Transcript DEXA-scans

Normalområder, krydskalibrering
og fejlkilder
Pernille hermann
Dept. of Endocrinology
Odense University Hospital
Typiske osteoporotiske brud
Osteoporose er aldersrelateret
Frakturer pr 10.000 personår
KVINDER
Landspatientregisteret 1999
500
Hofte
400
300
Ryg (RTG-incidens)
200
Colles
100
Ryg (indlæggelse)
0
50
60
70
Alder (år)
DSAM 2002 + Lancet 2002;1761
80
90
Definition af osteoporose
• …sygdom, hvor knoglemassen er nedsat og den
mikroskopiske knoglestruktur er forringet i en
sådan grad, at knoglernes brudstyrke er nedsat,
og patienten derfor har øget risiko for
knoglebrud….
Am J Med 1991;90;107
Normal knogle
Osteoporose
Årsager til knoglebrud
Ydre
Vejret, indretning, hjælpemidler..
Faldtraume
Indre
Medicinering, syn, muskelstyrke..
Knoglebrud
Peak bone mass
Arv, kost ….
Knogletab
Køn, alder, medicin ….
Knoglestyrke
(osteoporose)
Determinanter for knoglestyrke
materialemængde (knoglemasse)
Rumlig fordeling (struktur)
Materiale egenskaber (knogle kvalitet)
Styrke
Bone Mineral Density and Fracture Risk
Rate Ratio
Population Based study of Vertebral Fractures in 1098 Women
30
25
20
15
10
5
0
+ Fracture
- Fracture
Low
Medium
Ross et al: Ann Int Med 1991;114:919
High
BMD is an important but imperfect
determinant of bone strength
Post-mortem study
loading simulating fall
Prospective study on
hip fracture risk (Malmø)
8000
Strength (J)
R2 = 0,7984
6000
4000
2000
0
0,2
0,4
0,6
0,8
1
BMD (g/cm2)
Bouxsein et al. Calcif Tissue 1995; 56:99-103
Kanis et al. Osteoporos Int (2001) 12:989–995
Bone mineral density livet igennem
1) Peak Bone Mass
BMD
2) Post-menopausalt
Knogletab
3) Alders-relateret
Knogletab
Alder
Knogle remodellering
Hvilende
Formation
Aktivering
Resorption
Irreversibelt knogletab (1)
Negativ balance pr. remodelleringscyklus
Hvilende
Formation
Aktivering
Resorption
Irreversibelt knogletab (3)
Lis Mosekilde
Trabekulære perforationer
Årsager til knogletab
Reversibelt knogletab
Remodelleringsrummet
Smoking decreases BMD even in young men
Odense Androgen Study; Population-based study on 778 men aged 20-30 years
31% were smokers
BMD 2.4% lower even when adjusted for height and body weight
Effect of smoking may be mediated by lower serum IGF-I and/or vitamin-D
1,6
1,4
1,2
Non-smokers
BMD total hip
1,0
Smokers
TOBACCO
,8
1
,6
18
0
20
Age
Frost Nielsen et al. in preparation
22
24
26
28
30
32
Smoking increases the risk of hip fracture risk
Pooling of data from 3 Danish cohort-studies
N=13,393 women and 17,379 men; Follow-up 5-32 years
19% of hip fractures attributable to smoking
Risk of fracture risk normalized in ex-smokers after 5 years
Relative Risk
P<0.01 for both sexes
2
1,5
1
0,5
0
1,25
1
Ne
ve
r
Ex
-s
Hoidrup et al. Int J Epidemiol 2000;29:253
1,43
1,31
m
ok
er
s
No
n
-in
11
ha
lin
g
1,39
4g
/
>1
5
da
y
Men
Women
g/
da
y
Cushing’s syndrom
sekundært til
dermatomyositis og
prednisonbehandling
Fracture risk and dose of corticosteroids
Relative risk of fracture
compared with control
6
5
4
Hip fracture
Vertebral fracture
3
2
1
0
2.5 mg/d
van Staa TP, et al, 1998
2.5-7.5 mg/d
>7.5 mg/d
Osteoporose
80% Primær
• Postmenopausal
• Senil
20% Sekundær
•
•
•
•
Genetiske faktorer
Endokrine sygdomme
Medicin
Immobilisation
Glucocorticoider
Cyklosporin
Kemoterapi
Diagnosen Osteoporose
• Nedsat BMD
• T-score < -2,5 (NB gælder ikke for børn og unge)
Eller
• Sammenfald i columna uden relevant
traume
Behandlingsindikation
Danmark
• Postmenopauselle kvinder
• T-score < -2,5
• Mænd
• T-score<-3,0
Og mindst en klinisk risikofaktor
• Sammenfald i columna uden relevant
traume
• Hoftebrud uden relevant traume
Fortolkning af DXA
T< -2.5 altså
osteoporose
Z-score
T-score
Total
”Normal”
for alder
T-score
T=0
T= -1
osteopenia
osteoporosis
T= -2.5
DXA-baseret diagnose
• Afhænger af Referencematerialets
• Middelværdi
• Spredning (SD)
• Fejlkilder
• Tekniske
• Biologiske
• Knoglerelateret
• Ikke knoglerelateret
Influence of extern control
Hb-measurement in general practice before control is introduced in 1981
Number of clinics
10
9
Hb
measurements
8
7
6
Known
value
5
4
3
2
1
0
6
4
6,
8
6,
2
7,
6
7,
8
4
8,
8
8,
mmol/l
2
9,
6
9,
10
,4 0,8
0
1
1
Influence of extern control
Hb-measurement in general practice after control is introduced in 1984
Number of clinics
14
Hb
measurements
12
10
Known
value
8
6
4
2
0
mmol/l
Accuracy - Præcision
Accuracy without precision
Præcision without accuracy
Accuracy + præcision
Summeopgave
• Hvordan bestemmes
• Precision ?
