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Journal of Veterinary Internal Medicine Nov 2022Computed tomography (CT) findings of dogs with discospondylitis have not been widely described despite increased availability of this imaging modality.
BACKGROUND
Computed tomography (CT) findings of dogs with discospondylitis have not been widely described despite increased availability of this imaging modality.
OBJECTIVES
Describe the CT features of discospondylitis in a population of clinically affected dogs with discospondylitis diagnosed by magnetic resonance imaging (MRI).
ANIMALS
Forty-one dogs (63 affected discs) with MRI-identified discospondylitis presented to a single referral hospital between 2012 and 2022.
METHODS
Retrospective, single center, descriptive case series with analysis of MRI-identified discospondylitis sites and concomitant CT imaging. Computed tomographic features of MRI-affected sites including intervertebral disc space (IVDS), endplates, vertebral body, epidural space and paraspinal tissues were described.
RESULTS
The most frequently found changes were: (1) endplate involvement (87.3%) most frequently bilateral (94.5%), with erosion (61.9%) and multifocal osteolysis (67.3%); (2) periosteal proliferation adjacent to the IVDS (73%) and spondylosis (66.7%); and (3) vertebral body involvement (66.7%) involving one-third of the vertebra (85.7%) with multifocal osteolysis (73.5%). Other less prevalent features included an abnormal IVDS (narrowed or collapsed), sclerosis of the adjacent vertebral body or endplates, presence of disseminated idiopathic skeletal hyperostosis or vacuum artifact.
CONCLUSIONS AND CLINICAL IMPORTANCE
We determined that bilateral endplate erosion and periosteal proliferation were very common in dogs with discospondylitis. Careful evaluation of CT in all 3 planes (dorsal, sagittal, transverse) is necessary to identify an affected IVDS. These described CT features can aid in the diagnosis of discospondylitis in dogs but equivocal cases might still require MRI.
Topics: Animals; Dogs; Discitis; Dog Diseases; Intervertebral Disc; Lumbar Vertebrae; Magnetic Resonance Imaging; Osteolysis; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 36208075
DOI: 10.1111/jvim.16551 -
Orthopaedics & Traumatology, Surgery &... Oct 2010We report the case of an osteoblastoma of the hamate bone that was successfully treated by curettage. This tumor is very rare in a carpal bone and only nine cases have...
We report the case of an osteoblastoma of the hamate bone that was successfully treated by curettage. This tumor is very rare in a carpal bone and only nine cases have been reported in the literature. Pathological examination is mandatory before treatment due to the lack of distinctive clinical and radiological features. Osteoblastomas are benign, but potentially aggressive bone tumors. Treatment of the lesion may either be a conservative "intralesional resection" or radical "wide en bloc resection". The latter option, which has non-negligible functional consequences in the wrist, should be reserved for recurrence after curettage but may also be considered a primary immediate alternative for aggressive forms.
Topics: Adult; Biopsy; Bone Cysts; Bone Neoplasms; Curettage; Delayed Diagnosis; Hamate Bone; Humans; Magnetic Resonance Imaging; Male; Osteoblastoma; Osteolysis; Radiography
PubMed: 20692218
DOI: 10.1016/j.otsr.2010.02.014 -
Journal of Nuclear Medicine : Official... Feb 1979Migratory osteolysis is a recently recognized syndrome characterized by a migratory articular pain pattern of the lower extremities and associated radiographically with... (Comparative Study)
Comparative Study
Migratory osteolysis is a recently recognized syndrome characterized by a migratory articular pain pattern of the lower extremities and associated radiographically with localized and reversible juxta-articular osteoporosis. Serial bone scans, both dynamic and static, appear to offer a new and more sensitive means for diagnosing and monitoring of this condition. The dynamic studies suggest that augmented osseous blood flow is responsible, at least in part, for increased radioactivity in clinically involved areas and presumably is mediating the osteoporotic process.
