Cause Of Osteonecrosis Research Articles

Unraveling the Role of Endothelial Dysfunction in Osteonecrosis of the Femoral Head: A Pathway to New Therapies.

Osteonecrosis of the femoral head (ONFH) is a disabling disease characterized by the disruption of the blood supply to the femoral head, leading to the apoptosis and necrosis of bone cells and subsequent joint collapse. Total hip arthroplasty is not optimal since most patients are young. Multiple risk factors contribute to osteonecrosis, including glucocorticoid (GC) usage, excessive alcohol intake, hypercholesterolemia, and smoking. Continuous stimulation by many variables causes a chronic inflammatory milieu, with clinical repercussions including endothelial dysfunction, leading to thrombosis, coagulopathy, and poor angiogenesis. Immune cells are the primary regulators of inflammation. Innate and adaptive immune cells interact with endothelial cells to hinder the regeneration and repair of bone lesions. An in-depth examination of the pathological drivers of ONFH reveals that endothelial dysfunction may be a major cause of osteonecrosis. Understanding the involvement of endothelial dysfunction in the chronic inflammation of osteonecrosis could aid in the development of possible therapies. This review summarizes the role of endothelial cells in osteonecrosis and further explains the pathophysiological mechanism of endothelial dysfunction in this disease from the perspective of inflammation to provide new ideas for the treatment of osteonecrosis.

Cortistatin prevents glucocorticoid-associated osteonecrosis of the femoral head via the GHSR1a/Akt pathway

Long-term use of glucocorticoids (GCs) is known to be a predominant cause of osteonecrosis of the femoral head (ONFH). Moreover, GCs can mediate apoptosis of various cell types by exaggerating oxidative stress. We have previously found that Cortistatin (CST) antagonizes oxidative stress and improves cell apoptosis in several conditions. In this study, we detected that the CST expression levels were diminished in patients with ONFH compared with femoral neck fracture (FNF). In addition, a GC-induced rat ONFH model was established, which impaired bone quality in the femoral head. Then, administration of CST attenuated these ONFH phenotypes. Furthermore, osteoblast and endothelial cells were cultured and stimulated with dexamethasone (Dex) in the presence or absence of recombinant CST. As a result, Dex induced impaired anabolic metabolism of osteoblasts and suppressed tube formation in endothelial cells, while additional treatment with CST reversed this damage to the cells. Moreover, blocking GHSR1a, a well-accepted receptor of CST, or blocking the AKT signaling pathway largely abolished the protective function of CST in Dex-induced disorder of the cells. Taken together, we indicate that CST has the capability to prevent GC-induced apoptosis and metabolic disorder of osteoblasts in the pathogenesis of ONFH via the GHSR1a/AKT signaling pathway.

The role of immune cells in modulating chronic inflammation and osteonecrosis.

Osteonecrosis occurs when, under continuous stimulation by adverse factors such as glucocorticoids or alcohol, the death of local bone and marrow cells leads to abnormal osteoimmune function. This creates a chronic inflammatory microenvironment, which interferes with bone regeneration and repair. In a variety of bone tissue diseases, innate immune cells and adaptive immune cells interact with bone cells, and their effects on bone metabolic homeostasis have attracted more and more attention, thus developing into a new discipline - osteoimmunology. Immune cells are the most important regulator of inflammation, and osteoimmune disorder may be an important cause of osteonecrosis. Elucidating the chronic inflammatory microenvironment regulated by abnormal osteoimmune may help develop potential treatments for osteonecrosis. This review summarizes the inflammatory regulation of bone immunity in osteonecrosis, explains the pathophysiological mechanism of osteonecrosis from the perspective of osteoimmunology, and provides new ideas for the treatment of osteonecrosis.

Post-traumatic necrosis of the humeral head-Endoprosthesis or joint preservation

Humerus fractures play amajor role in daily clinical routine, and subsequent osteonecrosis is common after osteosyntheses. The current paper highlights the incidence and cause of osteonecrosis after proximal humerus fractures, with respect to presentation of anatomy and risk factors. Display of the literature and therapy options for humerus fracture and subsequent necrosis. Humerus fractures are the seventh most frequent fractures in humans. The complication rate is 40%, and the described rate of necrosis is up to 34%. Accordingly, the surgical revision rate is at 19% according to recent literature. The treatment of humerus head fracture must consider numerous variables. The individual type of fracture and the current individual situation of the patient must be included in the process of choosing the right treatment. Modern implants with screw locking features should be used, and for certain circumstances the direct implantation of aprosthesis should be considered. Thereby the expectations of the patient with respect to the postoperative activity level play amajor role.

