Abstract
Steroid-induced avascular necrosis of the femoral head (SANFH) significantly impairs patients’ quality of life, with long-term steroid use being a major contributing factor. The pathogenesis of SANFH remains complex and poorly understood. Bone marrow mesenchymal stem cells (BMSCs) possess multidirectional differentiation potential and are crucial for bone repair and regeneration, yet their precise mechanisms in SANFH treatment are not fully elucidated. In this study, 48 rabbits with early-stage SANFH were randomly assigned to four groups: control (Group A), core decompression (Group B), BMSCs embedded in fibrin sealant (FS) after decompression (Group C), and pravastatin administration combined with BMSCs in FS post-decompression (Group D). Blood lipid levels were monitored throughout the experiment, and femoral heads were assessed via MRI, HE staining, and VEGF immunohistochemical staining. Group C demonstrated reduced femoral head necrosis and increased new bone formation compared to the control. Group D showed significantly lower serum lipid content and femoral head necrosis than other groups, with HE staining revealing fewer empty lacunae and increased trabecular bone density. Additionally, VEGF expression was markedly elevated in Group D. These findings indicate that BMSCs embedded in biomaterials enhance the therapeutic efficacy for early SANFH, and the combination with pravastatin significantly improves outcomes, suggesting a promising new approach for clinical management of femoral head necrosis.
Similar content being viewed by others
Data availability
All data generated or analyzed during this study are included in this published article and its supplementary information files.
Abbreviations
- BMSCs:
-
Bone marrow mesenchymal stem cells
- SANFH:
-
Steroid-induced avascular necrosis of the femoral head
- VEGF:
-
vascular endothelial growth factor
- FS:
-
Fibrin sealant
References
Jiao, M. et al. Circular RNA and messenger RNA expression profile and competing endogenous RNA network in subchondral bone in osteonecrosis of the femoral head. DNA Cell Biol. 40 (1), 61–69 (2021).
Wang, X., Li, J., Man, D., Liu, R. & Zhao, J. Early detection of steroid-induced femoral head necrosis using 99mTc-Cys-Annexin V-based apoptosis imaging in a rabbit model. Mol. Med. 26 (1), 120 (2020).
Jiang, Y. et al. Tetramethylpyrazine enhances vascularization and prevents osteonecrosis in steroid-treated rats. Biomed Res Int 2015:315850. (2015).
Aimaiti, A. et al. Can bisphenol A diglycidyl ether (BADGE) administration prevent steroid-induced femoral head osteonecrosis in the early stage? Med. Hypotheses. 77 (2), 282–285 (2011).
He, P. et al. Effectiveness and safety of traditional Chinese medicine in the treatment of steroid-osteonecrosis of femoral head: A protocol for systematic review and meta-analysis. Med. (Baltim). 100 (30), e26811 (2021).
Bian, Y. et al. Pathogenesis of glucocorticoid-induced avascular necrosis: A microarray analysis of gene expression in vitro. Int. J. Mol. Med. 36 (3), 678–684 (2015).
Ebisawa, S. et al. Impact of combination therapy with Statin and Ezetimibe on secondary prevention for post-acute myocardial infarction patients in the Statin era. Int. J. Cardiol. Heart Vasc. 8, 154–160 (2015).
H W, S. Z. & Z, Q. M. W. Y. L. Recent advances in osteonecrosis of the femoral head: a focus on mesenchymal stem cells and adipocytes. J. Translational Med. 23 (1), 592 (2025).
Wang, T. et al. Role of mesenchymal stem cells on differentiation in steroid-induced avascular necrosis of the femoral head. Exp. Ther. Med. 13 (2), 669–675 (2017).
Wang, W. et al. Chitosan derivatives and their application in biomedicine. Int J. Mol. Sci. 21Â (2), 487 (2020).
Huo, S-C. & Yue, B. Approaches to promoting bone marrow mesenchymal stem cell osteogenesis on orthopedic implant surface. World J. Stem Cells. 12 (7), 545–561 (2020).
Albala, D. M. & Lawson, J. H. Recent clinical and investigational applications of fibrin sealant in selected surgical specialties. J. Am. Coll. Surg. 202 (4), 685–697 (2006).
Li S, Wang J, Ma R, Zhao C, Gao Z, Quan X, Zhang Q: Analysis of the efficacy of drilling decompression autologous bone marrow and allogeneic bone grafting in the treatment of HIV-positive patients with early osteonecrosis of the femoral head. BMC Musculoskelet. Disord. 24(1), 902 (2023).
Xi H, Tao W, Jian Z, Sun X, Gong X, Huang L, Dong T: Levodopa attenuates cellular apoptosis in steroid-associated necrosis of the femoral head. Exp. Ther. Med. 13(1), 69–74 (2017).
Wang T, Teng S, Zhang Y, Wang F, Ding H, Guo L: Role of mesenchymal stem cells on differentiation in steroid-induced avascular necrosis of the femoral head. Exp. Ther. Med. 13(2), 669–675.(2017).
Li Y, Xu Z, Chang S: Glucocorticoids induce osteonecrosis of the femoral head through the Hippo signaling pathway. Open Life Sci 16(1), 1130–1140 (2021).
