Expression Of TGF-β1and IGF-1in Patients With Nontraumatic Osteonecrosis Of Femoral Head

Objective:To investigate clinical and epidemiological survey of risk factors associated with non-traumatic osteonecrosis of the femoral head (NONFH) to provide reliable regional data for pathogenic factors, pathogenesis and treatment of the disease; to investigate expression of TGF-β1and IGF-1in local tissues in patients with clinically NONFH. And, the flow cytometry was adopted to determine the percentage and ratio of T lymphocyte subsets in peripheral blood.Methods:(Ⅰ) In Section1,212patients with newly diagnosed "NONFH" and176with newly diagnosed "traumatic femoral neck fractures (FNF)" who were admitted to the Department of Orthopaedics of the Huainan First People’s Hospital between October2006and October2014were assigned to the experimental group and the control group, respectively. Their general information (i.e., gender, age, history of alcoholism, history of glucocorticoid use, and family history) and special examination data (i.e., results of the blood biochemistry test and imaging examination) were collected, sorted out and analyzed.(Ⅱ) In Section2,20patients with "NONFH" and20with "traumatic FNF" who were admitted to the Department of Orthopaedics of the Huainan First People’s Hospital between October2013and October2014were assigned to the experimental group and the control group, respectively. Artificial total hip arthroplasty was performed under general anesthesia. Resected femoral head tissue specimens were biopsied introoperatively. Following decalcification, tissue structures were observed by HE staining. And, semi-quantitative research was made on expression of TGF-β1and IGF-1in local tissues immunohistochemically. The flow cytometry was adopted to determine the percentage and ratio of T lymphocyte subsets in peripheral blood.Results:(I) Results of Section1:A cohort of212patients with non-traumatic ONFH (male,68%; female,32%; with male-female ratio of2.12) was enrolled, with a mean age of39.9±10.1years. Among patients with non-traumatic ONFH,38%were idiopathic,36%were alcohol-induced,20%were glucocorticoid-induced, and6%were familial. Ficat-Arlet staging revealed that20(9%),49(23%),64(30%) and79(38%) patients were in stage Ⅰ, Ⅱ, Ⅲ and Ⅳ, respectively, and that the number of patients increased with the Ficat-Arlet stage. Results of lipid profile revealed higher levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and apolipoprotein B (APB) and lower levels of high density lipoprotein (HDL) and apolipoprotein A (APA) compared with controls (P<0.05).(Ⅱ) Results of Section2: Megascopically, femoral heads of patients with NONFH in the experimental group showed a rough surface and a dull color, with more distinct sclerosis, collapse and osteophyte formation, while those in the control group appeared smooth, without depression, particles and camosity. Pathologically, results of routine HE staining suggested osteocyte necrosis, disintegration, karyopyknosis and karyorrhexis. The bone lacunas where osteocytes were located were absent; circumferential lamellae showed structure disturbance, with osteolysis and minor new bone formation. In the control group, the bone lamellae of the femoral head aligned parallel and regularly; bone lacunas were located between or within bone lamellae, individually scattered, without osteonecrosis or granulation tissue. Immunohistochemical results suggested lower expression of TGF-β1and IGF-1in tissues in the experimental group than in the control group (P<0.01and P<0.05, respectively). Flowcytometry results show that the CD3+, CD4+percentages and CD4+/CD8+rate in experimental group were lower than control group(P<0.05, P<0.01and P<0.01, respectively), CD8+percentages in the experiment group were higher than those in the control group(P<0.05).Conclusions:(I) NONFH is2.12times more prevalent in males than females, with a mean age of onset of39.9±10.1years.(Ⅱ) Idiopathic, alcohol-induced and glucocorticoid-induced are major aetiological agents.(Ⅲ) Hyperlipemia is closed correlated with the conditions of patients with NONFH.(Ⅳ) Levels of TGF-β1and IGF-1are lower in local tissues in patients with NONFH than controls, suggestive of decreased vitality of repair of local femoral head in patient with NONFH.(V) NONFH patients suffer from imbalance between T lymphocyte subgroups in peripheral blood. The attack of NONFH resulted from cell immune imbalance.