NormalomrNormalområder, krydskalibreringåder, krydskalibrering og fejlkilder og fejlkilder

Pernille hermann

Dept. of Endocrinology

Odense University Hospital

Typiske osteoporotiske brudTypiske osteoporotiske brud

Osteoporose er aldersrelateretOsteoporose er aldersrelateret

0

100

200

300

400

500

50 60 70 80 90

Alder (år)

Fra

ktu

rer

pr

10.0

00 p

erso

når

KVINDERLandspatientregisteret 1999

DSAM 2002 + Lancet 2002;1761

Hofte

Colles

Ryg (indlæggelse)

Ryg (RTG-incidens)

Definition af osteoporoseDefinition 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;107Normal knogle

Osteoporose

Årsager til knoglebrudÅrsager til knoglebrud

Knoglebrud

Knoglestyrke(osteoporose)

Faldtraume

YdreVejret, indretning, hjælpemidler..

IndreMedicinering, syn, muskelstyrke..

Peak bone massArv, kost ….

KnogletabKøn, alder, medicin ….

Determinanter for knoglestyrkeDeterminanter for knoglestyrke

Styrke

Materiale egenskaber (knogle kvalitet)

Rumlig fordeling (struktur)

materialemængde (knoglemasse)

Bone Mineral Density and Fracture RiskBone Mineral Density and Fracture Risk

05

1015202530

Rat

e R

atio

Low Medium High

- Fracture

+ Fracture

Ross et al: Ann Int Med 1991;114:919

Population Based study of Vertebral Fractures in 1098 Women

BMD is an important but imperfect BMD is an important but imperfect determinant of bone strengthdeterminant of bone strength

R2 = 0,7984

0

2000

4000

6000

8000

0,2 0,4 0,6 0,8 1

BMD (g/cm2)

Str

eng

th (

J)

Post-mortem studyloading simulating fall

Bouxsein et al. Calcif Tissue 1995; 56:99-103

Prospective study on hip fracture risk (Malmø)

Kanis et al. Osteoporos Int (2001) 12:989–995

Bone mineral densityBone mineral density livet igennem livet igennem

Alder

BM

D1) Peak Bone Mass

2) Post-menopausalt Knogletab

3) Alders-relateretKnogletab

Hvilende

Aktivering Resorption

Formation

Knogle remodelleringKnogle remodellering

Hvilende

Aktivering Resorption

Formation

Irreversibelt knogletab (1)Irreversibelt knogletab (1)Negativ balance pr. remodelleringscyklus

Irreversibelt knogletab (3)Irreversibelt knogletab (3)L

is M

ose

kild

e

Trabekulære perforationer

Årsager til knogletabÅrsager til knogletab

Reversibelt knogletabReversibelt knogletabRemodelleringsrummet

Smoking decreases BMD even in young menSmoking decreases BMD even in young men

Age

3230282624222018

BM

D to

tal h

ip

1,6

1,4

1,2

1,0

,8

,6

TOBACCO

1

0

Odense Androgen Study; Population-based study on 778 men aged 20-30 years31% were smokers

BMD 2.4% lower even when adjusted for height and body weightEffect of smoking may be mediated by lower serum IGF-I and/or vitamin-D

Frost Nielsen et al. in preparation

Non-smokers

Smokers

Smoking increases the risk of hip fracture riskSmoking increases the risk of hip fracture risk

1 1,25 1,31 1,43 1,39

0

0,5

1

1,5

2

WomenMen

Relative Risk

Hoidrup et al. Int J Epidemiol 2000;29:253

Pooling of data from 3 Danish cohort-studiesN=13,393 women and 17,379 men; Follow-up 5-32 years

19% of hip fractures attributable to smokingRisk of fracture risk normalized in ex-smokers after 5 years

P<0.01 for both sexes

Cushing’s syndromCushing’s syndromsekundært tilsekundært til

dermatomyositis og dermatomyositis og prednisonbehandlingprednisonbehandling

Fracture risk and dose of corticosteroidsFracture risk and dose of corticosteroids

van Staa TP, et al, 1998

0

1

2

3

4

5

6

2.5 mg/d 2.5-7.5 mg/d >7.5 mg/d

Rel

ativ

e ris

k of

fra

ctur

e co

mpa

red

with

con

trol

Hip fractureVertebral fracture

OsteoporoseOsteoporose80% Primær

• Postmenopausal• Senil

20% Sekundær• Genetiske faktorer • Endokrine sygdomme• Medicin• Immobilisation

GlucocorticoiderCyklosporinKemoterapi

Diagnosen OsteoporoseDiagnosen Osteoporose

• Nedsat BMD• T-score < -2,5 (NB gælder ikke for børn og unge)

Eller

• Sammenfald i columna uden relevant traume

BehandlingsindikationBehandlingsindikationDanmarkDanmark

• 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 DXAFortolkning af DXA

Total

T< -2.5 altså

osteoporose”Normal”for alder

Z-score

T-score

T=0

T= -1

T= -2.5osteopenia

osteoporosis

T-score

DXA-baseret diagnoseDXA-baseret diagnose

• Afhænger af Referencematerialets• Middelværdi• Spredning (SD)

• Fejlkilder• Tekniske• Biologiske

• Knoglerelateret• Ikke knoglerelateret

Influence of extern controlInfluence of extern control Hb-measurement in general practice before control is introducedHb-measurement in general practice before control is introduced in 1981in 1981

0

1

2

3

4

5

6

7

8

9

10

Hbmeasure-ments

Knownvalue

mmol/l

Number of clinics

Influence of extern controlInfluence of extern controlHb-measurement in general practice after control is introduced inHb-measurement in general practice after control is introduced in 19841984

0

2

4

6

8

10

12

14Hbmeasure-ments

Knownvalue

mmol/l

Number of clinics

Accuracy - PræcisionAccuracy - Præcision

Accuracy without precision Præcision without accuracy

Accuracy + præcision

SummeopgaveSummeopgave

• Hvordan bestemmes• Precision ?• Akuratesse ?