Wang Z, Sun Q-M, Zhang F-Q, Zhang Q-L, Wang L-G, Wang W-J: Core decompression combined with autologous bone marrow stem cells versus core decompression alone for patients with osteonecrosis of the femoral head: A meta-analysis. Int. J. Surg. 69, 23–31 (2019).
Li M, Ma Y, Fu G, Zhang R, Li Q, Deng Z, Zheng M, Zheng Q: 10-year follow-up results of the prospective, double-blinded, randomized, controlled study on autologous bone marrow buffy coat grafting combined with core decompression in patients with avascular necrosis of the femoral head. Stem. Cell. Res. Ther. 11(1), 287 (2020).
Wang J, Wang T, Zhang F, Zhang Y, Guo Y, Jiang X, Yang B: Roles of circular RNAs in osteogenic differentiation of bone marrow mesenchymal stem cells (Review). Mol. Med. Rep. 26(1), (2022).
Zeng J, Deng J, He C, Xiong Q-A, Li X, Wang Z: IGF-1 Induces Osteogenic Differentiation of Rat Bone Marrow Mesenchymal Stem Cells by Promoting SOX4 via the MAPK/ERK Pathway. Int. J. Stem. Cells. 17(4), 418–426 (2024).
Wang P, Sun T-F, Li G, Zhang H-M, Liu F-J, Gao Z-H, Cao S-N, Sun G-D, Du H-T, Wang C-A et al: The Separation of Antler Polypeptide and Its Effects on the Proliferation and Osteogenetic Differentiation of Bone Marrow Mesenchymal Stem Cells. Evid. Based. Complement. Alternat. Med. 2020, 1294151 (2020).
Zhang H, Fu X, Zhang S, Li Q, Chen Y, Liu H, Zhou W, Wei S: Strategy of Stem Cell Transplantation for Bone Regeneration with Functionalized Biomaterials and Vascularized Tissues in Immunocompetent Mice. ACS Biomater Sci Eng 8(4), 1656–1666 (2022).
Ren X, Shao Z, Fan W, Wang Z, Chen K, Yu X: Untargeted metabolomics reveals the effect of lovastatin on steroid-induced necrosis of the femoral head in rabbits. J Orthop Surg Res 15(1), 497 (2020).
RenLim YW, Kim YS, Lee JW, Kwon SY: Stem cell implantation for osteonecrosis of the femoral head. Exp. Mol. Med. 45(11), e61 (2013).
Jiang L-Y, Yu X, Pang Q-J: Research in the precaution of recombinant human erythropoietin to steroid-induced osteonecrosis of the rat femoral head. J. Int. Med. Res. 45(4), 1324–1331 (2017).
Özmen E, İzol Özmen H, Atasoy S, Dursun M, Bilgiç B, Salduz A: The effects of prophylactic tadalafil use on VEGF expression in the rabbit model of steroid-induced femoral head avascular necrosis. Acta. Orthop. Traumatol. Turc. 57(5), 237–242 (2023).
Ding H, Wang Y, Lu Y: [Treatment of osteonecrosis of the femoral head with vascularized bone grafting]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 35(3), 381–386 (2021).
Apte RS, Chen DS, Ferrara N: VEGF in Signaling and Disease: Beyond Discovery and Development. Cell. 176(6), 1248–1264 (2019).
Tian ZJ, Liu BY, Zhang YT, Chen XZ, Qiao GY, Wang S, Ma ZL: MiR-145 silencing promotes steroid-induced avascular necrosis of the femoral head repair via upregulating VEGF. Eur. Rev. Med. Pharmacol. Sci. 21(17), 3763–3769 (2017).
Mazidi M, Rokni H, Sahebkar AH, Mohammadi A, Ghayour-Mobarhan M, Ferns GA: Simvastatin Treatment Does Not Affect Serum Vitamin D Concentrations in Patients with Dyslipidemia: A Randomized Double-blind Placebo-controlled Cross-over Trial. Int. J. Prev. Med. 7, 80. (2016).
Takenaka M, Hirade K, Tanabe K, Akamatsu S, Dohi S, Matsuno H, Kozawa O: Simvastatin stimulates VEGF release via p44/p42 MAP kinase in vascular smooth muscle cells. Biochem Biophys Res Commun 301(1), 198–203 (2003).
Wang S-F, Ji Q-H, Qiao X-F, Zhao P, Xue Y, Li Y-B: Efficacy of artificial femoral head replacement for femoral head avascular necrosis. Med. 98(17), e15411 (2019).
Author information
Authors and Affiliations
Contributions
Qing Yang: Methodology, Data curation, Validation. Yi Yang: Methodology. Gang Li: Methodology, supervision. Biao Li: Conceptualization and review. All authors agree to be accountable for all aspects of this work, ensuring its integrity and accuracy.
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
About this article
Cite this article
Yang, Q., Yang, Y., Li, B. et al. Pravastatin combined with fibrin sealant-embedded BMSCs enhances recovery in steroid-induced avascular necrosis of the femoral head. Sci Rep (2026). https://doi.org/10.1038/s41598-026-35663-7
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41598-026-35663-7
