title: Treatment of bone metastases before the onset of pain.
abstract: OBJECTIVE
  Bone metastases are often asymptomatic and are not diagnosed until after the onset of bone pain. However, bone structural integrity may have diminished considerably before pain onset, resulting in increased risk of skeletal-related events. Therefore, we evaluated whether bisphosphonate therapy was differentially beneficial depending on initiation before or after the onset of bone pain.
  
  
  METHODS
  Exploratory analyses were performed in patients with bone metastases from breast cancer or lung cancer/other solid tumors enrolled in two randomized trials comparing monthly zoledronic acid versus pamidronate (breast cancer) or placebo (lung cancer/other solid tumors). Analyses included proportion of patients with one or more skeletal-related events, time to first skeletal-related event, and skeletal morbidity rate in patients with and without baseline pain.
  
  
  RESULTS
  Approximately 80 % of patients reported baseline pain. Similar to overall trial results, zoledronic acid reduced the skeletal morbidity rate in all groups. Although some subsets lacked statistical power, benefits were generally greater in patients without baseline pain. For example, in breast cancer, zoledronic acid increased the 25th quartile of time to first skeletal-related event versus pamidronate by 522 days in patients with no baseline pain (median not reached for either group), but by only 10 days in patients with baseline pain. Similar trends were observed in lung cancer.
  
  
  CONCLUSIONS
  Benefits from zoledronic acid appeared to be greater if introduced before bone pain onset. Early diagnosis and treatment of bone metastases may delay onset of skeletal-related events.
authors.affiliation: Hopital de Santa Maria, Serviço de Oncologia, Instituto de Medicina Molecular, Av Professor Egas Moniz, 1649-039, Lisbon, Portugal. luiscosta.oncology@gmail.com
authors.forename: Luis
authors.initials: L
authors.lastname: Costa
authors.forename: Allan
authors.initials: A
authors.lastname: Lipton
authors.forename: Peyman
authors.initials: P
authors.lastname: Hadji
authors.forename: Yin-Miao
authors.initials: YM
authors.lastname: Chen
authors.forename: Paris
authors.initials: P
authors.lastname: Kosmidis
mesh_terms: D000368:Aged; D001859:Bone Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D001943:Breast Neoplasms / Q000150:complications / Q000473:pathology*; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D008175:Lung Neoplasms / Q000150:complications / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010146:Pain / Q000209:etiology / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid