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Spinal fusion surgery is an established treatment for various spinal disorders, like deformities, fractures and degenerative diseases. Two or more vertebrae are connected with implants for stabilization. Mostly a bone graft from the pelvis is used to induce bone growth between the vertebrae. To avoid this extra bone harvesting procedure and guarantee the required amount of bone graft, over the past decades a lot of research on bone graft substitutes has been done. Synthetic ceramics with a specific composition, structure and resorbability closely mimic patient’s own bone (autograft). Although several bone graft substitutes are commercially available for spinal fusion, clinical evidence of their performance is still limited. This thesis addresses several challenges in the clinical investigation of bone graft substitutes in lumbar spinal fusion and describes the results of a clinical trial on the efficacy of a synthetic ceramic. A systematic literature review shows that there is no standard method to accurately and reliably assess the spinal fusion status over time with diagnostic imaging. This complicates the comparison between studies and bone graft materials (Chapter 2). The efficacy of a promising microporous ceramic of ß-tricalcium phosphate and hydroxyapatite compared with autograft was investigated in a multicenter randomized controlled trial (RCT). To overcome some of the challenges in conducting a surgical RCT, an efficient intrapatient controlled design with each patient serving as his/her own control was used. The results of this clinical trial demonstrate that this ceramic bone graft substitute performs as good as autograft in spinal fusion. This is a big milestone in regenerative bone research (Chapter 3). Evaluation of the spinal fusion process between 1 and 2 years of follow-up suggests that bone growth after 1 year is the result of immobilization instead of bone grafting. The efficacy of a bone graft can be best assessed during the first year after surgery, at the location were the graft is placed (Chapter 4). Methodological analyses confirms that an intrapatient controlled trial design eliminates variability between patients and considerably reduces the required sample size. Furthermore, boundary conditions for the application of this efficient design are described (Chapter 5). Based on the observation that lumbar fusion patients do not perceive relevant pain from the bone graft donor site, the use of a bone graft substitute in these patients is mainly indicated when the quality or quantity of autograft is insufficient or when an additional incision has to be made for bone harvesting (Chapter 7). The findings of this thesis advance the clinical investigation as well as the application of bone graft substitutes in spinal fusion. Future research should be directed at further elaboration and validation of objective criteria to assess the spinal fusion status over time, and further improvement of the fusion performance of ceramic bone graft substitutes. |
