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Journal of Dental Research Jun 2020Medication-related osteonecrosis of the jaw (MRONJ) is a rare intraoral lesion that occurs in patients undergoing long-term and/or high-dose therapy with...
Medication-related osteonecrosis of the jaw (MRONJ) is a rare intraoral lesion that occurs in patients undergoing long-term and/or high-dose therapy with nitrogen-containing bisphosphonates, a RANKL inhibitor, antiangiogenic agents, or mTOR inhibitors. The presence of pathogenic bacteria is highly associated with advanced stages of MRONJ lesions; however, the exact role of indigenous microbes in MRONJ development is unknown. Here, we report that the normal oral flora in mice protects against inflammation-induced osteonecrosis. In mice that developed osteonecrosis following tooth extraction, there was increased bacterial infiltration when compared with healed controls. Antibiotic-mediated oral dysbiosis led to a local inhibition of bone resorption in the presence of ligature-induced periodontitis (LIP). There was no significant difference in empty lacunae, necrotic bone formation, osteoclast number, and surface area in antibiotic-treated as compared with conventionally colonized mice following extraction of healthy teeth after zoledronic acid infusions. However, extraction of LIP teeth led to increased empty lacunae, necrotic bone, and osteoclast surface area in antibiotic- and zoledronic acid-treated mice as compared with conventionally colonized mice. Our findings suggest that the presence of the indigenous microbiota protects against LIP-induced osteonecrosis.
Topics: Animals; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Diphosphonates; Female; Inflammation; Mice; Mice, Inbred C57BL; Microbiota; Osteonecrosis
PubMed: 32109361
DOI: 10.1177/0022034520908594 -
Operative Orthopadie Und Traumatologie Oct 2022The proximal femoral varus osteotomy (FVO) aims to re-centre the femoral head in the acetabular socket after prognostically unfavourable subluxation, e.g. in... (Review)
Review
OBJECTIVE
The proximal femoral varus osteotomy (FVO) aims to re-centre the femoral head in the acetabular socket after prognostically unfavourable subluxation, e.g. in Legg-Calve-Perthes disease (LCPD).
INDICATIONS
No unified indication criteria have been defined yet for containment therapy in LCPD. However, specific radiographic features related to deformity development, age at diagnosis or onset and classifications describing pathomorphological changes in the femoral head related to bone necrosis can support decisionmaking.
CONTRAINDICATIONS
Absolute contraindications-a hinge abducted joint; failure of femoral head reduction in the 20° abduction anteroposterior view; total epiphyseal necrosis. Relative contraindication-children < 6 years, in lateral pillar classification group A or Catteral group I and II.
SURGICAL TECHNIQUE
Lateral approach to the proximal femur. Insertion of the first K‑wire to mark the anteversion of the femoral neck. Additional K‑wires are placed parallel to the first via the positioner aiming block. Lokalise the optimal postion for the osteotomy. Insertion of additional K‑wires in the distal fragment an facilitate manipulation and serve as reference for derotation. After osteotomy proximal fixation of the plate with locking screws replacing the K-wires. Insertion of a cortical screw into the middle hole to achieve optimal interfragmentary compression. Remaining locking screws are inserted and cortical screw replaced by a locking screw.
POSTOPERATIVE MANAGEMENT
Mobilization with heel-touch weight-bearing on crutches for 6 weeks. Increased weightbearing after radiographic follow-up as soon as sufficient bone union is present. Implant removal after 9-12 months. Return to sports after 3 months.
RESULTS
The FVO has been used in the surgical treatment of severe LCPD for nearly 60 years and is established worldwide. Growing knowledge and consecutive optimization of the surgery indication together with the new implants contribute to improving clinical and radiological outcomes and reducing intraoperative and postoperative complications.
Topics: Acetabulum; Femur Head; Humans; Legg-Calve-Perthes Disease; Osteotomy; Treatment Outcome
PubMed: 35915149
DOI: 10.1007/s00064-022-00778-3 -
International Journal of Molecular... Jan 2024Osteonecrosis of the jaw is the progressive loss and destruction of bone affecting the maxilla or mandible in patients treated with antiresorptive and antiangiogenic... (Review)
Review
Osteonecrosis of the jaw is the progressive loss and destruction of bone affecting the maxilla or mandible in patients treated with antiresorptive and antiangiogenic agents without receiving prior radiation therapy. The pathogenesis involves the inflammatory pathway of receptor activator of nuclear factor NF-kB ligand and the macrophage colony-stimulating factor, essential for osteoclast precursors survival and proliferation and acting through its receptor c-Fms. Evidence has shown the role of non-coding RNAs in the pathogenesis of osteonecrosis of the jaw and this finding might be useful in diagnosis since these small RNAs could be considered as biomarkers of apoptotic activity in bone. Interestingly, it has been proved that miR-29 and miR-31-5p, acting on specific targets such as CALCR and RhoA, promote programmed-cell death and consequently the necrosis of bone tissue. Specific long non-coding RNAs, instead, have been detected both at reduced levels in patients with multiple myeloma and osteonecrosis, and associated with suppression of osteoblast differentiation, with consequences in the progression of mandible lesions. Among non-coding genic material, circular RNAs have the capability to modify the expression of specific mRNAs responsible for the inhibition of bisphosphonates activity on osteoclastogenesis.
