Point-counter-point debate: the association between recombinant human bone morphogenetic protein utilization and complications in spine surgery

Abstract

Bone morphogenetic proteins (BMPs) have been utilized in spine surgery for over 10 years as a bone graft substitute. Potential BMP-related adverse effects including retrograde ejaculation and heterotopic neuroforaminal bone formation have been described. Additionally, some studies have suggested an association between BMP and cancer. Inconsistencies exist in the published spine literature with regards to the incidence and association of complications with BMP utilization. In a point-counterpoint format, this article discusses the current evidence concerning the relationship between the utilization of BMP in spinal fusion and the risk of cancer, retrograde ejaculation (RE), neuroforaminal bone formation, and its role in anterior cervical spine surgery and adolescents.Keywords Bone morphogenetic protein . Retrograde ejaculation . Anterior cervical fusion . Neuroforaminal bone growth . Cancer Point-counterpointRetrograde Ejaculation (RE) RE occurs secondary to impaired function of the internal vesicle sphincter muscle. Anterior lumbar approaches, particularly at the L5-S1 level, carry a greater potential for damage to the superior hypogastric sympathetic plexus, which innervates the internal vesicle sphincter muscle. Other etiologies of RE including diabetes, benign prostate hypertrophy and its treatment, multiple sclerosis, pelvic trauma, and pelvic or rectal surgery [1][2][3][4][5][6]. RE following anterior lumbar spine surgery is also purported to be related to the surgical approach [7][8][9].Burkus et al first published a prospective, randomized, nonblinded FDA-approved study concerning the use of rhBMP-2 in ALIF [8]. Six males (4.1 %; 6/146) reported RE following surgery, of which 4 underwent a transperitoneal approach (TPA) (13.3 %; 4 of all 30 males that underwent TPA) and 2 underwent a retroperitoneal approach (RPA) (1.8 %; 2 of 116 males that underwent RPA). Since the difference in RE between the TPA and RPA groups was statistically significant the authors concluded that a TPA was associated with a higher risk of RE. No comparison in RE between the investigational and control group was performed. The reported differences between the 2 approaches persisted at the 2-year follow-up period [10]. However, in 2010 Smoljanovic et al reviewed the data by Burkus et al [11] and reported that all 6 patients with RE had received rhBMP-2. Thus, the prevalence of RE in the investigational group (rhBMP-2) would have been 7.7 % (6/78 males), which was significantly greater than the control group (ICBG). The reason for ignoring the relationship between RE and rhBMP-2 was questioned, which sparked an intense debate over the potential association between the utilization of rhBMP-2 and RE.Correlation between rhBMP-2 utilization and RE Curr Rev Musculoskelet Med (2014) 7:200-207 DOI 10.1007/s12178-014-9219-x patients (7.2 %) in the rhBMP-2 group developed RE while only 1 of 174 patients (0.6 %; 1/69) reported RE in the control group. Significant differences in RE were also evident among patients that underwent a singl...

Sexual and reproductive function in spinal cord injury and spinal surgery patients

“… 25 Unfortunately, many of the studies examining the effect of rhBMP-2 use on RE employed questionnaires without laboratory testing for RE, thus placing their results into question. Due to conflicting results from numerous studies, Mroz et al ., 26 Siemionow et al ., 27 Tannoury et al ., 28 as well the authors of this review believe that the matter of whether rhBMP-2 use is an independent risk factor for RE is still up for debate without a proven definitive causative effect.…”