RESUMEN
Autophagy may play an important role in the occurrence and development of glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH). Lithium is a classical autophagy regulator, and lithium can also activate osteogenic pathways, making it a highly promising therapeutic agent for GC-ONFH. We aimed to evaluate the potential therapeutic effect of lithium on GC-ONFH. For in vitro experiments, primary osteoblasts of rats were used for investigating the underlying mechanism of lithium's protective effect on GC-induced autophagy levels and osteogenic activity dysfunction. For in vivo experiments, a rat model of GC-ONFH was used for evaluating the therapeutic effect of oral lithium on GC-ONFH and underlying mechanism. Findings demonstrated that GC over-activated the autophagy of osteoblasts and reduced their osteogenic activity. Lithium reduced the over-activated autophagy of GC-treated osteoblasts through PI3K/AKT/mTOR signalling pathway and increased their osteogenic activity. Oral lithium reduced the osteonecrosis rates in a rat model of GC-ONFH, and restrained the increased expression of autophagy related proteins in bone tissues through PI3K/AKT/mTOR signalling pathway. In conclusion, lithium can restrain over-activated autophagy by activating PI3K/AKT/mTOR signalling pathway and up-regulate the expression of genes for bone formation both in GC induced osteoblasts and in a rat model of GC-ONFH. Lithium may be a promising therapeutic agent for GC-ONFH. However, the role of autophagy in the pathogenesis of GC-ONFH remains controversial. Studies are still needed to further explore the role of autophagy in the pathogenesis of GC-ONFH, and the efficacy of lithium in the treatment of GC-ONFH and its underlying mechanisms.
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Autofagia , Necrosis de la Cabeza Femoral , Glucocorticoides , Litio , Osteoblastos , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Autofagia/efectos de los fármacos , Glucocorticoides/farmacología , Glucocorticoides/efectos adversos , Ratas , Necrosis de la Cabeza Femoral/inducido químicamente , Necrosis de la Cabeza Femoral/patología , Necrosis de la Cabeza Femoral/tratamiento farmacológico , Necrosis de la Cabeza Femoral/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Transducción de Señal/efectos de los fármacos , Litio/farmacología , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Masculino , Osteogénesis/efectos de los fármacos , Ratas Sprague-Dawley , Proteínas Proto-Oncogénicas c-akt/metabolismo , Modelos Animales de Enfermedad , Fosfatidilinositol 3-Quinasas/metabolismo , Cabeza Femoral/patología , Cabeza Femoral/efectos de los fármacos , Cabeza Femoral/metabolismo , Osteonecrosis/inducido químicamente , Osteonecrosis/patología , Osteonecrosis/tratamiento farmacológico , Osteonecrosis/metabolismo , Osteonecrosis/prevención & controlRESUMEN
Glucocorticoids induced osteonecrosis of the femoral head (GIONFH) is a devastating orthopedic disease. Previous studies suggested that connexin43 is involved in the process of osteogenesis and angiogenesis. However, the role of Cx43 potentiates in the osteogenesis and angiogenesis of bone marrow-derived stromal stem cells (BMSCs) in GIONFH is still not investigated. In this study, BMSCs were isolated and transfected with green fluorescent protein or the fusion gene encoding GFP and Cx43. The osteogenic differentiation of BMSCs were detected after transfected with Cx43. In addition, the migration abilities and angiogenesis of human umbilical vein endothelial cells (HUVECs) were been detected after induced by transfected BMSCs supernatants in vitro. Finally, we established GC-ONFH rat model, then, a certain amount of transfected or controlled BMSCs were injected into the tibia of the rats. Immunohistological staining and micro-CT scanning results showed that the transplanted experiment group had significantly promoted more bone regeneration and vessel volume when compared with the effects of the negative or control groups. This study demonstrated for the first time that the Cx43 overexpression in BMSCs could promote bone regeneration as seen in the osteogenesis and angiogenesis process, suggesting that Cx43 may serve as a therapeutic gene target for GIONFH treatment.
