Aseptic necrosis of the femoral head, or ischemic necrosis of the femoral head (ANFH), is a lesion caused by poor local blood flow to the femoral head, resulting in further bone ischemia, increased intraosseous pressure, degeneration and necrosis of normal bone structure, fracture of bone trabeculae, and collapse of the femoral head, and can occur at any age, most often between 31 and 60 years old. In 1988, there were 2,500-3,000 cases of osteolytic osteonecrosis, disintegrative osteonecrosis, sclerotic osteonecrosis, hypertrophic osteonecrosis, rigid osteonecrosis, and ultrastructural variant osteonecrosis in Japan and 15,000-20,000 new patients in the United States in 1992. Although there are no national statistics in China, the literature is gradually increasing. Because of its high incidence and unpromising prognosis, it has attracted widespread attention from the medical community. At present, with more and more extensive and in-depth research on the pathogenesis and treatment of ANFH, people have basically formed a clearer understanding of it, but there are still many details and the biological mechanism of specific lesions are not known.
1. High-risk factors for the occurrence of ANFH
The etiology of aseptic necrosis of the femoral head is complex, and its pathogenesis involves osteoclastic factors, arterial factors, venous factors, extravascular factors in the bone, and neurovascular factors. In addition to trauma as the more obvious cause, it has been found in recent years that hormone consumption, excessive alcohol consumption, smoking, and high blood lipids also play an important role in the occurrence of ANFH.
In recent years, statistics have shown that the high-risk groups of ANFH include.
1.1 People with long-term glucocorticoid application
Since the first report by Pietrogrand in 1957, the number of cases of ischemic necrosis of the femoral head due to massive and long-term application of glucocorticoids has climbed to the first among all ischemic necrosis of the femoral head. A significant proportion of health care workers infected with SARS after World War I in 2003 were reported to have developed varying degrees of ANFH symptoms after receiving high doses of hormone therapy.
The following diseases cause patients to take large amounts of glucocorticoids for long periods of time.
1.1.1 Collagen diseases SLE: Ono K et al. reported:Treatment of lupus erythematosus with hormones at 30 mg of prednisone daily resulted in ANFH in 9 of 62 patients (14.1%) after 5 years; Zabinski et al. reported ANFH in 66 of 507 patients treated with prednisone 8 mg daily for rheumatoid arthritis (12.1%) Dermatomyositis, nodular arteriosclerosis, scleroderma, etc. The rate of femoral necrosis occurring with hormonal treatment varies.
1.1.2 Skin diseases aspergillosis, eczema, urticaria, psoriasis, exfoliative dermatitis
1.1.3 Hematologic diseases
1.1.4 Metabolic diseases Gout
1.1.5 respiratory diseases interstitial lung fibrosis asthma, etc.
1.1.6 Urological diseases Glomerulonephritis, post-transplantation, etc.
Fink et al. reported 43 cases of renal transplantation patients after 3 months of post-transplantation hormone therapy, 4 people 6 hip femoral head necrosis, necrosis rate of 9.3%
1.1.7 Neurological diseases such as polyneuritis, rheumatoid arthritis, peripheral neuritis.
1.1.8 Endocrine system such as hypopituitarism Hyperaldosteronism, etc.
1.1.9 Diseases of the reticuloendothelial system such as malignant reticulum, malignant lymphoma.
Enrici RM et al. reported that treatment of Hodgkin’s disease with hormones
disease in 784 individuals with a mean follow-up of 35 months, 9 had ANFH, with an incidence
1.15 %
1.1.10 Other diseases such as allergic rhinitis, acute cold, back and leg pain are also at risk
1.2 Long-term heavy drinkers and smokers
With the development of society, people interact more and more frequently, long-term heavy drinking is sometimes inevitable, and alcoholics are fond of alcohol, drinking without restraint. These factors lead to more and more patients with alcoholic ANFH. Smokers are also increasing, and research shows that smoking and ANFH are also closely related.
1.3 People with a history of hip trauma
The rapid development of transportation, transportation means are changing day by day, and the incidence of traffic accidents is increasing year by year. Fracture of the femoral neck, hip dislocation or hip trauma without fracture dislocation caused by carelessness in life, work and sports can cause damage to the blood vessels supplying the femoral head and lay a great hidden danger for future femoral head necrosis.
1.4 Others
Diving, flight crew, obesity, hypertension, diabetes, atherosclerosis, gout, radiotherapy, post-burn, hemoglobinopathies, etc. are also high-risk groups for ANFH.
