Fig 1 - available via license: Creative Commons Attribution 4.0 International
Content may be subject to copyright.
Histological appearance of hematoxylin and eosin stained femoral head. Typical images from the MC and M1 groups are shown. The diffuse presence of empty lacunae in the bone trabeculae accompanied by bone marrow cell necrosis was observed in the femoral head of M1 group. Scale bar: 100?m. doi:10.1371/journal.pone.0165490.g001
Source publication
Background
We previously reported that ethanol-containing liquid diet feeding induces osteonecrosis of the femoral head in male rats. Also, it was reported that a large amount of consumed ethanol and a long-term history of drinking were risk factors for osteonecrosis of the femoral head, and that the frequency of alcohol-induced osteonecrosis of th...
Citations
... Studies have shown that male patients with ONFH have a greater incidence than female patients with ONFH even if steroid hormones are also used 15 . In addition, another study showed that females are less prone to ONFH compared with males even with greater alcohol consumption and longer duration 16 . This proves that the underlying mechanism of gender difference leading to ONFH is unclear. ...
Objective:
To identify different key genes and pathways between males and females by studying differentially expressed genes (DEGs).
Methods:
The gene expression data of GSE123568 were downloaded from GEO database, including osteonecrosis of the femoral head (ONFH) samples from 3 females and 7 males, and DEGs between different gender were identified with R software. Protein-protein interaction (PPI) network was constructed to further analyze the interactions between overlapping DEGs, and finally, GO, KEGG and gene set enrichment analysis (GSEA) were conducted for enrichment analysis.
Results:
131 DEGs were identified between ONFH females and ONFH males, including 76 up-regulated genes and 55 down-regulated genes. And 10 hub genes were identified in PPI network, including SLC4A1, GYPA, CXCL8, IFIT1, GBP5, IFI44, IFI44L, IFIT3, KEL and AHSP. Functional enrichment analysis revealed that these genes were mainly enriched in cGMP-PKG signaling pathway, Fatty acid degradation, Non-alcoholic fatty liver disease, Systemic lupus erythematosus, Hematopoietic cell lineage and NO-cGMP-PKG signaling.
Conclusions:
NO-cGMP-PKG signaling may play an important role in the occurrence and development of ONFH. SLC4A1, GYPA, CXCL8, GBP5 and AHSP may be key genes associated with gender difference in the progression of ONFH, which may be ideal targets or prognostic markers for the treatment of ONFH.
... 69 The literature is limited in examining etiology-based implant survival, but a study of patients with osteonecrosis secondary to alcohol consumption showed excellent long-term outcomes. 82 It is also important to note that the study of patients with osteonecrosis requiring THA found that 46.6% of the patients would go on to require contralateral THA, especially if the contralateral hip had radiographic evidence of osteonecrosis at the time of the first THA, suggesting the need for a close follow-up. 83 Summary Osteonecrosis continues to be a condition of widely variant etiologies, treatments, and developmental profiles. ...
Osteonecrosis of the femoral head is a progressive and debilitating condition with a wide variety of etiologies including trauma, steroid use, and alcohol intake. Diagnosis and staging are based on imaging including MRI at any stage and plain radiography in more advanced lesions. The only definitive treatment is total hip arthroplasty, although numerous treatments including disphosphonates and core decompression are used to delay the progression. Lack of satisfactory conservative measures suggests the need for additional research of osteonecrosis including large patient registries to further understand this condition.
... As for the parameters "age" and "sex", their influence on ONFH therapy outcome has so far not been sufficiently evaluated. Shimizu et al. were able to show that alcohol-induced ONFH was more often triggered in male rats than in females and thereby supposed the presence of unknown sex-based factors for its predominant occurrence in men [23]. However, they did not provide a prognosis concerning therapy outcome depending on sex. ...
... Concerning the parameter "sex", it is known that the occurrence of ONFH is distributed unevenly between the sexes, affecting predominantly men [5,6]. However, apart from its uneven distribution which might be due to still unknown sex-based factors according to Shimizu et al., sex as a parameter influencing the long-term outcome of ONFH-therapy had not previously been evaluated [23]. The present study indicates that patients' sex seems to have no influence on therapy as the results of the calculated Kaplan-Meier estimator could not prove any significant sex-dependent differences in hip survival (p = 0.48). ...
Background:
Core decompression is a common surgical technique to treat osteonecrosis of the femoral head. The aim of this study is to evaluate the effect of the parameters "age" and "sex" on the outcome of this type of treatment.
Methods:
A prospective cohort study was performed. Eighty-six osteonecrotic hips with a mean follow-up of 32.5 months (± 24.8) after advanced core decompression were analysed regarding age- and sex-dependent treatment failure. Additionally, the modified Harris Hip Score and Numeric Rating Scale were compared regarding the parameters age and sex.
Results:
The mean hip survival of the male participants was 51.3 months (39.4% treatment failure), whereas females presented a longer, thus not significant, mean survival of 61.4 months (30% therapy failure; p = 0.48). The further evaluation revealed significantly better survival in the patients aged < 40 years (mean survival 66.09 months, 16% treatment failure) in comparison to those aged ≥ 40 years (mean survival 50.14 months, 46% therapy failure; p = 0.03). The modified Harris Hip Score and Numeric Rating Scale results of patients whose treatment did not fail during the study period were similar, irrespective of the patient's sex or age.