A case of completed course multifocal osteonecrosis (MFON) during pregnancy due to primary antiphospholipid syndrome

Osteonecrosis of both shoulders and hips is a rare presentation of primary antiphospholipid syndrome. A female patient aged 23 years old with no systemic diseases has her only complaint which was pain and limitations in both hips followed by both shoulders. Careful detailed history and clinical examination is essential for reaching optimum diagnosis thus good management. MRI for hip and shoulder joints is essential for the diagnosis of osteonecrosis. Exclusion of all causes of secondary osteonecrosis by history, clinical examination, and laboratory studies should be done before diagnosing the rare causes of osteonecrosis or the primary type. Pregnancy is an exacerbation factor for primary osteonecrosis. We recommend that the female patient with primary osteonecrosis should receive prophylactic antithrombotic during pregnancy. In conclusion, exclusion of all secondary causes of osteonecrosis is mandatory to reach an accurate diagnosis.

Construction and validation of steroid-induced rabbit osteonecrosis model

Osteonecrosis is a common orthopedic disease in clinic, resulting in joint collapse if appropriate treatment is not given in time. The clinical usage of high-dose steroid is one of the common causes of osteonecrosis. In several studies, the intravenous injection of steroid with or without lipopolysaccharide is the most commonly used strategy to construct osteonecrosis animal model. However, the injection dose, frequency, and interval of steroid and validation of successful model construction lack generally accepted protocol, and the survival and model formation rates are unsatisfactory. We have optimized the construction protocol of osteonecrosis animal model based on the previously reported ones and established a mature animal model of osteonecrosis for future studies.•A rabbit model of osteonecrosis was constructed by multiple injections of high-dose methylprednisolone.•The multidisciplinary biomedical examinations demonstrated the successful construction of osteonecrosis model in the rabbit.

ALCOHOL ABUSE AS AN UNDERESTIMATED CAUSE OF NON-TRAUMATIC OSTEONECROSIS OF THE FEMORAL HEAD (DESCRIPTION OF CLINICAL CASES)

Osteonecrosis of the femoral head is a severe degenerative-dystrophic disease, which is characterized by the destruction of the bone substance in the head in the most vulnerable (loaded) parts. Due to a rapid progression in the absence of proper surgical treatment, osteonecrosis of the femoral head, as a rule, results in disability. There is a wide range of causes that cause the development of osteonecrosis. According to the authors, alcohol abuse should be attributed to the underestimated causal factors of this pathology. The article presents two clinical observations which convincingly demonstrate the role of alcohol abuse as a cause of osteonecrosis. In a 44-year-old man prolonged alcohol abuse led to a progressive (within a year) advance of osteonecrosis in the heads of both femurs, and in a 26-year-old woman, along with a short-term intake of glucocorticoids, it contributed to the formation of multifocal non-traumatic osteonecrosis with damage to the pelvic, right knee, shoulder joints. The authors explain underestimated role of alcohol abuse as a causal factor of osteonecrosis as follows. Firstly, patients, as a rule, try not to display their addiction, and therefore, unlike other predictors of developing femoral bone osteonecrosis (injuries, serious somatic diseases, taking glucocorticoids), this fact is not reflected in medical documentation. Secondly, patients with idiopathic forms of osteonecrosis often do not have an "assigned" doctor who could dynamically follow up the patient and, consequently, monitor more carefully his condition and risk factors for osteonecrosis. When consulting such a patient, a subspecialist, as a rule, sets himself the task first of all to exclude "his disease", which makes the patient vulnerable in terms of finding out the causes of osteonecrosis. These clinical cases demonstrate the need to take into account alcohol abuse as a significant causal factor in the development of osteonecrosis.

