2-69
T-score and Z-score Compare patient BMD to reference values BMD (g/cm 2)
1.100
Peak Bone Mass = 1.047
1.050 AGE 20 25 30 35 40 45 50 55 60 65 70 80 85
Fem ale 1.019 1.040 1.047 1.041 1.024 0.999 0.967 0.930 0.892 0.854 0.815 0.752 0.731
1.000 0.950 0.900
T=-3,1
0.850 0.800 0.750
Z=-0,4
0.700 BMD = 0.700
0.650
AGE = 80
0.600 20
30
40
50
60
70
80
Reference Curve, Female total lumbar spine : SD = 0.11
90
AGE
2-70
Principe van de densitometrie Absorptie van X-stralenbundel
2-71
Absorptiometry Absorptie van fot onen (γ- or X-rays) hangt af van
– Materie: i.e. Dichtheid – Dikte – Foton of X-ray energie
Vereenvoudigde patient bestaat uit twee onbekenden:
bot en (zacht) weefsel Absorptiemetingen met één energie geven niet genoeg informatie om weefsel van bot te onderscheiden. Introductie van een extra factor:
two energies
DEXA
2-72
DXA Principle of Operation A = Attenuatie per energieniveau K = Correctiefactor voor de attenuatie in zacht weefsel
A High Energy
ALow Energy K*AHigh Energy ALow Energy - K*AHigh Energy
Dual Energy Subtraction (BMD) Image
2-73
Werkingsprincipe Detector Array
X-Ray Fan Beam
Object of Interest Table Mat
Calibration wheel Tank (X-Ray Source)
Table Top
Detectie Intern calibratie w iel, gesynchronis eerd met gepulste Dual Energy. Calibratie w iel bevat drie gekende segmenten : 1.Lucht 2.Weefseldata-punten voor iedere pixel in het beeld 3.Bot Ieder segment is gescand met Hoge en Lage energie Dit levert zes
Interne Calibratie 1. Opwekken van X-stralen
2-74
Automatische Calibratie Gepatenteerd Intern Referentie Systeem • De continue calibratie per pixel vergelijkt het “bekende” met het “onbekende” Lucht = patient gemeten Bot = botequivalent+ patient Weefsel = weefselequivalent+ patient
• Verzekert compatibiliteit en vergelijkbaarheid van data • Verzekert stabiliteit op lange termijn • Garandeert stabiliteit bij upgrades • Gecontroleerd met automatische dagelijkse QC dmv een QC fantoom.
2-75
Quantitative Ultrasound
2-76
Transverse Transmission Broadband Ultrasound Attenuation
Speed of Sound
SOS
Healthy Osteoporotic
Absorption
BUA
Time Frequency
Calcaneus Heel
Transmitter
waterbath
Receiver
2-77
Quantitative Ultrasound Clinical Use • Diagnosis of osteoporosis not possible • WHO criteria not applicable • Assessment of fracture risk possible (>60 to 65 years of age) similar to DXA • Use of threshold values DXA • Large variability not suitable for follow-up / assessment of treatment efficacy
2-78
Nieuwe “Explorer” serie Toestel Gebruik
2-79
Positionering Lumbale wervelzuil AP Lumbar spine
2-80
AP Spine
2-81
Positionering Heup Hip Scan
2-82
AP Femur
2-83
2-84
Voorarm
2-85
Why Measure Spine and Hip • Spine: trabecular, postmenopausal • Hip: cortical, elderly • Spine-Hip discordance - find lower BMD site • Fracture prediction - spine BMD for spine fractures - hip BMD for hip fractures • Flexibility in monitoring - with spine degenerative disease, may use hip
2-86
Hip-Spine Discordance PA Lumbar spine (T-score)
5 4 3 2 1 0 -1 -2 -3 -4 -5 -5
-4
-3
-2
-1
0
1
2
Femoral neck (T-score) Arlot M. et al, J Bone Miner Res 1997; 12:683
3
2-87
Hip-Spine Discordance due to Vertebral Fracture and Spinal Degenerative Disease L2-L4 T = -0.2 WHO = Normal
Femoral neck T = -2.7 WHO= Osteoporosis
2-88
Hip-Spine Discordance due to Early Menopausal Trabecular Bone Loss
2-89
IRIS: Integrated Radiology Information System
