Optimizing alveolar bone grafting: rhBMP-2 alternative under scrutiny
The treatment of alveolar clefts in patients with cleft lip and palate relies on secondary alveolar bone grafting (ABG), which is essential for stabilizing the maxillary arch and promoting tooth eruption. While autologous bone remains the gold standard, complications at the donor site and the limited amount of material for large defects are pushing surgeons to explore high-performance alternatives. Recombinant human bone morphogenetic protein-2 (rhBMP-2) presents itself as a serious candidate, capable of acting on the entire osteogenesis process.
The objective of this meta-analysis, registered under protocol PROSPERO CRD42023397628, is to synthesize data from 6 randomized controlled trials (RCTs) comparing the efficacy of rhBMP-2 to that of autologous grafting. The authors specifically evaluated the bone formation rate (BF%), radiographic volume and density, as well as postoperative morbidity and hospitalization costs.
The central hypothesis is based on the ability of rhBMP-2 to induce bone regeneration equivalent or superior to autografts, while eliminating the risks of complications associated with harvesting. This study seeks to determine whether, despite past controversies regarding inflammatory side effects, rhBMP-2 now offers reproducible and reliable clinical results for the practitioner.
Selection protocol and methodological rigor
This meta-analysis, registered on PROSPERO (CRD42023397628), was conducted according to PRISMA guidelines. The authors screened five international databases (PubMed, Cochrane Library, Embase, Web of Science, and Scopus) to identify randomized controlled trials (RCTs) published up to February 2023. Out of 190 initial publications, 6 RCTs meeting the inclusion criteria (patients aged 7 to 15 years, follow-up ≥ 3 months) were selected.
The experimental design systematically compares two protocols:
- Test group (rhBMP-2): Use of recombinant human bone morphogenetic protein. Administered concentrations ranged from 0.05 to 1.5 mg/mL for total doses between 2.1 and 4.2 mg.
- Control group (Autograft): Autologous bone graft, harvested exclusively from the iliac crest in 100% of the included studies.
L'évaluation de la qualité osseuse (volume, densité et taux de formation BF%) a été réalisée par imagerie tridimensionnelle (CT, CBCT ou NewTom). Les complications post-opératoires et la durée d'hospitalisation ont été intégrées aux résultats secondaires. L'analyse statistique a utilisé des modèles à effets fixes ou aléatoires selon l'hétérogénéité des données (I²), avec un seuil de significativité fixé à p < 0,05.
Cohort analysis and study characteristics
The synthesis covers 6 randomized controlled trials (RCTs) totaling 103 patients (57 in the rhBMP-2 groups and 46 in the autologous bone graft control groups). The subjects, aged 7 to 15 years, presented with cleft lip and palate (UCLP or unilateral alveolar clefts). Postoperative follow-up extended over a period ranging from 3 to 12 months.
Intervention protocols and dosages
The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) followed various concentration protocols according to the included studies:
- Concentrations: from 0.05 mg/mL to 1.5 mg/mL.
- Total doses: from 2.1 mg to 4.2 mg per site.
- Control group: Systematically an autologous bone graft, mainly harvested from the iliac crest.
Critères d'évaluation et mesures radiographiques
Studies used three-dimensional imaging (CT-scan, CBCT or NewTom) to evaluate the quality and quantity of newly formed bone tissue. The main parameters analyzed are:
| Author (Year) | Effectiveness (Test/Control) | rhBMP-2 dose | Measured criteria |
|---|---|---|---|
| Herford (2007) | 10 / 2 | 4.2 mg (1.05 mg/mL) | Filling rate (4 months), edema |
| Canan (2012) | 6 / 6 | 3.2 - 4.2 mg (1.5 mg/mL) | Volume, density, filling rate (3, 6, 12 months) |
| Neovius (2013) | 3 / 4 | 0.05 - 0.25 mg/mL | Bone volume (3 months), edema |
| Tanikawa (2020) | 8 / 8 | 3.2 - 4.2 mg (1.5 mg/mL) | Filling rate (6 and 12 months), oedema |
Clinical observations and complications
The qualitative data analysis reports several types of postoperative complications closely monitored by the authors. In addition to evaluating the bone formation rate (BF%), calculated by the ratio between the volume of bone formed and the volume of the actual graft, the studies documented:
- The incidence of postoperative edema (noted in Herford, Neovius and Tanikawa).
