Original Article | Vol 5 | Issue 2 | July-December 2025 | page: 13-19 | Yuanzhuo Xu, Yu Zhou, Wei Sun, Fuqiang Gao
DOI: https://doi.org/10.13107/jrs.2025.v05.i02.173
Open Access License: CC BY-NC 4.0
Copyright Statement: Copyright © 2025; The Author(s).
Submitted Date: 19 Oct 2025, Review Date: 18 Nov 2025, Accepted Date: Nov 2025 & Published: 30 Dec 2025
Author: Yuanzhuo Xu [1], Yu Zhou1 [1,2,3], Wei Sun [4], Fuqiang Gao [1,2,3]
[1] Department of Orthopedic Surgery, China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,
[2] Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA,
[3] Center for Hip Preservation, Osteonecrosis and Developmental Dysplasia of the Hip, China-Japan Friendship Hospital, Beijing, China,
[4] Department of Orthopedic Surgery, Capital Medical University, China-Japan Friendship School of Clinical Medicine, Beijing, China.
Address of Correspondence
Dr. Wei Sun,
Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
E-mail: wei.sun@pennmedicine.upenn.edu
Abstract
Introduction: 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.
Materials and 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
References:
1. Li Z, Shao W, Lv X, Wang B, Han L, Gong S, et al. Advances in experimental models of osteonecrosis of the femoral head. J Orthop Translat 2023;39:88-99.
2. Zhang J, Cao J, Liu Y, Zhao H. Advances in the pathogenesis of steroid-associated osteonecrosis of the femoral head. Biomolecules 2024;14:667.
3. Quan H, Ren C, He Y, Wang F, Dong S, Jiang H. Application of biomaterials in treating early osteonecrosis of the femoral head: Research progress and future perspectives. Acta Biomater 2023;164:15-73.
4. Zhao Y, Li S, Feng M, Zhang M, Liu Z, Yao Y, et al. Effects of puerarin-loaded tetrahedral framework nucleic acids on osteonecrosis of the femoral head. Small 2023;19:e2302326.
5. Chen CY, Rao SS, Yue T, Tan YJ, Yin H, Chen LJ, et al. Glucocorticoid-induced loss of beneficial gut bacterial extracellular vesicles is associated with the pathogenesis of osteonecrosis. Sci Adv 2022;8:eabg8335.
6. Huang C, Qing L, Xiao Y, Tang J, Wu P. Insight into steroid-induced ONFH: The molecular mechanism and function of epigenetic modification in mesenchymal stem cells. Biomolecules 2023;14:4.
7. Zhao D, Zhang F, Wang B, Liu B, Li L, Kim SY, et al. Guidelines for clinical diagnosis and treatment of osteonecrosis of the femoral head in adults (2019 version). J Orthop Translat 2020;21:100-10.
8. Wu CT, Kuo FC, Yen SH, Lin PC, Wang JW, Lee MS. Impaction bone grafting augmented with a wire coil by the lightbulb technique for osteonecrosis of the femoral head. J Arthroplasty 2022;37:2063-70.
9. Rosenwasser MP, Garino JP, Kiernan HA, Michelsen CB. Long term followup of thorough debridement and cancellous bone grafting of the femoral head for avascular necrosis. Clin Orthop Relat Res 1994;306:17-27.
10. Sun W, Li Z, Gao F, Shi Z, Zhang Q, Guo W. Recombinant human bone morphogenetic protein-2 in debridement and impacted bone graft for the treatment of femoral head osteonecrosis. PLoS One 2014;9:e100424.
11. Chu K, Wang Y, Liu B, Li Z, Wang Z, Zhang J, et al. Direct anterior approach versus posterior approach in total hip arthroplasty after ONFH with failed vascularized iliac crest bone grafting for hip preservation: A retrospective comparative study. BMC Musculoskelet Disord 2025;26:686.
12. Zhao D, Huang S, Lu F, Wang B, Yang L, Qin L, et al. Vascularized bone grafting fixed by biodegradable magnesium screw for treating osteonecrosis of the femoral head. Biomaterials 2016;81:84-92.
13. Lou P, Zhou G, Wei B, Deng X, Hou D. Bone grafting for femoral head necrosis in the past decade: A systematic review and network meta-analysis. Int J Surg 2023;109:412.
14. Xu J, Deng W, Zhu X, Han D, Zheng Y, Zheng Q. Potential efficacy and mechanisms of icariin for the animal model of osteonecrosis of the femoral head. Front Pharmacol 2025;16:1508971.
15. Sun ZB, Wang JW, Xiao H, Zhang QS, Kan WS, Mo FB, et al. Icariin may benefit the mesenchymal stem cells of patients with steroid-associated osteonecrosis by ABCB1-promoter demethylation: A preliminary study. Osteoporos Int 2015;26:187-97.
16. Yue J, Yu H, Liu P, Wen P, Zhang H, Guo W, et al. Preliminary study of icariin indicating prevention of steroid-induced osteonecrosis of femoral head by regulating abnormal expression of miRNA-335 and protecting the functions of bone microvascular endothelial cells in rats. Gene 2021;766:145128.
17. Huang Z, Cheng C, Cao B, Wang J, Wei H, Liu X, et al. Icariin protects against glucocorticoid-induced osteonecrosis of the femoral head in rats. Cell Physiol Biochem 2018;47:694-706.
18. Yu H, Yue J, Wang W, Liu P, Zuo W, Guo W, et al. Icariin promotes angiogenesis in glucocorticoid-induced osteonecrosis of femoral heads: In vitro and in vivo studies. J Cell Mol Med 2019;23:7320-30.
19. Yang X, Shi L, Li A, Gao F, Sun W, Li Z. Phase-contrast imaging with synchrotron hard X-ray reveals the effect of icariin on bone tissue morphology and microstructure in rabbits with early glucocorticoid-induced osteonecrosis of the femoral head. Front Cell Dev Biol 2023;11:1155532.
20. Harris WH. Traumatic arthritis of the hip after dislocation and acetabular fractures: Treatment by mold arthroplasty. An end-result study using a new method of result evaluation. J Bone Joint Surg Am 1969;51:737-55.
21. Ware JE Jr., Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992;30:473-83.
22. Huskisson EC. Measurement of pain. The Lancet 1974;304:1127-31.
23. Xie X, Pei F, Wang H, Tan Z, Yang Z, Kang P. Icariin: A promising osteoinductive compound for repairing bone defect and osteonecrosis. J Biomater Appl 2015;30:290-9.
24. Zhang X, Li H, Chen F, Chen Y, Chai Y, Liao J, et al. Icariin regulates miR-23a-3p-mediated osteogenic differentiation of BMSCs via BMP-2/Smad5/Runx2 and WNT/β-catenin pathways in osteonecrosis of the femoral head. Saudi Pharm J 2021;29:1405-15.
How to Cite this article: Xu Y, Sun W, Zhou Y, Gao F. Efficacy and safety of Icariin capsules in intervening post-operative bone grafting for hip osteonecrosis in ARCO stage II. Journal of Regenerative Science. July-Decemnber 2025;5(2):13-19.
|