• Modality Worklist • DIC OM 3 Image Storage • Remote Softcop y Interpreta tion • Electronic Report Generation
2-90
Dose Considerations
2-91
Dose considerations Pencil beam
Fan beam
PA spine
0,5 µSv
2,0 µSv
Femur excl ovaries
0,1 µSv
0,6 µSv
Femur incl. ovaries
1,4 µSv
5,4 µSv
Scatter dose at 1 m:
under 1 μSv/h
Comparison: • natural background:
about 1 mSv
(1 h ≈ 60 scans)
2-92
WHO Criteria for Postmenopausal Osteoporosis The T-score compares an individual’s BMD with the mean BMD value for a young reference population, and expresses the difference as a standard deviation score. T-score Normal
- 1.0 and above
Osteopenia
- 1.0 to - 2.5
Osteoporosis
- 2.5 and below
Severe (established) osteoporosis
- 2.5 and below, plus one or more osteoporotic fracture(s)
Kanis J.A. et al, J Bone Miner Res 1994; 9:1137-41
2-93
Prevalence of Osteoporosis in Women at Different Skeletal Sites 60%
Prevalence
50%
T-score ≤ -2.5
40% 30% 20% 10% 0% Spine
50-59 Hip
60-69 Mid-radius
Melton et al, J Bone Miner Res 1995; 10:175
70-79 Any site
80+
age 50+
Years
2-94
Bone Density and Fracture Risk ±2 SD
35
32
30
sRR = 2
BMD
2-Fold Change in Fracture Risk / SD
Standardizing Risk Ratios
25 20
16 15
60
1 SD
8 10
70 Age
5 0 -5
-4
-3
-2
T-score
-1
0
80
2-95
Gradients of Risk
Relative risk 12 10
BMD & hip fracture 8
BP & stroke 6
Cholesterol & MI
4 2 0
I
II
III
Quartile
IV
2-96
WHO Criteria Limited to Specific Populations, Skeletal Sites, and Devices • Only postmenopausal white women - not men, younger women, other ethnic groups • Only PA spine, hip (and forearm) DXA - not lateral spine, heel, finger, etc • Only for central DXA - not peripheral DXA, QCT, QUS, RA, etc
2-97
Diagnosis in Men • WHO´s diagnostic criteria may be used - BMD related to the risk of bone fracture - fracture risk increases ≈ 2 fold per 1SD reduction in BMD ( similar to the risk found in women ) • All manufacturers use gender specific T-scores - at the same BMD, T-scores are different depending on gender - best approach for now
2-98
Risk Factors that Provide Indications for the Diagnostic Use of Bone Densitometry 1.
Radiographic evidence of osteopenia or vertebral deformity, or both
2.
Previous fragility fracture
3.
Loss of height, thoracic kyphosis (after radiogra phic confirmation of vertebral deformities)
4.
Presence of strong risk factors: • Anorexia nervosa • Malabsorption • Primary • • • • •
hyperparathyroidism Post-transplantation Chronic renal failure Hyperthyroidism Prolonged immobilization Cushing’s syndrome
Kanis J., Lancet 2002; 359:1929
• • • • • • • •
Estrogen deficiency Corticosteroid therapy Premature menopause, < 45 yr Maternal family history of hip fracture Long-term secondary amenorrhea (> 1 yr) Low body mass index (<18 kg/m2 ) Primary hypogonadism Other disorders associated with osteoporosis
2-99
Osteoporose fracturen en BMD
50 40
Absolute Aantal
Fractuur incidentie
400
Vrouwen met fracturen
300
30 20
200
10
100
0
1.0
0.5
0.0
-0.5
-1.0
-1.5
-2.0
-2.5
-3.0
-3.5
0
E. Siris . Surge on Ge neral’s Workshop on Oste oporosis and Bone Health, Decem ber 2002
Aantal fracturen
Fractures/1,000 persoonjaren
Incidentie
2-100
VFx & BMD bepalen samen het risicoprofiel 75x méér risico indien meerdere VFx en lage BMD Ross 1991
Relatief Risico
75
Ann Intern Med;144 :919-23
25.1 14.9 10.2 7.4
4.4
1
Lage BMD Med BMD Hoge BMD
> 1 Fx 1 Fx geen Fx
2-101
Wijziging van het Osteoporose Paradigma
=
Wat we (W) niet meten ?