Topics: Humans; Diphosphonates; Osteonecrosis; Bone Density Conservation Agents; Multiple Myeloma; MicroRNAs
PubMed: 38338876
DOI: 10.3390/ijms25031598 -
Journal of Bone and Mineral Research :... Feb 2021Legg-Calvé-Perthes disease (LCPD) is a juvenile form of ischemic femoral head osteonecrosis, which produces chronic hip synovitis, permanent femoral head deformity, and...
Legg-Calvé-Perthes disease (LCPD) is a juvenile form of ischemic femoral head osteonecrosis, which produces chronic hip synovitis, permanent femoral head deformity, and premature osteoarthritis. Currently, there is no medical therapy for LCPD. Interleukin-6 (IL-6) is significantly elevated in the synovial fluid of patients with LCPD. We hypothesize that IL-6 elevation promotes chronic hip synovitis and impairs bone healing after ischemic osteonecrosis. We set out to test if anti-IL-6 therapy using tocilizumab can decrease hip synovitis and improve bone healing in the piglet model of LCPD. Fourteen piglets were surgically induced with ischemic osteonecrosis and assigned to two groups: the no treatment group (n = 7) and the tocilizumab group (15 to 20 mg/kg, biweekly intravenous injection, n = 7). All animals were euthanized 8 weeks after the induction of osteonecrosis. Hip synovium and femoral heads were assessed for hip synovitis and bone healing using histology, micro-CT, and histomorphometry. The mean hip synovitis score and the number of synovial macrophages and vessels were significantly lower in the tocilizumab group compared with the no treatment group (p < .0001, p = .01, and p < .01, respectively). Micro-CT analysis of the femoral heads showed a significantly higher bone volume in the tocilizumab group compared with the no treatment group (p = .02). The histologic assessment revealed a significantly lower number of osteoclasts per bone surface (p < .001) in the tocilizumab group compared with the no treatment group. Moreover, fluorochrome labeling showed a significantly higher percent of mineralizing bone surface (p < .01), bone formation rate per bone surface (p < .01), and mineral apposition rate (p = .04) in the tocilizumab group. Taken together, tocilizumab therapy decreased hip synovitis and osteoclastic bone resorption and increased new bone formation after ischemic osteonecrosis. This study provides preclinical evidence that tocilizumab decreases synovitis and improves bone healing in a large animal model of LCPD. © 2020 American Society for Bone and Mineral Research (ASBMR).
Topics: Animals; Bone Resorption; Femur Head; Humans; Legg-Calve-Perthes Disease; Osteogenesis; Osteonecrosis; Swine; Synovitis
PubMed: 33053220
DOI: 10.1002/jbmr.4191 -
Acta Bio-medica : Atenei Parmensis Jun 2023Symptomatic avascular necrosis (AVN) imposes a higher risk for acute care consumption in adults living with SCD. Symptomatic AVN, have higher rates of visits to the... (Review)
Review
Symptomatic avascular necrosis (AVN) imposes a higher risk for acute care consumption in adults living with SCD. Symptomatic AVN, have higher rates of visits to the emergency department, higher rates of admissions, and longer lengths of stay in hospitals. Properly timed diagnosis and early interventions can reduce morbidity and enhance the quality of life in these patients. Vaso-occlusion secondary to sickling leads to osteonecrosis of the joint/bone (AVN, dactylitis) and invites infection (osteomyelitis and septic arthritis). Understanding and awareness of the imaging features related to this major morbidity complication are essential for early diagnosis and prompt management. In about half of the patients with SCD, AVN can lead to chronic pain, particularly in the head of the femur and humerus. Humeral and femoral head AVN tend to be linked with each other. Vertebral bone compression and collapse secondary to AVN have also been reported. The diagnosis of AVN must be accurate, as the condition is complex requiring specific treatment according to the grade of bone and joint involvement. There are several classifications or staging systems used for grading bone and joint involvement. Knowledge of the image patterns and grade of affection in different joints and bones and the degree of progression of AVN lesions can markedly improve management decisions on AVN-specific surgical versus non-surgical interventions and improve patient outcomes. The aim of this report is to summarize the different imaging techniques and their role in the proper/early diagnosis and follow up of patients with AVN with detailed examples of the common sites involved.