Topics: Adult; Bone Resorption; Bone and Bones; Humans; Leg; Male; Osteolysis; Osteoporosis; Radiography; Radionuclide Imaging; Regional Blood Flow; Time Factors
PubMed: 430187
DOI: No ID Found -
International Journal of Molecular... Feb 2017Aseptic loosening (AL) due to osteolysis is the primary cause of joint prosthesis failure. Currently, a second surgery is still the only available treatment for AL, with... (Review)
Review
Aseptic loosening (AL) due to osteolysis is the primary cause of joint prosthesis failure. Currently, a second surgery is still the only available treatment for AL, with its associated drawbacks. The present review aims at identifying genes whose expression is altered in osteolysis, and that could be the target of new pharmacological treatments, with the goal of replacing surgery. This review also aims at identifying the molecular pathways altered by different wear particles. We reviewed preclinical and clinical studies from 2010 to 2016, analyzing gene expression of tissues or cells affected by osteolysis. A total of 32 in vitro, 16 in vivo and six clinical studies were included. These studies revealed that genes belonging to both inflammation and osteoclastogenesis pathways are mainly involved in osteolysis. More precisely, an increase in genes encoding for the following factors were observed: Interleukins 6 and 1β (IL16 and β), Tumor Necrosis Factor α (TNFα), nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1), Cathepsin K (CATK) and Tartrate-resistant acid phosphatase (TRAP). Titanium (Ti) and Polyethylene (PE) were the most studied particles, showing that Ti up-regulated inflammation and osteoclastogenesis related genes, while PE up-regulated primarily osteoclastogenesis related genes.
Topics: Animals; Clinical Studies as Topic; Disease Models, Animal; Gene Expression Regulation; Humans; Inflammation; Osteoclasts; Osteolysis; Signal Transduction
PubMed: 28245614
DOI: 10.3390/ijms18030499 -
Pediatric Blood & Cancer Mar 2014Rapid advances in evidence-based treatment schedules are a hallmark of modern oncology. In rare neoplastic diseases, however, clinical expertise is hard to build and... (Review)
Review
Rapid advances in evidence-based treatment schedules are a hallmark of modern oncology. In rare neoplastic diseases, however, clinical expertise is hard to build and evidence based on randomized trials almost impossible to collect. Gorham disease is a rare form of lymphatic proliferation accompanied by osteolysis, which usually occurs in young adults. Despite the fact that the clinical course of Gorham disease is often devastating and occasionally fatal, insights into its biological background are sparse and standardized treatment unavailable. Interestingly, recent knowledge on the mechanisms of lymphangiogenesis may help elucidate the pathophysiology of Gorham disease and lead to novel treatment targets. Here, we discuss our current understanding of Gorham disease, discuss established and emerging therapeutic strategies, and attempt to frame a treatment rationale.
Topics: Biomarkers; Bone Resorption; Humans; Immunohistochemistry; Osteolysis, Essential
PubMed: 24214028
DOI: 10.1002/pbc.24832 -
Current Osteoporosis Reports Feb 2023Multicentric carpotarsal osteolysis (MCTO) is an ultra-rare disorder characterized by osteolysis of the carpal and tarsal bones, subtle craniofacial deformities, and... (Review)
Review
PURPOSE OF REVIEW
Multicentric carpotarsal osteolysis (MCTO) is an ultra-rare disorder characterized by osteolysis of the carpal and tarsal bones, subtle craniofacial deformities, and nephropathy. The molecular pathways underlying the pathophysiology are not well understood.
RECENT FINDINGS
MCTO is caused by heterozygous mutations in MAFB, which encodes the widely expressed transcription factor MafB. All MAFB mutations in patients with MCTO result in replacement of amino acids that cluster in a phosphorylation region of the MafB transactivation domain and account for a presumed gain-of-function for the variant protein. Since 2012, fewer than 60 patients with MCTO have been described with 20 missense mutations in MAFB. The clinical presentations are variable, and a genotype-phenotype correlation is lacking. Osteolysis, via excessive osteoclast activity, has been regarded as the primary mechanism, although anti-resorptive agents demonstrate little therapeutic benefit. This paper appraises current perspectives of MafB protein action, inflammation, and dysfunctional bone formation on the pathogenesis of the skeletal phenotype in MCTO. More research is needed to understand the pathogenesis of MCTO to develop rational therapies.
