Normal Ranges For Bone Architecture in a General Population and DXA CrossCalibration' ADOQ Work Pack

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Normal Ranges For Bone Architecture in a General
Population and DXA Cross-Calibration. ADOQ Work
Package 3
University of Cambridge

• N. Dalzell,1 N. Morris, 2 S. Kaptoge,1 J. Reeve 1
• 1 University of Cambridge, Cambridge, UK
• 2 Hethersett Surgery, Norfolk, UK

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Objectives

• To define normal reference ranges for bone
  quality parameters measured by 3D pQCT.
• To coordinate standardization of DXA measurements
  across centres.
• Overall support for clinical studies.
• Compare Cambridge general population data with
  Toulouse astronaut controls data.

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Subject recruitment

• Location Norfolk Norwich county, UK
• Source General practitioners (GP) register
• Hethersett Surgery (Dr N. Morris)
• Sampling List of eligible subjects (ages 20-85)
  randomly sampled by the GP and passed on to the
  research coordinator (N. Dalzell) for invitation.
• Consenting subjects had 3D pQCT and DXA
  measurements as per protocol and answered
  questionnaire. Heel ultrasound also done.

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Subject accrual by year/month

• 125 subjects (52 male, 73 female) aged 20-73 yrs
  (mean48, SD 14) recruited by Apr 2006.

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DXA/pQCT Procedures

• Hip and spine BMD measured by Hologic QDR 1000W
  densitometer.
• Daily QC phantom and periodic measurement of ESP
• DXA data exported periodically (in 5.25 inch
  floppies) to statistician (S. Kaptoge) who put
  them in format up-loadable to ADOQ web.
• 3D pQCT data and scans uploaded directly to MEDES
  from Norwich.

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Data analysis

• Linear regression model on age and age2 for
  age-specific reference ranges by sex and site.
• Results based on 40 males and 62 females whose 3D
  pQCT data were uploaded by February 2006.
• Single model for both genders to test gender
  differences.
• Linear regression model to evaluate centre
  differences in Cambridge and Toulouse data.

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Bone area (mm2)
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Average bone density (mg/cm3)
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Trabecular bone volume Tissue volume
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Trabecular number (1/mm)
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Trabecular bone density (mg/cm3)
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Meta trabecular bone density (mg/cm3)
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Trabecular thickness (mm)
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Inner trabecular bone density (mg/cm3)
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Trabecular separation (mm)
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Ratio of meta to inner density
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Compact bone density (mg/cm3)
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Cortical thickness (mm)
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Equations for age-specific reference ranges
The (1-a)100 age-specific reference range
ß0 ß1Age ß2Age2 Z1-a/2RMSE
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Cambridge vs. Toulouse comparison

• Data received from Toulouse on 59 subjects (28
  male, 31 female) aged 25 45 years recruited as
  astronaut controls.
• Compared Toulouse astronaut control pQCT data
  with Cambridge general population data of the
  same age range.

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Bone area (mm2)
Plt0.0001
Plt0.0001
P-values shown when centre difference was
significant after adjusting for age, weight,
height
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Average bone density (mg/cm3)
P0.028
P-values shown when centre difference was
significant after adjusting for age, weight,
height
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Trabecular bone volume Tissue volume
P0.002
Plt0.0001
P-values shown when centre difference was
significant after adjusting for age, weight,
height
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Trabecular number (1/mm)
P-values shown when centre difference was
significant after adjusting for age, weight,
height
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Trabecular bone density (mg/cm3)
P0.002
Plt0.0001
P-values shown when centre difference was
significant after adjusting for age, weight,
height
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Meta trabecular bone density (mg/cm3)
P0.003
P0.001
P-values shown when centre difference was
significant after adjusting for age, weight,
height
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Trabecular thickness (mm)
P0.025
P0.003
P0.005
Plt0.0001
P-values shown when centre difference was
significant after adjusting for age, weight,
height
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Inner trabecular bone density (mg/cm3)
P0.003
P0.002
P0.034
Plt0.0001
P-values shown when centre difference was
significant after adjusting for age, weight,
height
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Trabecular separation (mm)
P-values shown when centre difference was
significant after adjusting for age, weight,
height
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Ratio of meta to inner density
P-values shown when centre difference was
significant after adjusting for age, weight,
height
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Compact bone density (mg/cm3)
Plt0.0001
Plt0.0001
P-values shown when centre difference was
significant after adjusting for age, weight,
height
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Cortical thickness (mm)
P0.003
P-values shown when centre difference was
significant after adjusting for age, weight,
height
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Comment on Cambridge Toulouse comparison

• After allowing for chance results from multiple
  comparisons the highly significant centre
  differences below survive the Bonferroni
  correction.
• ve difference implies higher values in Toulouse
  than Cambridge.

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DXA Cross-calibration

• European Spine Phantom (ESP) data received from
  all 5 ADOQ centres.
• St Etienne calibration pending since they mailed
  on CD phantom scan images that require Hologic
  machine to read instead of the measured BMD data
  values.
• Have requested the latter to be sent.

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DXA Cross-calibration results

• A two parameter exponential calibration curve
  fitted to 30 ESP measurements.
• Where y is measured density and x is specified
  density of each vertebrae.

• Estimated calibration parameters a and ß are
  summarized in Table 1 for each machine.

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Measured vs. Specified BMD
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Table of Cross-calibration parameters

• Table of estimated calibration parameters to be
  made available on the ADOQ website.

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Conclusions

• The results provide valuable insights into the
  effects of skeletal maturation on the radius and
  tibia.
• Informs about the range of values for bone
  quality parameters expected in normal subjects.
• Observed differences between Cambridge and
  Toulouse data need further thought.
• Pooled analyses of DXA data from ADOQ centres can
  now be readily done using the Cross-calibration
  results.