Bisphosphonate-induced osteonecrosis of the jaws: a literature review

Bisphosphonates are widely used, whether in osteoporosis or malignant bone disorders. Therefore, it is necessary that there is sufficient knowledge about the adverse effects of this drug, especially in relation to Osteonecrosis of the Jaws Developed by Bisphosphonates, which is a pathology generated in the gnathic bones. So, the following question was asked in the research problem: What is the current situation regarding the use of bisphosphonates and the onset of osteonecrosis of the jaw? Searches were carried out on digital library websites in search of articles and research in books by renowned authors. Inclusion and exclusion criteria for articles found were defined. The verification of each article was carried out so that it could have perspective and follow-up on the subject discussed. The following databases were used: PUBMED, BIREME and LILACS, and SCIELO between the years 2007 to 2019. It was concluded then that Bisphosphonates play a very important role as a cause of osteonecrosis of the jaws, where the prognosis will be worse if the patient is treated with intravenous rather than oral types.

Necrotising periodontal diseases and alcohol misuse - a cause of osteonecrosis?

'Necrotising periodontal diseases' is an umbrella term for necrotising gingivitis, necrotising periodontitis, necrotising stomatitis and noma. These rapidly destructive conditions are characterised by pain, interdental ulceration and gingival necrosis which, if left untreated, can result in osteonecrosis. Research indicates that patients with a history of alcohol misuse are at an increased risk of malnutrition, which negatively affects the immune response and predisposition to necrotising periodontal diseases. This article will discuss that osteonecrosis of the alveolar bone does not exclusively occur in association with antiresorptive medications, but can occur as a severe form of necrotising gingivitis. In this article, we will describe two cases to highlight the occurrence, presentation and management of necrotising periodontal diseases secondary to alcohol misuse.

Necrotising periodontal diseases and alcohol misuse - a cause of osteonecrosis?

'Necrotising periodontal diseases' is an umbrella term for necrotising gingivitis, necrotising periodontitis, necrotising stomatitis and noma. These rapidly destructive conditions are characterised by pain, interdental ulceration and gingival necrosis which, if left untreated, can result in osteonecrosis. Research indicates that patients with a history of alcohol misuse are at an increased risk of malnutrition, which negatively affects the immune response and predisposition to necrotising periodontal diseases. This article will discuss that osteonecrosis of the alveolar bone does not exclusively occur in association with antiresorptive medications, but can occur as a severe form of necrotising gingivitis. In this article, we will describe two cases to highlight the occurrence, presentation and management of necrotising periodontal diseases secondary to alcohol misuse.

Calycosin modulates inflammation via suppressing TLR4/NF-κB pathway and promotes bone formation to ameliorate glucocorticoid-induced osteonecrosis of the femoral head in rat.

Glucocorticoid (GC) administration is one of the main causes of osteonecrosis of the femoral head (ONFH). Inflammation, especially the TLR4/NF-κB pathway, has been demonstrated to play a pivotal role in the pathogenesis of GC-induced ONFH. Calycosin, the main bioactive extract of Astragali Radix, could substantially regulate the TLR4/NF-κB pathway. Therefore, in this study, we hypothesized that calycosin could exert beneficial effects in GC-induced ONFH. In vitro, effects of calycosin on the osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs) were determined using Alizarin red staining, alkaline phosphatase activity examination, and osteogenic-related gene assay. Meanwhile, inflammatory cytokines were detected by enzyme-linked immunosorbent assay. In vivo, 60 male Sprague-Dawley rats were randomly separated into three groups: the control group, the methylprednisolone (MPS) group, and the MPS + calycosin group. The results showed that calycosin could significantly promote dynamic bone formation and retard TLR4/NF-κB pathway. in vivo investigations indicated that calycosin could decrease the morbidity of ONFH and alleviate pathological manifestations within the femoral head. Meanwhile, calycosin could protect osseous blood supply and facilitate dynamic bone formation. The findings collectively demonstrated that calycosin could ameliorate GC-induced ONFH in rat and might become a potential candidate for pharmaceutical prevention of this intractable disease.

Osteonecrosis of the Jaw Beyond Bisphosphonates: Are There Any Unknown Local Risk Factors?

IntroductionBisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) is a complication of intravenous (IV) BP therapy. BP therapy locally affects the dentoalveolar area, while systemic effects are associated with parenteral/IV BP use. Despite numerous publications, the pathogenesis of BRONJ is not fully understood, as only some patients receiving IV BPs develop BRONJ.PurposeCan impaired bone remodeling (found in aseptic-ischemic osteonecrosis of the jaw [AIOJ], bone marrow defects [BMD], or fatty-degenerative osteonecrosis of the jaw [FDOJ]) represent a risk factor for BRONJ formation?Patients and MethodsA literature search clarified the relationship between AIOJ, BMD, FDOJ, and BRONJ, in which common characteristics related to signal cascades, pathohistology, and diagnostics are explored and compared. A case description examining non-exposed BRONJ is presented.DiscussionNon-exposed BRONJ variants may represent one stage in undetected BMD development, and progression to BRONJ results from BPs.ConclusionUnresolved wound healing at extraction sites, where wisdom teeth have been removed for example, may contribute to the pathogenesis of BRONJ. With IV BP administration, persisting AIOJ/BMD/FDOJ areas may be behind BRONJ development. Therapeutic recommendations include IV BP administration following AIOJ/BMD/FDOJ diagnosis and surgical removal of ischemic areas. BPs should not be regarded as the only cause of osteonecrosis.

A tree shrew model for steroid-associated osteonecrosis

Osteonecrosis is a common human disease in orthopedics. It is difficult to treat, and half of patients may need artificial joint replacement, resulting in a considerable economic burden and a reduction in quality of life. Hormones are one of the major causes of osteonecrosis and high doses of corticosteroids are considered the most dangerous factor. Because of the complexity of treatment, we still need a better animal model that can be widely used in drug development and testing. Tree shrews are more closely related to primates than rodents. As such, we constructed a successful tree shrew model to establish and evaluate steroid-associated osteonecrosis (SAON). We found that low-dose lipopolysaccharide (LPS) combined with high-dose methylprednisolone (MPS) over 12 weeks could be used to establish a tree shrew model with femoral head necrosis. Serum biochemical and histological analyses showed that an ideal model was obtained. Thus, this work provides a useful animal model for the study of SAON and for the optimization of treatment methods.

Tarsal Navicular Osteonecrosis in Children

Osteonecrosis (avascular, aseptic or ischemic bone necrosis) of the tarsal navicular in children may develop either spontaneously (primary, idiopathic, atraumatic or non-traumatic) or secondary to trauma (post-traumatic) and osteochondrosis. In both groups, of primary and secondary osteonecrosis, the clinical findings as well as the radiographic abnormalities are self-limited and usually resolve spontaneously irrespective of weight-bearing and immobilization treatment modalities. Köhler’s disease has been defined either as atraumatic navicular osteonecrosis or as an osteochondrosis process, based on the similar radiographic appearance of increased sclerosis and flattening detected in both asymptomatic and symptomatic children. Post-traumatic tarsal navicular osteonecrosis in children may follow microtrauma or overuse injuries, stress fractures, acute fractures, osteochondritis dissecans and severe foot injuries. This editorial aims to present the primary and secondary causes of osteonecrosis of the tarsal navicular in children and to describe the difficulties of the clinical and radiological evaluation in order to define an accurate diagnosis.

Highly Cross-Linked Polyethylene in Total Hip Arthroplasty in Patients Younger Than 50 Years With Osteonecrosis of the Femoral Head: A Minimum of 10 Years of Follow-Up

BackgroundPolyethylene wear and subsequent periprosthetic osteolysis remain a major concern of total hip arthroplasty (THA) failure in young, active patients with osteonecrosis of the femoral head (ONFH). The literature is lacking regarding the long-term performance of highly cross-linked polyethylene (HXLPE) in these patients. The purpose of this study is to evaluate long-term results for cementless THA using metal-on-HXLPE bearing couplings in patients younger than 50 years with ONFH. MethodsWe retrospectively evaluated the clinical and radiographic results of a consecutive series of 85 THAs (in 67 patients) performed with HXLPE liners (Durasul) in patients younger than 50 years who had ONFH. All procedures were performed at a single institution by a single surgeon using the same type of implants. The minimum duration of follow-up was 10 years (mean, 13.5 years; range, 10-17.3 years). Wear was measured using computer software. Osteolysis was evaluated with the use of radiography and computed tomography. ResultsThe mean Harris hip score was 49.3 points (range, 26-68 points) before surgery, which improved to 93.6 points (range, 87-98 points) after surgery. Neither femoral nor acetabular components displayed mechanical loosening, and no components had been revised by the final follow-up evaluation. Radiographs and computed tomography scans did not demonstrate osteolysis. The mean liner wear was 0.037 mm/y (range, 0-0.099 mm/y). With the data available, univariate regression analysis did not demonstrate that age, sex, weight, activity level, underlying cause of osteonecrosis, liner thickness, or cup inclination had any influence on liner penetration. ConclusionAlthough the long-term effects of HXLPE particles remain unknown, the implant survivorship rate and wear rate in our study are promising and support the continued use of metal-on-HXLPE bearing couplings in these high-risk patients because they do not produce any of the issues associated with hard-on-hard couplings. Level of EvidenceTherapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Etiologic Classification Criteria of ARCO on Femoral Head Osteonecrosis Part 1: Glucocorticoid-Associated Osteonecrosis

