Editorial. Anterior cervical fusion and rhBMP-2: a prospective study is needed to assess optimal dosing and delivery.

Some prior reports have suggested that the use of recombinant human bone morphogenetic protein–2 (rhBMP-2) in anterior cervical fusion (ACF) may be beneficial in select patients with risk factors for developing pseudarthrosis.1 However, other reports have provided evidence to suggest that there is potential for high complication rates (e.g., hematoma/seroma, cervical swelling, dysphagia) when using rhBMP-2 for ACF.2 As such, there are currently no clear guidelines or definitive recommendations regarding the usage of rhBMP-2 in patients undergoing ACF. The explanation for some of the discrepancies from prior rhBMP-2/ACF reports is likely multifactorial but could potentially be attributed to nonstandardized dosing and delivery of rhBMP-2.1–4 To address this important topic, Mendenhall et al. performed a retrospective study to evaluate the safety and efficacy of low-dose rhBMP-2 for use in patients undergoing ACF (both anterior cervical discectomy and corpectomy).5 The authors hypothesized that the higher doses of rhBMP-2 used in prior ACF studies may have led to the higher complication rates observed. In this study, Mendenhall and colleagues included a total of 198 patients (62 [31%] were smokers) who underwent stand-alone ACF (median of 2 levels fused; mean rhBMP-2 dose 0.50 ± 0.09 mg/level; both contained and noncontained delivery devices were used). The authors reported associated complications and fusion rates with a minimum of 1 year of radiographic follow-up. Briefly, 22 (11%) patients experienced dysphagia, 11 (6%) patients experienced cervical swelling, 2 (1%) patients underwent washout for hematoma, 1 (0.5%) patient had washout for seroma, 2 (1%) patients had pseudarthrosis requiring posterior cervical fusion, and 3 (2%) patients experienced a new postoperative neurological deficit (which was reported to have recovered by the last follow-up). Regarding rates of arthrodesis, study results demonstrated that 190 (96%) patients had solid arthrodesis over an average of 15 months of follow-up (with no statistically significant difference in fusion rates between smokers and nonsmokers). After carefully analyzing these study results, the authors concluded that use of low-dose rhBMP-2 may safely and effectively augment ACF and could potentially benefit select patients at risk for pseudarthrosis (e.g., smokers, multilevel ACF). The current study provides novel data that may impact surgical decision-making and could assist preoperative patient counseling. To better understand the potential impact of this study, it may be beneficial to briefly review the early safety and efficacy studies of rhBMP-2 usage for spine surgery. The first clinical studies of rhBMP-2 for spinal arthrodesis were performed in patients with lumbar degenerative disease.6,7 In 2000, Boden et al. reported their results from the first human clinical pilot trial assessing the feasibility of rhBMP-2 in single-level lumbar degenerative disease.6 In their study, patients received a tapered cylindrical threaded fusion cage filled with either rhBMP-2/collagen sponge or autogenous iliac crest bone (control).6 The study results demonstrated that arthrodesis occurred more reliably in those patients treated with rhBMP-2-filled fusion cages compared with controls.6 The authors reported no adverse events related to the rhBMP-2 treatment.6 Following this initial clinical pilot trial, Burkus et al. reported results from a multicenter prospective 2-year study comprised of 279 patients with degenerative lumbar disc disease.7 In this follow-up study, patients underwent lumbar interbody fusion using two tapered threaded fusion cages, and the investigational group received rhBMP-2 on an absorbable collagen sponge.7 The study results demonstrated that lumbar fusion using rhBMP-2 and a tapered titanium fusion cage yielded solid union and could potentially eliminate the need for harvesting iliac crest bone graft.7 These positive results culminated in FDA approval being granted to Medtronic for the use of rhBMP-2 in patients undergoing anterior lumbar interbody fusion (ALIF). Since then, there has been increasing use of rhBMP-2 in an off-label fashion, especially in patients with known risk factors for pseudarthrosis. This was demonstrated in an