To The Editor:
As a condition for market approval of InFUSE Bone Graft/LT-CAGE Lumbar Tapered Fusion Device (Medtronic Sofamor Danek, Memphis, Tennessee)1, the U.S. Food and Drug Administration (FDA) required that a post-approval study be conducted to obtain six-year postoperative data from patients enrolled in the initial FDA investigational device exemption (IDE) studies2,3. Long-term safety and efficacy data for this population of patients, all of whom had single-level anterior lumbar interbody fusion assisted with stand-alone interbody fusion cages and recombinant human bone morphogenetic protein-2 on an absorbable collagen sponge (rhBMP-2/ACS), were reported by Burkus et al. in their study entitled "Six-Year Outcomes of Anterior Lumbar Interbody Arthrodesis with Use of Interbody Fusion Cages and Recombinant Human Bone Morphogenetic Protein-2" (2009;91:1181-9). A total of 277 patients who were managed with the InFUSE device were enrolled at thirty-one sites, including 143 patients in the open surgery arm and 134 patients in the laparoscopic surgery arm. The 2009 report by Burkus et al. provides seventy-two-month follow-up data on 146 of the 277 patients enrolled in the study, including seventy male patients.
Data posted on the FDA's web site indicate that retrograde ejaculation developed postoperatively in eleven patients (7.9% of 140 male patients) from the rhBMP-2/ACS IDE study group but in only one patient (1.4% of seventy male patients) from the autologous iliac crest bone graft group1.
In 2003, Sasso et al., without providing the incidence data reported by the FDA, attributed the onset of retrograde ejaculation in the IDE study population to surgical technique4. However, in addition to demonstrating a disparity in the incidence of retrograde ejaculation (7.9% in the rhBMP-2 group as compared with 1.4% in the autologous iliac crest bone graft group), the FDA data show that retrograde ejaculation in some patients in the IDE study was first reported nine to nineteen months postoperatively1. Wong et al. showed that adherence of the neural structures to ectopic bone caused neurologic compromise as long as twelve months after posterior interbody fusions involving the use of rhBMP/ACS5. Furthermore, Chen et al. recently presented cases of delayed neural compression following the use of rhBMP-2 for transforaminal lumbar interbody fusion (twenty-three to fifty-one months after rhBMP-2 application)6.
As the superior hypogastric plexus, which enervates the internal vesical sphincter, is in the retroperitoneal space at the lumbosacral junction, it is possible that rhBMP-2-related ectopic bone formation could eventually compromise this plexus, prompting delayed-onset retrograde ejaculation. We understand that Burkus et al. reported that although progressive ossification was observed anterior to the implants2,3, no ectopic bone formation was observed outside the anular confines of the disc space2. However, a close look at Figure 1 in the report on the rhBMP-2 FDA-sanctioned pilot study reveals that there was bone formation anterior to the instrumented disc space7.
Although the IDE data on the FDA web site demonstrate that eleven patients managed with rhBMP-2 (7.9% of 140 male patients) developed retrograde ejaculation, the six-year follow-up report by Burkus et al. did not mention a single patient with permanent retrograde ejaculation, nor did it mention ectopic bone formation anterior to the instrumented disc spaces.
We are interested in the authors’ experiences with respect to several issues. Were any of the eleven rhBMP-2 IDE patients who were reported in the FDA database to have retrograde ejaculation included in the follow-up study by Burkus et al.? How many patients had ectopic bone formation anterior to the instrumented disc space? How many patients who were managed with rhBMP-2 in the IDE study had late-onset retrograde ejaculation?