Implantation of autologous Expanded Mesenchymal Stromal Cells in Hip Osteonecrosis through Percutaneous Forage: Evaluation of the Operative Technique

Abstract

Bone forage to treat early osteonecrosis of the femoral head (ONFH) has evolved as the channel to percutaneously deliver cell therapy into the femoral head. However, its efficacy is variable and the drivers towards higher efficacy are currently unknown. The aim of this study was to evaluate the forage technique and correlate it with the efficacy to heal ONFH in a multicentric, multinational clinical trial to implant autologous mesenchymal stromal cells expanded from bone marrow (BM-hMSCs). Methods: In the context of EudraCT 2012-002010-39, patients with small and medium-sized (mean volume = 13.3%, range: 5.4 to 32.2) ONFH stage II (Ficat, ARCO, Steinberg) C1 and C2 (Japanese Investigation Committee (JIC)) were treated with percutaneous forage and implantation of 140 million BM-hMSCs in a standardized manner. Postoperative hip radiographs (AP—anteroposterior and lateral), and MRI sections (coronal and transverse) were retrospectively evaluated in 22 patients to assess the femoral head drilling orientation in both planes, and its relation to the necrotic area. Results: Treatment efficacy was similar in C1 and C2 (coronal plane) and in anterior to posterior (transverse plane) osteonecrotic lesions. The drill crossed the sclerotic rim in all cases. The forage was placed slightly valgus, at 139.3 ± 8.4 grades (range, 125.5–159.3) with higher dispersion (f = 2.6; p = 0.034) than the anatomical cervicodiaphyseal angle. Bonferroni’s correlation between both angles was 0.50 (p = 0.028). More failures were seen with a varus drill positioning, aiming at the central area of the femoral head, outside the weight-bearing area (WBA) (p = 0.049). In the transverse plane, the anterior positioning of the drill did not result in better outcomes (p = 0.477). Conclusion: The forage drilling to deliver cells should be positioned within the WBA in the coronal plane, avoiding varus positioning, and central to anterior in the transverse plane. The efficacy of delivered MSCs to regenerate bone in ONFH could be influenced by the drilling direction. Standardization of this surgical technique is desirable.

Volume and location of bone regeneration after autologous expanded mesenchymal stromal cells in hip osteonecrosis

“…This would suggest that residual cysts may remain more frequently in the anterior region, which is consistent with Baba et al 39 who found a high bone-resorptive volume in the anterior femoral head of resected hips. A recommendation to aim the injection at the anterior femoral head, as previously suggested, 28 could be supported by this finding.…”

“…A third limitation is surgery and the injection placement of the cell therapy product, as analyzed in a recent paper. 28 However, the current study confirms that regeneration may extend in different areas of the femoral head lesion. Other aspects (tissue density and permeability, cell distribution after injection, cell progression, or survival within the lesion) may apply to explain variable bone regeneration.…”

“…The specific surgical technique and its variability has also been described elsewhere. 28 In brief, patients were positioned supine on a fracture table, and anteroposterior (AP) and axial views of the femoral neck and head were checked under fluoroscopy with a radiological C-arm. A guiding wire was drilled into the femoral head osteonecrotic lesion, and a 4 mm cannulated drill along the drilling guide was placed into the femoral head under fluoroscopy.…”

“…The lesion location in the transverse plane was similarly recorded on MRI transverse sections through the anterior-central-posterior (ACP) method. 28 Anterior, central, and posterior zones of the femoral head were identified at the central transverse section, with the acetabulum as the reference (from the anterior to the posterior edge). If the lesion surpassed the anterior acetabular edge, the notation was A2 (Anterior 2).…”

Invasive electrical stimulation in the treatment of avascular osteonecrosis of the femoral head — mid-term results

“…To avoid ONFH progression and eventual collapse of the femoral head, core decompression (CD) is considered to be the gold standard for all precollaptic stages 1,3,4 . In case of progressed ONFH, CD is augmented with bonemarrow injection, autologous bone grafting (ABG), or femoral osteotomy 3,[5][6][7][8][9][10] .…”