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International Journal of Infectious... Apr 2019Treatment of bone and joint infections can be challenging as antibiotics should penetrate through the rigid bone structure and into the synovial space. Several... (Review)
Review
Treatment of bone and joint infections can be challenging as antibiotics should penetrate through the rigid bone structure and into the synovial space. Several pharmacokinetic studies measured the extent of penetration of different antibiotics into bone and joint tissues. This review discusses the results of these studies and compares them with minimum inhibitory concentrations (MIC) of common pathogens implicated in bone and joint infections in order to determine which antibiotics may have a greater potential in the treatment of such infections. Clinical outcomes were also evaluated as data were available. More than 30 antibiotics were evaluated. Overall, most antibiotics, including amoxicillin, piperacillin/tazobactam, cloxacillin, cephalosporins, carbapenems, aztreonam, aminoglycosides, fluoroquinolones, doxycycline, vancomycin, linezolid, daptomycin, clindamycin, trimethoprim/sulfamethoxazole, fosfomycin, rifampin, dalbavancin, and oritavancin, showed good penetration into bone and joint tissues reaching concentrations exceeding the MIC and/or MIC breakpoints of common bone and joint infections pathogens. Few exceptions include penicillin and metronidazole which showed a lower than optimum penetration into bones, and the latter as well as flucloxacillin had poor profiles in terms of joint space penetration. Of note, studies on joint space penetration were fewer than studies on bone tissue penetration. Although clinical studies in osteomyelitis and septic arthritis are not available for all of the evaluated antibiotics, these pharmacokinetic results indicate that agents with good penetration profiles would have a potential utilization in such infections.
Topics: Anti-Bacterial Agents; Arthritis, Infectious; Bone and Bones; Humans; Joints; Osteomyelitis
PubMed: 30772469
DOI: 10.1016/j.ijid.2019.02.005 -
Frontiers in Immunology 2021Bone remodeling is tightly controlled by osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Fine tuning of the osteoclast-osteoblast balance... (Review)
Review
Bone remodeling is tightly controlled by osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Fine tuning of the osteoclast-osteoblast balance results in strict synchronization of bone resorption and formation, which maintains structural integrity and bone tissue homeostasis; in contrast, dysregulated bone remodeling may cause pathological osteolysis, in which inflammation plays a vital role in promoting bone destruction. The alveolar bone presents high turnover rate, complex associations with the tooth and periodontium, and susceptibility to oral pathogenic insults and mechanical stress, which enhance its complexity in host defense and bone remodeling. Alveolar bone loss is also involved in systemic bone destruction and is affected by medication or systemic pathological factors. Therefore, it is essential to investigate the osteoimmunological mechanisms involved in the dysregulation of alveolar bone remodeling. The inflammasome is a supramolecular protein complex assembled in response to pattern recognition receptors and damage-associated molecular patterns, leading to the maturation and secretion of pro-inflammatory cytokines and activation of inflammatory responses. Pyroptosis downstream of inflammasome activation also facilitates the clearance of intracellular pathogens and irritants. However, inadequate or excessive activity of the inflammasome may allow for persistent infection and infection spreading or uncontrolled destruction of the alveolar bone, as commonly observed in periodontitis, periapical periodontitis, peri-implantitis, orthodontic tooth movement, medication-related osteonecrosis of the jaw, nonsterile or sterile osteomyelitis of the jaw, and osteoporosis. In this review, we present a framework for understanding the role and mechanism of canonical and noncanonical inflammasomes in the pathogenesis and development of etiologically diverse diseases associated with alveolar bone loss. Inappropriate inflammasome activation may drive alveolar osteolysis by regulating cellular players, including osteoclasts, osteoblasts, osteocytes, periodontal ligament cells, macrophages, monocytes, neutrophils, and adaptive immune cells, such as T helper 17 cells, causing increased osteoclast activity, decreased osteoblast activity, and enhanced periodontium inflammation by creating a pro-inflammatory milieu in a context- and cell type-dependent manner. We also discuss promising therapeutic strategies targeting inappropriate inflammasome activity in the treatment of alveolar bone loss. Novel strategies for inhibiting inflammasome signaling may facilitate the development of versatile drugs that carefully balance the beneficial contributions of inflammasomes to host defense.
Topics: Alveolar Bone Loss; Animals; Bone and Bones; Humans; Inflammasomes; Osteolysis
PubMed: 34177950
DOI: 10.3389/fimmu.2021.691013 -
Endocrinology and Metabolism (Seoul,... Oct 2022Paget's disease of the bone is a prevalent bone disease characterized by disorganized bone remodeling; however, it is comparatively uncommon in East Asian countries,...
