Introduction

Osteonecrosis (ON) is a bone disease characterized by death of osteocytes and loss of associated hematopoietic elements usually occurring as focal lesions in weight bearing joints such as the hip. The pathophysiology of the disease is still unclear and osteonecrosis can be viewed as both a vascular and a bone disease. The number of mesenchymal stem cells (precursors of osteoblastic cells) has been shown to be depressed in patients with osteonecrosis. Also, the proliferation rate of the osteoblastic cells in the proximal femur may be depressed. These findings raised the possibility that osteonecrosis might be a disease of bone cells or bone metabolism. On this basis, we started this study to evaluate bone metabolism status among patients with osteonecrosis.

Introduction: Osteonecrosis (ON) of the femoral head is a disorder that can lead to femoral head collapse and subsequent total hip replacement. Core decompression is the most widely prescribed treatment for early stage ON but its efficacy is still controversial. Since ON might also be a disease of mesenchymal cells or bone cells, the possibility has been raised that bone marrow containing osteogenic precursors could be implanted into the necrotic lesion. The 2 year results of this controlled double blind pilot study of the effect of autologous bone marrow-mononuclear cell implantation into the necrotic lesion of the femoral head were encouraging but needed to be confirmed by long term follow-up.

Methods: We studied 19 patients suffering from stage 1 or 2 ON of the femoral head. Within this group, 24 individual hips were allocated to a program of either core decompression (control group) or to core decompression plus autologous bone marrow mononuclear cells implantation (bone marrow graft group). The treatment group was blinded to both patients and assessors. Primary outcomes sought were safety and feasibility. Feasibility of treatment was defined as; reduction in pain, improvement in joint symptoms, and a reduction in the progression of the ON from stage 1or 2 to subchondral fracture (stage 3).

Results: After 60 months, there was a significant reduction in pain, measured on a visual analog scale within the bone marrow graft group. There was also a significant reduction in joint symptoms measured by the Lequesne index and the WOMAC score over the same period. Bone marrow implantation reduced the number of hips monitored in this study that progressed to subchondral fracture (stage 3). In the bone marrow grafted group, 10 of the 13 hips remained at the stage 2 but only 3 of the 11 hips in the control group remained stable. Survival analysis showed a significant difference in the time to collapse between the two groups.

At 60 months, 3 of the 11 hips in the control group needed total hip replacement whereas only 2 of the 13 hips in the bone marrow graft group underwent prosthetic replacement.

Discussion: Long term results confirmed that autologous bone marrow-mononuclear cells implantation into the necrotic lesion could be an effective treatment of osteonecrosis of the femoral head.

Introduction: Abnormalities of mesenchymal stem cells and osteoblastic cells (Obs) might play a role in producing bone collapse due to insufficient repair of the necrotic area in osteonecrosis of the femoral head (ON). Osteoblast and osteocyte apoptosis should be increased at the osteonecrotic site.

Materials and Methods: We compared the TRAIL (TNF-related apoptosis-inducing ligand) cytotoxicity in primary Obs isolated from femoral heads from patients with ON or osteoarthritis (OA) and on two human osteosarcoma cell lines, MG-63 and SaOS₂.

Results and Discussion: We showed that ON but also OA Obs were sensitive to TRAIL. We also observed TRAIL cytotoxicity on MG-63 but not SaOS₂ cells. Moreover, we saw that TRAIL negatively regulated Akt and ERK survival pathways in MG-63 cells. We also investigated the IL-6 influences on apoptotic response of Obs to TRAIL. Even though decreased IL-6 and sIL-6R levels were observed at peripheral sites of the ON in regard to the levels produced in the iliac crest, IL-6 had no protective effects on TRAIL-induced apoptosis in ON Obs and only a weak protective effect in MG-63 cells. However, TRAIL stimulated IL-6 production in MG-63 cells and, cells and OA Obs, suggesting to a lesser extend, in SaOS₂ other roles of TRAIL in the bone environment.