**4. Concentrated bone marrow transplantation for the treatment of FHN**

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

limited success in preventing disease progression [2].

94 Advanced Techniques in Bone Regeneration

pressure.

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

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

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

**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.

bone grafting is not sufficient to prevent the collapse in cases of advanced FHN.

Core decompression offers not only a decrease in intramedullary pressure, but also a flow of living cells from regions surrounding the necrotic lesion. However, as FHN is not an isolated lesion of the femoral head, but rather involves the greater trochanteric area, the number of osteogenic cells throughout the trochanteric area is reduced [20, 21]. Hernigou et al. [22] and Gangji et al. [23] combined transplantation of concentrated autologous bone marrow from the iliac crest with core decompression with the aim of supplying osteoblastic cells. Gangji et al. [23] reported collapse of the femoral head to be significantly delayed with the use of concen‐ trated bone marrow transplantation, compared with sole core decompression, when per‐ formed in the early stage of FHN (i.e., ARCO stage 1 or 2), with a collapse rate of 63% for the sole core decompression group, compared to 10% for the concentrated bone marrow trans‐ plantation group. Since the initial work of Hernigou et al. [22] and Gangji et al. [23], a number of studies have reported their outcomes of using concentrated autologous bone marrow transplantation in combination with core decompression [24–28], with relevant information from these studies reported in **Figure 2** and **Table 2**. Although clinically acceptable results for the combination of cell transplantation and core decompression were reported for patients classified in the early stages of FHN progression [23, 24], for patients with advanced stages of FHN, this combined treatment is not sufficient to prevent collapse of the femoral head [23– 28]. The association between clinical stage of FHN and outcomes of the combined treatment was reported by Hernigou et al. [22], with 77% prevention of collapse for patients in stage 1 and 74% in stage 2, compared to 0% in stage 3 and 50% in stage 4. Therefore, additional treatment may be needed to enhance the positive effects of bone marrow transplantation. Martin et al. [29] used a combination of platelet rich plasma and bone marrow cells for transplantation after core decompression, with significant pain relief achieved in 86% of their cases, and with 79% of cases not progressing to collapse. Kang et al. [30] used a cancellous bone graft in combination with bone marrow transplantation after core decompression for both early and advanced stages of FHN, obtaining clinically successful outcomes in 80% of cases in stage 1, 65.7% in stage 2, 38.9% in stage 3, and 33.3% in stage 4.

Based on this evidence, it seems reasonable to suggest that for patients with the advanced stage of FHN (i.e., ARCO stage 3 or 4), providing initial strength to the femoral head is required to prevent further fracture and collapse. Bioactive scaffolding can provide the initial strength required. Yamasaki et al. [31] used interconnected porous calcium hydroxyapatite, in combi‐ nation with concentrated bone marrow transplantation for patients with stages 1 and 2 FHN and advanced stage 3A. They reported no progression of the collapse in 56.7% of their case series, mild collapse of <2 mm in 33.3% and >2 mm of collapse in 10%. Liu et al. [32] used porous hydroxyapatite, with and without bone marrow transplantation, to treat patients in the precollapse stage of FHN progression (i.e., stage 2). They reported that 78.6% of their cases treated with the combination of porous hydroxyapatite and bone marrow transplantation did not progress to collapse, compared to 41.7% for patients treated only with bone marrow transplantation. A histological study by Arlot et al. [33], however, reported osteomalacia and osteoporosis to persist despite clinical improvement after treatment for FHN. Therefore, remodeling of the necrotic bone is difficult to achieve [34, 35]. To address this issue, Wang et al. [36] performed curettage of the necrotic bone, instead of core decompression, packing the free bone graft with concentrated bone marrow cells. Progression to collapse was prevented in 75% of their patients in stage 2 and 100% in stage 3.


MSC, mesenchymal stem cell.

**Table 2.** Cell therapy according to the grade of osteonecrosis of the femoral head.