BackgroundGlucocorticoid usage, a leading cause of osteonecrosis of the femoral head (ONFH), and its prevalence was reported in 25%-50% of non-traumatic ONFH patients. Nevertheless, there have been no unified criteria to classify glucocorticoid-associated ONFH (GA-ONFH). In 2015, the Association Research Circulation Osseous addressed the issue of developing a classification scheme. MethodsIn June 2017, a task force was set up to conduct a Delphi survey concerning ONFH. The task force invited 28 experts in osteonecrosis/bone circulation from 8 countries. Each round of the Delphi survey consists of questionnaires, analysis of replies, and feedback reports to the panel. After 3 rounds of the survey, the panel reached a consensus on the classification criteria. The response rates were 100% (Round 1), 96% (Round 2), and 100% (Round 3), respectively. ResultsThe consensus on the classification criteria of GA-ONFH included the following: (1) patients should have a history of glucocorticoid use >2 g of prednisolone or its equivalent within a 3-month period; (2) osteonecrosis should be diagnosed within 2 years after glucocorticoid usage, and (3) patients should not have other risk factor(s) besides glucocorticoids. ConclusionAssociation Research Circulation Osseous established classification criteria to standardize clinical studies concerning GA-ONFH.

History of concentrated or expanded mesenchymal stem cells for hip osteonecrosis: is there a target number for osteonecrosis repair?

Despite multiple possible treatments, the risk of collapse remains the main problem of osteonecrosis. Heart failure (HF). In an effort to address the reverse this issue, curative strategies with regenerative medicine are increasingly being considered. The aim of this technology is to halt or reverse progression of the disease to collapse. The pioneering report by Hernigou published in 2002 was the first pilot study suggesting that injection of bone marrow stem cells was a safe approach able to improve osteonecrosis in patients with early stages. Since then, an impressive number of studies and trials employing unselected BM-derived cells (1000 the last 2years) showed that delivery of those cells to the site of osteonecrosis during core decompression was somehow able to ameliorate the patient with osteonecrosis. In order to translate the promise of this cell therapy into better clinical benefit, many questions need to be addressed. In this review, we therefore analyzed current clinical experience of the literature and our experience of 4000 cases to address these questions and particularly the number of cells that should be injected. After almost 20years of clinical research in this field, we are still far from having drawn conclusions on the number of cells we should inject in regenerating hip osteonecrosis. Findings are difficult to interpret due to heterogeneity of causes of osteonecrosis, as well as differences in the cells count, sample quality, and stages of osteonecrosis. The authors address specific issues, as cell quality, cell numbers, volume of osteonecrosis, concentration of cells, and ex vivo expansion. Bone marrow mesenchymal stem cells are supposed to be "functionally competent," but are collected from the bon, marrow of patients with diseases and risk factors of osteonecrosis. The recipient organ (bone osteonecrosis) is a tissue where several alterations have already occurred. These questions are addressed in this review. In this review, we analyzed current clinical experience regarding cell therapy and address issues that should be a guide for future cell-based therapeutic application in osteonecrosis.

Association of reduced sclerostin expression with collapse process in patients with osteonecrosis of the femoral head.

