title: Effect of oral bisphosphonates for osteoporosis on development of skeletal metastases in women with breast cancer: results from a pharmaco-epidemiological study.
abstract: BACKGROUND
  Treatment with bisphosphonates in women with breast cancer and established bone metastasis delays further skeletal-related events. Evidence is emerging that bisphosphonates are beneficial for secondary prevention of bone metastasis. The study aimed to estimate the effect of oral bisphosphonates for treatment or prevention of osteoporosis on development of bone metastasis in a population of women with breast cancer.
  
  
  METHODS
  A historical cohort of 21664 women diagnosed with breast cancer was created from health administrative data in Quebec, Canada. The primary outcome was time to develop bone metastasis; exposure was bisphosphonate use prediagnosis, postdiagnosis, both, or neither and a cumulative index of drug exposure. The sample was stratified according to stage (0-II or III) at time of diagnosis. Cox proportional hazards tested the effect of bisphosphonate use on time to develop bone metastases.
  
  
  RESULTS
  Taking bisphosphonates postdiagnosis of breast cancer only or continuing bisphosphonates started prior to diagnosis after diagnosis was associated with a reduction in risk of bone metastasis from 45% to 28% in women with local disease at diagnosis. In women with regional disease, postdiagnosis bisphosphonate use, with or without prediagnosis use, reduced risk by almost 50%. A statistically significant dose-response trend was observed relating increased use to lower risk (slope = 0.94, 95% confidence interval = 0.90 to 0.99). Bisphosphonates were also associated with a decreased risk of all-cause mortality similar to that of the development of bone metastasis.
  
  
  CONCLUSIONS
  Low-dose oral bisphosphonates administered for prevention or treatment of postmenopausal osteoporosis were associated with lower risk of skeletal metastasis in patients with early- or more advanced-stage breast cancer.
authors.affiliation: Department of Medicine (RK, NM), Division of Clinical Epidemiology (BG, LN, NM) and Department of Surgery (ANM), McGill University Health Centre, Montreal, Québec; Département de Médecine Familiale et de Médecine d'Urgence, Universite Laval, Centre de recherche du CHUQ, Quebec City, Québec (BG). richard.kremer@mcgill.ca nancy.mayo@mcgill.ca.
authors.forename: Richard
authors.initials: R
authors.lastname: Kremer
authors.affiliation: Department of Medicine (RK, NM), Division of Clinical Epidemiology (BG, LN, NM) and Department of Surgery (ANM), McGill University Health Centre, Montreal, Québec; Département de Médecine Familiale et de Médecine d'Urgence, Universite Laval, Centre de recherche du CHUQ, Quebec City, Québec (BG).
authors.forename: Bruno
authors.initials: B
authors.lastname: Gagnon
authors.affiliation: Department of Medicine (RK, NM), Division of Clinical Epidemiology (BG, LN, NM) and Department of Surgery (ANM), McGill University Health Centre, Montreal, Québec; Département de Médecine Familiale et de Médecine d'Urgence, Universite Laval, Centre de recherche du CHUQ, Quebec City, Québec (BG).
authors.forename: Ari N
authors.initials: AN
authors.lastname: Meguerditchian
authors.affiliation: Department of Medicine (RK, NM), Division of Clinical Epidemiology (BG, LN, NM) and Department of Surgery (ANM), McGill University Health Centre, Montreal, Québec; Département de Médecine Familiale et de Médecine d'Urgence, Universite Laval, Centre de recherche du CHUQ, Quebec City, Québec (BG).
authors.forename: Lyne
authors.initials: L
authors.lastname: Nadeau
authors.affiliation: Department of Medicine (RK, NM), Division of Clinical Epidemiology (BG, LN, NM) and Department of Surgery (ANM), McGill University Health Centre, Montreal, Québec; Département de Médecine Familiale et de Médecine d'Urgence, Universite Laval, Centre de recherche du CHUQ, Quebec City, Québec (BG). richard.kremer@mcgill.ca nancy.mayo@mcgill.ca.
authors.forename: Nancy
authors.initials: N
authors.lastname: Mayo
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000453:epidemiology* / Q000401:mortality / Q000517:prevention & control* / Q000556:secondary; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology*; D002170:Canada / Q000453:epidemiology; D015331:Cohort Studies; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008499:Medical Records; D008875:Middle Aged; D009367:Neoplasm Staging; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012189:Retrospective Studies; D012306:Risk; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates