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Current HIV/AIDS Reports Oct 2022People living with HIV (PLWH) are at an increased risk for osteoporosis, a disease defined by the loss of bone mineral density (BMD) and deterioration of bone quality,... (Review)
Review
PURPOSE OF REVIEW
People living with HIV (PLWH) are at an increased risk for osteoporosis, a disease defined by the loss of bone mineral density (BMD) and deterioration of bone quality, both of which independently contribute to an increased risk of skeletal fractures. While there is an emerging body of literature focusing on the factors that contribute to BMD loss in PLWH, the contribution of these factors to bone quality changes are less understood. The current review summarizes and critically reviews the data describing the effects of HIV, HIV disease-related factors, and antiretroviral drugs (ARVs) on bone quality.
RECENT FINDINGS
The increased availability of high-resolution peripheral quantitative computed tomography has confirmed that both HIV infection and ARVs negatively affect bone architecture. There is considerably less data on their effects on bone remodeling or the composition of bone matrix. Whether changes in bone quality independently predict fracture risk, as seen in HIV-uninfected populations, is largely unknown. The available data suggests that bone quality deterioration occurs in PLWH. Future studies are needed to define which factors, viral or ARVs, contribute to loss of bone quality and which bone quality factors are most associated with increased fracture risk.
Topics: Anti-Retroviral Agents; Bone Density; Bone and Bones; Fractures, Bone; HIV Infections; Humans; Osteoporosis
PubMed: 35726043
DOI: 10.1007/s11904-022-00613-1 -
Discovery Medicine May 2011The skeleton is an organ whose integrity is maintained by constant lifelong renewal involving coordinated removal of worn bone by osteoclasts and resynthesis of new bone... (Review)
Review
The skeleton is an organ whose integrity is maintained by constant lifelong renewal involving coordinated removal of worn bone by osteoclasts and resynthesis of new bone by osteoblasts. In young adult humans and animals this process is homeostatic with no net gain or loss of bone mass. With natural aging and exacerbated by numerous pathological conditions, bone removal exceeds bone formation, disrupting homeostasis and resulting in bone loss. Over time, skeletal decline reaches clinical significance with development of osteopenia and eventually osteoporosis, conditions that dramatically increase bone fragility and the risk of fracture. Bone fractures can be devastating with significant morbidity and mortality. Over the last decade, it has become clear that skeletal renewal is strongly influenced by the immune system, a consequence of deep integration and centralization of common cell types and cytokine mediators, which we have termed the "immuno-skeletal interface." Consequently, dysregulated skeletal renewal and bone loss is a common feature of inflammatory conditions associated with immune activation. Interestingly, bone loss is also associated with conditions of immunodeficiency, including infection by the human immunodeficiency virus (HIV) that leads to acquired immunodeficiency syndrome (AIDS). Disruptions to the immuno-skeletal interface drive skeletal deterioration contributing to a high rate of bone fracture in HIV infection. This review examines current knowledge concerning the prevalence and etiology of skeletal complications in HIV infection, the effect of antiretroviral therapies (ART) on the skeleton, and how disruption of the immuno-skeletal interface may underlie bone loss in HIV infection and ART.
Topics: Acquired Immunodeficiency Syndrome; Aging; Antiretroviral Therapy, Highly Active; Bone Diseases, Metabolic; Bone and Bones; HIV; Humans
PubMed: 21616037
DOI: No ID Found -
Journal of Infection and Public Health 2010Although uncommon, spontaneous and postoperative pyogenic spondylodiscitis entail major morbidity and may be associated with serious long-term sequelae. A review of the... (Review)
Review
Although uncommon, spontaneous and postoperative pyogenic spondylodiscitis entail major morbidity and may be associated with serious long-term sequelae. A review of the literature was done to advance our understanding of the diagnosis, treatment, and outcome of these infections. The principles of conservative treatment are to establish an accurate microbiological diagnosis, treat with appropriate antibiotics, immobilize the spine, and closely monitor for spinal instability and neurological deterioration. The purpose of surgical treatment is to obtain multiple intraoperative cultures of bone and soft tissue, perform a thorough debridement of infected tissue and decompression of neural structures, and reconstruct the unstable spinal column with bone graft with or without concomitant instrumentation. Appropriate management requires aggressive medical treatment and, at times, surgical interventions. If recognized early and treated appropriately, a full recovery can often be expected. Therefore, clinicians should be aware of the clinical presentation of such infections to improve patient outcome.
Topics: Anti-Infective Agents; Back Pain; Bacterial Infections; Debridement; Decompression, Surgical; Diagnosis, Differential; Discitis; Humans; Postoperative Complications; Spine; Treatment Outcome
PubMed: 20701886
DOI: 10.1016/j.jiph.2010.01.001 -
Frontiers in Bioscience (Scholar... Jun 2016As the populations of the Western world become older, they will suffer more and more from bone defects related to osteoporosis (non-union fractures, vertebral damages),... (Review)
Review
As the populations of the Western world become older, they will suffer more and more from bone defects related to osteoporosis (non-union fractures, vertebral damages), cancers (malignant osteolysis) and infections (osteomyelitis). Autografts are usually used to fill these defects, but they have several drawbacks such as morbidity at the donor site and the amount and quality of bone that can be harvested. Recent scientific milestones made in biomaterials development were shown to be promising to overcome these limitations. Cell interactions with biomaterials can be improved by adding at their surface functional groups such as adhesive peptides and/or growth factors. The development of such biomimetic materials able to control bone cell responses can only proceed if it is based on a sound understanding of bone cell behavior and regulation. This review focuses on bone physiology and the regulation of bone cell differentiation and function, and how the latest advances in biomimetic materials can be translated within promising clinical outcomes.
Topics: Age Factors; Aged; Animals; Biocompatible Materials; Biomimetic Materials; Bone and Bones; Humans
PubMed: 27100704
DOI: 10.2741/s460 -
Viruses Oct 2020Chikungunya virus (CHIKV) is an alphavirus, transmitted by mosquitoes, which causes Chikungunya fever with symptoms of fever, rash, headache, and joint pain. In about... (Review)
Review
Chikungunya virus (CHIKV) is an alphavirus, transmitted by mosquitoes, which causes Chikungunya fever with symptoms of fever, rash, headache, and joint pain. In about 30%-40% of cases, the infection leads to polyarthritis and polyarthralgia. Presently, there are no treatment strategies or vaccine for Chikungunya fever. Moreover, the mechanism of CHIKV induced bone pathology is not fully understood. The modulation of host machinery is known to be essential in establishing viral pathogenesis. MicroRNAs (miRNAs) are small non-coding RNAs that regulate major cellular functions by modulating gene expression. Fascinatingly, recent reports have indicated the role of miRNAs in regulating bone homeostasis and altered expression of miRNAs in bone-related pathological diseases. In this review, we summarize the altered expression of miRNAs during CHIKV pathogenesis and the possible role of miRNAs during bone homeostasis in the context of CHIKV infection. A holistic understanding of the different signaling pathways targeted by miRNAs during bone remodeling and during CHIKV-induced bone pathology may lead to identification of useful biomarkers or therapeutics.
Topics: Animals; Bone and Bones; Chikungunya Fever; Chikungunya virus; Gene Expression Regulation; Homeostasis; Host-Pathogen Interactions; Humans; Mice; MicroRNAs; Osteogenesis; Signal Transduction; Virus Replication
PubMed: 33114216
DOI: 10.3390/v12111207 -
Nature Reviews. Immunology Apr 2018Systemic inflammation mediated by Plasmodium parasites is central to malaria disease and its complications. Plasmodium parasites reside in erythrocytes and can... (Review)
Review
Systemic inflammation mediated by Plasmodium parasites is central to malaria disease and its complications. Plasmodium parasites reside in erythrocytes and can theoretically reach all host tissues via the circulation. However, actual interactions between parasitized erythrocytes and host tissues, along with the consequent damage and pathological changes, are limited locally to specific tissue sites. Such tissue specificity of the parasite can alter the outcome of malaria disease, determining whether acute or chronic complications occur. Here, we give an overview of the recent progress that has been made in understanding tissue-specific immunopathology during Plasmodium infection. As knowledge on tissue-specific host-parasite interactions accumulates, better treatment modalities and targets may emerge for intervention in malaria disease.
Topics: Animals; Blood Vessels; Bone and Bones; Brain; Digestive System; Erythrocytes; Host-Parasite Interactions; Humans; Lymphatic System; Malaria; Malaria, Cerebral; Models, Immunological; Organ Specificity; Plasmodium; Retina
PubMed: 29332936
DOI: 10.1038/nri.2017.138 -
Clinical Therapeutics Sep 2016An understanding of the pharmacokinetic (PK) and pharmacodynamic (PD) principles that determine response to antimicrobial therapy can provide the clinician with... (Review)
Review
PURPOSE
An understanding of the pharmacokinetic (PK) and pharmacodynamic (PD) principles that determine response to antimicrobial therapy can provide the clinician with better-informed dosing regimens. Factors influential on antibiotic disposition and clinical outcome are presented, with a focus on the primary site of infection. Techniques to better understand antibiotic PK and optimize PD are acknowledged.
METHODS
PubMed (inception-April 2016) was reviewed for relevant publications assessing antimicrobial exposures within different anatomic locations and clinical outcomes for various infection sites.
FINDINGS
A limited literature base indicates variable penetration of antibiotics to different target sites of infection, with drug solubility and extent of protein binding providing significant PK influences in addition to the major clearing pathway of the agent. PD indices derived from in vitro studies and animal models determine the optimal magnitude and frequency of dosing regimens for patients. PK/PD modeling and simulation has been shown an efficient means of assessing these PD endpoints against a variety of PK determinants, clarifying the unique effects of infection site and patient characteristics to inform the adequacy of a given antibiotic regimen.
