Bone Morphogenetic Protein for the Healing of Tibial Fracture: A Meta-Analysis of Randomized Controlled Trials

<div><p>Purpose</p><p>To review the evidence from RCTs on clinical outcomes and benefit of acute tibial fracture and nonunion treated with and without BMPs.</p><p>Material</p><p>We searched multiple databases (MEDLINE, EMABSE, BIOSIS and Cochrane central) as well as reference lists of articles and contacted authors. Evaluated outcomes included union rate, revision rate, hardware failure and infection. The weighted and standard mean difference (WMD and SMD) or the relative risk (RR) was calculated for continuous or dichotomous data respectively. The quality of the trial was assessed, and meta-analyses were performed with the Cochrane Collaboration’s REVMAN 5.0 software.</p><p>Results</p><p>Eight RCTs involving 1113 patients were included. For acute tibial fracture, BMP group was associated with a higher rate of union (RR, 1.16; 95% CI, 1.04 to 1.30) and a lower rate of revision (RR, 0.68; 95% CI, 0.54 to 0.85) compared with control group. No significant differences were found in rate of hardware failure and infection. The pooled RR for achieving union for tibial fracture nonunion was 0.98 (95% CI, 0.86 to 1.13). There was no significant difference between the two groups in the rate of revision (RR, 0.48; 95% CI, 0.13 to 1.85) and infection (RR, 0.61; 95% CI, 0.37 to 1.02).</p><p>Conclusion</p><p>Study on acute tibial fractures suggests that BMP is more effective that controls, for bone union and for decreasing the rate of surgical revision to achieve union. For the treatment of tibial fracture nonunion, BMP leads to similar results to as autogenous bone grafting. Finally, well-designed RCTs of BMP for tibial fracture treatment are also needed.</p></div

Forest plot of infection rate of acute tibial fracture treated with BMP versus control group.

<p>Note: a, b: The dose of 0.75 mg/ml and 1.5 mg/ml of BMP-2 are each compared to half of the control group</p

Forest plot of union rate of tibial nonunion treated with BMP versus control group.

<p>Forest plot of union rate of tibial nonunion treated with BMP versus control group.</p

Forest plot of revision rate of acute tibial fracture treated with BMP versus control group.

<p>Note: a, b: The dose of 0.75 mg/ml and 1.5 mg/ml of BMP-2 are each compared to half of the control group.</p

Forest plot of hardware failure rate of acute tibial fracture treated with BMP versus control group.

<p>Note: a, b: The dose of 0.75 mg/ml and 1.5 mg/ml of BMP-2 are each compared to half of the control group.</p

Forest plot of union rate of acute tibial fracture treated with BMP versus control group.

<p>Note: a, b: The dose of 0.75 mg/ml and 1.5 mg/ml of BMP-2 are each compared to half of the control group; SC: Intramedullary nail fixation and routine soft-tissue management.</p

Gene expression of MAG, MBP, MP22 and NCAM-1 in neuromas.

<p>Within the two groups, real-time quantitative PCR demonstrated that the expression of myelin-specific genes: MAG, MAP and PMP22, was markedly up-regulated and the expression of NCAM-1 was down-regulated at 8 weeks compared to 2 weeks (* vs 8 weeks in the no-capping group, all p<0.001; ♦ vs 2 weeks in the capping group, all p<0.001); moreover, between the two groups, significant differences in the expression levels of the four genes were noted both at 2-week and 8-week periods (*vs capping group at 2 weeks, all p<0.001; ♦ vs no-capping group at 8 weeks, all p<0.001).</p

Forest plot of infection rate of tibial nonunion treated with BMP versus control group.

<p>Forest plot of infection rate of tibial nonunion treated with BMP versus control group.</p

Relative mRNA expression of RhoA in the DRG (L4).

<p>The expression of RhoA in the L4 DRG was dramatically upregulated after surgery in comparison with the contralateral uninjured side at 2 weeks after surgery in both groups (both*p<0.001); however, its expression significantly dropped to the similar level of the uninjured contralateral side in the no-capping group at 8 weeks (▴p = 0.627), while it still remained in a higher level in the capping group in comparison with the contralateral side. (*p<0.001).</p

List of primers used for RT-PCR studies.

<p>List of primers used for RT-PCR studies.</p