Bot Densiteit
+
BMD = gr/cm2 Rel Risk
Fractuur
10 8 6 4 2 0
BMD (quartielen)
I
II III IV
2-102
10jaar - fractuurkans (%)
Leeftijd is de voornaamste risico factor
20
80
Leeftijd
Vrouwen
70 10
60 50 0 -3
-2
-1
T-score (SD)
0
1
2-103
Relatief risico (vs. BMI=25)
BMI en fractuurrisico 5 Alle fracturen Osteoporose # Heup fractuur
4 3 2 1 0 15
20
25
30
35
BMI ( kg/m2)
40
45
2-104
Risico voor heupfractuur ( man & vrouw )
Relatief Risico
3.0 2.0 1.0 0.0 Vroegere fractuur
Fam. (heup)
vrouw man
Roken Steroiden Alcohol ooit > 2 /dag Actueel
RA
2-105
Risk Factors for Osteoporotic Fracture With Relative Risk ≥ 2 (Major) • • • • • • • • • • • • •
Age > 70 years Menopause < 45 years Hypogonadism Fragility fracture Hip fracture in 1o relatives Glucocorticoids Malabsorption High bone turnover Anorexia nervosa BMI < 18 kg/m2 Immobilization Chronic renal failure Transplantation
With Relative Risk 1 - 2 (Moderate) • • • • • • • • • •
Estrogen deficiency Calcium intake < 500 mg/d Primary hyperparathyroidism Rheumatoid arthritis Bechterew Disease Anticonvulsants Hyperthyroidism Diabetes mellitus Smoking Excessive alcohol
Adapted from Brown J. et al. CMAJ 2002; 167(10 suppl):S1-S34
2-106
Secondary Causes of Osteoporosis Endocrinopathies • Hypercalciuria with or without renal stones • Hypogonadism (incl. hyperprolactinemia) • Hyperparathyroidism • Hyperthyroidism • Cushing's syndrome • Acromegaly?
Drugs • Excess glucocorticoids • Excess thyroid hormones • Anticoagulants (heparin, coumarins?) • GnRH antagonists, Aromatase inhibitoren • Anticonvulsants • Aluminum-containing antacids • Cyclosporine • Rifampicin • Exchange resins ? Methotrexate ? Loop diuretics
2-107
Risk Factors for Osteoporotic Fracture Non-modifiable:
• • • • • • •
Personal history of fracture History of fracture in 1°relative Caucasian race Advanced age Female Dementia Poor health/frailty
Potentially modifiable: • Current cigarette smoking • Low body weight (BMI < 18-20) • Estrogen deficiency: • Early menopause (< age 45 yr) • Bilateral ovariectomy • Premenopausal amenorrhea • Low calcium intake (lifelong) • Alcoholism • Impaired eyesight • Recurrent falls • Inadequate physical activity • Poor health/frailty
2-108
Specific Genetic Disorders • Ehlers-Danlos syndrome • Marfan's syndrome • Homocystinuria • Osteogenesis imperfecta
2-109
www.shef.ac.uk/FRAX
2-110
10 jaar fractuurisico www.shef.ac.uk/FRAX
2-111
Drempel voor BMD meting / Interventie in Verenigd Koninkrijk
Kanis JA et al Osteoporos Int 2008, 19:1395-408
2-112
Kost-effectiviteit
Totale kost
Nieuw
ke ” j i el pay p p to a h sc ess t aa ngn +/M lli i w “ Nieuw
Actuele Zorg
-
+
+ Nieuw
+ Nieuw
Gezondheidseffect (QALY) QALY = Quality Adjusted Life Years
2-113
Osteoporose • Veel voorkomend • Fractuur wervel-heup – Recidief fractuur – Kwaliteit van leven, mortaliteit • Diagnose – RX opname : protocol – BDM- DEXA – FRAX: risico factoren • Pathogenese • Behandeling