- The presence of oronasal fistulas and graft losses (Dickinson et al., 2008).
- L'exposition du matériau de greffe (Liang et al., 2017).
Les auteurs soulignent que bien que la rhBMP-2 soit approuvée comme alternative à l'autogreffe, les résultats en termes de volume et de densité osseuse restent sujets à une variabilité méthodologique entre les centres, nécessitant une analyse rigoureuse des taux de formation osseuse rapportés.
Clinical analysis of results
This meta-analysis, synthesizing data from 6 randomized controlled trials (RCTs), evaluates the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) compared to iliac autograft, the current gold standard for the treatment of alveolar clefts. The results show that rhBMP-2 acts on the entire osteogenesis process, from the mesenchymal progenitor cell to the osteoblast, thus promoting bone formation and revascularization. Clinically, the use of 1.5 mg/mL of rhBMP-2 achieves bone fill rates and volumes comparable to autologous bone, while eliminating complications related to the donor site. However, the use of rhBMP-2 is not without morbidity: studies by Herford (2007) and Tanikawa (2020) report postoperative inflammation and marked oedema, while risks of osteoclast-mediated bone resorption and ectopic bone formations are documented in the analysed literature.
Limits and perspective
The main weakness of this meta-analysis lies in the modest size of the included samples (n=5 to n=35 depending on the studies), which limits the overall statistical power. Furthermore, the variability of the evaluation criteria (fill rate vs density vs volume) and follow-up periods (3 to 12 months) complicates the standardization of recommendations. Although rhBMP-2 is approved as an alternative, the authors highlight that the results sometimes remain inconsistent, particularly regarding the final bone density compared to iliac autologous grafting.
Implications for practice
For the practitioner, rhBMP-2 represents a serious therapeutic option when the volume of available autologous bone is insufficient or to avoid iliac harvest surgery. The management of postoperative inflammation then becomes the critical point of clinical follow-up. The balance between the benefit of rapid regeneration and the risk of inflammatory side effects must guide the therapeutic choice, particularly in patients aged 7 to 15 years followed in these studies.
Summary of results
This meta-analysis of 6 randomized clinical trials (n=103 patients) demonstrates that rhBMP-2, used at concentrations ranging from 0.05 mg/mL to 1.5 mg/mL, offers bone regeneration and density results comparable to the standard iliac autograft. Although it eliminates donor site complications, its application remains marked by an increased prevalence of postoperative edema, highlighting a necessary trade-off between surgical comfort and inflammatory reactions.
In concrete terms, for the practitioner:
- Alternative to autograft: Consider rhBMP-2 as a viable option for wide alveolar clefts when autogenous bone volume is insufficient or to avoid morbidity from iliac harvesting.
- Postoperative anticipation: Plan for proactive inflammation management, as swelling is more frequent and more pronounced than with conventional grafting.
- Benefit-risk assessment: Despite high bone success rates, remain vigilant regarding potential risks of osteoclast-mediated resorption or ectopic bone formation described in clinical data.
Source
- Original title: The effectiveness of using recombinant human bone morphogenetic protein-2 in the reconstruction of alveolar clefts: a meta-analysis
- Authors: Hongtu Xu, Zhina Liu
- Publication: Frontiers in Oral Health - 2026-06-16
- DOI: https://doi.org/10.3389/froh.2026.1786495
Information intended for healthcare professionals. This content may contain errors or truncated summaries. We recommend always verifying with the original source article. Delynov disclaims all responsibility regarding the use of this information. This document is not intended for patients or the general public.