Long term exposure to antiangiogenic therapy, bevacizumab, induces osteonecrosis

Invest New Drugs. 2015 Oct;33(5):1144-7. doi: 10.1007/s10637-015-0283-x. Epub 2015 Aug 28.


Purpose: Bevacizumab, a monoclonal VEGF-A antibody, has been identified as an aetiology of osteonecrosis of the femoral head. Long exposure to anti VEGF therapy induced chronic hypoperfusion of normal tissues. Osteonecrosis is a musculo-skeletal disease secondary to cellular death of bone component mainly induced by corticosteroids, alcohol use, or connective tissue disorders.

Methods: The medical records of patients with metastatic colorectal carcinoma receiving Bevacizumab between January 2006 and November 2013 were retrospectively reviewed and we had looked for osteonecrosis. Every disorder of musculoskeletal mobility were examined by orthopaedist and evaluated by imaging.

Results: We report on osteonecrosis of humeral and femoral head in patient with metastatic colon adenocarcinoma receiving a long-term exposure to anti angiogenic based treatment (>6 months), lack of other factors predisposing to osteonecrosis. These observations, according to literature, suggests that long exposure to anti VEGF-A, Bevacizumab, promote bone hypoperfusion and may induced osteonecrosis either on the femoral head or the humeral head with an incidence of 4 out of 1000 patients.

Conclusions: With an incidence of 4 out of 1000 patients osteonecrosis is a rare side effect of anti-angiogenic agent. With the increasing utilisation and duration of exposure of anti-VEGF therapy some rare side effect due to chronic ischemia may appear. The clinician should be aware about uncommon symptoms.

Keywords: Anti-VEGF; Bevacizumab; Chemotherapy; Colon carcinoma.

Publication types

  • Case Reports

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Aged
  • Angiogenesis Inhibitors / adverse effects*
  • Bevacizumab / adverse effects*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Female
  • Humans
  • Male
  • Neoplasm Metastasis
  • Osteonecrosis / chemically induced*
  • Retrospective Studies
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*


  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factor A
  • Bevacizumab