Omaveloxolone ameliorates glucocorticoid-induced osteonecrosis of the femoral head by promoting osteogenesis and angiogenesis.

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.

[Research progress on mechanism of traditional Chinese medicine intervention in angiogenesis in prevention and treatment of nontraumatic avascular necrosis of femoral head].

Nontraumatic avascular necrosis of the femoral head(NANFH) is a common and refractory femoral head disease that causes bone death due to interruption of blood supply. Early clinical symptoms are atypical, such as hip pain and limited joint function. In the late stage, severe pain, shortening of the affected limb, claudication, and other serious symptoms are common, which se-riously affects the quality of life of patients. Therefore, it is of great significance to actively improve the clinical symptoms of NANFH to enhance the quality of life of patients. The pathogenesis of NANFH is complex, such as traumatic vascular circulatory disorders, the use of hormones or other drugs, alcoholism, and diabetes mellitus. These factors directly or indirectly lead to femoral head vascular damage, thrombosis, and coagulation system disorders, which reduce the blood supply to the acetabulum and femoral head, thus causing ischaemic death of the femoral head or even femoral head collapse. NANFH is mainly categorized as "bone impotence" and "bone paralysis" in traditional Chinese medicine(TCM). The treatment of NANFH with TCM has the characteristics and advantages of a long history, stable and reliable therapeutic effect, fewer adverse reactions, good patient tolerance, and high acceptance. Previous studies have shown that the promotion of angiogenesis is a key initiative in the prevention and treatment of NANFH, and TCM can promote fe-moral head angiogenesis by interfering with the expression of angiogenesis-related factors, which in turn can help to restore the blood supply of the femoral head and thus improve clinical symptoms of NANFH and prevent and treat NANFH. This article described the roles of blood supply interruption and angiogenesis in NANFH and the accumulated knowledge and experience of TCM in NANFH and summarized the role of angiogenesis-related factors in NANFH and the research progress on TCM intervention, so as to provide an idea for the subsequent research and a new basis for the clinical application of TCM in the treatment of NANFH.

[α2-macroglobulin alleviates glucocorticoid-induced avascular necrosis of the femoral head in mice by promoting proliferation, migration and angiogenesis of vascular endothelial cells].

OBJECTIVE: To explore the mechanism underlying the protective effect of α2-macroglobulin (A2M) against glucocorticoid-induced femoral head necrosis. METHODS: In a human umbilical vein endothelial cell (HUVEC) model with injuries induced by gradient concentrations of dexamethasone (DEX; 10-8-10-5 mol/L), the protective effects of A2M at 0.05 and 0.1 mg/mL were assessed by examining the changes in cell viability, migration, and capacity of angiogenesis using CCK-8 assay, Transwell and scratch healing assays and angiogenesis assay. The expressions of CD31 and VEGF-A proteins in the treated cells were detected using Western blotting. In BALB/c mouse models of avascular necrosis of the femoral head induced by intramuscular injections of methylprednisolone, the effects of intervention with A2M on femoral trabecular structure, histopathological characteristics, and CD31 expression were examined with Micro-CT, HE staining and immunohistochemical staining. RESULTS: In cultured HUVECs, DEX treatment significantly reduced cell viability, migration and angiogenic ability in a concentration- and time-dependent manner (P<0.05), and these changes were obviously reversed by treatment with A2M in positive correlation with A2M concentration (P<0.05). DEX significantly reduced the expression of CD31 and VEGF-A proteins in HUVECs, while treatment with A2M restored CD31 and VEGF-A expressions in the cells (P<0.05). The mouse models of femoral head necrosis showed obvious trabecular damages in the femoral head, where a large number of empty lacunae and hypertrophic fat cells could be seen and CD31 expression was significantly decreased (P<0.05). A2M treatment of the mouse models significantly improved trabecular damages, maintained normal bone tissue structures, and increased CD31 expression in the femoral head (P<0.05). CONCLUSION: A2M promotes proliferation, migration, and angiogenesis of DEX-treated HUVECs and alleviates methylprednisolone-induced femoral head necrosis by improving microcirculation damages and maintaining microcirculation stability in the femoral head.