Topics: Adult; Humans; Quality of Life; Radiography; Femur Head Necrosis; Humerus; Anemia, Sickle Cell
PubMed: 37326259
DOI: 10.23750/abm.v94i3.14714 -
Bulletin of the NYU Hospital For Joint... 2011Spontaneous osteonecrosis of the knee (SPONK) and osteo necrosis in the postoperative knee (ONPK) are two clinical entities that have the potential to cause significant... (Review)
Review
Spontaneous osteonecrosis of the knee (SPONK) and osteo necrosis in the postoperative knee (ONPK) are two clinical entities that have the potential to cause significant morbidity in affected patients. In addition to the knowledge of the patient population at risk and the classic presentation and imaging characteristics of SPONK and ONPK, the treating orthopaedic surgeon needs to maintain a high index of suspicion for these disorders since early diagnosis and treatment may allow for an improved clinical outcome. The following review presents the current knowledge regarding these two pathological processes of the knee.
Topics: Arthroscopy; Debridement; Decompression, Surgical; Humans; Knee Joint; Magnetic Resonance Imaging; Osteonecrosis; Osteotomy; Predictive Value of Tests; Radiography; Reoperation; Treatment Outcome
PubMed: 22196390
DOI: No ID Found -
Journal of Bone and Mineral Research :... Jul 2022Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a detrimental intraoral lesion that occurs in patients with long-term or high-dose use of anti-resorptive...
Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a detrimental intraoral lesion that occurs in patients with long-term or high-dose use of anti-resorptive agents such as bisphosphonates. Tooth extraction is a known risk factor for BRONJ, and such intervention is often performed to eliminate existing pathological inflammatory conditions. Previously, we determined that ligature-induced periodontitis (LIP) is a risk factor for the development of osteonecrosis in mice, but it remains unclear whether the chronicity of LIP followed by extraction influences osteonecrosis development. In this study, we assess the effect of short-term and long-term LIP (ligature placed for 3 weeks [S-LIP] or 10 weeks [L-LIP], respectively) on osteonecrosis development in mice receiving 250 μg/kg/week zoledronic acid (ZOL). When compared to S-LIP, L-LIP caused 70% (p ≤ 0.0014) more bone loss without altering microbe composition. In the presence of ZOL, bone loss mediated by LIP was prevented and bone necrosis was induced. When the ligated tooth was extracted, histologic hallmarks of osteonecrosis including empty lacunae and necrotic bone were increased by 88% (p = 0.0374) and 114% (p = 0.0457), respectively, in L-LIP compared to S-LIP. We also observed significant increases in serum platelet factor 4 (PF4) and macrophage inflammatory factor 1 γ (MIP1γ) in mice that received ZOL treatment and had tooth extractions compared to controls, which may be systemic markers of inflammation-associated osteonecrosis development. Additionally, CD3+ T cells were identified as the major immune population in both health and disease, and we observed a 116% (p = 0.0402) increase in CD3+IL23R+ T cells in L-LIP compared to S-LIP lesions following extraction. Taken together, our study reveals that extracting a periodontally compromised tooth increases the formation of necrotic bone compared to extracting a periodontally healthy tooth and that osteonecrosis may be associated with the duration of the preexisting pathological inflammatory conditions. © 2022 American Society for Bone and Mineral Research (ASBMR).
Topics: Animals; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Diphosphonates; Mice; Osteonecrosis; Periodontitis; Tooth Extraction; Zoledronic Acid
PubMed: 35598324
DOI: 10.1002/jbmr.4614 -
Sultan Qaboos University Medical Journal May 2021Bone failure due to avascular necrosis (AVN) is a complex pathological phenomenon. Analysis of molecular changes in the bone matrix may help to shed light on the disease...
Analysis of Bone Microarchitectural Changes and Structural Damage in Sickle Cell Disease-Induced Avascular Necrosis Using Raman Spectroscopy: Is there potential for medical management?
OBJECTIVES
Bone failure due to avascular necrosis (AVN) is a complex pathological phenomenon. Analysis of molecular changes in the bone matrix may help to shed light on the disease process and guide management. This study aimed to explore changes in bone quality and structural damage caused by sickle cell disease (SCD)-induced AVN using Raman spectroscopy.
