Five leukemic children with toxicity caused by methotrexate had clinical features including severe bone pain during periods of complete hematologic remission and roentgenographic evidence of marked osteoporosis and microfractures. Symptoms responded promptly to cessation of methotrexate therapy, although abnormal x-ray findings persisted for much longer periods. Methotrexate should be suspected as a cause of bone pain in leukemic children maintained with this drug.
O'Regan S, Melhorn DK, Newman AJ. Methotrexate-Induced Bone Pain in Childhood Leukemia. Am J Dis Child. 1973;126(4):489-490. doi:10.1001/archpedi.1973.02110190403008