title: Mild morphometric vertebral fractures predict vertebral fractures but not non-vertebral fractures.
abstract: In this meta-analysis of the control arms of four phase 3 trials, mild vertebral fractures were a significant risk factor for future vertebral fractures but not for non-vertebral fracture.
  
  
  BACKGROUND
  A prior vertebral fracture is a risk factor for future fracture that is commonly used as an eligibility criterion for treatment and in the assessment of fracture probability. The aim of this study was to determine the prognostic significance of a morphometric fracture according to the severity of fracture.
  
  
  METHODS
  We examined the control (placebo) treated arms of four phase 3 trials. Vertebral fracture status was graded at baseline in 7,623 women, and fracture outcomes were documented over the subsequent 20,000 patient-years. Fracture outcomes were characterised as a further vertebral fracture, a non-vertebral fracture or a clinical fracture (non-vertebral plus clinical vertebral fracture). The relative risk of fracture was computed from the merged β coefficients of each trial weighted according to the variance.
  
  
  RESULTS
  Mild vertebral fractures were a significant risk factor for vertebral fractures [risk ratio (RR) = 2.17; 95% CI = 1.70-2.76] but were not associated with an increased risk of non-vertebral fractures (RR = 1.08; 95% CI = 0.86-1.36). Moderate/severe vertebral fractures were associated with a high risk of vertebral fractures (RR = 4.23; 95% CI = 3.58-5.00) and a moderate though significant increase in non-vertebral fracture risk (RR = 1.64; 95% CI = 1.38-1.94).
  
  
  CONCLUSIONS
  Prior moderate/severe morphometric vertebral fractures are a strong and significant risk factor for future fracture. The presence of a mild vertebral fracture is of no significant prognostic value for non-vertebral fractures. These findings should temper the use of morphometric fractures in the assessment of risk and the design of phase 3 studies.
authors: WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield, S10 2RX, UK.
authors: H
authors: H
authors: Johansson
authors: A
authors: A
authors: Odén
authors: E V
authors: EV
authors: McCloskey
authors: J A
authors: JA
authors: Kanis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology; D058866:Osteoporotic Fractures / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012307:Risk Factors; D012720:Severity of Illness Index; D016103:Spinal Fractures / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D050071:Bone Density Conservation Agents
references: Osteoporos Int. 2001;12(6):438-44
references: 11446558
references: JAMA. 1999 Aug 18;282(7):637-45
references: 10517716
references: J Bone Miner Res. 1991 Mar;6(3):207-15
references: 2035348
references: Bone. 2009 Jun;44(6):1049-54
references: 19254788
references: J Bone Miner Res. 1993 Sep;8(9):1137-48
references: 8237484
references: BMJ. 1996 May 18;312(7041):1254-9
references: 8634613
references: Osteoporos Int. 1994 Jan;4(1):1-5
references: 8148565
references: Acta Orthop Scand. 1998 Oct;69(5):508-12
references: 9855234
references: J Bone Miner Res. 1999 Jan;14(1):90-101
references: 9893070
references: CMAJ. 2010 Nov 23;182(17):1864-73
references: 20940232
references: Osteoporos Int. 2007 Dec;18(12):1617-24
references: 17611706
references: Bone. 2003 Oct;33(4):522-32
references: 14555255
references: Bone. 1999 Mar;24(3):261-4
references: 10071920
references: J Bone Miner Res. 1999 May;14(5):821-8
references: 10320531
references: J Bone Miner Res. 2000 Apr;15(4):721-39
references: 10780864
references: N Engl J Med. 2004 Jan 29;350(5):459-68
references: 14749454
references: Maturitas. 2009 Feb 20;62(2):105-8
references: 19135323
references: Osteoporos Int. 1995;5(5):354-70
references: 8800786
references: Am J Med. 2007 May;120(5):381-7
references: 17466644
references: Osteoporos Int. 2004 Jan;15(1):20-6
references: 14593450
references: J Bone Miner Res. 2008 Dec;23(12):1923-34
references: 18665787
references: Osteoporos Int. 2004 Nov;15(11):887-96
references: 15071725
references: J Bone Miner Res. 1996 Jul;11(7):984-96
references: 8797120
references: Osteoporos Int. 2013 Jan;24(1):23-57
references: 23079689
references: Osteoporos Int. 1993 May;3(3):120-6
references: 8481587
references: JAMA. 2001 Jan 17;285(3):320-3
references: 11176842
references: Osteoporos Int. 1997;7(2):138-44
references: 9166394
references: Osteoporos Int. 2001;12(5):417-27
references: 11444092
references: J Bone Miner Res. 1992 Feb;7(2):221-7
references: 1570766
references: Bone. 2004 Aug;35(2):375-82
references: 15268886
references: J Clin Endocrinol Metab. 2005 May;90(5):2816-22
references: 15728210
references: Osteoporos Int. 2011 Jan;22(1):63-8
references: 20195843
references: Osteoporos Int. 2007 Jun;18(6):761-70
references: 17245546
references: J Bone Miner Res. 2003 Nov;18(11):1947-54
references: 14606506
references: J Bone Miner Res. 1993 Jul;8(7):817-22
references: 8352064
references: J Clin Endocrinol Metab. 2008 Jul;93(7):2463-5
references: 18544615
references: Bone. 2001 Dec;29(6):517-22
references: 11728921
references: Osteoporos Int. 1998;8(5):468-89
references: 9850356
references: J Bone Miner Res. 2005 Aug;20(8):1349-55
references: 16007332
references: J Bone Miner Res. 1992 Apr;7(4):449-56
references: 1535172
references: J Bone Miner Res. 2004 Dec;19(12):1933-44
references: 15537435
references: Osteoporos Int. 2011 Aug;22(8):2347-55
references: 21287148