Sclerostin is an osteocyte-derived protein that has a potent inhibitory effect on osteoblast activity. The osteocyte apoptosis induced by various causes of osteonecrosis of the femoral head (ONFH) plays a key role in the promotion of femoral head collapse. But the effect of altering sclerostin level on the collapse of ONFH has not been studied. Our aim was to assess the role of sclerostin level in the collapse of ONFH. Between May 2016 and November 2016, 236 subjects were enrolled in the present study. The patients were classified according to the Association Research Circulation Osseous (ARCO) classification. The clinical bone histomorphology, the expression position, and level of sclerostin as well as the plasma sclerostin level were evaluated. The sclerostin level was significantly lower in the non-traumatic ONFH group than those in the healthy control group (P = 0.002). The sclerostin level was negatively associated with ARCO stages (r = - 0.239, P = 0.009) and significantly lower in the postcollapse group (P = 0.025). The reduced expression of sclerostin may play a key role in the collapse process of ONFH and be predictive of the disease progression of ONFH.

Hip osteonecrosis and pregnancy in healthy women.

Osteonecrosis has been reported to be associated with pregnancy in the absence of other known risk factors for the disease. Few population-based data exist to support an association since the association is rare. We investigated the association of the femoral head and pregnancy to define if pregnancy was a risk factor and to define the risk period. Using a case-crossover method design among 652 patients who were healthy (without any known cause of osteonecrosis) during or after pregnancy, we defined the periods of risk based on the timing of reported osteonecrosis and pregnancy. We compared each patient's likelihood of osteonecrosis during a ten years period including fiveyears antepartum, pregnancy and fiveyears postpartum with nine month intervals for the ten year and three month intervals for the twoyears after gestation. For the 436 women who had only one child and one hip osteonecrosis, the incidence of osteonecrosis was 71.8% during pregnancy and the postpartum period, compared with 28.2% during the equivalent antepartum period for this population. Nine months after delivery, the risk of osteonecrosis declined progressively over time, from an odds ratio of 14.5 (95% confidence interval, 8.2-18.3) in last trimester of pregnancy. After the 27th month following onset of pregnancy, the relative risk was no more significantly different from the baseline risk observed in the antepartum period of women who had osteonecrosis before gestation. For women with several children, a subsequent pregnancy was not associated with osteonecrosis. A risk of hip osteonecrosis is present during the end of pregnancy and after delivery, and appears to decrease quickly.

Exosomes derived from human platelet-rich plasma prevent apoptosis induced by glucocorticoid-associated endoplasmic reticulum stress in rat osteonecrosis of the femoral head via the Akt/Bad/Bcl-2 signal pathway

An excess of glucocorticoids (GCs) is reported to be one of the most common causes of osteonecrosis of the femoral head (ONFH). In addition, GCs can induce bone cell apoptosis through modulating endoplasmic reticulum (ER) stress. Among the three main signal pathways in ER stress, the PERK (protein kinase RNA-like ER kinase)/CHOP (CCAAT-enhancer-binding protein homologous protein) pathway has been considered to be closely associated with apoptosis. Platelet-rich plasma (PRP) has been referred to as a concentration of growth factors and the exosomes derived from PRP (PRP-Exos) have a similar effect to their parent material. The enriched growth factors can be encapsulated into PRP-Exos and activate Akt and Erk pathways to promote angiogenesis. Activation of the Akt pathway may promote the expression of anti-apoptotic proteins like Bcl-2, while CHOP can inhibit B-cell lymphoma 2 (Bcl-2) expression to increase the level of cleaved caspase-3 and lead to cell death. Consequently, we hypothesized that PRP-Exos prevent apoptosis induced by glucocorticoid-associated ER stress in rat ONFH via the Akt/Bad/Bcl-2 signal pathway. To verify this hypothesis, a dexamethasone (DEX)-treated in vitro cell model and methylprednisolone (MPS)-treated in vivo rat model were adopted. Characterization of PRP-Exos, and effects of PRP-Exos on proliferation, apoptosis, angiogenesis, and osteogenesis of cells treated with GCs in vitro and in vivo were examined. Furthermore, the mechanism by which PRP-Exos rescue the GC-induced apoptosis through the Akt/Bad/Bcl-2 pathway was also investigated. The results indicate that PRP-Exos have the capability to prevent GC-induced apoptosis in a rat model of ONFH by promoting Bcl-2 expression via the Akt/Bad/Bcl-2 signal pathway under ER stress.