At present, the etiology of ANFH is relatively clear, which is due to prolonged and/or high-dose use of glucocorticoid-induced osteonecrosis of the femoral head. SANFH is a metabolic disease that occurs due to the use of glucocorticoid drugs, leading to impaired blood supply to the femoral head and death of bone cells and bone marrow composition, which in turn lead to structural change, collapse of the femoral head, and articular dysfunction [
8]. But in its pathogenesis, the medical profession has not yet had clear conclusions and the following several theories have been widely recognized.
Prolonged high-dose use of hormones can increase blood lipids and cause hyperlipidemia, leading blood tends to be stagnated. The fat embolism situation of the whole body is serious, and the femoral head tiny arteries form adipose suppository, which directly causes the partial blood stasis [
9]. The bone marrow cells are occupied by adipose cells, and the adipose cells fuse into pieces, inducing the death of marrow-derived cells, resulting in ANFH.
Theory of intraosseous pressure increasing
As early as 1981, Bünger et al. suggested that the increase of intraosseous pressure is the pathogenesis of ANFH [
10]. The medical profession believed that the increase in intraosseous pressure was due to excessive accumulation of adipose cells in the bone marrow, so that the pressure in the blood vessels increased, blood vessels spasm caused ischemia, and then form ANFH. But at the same time, some scholars pointed out that the increase in intraosseous pressure in the middle and late stage of the disease was a secondary change, and early ANFH did not appear in the intraosseous pressure phenomenon. Although there is no obvious evidence that indicates that the increase in intraosseous pressure is the primary or secondary change of ANFH, the theory of intraosseous hypertension has been universally recognized.
Osteoporosis theory
The negative effects of long-term use of glucocorticoids include osteoporosis. Glucocorticoids can overdecompose proteins and reduce their synthesis, resulting in the thinning of the trabeculae bone, at the same time against vitamin D, and reducing calcium absorption in the gastrointestinal tract, thus causing large amounts of calcium to be excreted. Taking large doses of steroid-like drugs are prone to become bone hyperplasia, which can reduce the number of trabecular bone and osteoblasts, thus lead to osteoporosis, and ultimately lead to the collapse of the femoral head bearing area, and even necrosis [
13]. In addition, in the process of differentiation of bone marrow stromal cells into adipocytes, hormones play a certain role in inducing the reduction of differentiation of osteoblasts. These are the traditional Chinese medicine factors that lead to osteoporosis and ANFH.
At present, the treatment methods of SANFH are diversified and the indications are various. And the treatment of this disease is mainly divided into non-surgical therapy and surgical therapy, and surgical therapy can be broadly divided into two categories: minimally invasive and joint replacement. The medical profession adopts treatment options mainly based on different indications and patient wishes and their physical and economic conditions. But it is aimed to improve the quality of life of patients. The hip joint is the main weight-bearing joint in the human body, and to reduce or avoid the hip joint weight is the main concern in the course of treatment, so as to obtain the maximum clinical effect. The surgical treatment has made a great progress with the increasing incidence of SANFH and development of modern medical research. Depending on the progression of the course, different methods of operation can be chosen. At present, the commonly used surgical methods in clinical practice are as follows: (1) the ARCO classification determines that the femoral head has not yet collapsed and can be conducted femoral head drilling decompression plus bone graft or femoral head drilling decompression plus tantalum rod support surgery. The purpose is to delay the collapse of the weight-bearing area of the femoral head, even without collapse. The operation is simple and widely used in young and middle-aged people. (2) Bone flap transplantation surgery is used relatively less in recent years; it is mainly used to promote bone flap and blood vessel crawling and the growth of new bone and to delay the time of joint replacement. (3) One of the new surgical methods in recent years, stem cell transplantation surgery, is also popular, but because of its high technical requirements and high cost, results in the range of use is very small, but the scope of surgery and the operation can promote the repair of ANFH, so the experimental research is also increasing. (4) Joint replacement is currently the most widely used surgical method in middle-aged and old people; the surgical technique is mature, the cost is relatively low, and the quality of life improved obviously. For the use of traditional Chinese medicine, every theory has its own unique insights. But generally speaking, tonifying liver and kidney and strengthening bones and muscles have been generally recognized [
14]. In addition, long-term application of hormones leads to hyperlipidemia, a systemic fat embolism. And small artery lumen at the end of the femoral head cartilage is rare [
15]. The fat clumps that adhere to the inner wall of the vessel form fat embolism. Bone marrow cells are occupied by fat cells. Fat cells fuse into pieces, resulting in hemopoietic cells in the bone marrow dead. Based on this theory, many factors, such as lipid-lowering drugs, anticoagulant blood, and vascular relaxant, which are used to control the necrosis of the femoral head caused by the proliferation of adipocytes, are widely used in clinical treatment [
16]. However, there is no clear and unified view on the usage, dose, and the application time.
PPARγ mRNA mainly plays a role in regulating fat, so it has great significance in the process of adipogenesis of cells in blood vessel and bone marrow [
17,
18]. Excessive differentiation of the adipose tissue leads to sparse trabecular bone, where bone fat cells are multiplied, resulting in osteoporosis, which can lead to minor fractures of bone in severe cases [
19,
20]. Through the experimental study on the adipogenic effect of bone marrow stromal stem cells from osteoporosis rats, Liu et al. [
21] found that regulating and inhibiting the expression of PPARγ mRNA can effectively reduce the incidence of osteoporosis. At the same time, it also confirmed that the low expression of PPARγ mRNA could reduce the risk of small fracture and reduce ANFH.
Osteocalcin mRNA is one of the most sensitive indexes in the process of osteogenic differentiation [
22]. The increase of its activity can accelerate the process of ALP activity combined with it and thus promote the bone formation of osteoblasts [
23]. On the other side, the combination of osteocalcin and calcium ions has a positive effect in promoting bone deposition and bone growth. Peng et al.’s exploration from the side reflects the activity of osteocalcin having a positive correlation with osteoblast differentiation and osteoclast apoptosis [
24]. Zhu et al. believe that one of the bone secretion hormones is osteocalcin, which regulates the pathogenesis of osteoblasts and osteoclasts and regulates adipocytes by converting osteoclasts into blood [
25]. Therefore, the high expression of osteocalcin can effectively reduce the differentiation of adipocytes, increase bone matrix, and strengthen sclerotin [
26,
27].