Methotrexate osteopathy in patients with osteosarcoma.

Purpose: To determine the frequency of osteopathy in patients treated with high-dose, short-term, intravenous methotrexate for osteosarcoma and whether this complication varies with patient age and methotrexate dose.

Materials And Methods: Radiographs and available scintigrams of 87 patients with osteosarcoma who received high-dose methotrexate were reviewed retrospectively for severe osteopenia, dense zones of provisional calcification, insufficiency fractures, and involvement of multiple bones. At least three of these radiographic abnormalities were required for the diagnosis of osteopathy. Patients with bone metastases were excluded.

Results: Eight patients (cumulative dose, 60-144 g/m2) exhibited adverse skeletal findings similar to those described in children with leukemia who received low-dose maintenance methotrexate. Images showed severe osteopenia (n = 8), dense zones of provisional calcification (n = 8), multiple bone involvement (n = 6), and insufficiency fractures (n = 6). Most commonly affected sites were the distal tibia (n = 7), distal radius and proximal humerus (n = 3), and calcaneus and public ramus (n = 2). The affected patients were significantly younger (mean age, 9.2 years; P < .001) than the 79 unaffected patients (mean age, 14.9 years).

Conclusion: Osteopathy occurs in approximately 9% of children who receive high-dose methotrexate for osteosarcoma and is substantially more likely to occur in younger patients. The complication rate was not directly dose dependent.