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• The Evidence of Actifuse
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The Evidence of Actifuse

Actifuse vs other synthetic bone grafts

Bone growth speed and volume^1,2

The presence of silicate in the Actifuse lattice structure enhances the speed and volume of bone ingrowth. Studies have shown that Actifuse, with its silicate substituted chemistry, forms mature lamellar bone at earlier time points than traditional synthetic bone graft substitutes (Graph 1). Furthermore, histology of the Actifuse implant shows extensive remodeling of the new trabecular network, thus improving the organization and strength of the host bone/graft composite structure.

Graph 1 Bone growth speed and volume

Actifuse was compared to β-TCP (Vitoss^TM) and calcium sulphate (Osteoset ^TM) in the distal femoral condyle of the New Zealand white rabbit. This model has been extensively studied as an example of a controlled defect and is a highly relevant for the study of bone defect repair. Histologic analysis allows for qualitative identification and assessment of cellular and tissue morphology and histomorphometry provides quantitative information about bone mass, architecture and rate of turnover. Plotting normalized bone volume (NBV) over time shows clear differences in the rate and pattern of bone formation between different materials (Graph 2a). Comparing bone graft volume (BGV) at the same time points provides insight into the role scaffold plays in bone formation.TOP

Graph 2a and 2b Normalized bone volume (NBV) and bone graft substitute volume (BGV) for calcium sulphate (Osteoset^TM), β-TCP (Vitoss^TM Morsels) and Actifuse over 12 weeks³

Actifuse versus autograft

Fusion across the posterolateral 'gutter' represents a challenging healing environment; it is both a large area not supported by bone and an area where bone is not normally present. A sheep (ovine) model, routinely used as a relevant indicator of the clinical performance of bone graft substitutes, was used to measure the efficacy of Actifuse in this indication. Actifuse was implanted alone (no blood, bone marrow aspirate (BMA) or local bone was added), representing the most challenging situation for a bone graft substitute.

The goal was to demonstrate that Actifuse could produce solid Postero lateral Fusion (PLF) equivalent to that seen with autograft.

During the study, various clinically relevant tests were conducted including:

• plain X-rays
• CT scans
• manual manipulations
• biomechanical tests
• histology
• histomorphometry analyses

These tests were carried out to assess exactly what was happening within the fusion mass. This is important as plain film X-rays cannot reliably distinguish between fibrous tissue, bone and graft material.

Across all measures, Actifuse demonstrated equivalence to autograft⁴ TOP

Histology

Histology demonstrated that a solid bridge of healthy bone was formed across the transverse processes by both Actifuse and autograft, a clinically significant marker of solid fusion. An increased amount of new bone at the edges of the fusion mass provides evidence of re-modeling in response to load and shows that the bone formed in and around Actifuse behaves in the same manner as naturally occurring bone (Graph 1).

Figure 1 Histologic demonstration of bone fusion with Actifuse and autograft

Bone Mineral Density (BMD)

BMD was assessed using peripheral quantitative computed tomography (pQCT). This measures the amount of mineral per given volume (Figure 2 and 3).

• With Actifuse at 2 months there was consolidation of the graft mass and incorporation of the granules has started
• After 4 months full incorporation of the granules can be seen
• At 6 months there is formation of bilateral pseudocortex and smoothing of the fusion mass as remodeling occurs

Figure 2 Bone mineral density measured by pQCT for Actifuse at 2, 4 and 6 months

Bone mineral density measured by pQCT for autograft at 2 and 6 months

Bone in the fusion mass

pQCT is a three dimensional measure of bone volume built up from individual CT slices. Quantitative analysis of the fusion mass using pQCT concluded that Actifuse showed an equivalent fusion volume compared to autograft (Graph 3). This is important because too little bone equates to incomplete fusion and an inability to support required load. The pQCT data correlates well with the histomorphometry. This is a two dimensional measure of bone area and confirms that the degree of inter-transverse bony bridging was equivalent between Actifuse and autograft. This is important because unless bone bridges, the fusion is ineffective.

Graph 3 Total fusion volume for autograft and Actifuse over 6 months

Histomorphometry

The Actifuse samples showed a significantly greater fusion volume versus autograft at 2 and 6 months (p=0.02 and p=0.007, respectively) (Graph 4). As fusion callus size is indicative of graft resorption and active bone incorporation, this is an important measure of Actifuse efficacy.

Graph 4 Histomorphometry

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1. Hing KA et al. Effect of silicon level on rate, quality and progression of bone healing within silicate substituted porous hydroxyapatite scaffolds. Biomaterials 2006; 27: 5014-5026.
2. Patel N et al. A comparative study on the in vivo behavior of hydroxyapatite and silicon substituted hydroxyapatite granules. J Mat Sci Mat Med 2002; 13 1199-1206.
3. Hing KA et al. Comparative performance of three ceramic bone graft substitutes. Spine J 2007; 7(4): 475-490.
4. Wheeler DA et al. Efficacy of silicated calcium phosphate graft in posterolateral lumbar fusion in sheep. Spine J 2007; 7 (3): 308-317.