The physiopathology of avascular necrosis of the femoral head: an update

Guerado, Enrique; Caso, Enrique

doi:10.1016/s0020-1383(16)30835-x

Cited by 125 publications

(115 citation statements)

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“…Osteonecrosis of the femoral head (ONFH) is a progressive degenerative disorder of the hip characterized by subchondral bone microfractures and subsequent collapse of the femoral head, eventually leading to dysfunction of the hip joint [1]. ONFH poses a huge socioeconomic burden, usually affecting young to middle aged individuals, with ~67% of asymptomatic patients rapidly progressing to symptomatic stages and thus requiring total hip arthroplasties (THA) [2].…”

Section: Introductionmentioning

confidence: 99%

“…The pathophysiologic mechanisms underlying steroid-induced ONFH are not fully understood. Recent studies suggest that the onset of ONFH is initiated by impaired microcirculation and necrosis of osteocytes, with magnetic resonance imaging (MRI) detecting pools of edema [1,8], but without noticeable changes in subchondral bone microstructure, as assessed by computed tomography (CT). Following bone necrosis, a repair process ensues whereby osteoclast-mediated bone resorption surpasses bone formation by osteoblasts, leading to net loss of subchondral trabecular bone [9].…”

Section: Introductionmentioning

confidence: 99%

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Steroid-induced osteonecrosis of the femoral head reveals enhanced reactive oxygen species and hyperactive osteoclasts

Chen

Liu

et al. 2020

Int. J. Biol. Sci.

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Steroid-induced osteonecrosis of the femoral head (ONFH) is a progressive bone disorder which typically results in femoral head collapse and hip joint dysfunction. It is well-accepted that abnormal osteoclast activity contributes to loss of bone structural integrity and subchondral fracture in ONFH. However, the pathophysiologic mechanisms underlying the recruitment and hyperactivation of osteoclasts in ONFH remain incompletely understood. We assessed the changes of reactive oxygen species (ROS) level and subsequent osteoclast alterations in steroid-induced osteonecrotic femoral heads from both patients and rat ONFH models. When compared with healthy neighboring bone, the necrotic region of human femoral head was characterized by robust up-regulated expression of osteoclast-related proteins [cathepsin K and tartrate-resistant acid phosphatase(TRAP)] but pronounced down-regulation of antioxidant enzymes (catalase, γ-glutamylcysteine synthetase [γ-GCSc], and superoxide dismutase 1 [SOD1]). In addition, the ratio of TNFSF11 (encoding RANKL)/TNFRSF11B (encoding OPG) was increased within the necrotic bone. Consistently, in rat ONFH models induced by methylprednisolone (MPSL) and imiquimod (IMI), significant bone loss in the femoral head was observed, attributable to increased numbers of TRAP positive osteoclasts. Furthermore, the decreased expression of antioxidant enzymes observed by immunoblotting was accompanied by increased ex-vivo ROS fluorescence signals of dihydroethidium (DHE) in rat ONFH models. Therefore, this study lends support to the rationale that antioxidant agents may be a promising therapeutic avenue to prevent or mitigate the progression of steroid-induced ONFH by inhibiting ROS level and hyperactive osteoclasts.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Steroid-induced osteonecrosis of the femoral head reveals enhanced reactive oxygen species and hyperactive osteoclasts

Chen

Liu

et al. 2020

Int. J. Biol. Sci.

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“…The mechanisms by which HIV induces epiphyseal necrosis are complex. Both role of HIV and antiretroviral therapy are evocated [1][2][3]15]. High serum IgE levels and loss of working ability in advance of osteonecrosis appeared for the first time as possible predictors of osteonecrosis in HIV patients, while long-term exposure to steroids, combined hyperlipemia and chronic treatment with other drugs in addition to antiretrovirals were confirmed.…”

Section: Discussionmentioning

confidence: 99%

“…Factors favouring necrosis of the femoral head are mainly represented by sickle cell disease, diabetes, alcoholism, corticotherapy, dyslipidaemia, aeroembolism, systemic lupus erythematosus, and upper extremity trauma of the femur [1,2]. In sub-Saharan Africa, hemoglobinopathies are by far the most important etiological factor of this necrosis, which is one of the most serious functional complications [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Epiphyseal Necrosis in Patients with HIV Infection and Free from Sickle Cell Disease

