Bevacizumab-associated osteonecrosis of the femur and tibia

Abstract

Osteonecrosis is a multifactorial process that can affect different skeletal structures of the body. Osteonecrosis of the jaw associated with bevacizumab, steroids and bisphosphonates, alone or in combination, is a well-documented phenomenon. There are few cases of involvement of the appendicular skeleton. Magnetic resonance imaging is the most sensitive method for diagnosis. We hereby report two cases of osteonecrosis in the right tibia and in bilateral femoral heads in patients with adenocarcinoma of the lung and ovarian papillary serous carcinoma, respectively, that developed the complication after long-term bevacizumab exposure. Long-term exposure to antiangiogenic treatment may be a potential risk factor. Oncologists should be aware that osteonecrosis is a rare but real toxicity associated with bevacizumab and other antiangiogenics, which can occur in locations different from the jaw.

Improvement of Bone Marrow Necrosis by Tyrosine Kinase Inhibitor Substitution in a Pediatric Patient With Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia

“…15 In fact, bone necrosis is induced by agents that target vascular endothelial growth factor, PDGFRβ, and c-KIT, such as bevacizumab, sunitinib, and sorafenib. 16 The second generation TKI, dasatinib, can cause vascular adverse events, such as pulmonary arterial hypertension and platelet dysfunction. 17 Furthermore, dasatinib inhibits BCR-ABL with a potency that is 2-log (~325-fold) higher than that of imatinib, 18 and its effects on PDGFR and c-KIT relative to BCR-ABL are lower, compared with that of imatinib.…”

“…In addition, the c-KIT receptor, which has an important role in stimulation of endothelial proliferation,14 is a known imatinib target 15. In fact, bone necrosis is induced by agents that target vascular endothelial growth factor, PDGFRβ, and c-KIT, such as bevacizumab, sunitinib, and sorafenib 16…”

Exploring the Impact of Novel Anti-Cancer Therapies on Jaw Osteonecrosis and Other Bones: A Comprehensive Review

“…Numerous reports have documented instances of osteonecrosis following bevacizumab treatment. While the majority of these reports involve cases of ONJ, there are also instances of osteonecrosis occurring in the wrist and knee [66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82]. In a phase II clinical trial involving 30 patients who received bevacizumab for NSCLC, the incidence rate of ONJ was found to be 10% [73].…”