Introduction

The goal of joint-preserving surgery for the treatment of osteonecrosis of the femoral head (ONFH) is to delay or prevent osteoarthritic development. Bone marrow is a source of osteogenic progenitors that are key elements in the process of bone formation and fracture healing. We established an easy-to-use method using a conventional manual blood bag centrifugation technique traditionally used for extracting buffy coats, for concentration of nucleated cells and platelets from clinical bone marrow aspirates to obtain osteogenic progenitors and growth factors. However, it is unclear whether the surgical goals are really achieved and if so in which patients. The purpose of this study was to identify demographic, clinical, and radiographic factors predicting total hip arthroplasty (THA) conversion after CABMAT for the treatment of idiopathic ONFH.

Summary Statement. Osteonecrosis of the femoral head (ONFH) is a multifactorial skeletal disorder. S100A9 represseses angiogenesis and vessel integrity in ONFH. It also may function as a marker of diagnosis in ONFH. Introduction. Osteonecrosis of the femoral head (ONFH) is a multifactorial skeletal disorder characterised by ischemic deterioration, bone marrow edema and eventually femoral head collapse and joint destruction. Several surgical, pharmaceutical and non-invasive biophysical modalities have been employed to alleviate this joint disorder. Our proteomic analysis showed that ONFH patients displayed increased expression of S100A9 protein when compared with healthy volunteers. This study is designed to evaluate the pathogenesis of S100A9 on the patients of ONFH. Patients & Methods. We collected 56 patients with ONFH including stage I, II, III and IV and 14 health volunteers. 20 ml of peripheral venous blood is drawn from each subject or prior to general anesthesia for hip arthroplasty. We compared the ELISA of S100A9, Osteocalcin, TRAP-5b, sVCAM-1. Immunohistochemistry of S100A9, vWF and VEGF are compared using femoral head harvested from late stages of ONFH and femoral neck fracture when received hip arthroplasty. In vitro angiogenic assay was performed by tube formation assay. Results. There were significant elevation of S100A9 in the serum of ONFH patients then in healthy volunteers. sVCAM-1 and TRAP-5b were increased and Osteocalcin was decreased in ONFH patient when comapred with healthy volunteers. The expression of S100A9 protein in ONFH tissue was significantly higher than femoral neck fracture tissue. In tube formation assay, we found S100A9 and the serum of ONFH patient supressed angiogenesis in vascular endothelial cell culture. Discussion/Conclusion. The expression of S100A9 significantly increased in the serum and femoral head tissue of patients with ONFH. S100A9 also supressed angiogenesis expression. The results indicated that S100A9 represseses angiogenesis and vessel integrity in ONFH. It also may function as a marker of diagnosis in ONFH

Introduction and Objective. Osteonecrosis of the femoral head (ONFH) is an evolving and disabling condition that often leads to subchondral collapse in late stages. It is the underlying diagnosis for approximately 3%–12% of total hip arthroplasties (THAs) and the most frequent aetiology for young patients undergoing THA. To date, the pathophysiological mechanisms underlying ONFH remain poorly understood. In this study, we investigated whether ONFH without an obvious etiological factor is related to impaired osteoblast activities, as compared to age-matched patients with primary OA. Materials and Methods. We cultured osteoblasts isolated from trabecular bone explants taken from the femoral head of patients with ONFH and from intertrochanteric region of patients with ONFH or with OA and compared their in vitro mineralisation capacity and secretion of paracrine factors. Results. Compared to patients with OA, osteoblasts obtained from the intertrochanteric region of patients with ONFH showed reduced mineralisation capacity, which further decreased in osteoblasts from the femoral head of the same patient. Lower mineralisation of osteoblasts from patients with ONFH correlated with lower mRNA levels of genes encoding osteocalcin and bone sialoprotein and higher osteopontin expression. Osteoblasts from the intertrochanteric region of patients with ONFH secreted lower osteoprtegerin levels than those from patients with OA, resulting in a higher receptor activator of NF-κB ligand (RANKL)-to-osteoprotegerin (OPG) ratio. Notably, the RANKL-to-OPG ratio, as well as the secretion of the proresorptive factors interleukin-6 and prostaglandin E. 2. , was higher in osteoblasts from the femoral head of patients with ONFH than in those from the intertrochanteric region. Conclusions. ONFH is associated with a reduced mineralisation capacity of osteoblasts and increased secretion of proresorptive factors

Introduction. Osteonecrosis of the femoral head (ONFH) is one of the most serious complications associated with corticosteroid therapy. In patients with ONFH, collapse of the femoral head often occurs and causes severe hip pain and impaired hip joint function. Despite the widely spread use of corticosteroids for treating various diseases and a known association between prevalence of ONFH and daily dose of corticosteroids, the pathomechanism for the development of ONFH has not been identified. Since hepatic cytochrome P4503A (CYP3A) is a predominant enzyme responsible for metabolizing corticosteroids and its activities varies more than 10-fold, low hepatic CYP3A activity leads to a remarkable increase of corticosteroid levels and its effect. We have previously reported that hepatic CYP3A levels are significantly lower in patients with corticosteroid-induced ONFH than that in control patients and patients with alcohol-related ONFH and that hepatic CYP3A activity inversely correlated with the incidence of osteonecrosis and extent of the necrotic area caused by the same dose of corticosteroids in a rabbit model, suggesting possible prevention of the corticosteroid-induced osteonecrosis by adjusting corticosteroid dose based on the level of individual hepatic CYP3A activity prior to corticosteroid therapy. To examine hepatic CYP3A activity, measuring clearance of administrated midazolam (MDZ) is a reliable method, as shown by the significant correlations between the clearance of midazolam and hepatic CYP3A levels measured by biopsy and the clearance of other CYP3A-specific substrates. However, the method is invasive and time consuming for measuring clearance of administrated MDZ, needing multiple blood samplings over half a day for each subject. The aim of this study was to develop the simple, safe and noninvasive methods for measuring the level of hepatic CYP3A activity, which is applicable to prevent the occurrence of corticosteroid-induced osteonecrosis prior to corticosteroid therapy. Methods. Thirty seven healthy male (n=20) and female (n=17), volunteers who had a mean age of 27 years received single oral administration of a small quantity of midazolam (50 mg/kg) and concentrations of total midazolam and its principal metabolite, 1-hydroxymidazolam (1-OH-midazolam), in each plasma at 15, 30, 45, 60, and 90 minutes and 2, 3, 4, 6, 9 and 12 hours post-drug administration were measured. Secondarily, the assessment of the Observer's Assessment of Alertness/Sedation (OAA/S) Scale was also used during the 12-hour post-administration period. Results. The best correlations between midazolam clearance and the ratio of 1- OH- midazolam/ midazolam plasma concentrations measured at each experimental time were observed at 4 hours (R2 = 0.83) post-dosing, and better correlations were found at 3 hours with a strong correlation (R2 = 0.81). Good correlations between midazolam clearance and OAA/S scale were found at 15 minutes (p = 0.04). Conclusion. A single midazolam plasma measurement taken at 4 hours post-oral administration may represent an accurate marker of CYP3A activity. This simple, safe and noninvasive method for measuring CYP3A activity could be used for patients prior to corticosteroid therapy, and the adjusting dose of corticosteroids, tailor-made medicine, depending on the CYP3A activity of the individual patient could avoid the occurrence of corticosteroid-induced osteonecrosis