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Necrosis de la Cabeza Femoral , Glucocorticoides , Ratas , Humanos , Animales , Glucocorticoides/efectos adversos , Glucocorticoides/metabolismo , Osteogénesis , Conexina 43/metabolismo , Cabeza Femoral/metabolismo , Cabeza Femoral/patología , Necrosis de la Cabeza Femoral/inducido químicamente , Necrosis de la Cabeza Femoral/patología , Necrosis de la Cabeza Femoral/terapia , Ratas Sprague-Dawley , Regeneración Ósea , Diferenciación Celular , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/patologíaRESUMEN
With the prevalence of coronavirus disease 2019, the administration of glucocorticoids (GCs) has become more widespread. Treatment with high-dose GCs leads to a variety of problems, of which steroid-induced osteonecrosis of the femoral head (SONFH) is the most concerning. Since hypoxia-inducible factor 1α (HIF-1α) is a key factor in cartilage development and homeostasis, it may play an important role in the development of SONFH. In this study, SONFH models were established using methylprednisolone (MPS) in mouse and its proliferating chondrocytes to investigate the role of HIF-1α in cartilage differentiation, extracellular matrix (ECM) homeostasis, apoptosis and glycolysis in SONFH mice. The results showed that MPS successfully induced SONFH in vivo and vitro, and MPS-treated cartilage and chondrocytes demonstrated disturbed ECM homeostasis, significantly increased chondrocyte apoptosis rate and glycolysis level. However, compared with normal mice, not only the expression of genes related to collagens and glycolysis, but also chondrocyte apoptosis did not demonstrate significant differences in mice co-treated with MPS and HIF-1α inhibitor. And the effects observed in HIF-1α activator-treated chondrocytes were similar to those induced by MPS. And HIF-1α degraded collagens in cartilage by upregulating its downstream target genes matrix metalloproteinases. The results of activator/inhibitor of endoplasmic reticulum stress (ERS) pathway revealed that the high apoptosis rate induced by MPS was related to the ERS pathway, which was also affected by HIF-1α. Furthermore, HIF-1α affected glucose metabolism in cartilage by increasing the expression of glycolysis-related genes. In conclusion, HIF-1α plays a vital role in the pathogenesis of SONFH by regulating ECM homeostasis, chondrocyte apoptosis, and glycolysis.
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Apoptosis , Cartílago , Condrocitos , Glucocorticoides , Glucólisis , Homeostasis , Subunidad alfa del Factor 1 Inducible por Hipoxia , Metilprednisolona , Animales , Masculino , Ratones , Apoptosis/efectos de los fármacos , Cartílago/metabolismo , Cartílago/patología , Cartílago/efectos de los fármacos , Condrocitos/metabolismo , Condrocitos/efectos de los fármacos , Condrocitos/patología , Modelos Animales de Enfermedad , Matriz Extracelular/metabolismo , Cabeza Femoral/patología , Cabeza Femoral/metabolismo , Necrosis de la Cabeza Femoral/inducido químicamente , Necrosis de la Cabeza Femoral/patología , Necrosis de la Cabeza Femoral/metabolismo , Necrosis de la Cabeza Femoral/genética , Glucocorticoides/efectos adversos , Glucocorticoides/farmacología , Glucólisis/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Metilprednisolona/efectos adversos , Metilprednisolona/farmacología , Ratones Endogámicos C57BLRESUMEN
Osteonecrosis of the femoral head (ONFH) involves necrosis of bone and bone marrow of the femoral head caused by ischemia with unknown etiology. Previous genetic studies on ONFH failed to produce consistent results, presumably because ONFH has various causes with different genetic backgrounds and the underlying diseases confounded the associations. Steroid-associated ONFH (S-ONFH) accounts for one-half of all ONFH, and systemic lupus erythematosus (SLE) is a representative disease underlying S-ONFH. We performed a genome-wide association study (GWAS) to identify genetic risk factors for S-ONFH in patients with SLE. We conducted a two-staged GWAS on 636 SLE patients with S-ONFH and 95 588 non-SLE controls. Among the novel loci identified, we determined S-ONFH-specific loci by comparing allele frequencies between SLE patients without S-ONFH and non-SLE controls. We also used Korean datasets comprising 148 S-ONFH cases and 37 015 controls to assess overall significance. We evaluated the functional annotations of significant variants by in silico analyses. The Japanese GWAS identified 4 significant loci together with 12 known SLE susceptibility loci. The four significant variants showed comparable effect sizes on S-ONFH compared with SLE controls and non-SLE controls. Three of the four loci, MIR4293/MIR1265 [odds ratio (OR) = 1.99, P-value = 1.1 × 10-9)], TRIM49/NAALAD2 (OR = 1.65, P-value = 4.8 × 10-8) and MYO16 (OR = 3.91, P-value = 4.9 × 10-10), showed significant associations in the meta-analysis with Korean datasets. Bioinformatics analyses identified MIR4293, NAALAD2 and MYO16 as candidate causal genes. MIR4293 regulates a PPARG-related adipogenesis pathway relevant to S-ONFH. We identified three novel susceptibility loci for S-ONFH in SLE.
