Through our primary outcome analysis, our study showed a higher proportion of fusion rates for LB (95.3%) compared to AIC (88.6%), ALG (87.8%), and ALP (85.8%). This finding was not expected since LB has less trabecular bone, which would theoretically result in less bone marrow and less availability of the pluripotent cells and growth factors25. Also, LB’s limited harvestable volume narrows its surgical recommendations, and it is commonly applied to the cervical spine (which involves a smaller area to cover and less body load to sustain compared to the lumbar spine).

Our sample mainly comprised AIC (2529) patients, followed by ALP (766), ALG (516), and LB (366) patients. This size discrepancy could explain the LB fusion effect among our pooled samples, which could exacerbate LB’s effect. Moreover, most studies did not present participants baseline assessments, and since the fusion quality of distinctive grafts can diverge by age, metabolic activity, or graft-bed preparation26.27, confirming LB graft fusions superiority to the other studied options is challenging. Similarly, most of the reviewed studies did not follow the FDA’s guidance for spinal fusion evaluations28increasing their assessment bias.

Additionally, the literature has often identified conflicting opinions regarding the optimal association between surgical techniques and patients’ underlying predictive factors for spinal fusions and spinal grafts. Other meta-analyzes, that have considered assorted graft materials or surgical approaches, have demonstrated higher fusion rates using rhBMP27.29.30 or when grafts are associated with the anterior lumbar interbody fusion technique31. Moreover, minimally invasive procedures did not demonstrate fusion rate differences compared to open surgical techniques32.

Considering the data inconsistencies in our primary analysis, which precluded further associations (eg, fusion rate × graft type × surgical technique), we performed a subgroup analysis of fusion rates with or without metallic implants. In this subgroup, LB presented lower fusion rates when associated with metallic implants, and this finding could be explained by LB limitations in graft volume availability33 and / or small patient sample.

Pseudarthrosis rates and adverse events were studied as secondary outcomes. Our pseudarthrosis analysis revealed that the reported data presented a higher proportional rate of pseudarthrosis in the lumbar spine (14.2%) than the cervical spine (4.1%), consistently with previous analyses6which was explained by the increased difficulty of stabilizing areas that support higher loads34.35. Furthermore, our analysis of bone graft types revealed that LB presented a higher pooled proportional pseudarthrosis rate (10.5%). However, some considerations are worth mentioning. Pseudarthrosis rates were not systematically assessed across the reviewed studies (AIC 17 of 51 analyzes; ALG 4 of 9 analyzes; ALP 6 of 20 analyzes; and LB 5 of 10 analyzes), which could have exacerbated the discrepancy between patient quantity and analyzed effects. Similarly, authors ‘descriptions of their results did not suggest that pseudarthrosis can be presumed to directly result from fusion rates’ missing from fusion rate analyzes. Moreover, the literature did not present a conclusive role governing bone grafts’ influence on pseudarthrosis rates6.

Greater pseudarthrosis rates have already been associated with advanced age (because of delayed bridging maturation and increased bone resorption)36degenerative disease, and construct length6. Longer fusions can enable loading distribution, minimizing excess motion and helping to decrease pseudarthrosis34.37. However, they can also increase points of load failure for each adjacent segment34, demand more grafts, and increase patients’ exposure to complications (due to an extensive surgical intervention). Nevertheless, our literature review examined a limited sample for this subgroup analysis, and it included many studies with moderate to high heterogeneity, reflecting pseudarthrosis evaluations’ diversity. For example, Choudhri et al.38 recommend CT imaging with fine-cut axial and multiplanar reconstruction to evaluate spinal fusions. Nonetheless, no radiographic gold standard is available with which to evaluate pseudarthrosis38 compared to open surgical exploration. Therefore, as in the literature, our review did not reveal a conclusive role governing bone grafts’ influence on pseudarthrosis rates6.

Moreover, many available studies presented substantial methodological flaws regarding adverse events, limiting analyzes. AIC pain corresponded to a 23.4% pooled proportional rate and a significant proportion of donor site morbidity (23.2%), corroborating the previously mentioned graft drawbacks already described in the literature11,12,13,14,15,16. Unsurprisingly, and as we have mentioned, foreign bodies can carry some inherent risks, which could explain ALP’s higher pooled proportional rates of infection (10.2%) and graft-related events (35.1%).

Our study faced other limitations. Heterogeneity was found in different aspects of the reviewed studies’ populations. This heterogeneity arose from clinical diversity in both treatment groups, supported by insufficient analyses, a small pool of subjects, differences on assessing patients’ baseline and outcomes, and the absence of systematic reports (eg, the use of tobacco or nonsteroidal anti-inflammatory drugs could have led to a misinterpretation of fusion rates). Moreover, a standard tool for data collection could improve data availability for fusion rate analysis and pseudarthrosis assessment. Furthermore, we did not include all available ALP grafts due to the high existent variability, which could wane proportional analysis. An example is the platelet rich plasma, which is gaining recognition as an important adjunct in the spinal graft market39. Finally, an overall higher RoB — which could influence appraisals of interventions effects — indicated a lack of structured randomized trials. Moreover, successful treatments should be interpreted in light of patients diminished exposure to nosocomial events, acceptable survival rates, and function after treatment.

Comparing the inputs of more than three decades of medical evolution is challenging, given technical improvements, instrumental variations, and a greater range of material. The competition for better outcomes versus materials will continue, as well the difficulty of medical updates and the discernment of industry interests. Structured clinical trials are highly encouraged to promote the availability of optimal, cost – benefit treatments for patients.

The findings of our analysis demonstrate substantial variety of spinal grafts and the need for more rigorous studies to better address and assist surgeons in choosing the best graft options. Standardized methods to evaluate spinal fusion and pseudarthrosis are encouraged.

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