Zoledronic Acid-Induced Lesions Mimicking Metastasis in Patients with Bone Cancers

Zoledronic acid (ZA) is used to treat osteoporosis, hypercalcemia, metabolic bone disease, cancer induced bone disease, and Paget’s disease of bone. In cancer patients with bone metastasis, it can decrease pain and occasionally induce shrinkage. For primary bone tumors, such as osteosarcoma and Ewing sarcoma, zoledronic acid has been trialed as part of combination chemotherapy strategy in high-risk patients. Osteonecrosis of the jaw is a well described side effect of ZA, but osteonecrosis of other bones is very rare. We describe three patients with relapsed primary bone tumors on zoledronic acid who had presumed relapse with new bony metastasis, that was subsequently contradicted by alternative imaging and biopsy. We hypothesize that these false positive results were due to zoledronic acid inhibiting the cycle of tumor cell proliferation and bone resorption causing bony infarcts in a tumor dependent pathway that increases osteoblast activity. We hope that awareness of this rare phenomenon will encourage practitioners to prove bone metastasis in primary bone cancers by biopsy, or alternative imaging before concluding current therapy has failed.