Clinical application of bone morphogenetic proteins for bone healing: a systematic review

Abstract

Purpose This paper documents the existing evidence on bone morphogenetic proteins (BMPs) use for the treatment of bone fractures, non-union, and osteonecrosis, through a review of the clinical literature, underlying potential and limitations in terms of cost effectiveness and risk of complications. Methods A systematic review was performed on the PubMed database using the following string: (bone morphogenetic proteins OR BMPs) and (bone repair OR bone regeneration) including papers from 2000 to 2016. The search focused on clinical trials dealing with BMPs application to favor bone regeneration in bone fractures, non-union, and osteonecrosis, in English language, with level of evidence I, II, III, and IV. Relevant data (type of study, number of patients, BMPs delivery material, dose, site, follow-up, outcome, and adverse events) were extracted and analyzed. Results Forty-four articles met the inclusion criteria: 10 randomized controlled trials (RCTs), 7 comparative studies, 18 case series, and 9 case reports. rhBMP-2 was documented mainly for the treatment of fractures, and rhBMP-7 mainly for non-unions and osteonecrosis. Mixed results were found among RCTs and comparative papers: 11 reported positive results for BMPs augmentation, 3 obtained no significant effects, and 2 showed negative results. The only study comparing the two BMPs showed a better outcome with rhBMP-2 for non-union treatment. Conclusion Clinical evidence on BMPs use for the treatment of fractures, non-union, and osteonecrosis is still controversial, with the few available reports being mainly of low quality. While positive findings have been described in many studies, mixed results are still present in the literature in terms of efficacy and adverse events. The difficulties in drawing clear conclusions are also due to the studies heterogeneity, mainly in terms of different BMPs applied, with different concomitant treatments for each bone pathology. Therefore, further research with well-designed studies is needed in order to understand the real potential of this biological approach to favour bone healing.

Optimising proliferation and migration of mesenchymal stem cells using platelet products: A rational approach to bone regeneration

“…For biological stimulation, while autologous bone graft remains the gold standard, recently, other forms have gained popularity including bone marrow aspirates (BMA) and/or growth factors . Since their introduction to the clinical setting, bone morphogenetic proteins (BMPs) have been extensively used for the treatment of nonunion fractures . There are numerous publications reporting on the clinical results of BMP‐2 and BMP‐7 .…”

“…5,6 Since their introduction to the clinical setting, bone morphogenetic proteins (BMPs) have been extensively used for the treatment of nonunion fractures. 7 There are numerous publications reporting on the clinical results of BMP-2 and BMP-7. [8][9][10] However, since the withdrawal of BMP-7 from the market and the license limitation of BMP-2 to be used for the management of open tibial fractures, other inductive molecules gained popularity such as demineralized bone matrix (DBM), 11 teriparatide, 12 and platelet products (PP).…”

Effects of Intermittent Administration of Parathyroid Hormone and Parathyroid Hormone‐Related Protein on Fracture Healing: A Narrative Review of Animal and Human Studies

“…In long bones, nearly 10% of fractures are associated with impaired healing . Bone grafting procedures or local applications of osteoinductive cytokines, such as bone morphogenetic protein‐2 and ‐7, are applied to promote repair of fractures with compromised healing . However, these procedures generally involve surgical intervention and therefore have a risk of potential infection and morbidity.…”

“…(2,3) Bone grafting procedures or local applications of osteoinductive cytokines, such as bone morphogenetic protein-2 and -7, are applied to promote repair of fractures with compromised healing. (4) However, these procedures generally involve surgical intervention and therefore have a risk of potential infection and morbidity. For this reason, the establishment of noninvasive therapy to promote healing in situations of compromised fracture repair is of great importance.…”

Bioengineering strategies for bone and cartilage tissue regeneration using growth factors and stem cells

“…Li et al (2003) compared the osteogenic activities of human BMPs (2, 4, 6, 7, and 9), and produced results similar to another study by Kang et al (2004) that compared 14 BMPs and their osteogenic potential. The most potent molecules in the BMP family are still under investigation in the preclinical stage (Krishnakumar, Roffi, Reale, Kon, & Filardo, 2017). Based on these findings, it is clear that many unanswered questions exist in terms of mechanisms of action and effectiveness of individual BMPs.…”