Recombinant human bone morphogenetic protein 2 labeled use in spinal surgery and sexual dysfunction.

Dear Sir,

We have read with great interest the recent review article by Epstein, entitled “Pros, cons, and costs of INFUSE in spinal surgery”.[6] We would like to congratulate the author on the thorough review of the current findings on the controversial topic of the “off-label” use of bone morphogenetic protein INFUSE™ [recombinant human bone morphogenetic protein-2 (rhBMP-2); Medtronic, Memphis, TN, USA] in cervical, thoracic, and lumbar spine surgery.[6]

We would also like to commend the author for listing sexual dysfunction among the complications reported in conjunction with the application of INFUSE™ and the LT Cage™,[6] as it is a complication that has not been mentioned in this context until recently.[17-22] Sexual dysfunction, particularly retrograde ejaculation (RE), was so far encountered only after anterior lumbar interbody fusion (ALIF), a procedure in which the application of INFUSE was approved by the US Food and Drug Administration (FDA).[14] It has been described in the articles by Burkus et al.[2] and Sasso et al.,[13] and clearly stated as “a potential adverse event which may occur with spinal fusion surgery with the INFUSE™ Bone Graft/LT-CAGE™ Lumbar Tapered Fusion Device” in the FDA Device Approval Summary of Safety and Effectiveness Data.[14]

The underlying mechanism of the dysfunction is the inability of the internal vesical sphincter to contract during ejaculation, resulting in retrograde flow of semen to the urinary bladder.[13] As the muscle is innervated by the superior hypogastric plexus, i.e., a thin, retroperitoneal plexus of nerves overlying the lumbosacral junction, damage to the plexus during (or after) ALIF can denervate the bladder neck sphincter.

To the best of our knowledge, we were the first to point out the connection between sexual dysfunction and rhBMP-2 use in spinal surgery.[17-22] The authors of the studies[192022] have categorically denied this causal relationship, although they did not provide any explanation for the appearance of the dysfunction, months after the surgical procedures (according to the FDA's reporting),[14] which is in concordance with current findings on late inflammatory reactions and/or pressure exerted by the ectopic bone on the superior hypogastric plexus.

Finally, by examining the articles cited by Epstein,[13-57-12151623-25] we did not find any mention of sexual dysfunction as a complication. Therefore, we would like to know what source the author referred to when stating sexual dysfunction as a complication of, if we understood correctly, “off-labeled” application of INFUSE™ in spinal surgery?

In the study I published in January in Surgical Neurology International entitled “Pros, Cons, and Costs of INFUSE in Spinal Surgery”, I reported that INFUSE and the LT Cage, were associated with sexual dysfunction.[26] I would like to clarify that I was referring to retrograde ejaculation alone.

The authors of this commentary further expanded upon the etiology and physiology of retrograde ejaculation which may occur when recombinant human bone morphogenetic protein-2 [rhBMP-2] [INFUSE: Medtronic, Memphis, TN USA] is utilized to perform anterior lumbar interbody fusions [ALIF] with the LT Lumbar Tapered Fusion Device.[27-29]

The authors go on to discuss the actual mechanism of retrograde ejaculation: the “inability of the internal vesical sphincter to contract during ejaculation, resulting in retrograde flow of semen to the urinary bladder”. Retrograde ejaculation occurs, therefore, secondary to interference with the superior hypogastric plexus, “a thin retroperitoneal plexus of nerves overlying the lumbosacral junction”. Trauma to this plexus, therefore, likely occurs during ALIF, resulting in "denervation of the bladder neck sphincter".

The authors of this commentary further note that other studies have failed to recognize the “causal relationship” between the ALIF and retrograde ejaculation. The failure to acknowledge this complication in multiple studies is even more disturbing as the retrograde ejaculation appears to directly follow ALIFs, often lasting for several postoperative months.