Clinical use of bone morphogenetic proteins BMP-2 and BMP-7: analysis of current clinical trials
- Authors: Mukhametov U.F.1, Lyulin S.V.2, Borzunov D.Y.3, Gareev I.F.4
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Affiliations:
- Kuvatov Republican Clinical Hospital
- Medical Center Carmel
- Ural State Medical University
- Bashkir State Medical University
- Issue: Vol 15, No 1 (2023)
- Pages: 5-20
- Section: Reviews
- URL: https://journals.eco-vector.com/vszgmu/article/view/112617
- DOI: https://doi.org/10.17816/mechnikov112617
- ID: 112617
Cite item
Abstract
Bone morphogenetic proteins have been used in clinical practice in orthopedics, spine surgery, and maxillofacial surgery for nearly a decade. According to research findings, in most cases the frequency of coalescence when using bone morphogenetic proteins is comparable to or higer that the corresponding indicator when using an autograft. To date, BMP-2 and BMP-7 are commercially available for clinical use and have shown efficacy equal to that of autograft in bone defect replacement.
This study analyzes existing clinical trials registered on the clinicaltirals.gov website for the therapeutic use of BMP-2 and BMP-7 in pathologies of the musculoskeletal system.
The search strategy was to use the material from the clinicaltrials.gov website, which focuses on key terms such as bonemorphogenetic protein 2 or BMP-2, bone morphogenetic protein 7 or BMP-7, recombinant bone morphogenetic protein 2 or rhBMP-2”, “recombinant bone morphogenetic protein 7 or rhBMP-7”, “InductOs”, “Op1”, “bone” and “diseases of the musculoskeletal system”. The inclusion and exclusion criteria were divided into two stages.
By October 2022, about 85 clinical trials had been registered using BMP-2 and about 12 using BMP-7. Most of the studies are in Phase 2, Phase 2–3, or Phase 4. Most of them focus on areas such as tibial trauma therapy and spinal surgery. However, only 12 clinical trials using BMP-2 provide meaningful results. All the clinical trials have similar preparation methods, and 12 clinical trials have provided positive results without serious side effects.
There is a wide potential for clinical use of BMP-2. Many preclinical and clinical studies on the use of BMP-2 and BMP-7 are currently underway; their future results will further explore their therapeutic potential in treating musculoskeletal diseases.
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About the authors
Ural F. Mukhametov
Kuvatov Republican Clinical Hospital
Email: ufa.rkbkuv@doctorrb.ru
ORCID iD: 0000-0003-3694-3302
MD, Cand. Sci. (Med.)
Russian Federation, 3 Lenin St., Ufa, 450008Sergey V. Lyulin
Medical Center Carmel
Email: carmel74@yandex.ru
ORCID iD: 0000-0002-2549-1059
SPIN-code: 4968-8680
Scopus Author ID: 6701421057
MD, Dr. Sci. (Med.)
Russian Federation, ChelyabinskDmitry Yu. Borzunov
Ural State Medical University
Email: borzunov@bk.ru
ORCID iD: 0000-0003-3720-5467
SPIN-code: 6858-8005
Scopus Author ID: 17433431500
MD, Dr. Sci. (Med.), Professor
Russian Federation, EkaterinburgIlgiz F. Gareev
Bashkir State Medical University
Author for correspondence.
