macrophages are recruited in order to remove the necrotic graft tissue [14]. Most of the graft cells do not survive; however, surface osteoblasts sur­vive and begin to produce new bone. As soon as 48 h after the surgery, host vessels along with osteoblastic and osteoclastic precursors infiltrate the trabecular surfaces of the cancellous graft. While new blood vessels begin to form through­out the graft, osteoclasts begin to resorb it. As the vascular ingrowth progresses, osteoblasts line the dead trabecular surfaces and produce osteoid. Through remodeling, which lasts several months, necrotic bone is resorbed by osteoclasts while osteoblasts form new bone [9, 13]. Thus, the incorporation of cancellous autograft occurs through simultaneous bone formation and resorp­tion [14]. Over the next 6–12 months following the grafting, newly formed osteoid is mineralized into bone and becomes fully integrated with the surrounding host bone. Integration is typically complete 1 year after the surgery [9, 13, 14].

tions associated with the use of BMP could be “substantial.” In 2011 Carragee et al. published an article questioning the veracity and reporting bias of the initial validation studies for rhBMP-2 [91]. They found that the rate of complications was 10–50 times higher than what was reported in the validation studies, critical methodological flaws within the studies themselves, and serious deficiencies within the peer review process that evaluated these studies. Faced with controversy and questions, Medtronic turned over all data to the Yale Open Data Analysis (YODA) Project. YODA was created as a new model to evaluate industry-sponsored clinical trials, with the goal of increasing transparency, disseminating data, and increasing the benefit with mitigation of risk to patients. YODA selected two different sites to the review the data, the Oregon Health and Science University and University of York in the United Kingdom. At the Oregon Health Sciences University, Fu et al. [92] reviewed 13 randomized control trials, 31 other cohort studies, 47 inter­vention series, and 34 case series and reports. Simmonds et al. at the York University reviewed 11 randomized control trials and 43 other publi­cations [93]. Both papers commented on the methodological flaws in the validation studies, namely, a lack of blinding among physicians and patients. At the same time, both studies agreed that there were no significant differences in clini­cal outcomes between ICBG and rhBMP-2, a sig­nificantly higher risk with its use in anterior cervical fusions, and increased relative risk that did not reach significance with its use in both anterior and posterior lumbar fusions. There was a significantly increased risk of back and leg pain in the immediate postsurgical period when rhBMP-2 was used in posterolateral fusions. Fu et al. concluded that they could see no clear indi­cation for the use of rhBMP-2 as there was no significant benefit in measured clinical outcomes. They also stated that though the overall rates of cancer were low, there was an increased risk of cancer with rhBMP-2 at 24 months; however, at 48 months these differences were no longer sig­nificant. Simmons et al. concluded the use of rhBMP-2 resulted in increased fusion rates that did not translate into improved clinical outcomes