title: Double-blind controlled trial of oral clodronate in patients with bone metastases from breast cancer.
abstract: OBJECTIVE
  Osteolytic metastases often give rise to hypercalcemia, fracture, and bone pain, and occur commonly in patients with recurrent breast cancer. We assessed the bisphosphonate, clodronate, which has proven to be a useful treatment for hypercalcemia and may be a potent inhibitor of tumor-induced osteolysis, for its effect on reducing the osseous complications of metastatic breast cancer.
  
  
  METHODS
  We studied 173 patients with bone metastases due to breast cancer in a randomized, double-blind, placebo-controlled trial of oral clodronate 1,600 mg/d (85 patients) compared with an identical placebo (88 patients).
  
  
  RESULTS
  The patients in each wing were comparable in their clinical, radiologic, and biochemical characteristics at trial entry. In patients who received clodronate, there was a significant reduction compared with placebo in the total number of hypercalcemic episodes (28 v 52; P < .01), in the number of terminal hypercalcemic episodes (seven v 17; P < .05), in the incidence of vertebral fractures (84 v 124 per 100 patient-years; P < .025), and in the rate of vertebral deformity (168 v 252 per 100 patient-years; P < .001). The combined rate of all morbid skeletal events was significantly reduced (218.6 v 304.8 per 100 patient-years; P < .001). Trends were seen in favor of clodronate for nonvertebral fracture rates and radiotherapy requirements for bone pain (particularly spinal pain). No significant survival differences and no significant differences in side effects were observed between the two groups.
  
  
  CONCLUSIONS
  These findings indicate that oral clodronate has a beneficial effect on the skeletal morbidity associated with breast cancer and should be considered as antiosteolytic therapy in affected patients. It deserves further investigation as an adjuvant therapy in operable breast cancer and in patients with nonosseous recurrence who are at high risk for bone metastases.
authors.affiliation: Department of Medicine, Tom Baker Cancer Center, Calgary, Alberta, Canada.
authors.forename: A H
authors.initials: AH
authors.lastname: Paterson
authors.forename: T J
authors.initials: TJ
authors.lastname: Powles
authors.forename: J A
authors.initials: JA
authors.lastname: Kanis
authors.forename: E
authors.initials: E
authors.lastname: McCloskey
authors.forename: J
authors.initials: J
authors.lastname: Hanson
authors.forename: S
authors.initials: S
authors.lastname: Ashley
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D001943:Breast Neoplasms / Q000473:pathology*; D002118:Calcium / Q000097:blood / Q000652:urine; D004002:Clodronic Acid / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005598:Fractures, Spontaneous / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D008875:Middle Aged
chemical_list: D004002:Clodronic Acid; D002118:Calcium