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1.
Front Endocrinol (Lausanne) ; 15: 1344917, 2024.
Article En | MEDLINE | ID: mdl-38745949

Background: Previous studies have reported that the occurrence and development of osteonecrosis is closely associated with immune-inflammatory responses. Mendelian randomization was performed to further assess the causal correlation between 41 inflammatory cytokines and osteonecrosis. Methods: Two-sample Mendelian randomization utilized genetic variants for osteonecrosis from a large genome-wide association study (GWAS) with 606 cases and 209,575 controls of European ancestry. Another analysis included drug-induced osteonecrosis with 101 cases and 218,691 controls of European ancestry. Inflammatory cytokines were sourced from a GWAS abstract involving 8,293 healthy participants. The causal relationship between exposure and outcome was primarily explored using an inverse variance weighting approach. Multiple sensitivity analyses, including MR-Egger, weighted median, simple model, weighted model, and MR-PRESSO, were concurrently applied to bolster the final results. Results: The results showed that bFGF, IL-2 and IL2-RA were clinically causally associated with the risk of osteonecrosis (OR=1.942, 95% CI=1.13-3.35, p=0.017; OR=0.688, 95% CI=0.50-0.94, p=0.021; OR=1.386, 95% CI=1.04-1.85, p = 0.026). there was a causal relationship between SCF and drug-related osteonecrosis (OR=3.356, 95% CI=1.09-10.30, p=0.034). Conclusion: This pioneering Mendelian randomization study is the first to explore the causal link between osteonecrosis and 41 inflammatory cytokines. It conclusively establishes a causal association between osteonecrosis and bFGF, IL-2, and IL-2RA. These findings offer valuable insights into osteonecrosis pathogenesis, paving the way for effective clinical management. The study suggests bFGF, IL-2, and IL-2RA as potential therapeutic targets for osteonecrosis treatment.


Cytokines , Genetic Predisposition to Disease , Genome-Wide Association Study , Mendelian Randomization Analysis , Osteonecrosis , Humans , Osteonecrosis/genetics , Cytokines/genetics , Polymorphism, Single Nucleotide , Interleukin-2/genetics , Fibroblast Growth Factor 2/genetics , Inflammation/genetics
2.
Semin Arthritis Rheum ; 66: 152444, 2024 Jun.
Article En | MEDLINE | ID: mdl-38604118

OBJECTIVE: Avascular necrosis (AVN) is a devastating complication often necessitating arthroplasty, particularly common in systemic lupus erythematosus (SLE). Limited research exists on arthroplasty trends since new steroid-sparing agents. We analyzed trends and characteristics associated with AVN and AVN-related arthroplasties among SLE and RA hospitalizations using two decades of data from the U.S. National Inpatient Sample (NIS). METHODS: This cross-sectional study used NIS (2000-2019) to identify hospitalized adults with SLE and RA, with or without AVN, using ICD codes. AVN was further grouped by arthroplasty status. Primary outcomes were AVN and AVN-related arthroplasty rates and time trends in SLE and RA. Baseline sociodemographics and comorbidities were compared. Analyses used STATA and Joinpoint regression to calculate annual percent change (APC). RESULTS: Overall, 42,728 (1.3 %) SLE and 43,600 (0.5 %) RA hospitalizations had concomitant AVN (SLE-AVN and RA-AVN). Of these, 16,724 (39 %) and 25,210 (58 %) underwent arthroplasties, respectively. RA-AVN increased (APC: 0.98*), with a decrease in arthroplasties (APC: -0.82*). In contrast, SLE-AVN initially increased with a breakpoint in 2011 (APC 2000-2011: 1.94* APC 2011-2019 -2.03), with declining arthroplasties (APC -2.03*). AVN hospitalizations consisted of individuals who were younger and of Black race; while arthroplasties were less likely in individuals of Black race or Medicaid coverage. CONCLUSION: We report a breakpoint in rising SLE-AVN after 2011, which may relate to newer steroid-sparing therapies (i.e., belimumab). AVN-associated arthroplasties decreased in SLE and RA. Fewer AVN-associated arthroplasties were noted for Black patients and those with Medicaid, indicating potential disparities. Further research should examine treatment differences impacting AVN and arthroplasty rates.


Arthritis, Rheumatoid , Hospitalization , Lupus Erythematosus, Systemic , Osteonecrosis , Humans , Lupus Erythematosus, Systemic/complications , Female , Arthritis, Rheumatoid/surgery , Arthritis, Rheumatoid/complications , Male , Middle Aged , Cross-Sectional Studies , Adult , United States/epidemiology , Hospitalization/statistics & numerical data , Hospitalization/trends , Osteonecrosis/epidemiology , Osteonecrosis/surgery , Osteonecrosis/etiology , Aged , Arthroplasty/trends
4.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 38(4): 405-411, 2024 Apr 15.
Article Zh | MEDLINE | ID: mdl-38632058

Objective: To analyze the correlation between postoperative complications and combined deflection angle classification adduction type (CDAC-ADT) of femoral neck fractures after cannulated screw internal fixation. Methods: The clinical data of 121 patients with CDAC-ADT femoral neck fracture admitted between January 2018 and December 2021 and met the selected criteria were retrospectively analyzed. There were 69 males and 52 females, the age ranged from 19 to 79 years (mean, 48.1 years). The causes of injury included 52 cases of traffic accident, 24 cases of falling from height, and 45 cases of fall. The time from injury to operation ranged from 2 to 12 days, with an average of 6.0 days. Among them, there were 18 cases of CDAC-ADT type Ⅰ, 46 cases of type Ⅱ, and 57 cases of type Ⅲ; 6 cases of Garden type Ⅱ, 103 cases of type Ⅲ, and 12 cases of type Ⅳ; and according to the location of the fracture line, there were 26 cases of subcapitate type, 88 cases of transcervical type, and 7 cases of basal type. All patients were treated with cannulated screw internal fixation. The occurrence of complications (including internal fixation failure, fracture nonunion, and osteonecrosis of the femoral head) was recorded, and the correlation between complications and CDAC-ADT typing, Garden typing, and fracture line location were analyzed. Results: The patients were followed up 8-44 months, with a mean of 24.9 months. There were 10 cases of internal fixation failure, 7 cases of fracture nonunion, and 30 cases of osteonecrosis of the femoral head after operation. Correlation analysis showed that patients' CDAC-ADT typing was significantly correlated with the overall incidence of complication and the incidence of internal fixation failure, fracture nonunion, and osteonecrosis of the femoral head ( P<0.05), and the Pearson coefficient of contingency were 0.435, 0.251, 0.254, and 0.241, respectively. Garden typing did not correlate with the overall incidence of complication and the incidence of internal fixation failure and fracture nonunion ( P>0.05), but correlated with the incidence of osteonecrosis of the femoral head ( P<0.05), and the Pearson coefficient of contingency was 0.251. Fracture line position typing had no correlation with the overall incidence of complication and the incidence of internal fixation failure, fracture nonunion, and osteonecrosis of the femoral head ( P>0.05). Conclusion: CDAC-ADT typing has obvious correlation with postoperative complications of femoral neck fracture and can be used to predict complications of femoral neck fracture.


Chlorambucil/analogs & derivatives , Docosahexaenoic Acids , Femoral Neck Fractures , Fractures, Ununited , Malocclusion , Osteonecrosis , Male , Female , Humans , Young Adult , Adult , Middle Aged , Aged , Retrospective Studies , Femoral Neck Fractures/surgery , Fracture Fixation, Internal , Postoperative Complications , Treatment Outcome
5.
BMC Musculoskelet Disord ; 25(1): 286, 2024 Apr 13.
Article En | MEDLINE | ID: mdl-38614975

OBJECTIVE: Femoral neck fractures (FNFs) are among the most common fractures in elderly individuals. Surgery is the main treatment for FNFs, and osteonecrosis of the femoral head (ONFH) is one of the unacceptable complications. This study aimed to assess both the clinical and radiological outcomes in patients with FNFs treated with three parallel cannulated screws and to identify relationship between screws position and ONFH. PATIENTS AND METHODS: A total of 100 patients who were treated with closed reduction and fixed with 3 parallel cannulated screws met the inclusion criteria between January 2014 and December 2020 at authors' institution. The follow-up duration, age, sex, affected side, and injury-to-surgery interval were collected; the neck-shaft angle of both hips, screw-apex distance (SAD) and the tip-apex distance (TAD)were measured; and the Garden classification, quality of reduction and presence of ONFH were evaluated. RESULTS: The sample consisted of 37 males and 63 females, with 60 left and 40 right hips affected. The mean age of patients was 54.93 ± 12.24 years, and the mean follow-up was 56.3 ± 13.38 months. The overall incidence of ONFH was 13%. No significant difference was observed in the incidence of ONFH by affected side, age, fracture displacement, injury-to-surgery interval, neck-shaft angle deviation, or reduction quality. The SAD was significantly shorter in ONFH patients than in normal patients for all three screws (p = 0.02, 0.02, and 0.01, respectively). CONCLUSIONS: The short SAD of all screws is associated with femoral head necrosis of FNFs treated with 3 cannulated screws. The short SAD indicated that screws malpositioning in the weight-bearing area of the femoral head, potentially harming the blood supply and compromising the anchorage of the primary compressive trabeculae in this region.