• Akuratesse ?
European Spine Phantom 04-221
• International
standardised
• phantom
• 3 vertebrae
hydroxyapatit
• Known values
0,5 g/cm2
1,0 g/cm2
1,5 g/cm2
Results
Measured BMD versus known BMD
BMD g/cm2
1,65
L3 variation
2,3%-10,8%
1,45
ESP L3
1,25
L2 variation
1,3%-11,4%
1,05
ESP L2
0,85
L1 variation
2,5%-24,6%
0,65
ESP L1
0,45
1
2
3
4
5
6
7
8
9
10
Scanner number
11
12
13
14
15
16
Definition of reference values
Definition of reference values
Mean
BMD
Definition of reference values
+ / - 1 SD= 66% of the population
BMD
Definition of reference values
+ / - 2 SD= 95% of the population
= ”Normal”
Low cut-off value
BMD
High cut-off value
BMD in a population
5% of population
95% of population
5% of population
Osteoporosis defined by T-score
T=0
T= -1
osteopenia
osteoporosis
T= -2.5
BMD for total lumbar spine
Comparison with Hologic database
1,6
1,4
OAS: 1,073 (0,125)
Hologic: 1,084* (0,11**)
+ 2SD OAS
+ 2SD Hologic
1,2
Mean Hologic
BMD of total spine (g/cm2)
OAS Mean
1,0
- 2SD Hologic
- 2SD OAS
,8
,6
19
20
Age (years)
21
22
23
24
25
26
27
28
29
30
Prævalens af osteoporose i patient-kohorten
defineret på baggrund af ”maksimale” og
”minimale” normalområde
Patienter med Osteoporose
18
275
250
28
39
3
4
225
200
175
150
125
100
75
50
25
0
Skanner
5
Prævalens af osteoporose i patientkohorten defineret på baggrund af lokal
DXA-skanner og lokalt normalområde
Patienter med osteoporose (n)
300
240
250
209 211
216 216
222 228
217 222
197
200
203 204 209 197
146 147
150
115
100
50
0
”Reference”
1
2
3
4
5
6
7
8
1
9
10
DXA SKANNER
11 12
13 14
15
16
Reproduceability of DEXA
Lumbar spine
Femur
Precision
Error
Accuracy
Error
Least detectable difference
1%
2%
5-8%
5-8%
2.8%
5.6%
Least detectable difference=2*√(2 * CV)
Biologiske
fejlkilder
Osteomalacia
treated
with vitamin-D
Foreign bodies e.g. navel rings
Effect of osteoarthrosis
Score
0
1
2
Reid et al. JCEM 1991:72:1372-74
n
47
61
21
BMD
1.01
1.04
1.08
BMD in bone marrow transplantation
Nysom et al. Bone Marrow Transplantation 2000; 25: 191-196
BMD is underestimated in GHD by
DEXA using area-based BMD
Real density 1 g/cm3
Apparently 2 g/cm2 and
1 g/cm2
Areal BMD
size matters
True density = 1 g/cm2
Size
BMC
Area
BMD
1x1x1
1g
1 cm2
1g/cm2
2x2x2
8g
4 cm2
2g/cm2
Bone remodelling
Quesence
Formation
Activation
Resorption
Remodelling Space
Effect of anti-resorptive treatment on BMD
1,1
BMD
Anti-resorptive treatment
1
Placebo
Filling of
remodelling
space
0,9
-1
0
1
2
Years
Modified from Parfitt Miner Electrolyte Metab 1980;4:273
3
4
BMDarea and BMDvolume in relation
to sex and age
Normal volunteers
BMDarea
Lu et al. J Clin Endocrinol Metab 1996; 81: 1586–90
BMDvolume
Error due to rotation in the hip
1,4
1,2
1
0,8
0,6
0,4
0,2
±13%
20 40 60 80
Errors due to non-uniform distribution of fat
X-ray tube
- 1 cm of fat = + 0.044 g/cm2
(4% error)
Sensor
Tothil et al Br J Radiol 1992:65:807-13
Bone related errors in DEXA-scans
•
•
•
•
•
Positioning
Missing third dimension
Bone turnover
Osteoarthrosis
Posterior vertebral arch (or ribs and
pelvis)
• Vertebral fractures
• Osteomalacia
Soft tissue related errors in DEXA
• Inhomogenous soft tissue (fat)
• Extraskeletal calcifications
• Aortic calcifications
• Intervertebral discs
Spørgsmål ?
58