Email: ilgiz_gareev@mail.ru
ORCID iD: 0000-0002-4965-0835
SPIN-code: 3839-0621
Scopus Author ID: 57206481534
MD, PhD
Russian Federation, 3 Lenin St., Ufa, 450008References
- Sampath TK, Reddi AH. Discovery of bone morphogenetic proteins — A historical perspective. Bone. 2020;140:115548. doi: 10.1016/j.bone.2020.115548
- Gomez-Puerto MC, Iyengar PV, García de Vinuesa A, et al. Bone morphogenetic protein receptor signal transduction in human disease. J Pathol. 2019;247(1):9–20. doi: 10.1002/path.5170
- Mukhametov UF, Lyulin SV, Borzunov DY, Gareev IF. Stimulation of bone regeneration using bone morphogenetic proteins: modern concepts. Herald of North-Western State Medical University named after I.I. Mechnikov. 2021;13(4):15–30. (In Russ.) doi: 10.17816/mechnikov82711
- Mukhametov U, Lyulin S, Borzunov D, et al. Functions of the bone morphogenetic protein signaling pathway through non-coding RNAs. Noncoding RNA Res. 2022;7(3):178–183. doi: 10.1016/j.ncrna.2022.07.002
- Jain AP, Pundir S, Sharma A. Bone morphogenetic proteins: The anomalous molecules. J Indian Soc Periodontol. 2013;17(5):583–586. doi: 10.4103/0972-124X.119275
- Indjeian VB, Kingman GA, Jones FC, et al. Evolving new skeletal traits by cis-regulatory changes in bone morphogenetic proteins. Cell. 2016;164(1–2):45–56. doi: 10.1016/j.cell.2015.12.007
- Dumic-Cule I, Peric M, Kucko L, et al. Bone morphogenetic proteins in fracture repair. Int Orthop. 2018;42(11):2619–2626. doi: 10.1007/s00264-018-4153-y
- Hinsenkamp M, Collard JF. Growth factors in orthopaedic surgery: demineralized bone matrix versus recombinant bone morphogenetic proteins. Int Orthop. 2015;39(1):137–147. doi: 10.1007/s00264-014-2562-0
- Son HJ, Lee MN, Kim Y, et al. Bone generation following repeated administration of recombinant bone morphogenetic protein 2. Tissue Eng Regen Med. 2021;18(1):155–164. doi: 10.1007/s13770-020-00290-4
- Von Rüden C, Morgenstern M, Hierholzer C, et al. The missing effect of human recombinant Bone Morphogenetic Proteins BMP-2 and BMP-7 in surgical treatment of aseptic forearm nonunion. Injury. 2016;47(4):919–924. doi: 10.1016/j.injury.2015.11.038
- Poynton AR, Lane JM. Safety profile for the clinical use of bone morphogenetic proteins in the spine. Spine (Phila Pa 1976). 2002;27(16 Suppl 1):S40–48. doi: 10.1097/00007632-200208151-00010
- Bannwarth M, Smith JS, Bess S, et al. Use of rhBMP-2 for adult spinal deformity surgery: patterns of usage and changes over the past decade. Neurosurg Focus. 2021;50(6):E4. doi: 10.3171/2021.3.FOCUS2164
- Papanagiotou M, Dailiana ZH, Karachalios T, et al. RhBMP-7 for the treatment of nonunion of fractures of long bones. Bone Joint J. 2015;97–B(7):997–1003. doi: 10.1302/0301-620X.97B7.35089
- Mukhametov UF, Lyulin SV, Borzunov DYu, et al. Heterotopic ossification as a side effect of the use of recombinant human bone morphogenetic proteins. Orthopaedic Genius. 2022;28(1):123–132. (In Russ.) doi: 10.18019/1028-4427-2022-28-1-123-132
- McGrath M, Feroze AH, Nistal D, et al. Impact of surgeon rhBMP-2 cost awareness on complication rates and health system costs for spinal arthrodesis. Neurosurg Focus. 2021;50(6):E5. doi: 10.3171/2021.3.FOCUS2152
- Nosho S, Ono M, Komori T, et al. Preclinical bioequivalence study of E. coli-derived rhBMP-2/β-TCP and autogenous bone in a canine guided-bone regeneration model. J Prosthodont Res. 2022;66(1):124–130. doi: 10.2186/jpr.JPR_D_20_00226
- Chen H, Yu Y, Wang C, et al. The regulatory role of sulfated polysaccharides in facilitating rhBMP-2-induced osteogenesis. Biomater Sci. 2019;7(10):4375–4387. doi: 10.1039/c9bm00529c
- Kisiel M, Ventura M, Oommen OP, et al. Critical assessment of rhBMP-2 mediated bone induction: an in vitro and in vivo evaluation. J Control Release. 2012;162(3):646–653. doi: 10.1016/j.jconre.l.2012.08.004
- Khan SN, Lane JM. The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in orthopaedic applications. Expert Opin Biol Ther. 2004;4(5):741–748. doi: 10.1517/14712598.4.5.741
- Bobyn J, Rasch A, Little DG, Schindeler A. Posterolateral inter-transverse lumbar fusion in a mouse model. J Orthop Surg Res. 2013;8:2. doi: 10.1186/1749-799X-8-2
- Hosseinpour S, Rad MR, Khojasteh A, Zadeh HH. Antibody administration for bone tissue engineering: a systematic review. Curr Stem Cell Res Ther. 2018;13(4):292–315. doi: 10.2174/1574888X13666180207095314
- Mukhametov UF, Liulin SV, Borzunov DYu, et al. The risk of tumor with the use of recombinant human bone morphogenetic proteins. Orthopaedic Genius. 2022;28(4):592–598. (In Russ.) doi: 10.18019/1028-4427-2022-28-4-592-598