Femoral Neck Fractures , Fenofibrate , Osteonecrosis , Adult , Aged , Female , Male , Humans , Middle Aged , Femur Head/diagnostic imaging , Femur Head/surgery , Femoral Neck Fractures/diagnostic imaging , Femoral Neck Fractures/surgery , Necrosis , Bone Screws/adverse effects
6.
Int J Mol Sci ; 25(7)2024 Mar 25.
Article En | MEDLINE | ID: mdl-38612458

Certain genetic factors, including single-nucleotide polymorphisms (SNPs) in the SIRT1 gene, have been linked to medication-related osteonecrosis of the jaw (MRONJ). This study examined four SNPs in the SIRT1 gene and implemented multivariate statistical analysis to analyze genetic and clinical factors in MRONJ patients. Genomic DNA was isolated from peripheral blood samples of 63 patients of European origin treated for MRONJ, and four SNP genotypes in the gene encoding the SIRT-1 protein were determined by Sanger sequencing. The allele frequencies measured in the MRONJ population were compared with allele frequencies measured in the European population in the National Center for Biotechnology Information Allele Frequency Aggregator (NCBI ALFA) database. Genetic and clinical factors were examined with multivariate statistical analysis. A C:A allele distribution ratio of 77.8:22.2 was measured in the rs932658 SNP. In the ALFA project, a C:A allele distribution ratio of 59.9:40.1 was detected in the European population, which was found to be a significant difference (p = 4.5 × 10-5). Multivariate statistical analysis revealed a positive correlation (0.275) between the genotype of SNP rs932658 and the number of stages improved during appropriate MRONJ therapy. It is concluded that allele A in SNP rs932658 in the SIRT1 gene acts as a protective factor in MRONJ.


Osteonecrosis , Polymorphism, Single Nucleotide , Humans , Sirtuin 1/genetics , Genotype , Alleles
7.
Sci Rep ; 14(1): 9371, 2024 04 23.
Article En | MEDLINE | ID: mdl-38654114

A wealth of evidence intimates a profound connection between the immune system and osteonecrosis, albeit the specific immune factors underlying this connection remain largely veiled. A bidirectional Mendelian randomization (MR) study was conducted based on genome-wide association study summary data to identify causal links between 731 immune factors and osteonecrosis including drug-induced osteonecrosis. Preliminary MR analysis was accomplished utilizing the inverse-variance weighted method under a multiplicative random effects model, and heterogeneity and potential horizontal pleiotropy were evaluated through Cochrane's Q-test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis. Upon false discovery rate correction, the gene-predicted level of one immune factor (CD62L - monocyte %monocyte) exhibited a significant positive correlation with osteonecrosis, while eight immune traits associated with monocytes, dendritic cells, and NK cells demonstrated significant causal effects with drug-induced osteonecrosis. Reverse MR revealed no significant correlations. This MR research provides genetic evidence for the causal associations between a broad spectrum of immune factors and osteonecrosis. Such a study aids in unraveling the intricate interaction patterns between the immune and skeletal systems, elucidating the pathogenesis of osteonecrosis, and identifying potential novel therapeutic approaches.


Genome-Wide Association Study , Mendelian Randomization Analysis , Osteonecrosis , Humans , Osteonecrosis/genetics , Osteonecrosis/immunology , Osteonecrosis/etiology , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Immunologic Factors/genetics , Monocytes/immunology , Monocytes/metabolism
8.
JBJS Case Connect ; 14(2)2024 Apr 01.
Article En | MEDLINE | ID: mdl-38579102

CASE: A 27-year-old woman developed capitellar osteonecrosis after long-term corticosteroid use to treat non-Hodgkin lymphoma. She underwent an osteochondral reconstruction using a lateral femoral condyle (LFC) allograft. This graft was selected because it has a similar radius of curvature to the capitellum. The patient had osseous integration, painless, near full range of motion of her elbow 6 months postoperatively and good shoulder function 1.0 year postoperatively. CONCLUSION: The LFC allograft should be considered a viable option in treating capitellar osteonecrosis.


