A pilot study of regenerative therapy using controlled release of recombinant human fibroblast growth factor for patients with pre-collapse osteonecrosis of the femoral head

Abstract

Purpose We evaluated the safety and clinical outcomes of a single local administration of gelatin hydrogel impregnated with recombinant human fibroblast growth factor (rhFGF)-2 for the treatment of the precollapse stage of osteonecrosis of the femoral head (ONFH). Methods Patients with ONFH (precollapse stage ≤2) received a single local administration of 800 μg of rhFGF-2-impregnated gelatin hydrogel and were followed up for one year. The surgery was performed using a minimally invasive technique involving a 1-cm skin incision, and walking was allowed from day one postoperatively. The primary outcomes included occurrence of adverse events and complications. The secondary outcomes included changes in the Harris hip scores, visual analog scale for pain scores, University of California, Los Angeles (UCLA) activity scores, and radiological images. Results We included ten patients, of which five experienced 14 adverse events, including one complication from spinal anesthesia. However, patients completely recovered from all adverse events. The mean clinical scores significantly improved by one year postoperatively compared with the pre-operative scores (before vs. after: visual analog score for pain, 21.2 vs. 5.3 mm; UCLA activity score, 5.5 vs. 6.6; Harris hip score, 81.0 vs. 96.9 points). There was only one case of femoral head collapse; however, this occurred in a hip with extensive necrosis. Stage progression and collapse did not occur in the other nine cases. Computed tomography confirmed bone regeneration in the femoral heads. Conclusions Clinical application of rhFGF-2-impregnated gelatin hydrogel for patients with precollapse ONFH was feasible and safe.

Extremely early stage osteonecrosis of the femoral head in a patient with hip pain secondary systemic steroid pulse therapy for Vogt-Koyanagi-Harada syndrome: A case report

“…This surgical treatment is based on translational clinical research in an experimental animal study by the authors [18] . We reported the first clinical application of recombinant human fibroblast growth factor-2-impregnated gelatin hydrogel for patients with precollapse stage of ONFH with good clinical results and safety [11] . Femoral head collapse progresses until severe secondary osteoarthritis develops, destroying both the femoral head and the acetabulum.…”

“…This novel treatment strategy has shifted the concept of early diagnosis and aggressive intervention. In particular, to prevent femoral head collapse, precollapse stage of ONFH has become a research target for various regenerative therapies, such as cell therapy [6] , [7] , [8] , bone substitutes [9] , [10] , and growth factors [11] , [12] , [13] . In any case, early diagnosis of ONFH is crucial to allow prevention of femoral head collapse using recently developed therapies.…”

“…Because the collapse rate of ONFH is high [4] , a recent strategy of ONFH treatment has shifted the approach to early diagnosis and early intervention [1] , [5] . Many joint-preserving therapies are being studied for the purpose of preventing femoral head collapse [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] . Magnetic resonance imaging (MRI) can be useful for early diagnosis, but the symptoms corresponding to the initial stage are usually absent or present as slight pain, that intensifies after the femoral head collapses.…”

A Strategy of Bone Regeneration for the Treatment of Idiopathic Femoral Head Necrosis

“…Papanagiotou et al did report that BMP-7 in combination with autologous, nonvascularized, fibular grafting, is effective for shortening operative time and the postoperative rehabilitation period. Kuroda et al [71] used recombinant FGF-2 impregnated with gelatin hydrogel for minimally invasive surgical treatment of patients in early stages of FHN. In their case series, 10% of hips progressed to collapse 1-year posttreatment, with improvement in radiographic clinical score in all other cases.…”

The management of platelet-rich plasma in ONFH treatment: A systematic review

“…PRP is defined as a sample of autologous blood with concentrations of platelets above baseline values [17]. PRP contains additional growth factors as well as platelets, such as platelet-derived growth factor (PDGF), transforming growth factor-β(TGF-β), basic fibroblast growth factor (bFGF), endothelial growth factor (EGF), and vascular endothelial growth factor (VEGF), which have an important role in tissue repair, regeneration, and differentiation of mesenchymal stem cells (MSCs) [16,18]. Its use in orthopaedics began early within decade as PRP was used with bone grafts to augment spinal fusion and fracture healing [19].…”