Conclusions:
The study shows that the number of therapy failures is significantly higher in older patients, with 40 years of age marking the borderline. Patients' sex does not seem to affect the outcome of treatment, and postoperative clinical scores appear to be identical with individuals not affected by therapy failure. Since age and sex are unalterable parameters, the study helps to provide valuable predictions regarding the chances of long-term hip survival after treatment of osteonecrosis.
... Furthermore, an addiction to alcohol and long drinking period were reported as risk factors for FHN. In comparing gender diference, studies indicated for males a greater frequency of alcohol-induced FHN with respect to females [20,21]. Indeed, Shimizu et al. showed a bigger susceptibility of males in developing FHN in response to alcohol consumption. ...
... Speciically, females did not develop osteonecrosis for alcohol consumption for both short-time and long-time periods. However, further investigations are needed among sex-related factors responsible for this evidence [20]. ...
Femoral head necrosis (FHN) is a disease process resulting from inadequate blood perfu-sion of subchondral bone. While the etiology of this disease is still not fully understood, there are multiple traumatic and atraumatic factors that are associated with the disease. Pathophysiology of the disease is characterized by the death of bone marrow and osteo-cytes. If left untreated, the disease may progress to joint collapse. While initial stages of the disease are asymptomatic, painful limitation of active and passive motion of the hip is eventually present. The current body of literature cannot identify an optimal treatment protocol for FHN. Postcollapse cases require surgical intervention, core decom-pression, or total hip arthroplasty. However, current strides in conservative management are being made. One of the possible conservative modalities that may efectively delay hip arthroplasty or even prevent the need for a surgical approach is hyperbaric oxygen (HBO 2) therapy. HBO 2 increases extracellular oxygen concentration and reduces cellular ischemia and edema by inducing vasoconstriction. Studies have reported radiographic improvement, reduction in pain, and increases in range of motion for early stages of the disease. Hyperbaric oxygen therapy has also been shown to stimulate angiogenesis and enhance osteoclast and osteoblast function for remodeling and repair.
... It affects patients relatively young and has significant psycho-socio-economic consequences because of its crippling nature [1,2]. The male sex seems to be more affected [3,4]. Patients with rheumatic diseases are at an increased risk for avascular necrosis [5,6] that is extended to those receiving high dose corticosteroids [5]. ...
Aim of the work: To determine the epidemiological and semiological profile of osteonecrosis of the femoral head (ONFH) during a rheumatology consultation in northern Togo. Patients and methods: The study was conducted from April 2012 to July 2016 on the files of patients with an ONFH seen in rheumatological consultation at Kara Teaching Hospital (Togo). The diagnosis was based on plain X-ray and the lesions classified according to Arlet and Ficat. No patient performed MRI. Results: Fifty-six of 2591 patients (2.16%) had an ONFH; they were 60.71% women and 39.29% men. The mean age was 41.39. ±. 15.32. years and disease duration 4.72. ±. 4.12. years. None of the patients was associated with another rheumatic disease or received corticosteroids. The pain was over the greater trochanter in 30 cases, at the groin in 24 and the buttocks in 12. Low back pain was present in 27 patients and was referred to the ipsilateral knee in 28. Radiologic lesions of ONFH were overlapping with stage II in 15 patients, stage III in 20 and stage IV in 32. Involvement was unilateral in 69.64% of cases and bilateral in 30.36%. The main risk factors of ONFH were: sickle cell disease (28.57%), hypertriglyceridemia (17.85%) and hypercholesterolemia (14.28%), alcoholism (14.28%), and diabetes in two patients. 17 patients were overweight/obese and 3 were human immunodeficiency virus (HIV) positive. Conclusion: ONFH is frequent in northern Togo and sickle cell disease is the main risk factor. An important part of evolved forms is noted in relation with a diagnostic delay.
Backgrounds
Osteonecrosis of the femoral head (ONFH) is one of the common and complicated diseases in the orthopedic clinic. Previous studies indicate that genetic factors play a crucial role in the occurrence of ONFH. This case-control study aimed to investigate the associations of MIR137HG genetic polymorphisms with the alcohol-induced ONFH risk.
Methods
A total of 731 participants were recruited to detect the effect of MIR137HG SNPs on the alcohol-induced ONFH risk in a Chinese male population. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the associations. Multifactor dimensionality reduction (MDR) was used to analyze the SNP-SNP interaction with the alcohol-induced ONFH risk.
Results
Our study showed that rs7549905 played a protective role in alcohol-induced ONFH risk (OR 0.57, p=0.045). Stratified analysis indicated that rs9440302 was associated with an increased risk of patients aged> 45 years (OR 2.00, p= 0.038), and rs7549905 showed a reduced risk in patients aged≤ 45 years (OR 0.43, p= 0.023). In addition, we found that rs9440302 and rs7554283 exhibited a significantly increased susceptibility of III-IV grade alcohol-induced ONFH patients (OR 2.34, p= 0.003; OR 2.13, p= 0.011, respectively). We also observed that rs12138817 was related to an increased risk in patients with> 21 months of course (OR 1.77, p= 0.043). Interestingly, rs17371457 showed a significant correlation with low‐density lipoprotein‐cholesterol (p= 0.040).
Conclusion
Our study suggests that MIR137HG genetic variants are associated with the alcohol-induced ONFH susceptibility in a Chinese male population, which may give scientific evidence for exploring molecular mechanisms of the alcohol-induced ONFH.
