Longer follow-up continues to reveal no increased risk of cancer with the use of recombinant human bone morphogenetic protein in spine fusion.

BACKGROUND CONTEXT: Large observational studies on potential oncogenic effects of recombinant human bone morphogenetic protein (rhBMP) in spine fusion surgery are limited by relatively short follow-up times.

PURPOSE: To study the possible association between rhBMP and cancer risk in a long-term follow-up study.

STUDY

DESIGN

A retrospective cohort study using a combination of the Washington State Comprehensive Hospital Abstract Reporting System, the Washington State Cancer Registry, State of Washington death certificates, and the Washington State Department of Licensing.

PATIENT SAMPLE: Participants were adults age ≥21 years who underwent spine fusion surgery enhanced by rhBMP for degenerative spine disease between January 1, 2002 and December 31, 2010. A comparison group matching each patient receiving rhBMP with three patients not receiving rhBMP was created using the indicators of age, sex, and year of treatment. We excluded patients receiving spine fusion for vertebral fractures or infection, and those with a diagnosis of cancer before or at the index procedure.

OUTCOME MEASURES: The primary outcome was the first diagnosis of any cancer as identified in the records of the state cancer registry or death certificate through the end of 2015.

METHODS

We compared cancer risk between those receiving spine fusion with and without rhBMP using survival analysis. We calculated incidence rates (hazards) by computing the ratio of the number of events and total time at risk. Unadjusted hazard ratios (HR) and adjusted HR (aHR) and their respective 95% confidence intervals (CI) were calculated assuming a Cox proportional hazard regression model. We adjusted the model to include the site of surgery (lumbar vs. cervical) as a covariate as this differed in frequency between the two treatment groups. To assess whether rhBMP adversely affects the progression of cancer, we compared mortality between rhBMP users and nonusers in those who developed cancer. Research support toward this study was received from Medtronic Sofamor Danek USA. The investigators alone, and not Medtronic, were solely responsible for the design, conduct, analysis, and reporting of this study.

RESULTS

We included 16,914 patients who had spine fusion, of whom 4,246 received rhBMP. During the study period, 1,342 patients were diagnosed with some form of cancer. The incidence rate was similar between the two groups: 11.2 per 1,000 person years in the rhBMP group and 10.4 per 1,000 person years in the non-rhBMP group, with an aHR of 0.96; 95% CI, 0.85 to 1.10. Similarly, rhBMP use was not associated with an increased risk of commonly occurring individual cancer types, nor with cancer specific mortality after a cancer diagnosis, aHR, 0.92; 95% CI, 0.69 to 1.22.

CONCLUSIONS

Long-term follow-up confirms previous findings that rhBMP application treated with elective spinal fusion did not result in an increased cancer risk in a large population of US adults.