2.Pathological mechanism
2.1 Trauma to the hip
Femoral neck fractures complicated by femoral head necrosis are the most common, accounting for about 30% of such fractures. K.E. Nikolopoulos et al. reported that among 84 patients with femoral neck fracture after internal fixation, ANFH occurred in 9 of 46 patients without displaced fracture and 2 with bone discontinuity after an average follow-up of 4.7 years; among 35 patients with displaced fracture, ANFH occurred in 15 and bone discontinuity occurred in 6.
Since the concept of non-traumatic femoral head necrosis was first introduced by Frenchman Welfling in 1951, the research on femoral head necrosis caused by factors other than trauma has become more and more extensive.
2.2 Hormone
After years of animal experiments and clinical research, many theories and hypotheses have been formed, among which the lipid embolism theory, intraosseous hypertension theory, osteoclastic fat deposition theory, microvascular injury theory, osteoporosis theory, cytotoxic action theory, vascular and hemodynamic theory, etc. have been accepted to some extent.
2.2.1 Fat embolism theory
Phemister first proposed the fat embolism theory as a possible cause of bone ischemia, Jones, Takuaki
Yamamoto domestic Wang Kunzheng, Huang Gongyi, Li Zirong, etc. have found a large number of fat emboli in the necrotic femoral head of clinical patients or in the experimental femoral head necrosis bone in animals, the emboli are located in the terminal artery, also can be because of intravascular pressure through the capillaries into the small vein side, because the microcirculation of bone is semi-closed, the pipeline system within the hard shell, unlike the microcirculation of other tissues have expansion Because the microcirculation of bone is semi-closed, the pipeline system inside the hard shell, unlike the microcirculation of other tissues, has no room for expansion, the vasodilation is limited by the bone tissue and loses its compensatory capacity, so when fat emboli form, the vascular pressure increases and blocks.
2.2.2 Osteoclastic fatty necrosis theory
Moran believes that osteocyte fatty degeneration is the main factor of ANFH. In high magnification electron microscopy, lipid deposition in osteocytes can be divided into three stages: 1. early stage Lipid deposition in the interstitium outside the osteocyte, which can be seen as a pseudopod; 2. middle stage Lipid deposition inside and outside the osteocyte simultaneously, which is the result of active phagocytosis and encapsulation of the gradually increasing extracellular lipid by the osteocyte; 3. late stage Lipid deposition inside the osteocyte.
Patients with hyperlipidemia are also prone to ANFH, however, the exact mechanism of how lipids cross the cell membrane and enter the cytoplasm is still not precisely understood.
2.2.3 Intraosseous hypertension and venous stasis theory
Larson et al. reported a close association between increased intraosseous pressure and osteonecrosis as early as 1938, and Ficat et al. reported that 91.7% of patients with stage I and II femoral head necrosis had stopped necrosis and improved after decompression surgery at an average follow-up of 7.9 years. The blood flow velocity in the femoral head of the experimental and control groups was measured by radioactive particle technique and found to be significantly different. Moreover, the microcirculatory anatomy of the femoral head showed that the number of veins exceeded the number of arteries several times, and blood was easily stagnated. These further suggest that intraosseous hypertension and slowed blood flow are indeed inevitably associated with hormonal ischemic necrosis of the femoral head.
2.2.4 Microvascular injury theory
Hormone use causes hyperlipidemia, lipolysis, and increased free fatty acids (FFA) in the blood, combined with increased prostaglandin E2 in the blood and bone, leading to vascular inflammation and damage. The small arteries in the femoral head are the terminal arteries, and once damaged, the collateral circulation is difficult to compensate, resulting in ischemia and leading to ANFH.Animal experiments and clinically resected specimens have shown structural destruction of small arteries in subchondral bone and cancellous bone in osteonecrotic specimens, mainly manifested by degenerative changes in the middle layer of the artery, smooth muscle cell necrosis, elastic fiber disruption and intimal hyperplasia.Jones suggested that due to the fatty cell metabolism and morphological changes in the bone marrow, the arterial wall is damaged. Jones believes that due to the metabolic and morphological changes of the cells in the bone marrow, blockage of the terminal arteries and damage to the endothelial cells, elevated PGE2 and TXA2 cause increased platelet activity, resulting in intravascular coagulation, secondary fibrinolysis, ischemia-reperfusion injury, and oxygen free radical damage to the endothelial cells, resulting in microscopic hemorrhage between bone marrow cells and extravasation of red blood cells with iron-containing heme deposits. Short-term intake of large amounts of hormones can cause abnormal blood rheology. This is manifested as a significant increase in whole blood viscosity, plasma viscosity and erythrocyte aggregation, and a hypercoagulable state of blood. This leads to local ischemia and hypoxia and acidosis, platelet aggregation, and intravascular coagulation (IC), which can cause vascular occlusion without the presence of thrombus and lead to ANFH.
2.2.5 Osteoporosis theory
Hormones can reduce the synthesis and secretion of sex hormones in the ovaries, testes and adrenal glands, reduce gastrointestinal calcium absorption, increase renal calcium excretion, indirectly stimulate hyperparathyroidism, cause high blood calcium in the body, and make the intestinal absorption of calcium impaired, thus further reducing bone mass. At the same time, hormones can directly inhibit the function of osteoblasts and directly stimulate the activity of osteoclasts, increasing the sensitivity of bone tissue to PTH and 1,25-(OH)2-D3, resulting in overall bone salt loss, osteoporosis, and minor fractures of bone trabeculae. Under prolonged weight bearing, the stress area collapses and bone marrow cells and capillaries are compressed, leading to ANFH
2.2.6 Cytotoxic effects
Warner et al. suggest that hormone-induced ANFH is a direct cytotoxic effect of hormones on femoral bone cells.
2.3 Excessive alcohol consumption
The mechanisms of alcoholic osteonecrosis occurrence are still inexact mainly the following theories.
2.3.1 Fat embolism theory
Alcohol consumption can lead to hyperlipidemia, and when the fatty material in the peripheral circulation increases and gathers into fat globules, the blood flow becomes sluggish and embolizes in the microcirculatory arteries of the femoral head, leading to ANFH.
2.3.2 Disorders of lipid metabolism
The increase of alcohol metabolites in the body can increase free radicals leading to a decrease in the activity of SOD, one of the main scavengers of free radicals. Own radicals have a strong role in triggering lipid peroxidation, resulting in enhanced LPO development and dysfunction of membrane receptors, proteases and ion channels. The cell membrane and subcellular organelles are the main sites of peroxisomal damage, which leads to vascular endothelial cell damage, fibrous degeneration and atherosclerosis of small arteries by affecting the permeability of cell membrane, resulting in ANFH, and accelerates the occurrence of ANFH due to the elevation of FFA and prostaglandins in blood, both of which cause changes in vascular permeability.
2.3.3 Adipocyte hypertrophy and osteoclastic steatosis
2.2.4 Long-term alcohol consumption produces an effect similar to Charcot arthropathy, weakening the normal protective pain response and causing collapse and necrosis of weight-bearing joints when there is osteoporosis; in addition, long-term alcohol consumption can also lead to osteoporosis.
2.4 Smoking
Studies have shown that smoking has a positive effect on osteonecrosis by several mechanisms.
2.4.1 Low fibrinolysis
Smoking decreases the activity of activating fibrinogen activators and is more likely to cause ANFH in the presence of familial hypofibrinolysis and coagulation abnormalities, while active smoking in adults can also contribute to platelet agglutination and hemoglobin carboxylation via the prothrombin pathway.
2.4.2 Osteoporosis
2.4.3 Increased free radicals
The intake of large amounts of free radicals (NO compounds, etc.) into the body during smoking accelerates the oxidative and antioxidant processes in the body, resulting in increased V-C V-E,β-CAR digestion, decreased erythrocyte autoperoxide dismutase activity, and increased peroxisome content, leading to an imbalance in the oxidative and peroxidative balance in the body. The free radical response is intensified.
2.4.4 Allergic reactions
Smoking can cause allergic reactions in humans, leading to intravascular coagulation and predisposition to ANFH
2.5
Decompression sickness (diving sickness) The incidence among tunnel or caisson workers, navy divers and shellfish divers is about 20%. After inhaling compressed air while working in deep water, the blood and tissues contain high concentrations of nitrogen, which can cause bone ischemic necrosis due to obstruction of the intramedullary vessels when divers rapidly decompress by fast surfacing. Similarly, a similar situation can occur when a high-altitude pilot rises rapidly from normal atmospheric pressure to a low oxygen pressure environment.
2.6 Radiotherapy and chemotherapy When radiotherapy is administered to women with cervical cancer, the pelvic area is the area where radiation is concentrated many times. A. G. Macdonald and J. D. Bissett have reported cases of ANFH in prostate cancer patients after treatment with deacetylciclopirogesterone acetate and radiation therapy “24”.
2.7 Sickle cell disease is caused by malformation of blood red blood cells and loss of their flexibility and deformability, which prevents them from passing through capillaries and sinus junctions, resulting in intravascular infarction, in addition to extensive necrosis due to increased blood viscosity, stagnant blood flow, bone marrow fibrosis, and narrowing of the marrow lumen.