title: Impact of clinical fractures on health-related quality of life is dependent on time of assessment since fracture: results from the FREEDOM trial.
abstract: In the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) study, women with incident clinical fractures reported significant declines in health-related quality of life (HRQoL). The largest declines were observed when the assessment was <3 months post fracture. The largest impact of incident clinical fractures was on physical function, and that of incident clinical vertebral fractures was on back pain.
  
  
  BACKGROUND
  In the FREEDOM trial, denosumab significantly reduced the risk of new vertebral, hip, and nonvertebral fractures. We evaluated the effect of denosumab on HRQoL and the association between incident clinical fractures and HRQoL.
  
  
  METHODS
  The FREEDOM trial enrolled 7,868 women aged 60-90 years with a total hip and/or lumbar spine BMD T-score <-2.5 and not <-4.0 at either site. Women were randomized to receive denosumab 60 mg or placebo every 6 months, in addition to daily calcium and vitamin D. HRQoL was assessed with the Osteoporosis Assessment Questionnaire-Short Version (OPAQ-SV) at baseline and every 6 months for 36 months. The OPAQ-SV assesses physical function, emotional status, and back pain. Higher scores indicate better health status.
  
  
  RESULTS
  No statistically significant differences in mean change in HRQoL from baseline to end of study were found when comparing treatment groups. Compared with women without any incident fractures during the study, women with incident clinical fractures reported significant declines in physical function (-4.0 vs. -0.5) and emotional status (-5.0 vs. -0.8) at month 36 (P < 0.001 for both). Importantly, time-dependent covariate analyses demonstrated that the largest declines were observed when the assessment was <3 months post fracture. The largest impact of incident clinical fractures was on physical function, and that of incident clinical vertebral fractures was on back pain.
  
  
  CONCLUSIONS
  These findings not only demonstrate that incident clinical fractures impact HRQoL but also contribute new information regarding the impact of these fracture events on HRQoL over time.
authors.affiliation: Cedars-Sinai/UCLA and OMC Clinical Research Center, 8641 Wilshire Boulevard, Suite 301, Beverly Hills, CA 90211, USA. stuarts@omcresearch.org
authors.forename: S
authors.initials: S
authors.lastname: Silverman
authors.forename: H N
authors.initials: HN
authors.lastname: Viswanathan
authors.forename: Y-C
authors.initials: YC
authors.lastname: Yang
authors.forename: A
authors.initials: A
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Boonen
authors.forename: S
authors.initials: S
authors.lastname: Ragi-Eis
authors.forename: P
authors.initials: P
authors.lastname: Fardellone
authors.forename: N
authors.initials: N
authors.lastname: Gilchrist
authors.forename: P
authors.initials: P
authors.lastname: Lips
authors.forename: M
authors.initials: M
authors.lastname: Nevitt
authors.forename: S
authors.initials: S
authors.lastname: Palacios Gil-Antuñano
authors.forename: K
authors.initials: K
authors.lastname: Pavelka
authors.forename: D
authors.initials: D
authors.lastname: Revicki
authors.forename: J
authors.initials: J
authors.lastname: Simon
authors.forename: D
authors.initials: D
authors.lastname: Macarios
authors.forename: E S
authors.initials: ES
authors.lastname: Siris
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001416:Back Pain / Q000209:etiology / Q000534:rehabilitation; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D000069448:Denosumab; D005260:Female; D006621:Hip Joint / Q000503:physiopathology; D006801:Humans; D008159:Lumbar Vertebrae / Q000503:physiopathology; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology / Q000534:rehabilitation; D058866:Osteoporotic Fractures / Q000517:prevention & control / Q000523:psychology / Q000534:rehabilitation*; D011594:Psychometrics; D011788:Quality of Life; D053245:RANK Ligand / Q000037:antagonists & inhibitors; D016103:Spinal Fractures / Q000150:complications / Q000517:prevention & control / Q000523:psychology / Q000534:rehabilitation; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D053245:RANK Ligand; D000069448:Denosumab