METHODS
A total of 10 necrotic femoral heads were obtained from seven SCD patients who underwent total hip replacements. The femoral heads were cut in half and scanned using Raman spectroscopy in correlation with preoperative magnetic resonance imaging to identify necrotic and healthy control areas. Subsequently, samples were examined to determine changes in bone mineralisation, crystallinity, carbonate content, collagen cross-linking and mineral and collagen fibril orientation.
RESULTS
Significant changes were observed in bone mineral content, mineral-to-organic content and collagen fibril orientation in necrotic compared to control areas ( ≤0.050).
CONCLUSION
The necrotic samples displayed severe structural damage and loss of mineral and organic contents. Similar Raman signals have been reported in other metabolic bone diseases such as osteoporosis, thereby potentially supporting the use of medical treatment in AVN to promote bone quality.
Topics: Anemia, Sickle Cell; Bone Density; Bone Remodeling; Calcification, Physiologic; Extracellular Matrix; Femur Head; Femur Head Necrosis; Humans; Necrosis; Spectrum Analysis, Raman
PubMed: 34221479
DOI: 10.18295/squmj.2021.21.02.020 -
Revista Paulista de Pediatria : Orgao... 2022To systematically establish whether there is an association between polymorphisms and avascular necrosis in patients with sickle cell disease.
OBJECTIVE
To systematically establish whether there is an association between polymorphisms and avascular necrosis in patients with sickle cell disease.
DATA SOURCE
The review, conducted according to PRISMA guidelines and registered with PROSPERO, was based on research of studies in PubMed, SciELO, LILACS, BVS databases and in the gray literature (Google Scholar and Open Gray) published until June 2020. The STROBE initiative was used to analyze the articles' quality.
DATA SYNTHESIS
Ten articles were selected from the databases and two were included through manual search, totaling 12 studies. All samples gathered 2,362 patients. According to STROBE, seven studies fully and/or partially covered more than 70% of the essential items and two studies reached less than 60%, with an overall variation of 86.4-54.5%. The results indicate that polymorphisms in the genes of the bone morphogenetic protein 6 (BMP6), Klotho (KL) and Annexin A2 (ANXA2) may be associated with osteonecrosis in the context of sickle cell disease. Six articles addressed the polymorphism in the MTHFR enzyme gene, but only one found a positive association. Polymorphisms associated with the DARC receptor, the ITGA4 gene, CD36 and thrombophilia protein genes were not associated in any of the studies.
CONCLUSIONS
The results indicate that the polymorphisms in BMP6, Klotho and ANXA2 genes may be associated with avascular necrosis in patients with sickle cell disease. However, in order to confirm these genetic changes as risk factors, further studies with greater statistical power and methodological rigor are needed.
Topics: Anemia, Sickle Cell; Humans; Osteonecrosis; Polymorphism, Genetic; Risk Factors
PubMed: 35584416
DOI: 10.1590/1984-0462/2022/40/2021013IN -
Revue Medicale de Liege Nov 2018Bone pain associated with bone marrow infiltration is often present at diagnosis of pediatric acute lymphoblastic leukemia (ALL). It sometimes signs the presence of... (Review)
Review
Bone pain associated with bone marrow infiltration is often present at diagnosis of pediatric acute lymphoblastic leukemia (ALL). It sometimes signs the presence of pathological fracture, lytic lesions, arthritis, or osteitis associated to ALL that can delay the diagnosis. During treatment, bone complications (pain, osteopenia, fracture, avascular necrosis, ...) are also reported. In order to describe bone involvement (BI) of pediatric LLA, we reviewed the records of 104 patients followed in our unit. The overall incidence of BI was 67 %. At diagnosis, 50 % of patients had BI and in 19 %, the diagnosis of ALL was delayed. During and after treatment, respectively 28 % and 37 % of patients presented bone complications (pain, fractures, avascular necrosis, osteopenia). Patients with BI had a lower leukocytosis inferior to 10x109/l (p = 0.005) and an ALL of average risk (p = 0.019). 38 % of patients with BI during treatment were over 10 years old and 55 % were girls (vs. 21 % and 38 % in the entire cohort, respectively). Osteoporosis was more severe at diagnosis than during treatment, suggesting the presence of constitutional promoting factors. In our cohort, the majority of BI was resolved at the end of treatment with no long-term sequelae.
Topics: Bone Diseases, Metabolic; Child; Female; Fractures, Spontaneous; Humans; Male; Osteonecrosis; Pain; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies
PubMed: 30431247
DOI: No ID Found