Osteoporosis Dexa Score
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OSTEOPOROSIS
A systemic skeletal disease characterizedby low bone mass and microarchitectural deterioration of bone tissue leading toenhanced bone fragility and a consequentincrease in fracture risk.
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CASE
A 42 year old woman asks for advice
about osteoporosis therapy. A DXA scandone at her request after a screeningstudy at a health fair showed low BMD,confirmed low BMD with a T score of-2.5 at the femoral neck.
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Medical History
Normal menses.
Weight stable, BMI 22
Mother and maternal grandmother both
have severe osteoporosis No renal or hepatic disease. No exogenous glucocorticoids Normal PTH, TSH and vitamin D
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QUESTIONS
DOES SHE HAVE OSTEOPOROSIS?
WHAT FURTHER STUDIES SHOULD BEDONE?
IS THERAPY APPROPRIATE?
WHAT THERAPY?
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Osteoporosis Prevalence
Affects 200 million women worldwide1
_
1/3 of women aged 60 to 70 - 2/3 of women aged 80 or older
Approximately 30% of women over the age
of 50 have one or more vertebral fractures2
Approximately one in five men over the age
of 50 will have an osteoporosis-related
fracture in their remaining lifetime1
1.
IOF, 2005 (www.osteofound.org)
2.
Dennison E & Cooper C, Horm
Res, 2000;54 suppl
1:58-63
http://www.osteofound.org/http://www.osteofound.org/ -
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All fractures are associated with morbidity
Cooper
C, Am
J Med, 1997;103(2A):12S-17S
40%
Unable to walkindependently
30%
Permanentdisability
20%
Death within
one year
80%
Oneyea
rafteran
hipfr
acture:
Pa t i
e nt s
( %)
Unable to carry out atleast one independentactivity of daily living
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OSTEOPOROSIS
Densitometric Definition:Bone density 2.5 SD or more below themean for young adult women (T scoreless than or equal to -2.5)
Karis, JA et al,J
Bone Miner. Res., 1994
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Bone Mineral Density
Measurement
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DXA
Dual energy x-ray absorptiometry
Measure of x-ray energy using 2
energy levels.
Assumes a 2 compartment model.
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DXA TERMS
T-score:
(BMD of patient
BMD of young-normal)
__________________________________
SD of young normal
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DXA TERMS
Z-score:
(BMD of patient BMD of agematched normals)___________________________________
SD of age matched normals
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Interpretation of bone mineral
density (BMD)
Z score: -1.0 (age-dependent)T score: -2.5 (age-independent)
BMD of patient A is 0.72 g/cm
0.72
T Z
+ 1SD
- 1SD
Age (yr)
A
BMD
g/cm2
59
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Raisz L. N Engl J Med 2005;353:164-171
Dual-Energy X-Ray Absorptiometry of the Spine and Hip of a 66-Year-Old PostmenopausalWoman
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DXA
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Vertebral body
normal osteoporotic
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DXA Sources of Error
Osteoarthritis
Laminectomy Previous Fracture Osteomalacia Overlying MetalHardware Soft TissueCalcifications
Severe Scoliosis
Extreme obesity orascites
Vertebral deformities
Inadequate referencepopulation ranges Poor operatingproceduresAdapted from Kanis, Lancet:359:1929, 2002 andBecker, The Endocrine Society, 2005
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Diagnosis in Postmenopausal
WomenWHO criteria should be used
Normal = T-score -1 or greater
Osteopenia = T-score between -1 and- 2.5
Osteoporosis = T-score -2.5 or less
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Diagnosis in Premenopausal
Women
WHO criteria should not apply to healthy
pre-menopausal women. Z-scores should be used. Osteoporosis may be diagnosed if there islow BMD with risk factors. The diagnosis of osteoporosis should notbe made on densitometric criteria alone.
