gms | German Medical Science

Objectives: Spinal fusion is the standard treatment of various spinal disorders, but pseudarthrosis following spinal fusion is still common, with an incidence of 5% to 35%. Our previous studies have proven that calcium sulfate/hydroxyapatite (CaS/HA) local co-delivery of bone morphogenetic protein 2 (BMP-2) and zoledronic acid (ZA) can obtain a higher bone volume in an ectopic muscle pouch model and in a femoral bone defect model. The aim of this study was to evaluate whether local application of BMP-2 and ZA released from a resorbable CaS/HA scaffold is favorable for posterolateral lumbar spinal fusion.

Methods: Based on the treatment and the implant type, 7 groups were set up in this study (CaS/HA, CaS/HA + BMP-2, CaS/HA + systemic ZA, CaS/HA + local ZA, CaS/HA + BMP-2 + systemic ZA, CaS/HA + BMP-2 + local ZA, SHAM (previous study of our group)). This in vivo study was performed on 132, 8-week-old male Wistar rats (n = 12 per group at 3 weeks and n = 10 per group at 6 weeks). A posterolateral intertransverse process spinal fusion at L4 to L5 was performed bilaterally by implanting group dependent scaffolds. At the time endpoints of 3 and 6 weeks, the animals were euthanized for µCT, histological staining, or mechanical testing.

Results and conclusion: µCT evaluation showed, that the CaS/HA + BMP-2 + local ZA group had the highest bone volume and bone mineral density at 6 weeks among all treated groups (Figure 1A). Biomechanical testing revealed significantly higher breaking force in CaS/HA + BMP + local ZA group than other groups at 6 weeks (Figure 1B). Histological staining results showed more newly formed bone in the CaS/HA + BMP-2 + local ZA group than any other group at 3 weeks. Staining for osteoclasts showed a reduced osteoclast activity within the scaffold when local ZA was present.

The CaS/HA-based biomaterial functionalized with the bioactive molecules rhBMP-2 and ZA enhanced bone formation and concomitant fusion outcome. The anabolic and anti-catabolic coupling effects of rhBMP-2 and ZA result in more net bone formation in spinal fusion surgery and may potentially lead to overall BMP-2 dose reduction. The carrier properties of the CaS/HA biomaterial are optimal for controlled co-delivery of both BMP-2 and ZA. All components in this study are already approved for clinical use. The treatment regime of combining CaS/HA biomaterial with co-delivery of BMP-2 and ZA may soon translate into clinical use as an alternative to autologous bone grafting for challenging procedures of posterolateral lumbar spinal fusion.