Osteochondritis Dissecans , Osteonecrosis , Female , Humans , Adult , Elbow , Osteochondritis Dissecans/surgery , Bone Transplantation , Epiphyses/surgery , Osteonecrosis/surgery , Allografts
9.
Acta Orthop Belg ; 90(1): 154-159, 2024 Mar.
Article En | MEDLINE | ID: mdl-38669667

Mueller-Weiss Syndrome (MWS), characterized by spontaneous adult-onset tarsal navicular osteonecrosis, is an uncommon cause of chronic midfoot pain that can lead to functional impairment and progressive deformities. This study aimed to present clinical and radiological outcomes of talonavicular-cuneiform (TNC) arthrodesis in the treatment of patients with MWS. A retrospective study was performed on 8 consecutive patients (6 female, 2 male; mean age = 50 years; range = 33-64) who underwent TNC arthrodesis using plate fixation with autologous bone grafting for the treatment of MWS. To evaluate clinical status, the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Midfoot Score was performed immediately preoperatively and at the final follow-up. In radiographic evaluation, talus-first metatarsal angle (Meary's angle) was measured preoperatively and at the final follow-up. Solid fusion was also examined on postoperative radiographs and computerised tomography. The mean follow-up was 35 months (range = 24-52). The mean AOFAS improved from 37 (range = 24-53) preoperatively to 85 (range = 80-93) at the final follow-up (p < 0.001). No major intra- operative complications were observed in any of the patients. According to the Maceira and Rochera radiological staging system, 5 feet was stage 3, and 3 feet was stage 4. The mean union time was 10 months (range = 5-15). Radiographic solid fusion was achieved in all but one foot that developed talonavicular non-union. TNC arthrodesis using plate fixation with autologous bone grafting seems to be an effective surgical method for reconstruction of MWS.


Arthrodesis , Osteonecrosis , Tarsal Bones , Humans , Arthrodesis/methods , Female , Male , Retrospective Studies , Adult , Middle Aged , Tarsal Bones/surgery , Osteonecrosis/surgery , Osteonecrosis/diagnostic imaging , Bone Transplantation/methods , Treatment Outcome , Syndrome , Talus/surgery , Talus/diagnostic imaging , Tarsal Joints/surgery
10.
J Orthop Surg Res ; 19(1): 243, 2024 Apr 16.
Article En | MEDLINE | ID: mdl-38622659

Inflammatory reactions are involved in the development of steroid-induced osteonecrosis of the femoral head(ONFH). Studies have explored the therapeutic efficacy of inhibiting inflammatory reactions in steroid-induced ONFH and revealed that inhibiting inflammation may be a new strategy for preventing the development of steroid-induced ONFH. Exosomes derived from M2 macrophages(M2-Exos) display anti-inflammatory properties. This study aimed to examine the preventive effect of M2-Exos on early-stage steroid-induced ONFH and explore the underlying mechanisms involved. In vitro, we explored the effect of M2-Exos on the proliferation and osteogenic differentiation of bone marrow-derived mesenchymal stem cells(BMMSCs). In vivo, we investigated the role of M2-Exos on inflammation, osteoclastogenesis, osteogenesis and angiogenesis in an early-stage rat model of steroid-induced ONFH. We found that M2-Exos promoted the proliferation and osteogenic differentiation of BMMSCs. Additionally, M2-Exos effectively attenuated the osteonecrotic changes, inhibited the expression of proinflammatory mediators, promoted osteogenesis and angiogenesis, reduced osteoclastogenesis, and regulated the polarization of M1/M2 macrophages in steroid-induced ONFH. Taken together, our data suggest that M2-Exos are effective at preventing steroid-induced ONFH. These findings may be helpful for providing a potential strategy to prevent the development of steroid-induced ONFH.


Bone Resorption , Exosomes , Femur Head Necrosis , Osteonecrosis , Rats , Animals , Osteogenesis , Exosomes/metabolism , Femur Head/metabolism , Osteonecrosis/prevention & control , Inflammation/metabolism , Macrophages/metabolism , Steroids/adverse effects , Femur Head Necrosis/chemically induced , Femur Head Necrosis/prevention & control , Femur Head Necrosis/metabolism
11.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(2): 366-370, 2024 Apr 18.
Article Zh | MEDLINE | ID: mdl-38595260