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Necrosis de la Cabeza Femoral , Lupus Eritematoso Sistémico , Esteroides , Carboxipeptidasas/genética , Proteínas Portadoras/genética , Cabeza Femoral , Necrosis de la Cabeza Femoral/inducido químicamente , Necrosis de la Cabeza Femoral/complicaciones , Necrosis de la Cabeza Femoral/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Lupus Eritematoso Sistémico/genética , MicroARNs/genética , Cadenas Pesadas de Miosina/genética , Polimorfismo de Nucleótido Simple , Esteroides/efectos adversosRESUMEN
Osteoarthritis is the most common chronic joint disease, characterized by the abnormal remodeling of joint tissues including articular cartilage and subchondral bone. However, there are currently no therapeutic drug targets to slow the progression of disease because disease pathogenesis is largely unknown. Thus, the goals of this study were to identify metabolic differences between articular cartilage and subchondral bone, compare the metabolic shifts in osteoarthritic grade III and IV tissues, and spatially map metabolic shifts across regions of osteoarthritic hip joints. Articular cartilage and subchondral bone from 9 human femoral heads were obtained after total joint arthroplasty, homogenized and metabolites were extracted for liquid chromatography-mass spectrometry analysis. Metabolomic profiling revealed that distinct metabolic endotypes exist between osteoarthritic tissues, late-stage grades, and regions of the diseased joint. The pathways that contributed the most to these differences between tissues were associated with lipid and amino acid metabolism. Differences between grades were associated with nucleotide, lipid, and sugar metabolism. Specific metabolic pathways such as glycosaminoglycan degradation and amino acid metabolism, were spatially constrained to more superior regions of the femoral head. These results suggest that radiography-confirmed grades III and IV osteoarthritis are associated with distinct global metabolic and that metabolic shifts are not uniform across the joint. The results of this study enhance our understanding of osteoarthritis pathogenesis and may lead to potential drug targets to slow, halt, or reverse tissue damage in late stages of osteoarthritis.
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Cartílago Articular , Osteoartritis , Humanos , Osteoartritis/patología , Cartílago Articular/metabolismo , Cabeza Femoral/diagnóstico por imagen , Cabeza Femoral/metabolismo , Radiografía , Aminoácidos/metabolismo , LípidosRESUMEN
With the substantial increase in the overuse of glucocorticoids (GCs) in clinical medicine, the prevalence of glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH) continues to rise in recent years. However, the optimal treatment for GC-ONFH remains elusive. Rotating magnetic field (RMF), considered as a non-invasive, safe and effective approach, has been proved to have multiple beneficial biological effects including improving bone diseases. To verify the effects of RMF on GC-ONFH, a lipopolysaccharide (LPS) and methylprednisolone (MPS)-induced invivo rat model, and an MPS-induced invitro cell model have been employed. The results demonstrate that RMF alleviated bone mineral loss and femoral head collapse in GC-ONFH rats. Meanwhile, RMF reduced serum lipid levels, attenuated cystic lesions, raised the expression of anti-apoptotic proteins and osteoprotegerin (OPG), while suppressed the expression of pro-apoptotic proteins and nuclear factor receptor activator-κB (RANK) in GC-ONFH rats. Besides, RMF also facilitated the generation of ALP, attenuated apoptosis and inhibits the expression of pro-apoptotic proteins, facilitated the expression of OPG, and inhibited the expression of RANK in MPS-stimulated MC3T3-E1 cells. Thus, this study indicates that RMF can improve GC-ONFH in rat and cell models, suggesting that RMF have the potential in the treatment of clinical GC-ONFH.
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Diferenciación Celular , Necrosis de la Cabeza Femoral , Glucocorticoides , Osteoblastos , Ratas Sprague-Dawley , Animales , Osteoblastos/metabolismo , Osteoblastos/efectos de los fármacos , Necrosis de la Cabeza Femoral/inducido químicamente , Necrosis de la Cabeza Femoral/patología , Necrosis de la Cabeza Femoral/metabolismo , Necrosis de la Cabeza Femoral/terapia , Ratas , Diferenciación Celular/efectos de los fármacos , Masculino , Campos Magnéticos , Magnetoterapia/métodos , Cabeza Femoral/patología , Cabeza Femoral/metabolismo , Modelos Animales de Enfermedad , Rotación , RatonesRESUMEN
Steroid (glucocorticoid)-induced necrosis of the femoral head (SONFH) represents a prevalent, progressive, and challenging bone and joint disease characterized by diminished osteogenesis and angiogenesis. Omaveloxolone (OMA), a semi-synthetic oleanocarpane triterpenoid with antioxidant, anti-inflammatory, and osteogenic properties, emerges as a potential therapeutic agent for SONFH. This study investigates the therapeutic impact of OMA on SONFH and elucidates its underlying mechanism. The in vitro environment of SONFH cells was simulated by inducing human bone marrow mesenchymal stem cells (hBMSCs) and human umbilical vein endothelial cells (HUVECs) using dexamethasone (DEX).Various assays, including CCK-8, alizarin red staining, Western blot, qPCR, immunofluorescence, flow cytometry, and TUNNEL, were employed to assess cell viability, STING/NF-κB signaling pathway-related proteins, hBMSCs osteogenesis, HUVECs migration, angiogenesis, and apoptosis. The results demonstrate that OMA promotes DEX-induced osteogenesis, HUVECs migration, angiogenesis, and anti-apoptosis in hBMSCs by inhibiting the STING/NF-κB signaling pathway. This experimental evidence underscores the potential of OMA in regulating DEX-induced osteogenesis, HUVECs migration, angiogenesis, and anti-apoptosis in hBMSCs through the STING/NF-κB pathway, thereby offering a promising avenue for improving the progression of SONFH.
