic functions whose understanding has undergone more revisions and paradigm shifts than that of any other organ.
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    Role of TGF-β in a Mouse Model of High Turnover Renal Osteodystrophy
    (Oxford University Press, 2014) Liu, Shiguang; Song, Wenping; Boulanger, Joseph H.; Tang, Wen; Sabbagh, Yves; Kelley, Brian; Gotschall, Russell; Ryan, Susan; Phillips, Lucy; Malley, Katie; Cao, Xiaohong; Xia, Tai-He; Zhen, Gehua; Cao, Xu; Ling, Hong; Dechow, Paul C.; Bellido, Teresita M.; Ledbetter, Steven R.; Schiavi, Susan C.; Medicine, School of Medicine
    Altered bone turnover is a key pathologic feature of chronic kidney disease-mineral and bone disorder (CKD-MBD). Expression of TGF-β1, a known regulator of bone turnover, is increased in bone biopsies from individuals with CKD. Similarly, TGF-β1 mRNA and downstream signaling is increased in bones from jck mice, a model of high-turnover renal osteodystrophy. A neutralizing anti-TGF-β antibody (1D11) was used to explore TGF-β's role in renal osteodystrophy. 1D11 administration to jck significantly attenuated elevated serum osteocalcin and type I collagen C-telopeptides. Histomorphometric analysis indicated that 1D11 administration increased bone volume and suppressed the elevated bone turnover in a dose-dependent manner. These effects were associated with reductions in osteoblast and osteoclast surface areas. Micro-computed tomography (µCT) confirmed the observed increase in trabecular bone volume and demonstrated improvements in trabecular architecture and increased cortical thickness. 1D11 administration was associated with significant reductions in expression of osteoblast marker genes (Runx2, alkaline phosphatase, osteocalcin) and the osteoclast marker gene, Trap5. Importantly, in this model, 1D11 did not improve kidney function or reduce serum parathyroid hormone (PTH) levels, indicating that 1D11 effects on bone are independent of changes in renal or parathyroid function. 1D11 also significantly attenuated high-turnover bone disease in the adenine-induced uremic rat model. Antibody administration was associated with a reduction in pSMAD2/SMAD2 in bone but not bone marrow as assessed by quantitative immunoblot analysis. Immunostaining revealed pSMAD staining in osteoblasts and osteocytes but not osteoclasts, suggesting 1D11 effects on osteoclasts may be indirect. Immunoblot and whole genome mRNA expression analysis confirmed our previous observation that repression of Wnt/β-catenin expression in bone is correlated with increased osteoclast activity in jck mice and bone biopsies from CKD patients. Furthermore, our data suggest that elevated TGF-β may contribute to the pathogenesis of high-turnover disease partially through inhibition of β-catenin signaling.