Herpes zoster of trigeminal nerve was a common skin disease caused by varicella-zoster virus infection. Simple involvement of the third branch of trigeminal nerve was rare, and so were oral complications such as pulpitis, periodontitis, spontaneous tooth loss, bone necrosis, etc. This article presented a case of herpes zoster on the third branch of the left trigeminal nerve complicated with left mandibular osteonecrosis. We reported the case of a 64-year-old man with sudden pain in the left half of the tongue 1 month ago, and then herpes on the left facial skin appeared following with acute pain.The local hospital diagnosed it as herpes zoster and treated it with external medication. A few days later, he developed gum pain in the left mandibular posterior tooth area. He was admitted to Peking University School and Hospital of Stomatology one week ago with loose and dislodged left posterior tooth accompanied by left mandibular bone surface exposure. Clinical examination showed bilateral symmetry and no obvious restriction of mouth opening. Visible herpes zoster pigmentation and scarring on the left side of the face appeared. The left mandibular posterior tooth was missing, the exposed bone surface was about 1.5 cm×0.8 cm, and the surrounding gingiva was red and swollen, painful under pressure, with no discharge of pus. The remaining teeth in the mouth were all Ⅲ degree loosened. Imageological examination showed irregular low-density destruction of the left mandible bone, unclear boundary, and severe resorption of alveolar bone. The patient was diagnosed as left mandibular osteonecrosis. Under general anesthesia, left mandibular lesion exploration and curettage + left mandibular partial resection + adjacent flap transfer repair were performed. The patient was re-exmained 6 months after surgery, there was no redness, swelling or other abnormality in the gums and the herpes pigmentation on the left face was significantly reduced. Unfortunately, the patient had complications of postherpetic neuralgia. This case indicate that clinicians should improve their awareness of jaw necrosis, a serious oral complication of trigeminal zoster, and provide early treatment. After the inflammation was initially controlled, surgical treatment could be considered to remove the necrotic bone, curettage the inflammatory granulation tissue, and extraction of the focal teeth to avoid further deterioration of the disease.


Herpes Zoster , Osteonecrosis , Male , Humans , Middle Aged , Herpesvirus 3, Human , Herpes Zoster/complications , Herpes Zoster/diagnosis , Herpes Zoster/drug therapy , Trigeminal Nerve , Osteonecrosis/surgery , Osteonecrosis/complications , Mandible , Pain
12.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 38(4): 493-497, 2024 Apr 15.
Article Zh | MEDLINE | ID: mdl-38632072

Objective: To summarize the surgical treatment methods for avascular necrosis of the talus. Methods: The recent domestic and international literature related to avascular necrosis of the talus was extensively conducted. The pathogenesis, surgical treatment methods, and prognosis were summarized. Results: The clinical symptoms of avascular necrosis of the talus at early stage are not obvious, and most patients have progressed to Ficat-Arlet stages Ⅲ-Ⅳ and require surgical treatment. Currently, surgical treatments for this disease include core decompression, vascularized bone flap transplantation, arthroplasty, and arthrodesis, etc. Early avascular necrosis of the talus can be treated conservatively, and if treatment fails, core decompression can be considered. Arthrodesis is a remedial surgery for patients with end-stage arthritis and collapse, and in cases of severe bone loss, tibiotalocalcaneal arthrodesis and bone grafting are required. Vascularized bone flap transplantation is effective and plays a role in all stages of avascular necrosis of the talus, but the appropriate donor area for the flap still needs further to be studied. Conclusion: The surgical treatment and the system of treatment for different stages of avascular necrosis of the talus still need to be refined.


Osteonecrosis , Talus , Humans , Talus/surgery , Surgical Flaps/blood supply , Bone Transplantation/methods , Arthrodesis/methods , Osteonecrosis/therapy
13.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1343-1352, 2024 Mar.
Article Zh | MEDLINE | ID: mdl-38621982