European Spine Phantom 04-221 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

ResultsResults

0,45

0,65

0,85

1,05

1,25

1,45

1,65

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

L3 variation2,3%-10,8%

ESP L3

L2 variation1,3%-11,4%

ESP L2

L1 variation2,5%-24,6%

ESP L1

Scanner number

Measured BMD versus known BMDBMD g/cm2

Definition of reference valuesDefinition of reference values

Definition of reference valuesDefinition of reference values

BMD

Mean

Definition of reference valuesDefinition of reference values

BMD

+ / - 1 SD= 66% of the population

Definition of reference valuesDefinition of reference values

BMD

+ / - 2 SD= 95% of the population= ”Normal”

High cut-off valueLow cut-off value

BMD in a population

95% of population

5% of population

5% of population

T=0

T= -1

T= -2.5osteopenia

osteoporosis

Osteoporosis defined by T-score

BMD for total lumbar spineBMD for total lumbar spineComparison with Hologic databaseComparison with Hologic database

OAS: 1,073 (0,125)

Hologic: 1,084* (0,11**)

Age (years)

302928272625242322212019

BM

D o

f to

tal s

pin

e (

g/c

m2)

1,6

1,4

1,2

1,0

,8

,6

+ 2SD OAS

- 2SD OAS

Mean Hologic

+ 2SD Hologic

- 2SD Hologic

OAS Mean

Prævalens af osteoporose i patient-kohorten Prævalens af osteoporose i patient-kohorten defineret på baggrund af ”maksimale” og defineret på baggrund af ”maksimale” og

”minimale” normalområde”minimale” normalområde

0

25

50

75

100

125

150

175

200

225

250

275

3 4 5

Patienter med Osteoporose

28 39

18

Skanner

Prævalens af osteoporose i patient-Prævalens af osteoporose i patient-kohorten defineret på baggrund af lokal kohorten defineret på baggrund af lokal DXA-skanner og lokalt normalområdeDXA-skanner og lokalt normalområde

0

50

100

150

200

250

300

1

DXA SKANNER

209 211

115

216 216240

146 147

217 222197

222 228203 204 209

197

1 2 3 4 5 6 7 8 9 10 11 12 13 14 1615

”Re

fere

nce

”

Patienter med osteoporose (n)

Reproduceability of DEXAReproduceability of DEXA

Precision Accuracy Least detect- Error Error able difference

Lumbar spine 1% 5-8% 2.8%

Femur 2% 5-8% 5.6%

Least detectable difference=2*√(2 * CV)

Osteomalacia treated with vitamin-DOsteomalacia treated with vitamin-DBiologiske fejlkilder

Foreign bodies Foreign bodies e.g. navel ringse.g. navel rings

Effect of osteoarthrosisEffect of osteoarthrosis

Score n BMD

0 47 1.01

1 61 1.04

2 21 1.08

Reid et al. JCEM 1991:72:1372-74

BMD in bone marrow transplantationBMD in bone marrow transplantation

Nysom et al. Bone Marrow Transplantation 2000; 25: 191-196

BMD is underestimated in GHD by BMD is underestimated in GHD by DEXA using area-based BMDDEXA using area-based BMD

Real density 1 g/cm3

Apparently 2 g/cm2 and 1 g/cm2

Areal BMDAreal BMDsize matterssize matters

Size BMC Area BMD

1 x 1 x 1 1g 1 cm2 1g/cm2

2 x 2 x 2 8g 4 cm2 2g/cm2

True density = 1 g/cm2

Quesence

Activation Resorption

Formation

Bone remodellingBone remodelling

Remodelling SpaceRemodelling Space

Effect of anti-resorptive treatment on BMDEffect of anti-resorptive treatment on BMD

0,9

1

1,1

-1 0 1 2 3 4

Modified from Parfitt Miner Electrolyte Metab 1980;4:273

BM

D

Years

Anti-resorptive treatment

PlaceboFilling of

remodelling space

BMDBMDareaarea and BMD and BMDvolumevolume in relation in relation to sex and ageto sex and age

Lu et al. J Clin Endocrinol Metab 1996; 81: 1586–90

Normal volunteers

BMDarea BMDvolume

Error due to rotation in the hipError due to rotation in the hip

0,20,40,60,8

11,21,4

20 40 60 80

±13%

Errors due to non-uniform distribution of fatErrors due to non-uniform distribution of fat

X-ray tube

Sensor

- 1 cm of fat = + 0.044 g/cm2 (4% error)

Tothil et al Br J Radiol 1992:65:807-13

Bone related errors in DEXA-scansBone 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 DEXASoft tissue related errors in DEXA• Inhomogenous soft tissue (fat)

• Extraskeletal calcifications• Aortic calcifications• Intervertebral discs

Spørgsmål ?Spørgsmål ?

58