This article reviews the risks of osteoporosis and osteonecrosis associated with glucocorticoid use, which are present even in the absence of low bone mineral density, and discusses strategies to ...reduce the risk of fractures and the data to support the strategies.
Foreword
This
Journal
feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author's clinical recommendations.
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A 55-year-old woman with severe, persistent asthma requiring glucocorticoid therapy for the past 3 months presents for care. Her medications include albuterol, inhaled fluticasone with salmeterol, montelukast, and prednisone (at a dose of 10 mg per day). In the past, she received several intermittent courses of prednisone at a dose of 15 mg or more per day. Her weight is 45.5 kg (100 lb), and her height 157.5 cm (62 in.); the body-mass index (the weight in kilograms divided by the square of the height in meters) is 18. Scattered wheezing is heard during expiration. Findings on vertebral percussion . . .
Carbapenem-resistant Enterobacteriaceae (CRE) are a serious public health threat. Infections due to these organisms are associated with significant morbidity and mortality. Mechanisms of drug ...resistance in gram-negative bacteria (GNB) are numerous; β-lactamase genes carried on mobile genetic elements are a key mechanism for the rapid spread of antibiotic-resistant GNB worldwide. Transmissible carbapenem-resistance in Enterobacteriaceae has been recognized for the last 2 decades, but global dissemination of carbapenemase-producing Enterobacteriaceae (CPE) is a more recent problem that, once initiated, has been occurring at an alarming pace. In this article, we discuss the evolution of CRE, with a focus on the epidemiology of the CPE pandemic; review risk factors for colonization and infection with the most common transmissible CPE worldwide, Klebsiella pneumoniae carbapenemase–producing K. pneumoniae; and present strategies used to halt the striking spread of these deadly pathogens.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Glucocorticoid administration is the most common cause of secondary osteoporosis and the leading cause of nontraumatic osteonecrosis. In patients receiving long-term therapy, glucocorticoids induce ...fractures in 30% to 50% and osteonecrosis in 9% to 40%. This article reviews glucocorticoid-induced osteoporosis and osteonecrosis, addressing the risk factors, pathogenesis, evaluation, treatment, and uncertainties in the clinical management of these disorders.
Awareness of the need for prevention of glucocorticoid-induced fractures is growing, but glucocorticoid administration is often overlooked as the most common cause of nontraumatic osteonecrosis. ...Glucocorticoid-induced osteonecrosis develops in 9–40% of patients receiving long-term therapy although it may also occur with short-term exposure to high doses, after intra-articular injection, and without glucocorticoid-induced osteoporosis. The name, osteonecrosis, is misleading because the primary histopathological lesion is osteocyte apoptosis. Apoptotic osteocytes persist because they are anatomically unavailable for phagocytosis and, with glucocorticoid excess, decreased bone remodeling retards their replacement. Glucocorticoid-induced osteocyte apoptosis, a cumulative and unrepairable defect, uniquely disrupts the mechanosensory function of the osteocyte–lacunar–canalicular system and thus starts the inexorable sequence of events leading to collapse of the femoral head. Current evidence indicates that bisphosphonates may rapidly reduce pain, increase ambulation, and delay joint collapse in patients with osteonecrosis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
SUMMARYAntimicrobial stewardship is a bundle of integrated interventions employed to optimize the use of antimicrobials in health care settings. While infectious-disease-trained physicians, with ...clinical pharmacists, are considered the main leaders of antimicrobial stewardship programs, clinical microbiologists can play a key role in these programs. This review is intended to provide a comprehensive discussion of the different components of antimicrobial stewardship in which microbiology laboratories and clinical microbiologists can make significant contributions, including cumulative antimicrobial susceptibility reports, enhanced culture and susceptibility reports, guidance in the preanalytic phase, rapid diagnostic test availability, provider education, and alert and surveillance systems. In reviewing this material, we emphasize how the rapid, and especially the recent, evolution of clinical microbiology has reinforced the importance of clinical microbiologists' collaboration with antimicrobial stewardship programs.
Abstract Glucocorticoid administration is required for many inflammatory and autoimmune diseases, but use of these drugs is associated with skeletal side effects including bone loss, fractures, and ...osteonecrosis. Fractures often occur without a reduction in bone mineral density, strongly suggesting that glucocorticoid excess adversely affects other aspects of bone strength. Although the primary effects of glucocorticoid excess on the skeleton are directly on bone cells, a vascular connection between these cells and the loss of bone strength appears likely. This review examines this connection and how it may explain the greater decline in bone strength than loss of bone mass that occurs with glucocorticoid excess.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Osteocyte apoptosis Jilka, Robert L; Noble, Brendon; Weinstein, Robert S
Bone (New York, N.Y.),
06/2013, Volume:
54, Issue:
2
Journal Article
Peer reviewed
Open access
Abstract Apoptotic death of osteocytes was recognized over 15 years ago, but its significance for bone homeostasis has remained elusive. A new paradigm has emerged that invokes osteocyte apoptosis as ...a critical event in the recruitment of osteoclasts to a specific site in response to skeletal unloading, fatigue damage, estrogen deficiency and perhaps in other states where bone must be removed. This is accomplished by yet to be defined signals emanating from dying osteocytes, which stimulate neighboring viable osteocytes to produce osteoclastogenic cytokines. The osteocyte apoptosis caused by chronic glucocorticoid administration does not increase osteoclasts; however, it does negatively impact maintenance of bone hydration, vascularity, and strength. This article is part of a Special Issue entitled "The Osteocyte".
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In this cluster-randomized study at ICUs in six hospitals, chlorhexidine-impregnated washcloths were associated with significantly lower rates of bloodstream infections and acquisition of ...multidrug-resistant organisms than were nonantimicrobial washcloths.
Multidrug-resistant organisms (MDROs), including methicillin-resistant
Staphylococcus aureus
(MRSA) and vancomycin-resistant enterococcus (VRE), have become endemic in many acute care and long-term care facilities.
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Infections with these organisms are often difficult to treat, owing to a dwindling armamentarium of active antimicrobial agents. The Centers for Disease Control and Prevention (CDC) has promulgated a variety of strategies, including hand hygiene and the use of isolation precautions, to limit the spread of these organisms among patients, but these strategies require consistent adherence to practices by large numbers of health care personnel during frequent patient encounters and can be difficult to sustain.
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Osteoclasts resorb the mineralized matrices formed by chondrocytes or osteoblasts. The cytokine receptor activator of nuclear factor-κB ligand (RANKL) is essential for osteoclast formation and ...thought to be supplied by osteoblasts or their precursors, thereby linking bone formation to resorption. However, RANKL is expressed by a variety of cell types, and it is unclear which of them are essential sources for osteoclast formation. Here we have used a mouse strain in which RANKL can be conditionally deleted and a series of Cre-deleter strains to demonstrate that hypertrophic chondrocytes and osteocytes, both of which are embedded in matrix, are essential sources of the RANKL that controls mineralized cartilage resorption and bone remodeling, respectively. Moreover, osteocyte RANKL is responsible for the bone loss associated with unloading. Contrary to the current paradigm, RANKL produced by osteoblasts or their progenitors does not contribute to adult bone remodeling. These results suggest that the rate-limiting step of matrix resorption is controlled by cells embedded within the matrix itself.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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