A research strategy combining transcriptome data mining and experimental verification was adopted to identify the marker genes characterizing the syndrome elements of phlegm, stasis, and deficiency in steroid-induced osteonecrosis of the femoral head(SONFH). Firstly, the common differentially expressed gene sets of SONFH with the syndromes of phlegm-stasis obstructing collaterals, vessel obstruction, and liver-kidney deficiency were obtained from the clinical transcriptomic analysis of a previous study. The differential expression trend analysis and functional gene mining were then employed to predict the candidate marker gene sets representing phlegm, stasis, and deficiency. The whole blood samples from SONFH patients, whole blood samples from SONFH rats, and affected femoral head tissue samples were collected for qPCR, which aimed to determine the expression levels of the candidate marker genes mentioned above. Furthermore, the receiver operating characteristic curve(ROC) was established to objectively evaluate the syndrome differentiation effectiveness of the candidate marker genes mentioned above. The transcriptome data analysis results showed that the candidate marker genes for phlegm was ELOVL fatty acid elongase 6(ELOVL6), and those for stasis were ankyrin 1(ANK1), glycophorin A/B(GYPA/B), and Rh-associated glycoprotein(RHAG). The candidate marker genes for deficiency were solute carrier family 2 member 1(SLC2A1) and stomatin(STOM). The qPCR results showed that compared with that in the non-SONFH group, ELOVL6 had the lowest expression level in the peripheral blood of the SONFH patients with the syndrome of phlegm-stasis obstructing collaterals(P<0.05). Compared with that in the normal control group, ELOVL6 had the lowest expression level in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 4 weeks(P<0.01), and it showed better syndrome differentiation effectiveness of rats modeled for 4 weeks(AUC=0.850, P=0.006) than at other modeling time points(8, 12, 16, and 21 weeks, AUC of 0.689, 0.766, 0.588, and 0.662, respectively). Compared with that in the non-SONFH group, the expression levels of ANK1, GYPA, and RHAG were the lowest in the peripheral blood of SONFH patients with the vessel obstruction syndrome(P<0.05). The expression levels of the three genes were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 12 weeks(P<0.05, P<0.01), and their syndrome differentiation effectiveness in the rats modeled for 12 weeks(GYPA: AUC=0.861, P=0.012; ANK1: AUC=0.855, P=0.006; RHAG: AUC=0.854, P=0.009) was superior to that for 4, 8, 16, and 21 weeks(GYPA: AUC=0.646, 0.573, 0.691, and 0.617, respectively; ANK: AUC1=0.630, 0.658, 0.657, and 0.585, respectively; RHAG: AUC=0.592, 0.511, 0.515, and 0.536, respectively). Compared with the non-SONFH group, both SLC2A1 and STOM had the lowest expression levels in the peripheral blood of patients with the syndrome of liver and kidney deficiency(P<0.05). Compared with the normal control group, their expression levels were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 21 weeks(P<0.05, except STOM in the peripheral blood of rats). Moreover, the syndrome differentiation effectiveness of SLC2A1 in the rats modeled for 21 weeks(AUC=0.806, P=0.009) was superior to that for 4, 8, 12, and 16 weeks(AUC=0.520, 0.580, 0.741, 0.774, respectively), and STOM was meaningless in syndrome differentiation. In summary, the candidate marker gene for phlegm in SONFH is ELOVL6; the candidate marker genes for stasis are GYPA, RHAG, and ANK1; the candidate marker gene for deficiency is SLC2A1. The results help to reveal the biological connotations of phlegm, stasis, and deficiency in SONFH at the genetic level.


Animal Experimentation , Osteonecrosis , Vascular Diseases , Humans , Rats , Animals , Transcriptome , Femur Head , Syndrome , Steroids/adverse effects
14.
Bone ; 183: 117094, 2024 Jun.
Article En | MEDLINE | ID: mdl-38582289

The present study aimed to establish and evaluate a preclinical model of steroid-associated osteonecrosis (SAON) in mice. Sixteen 24-week-old male C57BL/6 mice were used to establish SAON by two intraperitoneal injections of lipopolysaccharide (LPS), followed by three subcutaneous injections of methylprednisolone (MPS). Each injection was conducted on working day, with an interval of 24 h. Six cycles of injections were conducted. Additional twelve mice (age- and gender-matched) were used as normal controls. At 2 and 6 weeks after completing induction, bilateral femora and bilateral tibiae were collected for histological examination, micro-CT scanning, and bulk RNA sequencing. All mice were alive until sacrificed at the indicated time points. The typical SAON lesion was identified by histological evaluation at week 2 and week 6 with increased lacunae and TUNEL+ osteocytes. Micro-CT showed significant bone degeneration at week 6 in SAON model. Histology and histomorphometry showed significantly lower Runx2+ area, mineralizing surface (MS/BS), mineral apposition rate (MAR), bone formation rate (BFR/BS), type H vessels, Ki67+ (proliferating) cells, and higher marrow fat fraction, osteoclast number and TNFα+ areas in SAON group. Bulk RNA-seq revealed changed canonical signaling pathways regulating cell cycle, angiogenesis, osteogenesis, and osteoclastogenesis in the SAON group. The present study successfully established SAON in mice with a combination treatment of LPS and MPS, which could be considered a reliable and reproducible animal model to study the pathophysiology and molecular mechanism of early-stage SAON and to develop potential therapeutic approaches for the prevention and treatment of SAON.


Lipopolysaccharides , Osteonecrosis , Male , Mice , Animals , Disease Models, Animal , Mice, Inbred C57BL , Osteonecrosis/drug therapy , Steroids , Osteogenesis , Methylprednisolone/therapeutic use
15.
BMC Oral Health ; 24(1): 409, 2024 Apr 02.
Article En | MEDLINE | ID: mdl-38566112

