title: Long term exposure to antiangiogenic therapy, bevacizumab, induces osteonecrosis.
abstract: OBJECTIVE
  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.
authors: Department of Gastroenterology and Digestive Oncology, Cochin Teaching Hospital, AP-HP, Université Paris Descartes, 27, rue du faubourg Saint Jacques, F75014, Paris, France.
authors: Tessa
authors: T
authors: Tabouret
authors: Department of Orthopaedics, Hopital Européen Georges Pompidou, Université Paris Descartes, Paris, France.
authors: Thomas
authors: T
authors: Gregory
authors: Department of Gastroenterology and Digestive Oncology, Cochin Teaching Hospital, AP-HP, Université Paris Descartes, 27, rue du faubourg Saint Jacques, F75014, Paris, France.
authors: Marion
authors: M
authors: Dhooge
authors: Department of Gastroenterology and Digestive Oncology, Cochin Teaching Hospital, AP-HP, Université Paris Descartes, 27, rue du faubourg Saint Jacques, F75014, Paris, France.
authors: Catherine
authors: C
authors: Brezault
authors: Department of Medical Oncology, Gustave Roussy Cancer Institute, Villejuif, France.
authors: Olivier
authors: O
authors: Mir
authors: Department of Gastroenterology and Digestive Oncology, Cochin Teaching Hospital, AP-HP, Université Paris Descartes, 27, rue du faubourg Saint Jacques, F75014, Paris, France.
authors: Johann
authors: J
authors: Dréanic
authors: Department of Gastroenterology and Digestive Oncology, Cochin Teaching Hospital, AP-HP, Université Paris Descartes, 27, rue du faubourg Saint Jacques, F75014, Paris, France.
authors: Stanislas
authors: S
authors: Chaussade
authors: Department of Gastroenterology and Digestive Oncology, Cochin Teaching Hospital, AP-HP, Université Paris Descartes, 27, rue du faubourg Saint Jacques, F75014, Paris, France. romain.coriat@cch.aphp.fr.
authors: Romain
authors: R
authors: Coriat
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D000068258:Bevacizumab / Q000009:adverse effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D010020:Osteonecrosis / Q000139:chemically induced*; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
keywords: Anti-VEGF; Bevacizumab; Chemotherapy; Colon carcinoma