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Necrosis de la Cabeza Femoral , Glucocorticoides , Neovascularización Fisiológica , Osteogénesis , Humanos , Angiogénesis , Apoptosis/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Dexametasona/farmacología , Cabeza Femoral/patología , Cabeza Femoral/efectos de los fármacos , Cabeza Femoral/irrigación sanguínea , Cabeza Femoral/metabolismo , Necrosis de la Cabeza Femoral/inducido químicamente , Necrosis de la Cabeza Femoral/patología , Necrosis de la Cabeza Femoral/tratamiento farmacológico , Necrosis de la Cabeza Femoral/metabolismo , Glucocorticoides/farmacología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Neovascularización Fisiológica/efectos de los fármacos , FN-kappa B/metabolismo , Osteogénesis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Triterpenos/farmacologíaRESUMEN
Femoroacetabular impingement (FAI), characterized by a pathological contact between the proximal femur and acetabulum, is a common precursor of hip osteoarthritis. Cam morphology is a bony prominence that causes FAI and frequently forms on the anterosuperior femoral head-neck junction. Despite anatomical consensus regarding the femoral head-neck junction as a boundary area covered by the articular cartilage and joint capsule, it remains unclear whether the joint capsule is continuous with the anterosuperior articular cartilage. For the anatomical consideration of cam morphology formation, this study aimed to investigate the histological characteristics of the capsular attachment on the anterosuperior femoral head-neck junction, particularly focusing on the presence or absence of continuity of the joint capsule to the articular cartilage. A total of 21 anterosuperior regions (seven hips each for the 12:00, 1:30, and 3:00 positions) from seven hips (three males and four females; mean age at death, 68.7 years) were histologically analyzed in this study for quantitative evaluation of the capsular thickness using histological sections stained with Masson's trichrome, as well as qualitative evaluation of the capsular attachment. The present study showed that the joint capsule, which folded proximally to the femoral head-neck junction from the recess, exhibited a blend of the fibrous and synovial regions. Notably, it not only continued with the superficial layer of the articular cartilage, but also attached to the articular cartilage via the fibrocartilage. This continuous region was relatively fibrous with dense connective tissue running in the longitudinal direction. The capsular thickness at the recess point (mean, 1.7 ± 0.9 mm) and those at the distal end of the articular cartilage (0.35 ± 0.16 mm) were significantly greater than the control value for the most superficial layer thickness of the articular cartilage (0.019 ± 0.003 mm) (Dunnett's T3, both p-value <0.001). Based on the fibrous continuity between the joint capsule and articular cartilage and its thickness, this study suggests the anatomical possibility that some mechanical stress can be transmitted from the joint capsule to the articular cartilage at the frequent sites of cam morphology.
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Pinzamiento Femoroacetabular , Cabeza Femoral , Cuello Femoral , Cápsula Articular , Humanos , Masculino , Femenino , Pinzamiento Femoroacetabular/patología , Cabeza Femoral/patología , Cápsula Articular/patología , Anciano , Cuello Femoral/patología , Persona de Mediana Edad , Cartílago Articular/patología , Articulación de la Cadera/patologíaRESUMEN
Enhanced adipogenic differentiation of mesenchymal stem cells (MSCs) is considered as a major risk factor for steroid-induced osteonecrosis of the femoral head (SOFNH). The role of microRNAs during this process has sparked interest. miR-486-5p expression was down-regulated significantly in femoral head bone tissues of both SONFH patients and rat models. The purpose of this study was to reveal the role of miR-486-5p on MSCs adipogenesis and SONFH progression. The present study showed that miR-486-5p could significantly inhibit adipogenesis of 3T3-L1 cells by suppressing mitotic clonal expansion (MCE). And upregulated expression of P21, which was caused by miR-486-5p mediated TBX2 decrease, was responsible for inhibited MCE. Further, miR-486-5p was demonstrated to effectively inhibit steroid-induced fat formation in the femoral head and prevented SONFH progression in a rat model. Considering the potent effects of miR-486-5p on attenuating adipogenesis, it seems to be a promising target for the treatment of SONFH.