Topics: Humans; Osteolysis; Mutation; Mutation, Missense; Carpal Bones; Phenotype
PubMed: 36477366
DOI: 10.1007/s11914-022-00762-7 -
Theranostics 2020Wear particle-induced periprosthetic osteolysis (PPO) is a common long-term complication of total joint arthroplasty, and represents the major cause of aseptic...
Genetic and pharmacological activation of Hedgehog signaling inhibits osteoclastogenesis and attenuates titanium particle-induced osteolysis partly through suppressing the JNK/c-Fos-NFATc1 cascade.
Wear particle-induced periprosthetic osteolysis (PPO) is a common long-term complication of total joint arthroplasty, and represents the major cause of aseptic loosening and subsequent implant failure. Previous studies have identified the central role of osteoclast-mediated bone resorption in the pathogenesis of PPO. Thus, therapeutic approaches of inhibiting osteoclast formation and activity are considered to be of great potential to prevent and treat this osteolytic disease. Hedgehog (Hh) signaling has been shown to play an important role in promoting osteoblast differentiation and bone formation. While Hh signaling is also implicated in regulating osteoclastogenesis, whether it can directly inhibit osteoclast differentiation and bone resorption remains controversial. Moreover, its potential therapeutic effects on PPO have never been assessed. In this study, we explored the cell-autonomous role of Hh signaling in regulating osteoclastogenesis and its therapeutic potential in preventing wear particle-induced osteolysis. Hh signaling was activated in macrophages by genetically ablating in these cells using or by treating them with purmorphamine (PM), a pharmacological activator of Smoothened (Smo). cell-autonomous effects of Hh pathway activation on RANKL-induced osteoclast differentiation and activity were evaluated by TRAP staining, phalloidin staining, qPCR analyses, and bone resorption assays. evaluation of its therapeutic efficacy against PPO was performed in a murine calvarial model of titanium particle-induced osteolysis by μCT and histological analyses. Mechanistic details were explored in RANKL-treated macrophages through Western blot analyses. We found that deletion or PM treatment potently activated Hh signaling in macrophages, and strongly inhibited RANKL-induced TRAP osteoclast production, F-actin ring formation, osteoclast-specific gene expression, and osteoclast activity . Furthermore, we found that deletion or PM administration significantly attenuated titanium particle-induced osteoclast formation and bone loss . Our mechanistic study revealed that activation of Hh signaling suppressed RANKL-induced activation of JNK pathway and downregulated protein levels of two key osteoclastic transcriptional factors, c-Fos and its downstream target NFATc1. Both genetic and pharmacological activation of Hh signaling can cell-autonomously inhibit RANKL-induced osteoclast differentiation and activity and protect against titanium particle-induced osteolysis . Mechanistically, Hh signaling hinders osteoclastogenesis partly through suppressing the JNK/c-Fos-NFATc1 cascade. Thus, Hh signaling may serve as a promising therapeutic target for the prevention and treatment of PPO and other osteolytic diseases.
Topics: Animals; Cell Differentiation; Cells, Cultured; Disease Models, Animal; Gene Knock-In Techniques; Hedgehog Proteins; JNK Mitogen-Activated Protein Kinases; Macrophages; Male; Mice; Mice, Inbred C57BL; Morpholines; NFATC Transcription Factors; Osteoclasts; Osteogenesis; Osteolysis; Proto-Oncogene Proteins c-fos; Purines; Rabbits; Repressor Proteins; Signal Transduction; Titanium
PubMed: 32550895
DOI: 10.7150/thno.44793 -
Current Opinion in Pharmacology Aug 2009Skeletal distortions impose grave health disparities with potentially devastating consequences, including bone pain, immobility, and morbidity. Bone erosion is chiefly... (Review)
Review
Skeletal distortions impose grave health disparities with potentially devastating consequences, including bone pain, immobility, and morbidity. Bone erosion is chiefly caused by hyperactive osteoclasts summoned to bone in response to circulating factors produced by tumor and inflammatory cells. Intense research in the past two decades has identified crucial elements and intricate circulatory systems that maintain and exacerbate inflammatory osteolysis. This progress led to better understanding of the mechanisms underlying this response and to developing advanced therapeutic interventions. Nevertheless, the multifactorial causes of inflammatory osteolysis continue to impose a great challenge for these therapies. This article provides an overview of some of the prominent facets contributing to this process.
