This study design was approved by the Institutional Review Board of Guangdong Provincial People’s Hospital and was performed in strict accordance with the ethical standards stipulated in the 1964 Declaration of Helsinki and its later amendments. Signed informed consent for participation was obtained from all study patients. The trial protocol was submitted to ClinicalTrials.gov, and the trial registration number is NCT01613612.
Based on the results of Gangi et al, we determined that at least 20 patients per group were necessary to detect the difference by using Wilcoxon-Mann-Whitney test with a bilateral α of 0.017 and a power of 80%. We included a minimum of 26 patients in each group in order to compensate the patients lost to the follow-up.
We recruited the eligible patients from those administrated in the Center of Orthopedics Surgery from June 2009 to October 2010. Plain radiograph of bilateral hips at the anteroposterior and frog-leg lateral positions and magnetic resonance imaging (MRI) were taken for all patients. We confirmed the diagnosis of ANFH based on the clinical history and the radiographic lesions in the femoral head.
Inclusion criteria were as follows: the subjects (1) were 18 to 55 years old; (2) had notable hip pain; (3) had normal, minor, or mixed osteopenia or were detected the presence of crescent sign in the plain radiograph; (4) stopped steroid treatment for at least 6 months.
Exclusion criteria were included: (1) < 18 or > 55 years old; (2) terminal stage of ANFH with the presence of secondary osteoarthritic changes such as osteophyte formation, narrowed joint gap, osteosclerosis, etc.; (3) history of fracture in the proximal femur, tumor and any other concomitant lower extremity diseases; (4) previous history of any surgical treatment in terms of core decompression, bone-grafting, titanium implantation, osteotomy; (5) inflammatory arthritis, including rheumatoid arthritis, suppurative arthritis and gouty arthritis; (6) having received steroid treatment in the last 6 months; (7) pregnancy.
After meeting the inclusion criteria, we provided the informed consent to the participants and assessed their baseline characteristics. The hips were randomly allocated to receive core decompression (CD) + autologous bone graft (BG) or core decompression + autologous bone graft + BBC (CD + BG + BBC) by a randomization schedule, which was generated by computer-based block randomization.
All surgical procedures were performed under continuous epidural anesthesia. For core decompression of the femoral head, we firstly determined the optimal entrance point for drilling, and then a 1.5-cm incision was made at the level of the greater trochanter. A 3.0 mm diameter Kirschner wire (k-wire) was introduced toward the necrotic area with the tip placed at the subchondral bone area approximately 2 to 3 mm from the articular cartilage. Next, a 10-mm diameter trephine was drilled through the k-wire to the necrotic region. A cylinder of bone from the femoral neck and head was obtained. The necrotic proximal part was eliminated and the healthy part was used for BBC grafting. The necrotic tissue remained in the femoral head was removed by the bone curette. All the above steps were performed under C-arm X-ray guidance.
For bone marrow collection, a 50-mL syringe, heparinized in advance, was used to harvest the bone marrow from the superior posterior iliac spine. Bone marrow was centrifuged at 1500 revolutions per minute for 10 minutes in a bench-top centrifuge (Ependoff, AG 22331, Hamburg, Germany) with a sterilized chamber. The bone marrow was separated into three phases after centrifuge. We collected a total of 1 mL of bone marrow concentrate from the interface containing enriched bone marrow cells by a sterilized transfer pip pet, and then bone marrow concentrate was seeded on the cylindrical bone drop by drop in order to allow the cells to anchor on the bone surface. 10 µL of bone marrow concentrate was kept for cell counting after the surgery. The average bone marrow cells loaded to the cylindrical bone were approximately 3 × 109 nucleated cells.
The bone graft with or without BBC was inserted into the necrotic region with the guidance of C-arm X-ray. After surgery, the patients were instructed to remain non-weight-bearing for 4 weeks. Surgical complications were monitored after operation.
Preoperatively, the blinded evaluators collected the baseline demographic information, including age, sex, etiological factors, presurgical Ficat stage of ANFH, and location of defect. Plain X-ray radiograph and MRI were used to determine Ficat stage of ANFH and the location of necrotic lesion. All participants were followed at 24, 60, 120 months postoperatively. Anteroposterior and frog-leg lateral radiographs were taken at each time of clinical assessment. Radiographic progression of the ANFH was determined based on Ficat classification system. The primary outcomes included visual analogue scale (VAS), Lequesne algofunctional index and Western Ontario and McMaster Universities Arthritis Index (WOMAC) osteoarthritis scoring. Secondary outcome was the clinical failure rate of the operated hips at 5 years and at the time of the final follow-up. The clinical failure rate was defined as the proportion of hips that progressed to Ficat stage IV or subjected to THA.
The SPSS 22.0 software package (IBM Inc. USA) was used for statistical analysis. The data was described as median, maximum and minimum value. Chi-square test and Fisher’s exact test were used for categorical variables. The statistical significance of demographic data and functional assessments between two groups were determined by Wilcoxon-Mann-Whitney test. The clinical survival was compared between each group with Kaplan-Meier survivorship analysis and the statistical significance was determined by log-rank test. COX proportional-hazards regression model was employed to detect the risk factors affecting the survival of femoral head. The level of statistical significance for all tests was defined at P < 0.05.