• Claudia Prattes, Andreas Leithner, Joanna Szkandera, Georg Prattes, Ernst-Christian Urban, Andrea Eder-Halbedl, and Volker Strenger.
• Department of Orthopaedics and Trauma, Medical University of Graz, Auenbruggerplatz 5, 8036, Graz, Austria.
• Wien. Klin. Wochenschr. 2024 Nov 11.

BackgroundBesides surgery, chemotherapy including high-dose methotrexate is a mainstay of osteosarcoma treatment. Methotrexate is known to accumulate in tissues and cavities, so-called third spaces (e.g., periprosthetic seromas) leading to local toxicity and delayed elimination (third space effect). We compared the concentrations of methotrexate in serum and periprosthetic seromas to evaluate a potential toxic risk based on a third space effect.MethodsIn 45 osteosarcoma patients who were treated with endoprosthesis and high-dose methotrexate (HDMTX) between 1991 and 2011 we retrospectively analyzed methotrexate concentrations in periprosthetic seromas and serum. Differences were assessed by means of the Wilcoxon test.ResultsA total of 112 periprosthetic seroma punctures were performed in 18 out of 45 patients. At 24 h the periprosthetic seroma concentrations were in median 14.86-fold (range 1.49-42.97-fold, p = 0.001), at 48 h in median 8.50-fold (range 1.36-52.56, p < 0.001) and at 72 h in median 2.66-fold (range 0.66-5.82, p = 0.015) of the corresponding serum concentrations. At 24 h highly toxic concentrations (≥ 20 μmol/l) were observed in 30% of all analyzed seromas (median 109.83 μmol/l, range 4.91-170.71 μmol/l). A significantly higher serum concentration (range 0.16-0.75 μmol/l, median 0.36 µmol/l) was found in patients with prior puncture than patients without puncture at 45 h after HDMTX.ConclusionMethotrexate concentrations of periprosthetic seromas are significantly higher than corresponding serum concentrations possibly contributing to a third space effect. To avoid severe adverse effects punctures of these effusions should be considered.© 2024. The Author(s).

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