Metal ion exposure after oncologic megaprosthesis salvage surgery: a systematic review.

J Bone Oncol · Aug 2026 · Recent

Fa-Binefa M, Rojas-Sayol R, Esteve-Perez M, Peiró-Ibañez A, Trullols-Tarragó L, Gracia-Alegria I

Oncology Orthopaedic Surgery Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

Orthopaedic Oncology

SUMMARY — THE REDUCTIONA systematic review of 247 oncologic megaprosthesis patients found blood cobalt, chromium, and titanium levels rise over time (some exceeding typical thresholds), though clinical significance for toxicity or ARMD remains unclear.
Abstract, as published

BACKGROUND: Megaprostheses may contain multiple modular junctions and, depending on implant design, specific coupling or hinge mechanisms that can contribute to fretting, wear, corrosion, and systemic metal ion release. This systematic review evaluated blood metal ion levels in patients undergoing limb-salvage oncologic surgery with a megaprosthesis.

MATERIAL AND METHODS: A systematic review was conducted following PRISMA guidelines. PubMed, Scopus, and Web of Science were searched from inception to September 16, 2024. Studies were eligible if they reported metal ion levels after upper or lower oncologic megaprosthesis reconstruction. Data were extracted for cobalt, chromium, titanium, aluminium, molybdenum, and silver at prespecified postoperative intervals (0-2 months, 2-12 months, and > 12 months), together with study and patient characteristics, anatomical location/reconstruction type, and reported complications. Data were summarized using arithmetic means and sample-size-weighted means.

RESULTS: Thirteen studies comprising 16 cohorts and 247 patients were included. Blood cobalt, chromium, and titanium concentrations were higher in later postoperative intervals. At >12 months, mean cobalt, chromium, and titanium concentrations were 8.2 ppb, 4.2 ppb, and 8.1 ppb, respectively; upper-quartile values reached 21.1 ppb for cobalt, 11.7 ppb for chromium, and 9.6 ppb for titanium. Silver concentrations were 8.2, 2.9, and 9.2 ppb at 0-2, 2-12, and > 12 months, respectively, whereas aluminium and molybdenum were only reported beyond 12 months, with mean values of 7.8 and 0.5 ppb. No included study consistently linked elevated ion levels with systematically assessed ARMD, pseudotumor formation, renal failure, or cardiac toxicity.

CONCLUSION: Blood cobalt, chromium, and titanium concentrations appeared higher in later postoperative intervals after oncologic limb-salvage reconstruction with megaprostheses. Some patients may exceed commonly cited thresholds, particularly for cobalt, but the clinical significance remains uncertain because relevant outcomes were inconsistently assessed.

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