title: Management of anastrozole-induced bone loss in breast cancer patients with oral risedronate: results from the ARBI prospective clinical trial.
abstract: BACKGROUND
  The aim of this multicenter, phase III, prospective open label clinical trial was to investigate the effect of risedronate (R) on bone mineral density (BMD) in postmenopausal, early breast cancer (BC) patients scheduled to receive anastrozole (A).
  
  
  METHODS
  Pre-treatment BMD of 213 patients with hormone receptor-positive BC was evaluated at lumbar spine (LS) and hip (HP). Patients were categorized according to their baseline BMD T-score as being at low, moderate and high risk of osteoporosis. Low risk patients received anastrozole only (A), moderate risk were randomized to anastrozole +/- risedronate (A+/-R) administration and high risk patients received anastrozole + risedronate (A+R). Anastrozole was given at a dosage of 1 mg/day while oral risedronate was given at 35 mg/week. BMD was then assessed at 12 and 24 months. All patients received daily supplements of calcium (1000 mg/day) and vitamin D (400 IU/day).
  
  
  RESULTS
  At 24 months, in the moderate risk group, treatment with A+R resulted in a significant increase in BMD at LS and HP compared to treatment with A only (5.7% v -1.5%, Wilcoxon test P = 0.006, and 1.6% v -3.9% Wilcoxon test P = 0.037, respectively), while no significant difference was found at 12 months; 24.3% of the patients moved to normal BMD region. In the high risk group, a significant increase for LS was detected both at 12 and 24 months (6.3% and 6.6%, P < 0.001) but not for HP; BMD in 14% of patients improved to the osteopenic region. In the low risk group, a significant decrease of BMD was detected at 12 months for LS and HP (-5.3% P < 0.001 and -2.4% P < 0.001, respectively,); at 24 months, a significant decrease of BMD was detected only for LS (-2.5%, P < 0.001). However, 22% of patients became osteopenic and only 4% became osteoporotic.
  
  
  CONCLUSIONS
  The addition of oral risedronate in post-menopausal breast cancer patients receiving anastrozole has a favorable effect on BMD. Patients with pre-treatment osteopenic to osteoporotic status should be treated with a combination of both therapies in order to avoid bone loss induced by aromatase inhibition. Patients with normal BMD before starting treatment with anastrozole have a very low risk to develop osteoporosis.
authors.affiliation: Hellenic Society of Breast Surgeons, 6 Eslin Street, Athens, Greece. cmarkop@hol.gr
authors.forename: Christos
authors.initials: C
authors.lastname: Markopoulos
authors.forename: Evagelos
authors.initials: E
authors.lastname: Tzoracoleftherakis
authors.forename: Athanassios
authors.initials: A
authors.lastname: Polychronis
authors.forename: Basileios
authors.initials: B
authors.lastname: Venizelos
authors.forename: Urania
authors.initials: U
authors.lastname: Dafni
authors.forename: Grigorios
authors.initials: G
authors.lastname: Xepapadakis
authors.forename: John
authors.initials: J
authors.lastname: Papadiamantis
authors.forename: Vasilios
authors.initials: V
authors.lastname: Zobolas
authors.forename: John
authors.initials: J
authors.lastname: Misitzis
authors.forename: Kyriakos
authors.initials: K
authors.lastname: Kalogerakos
authors.forename: Angeliki
authors.initials: A
authors.lastname: Sarantopoulou
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Siasos
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Koukouras
authors.forename: Zoh
authors.initials: Z
authors.lastname: Antonopoulou
authors.forename: Spyros
authors.initials: S
authors.lastname: Lazarou
authors.forename: Helen
authors.initials: H
authors.lastname: Gogas
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000077384:Anastrozole; D047072:Aromatase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D018771:Arthralgia / Q000139:chemically induced; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D004415:Dyspepsia / Q000139:chemically induced; D012968:Etidronic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D015663:Osteoporosis, Postmenopausal / Q000139:chemically induced / Q000517:prevention & control*; D010352:Patient Dropouts / Q000706:statistics & numerical data; D011446:Prospective Studies; D000068296:Risedronic Acid; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D047072:Aromatase Inhibitors; D050071:Bone Density Conservation Agents; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; D000068296:Risedronic Acid; D012968:Etidronic Acid
references.citation: J Clin Oncol. 1998 Dec;16(12):3890-9
references.pmid: 9850035
references.citation: Breast Cancer Res Treat. 2010 Feb;119(3):643-51
references.pmid: 19941160
references.citation: Cancer. 2008 Mar 1;112(5):1001-10
references.pmid: 18205185
references.citation: Lancet. 2002 Jun 22;359(9324):2131-9
references.pmid: 12090977
references.citation: J Steroid Biochem Mol Biol. 2005 May;95(1-5):151-4
references.pmid: 15970439
references.citation: J Natl Compr Canc Netw. 2006 Nov;4(10):971-9
references.pmid: 17112447
references.citation: J Clin Oncol. 2010 Aug 1;28(22):3577-81
references.pmid: 20567021
references.citation: Am J Clin Oncol. 2008 Dec;31(6):595-605
references.pmid: 19060594
references.citation: J Natl Compr Canc Netw. 2007 Feb;5(2):118-47
references.pmid: 17335683
references.citation: N Engl J Med. 2009 Feb 12;360(7):679-91
references.pmid: 19213681
references.citation: Clin Breast Cancer. 2009 Jun;9 Suppl 1:S18-27
references.pmid: 19561003
references.citation: N Engl J Med. 2005 Dec 29;353(26):2747-57
references.pmid: 16382061
references.citation: Breast. 2007 Dec;16 Suppl 3:S10-5
references.pmid: 18023583
references.citation: Postgrad Med J. 2002 Sep;78(923):526-32
references.pmid: 12357012
references.citation: Ann Oncol. 2009 Jul;20(7):1203-9
references.pmid: 19218306
references.citation: J Clin Oncol. 2010 Feb 20;28(6):967-75
references.pmid: 20065185
references.citation: Semin Oncol. 2007 Dec;34(6 Suppl 4):S11-6
references.pmid: 18068485
references.citation: J Clin Oncol. 2003 Jan 1;21(1):28-34
references.pmid: 12506166
references.citation: Clin Cancer Res. 2008 Oct 1;14(19):6336-42
references.pmid: 18829518
references.citation: Lancet Oncol. 2007 Feb;8(2):119-27
references.pmid: 17267326
references.citation: Clin Breast Cancer. 2009 May;9(2):77-85
references.pmid: 19433387
references.citation: J Clin Oncol. 2005 Jan 20;23(3):619-29
references.pmid: 15545664
references.citation: J Rheumatol. 2009 Mar;36(3):478-90
references.pmid: 19286860
references.citation: Endocrinol Metab Clin North Am. 2003 Mar;32(1):1-13, v
references.pmid: 12699289
references.citation: Lancet. 2005 Jan 1-7;365(9453):60-2
references.pmid: 15639680
references.citation: J Bone Miner Res. 2006 Aug;21(8):1215-23
references.pmid: 16869719
references.citation: J Clin Oncol. 2007 Mar 1;25(7):820-8
references.pmid: 17159195
references.citation: Ann Oncol. 2008 Aug;19(8):1407-1416
references.pmid: 18448451
references.citation: Lancet Oncol. 2003 May;4(5):284-92
references.pmid: 12732166
references.citation: Cancer. 2003 Nov 1;98(9):1802-10
references.pmid: 14584060