**Abstract**

Lumbar and cervical fusions are one of the most common types of spine surgeries performed globally with approximated 450,000 spinal fusion surgeries performed annually. (give reference) Bone Morphogenetic Proteins (BMPs) are secreted cytokines with several functions, within the TGF-b superfamily. BMP act as a disulfide-linked homo- or heterodimers and have been recognized as strong and effective regulators of important biological processes like formation and repair of osteocytes and chondrocytes, cell proliferation during embryonic development. Recombinant human bone morphogenetic protein 2 (rhBMP-2) is a very effective osteogenic growth factor that has been demonstrated to be effective in different types of spinal fusions and reduces the reliance on the use autologous iliac crest bone graft. In recent years there have been limitations regarding the use of rhBMP-2 because of issues like high costs, benefits, and safety issues about rhBMP-2. In this review, a comprehensive overview about the application of rhBMP-2 in spinal fusion surgery is given.

**Keywords:** Recombinant Bone Morphogenetic Proteins, Spinal fusion surgery, TGF-b, cytokines

### **1. Introduction**

The use of osteobiologics to improve the outcome of spinal fusion has contributed to an increase in spinal fusion surgical procedures worldwide [1]. There are many different types of bone graft fusion materials currently on the market, however there is still a need for a cost effective biological material to achieve a successful permanent arthrodesis [2]. Presently iliac crest autograft, used for spinal fusion surgeries, is desirable as it possess osteo-biological properties with reduced risk of diseases transmission and graft rejection [3]. However, according to some studies, autograft has been linked to longer surgery time, few donor site availability [4], and chronic donor site pain [5, 6]. These limitations and disadvantages have led to novel therapeutic bone graft options for spinal fusion surgery [5, 7], like BMPs.

Marshall Urist was the first to describe BMP in 1965. It belongs to the transforming growth factor-ß family. There are various types of BMP molecules that exist, however few of them have been associated with osteoblast differentiation and bone development [7]. Recombinant rhBMP-2 is the market available form of BMP-2 FDA approved for anterior lumbar interbody fusion (ALIF) [8]. There have been several clinical studies on the anterior lumbar interbody fusions and all have reported effective fusion rates, reduced operative time, reduced blood loss, and reduced hospital duration with the administration of rhBMP-2 when compared to iliac crest bone graft (ICBG) [9]. However, there have been conflicting reports as to whether rhBMP-2 is efficient in spinal fusion. A well-done study was performed by Papakostidis et al., who investigated the benefits of rhBMP-2 in promoting posterolateral fusion. They concluded in their report that rhBMP-2 significantly increases rates of fusion, reduced hospital stay with the administration of BMP-2, compared to autologous iliac crest bone graft [10]. Lee et al. also confirmed the efficacy of the administration of rhBMP-2 in elderly patients undergoing posterolateral lumbar fusion at a single operative level [11]. Similarly, researchers like Meisel and colleagues also reported a 95–100% successful arthrodesis with use of BMP-2 when performing posterior lumbar interbody fusion [12]. However, recent systematic reviews question the efficacy and use of BMP-2 over iliac crest bone graft as noted in the Yale University Open Data base (YODA) Project and FDA reports. Including 13 randomized-controlled and 31 cohort studies, the study reported that for spinal fusion, rhBMP and iliac crest bone graft have similar efficacy. However, incidence of adverse event might be greater in anterior lumbar-body fusion and anterior cervical spine fusion. Furthermore, rhBMP can increase 24-month cancer risk [8]. These reports concluded that there were no substantial clear benefits of the administration of BMP-2 in spine fusion over autologous bone graft, and in fact there were more complications linked with BMP-2 use [13] (**Figure 1**).

**Figure 1.**

*Lateral radiograph of the cervical spine demonstrating massive soft- tissue swelling (arrows) following anterior cervical diskectomy and fusion surgery using rhBMP-2. Image was culled from.*
