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Vol. 76, No. 3, 2009
Issue release date: March 2009
Oncology 2009;76:209–211

Combination of Bisphosphonates and Antiangiogenic Factors Induces Osteonecrosis of the Jaw More Frequently than Bisphosphonates Alone

Christodoulou C. · Pervena A. · Klouvas G. · Galani E. · Falagas M.E. · Tsakalos G. · Visvikis A. · Nikolakopoulou A. · Acholos V. · Karapanagiotidis G. · Batziou E. · Skarlos D.V.
aSecond Oncology Department, Metropolitan Hospital and bAlfa Institute of Biomedical Sciences (AIBS), Athens, Greece

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Background: The use of bisphosphonates is associated with osteonecrosis of the jaw (ONJ). Antiangiogenic agents are used with increasing frequency and may induce the risk of ONJ, especially when administered concurrently with bisphosphonates. Patients and Methods: We retrospectively reviewed data of 116 patients receiving bisphosphonates, 78 zoledronic acid and 38 ibandronic acid, with or without antiangiogenic agents for osseous metastases from various tumors in our department from June 2007 to June 2008. Results: ONJ developed in: 2 patients with breast cancer and 1 with colon cancer receiving concurrently bisphosphonates and bevacizumab, 1 patient with renal cell carcinoma receiving sunitinib and zoledronic acid concurrently, and 1 patient with prostate cancer receiving zoledronic acid without antiangiogenic agents. The incidences of ONJ among patients receiving bisphosphonates with or without antiangiogenic agents were 16 and 1.1%, respectively. The difference was statistically significant (p = 0.008). The treatment duration of bisphosphonates did not differ significantly between the 2 groups. Conclusions: The combination of bisphosphonates and antiangiogenic factors induces ONJ more frequently than bisphosphonates alone. These preliminary observations should be evaluated in large cohorts of patients and in prospective studies.

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  1. Assouline-Dayan Y, Chang C, Greenspan A, Shoenfeld Y, Gershwin ME: Pathogenesis and natural history of osteonecrosis. Semin Arthritis Rheum 2002;32:94–124.
  2. Marx RE: Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 2003;61:1115–1117.
  3. Durie BG, Katz M, Crowley J: Osteonecrosis of the jaw and bisphosphonates. N Engl J Med 2005;353:99–102.
  4. Bamias A, Kastritis E, Bamia C, Moulopoulos LA, Melakopoulos I, Bozas G, Koutsoukou V, Gika D, Anagnostopoulos A, Papadimitriou C, Terpos E, Dimopoulos MA: Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol 2005;23:8580–8587.
  5. Dimopoulos MA, Kastritis E, Anagnostopoulos A, Melakopoulos I, Gika D, Moulopoulos LA, Bamia C, Terpos E, Tsionos K, Bamias A: Osteonecrosis of the jaw in patients with multiple myeloma treated with bisphosphonates: evidence of increased risk after treatment with zoledronic acid. Haematologica 2006;91:968–971.
  6. Wood J, Bonjean K, Ruetz S, Bellahcène A, Devy L, Foidart JM, Castronovo V, Green JR: Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther 2002;302:1055–1061.
  7. Vincenzi B, Santini D, Dicuonzo G, Battistoni F, Gavasci M, La Cesa A, Grilli C, Virzì V, Gasparro S, Rocci L, Tonini G: Zoledronic acid-related angiogenesis modifications and survival in advanced breast cancer patients. J Interferon Cytokine Res 2005;25:144–151.

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