IMPLICATIONS
Appreciation of the PK properties of an antibiotic and its PD measure of efficacy can maximize the utility of these life-saving drugs. Unfortunately, clinical data remain limited for a number of infection site-antibiotic exposure relationships. Modeling and simulation can bridge preclinical and patient data for the prescription of optimal antibiotic dosing regimens, consistent with the tenets of personalized medicine.
Topics: Animals; Anti-Bacterial Agents; Bacteremia; Bacterial Infections; Bone and Bones; Dose-Response Relationship, Drug; Humans; Lung; Soft Tissue Infections
PubMed: 27449411
DOI: 10.1016/j.clinthera.2016.06.015 -
Orthopaedics & Traumatology, Surgery &... Jun 2021
Topics: Arthritis, Infectious; Bone and Bones; Humans; Prosthesis-Related Infections
PubMed: 33857682
DOI: 10.1016/j.otsr.2021.102928 -
Current HIV/AIDS Reports Dec 2016Clinical data accumulated over the past two decades attests to a significant decline in bone mineral density (BMD) in patients infected by HIV, which does not remit but... (Review)
Review
Clinical data accumulated over the past two decades attests to a significant decline in bone mineral density (BMD) in patients infected by HIV, which does not remit but may actually intensify with anti-retroviral therapy (ART). Long generally perceived as an aberration without clinical consequences in relatively young HIV-infected cohorts, recent studies have documented marked increases in fracture incidence in HIV-infected men and women over a wide age continuum. Fractures are associated with chronic pain, crippling morbidity, and increased mortality, undermining the gains in quality of life achieved though ART. As bone loss and resulting increases in fracture incidence are a natural consequence of aging, there is now concern regarding the long-term consequences of HIV/ART-associated premature bone loss, given the transition of the HIV/AIDS population into an older age demographic. The development of guidelines for diagnosis and treatment of bone disease within the context of HIV and ART has been an important recent step in raising awareness of the problem and the implications of bone fracture for patient health. Significant progress has also been made in recent years in dissecting the complex and multifactorial mechanisms driving bone loss in HIV/ART and the role of underlying immunological disruption in skeletal dysmorphogenesis. This review examines recent progress in the field and studies by Women's Interagency HIV Study (WIHS)-associated investigators, inside and outside of the WIHS cohort, aimed at identifying skeletal abnormalities, quantifying facture incidence, management, and understanding underlying mechanisms in people living with HIV in the context of chronic ART.
Topics: Anti-Retroviral Agents; Bone Density; Bone Diseases, Metabolic; Bone and Bones; Female; Fractures, Bone; HIV Infections; Humans; Male; Quality of Life
PubMed: 27678124
DOI: 10.1007/s11904-016-0336-6 -
Physiological Reviews Oct 2015Histone deacetylases (Hdacs) are conserved enzymes that remove acetyl groups from lysine side chains in histones and other proteins. Eleven of the 18 Hdacs encoded by... (Review)
Review
Histone deacetylases (Hdacs) are conserved enzymes that remove acetyl groups from lysine side chains in histones and other proteins. Eleven of the 18 Hdacs encoded by the human and mouse genomes depend on Zn(2+) for enzymatic activity, while the other 7, the sirtuins (Sirts), require NAD2(+). Collectively, Hdacs and Sirts regulate numerous cellular and mitochondrial processes including gene transcription, DNA repair, protein stability, cytoskeletal dynamics, and signaling pathways to affect both development and aging. Of clinical relevance, Hdacs inhibitors are United States Food and Drug Administration-approved cancer therapeutics and are candidate therapies for other common diseases including arthritis, diabetes, epilepsy, heart disease, HIV infection, neurodegeneration, and numerous aging-related disorders. Hdacs and Sirts influence skeletal development, maintenance of mineral density and bone strength by affecting intramembranous and endochondral ossification, as well as bone resorption. With few exceptions, inhibition of Hdac or Sirt activity though either loss-of-function mutations or prolonged chemical inhibition has negative and/or toxic effects on skeletal development and bone mineral density. Specifically, Hdac/Sirt suppression causes abnormalities in physiological development such as craniofacial dimorphisms, short stature, and bone fragility that are associated with several human syndromes or diseases. In contrast, activation of Sirts may protect the skeleton from aging and immobilization-related bone loss. This knowledge may prolong healthspan and prevent adverse events caused by epigenetic therapies that are entering the clinical realm at an unprecedented rate. In this review, we summarize the general properties of Hdacs/Sirts and the research that has revealed their essential functions in bone forming cells (e.g., osteoblasts and chondrocytes) and bone resorbing osteoclasts. Finally, we offer predictions on future research in this area and the utility of this knowledge for orthopedic applications and bone tissue engineering.
Topics: Animals; Bone Development; Bone and Bones; Histone Deacetylases; Humans; Skeleton
PubMed: 26378079
DOI: 10.1152/physrev.00004.2015