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MicroARNs , Osteonecrosis , Animales , Ratas , Adipogénesis/genética , Diferenciación Celular/genética , Cabeza Femoral/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Osteonecrosis/inducido químicamente , Osteonecrosis/metabolismo , Esteroides/efectos adversosRESUMEN
The study was aimed to investigate microarchitecture of osteochondral junction in patients with osteonecrosis of the femoral head (ONFH). We hypothesis that there were microarchitecture alternations in osteochondral junction and regional differences between the necrotic region (NR) and adjacent non-necrotic region(ANR) in patients with ONFH. Femoral heads with ONFH or femoral neck fracture were included in ONFH group (n = 11) and control group (n = 11). Cylindrical specimens were drilled on the NR/ANR of femoral heads in ONFH group and matched positions in control group (CO.NR/ CO.ANR). Histology, micro-CT, and scanning electron microscope were used to investigate microarchitecture of osteochondral junction. Layered analysis of subchondral bone plate was underwent. Mankin scores on NR were higher than that on ANR or CO.NR, respectively (P < 0.001, P < 0.001). Calcified cartilage zone on the NR and ANR was thinner than that on the CO.NR and CO.ANR, respectively (P = 0.002, P = 0.002). Tidemark roughness on the NR was larger than that on the ANR (P = 0.002). Subchondral bone plate of NR and ANR was thicker than that on the CON.NR and CON.ANR, respectively (P = 0.002, P = 0.009). Bone volume fraction of subchondral bone plate on the NR was significantly decreasing compared to ANR and CON.NR, respectively (P = 0.015, P = 0.002). Subchondral bone plate on the NR had larger area percentages and more numbers of micropores than ANR and CON.NR (P = 0.002/0.002, P = 0.002/0.002). Layered analysis showed that bone mass loss and hypomineralization were mainly on the cartilage side of subchondral bone plate in ONFH. There were microarchitecture alternations of osteochondral junction in ONFH, including thinned calcified cartilage zone, thickened subchondral bone plate, decreased bone mass, altered micropores, and hypomineralization of subchondral bone plate. Regional differences in microarchitecture of osteochondral junction were found between necrotic regions and adjacent non-necrotic regions. Subchondral bone plate in ONFH had uneven distribution of bone volume fraction and bone mineral density, which might aggravate cartilage degeneration by affecting the transmission of mechanical stresses.
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Enfermedades Óseas Metabólicas , Cartílago Articular , Necrosis de la Cabeza Femoral , Humanos , Cabeza Femoral/patología , Densidad Ósea , Cartílago Articular/patología , Estrés Mecánico , Enfermedades Óseas Metabólicas/patologíaRESUMEN
INTRODUCTION: Vitamin D deficiency causes osteoporosis, bone mineralization disorders, and osteomalacia. Osteomalacia is diagnosed using blood biochemical tests, clinical symptoms, and imaging; however, accurate detection of mineralization disorders requires tissue observation. We investigated the prevalence of bone mineralization disorders and their relationship with serum 25-hydroxyvitamin D (25OHD) levels in patients with untreated osteoporosis with femoral neck fractures. MATERIALS AND METHODS: A non-demineralized specimen was prepared from the femoral head removed during surgery in 65 patients. Bone histomorphometry of cancerous bone in the femoral head center was conducted. Osteoid volume per bone volume (OV/BV) and osteoid thickness (O.Th) were measured as indicators of mineralization disorder. RESULTS: The mean serum 25OHD level (11.9 ± 5.7 ng/mL) was in the deficiency range (< 12 ng/mL). There were no clinically diagnosed cases of osteomalacia (OV/BV > 10% and O.Th > 12.5 µm); however, one case of mineralization disorder, considered histologically pre-osteomalacia (OV/BV > 5% and O.Th < 12.5 µm), was observed (OB/BV, 17.6%; O.Th, 12.3 µm). Excluding this case, those with severe (25OHD < 12 ng/mL, at risk of osteomalacia; n = 39) and non-severe deficiency (25OHD ≥ 12 ng/mL; n = 25) did not significantly differ in OV/BV (%; 0.77 ± 0.54 vs. 0.69 ± 0.38, p = 0.484) or O.Th (µm; 5.32 ± 1.04 vs. 5.13 ± 0.78, p = 0.410). Further, 25OHD and OV/BV were not significantly correlated (R = - 0.124, p = 0.327). CONCLUSION: This is the first study in the twenty-first century to examine serum 25OHD concentrations and bone mineralization disorders in Japanese patients with osteoporosis. The results indicate that vitamin D deficiency does not necessarily cause bone mineralization disorders and rarely leads to osteomalacia.
