Efficacy and Safety of Icariin Capsules in Intervening Post-operative Bone Grafting for Hip Osteonecrosis in ARCO Stage II

Background: Both hip-preserving surgery and pharmacological therapy can effectively improve symptoms in patients with early-stage osteonecrosis of the femoral head (ONFH) and are expected to delay the need for total hip arthroplasty. However, the clinical efficacy of combining hip-preserving surgery with drug therapy has not yet been widely substantiated. Therefore, we conducted a randomized clinical trial to compare the clinical outcomes of impacted bone graft (IBG) combined with Icariin (ICA) versus IBG alone. Purposes: The aim of this study was to clinically observe and evaluate the interventional therapeutic effect of ICA in patients with corticosteroid-induced ONFH following hip-preserving surgery, by comparing the femoral head collapse rate with a placebo control group, thereby providing a reliable basis for expanding the clinical application indications of ICA. Methods: This was a prospective randomized clinical trial. Patients with early-stage steroid-induced ONFH (ARCO stage II) who underwent hip-preserving surgery were eligible. Between September 2021 and August 2022, we randomized 46 patients to receive either IBG plus ICA or IBG alone. At the 1-year follow-up, 87% of patients (20 out of 23) in both the IBG+ICA and IBG groups were available for assessment. The observed indicators included patient-reported outcome measures ([PROMs], including Harris Hip Score [HHS], the 36-item short form health survey [SF-36], and Visual Analog Scale [VAS]) and the progression of femoral head collapse on imaging, assessed preoperatively and within 1 year postoperatively. No significant differences were noted in baseline characteristics such as age, gender, affected side, and PROMs between the two groups. Results: We found no statistically significant difference in the improvement of the HHS (4.7 ± 3.6 vs. 4.0 ± 3.5, respectively; mean difference 0.7 [95% confidence interval [CI] −1.5–3.0]; P = 0.505) or the VAS score (0.28 ± 0.29 vs. 0.14 ± 0.25, respectively; mean difference 0.14 [95% CI −0.03–0.32]; P = 0.099) between the IBG + ICA group and the IBG group at 3 months postoperatively. However, significant differences began to emerge by 6 months postoperatively (HHS at 6 months: 8.4 ± 3.0 vs. 5.4 ± 2.8, respectively; mean difference 3.0 [95% CI 1.1–4.8]; P = 0.003; HHS at 12 months: 10.8 ± 3.3 vs. 7.7 ± 3.4, respectively; mean difference 3.1 [95% CI 1.0–5.3]; P = 0.005; VAS at 6 months: 0.48 ± 0.27 vs. 0.30 ± 0.17, respectively; mean difference 0.18 [95% CI 0.03–0.32]; P = 0.021; VAS at 12 months: 0.84 ± 0.26 vs. 0.50 ± 0.25, respectively; mean difference 0.34 [95% CI 0.18–0.51]; P < 0.001). Furthermore, the IBG+ICA group demonstrated a significantly greater improvement in the SF-36 score at 12 months postoperatively compared to the IBG group (7.9 ± 3.1 vs. 3.5 ± 3.2, respectively; mean difference 4.4 [95% CI 2.4–6.4]; P < 0.001). No significant difference in the progression of femoral head collapse was observed between the two groups. Furthermore, no drug-related adverse reactions were reported. Conclusion: Based on the 1-year follow-up of the two groups of patients and the analysis results, IBG + ICA did not bring more significant clinical symptom improvement to the patients compared to IBG at 3 months postoperatively. However, from 6 months postoperatively, the former showed better clinical efficacy. There was no significant difference in the impact on the progression of femoral head collapse between the two intervention methods within the 1-year follow-up period postoperatively. The safety of ICA during the perioperative period has been confirmed. For patients with severe pain or poor quality of life due to early ONFH, IBG+ICA treatment may be a good choice to improve the patient’s pain and quality of life. Keywords: Icariin, Impacted bone graft, Hip osteonecrosis, Outcomes, Statistical Package for the Social Sciences