Assessment of Vertebral Fracture - Vietsciences

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					                Assessment of
               Vertebral Fracture

          Tuan Van Nguyen and Nguyen Dinh Nguyen
             Bone and Mineral Research Program
             Garvan Institute of Medical Reseach
                      Sydney, Australia



Vietnam Osteoporosis Workshop, HCMC 2006
                 Vertebral fracture

    • The most common osteoporotic fracture
    • Patient’s and public health problem:
       – Increased risk of subsequent fractures
       – Quality of life: pain, disability
       – Increased morbidity and mortality risk
       – Costs



Vietnam Osteoporosis Workshop, HCMC 2006
750,000 Spine Fractures each year
  • Most common fragility fx
  • 5-10% increase in all-cause
    mortality*
  • Acute or chronic back pain
      ~2/3 of the fractures are
        clinically silent
  • Height loss
  • Gastrointestinal / respiratory
    difficulties
  • Depression, loss of self-esteem
  • Impact on activities of daily living
                                   *Cooper C et al. Am J Epidemiol 1993;137:1001-1005
Vietnam Osteoporosis Workshop, HCMC 2006
   Prevalence of Vertebral fracture




                                   -Critically dependent on the criterion used.
                                   -Irrespective of the criterion used,
                                   prevalence of VD higher in men than in
                                   women:
                                         -25% vs 20% (3SD)
                                         -17% vs 12% (4SD)
                                         -27% vs 25% (25%)

                                   (Source: Jones G, Nguyen TV et al., Osteoporos Int.
                                   1996;6:233-39)
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    Incidence of vertebral fracture




        Incidence (per 10,000 person-years) of vertebral fracture
        (using McCloskey-Kanis method), stratified by age and gender
        (Source: The EPOS Group, 2002)

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      Association between prevalent vertebral
        fracture and subsequent fractures
          Subsequent fracture (%/3y)




                                       Prevalent vertebral fracture

                                                 (Source: Delmas et al. BONE, 2003; 33:522-32.)
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                     Terminology
  Vertebral deformity/                      Clinical
   Vertebral fracture                  vertebral fracture
        Asymptomatic                         Symptomatic

     • ∆ = imaging                         • ∆ = imaging
                                           • Symptom
        Imaging diagnosis: X-ray, DXA, CT, MRI


IOF recommends to report as “Vertebral fracture”
Vietnam Osteoporosis Workshop, HCMC 2006
          Endpoint for clinical trials
  • Trials of treatment of patients with existing
    vertebral fractures:
      – morphometric evidence of at least one
        baseline vertebral deformity
      – or the presence of at least one “definite”
        fracture according to SQ method.
  • Trials of primary or secondary prevention
    of vertebral fracture: may use QM or SQ or
    a combination.
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           Types of vertebral fracture


                                               Normal


                                               End-plate

                      Concave     Bi-concave


                                               Wedge fracture


                                               Compression fracture
                                                     (crush)

Vietnam Osteoporosis Workshop, HCMC 2006
     Assessment of vertebral fracture



 Prevalent vertebral fracture         Incident vertebral fracture



   • Semi-quantitative
                                      • Quantitative morphometry
   • Quantitative morphometry
                                      • Semi-quantitative
   • Algorithm-based qualitative




Vietnam Osteoporosis Workshop, HCMC 2006
    Approaches to the identification of
           vertebral fracture

• Semi-quantitative method (SQ) or visual
  method
• Quantitative vertebral morphometry (QM)
    – X-Ray
    – Lateral vertebral assessment (LVA): DXA

• Algorithm-based qualitative assessment (ABQ)

Vietnam Osteoporosis Workshop, HCMC 2006
             Semi-quantitative grading
               (Genant et al 1993)
                                                                 Grade

                                                                 0
                                 Normal




                                                                 1 (~20-25%)
                Anterior          Middle
                               Mild fracture         Posterior



                                                                 2 (~25-40%)
                Anterior          Middle             Posterior
                              Moderate fracture



                                                                 3 (~40%)
                Anterior          Middle             Posterior
                              Severe fracture



                             (Source: Genant HK et al, JBMR 1993; 8:1137-1148)
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            SQ: visual normal spine




  T spine                                  L spine
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           SQ Mild                         SQ Severe

                                                   3

               1




                   1




                                               3


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     Morphometric measurements