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Fracturas del Cuello Femoral , Osteomalacia , Osteoporosis , Deficiencia de Vitamina D , Vitamina D/análogos & derivados , Humanos , Estudios Transversales , Osteomalacia/patología , Densidad Ósea , Calcifediol , Deficiencia de Vitamina D/complicaciones , Cabeza Femoral/patologíaRESUMEN
RESEARCH HIGHLIGHTS: Large number of bacteria isolated from femoral heads of clinically healthy broilers.The prevailing taxa in femoral heads were Escherichia/Shigella and Enterococcus spp.Continuous presence of bacteria in blood and liver of clinically healthy broilers.Enterobacteriaceae, Enterococcaceae, and Staphylococcaceae prevail in blood and liver.
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Cabeza Femoral , Enfermedades de las Aves de Corral , Humanos , Animales , Enterobacteriaceae , Pollos , Enterococcaceae , Bacterias , Enfermedades de las Aves de Corral/microbiologíaRESUMEN
BACKGROUND: The imbalance between osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is not only the primary pathological feature but also a major contributor to the pathogenesis of steroid-induced osteonecrosis of the femoral head (SONFH). Cellular senescence is one of the main causes of imbalanced BMSCs differentiation. The purpose of this study was to reveal whether cellular senescence could participate in the progression of SONFH and the related mechanisms. METHODS: The rat SONFH model was constructed, and rat BMSCs were extracted. Aging-related indicators were detected by SA-ß-Gal staining, qRT-PCR and Western Blot experiments. Using H2O2 to construct a senescent cell model, and overexpressing and knocking down miR-601 and SIRT1 in hBMSCs, the effect on BMSCs differentiation was explored by qRT-PCR, Western Blot experiment, oil red O staining (ORO), alizarin red staining (ARS), and luciferase reporter gene experiment. A rat SONFH model was established to test the effects of miR-601 and metformin in vivo. RESULTS: The current study showed that glucocorticoids (GCs)-induced BMSCs senescence, which caused imbalanced osteogenesis and adipogenesis of BMSCs, was responsible for the SONFH progression. Further, elevated miR-601 caused by GCs was demonstrated to contribute to BMSCs senescence through targeting SIRT1. In addition, the anti-aging drug metformin was shown to be able to alleviate GCs-induced BMSCs senescence and SONFH progression. CONCLUSIONS: Considering the role of BMSCs aging in the progression of SONFH, this provides a new idea for the prevention and treatment of SONFH.
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Células Madre Mesenquimatosas , Metformina , MicroARNs , Osteonecrosis , Animales , Ratas , Cabeza Femoral , Glucocorticoides , Peróxido de Hidrógeno , MicroARNs/genética , Sirtuina 1/genéticaRESUMEN
BACKGROUND: Avascular osteonecrosis of the femoral head (AVN) often results in total hip arthroplasty (THA). The cause for increased THA revision rates among patients with AVN is not yet fully understood. PURPOSE: To perform a comparative radiological analysis of implant integration between patients with AVN and osteoarthritis (OA). MATERIAL AND METHODS: After a matched pair analysis of 58 patients, 30 received THA due to OA, 28 due to AVN. X-ray images were evaluated after one week ("baseline") and on average 37.58 months postoperatively ("endline"). The prosthesis was grouped into 10 regions of interest (ROI): seven femoral and three acetabular. Incidence, width, and extent of "radiolucent lines" were measured within each zone. RESULTS: Between baseline and endline, width and extent progressed more noticeably in all femoral and acetabular zones among patients with AVN. In femoral ROI 1, the width increased in 40% of AVN cases compared to 6.7% of OA cases. For acetabular ROI 3, the width increased in 26.7% of AVN cases compared to no perceived changes in the OA group. No signs of prosthetic loosening were found in the AVN group. CONCLUSION: The increase of width and extent of radiolucent lines over time in patients with AVN could be a sign of lack of osteointegration. However, prosthetic loosening in absence of clinical symptoms cannot be deduced from radiological findings after medium-term postoperative follow-up. Further long-term studies are required to monitor how radiolucent lines develop in respect to long-term implant loosening. Dependent on bone quality, individually adapted reaming and broaching of the implant site are recommended.
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Artroplastia de Reemplazo de Cadera , Necrosis de la Cabeza Femoral , Prótesis de Cadera , Osteoartritis , Humanos , Prótesis de Cadera/efectos adversos , Necrosis de la Cabeza Femoral/diagnóstico por imagen , Necrosis de la Cabeza Femoral/cirugía , Cabeza Femoral , Resultado del Tratamiento , Falla de Prótesis , Estudios RetrospectivosRESUMEN
BACKGROUND: In total hip arthroplasty (THA) after failed transtrochanteric rotational osteotomy (TRO) for osteonecrosis of the femoral head (ONFH), deformity of the proximal femur has been reported to affect stem placement. The aims of this study were to evaluate the morphological changes in the proximal femur, muscle atrophy, and soft tissue thickening in THA after TRO and the clinical outcomes. METHODS: The TRO group included 17 patients (18 hips) who underwent THA after failed TRO. The control group included 21 patients (28 hips) who underwent primary THA for ONFH. To evaluate the deformity of the proximal femur before THA, we measured the anteroposterior and mediolateral diameters of the femur on computed tomographic slices 5 mm proximal to the lesser trochanter. To evaluate muscle atrophy and soft tissue thickening, we measured the thicknesses of the psoas major, iliac, and gluteus medius muscles and the anterior capsule of the hip joint. RESULTS: The ratio of the anteroposterior to mediolateral diameters of the proximal femur was significantly greater in the TRO group (p < 0.01). The thicknesses of the muscles did not differ between the two groups, whereas the anterior capsule was significantly thicker in the TRO group (p < 0.05). Varus or valgus stem alignment (> 3°) was frequent in the TRO group (p < 0.01). CONCLUSIONS: The round shape of the proximal femur was deformed after TRO compared with primary THA for ONFH, which may have caused malposition of the stem. In addition, we should pay attention to anterior protrusion of the proximal femur and thickening of the anterior capsule.
Asunto(s)
Artroplastia de Reemplazo de Cadera , Osteonecrosis , Humanos , Artroplastia de Reemplazo de Cadera/efectos adversos , Cabeza Femoral , Atrofia Muscular , OsteotomíaRESUMEN
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.
Asunto(s)
Fracturas del Cuello Femoral , Fenofibrato , Osteonecrosis , Adulto , Anciano , Femenino , Masculino , Humanos , Persona de Mediana Edad , Cabeza Femoral/diagnóstico por imagen , Cabeza Femoral/cirugía , Fracturas del Cuello Femoral/diagnóstico por imagen , Fracturas del Cuello Femoral/cirugía , Necrosis , Tornillos Óseos/efectos adversosRESUMEN
Osteochondral autograft transplantation (OAT) has been commonly applied in the knee and ankle while the technique has not yet been a popularity in the femoral head. In this article, we present a 28-year-old female patient, who has a history of 1-year-use of glucocorticoid in the treatment of idiopathic thrombocytopenic purpura, with steroid-induced osteonecrosis of the femoral head (SONFH). She underwent surgical hip dislocation, osteochondroplasty, OAT, and internal fixation. Her Harris Hip Score improved from 64 to 82 in 36 months to follow-up. The case is valuable considering that a single, instead of several, 1.5 cm autograft was harvested from the non-bearing part of the same femoral head. This modification dispensed with the need of surgery for harvesting autograft from knee or ankle and reduced the structural vulnerability brought by the multihole donor part of the femoral head.
Asunto(s)
Osteonecrosis , Púrpura Trombocitopénica Idiopática , Humanos , Femenino , Adulto , Cabeza Femoral/diagnóstico por imagen , Cabeza Femoral/cirugía , Autoinjertos , Trasplante Óseo/métodos , Osteonecrosis/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: To analyze the risk factors for the development of avascular necrosis (AVN) of the femoral head after reduction surgery in children with developmental hip dysplasia (DDH), and to establish a prediction nomogram. METHODS: The clinical data of 134 children with DDH (169 hips) treated with closure reduction or open reduction from December 2016 to December 2019 were retrospectively analyzed. Independent risk factors for AVN after DDH reduction being combined with cast external immobilization were determined by univariate analysis and multivariate logistic regression and used to generate nomograms predicting the occurrence of AVN. RESULTS: A total of 169 hip joints in 134 children met the inclusion criteria, with a mean age at surgery of 10.7 ± 4.56 months (range: 4-22 months) and a mean follow-up duration of 38.32 ± 27.00 months (range: 12-94 months). AVN developed in 42 hip joints (24.9%); univariate analysis showed that the International Hip Dysplasia Institute (IHDI) grade, preoperative development of the femoral head ossification nucleus, cartilage acetabular index, femoral head to acetabular Y-shaped cartilage distance, residual acetabular dysplasia, acetabular abduction angle exceeding 60°, and the final follow-up acetabular index (AI) were associated with the development of AVN (P < 0.05). Multivariate logistic regression analysis showed that the preoperative IHDI grade, development of the femoral head ossification nucleus, acetabular abduction angle exceeding 60°, and the final follow-up AI were independent risk factors for AVN development (P < 0.05). Internal validation of the Nomogram prediction model showed a consistency index of 0.833. CONCLUSION: Preoperative IHDI grade, preoperative development of the femoral head ossification nucleus, final AI, and acetabular abduction angle exceeding 60° are risk factors for AVN development. This study successfully constructed a Nomogram prediction model for AVN after casting surgery for DDH that can predict the occurrence of AVN after casting surgery for DDH.