BACKGROUND: Herpes zoster (HZ) is one of the most common skin diseases caused by viruses. Facial HZ develops when the varicella-zoster virus affects the trigeminal nerve, and alveolar osteonecrosis is a rare complication. However, the exact pathogenesis of postherpetic alveolar osteonecrosis remains unclear. CASE DESCRIPTION: We encountered a patient who presented to the dermatology clinic with facial HZ and tooth exfoliation in the upper right jaw, and panoramic radiography revealed decreased bone density and poor alveolar socket healing in his right maxilla. Biopsy of the alveolar process revealed fragments of nonvital lamellar bone, which were devoid of osteoblasts and osteocytes and were surrounded by numerous neutrophils and bacterial aggregates. Thus, the diagnosis of alveolar osteonecrosis following facial HZ was confirmed. He then underwent resection of the osteonecrotic tissue. The pathological findings of postoperative tissue were similar to those of previous biopsies. Varicella-zoster virus and multiple types of bacteria were detected through next-generation sequencing, and the species of bacteria were consistent with the results of bacterial culture. Antibiotics and valaciclovir were administered during the perioperative period. The patient showed good recovery at the 9-month follow-up. CONCLUSIONS: The coexistence of bacterial and viral infection may play an important role in the pathogenesis of alveolar osteonecrosis following HZ. To our knowledge, we are the first to directly explore microbial pathogens in a case of postherpetic alveolar osteonecrosis through next-generation sequencing and bacterial culture. We recommend that oral examinations be carefully conducted for patients who are diagnosed with facial HZ, even if their facial rashes have faded away. We suggest that a prolonged and full-dose antiviral therapy course may be beneficial for the treatment of facial HZ with intraoral lesions. The implementation of dental preventive measures should be considered for patients with facial HZ. The application of antibiotics and excision of necrotic bone may reduce the abundance of bacteria in lesions and improve wound healing.


Herpes Zoster , Osteonecrosis , Male , Humans , Herpesvirus 3, Human , Herpes Zoster/complications , Herpes Zoster/drug therapy , Tooth Exfoliation/etiology , Osteonecrosis/complications , Anti-Bacterial Agents/therapeutic use
16.
Clin Med Res ; 22(1): 37-43, 2024 Mar.
Article En | MEDLINE | ID: mdl-38609146

The anti-inflammatory and immunosuppressive properties of steroids allow their use in a wide variety of rheumatological diseases, asthma, inflammatory bowel disease, cancer therapy, and severe viral infections. Though life-saving or organ-saving, long-term clinical use leads to a vast array of complications. Osteoporosis is the most common orthopedic side effect of steroid abuse, while osteonecrosis is a rare occurrence. The risk of osteonecrosis appears to be dose and duration dependent, but several patient factors also play a major role and usually affect the femoral head followed by the knee joint. The long-term effects of steroids must be explained to all patients on therapy, but this risk is missed in individuals who abuse steroids for recreational or performance-enhancing purposes. We describe a male, aged 29 years, who presented with dull aching bilateral knee pain of 2-years' duration after a long-term steroid abuse for weight and muscle mass gain. Radiological and magnetic resonance imaging studies confirmed osteonecrosis of femoral and tibial condyles and secondary degenerative arthritis of the knee joint. Prompt suspicion, early diagnosis, and intervention in osteonecrosis of knee joints, and termination of steroids may reverse the pathology and prevent progression of disease.


Knee Joint , Osteonecrosis , Humans , Male , Knee Joint/diagnostic imaging , Tibia , Femur , Osteonecrosis/diagnosis , Osteonecrosis/diagnostic imaging , Pain , Steroids
17.
Sci Rep ; 14(1): 7914, 2024 04 04.
Article En | MEDLINE | ID: mdl-38575664

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction associated with antiresorptive drugs such as bisphosphonates and denosumab. When dealing with advanced and/or multiple MRONJ lesions undergoing surgical therapy, the extent of surgery is often a topic of discussion. The aim of this study was to identify the differences in bone density in and around the MRONJ lesion before and after surgical treatment to evaluate the needed surgical extend of the modelling osteotomy. In this retrospective study 26 patients with MRONJ lesions that were surgically treated in our department were observed. Length, width and bone density were measured in panoramic radiograph pre and postoperatively with the Imaging processing software Sidexis and ImageJ (Fiji). The necrotic area, the surrounding sclerotic area as well as the healthy contralateral side were observed. Measurements were performed by two independent observers. Pearson correlation was calculated to determine the interobserver variability. Bone density was significantly reduced in the necrotic bone area compared to the healthy unaffected contralateral reference side. The sclerotic bone area surrounding the necrosis showed increased bone density compared to the contralateral unaffected reference side. The density of the sclerotic bone area was increased in the previously affected MRONJ area in the postoperative panoramic radiograph. The pre and postoperative density showed no significant correlation to healing behaviour. The focus of the modelling osteotomy in surgical treatment of mature MRONJ lesions should be predominantly on the parts that appear necrotic and less dense in the panoramic radiograph as sclerotic areas might be an expression of bone reaction.


