title: The effect of titanium particulate on development and maintenance of a posterolateral spinal arthrodesis: an in vivo rabbit model.
abstract: METHODS
  The current study was undertaken to determine if the presence of titanium wear particulate deleteriously influences early osseointegration of posterolateral bone graft or disrupts an established posterolateral fusion mass.
  
  
  OBJECTIVE
  Using an in vivo animal model to evaluate the effect(s) of titanium wear particulate on a posterolateral spinal arthrodesis based on serologic, histologic, and immunocytochemical analyses.
  
  
  BACKGROUND
  The effect of unintended wear particulate resulting from micromotion between the interconnection mechanisms in spinal instrumentation remains a clinical concern.
  
  
  METHODS
  Thirty-four New Zealand White rabbits were randomized into two groups based on postoperative time periods of 2 months (Group 1, n = 14) and 4 months (Group 2, n = 20). Group 1 underwent a posterolateral arthrodesis at L5-L6 using tricortical iliac autograft or tricortical iliac autograft + titanium particulate. Group 2 received iliac autograft at the initial surgery and were reoperated on after 8 weeks and treated with posterolateral arthrodesis exposure alone or titanium particulate. Postoperative analysis included serologic quantification of systemic cytokines. Postmortem microradiographic, immunocytochemical, and histopathologic assessment of the intertransverse fusion mass quantified the extent of osteolysis, local pro-inflammatory cytokines, osteoclasts, and inflammatory infiltrates.
  
  
  RESULTS
  Serologic analysis of systemic cytokines indicated no significant differences in cytokine levels (P > 0.05) between the titanium or autograft treatments. Immunocytochemistry indicated increased levels of local cytokines (tumor necrosis factor-alpha) at the titanium-treated posterolateral arthrodesis sites at both time periods (P < 0.05). Osteoclast cell counts and regions of osteolytic resorption lacunas were higher in the titanium-treated versus autograft-alone groups (P < 0.05), and the extent of cellular apoptosis was markedly higher in the titanium-treated sites at both time intervals. Electron microscopy indicated definitive evidence of phagocytized titanium particles and foci of local, chronic, inflammatory changes in the titanium-treated sites.
  
  
  CONCLUSIONS
  Titanium particulate debris introduced at the level of a spinal arthrodesis elicits a cytokine-mediated particulate-induced response favoring pro-inflammatory infiltrates, increased expression of intracellular tumor necrosis factor-alpha, increased osteoclastic activity, and cellular apoptosis. The presence of titanium particulate debris, secondary to motion between spinal implants, may serve as the impetus for late-onset inflammatory-infectious complications and long-term osteolysis of an established posterolateral fusion mass in the clinical setting.
authors.affiliation: Orthopaedic Research Laboratory, Union Memorial Hospital, Baltimore, MD 21218, USA. bcspine@aol.com
authors.forename: Bryan W
authors.initials: BW
authors.lastname: Cunningham
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Orbegoso
authors.forename: Anton E
authors.initials: AE
authors.lastname: Dmitriev
authors.forename: Nadim J
authors.initials: NJ
authors.lastname: Hallab
authors.forename: John C
authors.initials: JC
authors.lastname: Sefter
authors.forename: Paul C
authors.initials: PC
authors.lastname: McAfee
mesh_terms: D000135:Acid Phosphatase / Q000096:biosynthesis; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016025:Bone Transplantation; D002452:Cell Count; D016207:Cytokines / Q000097:blood; D007085:Ilium / Q000637:transplantation; D007150:Immunohistochemistry; D020007:Implants, Experimental / Q000009:adverse effects*; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology / Q000601:surgery*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D023421:Models, Animal; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D010014:Osteolysis / Q000139:chemically induced / Q000473:pathology; D010316:Particle Size; D011817:Rabbits; D011859:Radiography; D013123:Spinal Fusion / Q000009:adverse effects / Q000379:methods; D014025:Titanium / Q000009:adverse effects*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D014025:Titanium; D000135:Acid Phosphatase