Paget's disease of the bone is a prevalent bone disease characterized by disorganized bone remodeling; however, it is comparatively uncommon in East Asian countries, including China, Japan, and Korea. The exact cause still remains unknown. In genetically susceptible individuals, environmental triggers such as paramyxoviral infections are likely to cause the disease. Increased osteoclast activity results in increased bone resorption, which attracts osteoblasts and generates new bone matrix. Fast bone resorption and formation lead to the development of disorganized bone tissue. Increasing serum alkaline phosphatase or unique radiographic lesions may serve as the diagnostic indicators. Common symptoms include bone pain, bowing of the long bones, an enlarged skull, and hearing loss. The diagnosis is frequently confirmed by radiographic and nuclear scintigraphy of the bone. Further, bisphosphonates such as zoledronic acid and pamidronate are effective for its treatment. Moreover, biochemical monitoring is superior to the symptoms as a recurrence indicator. This article discusses the updates of Paget's disease of bone with a clinical case.
Topics: Humans; Osteitis Deformans; Diphosphonates; Pamidronate; Bone and Bones; Bone Resorption
PubMed: 36327984
DOI: 10.3803/EnM.2022.1575 -
Proceedings of the National Academy of... Jul 2021Oral commensal bacteria actively participate with gingival tissue to maintain healthy neutrophil surveillance and normal tissue and bone turnover processes. Disruption...
Oral commensal bacteria actively participate with gingival tissue to maintain healthy neutrophil surveillance and normal tissue and bone turnover processes. Disruption of this homeostatic host-bacteria relationship occurs during experimental gingivitis studies where it has been clearly established that increases in the bacterial burden increase gingival inflammation. Here, we show that experimental gingivitis resulted in three unique clinical inflammatory phenotypes (high, low, and slow) and reveal that interleukin-1β, a reported major gingivitis-associated inflammatory mediator, was not associated with clinical gingival inflammation in the slow response group. In addition, significantly higher levels of spp. were also unique to this group. The low clinical response group was characterized by low concentrations of host mediators, despite similar bacterial accumulation and compositional characteristics as the high clinical response group. Neutrophil and bone activation modulators were down-regulated in all response groups, revealing novel tissue and bone protective responses during gingival inflammation. These alterations in chemokine and microbial composition responses during experimental gingivitis reveal a previously uncharacterized variation in the human host response to a disruption in gingival homeostasis. Understanding this human variation in gingival inflammation may facilitate the identification of periodontitis-susceptible individuals. Overall, this study underscores the variability in host responses in the human population arising from variations in host immune profiles (low responders) and microbial community maturation (slow responders) that may impact clinical outcomes in terms of destructive inflammation.
Topics: Adolescent; Adult; Bone and Bones; Chemokines; Gingiva; Gingivitis; Homeostasis; Humans; Inflammation; Phylogeny; Time Factors; Young Adult
PubMed: 34193520
DOI: 10.1073/pnas.2012578118 -
Frontiers in Immunology 2022Chronic recurrent and multifocal osteomyelitis (CRMO) is a nonsporadic autoinflammatory disorder. Currently, it is diagnosed based on clinical, radiologic, pathological,... (Review)
Review
Chronic recurrent and multifocal osteomyelitis (CRMO) is a nonsporadic autoinflammatory disorder. Currently, it is diagnosed based on clinical, radiologic, pathological, and longitudinal data. Numerous aspects should be highlighted due to increased knowledge in imaging and immunology. We emphasize the use of whole-body MRI, which is a non-invasive diagnostic strategy. A literature review was carried out on longitudinal studies. Commonly, the mean age at diagnosis is 11 years, ranging between 3 and 17. The most common sites are the long bone metaphysis, particularly femoral and tibial metaphysis. In addition, the pelvis, spine, clavicle, and mandible may be involved. In long bones, the radiologic appearance can show typical structure, mixed lytic and sclerotic, sclerotic or lytic. It is frequently metaphyseal or juxta-physeal, with hyperostosis or periosteal thickening. The involvement of the vertebral skeleton is often multifocal. Therefore, whole-body MRI is essential in identifying subclinical lesions. CRMO is a polymorphic disorder in which whole-body MRI is beneficial to demonstrate subclinical edema. Vertebral collapse requires long-term monitoring.
Topics: Bone and Bones; Child; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Osteomyelitis
PubMed: 36072576
DOI: 10.3389/fimmu.2022.959575 -
Nature Communications Jan 2018Microbial metabolites are known to modulate immune responses of the host. The main metabolites derived from microbial fermentation of dietary fibers in the intestine,...
Microbial metabolites are known to modulate immune responses of the host. The main metabolites derived from microbial fermentation of dietary fibers in the intestine, short-chain fatty acids (SCFA), affect local and systemic immune functions. Here we show that SCFA are regulators of osteoclast metabolism and bone mass in vivo. Treatment of mice with SCFA as well as feeding with a high-fiber diet significantly increases bone mass and prevents postmenopausal and inflammation-induced bone loss. The protective effects of SCFA on bone mass are associated with inhibition of osteoclast differentiation and bone resorption in vitro and in vivo, while bone formation is not affected. Mechanistically, propionate (C3) and butyrate (C4) induce metabolic reprogramming of osteoclasts resulting in enhanced glycolysis at the expense of oxidative phosphorylation, thereby downregulating essential osteoclast genes such as TRAF6 and NFATc1. In summary, these data identify SCFA as potent regulators of osteoclast metabolism and bone homeostasis.