Topics: Animals; Bone Density; Bone Neoplasms; Bone Resorption; Humans; Inflammation; Inflammation Mediators; Osteolysis
PubMed: 19577517
DOI: 10.1016/j.coph.2009.06.007 -
BioMed Research International 2013The leading complication of total joint replacement is periprosthetic osteolysis, which often results in aseptic loosening of the implant, leading to revision surgery.... (Review)
Review
Extracellular matrix degradation and tissue remodeling in periprosthetic loosening and osteolysis: focus on matrix metalloproteinases, their endogenous tissue inhibitors, and the proteasome.
The leading complication of total joint replacement is periprosthetic osteolysis, which often results in aseptic loosening of the implant, leading to revision surgery. Extracellular matrix degradation and connective tissue remodeling around implants have been considered as major biological events in the periprosthetic loosening. Critical mediators of wear particle-induced inflammatory osteolysis released by periprosthetic synovial cells (mainly macrophages) are inflammatory cytokines, chemokines, and proteolytic enzymes, mainly matrix metalloproteinases (MMPs). Numerous studies reveal a strong interdependence of MMP expression and activity with the molecular mechanisms that control the composition and turnover of periprosthetic matrices. MMPs can either actively modulate or be modulated by the molecular mechanisms that determine the debris-induced remodeling of the periprosthetic microenvironment. In the present study, the molecular mechanisms that control the composition, turnover, and activity of matrix macromolecules within the periprosthetic microenvironment exposed to wear debris are summarized and presented. Special emphasis is given to MMPs and their endogenous tissue inhibitors (TIMPs), as well as to the proteasome pathway, which appears to be an elegant molecular regulator of specific matrix macromolecules (including specific MMPs and TIMPs). Furthermore, strong rationale for potential clinical applications of the described molecular mechanisms to the treatment of periprosthetic loosening and osteolysis is provided.
Topics: Extracellular Matrix; Humans; Matrix Metalloproteinases; Osteolysis; Prosthesis Failure; Proteasome Endopeptidase Complex; Tissue Inhibitor of Metalloproteinases
PubMed: 23862137
DOI: 10.1155/2013/230805 -
Blood Cancer Journal Jan 2018Osteolytic bone disease is the hallmark of multiple myeloma, which deteriorates the quality of life of myeloma patients, and it affects dramatically their morbidity and... (Review)
Review
Osteolytic bone disease is the hallmark of multiple myeloma, which deteriorates the quality of life of myeloma patients, and it affects dramatically their morbidity and mortality. The basis of the pathogenesis of myeloma-related bone disease is the uncoupling of the bone-remodeling process. The interaction between myeloma cells and the bone microenvironment ultimately leads to the activation of osteoclasts and suppression of osteoblasts, resulting in bone loss. Several intracellular and intercellular signaling cascades, including RANK/RANKL/OPG, Notch, Wnt, and numerous chemokines and interleukins are implicated in this complex process. During the last years, osteocytes have emerged as key regulators of bone loss in myeloma through direct interactions with the myeloma cells. The myeloma-induced crosstalk among the molecular pathways establishes a positive feedback that sustains myeloma cell survival and continuous bone destruction, even when a plateau phase of the disease has been achieved. Targeted therapies, based on the better knowledge of the biology, constitute a promising approach in the management of myeloma-related bone disease and several novel agents are currently under investigation. Herein, we provide an insight into the underlying pathogenesis of bone disease and discuss possible directions for future studies.
Topics: Humans; Multiple Myeloma; Neoplasm Proteins; Osteoblasts; Osteoclasts; Osteolysis; Signal Transduction
PubMed: 29330358
DOI: 10.1038/s41408-017-0037-4