• Typically based on placement of 6 points that
  define:
    – the anterior height (Ha)
    – the middle height (Hm)
    – the central height (Hc)
    – and the posterior height (Hp)
      of the Vertebral body



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       MQ: types of measurement
              X-Ray                        Lateral Vertebral
         (Standard but not                   Assessment
          “Gold standard”)                   (LVA): DXA




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        Electronic Cursor for Morphometry




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 MQ: Placement of six digitizing points
for different projections of the vertebrae




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       QM with Six-Point Placements




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               Defining vertebral fracture
                                 Parameters:
                                 - Ha/Hp
                      Ha         - Hc/Hp
                 Hc
 Hpi
                                 -Hpi/Hpi+1; Hpi/Hpi-1
 (Hpi+1)
                           Ha
       Hpi-1                    Types of fracture:

       (Hpi)                    - Wedge: ¯Ha, ¯ Ha/Hp
                                - Biconcave (end-plate): ¯Hc, ¯ Hc/Hp
                                - Crush: ¯ Hpi/Hpi+1 or ¯ Hpi/Hpi-1

Vietnam Osteoporosis Workshop, HCMC 2006
                 Major contributions to quantitative morphometric
                              assessments of Vert fx
  Reference                    Measurement       Parameters calculated            Fracture definition
  (Minne et al., 1988)         Ha , Hm , Hp      Spine Deformity Index            Below lower limit of normative values. Values are
                                                                                  adjusted to the dimensions of the T4> 2SD from mean.
  (Kleerekoper et al.,         Ha , Hm , Hp      Wedge ratio, biconcave ratio,    Any ratio £ 0.85. Vertebral dimensions adjusted for
  1984)                                          compress ratio.                  specific level.
  (Gallagher et al., 1988;     Hp, Width         Wedge angle, PRH, PDAH,          Below lower limit of normative values. Values are
  Hedlund and Gallagher,                         area                             adjusted to the dimensions of the T4> 2SD from mean.
  1988; Hedlund et al.,
  1989)
  (Davies et al., 1989;        Ha , Hp           Wedge variable (»PRH),           Below 1st decile above 10th decile of normative value
  Davies et al., 1993)                           relative posterior height.       (Minne et al., 1988); cutoff values adjusted to visual
                                                                                  interpretation (Davies et al., 1993).
  (Harrison et al., 1990)      Ha , Hm , Hp      Wedge ratio, biconcave ratio,    Any ratio £ 0.75, mean height 15% less than adjacent
                                                 compress ratio.                  vertebrae.
  (Raymakers et al., 1990)     Ha , Hm , Hp      Spine Fracture Index             15% difference from expected value
  (Eastell et al., 1991)       Ha , Hm , Hp      Wedge ratio, biconcave ratio,    >3SD and <4SD from mean (grade 1); >4SD from mean
                                                 compress ratio.                  (grade 2).
  (Smith-Bindman et al.,       Ha , Hm , Hp      Index of Radiographic Area       Adjusted height or area below 1st percentile of
  1991)                                                                           normative values.
  (Black et al., 1991)         Ha , Hm , Hp      Wedge ratio, biconcave ratio,    Different cutoff values trim-curved normative data.
                                                 compress ratio.
  (Ross et al., 1993)          Ha , Hm , Hp      Height reduction.                3SD below individually adjusted Z-scores.
  (McCloskey et al., 1993)     Ha , Hm , Hp      Predicted wedge, biconcave       3SD below mean for two criteria
                                                 and posterior ratios.
 PDAH, percent difference in anterior height between adjoining vertebrae; PRH, percent reduction of anterior to posterior height. Ha,
 anterior; Hm, middle; and Hp, posterior height of each vertebral body 2006
Vietnam Osteoporosis Workshop, HCMC from T12 to L4.
           QM: Eastell et al. 1991
                          Har     Hmr         Hpr      Type of fracture




     Ha                            Hm                               Hp

          Wedge                 Bi-concavity             Compression


                                                     Degree of fracture

                                H(a,m,p) –               -4SD< Grade 1 <-3SD
                                H(ar,mr,pr)
                                   SD                     Grade 2 ≤ -4SD
                                        (ar,mr,pr)


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                    Lateral Vertebral Assessment
                             (using DXA):




                                Qualitative and quantitative

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        Six-point video-assisted
      Lateral Vertebral Assessment




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     Visual Assessment of Vertebral Fracture
             Using Lateral DXA Scan

  • VFA showed good sensitivity (>80%) in identifying
    moderate/severe XSQ deformities

  • Excellent negative predictive value (>90%) in distinguishing
    subjects without from those with vertebral deformities on a
    per subject basis.