Topics: Animals; Bone Density; Bone Resorption; Bone and Bones; Butyrates; Dietary Fiber; Fatty Acids, Volatile; Female; Gene Expression; Glycolysis; Humans; Mice, Inbred C57BL; Osteoclasts; Propionates; Protective Agents
PubMed: 29302038
DOI: 10.1038/s41467-017-02490-4 -
Nature Communications Nov 2021Clinically, it is difficult to endow implants with excellent osteogenic ability and antibacterial activity simultaneously. Herein, the self-activating implants modified...
Clinically, it is difficult to endow implants with excellent osteogenic ability and antibacterial activity simultaneously. Herein, the self-activating implants modified with hydroxyapatite (HA)/MoS coating are designed to prevent Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) infections and accelerate bone regeneration simultaneously. The electron transfer between bacteria and HA/MoS is triggered when bacteria contacted with the material. RNA sequencing data reveals that the expression level of anaerobic respiration-related genes is up-regulated and the expression level of aerobic respiration-related genes is down-regulated when bacteria adhere to the implants. HA/MoS presents a highly effective antibacterial efficacy against both S. aureus and E. coli because of bacterial respiration-activated metabolic pathway changes. Meanwhile, this coating promotes the osteoblastic differentiation of mesenchymal stem cells by altering the potentials of cell membrane and mitochondrial membrane. The proposed strategy exhibits great potential to endow implants with self-activating anti-infection performance and osteogenic ability simultaneously.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bone Regeneration; Bone and Bones; Cell Differentiation; Cell Membrane; Cell Proliferation; Cell Respiration; Communicable Diseases; Disease Models, Animal; Drug Implants; Durapatite; Electron Transport; Escherichia coli; Escherichia coli Infections; Male; Mesenchymal Stem Cells; Osteogenesis; Rats; Rats, Sprague-Dawley; Staphylococcal Infections; Staphylococcus aureus; Up-Regulation
PubMed: 34824260
DOI: 10.1038/s41467-021-27217-4 -
Journal of Ultrasound Sep 2020The assessment of bone mainly relies on standard radiographs, CT, MRI, and bone scintigraphy depending on the anatomic region complexity and clinical scenario.... (Review)
Review
The assessment of bone mainly relies on standard radiographs, CT, MRI, and bone scintigraphy depending on the anatomic region complexity and clinical scenario. Ultrasound (US), due to different acoustic impedance between soft tissues and the bone cortex, only allows the evaluation of the bone surfaces. Nevertheless, US can be useful in the evaluation of several bone disorders affecting the limbs as a result of its tomographic capabilities and high definition. This pictorial review article summarises our clinical experience in adults and reviews the literature on US bone examination. We first present the US appearance of normal bone and the main congenital anatomic variations, after which we illustrate the US findings of a variety of bone disorders. Although US has limits in bone assessment, its analysis must be a part of every musculoskeletal US examination.
Topics: Bone Diseases; Bone and Bones; Humans; Ultrasonography
PubMed: 32419074
DOI: 10.1007/s40477-020-00477-4 -
International Journal of Molecular... Apr 2021Bone substitutes have been applied to treat osseous defects for a long time. To prevent implant related infection (IRI) and enhance bone healing functionalized... (Review)
Review
Bone substitutes have been applied to treat osseous defects for a long time. To prevent implant related infection (IRI) and enhance bone healing functionalized biomaterials, antibiotics and osteoinductive substances have been introduced. This study gives an overview of the current available surface-coated bone substitutes and provides an outlook for future perspectives.
Topics: Animals; Bacterial Infections; Biocompatible Materials; Bone Substitutes; Bone and Bones; Humans
PubMed: 33922517
DOI: 10.3390/ijms22094412 -
Chinese Journal of Traumatology =... Dec 2020In this paper, we review the results of previous studies and summarize the effects of various factors on the regulation of bone metabolism in traumatic bone infections.... (Review)
Review
In this paper, we review the results of previous studies and summarize the effects of various factors on the regulation of bone metabolism in traumatic bone infections. Infection-related bone destruction incorporates pathogens and iatrogenic factors in the process of bone resorption dominated by the skeletal and immune systems. The development of bone immunology has established a bridge of communication between the skeletal system and the immune system. Exploring the effects of pathogens, skeletal systems, immune systems, and antibacterials on bone repair in infectious conditions can help improve the treatment of these diseases.
Topics: Anti-Bacterial Agents; Bone and Bones; Cellular Microenvironment; Humans; Immune System; Lymphocyte Subsets; Osteitis; Osteoblasts; Osteoclasts; Staphylococcal Infections
PubMed: 32847694
DOI: 10.1016/j.cjtee.2020.05.009