115. Is the use of rh-BMP associated with increased incidence of cancer?

Abstract

<h3>BACKGROUND CONTEXT</h3> Recombinant human bone morphogenetic protein (rhBMP) is frequently used in spinal arthrodesis to stimulate bone fusion. However, there is a potential concern for rhBMP in the promotion of tumor growth due to presence of BMP receptors on a variety of cancer cells. <h3>PURPOSE</h3> The study was conducted to determine if there is an increased risk of developing cancer after exposure to rhBMP and if the risk is dose and/or exposure dependent. <h3>STUDY DESIGN/SETTING</h3> Level I evidence. <h3>PATIENT SAMPLE</h3> This study included 467,916 patients. <h3>OUTCOME MEASURES</h3> Incidence of cancer. <h3>Methods</h3> We conducted a systematic review of electronic databases using different MeSH terms from 2000 to 2020. Pooled and subgroup analyses were performed using fixed and random effect models based upon the heterogeneity (I2). The results were reported as odds ratio (OR) with 95% confidence interval (CI). Further scatter log plot was conducted to determine the dose-response relationship between rh-BMP and incidence of cancer. <h3>Results</h3> A total of 467,916 patients from 25-studies (10 randomized controlled trials, 14 retrospective cohort studies and 1 case-control study) were included. In our study, 110,808 patients (62.5% females) received rhBMP while the remaining 357,108 patients (58.4% females) were in the control group. There was no statistically significant difference in terms of age (p=0.37), body mass index (p=0.51) and mean follow-up (p=0.28) between the two groups. There did not exist any statistically significant difference in terms of cancer incidence between the treatment and control group (OR: 95% CI: 0.63-4.36, p=0.30). However, the patients receiving rhBMP2 had significantly higher risk of cancer than those receiving rh BMP7 (p=0.03) at a mean follow-up of 33.5±20.2 months. Furthermore, lower doses of rhBMP were associated with none-to-minimal incidence of cancer while those receiving higher doses were associated with increased risk of cancer. The steepest point of the dose-response curve corresponded with an EC50 of 8mg rhBMP. <h3>Conclusions</h3> Our study did not demonstrate any risk of tumorigenesis or metastasis with rhBMP administration compared to the placebo group. However, there was a dose-dependent correlation of rhBMP with cancer. Further prospective studies are needed to validate our results. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.