title: Effect of co-morbidities on fracture risk: findings from the Global Longitudinal Study of Osteoporosis in Women (GLOW).
abstract: BACKGROUND
  Greater awareness of the relationship between co-morbidities and fracture risk may improve fracture-prediction algorithms such as FRAX.
  
  
  METHODS
  We used a large, multinational cohort study (GLOW) to investigate the effect of co-morbidities on fracture risk. Women completed a baseline questionnaire detailing past medical history, including co-morbidity history and fracture. They were re-contacted annually to determine incident clinical fractures. A co-morbidity index, defined as number of baseline co-morbidities, was derived. The effect of adding the co-morbidity index to FRAX risk factors on fracture prevention was examined using chi-squared tests, the May-Hosmer test, c index and comparison of predicted versus observed fracture rates.
  
  
  RESULTS
  Of 52,960 women with follow-up data, enrolled between October 2006 and February 2008, 3224 (6.1%) sustained an incident fracture over 2 years. All recorded co-morbidities were significantly associated with fracture, except for high cholesterol, hypertension, celiac disease, and cancer. The strongest association was seen with Parkinson's disease (age-adjusted hazard ratio [HR]: 2.2; 95% CI: 1.6-3.1; P<0.001). Co-morbidities that contributed most to fracture prediction in a Cox regression model with FRAX risk factors as additional predictors were: Parkinson's disease, multiple sclerosis, chronic obstructive pulmonary disease, osteoarthritis, and heart disease.
  
  
  CONCLUSIONS
  Co-morbidities, as captured in a co-morbidity index, contributed significantly to fracture risk in this study population. Parkinson's disease carried a particularly high risk of fracture; and increasing co-morbidity index was associated with increasing fracture risk. Addition of co-morbidity index to FRAX risk factors improved fracture prediction.
authors.affiliation: MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK. emd@mrc.soton.ac.uk
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Dennison
authors.forename: Juliet E
authors.initials: JE
authors.lastname: Compston
authors.forename: Julie
authors.initials: J
authors.lastname: Flahive
authors.forename: Ethel S
authors.initials: ES
authors.lastname: Siris
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Gehlbach
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Adachi
authors.forename: Steven
authors.initials: S
authors.lastname: Boonen
authors.forename: Roland
authors.initials: R
authors.lastname: Chapurlat
authors.forename: Adolfo
authors.initials: A
authors.lastname: Díez-Pérez
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Anderson
authors.forename: Frederick H
authors.initials: FH
authors.lastname: Hooven
authors.forename: Andrea Z
authors.initials: AZ
authors.lastname: LaCroix
authors.forename: Robert
authors.initials: R
authors.lastname: Lindsay
authors.forename: J Coen
authors.initials: JC
authors.lastname: Netelenbos
authors.forename: Johannes
authors.initials: J
authors.lastname: Pfeilschifter
authors.forename: Maurizio
authors.initials: M
authors.lastname: Rossini
authors.forename: Christian
authors.initials: C
authors.lastname: Roux
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Saag
authors.forename: Philip
authors.initials: P
authors.lastname: Sambrook
authors.forename: Stuart
authors.initials: S
authors.lastname: Silverman
authors.forename: Nelson B
authors.initials: NB
authors.lastname: Watts
authors.forename: Susan L
authors.initials: SL
authors.lastname: Greenspan
authors.forename: Melissa
authors.initials: M
authors.lastname: Premaor
authors.forename: Cyrus
authors.initials: C
authors.lastname: Cooper
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000453:epidemiology; D058866:Osteoporotic Fractures / Q000453:epidemiology*; D010300:Parkinson Disease / Q000453:epidemiology; D016016:Proportional Hazards Models; D012307:Risk Factors