Bisphosphonate-Associated Osteonecrosis of the Jaw , Bone Density Conservation Agents , Osteonecrosis , Humans , Bisphosphonate-Associated Osteonecrosis of the Jaw/diagnostic imaging , Bisphosphonate-Associated Osteonecrosis of the Jaw/surgery , Bisphosphonate-Associated Osteonecrosis of the Jaw/drug therapy , Denosumab/adverse effects , Retrospective Studies , Osteonecrosis/chemically induced , Osteonecrosis/diagnostic imaging , Osteonecrosis/surgery , Bone Density Conservation Agents/adverse effects , Diphosphonates/adverse effects , Necrosis/chemically induced
18.
JBJS Case Connect ; 14(2)2024 Apr 01.
Article En | MEDLINE | ID: mdl-38669356

CASE: Capitate avascular necrosis should be entertained in a differential diagnosis of young, active adults with midcarpal wrist pain. We present a case study of a 30-year-old laborer who developed avascular necrosis (AVN) of his right proximal capitate. Grip strength and wrist motion were limited on examination, with advanced imaging confirming AVN. A diagnostic arthroscopy confirmed the pathology. Treatment was completed with a medial femoral trochlea vascularized flap for cartilaginous resurfacing. At 10-month follow-up, the patient's capitate was healed with stable fixation, and he is working full-time as a laborer without restrictions. CONCLUSION: AVN of the capitate is a unique and challenging articular pathology that requires a thoughtful preoperative evaluation and meticulous surgical technique to reconstruct. The medial femoral trochlea (MFT) vascularized bone transfer with cartilaginous resurfacing is 1 available treatment option. This flap is harvested from the medial femur using microsurgical techniques, based on the descending genicular artery. Using a 2-surgeon approach, simultaneous dissection of the AVN is completed at the wrist. This flap is a vascularized option that can be used for both AVN and nonunion with structural deformity before salvage surgeries.


Capitate Bone , Osteonecrosis , Surgical Flaps , Humans , Male , Adult , Osteonecrosis/surgery , Osteonecrosis/diagnostic imaging , Capitate Bone/surgery , Capitate Bone/diagnostic imaging , Surgical Flaps/blood supply , Femur/surgery , Femur/pathology , Femur/transplantation , Femur/blood supply
19.
J Orthop Trauma ; 38(6): 220-224, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38457751

OBJECTIVES: To determine if talar neck fractures with concomitant ipsilateral foot and/or ankle fractures (TNIFAFs) are associated with higher rates of avascular necrosis (AVN) compared with isolated talar neck fractures (ITNs). DESIGN: Retrospective cohort. SETTING: Single level I trauma center. PATIENT SELECTION CRITERIA: Skeletally mature patients who sustained talar neck fractures from January 2008 to January 2017 with at least 6-month follow-up. Based on radiographs at the time of injury, fractures were classified as ITN or TNIFAF and by Hawkins classification. OUTCOME MEASURES AND COMPARISONS: The primary outcome was the development of AVN based on follow-up radiographs, with secondary outcomes including nonunion and collapse. RESULTS: There were 115 patients who sustained talar neck fractures, with 63 (55%) in the ITN group and 52 (45%) in the TNIFAF group. In total, 63 patients (54.7%) were female with the mean age of 39 years (range, 17-85), and 111 fractures (96.5%) occurred secondary to high-energy mechanisms of injury. There were no significant differences in demographic or clinical characteristics between groups ( P > 0.05). Twenty-four patients (46%) developed AVN in the TNIFAF group compared with 19 patients (30%) in the ITN group ( P = 0.078). After adjusting for Hawkins classification and other variables, the odds of developing AVN was higher in the TNIFAF group compared with the ITN group [odds ratio, 2.43 (95% confidence interval, 1.01-5.84); ( P = 0.047)]. CONCLUSIONS: This study found a significantly higher likelihood of AVN in patients with talar neck fractures with concomitant ipsilateral foot and/or ankle fractures compared to those with isolated talar neck fractures after adjusting for Hawkins classification and other potential prognostic confounders. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Ankle Fractures , Fractures, Bone , Osteonecrosis , Talus , Humans , Female , Male , Adult , Talus/injuries , Talus/diagnostic imaging , Retrospective Studies , Middle Aged , Ankle Fractures/complications , Ankle Fractures/surgery , Aged , Adolescent , Young Adult , Osteonecrosis/etiology , Fractures, Bone/complications , Fractures, Bone/diagnostic imaging , Aged, 80 and over , Risk Factors , Cohort Studies
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