Es¹,

Houzou²,

Kakpovi³

et al. 2018

J Autoimmune Disord

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We report a series of 17 cases of epiphyseal necrosis observed in nine women aged 40 years on average. These nine patients, with HIV1 infection, were free from other risk factors of bone necrosis, especially SS and sickle cell disease. The necrosis affected the two femoral heads in 6 patients, one femoral head in one patient, one humeral head in one patient, and the two femoral heads and one humeral head in the last patient. The necrosis revealed HIV1 infection in 4 patients. It has complicated the course of HIV1 infection in other 5 patients, despite antiretroviral therapy.These observations argue in favor of the etiological role of HIV infection in the occurrence of epiphyseal necrosis. The relatively young age of the patients and the high number of bilateral involvement testify to the severity of the necrosis induced by HIV.

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“…Avascular necrosis of the femoral head (ANFH), an uncommon disorder that occurs most frequently between the ages of 30-60 years, is characterized by apoptosis of bone cells resulting from disruption of microcirculatory blood flow to the femoral head, eventually leading to decreased local pH (acidification) (Bolland et al, 2010;Guerado and Caso, 2016). Development of ANFH is a complex process involving multiple factors, pathways, and stages.…”

Section: Introductionmentioning

confidence: 99%

OGR1 mediates the inhibitory effects of acidic environment on proliferation and angiogenesis of endothelial progenitor cells

Ding

Zhang

et al. 2019

Cell Biology International

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Ovarian cancer G-protein-coupled receptor 1 (OGR1), an acid-sensitive receptor, plays a key proton-sensing role through stimulation of inositol phosphate formation. Avascular necrosis of the femoral head is characterized by apoptosis of bone cells mainly resulting from deficient local blood perfusion, eventually leading to acidification with disruption of endothelial progenitor cells' (EPCs) function. However, whether EPCs express OGR1 has not been demonstrated. This study attempted to whether OGR1 mediates the effects of acid on proliferation, migration, and angiogenesis in EPCs. FITC-UEA-I and Dil-Ac-LDL double-staining methods were used to identify EPCs. Expression of OGR1 was analyzed by RT-PCR (reverse transcription PCR) and western blot after incubation in media ranging in pH, cell counting kit-8 and cell cycle analysis were used to analyze proliferation and cell cycle distribution. Scratch test, transwell migration assay, and tube formation experiments were performed to analyze migration and vascularization of EPCs after silencing OGR1 with small interfering RNA (siRNA). The result show EPCs were positive for FITC-UEA-I and Dil-Ac-LDL double-staining and expressed OGR1. The expression of OGR1 increased gradually with decreased pH and was highest in pH 6.4 medium. Incubation in pH 6.4 medium inhibited proliferation of EPCs and caused cell cycle arrest. Silencing of OGR1 using siRNA partially reversed the effect of acidic environment on EPCs. Migration and angiogenesis of EPCs were inhibited in pH 6.4 medium, and silencing of OGR1 partially reversed this effect. The results demonstrated expression of OGR1 in EPCs, and the OGR1 mediated the effects of acidic environment on proliferation, migration, and angiogenesis of EPCs.Keywords: acidic environment; avascular necrosis of the femoral head; endothelial progenitor cell; ovarian cancer G-protein-coupled receptor 1Abbreviations: ANFH, avascular necrosis of the femoral head; BSA, bovine serum albumin; EPCs, endothelial progenitor cells; FBS, fetal bovine serum; GPCR, G-protein-coupled receptors; OGR1, ovarian cancer G-protein-coupled receptor 1; PBS, phosphate-buffered saline; PI, propidium iodide; TFx, trochanteric fractures Shenglong Ding, Ji Xu, and Qichen Zhang contributed equally to this work.

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The physiopathology of avascular necrosis of the femoral head: an update

Cited by 125 publications

References 126 publications

Steroid-induced osteonecrosis of the femoral head reveals enhanced reactive oxygen species and hyperactive osteoclasts

Steroid-induced osteonecrosis of the femoral head reveals enhanced reactive oxygen species and hyperactive osteoclasts

Epiphyseal Necrosis in Patients with HIV Infection and Free from Sickle Cell Disease

OGR1 mediates the inhibitory effects of acidic environment on proliferation and angiogenesis of endothelial progenitor cells

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