Serum Titanium Levels Remain Elevated But Urine Titanium is Undetectable in Children With Early Onset Scoliosis Undergoing Growth-Friendly Surgical Treatment: A Prospective Study

Abstract

Background: Elevated serum titanium levels have been found in patients with early onset scoliosis (EOS) treated with traditional growing rods (TGR), magnetically controlled growing rods (MCGR), and vertical expandable prosthetic titanium rib (VEPTR). No studies have investigated whether serum titanium remains persistently elevated and if titanium is excreted. Our purpose was to compare serum titanium levels in patients with EOS with growth-friendly instrumentation to age-matched controls and evaluate urine titanium and serial serum titanium levels in patients with EOS. Methods: This was a prospective case-control study. Patients with EOS with TGR, MCGR, or VEPTR underwent urine titanium and serial serum titanium collection at a minimum 6-month interval. Control patients did not have a history of metal implant insertion and underwent serum titanium collection before fracture fixation. Results: Twenty patients with EOS (6 TGR, 8 MCGR, and 6 VEPTR) and 12 controls were analyzed. The control group had no detectable serum titanium (0 ng/mL), whereas the patients with EOS had a median serum titanium of 4.0 ng/mL (P < 0.001). Analysis of variance showed significantly higher median serum titanium levels in the MCGR and VEPTR groups than the TGR group at time point 1 (5.5 vs 6.0 vs 2.0 ng/mL, P = 0.01) and time point 2 (6.5 vs 7.5 vs 2.0 ng/mL, P < 0.001). Binary comparisons showed a significant difference in serum titanium level between TGR and MCGR (time point 1: P = 0.026, time point 2: P = 0.011) and TGR and VEPTR (time point 1: P = 0.035, time point 2: P = 0.003). However, there was no difference between MCGR and VEPTR (time point 1: P = 0.399, time point 2: P = 0.492) even though the VEPTR group had a longer duration of follow-up (P = 0.001) and a greater number of lengthenings per patient at the first serum collection (P = 0.016). No patients with EOS had detectable urine titanium. Conclusions: Patients with EOS treated with titanium alloy growth-friendly instrumentation had elevated serum titanium levels compared with age-matched controls that persisted over time with no evidence of renal excretion. Additional studies are necessary to assess for local and systemic accumulation of titanium and the significance of long-term exposure to titanium in growing children. Level of Evidence: Level III, therapeutic.