title: Fracture incidence and characterization in patients on osteoporosis treatment: the ICARO study.
abstract: None of the available osteoporosis therapies have been shown to completely abolish the risk of fractures. In clinical practice, the outcome may be even poorer. In 880 patients prescribed with antiresorptives (alendronate, risedronate, and raloxifene) for >1 year, a fragility fracture was recorded in 8.9%/year of them. This incidence is considerably higher than that observed in randomized clinical trials, and it was significantly related to poor compliance and lack of supplementation with calcium and vitamin D.
  
  
  BACKGROUND
  Osteoporotic fracture is one of the most important public health concerns among the elderly. Currently available therapies have been shown to significantly decrease the risk of fracture, although none of them completely abolishes this risk. In clinical practice, poor treatment response may also result from a number of other factors.
  
  
  METHODS
  The Incidence and ChAracterization of inadequate clinical Responders in Osteoporosis (ICARO) is a multicenter, observational study carried out in Italy. It aimed to analyze, in postmenopausal women with established osteoporosis, the risk factors for an "inadequate clinical response" to drug therapy, defined as the occurrence of new vertebral or nonvertebral fragility fractures in patients prescribed, for at least 1 year, alendronate, risedronate, or raloxifene, with a compliance >50%.
  
  
  RESULTS
  In 880 patients treated with antiresorptive agents for a median of 2.0 years (95% CI: 1.0-4.5) years, the "inadequate clinical responder (ICR)" subjects over the observation period were 220 (25%), with an annual incidence of 8.9%. ICRs, compared with "adequate clinical responders (ACRs)," had more pretreatment fractures and were treated longer (2.8 versus 1.8 years; p < 0.001). After multiple adjustment for these confounding factors, significant determinants of inadequate clinical response were a poorer treatment compliance and a less frequent co-administration of calcium and vitamin D supplements.
  
  
  CONCLUSIONS
  The incidence of fractures during treatment with antiresorptive agents in a clinical setting is considerably higher than that observed in randomized clinical trials. Inadequate compliance to treatment and lack of supplementation of calcium and vitamin D are major determinants of this poor response.
authors.affiliation: Rheumathology Department, University of Verona, Valeggio Sul Mincio Hospital VR, Verona, Italy.
authors.forename: Silvano
authors.initials: S
authors.lastname: Adami
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Isaia
authors.forename: Giovanni
authors.initials: G
authors.lastname: Luisetto
authors.forename: Salvatore
authors.initials: S
authors.lastname: Minisola
authors.forename: Luigi
authors.initials: L
authors.lastname: Sinigaglia
authors.forename: Raffaella
authors.initials: R
authors.lastname: Gentilella
authors.forename: Donato
authors.initials: D
authors.lastname: Agnusdei
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Iori
authors.forename: Ranuccio
authors.initials: R
authors.lastname: Nuti
mesh_terms: D000368:Aged; D019386:Alendronate / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D012968:Etidronic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D007558:Italy; D008875:Middle Aged; D010024:Osteoporosis / Q000150:complications / Q000188:drug therapy*; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use; D012189:Retrospective Studies; D000068296:Risedronic Acid; D012307:Risk Factors; D014807:Vitamin D / Q000627:therapeutic use
chemical_list: D050071:Bone Density Conservation Agents; D014807:Vitamin D; D020849:Raloxifene Hydrochloride; D000068296:Risedronic Acid; D012968:Etidronic Acid; D019386:Alendronate