Research progress of bone morphogenetic protein 2 in hip preservation treatment for femoral head necrosis

doi:10.3877/cma.j.issn.1674-134X.2025.04.009

Abstract

Abstract:

Osteonecrosis of the femoral head (ONFH) is a necrosis of bone tissue caused by interrupted blood supply, often leading to femoral head collapse and loss of hip joint function. For young patients, hip preservation surgery has become an important option as it reduces the risk of hip replacement surgery and functional limitations. In recent years, bone morphogenetic protein 2 (BMP2) has gradually become an innovative strategy for treating femoral head necrosis due to its key role in bone formation. BMP2 can promote osteogenesis and angiogenesis, significantly enhancing the effectiveness of hip preservation treatment for femoral head necrosis when combined with bone repair materials through local delivery systems. When used in conjunction with quadratus femoris muscle-bone flap transplantation, BMP2 has demonstrated unique advantages in accelerating bone regeneration and improving surgical efficacy, providing strong support for emerging treatment methods.

Key words: Femur head necrosis, Hip, Bone morphogenetic protein 2

Yaolin Zhang, Teng Wang, Xi Yang, Huan Luo, Yongqing Xu. Research progress of bone morphogenetic protein 2 in hip preservation treatment for femoral head necrosis[J]. Chinese Journal of Joint Surgery(Electronic Edition), 2025, 19(04): 472-477.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhgjwkzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-134X.2025.04.009

