title: Oral bisphosphonates: A review of clinical use in patients with bone metastases.
abstract: BACKGROUND
  This study was conducted to review the efficacy and safety of oral bisphosphonates for the treatment of bone metastases in cancer patients.
  
  
  METHODS
  Available published clinical studies of oral bisphosphonates in bone metastases from 1980 to the present were identified through a MEDLINE search and from literature references. Data were reviewed for efficacy and safety, with an emphasis on double blind, placebo-controlled studies; clinically relevant endpoints; and appropriate study methodology.
  
  
  RESULTS
  Etidronate, alendronate, pamidronate, risedronate, and tiludronate currently are available in the U.S. as either intravenous and/or oral formulations. Although newer bisphosphonates are more potent, oral bioavailability remains < 1%. Oral etidronate has been found to be ineffective in patients with multiple myeloma and prostate carcinoma bone metastases. Pamidronate has been found to be effective in reducing skeletal morbidity associated with bone metastases in both multiple myeloma and breast carcinoma patients when given intravenously, but is ineffective orally in multiple myeloma patients. To the authors' knowledge, there are no double blind, placebo-controlled trials of oral pamidronate in patients with breast carcinoma and bone metastases. Several clinical trials with clodronate, a bisphosphonate that is not available in the U.S., have shown mixed results in patients with myeloma and breast carcinoma bone metastases. To the authors' knowledge, there are no published trials evaluating oral alendronate, tiludronate, or risedronate in patients with metastases to bone.
  
  
  CONCLUSIONS
  Oral bisphosphonates do not appear to be as effective as intravenous administration in reducing skeletal complications in patients with metastases to bone lesions. Low oral bioavailability is the most likely reason for this difference. Oral dosing should not be substituted for intravenous administration in the treatment of malignant osteolysis.
authors.affiliation: Hamilton Regional Cancer Center, Hamilton, Ontario, Canada.
authors.forename: P P
authors.initials: PP
authors.lastname: Major
authors.forename: A
authors.initials: A
authors.lastname: Lipton
authors.forename: J
authors.initials: J
authors.lastname: Berenson
authors.forename: G
authors.initials: G
authors.lastname: Hortobagyi
mesh_terms: D019386:Alendronate / Q000627:therapeutic use; D001682:Biological Availability; D015519:Bone Density / Q000187:drug effects*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary*; D001862:Bone Resorption / Q000517:prevention & control*; D001943:Breast Neoplasms / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D004002:Clodronic Acid / Q000627:therapeutic use; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D012968:Etidronic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D000077557:Ibandronic Acid; D007093:Imidazoles / Q000627:therapeutic use; D008297:Male; D009101:Multiple Myeloma / Q000473:pathology; D000077268:Pamidronate; D011471:Prostatic Neoplasms / Q000473:pathology; D011725:Pyridines / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D000068296:Risedronic Acid; D000077211:Zoledronic Acid
chemical_list: C092994:2-(3-methoxyphenylmethylthionyl)-imidazo(4,5-c)pyridine; D004164:Diphosphonates; D007093:Imidazoles; D011725:Pyridines; D004002:Clodronic Acid; C058651:tiludronic acid; D000077211:Zoledronic Acid; C055774:olpadronic acid; D000068296:Risedronic Acid; D012968:Etidronic Acid; D000077268:Pamidronate; D002118:Calcium; D000077557:Ibandronic Acid; D019386:Alendronate