title: Incidence of skeletal-related events over time from solid tumour bone metastases reported in randomised trials using bone-modifying agents.
abstract: OBJECTIVE
  Skeletal-related events (SREs) in patients with bone metastases decrease a patient's quality of life and functional status. Although bone-modifying agents have been found to reduce the time to first on-trial SRE and decrease the total incidence of SREs in randomised clinical trials, standard practice in the management of bone metastases has changed concurrently. The purpose of this study was to investigate if advances in bone-targeted therapies have decreased the incidence of individual types of SREs and to delineate the trend of SREs.
  
  
  METHODS
  A literature review was conducted in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials to identify phase III, randomised bisphosphonate and other bone-targeted therapy trials from 1980 to September 2011. For all studies, a mean year of enrolment ([start of enrolment + end of enrolment]/2) was calculated. The incidences of SREs were tabulated and expressed as percentages of on-trial patients. Generalised linear mixed models were used to search for the trends of SREs over time for all placebo and intervention arms. Regression coefficients were interpreted as the odds ratio, which was calculated using the exponential of the slope. Ninety-five per cent confidence intervals were also calculated.
  
  
  RESULTS
  In total, 20 eligible studies were identified that reported SRE data from phase III trials, of which 11 were suitable for the quantitative analysis. Most of the articles included patients with breast cancer and the remaining involved patients with prostate, renal cell, bladder and lung cancer or other solid tumours. Enrolment periods for all included data ranged from 1990 to 2009. Statistically significant overall downward trends in pathological fractures and the need for surgery were seen over time. Also significant differences between intervention and placebo were seen with all SREs.
  
  
  CONCLUSIONS
  The decrease in SREs over time may not only be a result of the development of new generation bone-targeted agents, but also due to better systemic management and awareness of events associated with bone metastases.
authors.affiliation: Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Poon
authors.forename: L
authors.initials: L
authors.lastname: Zeng
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: H
authors.initials: H
authors.lastname: Lam
authors.forename: U
authors.initials: U
authors.lastname: Emmenegger
authors.forename: E
authors.initials: E
authors.lastname: Wong
authors.forename: G
authors.initials: G
authors.lastname: Bedard
authors.forename: N
authors.initials: N
authors.lastname: Lao
authors.forename: R
authors.initials: R
authors.lastname: Chow
authors.forename: E
authors.initials: E
authors.lastname: Chow
mesh_terms: D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000453:epidemiology* / Q000556:secondary / Q000628:therapy; D005598:Fractures, Spontaneous / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D015994:Incidence; D016032:Randomized Controlled Trials as Topic
chemical_list: D050071:Bone Density Conservation Agents