Research progress in the pathogenesis of hormone-induced femoral head necrosis based on microvessels: a systematic review.

Hormonal necrosis of the femoral head is caused by long-term use of glucocorticoids and other causes of abnormal bone metabolism, lipid metabolism imbalance and blood microcirculation disorders in the femoral head, resulting in bone trabecular fracture, bone tissue necrosis collapse, and hip dysfunction. It is the most common type of non-traumatic necrosis of the femoral head, and its pathogenesis is complex, while impaired blood circulation is considered to be the key to its occurrence. There are a large number of microvessels in the femoral head, among which H-type vessels play a decisive role in the "angiogenesis and osteogenesis coupling", and thus have an important impact on the occurrence and development of femoral head necrosis. Glucocorticoids can cause blood flow injury of the femoral head mainly through coagulation dysfunction, endothelial dysfunction and impaired angiogenesis. Glucocorticoids may inhibit the formation of H-type vessels by reducing the expression of HIF-1α, PDGF-BB, VGEF and other factors, thus causing damage to the "angiogenesis-osteogenesis coupling" and reducing the ability of necrosis reconstruction and repair of the femoral head. Leads to the occurrence of hormonal femoral head necrosis. Therefore, this paper reviewed the progress in the study of the mechanism of hormone-induced femoral head necrosis based on microvascular blood flow at home and abroad, hoping to provide new ideas for the study of the mechanism of femoral head necrosis and provide references for clinical treatment of femoral head necrosis.

Osteotomia periacetabular de Ganz: anatomía vascular en relacion co el acetabulo y la cabeza femoral / Ganz periacetabular osteotomy: vascular anatomy in relation with the acetabulum and femoral head

Introducción: Esta presentación estudia el fundamento vascular de la técnica quirúrgica propuesta por Ganz, evaluando la relación entre esta cirugía y la anatomía vascular del acetábulo y la cabeza femoral. Materiales y métodos: La evaluación se realizó mediante el estudio de la irrigación acetabular en descripciones clásicas sobre el tema; la opinión de cirujanos reconocidos en la materia, entre ellos el profesor Ganz; el análisis de bibliografía que estuviera en desacuerdo con los conocimientos clásicos al respecto y el estudio de la irrigación mediante trabajos de disección cadavérica en dos preparados inyectados con látex coloreado. Resultados: La irrigación del acetábulo y la cabeza femoral está dada por un sistema arterial interno y otro externo, que ordena las arterias según su zona de irrigación y no según su origen. Durante la osteotomía periacetabular se lesionan varias de estas arterias. Conclusiones: Los vasos remanentes, asociados fundamentalmente con la prolífica red de anastomosis involucrada, aseguran la irrigación del acetábulo y la cabeza femoral.

Femur mineral density of broilers with femoral degeneration fed high nutritional density diets / Densidad mineral del fémur de pollos de engorde con degeneración femoral alimentados con dietas de alta densidad nutricional

A study was carried out in the experimental facilities of FMVZ/UNESP-Botucatu, with the aim of following-up the development and the incidence of femoral degeneration (FD). A total of 305 one-day-old male broilers were housed in six pens of 5m² each. A completely randomized experimental design, with 3 treatments (T1traditional nutritional density diet; T2high nutritional density diet) of 3 replicates each was applied. Femoral head of the broilers were submitted to gross examination at 0, 7, 14, 21, 28, 35, and 42 days of aged. At 42 days of age, 60 birds (30 per treatment) were submitted to the Veterinary Hospital of FMVZ to determine bone mineral density by radiography. Birds were then sacrificed for gross examination of the legs, and FD scoring. Five legs per treatment within each FD score were submitted to computed tomography for femur head integrity and bone mineral density. Treatments did not influence FD incidence, and the first gross FD lesions appeared when birds were 28 days old. It was concluded that radiographic optical densitometry and computed tomography are efficient methods to evaluate femoral degeneration, and both techniques expressed the same profile. In addition, using radiographic optical densitometry and computed tomography, these results also allowed us to establish bone mineral density value ranges within each gross FD score. These finding may provide an excellent non-invasive tool to describe femoral degeneration.

Se realizó un estudio en las instalaciones experimentales de FMVZ/UNESP-Botucatu, con el objetivo de seguir el desarrollo y la incidencia de degeneración femoral en pollos. Se utilizaron 305 polluelos de un día, machos, distribuidos en seis corrales de 5m² cada uno. Se adoptó un delineamiento experimental totalmente al azar, con dos tratamientos de 3 repeticiones cada uno. Se alimentaron las aves del T1 con dietas con densidad nutricional convencional, mientras el T2 consistió de una dieta con alta densidad nutricional. Se realizaron análisis macroscópicos de la cabeza del fémur de aves de 0, 7, 14, 21, 28, 35 y 42 días de edad. A los 42 días de edad, se llevaron 60 aves (30 por tratamiento) al Hospital Veterinario de FMVZ, para hacer radiografías para el análisis de la densidad mineral ósea. Posteriormente, se sacrificaron los pollos para el análisis macroscópico de las piernas y se atribuyeron puntajes para DF. Se seleccionaron cinco muslos por tratamiento dentro de cada puntaje de DF, que fueron sometidas a tomografía para evaluación de la integridad y de la densidad ósea de la cabeza del fémur. Los tratamientos no tuvieron influencia en la incidencia de DF, y a partir de los 28 días de vida, las aves presentaron lesiones macroscópicas. Se estableció que la densitometría ósea y la tomografía son métodos eficaces para evaluar la DF, además que ambos expresan el mismo perfil. Por otra parte, se encontraron intervalos de valores para densidad mineral ósea obtenida por densitometría óptica radiográfica y por tomografía en función de los puntajes macroscópicos de DF. Esos hallazgos son una importante herramienta no invasiva para la caracterización de degeneración femoral.

Osteonecrosis en fracturas del cuello del femur / Osteonecrosis in femoral neck fractures

Introducción: La osteonecrosis de la cabeza femoral, posterior a una fractura del cuello del fémur, se produce por la lesión vascular que ocurre en el momento de la lesión. La posibilidad de osteonecrosis suele ser un factor condicionante cuando se tiene que optar por un tratamiento, por lo tanto es frecuente que se presente la disyuntiva de preservar o no la cabeza femoral. El objetivo de este trabajo es comunicar el índice de osteonecrosis ocurrido luego del tratamiento con osteosíntesis a cielo cerrado. Materiales y métodos: Entre 1989 y 2005, se trataron mediante osteosíntesis a cielo cerrado con clavos de Leoncio Fernández 38 fracturas del cuello del fémur en 26 pacientes mujeres y 12 varones. La cirugía se realizó dentro de las primeras 24 horas de ocurrida la lesión. Veintiséis eran fracturas desplazadas (Garden III y IV) y 12, sin desplazamiento (Garden I y II). Resultados: Sólo 5 caderas de las 38 (13 por ciento) desarrollaron osteonecrosis. De las 26 fracturas con desplazamiento, 4 presentaron osteonecrosis (15 por ciento) y de las 12 sin desplazamiento, la presentó una sola (8 por ciento). Todas las fracturas consolidaron entre los 45 y los 90 días. Conclusiones: Las fracturas del cuello del fémur tratadas mediante osteosíntesis en forma temprana tienen un bajo índice de osteonecrosis. La técnica quirúrgica y el tipo de osteosíntesis utilizados pueden determinar el resultado final. Los bajos índices de osteonecrosis nos alientan, en muchas fracturas del cuello del fémur, a utilizar osteosíntesis en lugar de un reemplazo protésico

Irrigaçäo do colo e cabeça femorais no quadril artrósico / Blood supply femoral head and neck in osteoarthrosis of the hip

Um grupo de 11 espécimes obtidos de quadris artrósicos, durante sua substituiçäo, foi comparado com um grupo de 9 espécimes retirados durante autópsias de adulto sem patologia conhecida do quadril. O estudo histológico de lâminas obtidas pelo corte transversal do colo e cabeça femorais, em diversos níveis, confirmou as descriçöes de Harrison, Schajowicz e Trueta e de Trueta e Harrison. Conceitos novos, sugeridos em correlaçäo com a técnica de artroplastia de dupla taça por Freeman e Hedley, näo puderam ser confirmados