Asunto(s)
Displasia del Desarrollo de la Cadera , Necrosis de la Cabeza Femoral , Nomogramas , Humanos , Masculino , Femenino , Necrosis de la Cabeza Femoral/etiología , Necrosis de la Cabeza Femoral/cirugía , Necrosis de la Cabeza Femoral/diagnóstico por imagen , Factores de Riesgo , Estudios Retrospectivos , Displasia del Desarrollo de la Cadera/cirugía , Displasia del Desarrollo de la Cadera/diagnóstico por imagen , Lactante , Cabeza Femoral/cirugía , Cabeza Femoral/diagnóstico por imagen , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Luxación Congénita de la Cadera/cirugía , Luxación Congénita de la Cadera/diagnóstico por imagen , Estudios de SeguimientoRESUMEN
Femoral head varus is an important complication in intertrochanteric fracture patients treated with proximal femoral nail anti-rotation (PFNA) fixation. Theoretically, extending the length of the intramedullary nail could optimize fixation stability by lengthening the force arm. However, whether extending the nail length can optimize patient prognosis is unclear. In this study, a review of imaging data from intertrochanteric fracture patients with PFNA fixation was performed, and the length of the intramedullary nail in the femoral trunk and the distance between the lesser trochanter and the distal locking screw were measured. The femoral neck varus status was judged at the 6-month follow-up. The correlation coefficients between nail length and femoral neck varus angle were computed, and linear regression analysis was used to determine whether a change in nail length was an independent risk factor for femoral neck varus. Moreover, the biomechanical effects of different nail lengths on PFNA fixation stability and local stress distribution have also been verified by numerical mechanical simulations. Clinical review revealed that changes in nail length were not significantly correlated with femoral head varus and were also not an independent risk factor for this complication. In addition, only slight biomechanical changes can be observed in the numerical simulation results. Therefore, commonly used intramedullary nails should be able to meet the needs of PFNA-fixed patients, and additional procedures for longer nail insertion may be unnecessary.
Asunto(s)
Clavos Ortopédicos , Fijación Intramedular de Fracturas , Fracturas de Cadera , Humanos , Fenómenos Biomecánicos/fisiología , Fijación Intramedular de Fracturas/instrumentación , Fijación Intramedular de Fracturas/métodos , Fijación Intramedular de Fracturas/efectos adversos , Femenino , Masculino , Anciano , Fracturas de Cadera/cirugía , Fracturas de Cadera/diagnóstico por imagen , Cabeza Femoral/cirugía , Cabeza Femoral/diagnóstico por imagen , Anciano de 80 o más Años , Factores de Riesgo , Persona de Mediana Edad , Simulación por ComputadorRESUMEN
BACKGROUND: Postoperative low back pain (LBP) following total hip arthroplasty (THA) is classified as secondary hip-spine syndrome. The purpose of this study was to explore the correlations between cup orientation of THA and postoperative LBP in patients with osteonecrosis of the femoral head (ONFH). METHODS: A retrospective cohort study included 364 ONFH patients who underwent bilateral THA between January 2011 and December 2020. Among them, 53 patients (14.6%) experienced postoperative LBP at the end of follow-up and were designated as pain group (PG). A control group (CG) consisting of 106 patients with similar age, sex, and body mass index (BMI) to those in the PG was selected. Postoperative LBP in the PG was assessed using the visual analogue scale (VAS). Demographic data, clinical information, and radiographic criteria were evaluated as potential predictors of LBP. RESULTS: Patients in PG (mean age, 47.3 years [range, 27 to 75 years]; 42 [79%] male) had a mean VAS score of 4.6 (range, 1 to 9) compared with 0 for the patients in CG (mean age, 47.6 years [range, 19 to 77 years]; 84 [79%] male). There were no significant differences in clinical data between the two groups (p > 0.05). Preoperative radiographic variables also showed no significant differences between the PG and CG (p > 0.05). However, the postoperative inclination, anteversion, and standing ante-inclination (AI) were significantly lower in the PG compared to the CG, whereas the sitting and standing sacral slope (SS) were significantly higher (p < 0.05). Moreover, the variations in standing AI, standing and sitting pelvic tilt (PT) were significantly lower in the PG compared to the CG, while the variations in standing and sitting SS and lumbar lordosis (LL) were significantly higher (p < 0.05). The variation in standing AI in the PG showed a significantly correlation with the variation of standing SS, standing PT, and LL (p < 0.05). CONCLUSION: Postoperative LBP in ONFH patients after bilateral THA is significantly associated with the intraoperative cup orientation. The variation in standing AI is correlated with the variations in standing SS, standing PT, and LL, potentially contributing to the development of postoperative LBP.