  • Poor sensitivity to detect mild vertebral fractures, especially
    at the upper thoracic spine.


                                   (Source: J. Rea et al Osteoporos Int 2000)
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      Inter-agreement between expert
                readers (SQ)
                        Visual XA          Visual XA         Visual MXA
                           (A)                (B)                (A)

     Visual XA              0.86                  -                     -
        (B)

    Visual MXA              0.86               0.87                0.86
        (B)
    Visual XR, visual assessment of spinal radiographs
    Visual MXA, visual and quantitative assessment of MXA scan images
                                    (Source: Ferrar et al. JBMR 2003;18:933-938)
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         Concordance between
   the three MQ and the SQ methods
Criterion                                Kappa
                       French      Mixed European          Argentinean

Mean-3SD cutoff         0.73               0.76                 0.73

0.85 x mean cutoff      0.78               0.78                 0.79

3SD/PPH cutoff          0.76               0.73                 0.76



                               (Source: Szulc et al. BONE, 2003;27:841-846)

Vietnam Osteoporosis Workshop, HCMC 2006
          SQ and MQ: A comparison
  Semi-quantitative (SQ)                     Quantitative or
                                         Morphometric approach
Make use of the entire spectrum of     Obtain an objective and reproducible
visible features                       measurement
Using expertises of Radiologists and   Using rigorous defined points placement
Clinicians                             and well-defined algorithms
Quick performance                      Slower
Identify more fracture                 Less
More false-positive rate               High sensitivity, lack of specificity
Not complicated                        Complicated and tedious
Widely applied in clinical practices   Used in epidemiological studies or clinical
                                       trials


               Algorithm-based qualitative assessment (ABQ)
Vietnam Osteoporosis Workshop, HCMC 2006
   Algorithm-based qualitative (ABQ)
               approach

      • Differs from SQ method:
          – Focusing only on depression of the central
            endplate.
          – Introducing the concept of differential
            diagnosis of short vertebral height.

      • Reduce false positive rate

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  Depression of endplate?
                                  No                                    No
   Yes                                        Short vert. height?                 Normal

     Close to centre of
                             No
                                                                  Yes
         endplate?
                                                                                      Yes
                                  Scheuermann’s disease, childhood fracture,
   Yes
                                  Scoliosis, variant in vert. body size
                             No
     True depression?
                                  Anterior location: step-like endplate in thoracic   Yes
                                  vertebrae (variant)
   Yes                            Posterior location: Cupid’s bow or balloon disc
                                  in lumbar vertebrae

    Whole of endplate
                             No
                                                                                      Yes
   depressed within rim?          Check for oblique projection or scoliosis

   Yes
                            Yes           Focused area: Schrnol’s nodes
    Prior trauma, tumor,
    metabolic disease?                                         Yes
                                  Non-fracture deformity, developmental
   No                             variant, non-osteoporotic fx or abnormal
                                  appearances due to other diseases
  Osteoporotic fracture           or conditions
Vietnam Osteoporosis Workshop, HCMC 2006
                 Assessment of
            incident vertebral fracture
 • Semi-quantitative: has not been adequately studied
 • Quantitative Morphometry:
    – A new fracture: ≥ 15% reduction in any one of the three
      measured vertebral heights (Ha, Hm or Hp)
    – More stringent criteria: ≥ 20% change or a change > 3SD
      of the mean differences (on repeated X-ray) for that
      vertebral level.

 • The best definition: has not been established

Vietnam Osteoporosis Workshop, HCMC 2006
      SQ Incident mild vertebral fx




                    0                      1




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       SQ Incident moderate Vert fx




                   0                       2




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 SQ Incident severe & moderate Fxs


                       1                   3


                                               2
                           0




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                         Summary
 • Assessment methods:
    – No “gold standard” for the identification
    – Three methods: SQ, QM and ABQ

 • Vertebral fracture:
    – Serious but mostly asymptomatic
    – Apprx. ¼ vertebral deformities are symptomatic


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                              Lời Cảm tạ

                     • Chúng tôi xin chân thành cám
                       ơn Công ty Dược phẩm
                       Bridge Healthcare, Australia là
                       nhà tài trợ cho hội thảo.




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                       Thank you!




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          Orthograde                       Oblique




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