**3. The treatment of FHN without cell-based therapy**

Nonoperative treatment, which aims to offload forces exerted on the femoral head through limited weight bearing, activity modification, and physical therapy, has been shown to have limited success in preventing disease progression [2].

In the early stage of FHN (i.e., ARCO stage 1), intramedullary pressure is elevated and core decompression surgery is performed by drilling through the necrotic region, with a 6 or 8 mm short trephine drill, to reduce the pressure [7]. Core decompression treatment is more effective than conservative treatment [11], with clinically satisfactory results of core decompression obtained in 63.5% of cases of early FHN, compared to 22.7% with conservative treatment [12]. The clinical benefits of core decompression, however, have been questioned [13, 14]. Foremost, core decompression is not indicated for advanced stages of FHN. Mont et al. [15] reported satisfactory outcomes of core decompression of only 29% in patients with Steinberg stage 3 FHN, with 41% of patients in stage 3 and 92% in stage 4 requiring arthroplasty. In advanced stages of FHN, bone fragility is a more important consideration than elevated intrafemoral pressure.

Multiple microfractures of the subchondral bone are often present in advanced stages of FHN [16] and, therefore, reinforcing initial bone strength to prevent collapse of the femoral head is an important component of treatment at this stage. Vascularized bone grafts can offer reflux of blood flow and initial strength. Vascularized bone grafting is indicated for advanced stages of FHN [2, 17–19]. However, a radiographic study of outcomes after vascularized bone grafting by Ishizaka et al. [17] indicated continued progression of collapse in 50% of cases classified as Ficat stage 2 hips, and in 46% of cases classified as Ficat stage 3 hips. Therefore, vascularized bone grafting is not sufficient to prevent the collapse in cases of advanced FHN.

**Figure 2** Cell-based therapy for osteonecrosis of the femoral head, combining concentrated bone marrow transplanta‐ tion with core decompression is shown in the left panel. The right panel shows cultured mesenchymal stromal cell transplantation, combined with biomaterials, after removal of necrotic bone.
