Efficacy of Recombinant Human BMP2 and PDGF-BB in Orofacial Bone Regeneration: A Systematic Review and Meta-analysis

Abstract

With the rapid development of tissue engineering therapies, there is a growing interest in the application of recombinant human growth factors (rhGFs) to regenerate human orofacial bones. However, despite reports of their ability to promote orofacial bone regeneration in animal experiments, their benefits in human clinical treatments remain unclear. Furthermore, the appropriate concentrations or indications of a specific rhGF remain ambiguous. Therefore it is essential to collect data from diverse clinical trials to evaluate their effects more precisely. Here we reviewed randomized clinical trials (RCT) that focused on the utilization of rhGFs in orofacial bone regeneration. Data from included studies were extracted, pooled and then quantitatively analyzed according to a pre-established protocol. Our results indicate that all current concentrations of rhBMP-2 produces insufficient effect on promoting either tooth extraction socket healing, sinus augmentation or reconstruction of alveolar clefts. However, 0.3 mg/ml rhPDGF-BB promotes the healing of tooth extraction sockets, though the effect does not reach a level of statistical significance. Summarily, we recommend concentrations of 0.3 mg/ml rhPDGF-BB only for the healing of tooth extraction sockets.

Figure 1

Forest plot of comparison: The effect of rhBMP-2 for alveolar reconstruction in CLP patients and for the healing of tooth extraction socket. (A) The measurement of bone formation rate when utilizing a concentration of 1.5 mg/ml rhBMP-2 in CLP patients. (B) The measurement of increased bone volume when utilizing a concentration of 1.5 mg/ml rhBMP-2 in CLP patients. (C) The measurement of the primary outcome of tooth extraction socket healing, namely alveolar bone height change, when utilizing only a concentration of 1.5 mg/ml rhBMP-2. (D) The measurement of the primary outcome of tooth extraction socket healing, namely alveolar bone height change, when taking the results of utilizing three concentrations of rhBMP-2 (0.05 mg/ml, 0.75 mg/ml, 1.5 mg/ml) into consideration. Risk of bias legends: A-random sequence generation (selection bias); B-allocation concealment (selection bias); C-blinding of participants and personnel (performance bias); D-blinding of outcome assessment (detection bias); E-incomplete outcome data (attrition bias); F-selective reporting (reporting bias); G-other bias. +: low risk; ?: unclear risk; −: high risk. All following figures of the risk of bias share the same legends of this figure, therefore this section of legends will not be presented repeatedly in the below figures.

Figure 2

Forest plot of comparison: The effect of only 1.5 mg/ml rhBMP-2 for the healing of tooth extraction socket; outcome: alveolar bone width change. (A) The assessment of alveolar bone width change at the 25% distance from alveolar crest to socket bottom. (B) The assessment of alveolar bone width change at the 50% distance from alveolar crest to socket bottom. (C) The assessment of alveolar bone width change at the 75% distance from alveolar crest to socket bottom.

Figure 3

Forest plot of comparison: The effect of three concentration of rhBMP-2 (0.05 mg/ml, 0.75 mg/ml, and 1.5 mg/ml) for the healing of tooth extraction socket; outcome: alveolar bone width change. (A) The assessment of alveolar bone width change at the 25% distance from alveolar crest to socket bottom. (B) The assessment of alveolar bone width change at the 50% distance from alveolar crest to socket bottom. (C) The assessment of alveolar bone width change at the 75% distance from alveolar crest to socket bottom.

Figure 4

Forest plot of comparison: The effect of rhBMP-2 for sinus augmentation and the effect of rhPDGF-BB for the healing of tooth extraction socket. (A) The assessment of 1.5 mg/ml rhBMP-2 for sinus augmentation; outcome: alveolar bone height change. (B) The assessment of 0.75 mg/ml and 1.5 mg/ml rhBMP-2 for sinus augmentation; outcome: alveolar bone height change. (C) The assessment of 1.5 mg/ml and 1 mg/ml rhBMP-2 for sinus augmentation; outcome: morphometric bone formation rate. (D) The effect of 0.3 mg/ml rhPDGF-BB on the healing of tooth extraction socket; outcome: bone formation rate.