https://zhgjwkzz.cma-cmc.com.cn/EN/Y2025/V19/I04/472

References 49

[1]	Li L, Zhao S, Leng Z, et al. Pathological mechanisms and related markers of steroid-induced osteonecrosis of the femoral head [J/OL]. Ann Med, 2024, 56（1）: 2416070.DOI:10.1080/07853890.2024.2416070.
[2]	Walsh DW, Godson C, Brazil DP, et al. Extracellular BMP-antagonist regulation in development and disease: tied up in knots [J]. Trends Cell Biol, 2010, 20（5）: 244-256.
[3]	Murphy J, Pak S, Shteynman L, et al. Mechanisms and preventative strategies for persistent pain following knee and hip joint replacement surgery: a narrative review[J/OL]. Int J MolSci, 2024, 25（9）: 4722. DOI:10.3390/ijms25094722.
[4]	朱诗白, 张啸天, 陈曦, 等.股骨头坏死的保髋治疗[J/OL]. 中华关节外科杂志（电子版）, 2020, 14 （06）:741-746.
[5]	Mo L, Li J, Wang Z, et al. Influence of less invasive hip preservation surgery on subsequent hip arthroplasty for osteonecrosis of the femoral head [J]. J Hip Preserv Surg, 2022, 9（3）: 197-205.
[6]	Rainov NG, Schneiderhan R, Haritonov D. Triangular titanium implants for sacroiliac joint fusion[J/OL]. Acta Neurochir, 2024, 166（1）: 462. DOI:10.1007/s00701-024-06357-8.
[7]	Goyal S, Shrivastav S, Ambade R, et al. New technique of reverse bone grafting with core decompression and enriching with regenerative medicine techniques for grade 2 and grade 3 avascular necrosis of both hips [J/OL]. Cureus, 2023, 15（12）: e51425. DOI:10.7759/cureus.51425.
[8]	徐永清, 浦路桥, 李川, 等. 保留后上支持动脉的股方肌骨瓣治疗股骨头坏死的临床研究 [J/OL]. 中华关节外科杂志（电子版）, 2022, 16 （06）:664-669.
[9]	杨飞, 曲彦隆, 杨鹏. 骨形态发生蛋白对人工关节周围诱导成骨的影响 [J/OL]. 中华关节外科杂志（电子版）, 2011, 5（6）: 770-773.
[10]	Xu X, Hui W, Liu N, et al. Effects of ergosteroside combined risedronate on fracture healing and BMP-2, BMP-7 and VEGF expression in rats[J/OL]. Acta Cir Bras, 2021, 36（11）: e361107. DOI:10.1590/ACB361107.
[11]	Gao H, Wang X. Serum miRNA-142 and BMP-2 are markers of recovery following hip replacement surgery for femoral neck fracture[J/OL]. ExpTher Med, 2020, 20（5）: 105. DOI:10.3892/etm.2020.9235.
[12]	Urist MR. Bone: formation by autoinduction. 1965[J]. Clin Orthop Relat Res, 2002（395）: 4-10.
[13]	Ripamonti U, Petit JC. Bone morphogenetic proteins, cementogenesis, myoblastic stem cells and the induction of periodontal tissue regeneration [J]. Cytokine Growth Factor Rev, 2009, 20（5-6）: 489-499.
[14]	李明军, 冯玉娇, 齐保闯, 等. 负载rh-BMP2的羟基磷灰石人工骨治疗胫骨平台骨折骨缺损的临床疗效研究[J]. 生物骨科材料与临床研究, 2023, 20（6）: 56-61.
[15]	Li Z, Wang W, Xu H, et al. Effects of altered CXCL12/CXCR4 axis on BMP2/Smad/Runx2/Osterix axis and osteogenic gene expressions during osteogenic differentiation of MSCs [J]. Am J Transl Res, 2017, 9（4）: 1680-1693.
[16]	Qiu WX, Ma XL, Lin X, et al. Deficiency of Macf1 in osterix expressing cells decreases bone formation by Bmp2/Smad/Runx2 pathway[J]. J Cell Mol Med, 2020, 24（1）: 317-327.
[17]	Xu HJ, Liu XZ, Yang L, et al. Runx2 overexpression promotes bone repair of osteonecrosis of the femoral head （ONFH）[J]. Mol Biol Rep, 2023, 50（6）: 4769-4779.
[18]	Li T, Xiao K, Xu Y, et al. Identification of long non-coding RNAs expressed during the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells obtained from patients with ONFH [J]. Int J Mol Med, 2020, 46（5）: 1721-1732.
[19]	Leknes KN, Yang J, Qahash M, et al. Alveolar ridge augmentation using implants coated with recombinant human bone morphogenetic protein-2: radiographic observations [J]. Clin Oral Implants Res, 2008, 19（10）: 1027-1033.
[20]	Högel F, Militz M, Bühren V, et al. Percutaneous administration of recombinant human bone morphogenetic protein-7 （rhBMP-7） after callus distraction. Two case reports [J]. Unfallchirurg, 2011, 114（2）: 167-171.
[21]	Zhu XX, Meng XY, Chen G, et al. Nesfatin-1 enhances vascular smooth muscle calcification through facilitating BMP-2 osteogenic signaling[J/OL]. Cell Commun Signal, 2024, 22（1）: 488. DOI:10.1186/s12964-024-01873-7.
[22]	Liu K, Meng CX, Lv ZY, et al. Enhancement of BMP-2 and VEGF carried by mineralized collagen for mandibular bone regeneration [J]. Regen Biomater, 2020, 7（4）: 435-440.
[23]	Chen WC, Chung CH, Lu YC, et al. BMP-2 induces angiogenesis by provoking integrin α6 expression in human endothelial progenitor cells [J]. BiochemPharmacol, 2018, 150: 256-266.
[24]	Rong K, Li X, Jiang W, et al. Alendronate alleviated femoral head necrosis and upregulated BMP2/EIF2AK3/EIF2A/ATF4 pathway in liquid nitrogen treated rats [J]. Drug Des Devel Ther, 2021, 15: 1717-1724.
[25]	Rifas L. T-cell cytokine induction of BMP-2 regulates human mesenchymal stromal cell differentiation and mineralization [J]. J Cell Biochem, 2006, 98（4）: 706-714.
[26]	Wang Z, Zhang Y, Suo Y, et al. Cannulated screw internal fixation combined with Quadratusfemoris muscle bone flap transplantation in the treatment of femoral neck fracture in young adults [J]. Minerva Pediatr, 2022, 74（3）: 383-385.
[27]	Kanakaris NK, Giannoudis PV. Clinical applications of bone morphogenetic proteins: current evidence[J]. J Surg Orthop Adv, 2008, 17（3）: 133-146.
[28]	Wang XJ, Zhang ZH, Li L, et al. Quadratusfemoris muscle pedicle bone flap transplantation in the treatment of femoral neck fracture for Chinese young and middle-aged patients: a systematic review and meta-analysis [J]. Chin J Traumatol, 2017, 20（6）: 347-351.
[29]	Chen S, Fu K, Cai Q, et al. Development of a risk-predicting score for hip preservation with bone grafting therapy for osteonecrosis[J/OL]. iScience, 2024, 27（4）: 109332.DOI:10.1016/j.isci.2024.109332.
[30]	Chun YS, Lee DH, Won TG, et al. Cell therapy for osteonecrosis of femoral head and joint preservation [J/OL]. J Clin Orthop Trauma, 2021, 24: 101713.DOI:10.1016/j.jcot.2021.101713.
[31]	Chae DS, Han S, Lee MK, et al. BMP-2 genome-edited human MSCs protect against cartilage degeneration via suppression of IL-34 in collagen-induced arthritis [J/OL]. Int J Mol Sci, 2023, 24（9）: 8223. DOI:10.3390/ijms24098223.
[32]	Wang W, Yeung KWK. Bone grafts and biomaterials substitutes for bone defect repair: a review [J]. Bioact Mater, 2017, 2（4）: 224-247.
[33]	Haider A, Kim S, Huh MW, et al. BMP-2 grafted nHA/PLGA hybrid nanofiber scaffold stimulates osteoblastic cells growth[J/OL]. Biomed Res Int, 2015, 2015: 281909.DOI:10.1155/2015/281909.
[34]	Bedair TM, Lee CK, Kim DS, et al. Magnesium hydroxide-incorporated PLGA composite attenuates inflammation and promotes BMP2-induced bone formation in spinal fusion[J/OL]. J Tissue Eng, 2020, 11: 2041731420967591.DOI:10.1177/2041731420967591.
[35]	Ma C, Park MS, Alves do Monte F, et al. Local BMP2 hydrogel therapy for robust bone regeneration in a porcine model of Legg-Calvé-Perthes disease[J/OL]. NPJ Regen Med, 2023, 8（1）: 50. DOI:10.1038/s41536-023-00322-2.
[36]	Zhang Y, Yang S, Zhou W, et al. Addition of a synthetically fabricated osteoinductive biphasic calcium phosphate bone graft to BMP2 improves new bone formation[J]. Clin Implant Dent Relat Res, 2016, 18（6）: 1238-1247.
[37]	Dong R, Kang M, Qu Y, et al. Incorporating hydrogel （with low polymeric content） into 3D-printed PLGA scaffolds for local and sustained release of BMP2 in repairing large segmental bone defects[J/OL]. Adv Healthc Mater, 2025, 14（2）: e2403613. DOI:10.1002/adhm.202403613.
[38]	李子荣, 孙伟, 史振才, 等. 加入和未加骨形态发生蛋白2的打压植骨术治疗股骨头坏死[J]. 中国骨与关节外科, 2012, 5（5）: 377-381.
[39]	Lou J, Meyer C, Chen A, et al. Immobilization of BMP-2 in porous hydrogels to spatially regulate osteogenesis[J]. J Control Release, 2025, 379: 944-950.
[40]	Huang CC, Kang M, Lu Y, et al. Functionally engineered extracellular vesicles improve bone regeneration[J]. Acta Biomater, 2020, 109: 182-194.
[41]	Zheng Z, Yin W, Zara JN, et al. The use of BMP-2 coupled–Nanosilver-PLGA composite grafts to induce bone repair in grossly infected segmental defects[J]. Biomaterials, 2010, 31（35）: 9293-9300.
[42]	Darjanki CM, Hananta JS, Prahasanti C, et al. Expression of VEGF and BMP-2 in Osteoblast cells exposed to a combination of polymethylmethacrylate （PMMA） and hydroxyapatite （HAp）[J]. J Oral Biol Craniofac Res, 2023, 13（2）: 243-248.
[43]	Dashtimoghadam E, Fahimipour F, Tongas N, et al. Microfluidic fabrication of microcarriers with sequential delivery of VEGF and BMP-2 for bone regeneration[J/OL]. Sci Rep, 2020, 10（1）: 11764. DOI:10.1038/s41598-020-68221-w.
[44]	Vantucci CE, Krishan L, Cheng A, et al. BMP-2 delivery strategy modulates local bone regeneration and systemic immune responses to complex extremity trauma[J]. Biomater Sci, 2021, 9（5）: 1668-1682.
[45]	Sharma S, Sapkota D, Xue Y, et al. Delivery of VEGFA in bone marrow stromal cells seeded in copolymer scaffold enhances angiogenesis, but is inadequate for osteogenesis as compared with the dual delivery of VEGFA and BMP2 in a subcutaneous mouse model[J/OL]. Stem Cell Res Ther, 2018, 9（1）: 23. DOI:10.1186/s13287-018-0778-4.
[46]	Freeman FE, Pitacco P, Van Dommelen LHA, et al. Development of a 3D bioprinted scaffold with spatio-temporally defined patterns of BMP-2 and VEGF for the regeneration of large bone defects[J/OL]. Bio Protoc, 2021, 11（21）: e4219. DOI:10.21769/BioProtoc.4219.
[47]	Guo T, Yuan X, Li X, et al. Bone regeneration of mouse critical-sized calvarial defects with human mesenchymal stem cell sheets co-expressing BMP2 and VEGF[J]. J Dent Sci, 2023, 18（1）: 135-144.
[48]	Geng Y, Duan H, Xu L, et al. BMP-2 and VEGF-A modRNAs in collagen scaffold synergistically drive bone repair through osteogenic and angiogenic pathways[J/OL]. Commun Biol, 2021, 4（1）: 82. DOI:10.1038/s42003-020-01606-9.
[49]	Liu Z, Xu Z, Wang X, et al. Preparation and biocompatibility of core-shell microspheres for sequential, sustained release of BMP-2 and VEGF[J/OL]. Biomed Res Int, 2022, 2022: 4072975.DOI:10.1155/2022/4072975.

Please choose a citation manager

Content to export