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A prospective study of tissue surrounding spinal instrumentation was performed using histologic and chemical analysis.To identify and quantify the amount of metal debris generated by titanium pedicle screw instrumentation and to evaluate the histologic response in the spinal tissues.Microscopic metal particles from the soft tissue surrounding joint arthroplasties have been shown to activate a macrophage response that leads to bone resorption and increased inflammation. The use of titanium spinal implants for spine surgery projects the possibility of generating wear debris in the spine.Nine patients with titanium instrumentation from a prior lumbar decompression and fusion procedure who were undergoing reoperation were entered into this study. Tissue samples were collected from areas near the pedicle screw–rod junction, the scar tissue overlying the dura, and the pedicle screw holes. Metal levels for titanium were determined by electrothermal atomic absorption spectroscopy, and histologic analysis was performed by light and electron microscopy.Tissue concentrations of titanium were highest in patients with a pseudarthrosis (30.36 μg/g of dry tissue). Patients with a solid fusion had low concentrations of titanium (0.586 μg/g of dry tissue). Standard light microscopy identified metal particles in the soft tissues. Transmission electron microscopy demonstrated macrophages with numerous secondary lysosomes containing electron-dense bodies and collagenous stroma with electron-dense rod-like profiles consistent with metal debris.Wear debris is generated by the use of titanium spinal instrumentation in patients with a pseudarthrosis. These particles activate a macrophage cellular response in the spinal tissues similar to that seen in surrounding joint prostheses. Patients with a solid spinal fusion have negligible levels of particulate matter.