10 Y F t Ri k d
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Hipfracturerisk(%
per10Ye
ars)
-3
60
70
80
0
5
10
15
20
50
BMD T-score
-2.5 -2 -1.5 -1 -0.5 0 0.5 1
10-Year Fracture Risk: age andBMD
ForagivenBM
D,
F
oragivenBM
D,
riskincreaseswith
riskincreaseswith
ageage
Kanis JA et al, Osteoporos Int, 2001;12:989-995
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Vertebrae
Hip
Wrist
50
60
70
80
40
30
20
10
Age (Years)
Annualincidenc
e
per100
0women
Incidence of
osteoporotic fractures in women
Wasnich
RD, Osteoporos
Int
1997;7 Suppl
3:68-72
http://creative.gettyimages.com/source/search/ImageEnlarge.aspx?MasterID=ca60468&s=ImageDetailSearchState%7C3%7C5%7C0%7C6%7C0%7C1%7C0%7C0%7C1%7C38%7C60%7C9%7C1%7C0%7C(%22Une+seule+femme%3aSeulement+des+femmes%22+et+%2260-65+ans%3aSexag%e9naire%22+et+%22T%eate+et+%e9paules%3aComposition%22)+ou+(%22Une+seule+femme%3aSeulement+des+femmes%22+et+%2255-60+ans%3aAdulte+quinquag%e9naire%22+et+%22T%eate+et+%e9paules%3aComposition%22)%7C%7C1%7C0&pk=6 -
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Rationale for Diagnosis Position
in Premenopausal Woman
Premenopausal women do not have same
relationship between BMD and fracturerisk as postmenopausal women, thereforeWHO classification does not apply
Major risk factors in premenopausal
women elevate fracture risk sufficiently sothat osteoporosis may be diagnosed if lowBMD is also present
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Bone Remodeling
Hematopoietic cellsMesenchymal
cells
OsteoblastOsteoclast
Lining cells
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Pathogenesis of osteoporosis
Resorbed cavitytoo large Newly formed packetof bone too small
Formation does not
match resorptionIncreased numbers of
remodeling units
INCREASED BONE LOSS
Low BMD in Premenopausal
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Low BMD in PremenopausalWomen
Low peak bone mass
Accelerated bone loss
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Determinants of Peak Bone Mass
Genetics
Lifestyle
PEAK BONE MASS 20-22 years of age HormonesNutrition
Candidates genes involved in the
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Candidates genes involved in thegenetics
of peak bone
mass and/or
osteoporosisReceptors
Vitamine D Receptor
(VDR)
Estrogen
receptors
Calcitonin
receptor
Calcium
sensing
receptor
PTH
Androgen
Osteoprotegerin
Glucocorticoids
Tumor
necrosis
factor
Bone-associated
proteins
Collagen
type
1
Osteocalcin
Growth
factor
and cytokines
Interleukin
6
TGF-
Beta
IGF-I
Bone
morphogenetic
protein
2
Interleukin-1 receptor
antagonist
Tumor
necrosis
factor
alpha
Enzymes
Aromatase
Methylenetetrahydrofolate
reductaseMiscellaneous
Apolipoprotein
E
Heparin
sulfate
glycoprotein
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Changes in BMD in response to calcium fortifiedfoods in prepubertal
girls
distributed according
their spontaneous calcium intake
Placebo
Calciumsupplemented
Yearly
BMD increase
0
10
20
30
mg/cm
2xyr
low highCalcium intake
Bonjour JP et al, J Clin
Invest 1997;99:1287-1294
P
0.01
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Effect of physical exercise on PBM
Peak total body BMC(g/year) Peak femoral neck BMC(g/year)Peak lumbar spine BMC(g/year)
Bailey
DA et al, J Bone
Miner Res, 1999;14:1672-1679
100
200
300
400500
0Girls Boys
10
1214
16
2
4
6
8
0Girls Boys
0.50.60.70.8
0.20.3
0.4
0Girls Boys
1
0.1
0.9
Inactive Average Active
**
**
** ***
*
Significantly greater than inactive,
*P0.005, **P0.001
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Disorders Causing Bone Loss
Estrogen deficiency
Premature menopause 1y.
Primary hypogonadism
Other disorder associated with
Osteoporosis
Maternal/ family history of hip
fracture
Prolonged immobilization
Anorexia nervosa
Malabsorption
syndromes
Primary
Hyperparathyroidism
Hyperthyroidism
Corticosteroid therapy
Cushings syndrome
Post-transplantation
Chronic renal failure
Drugs
Kanis
JA, Lancet, 2002;359:1929-1936
Secondary
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Secondaryosteoporosis
Endocrine Nutritional Drug-induced Immobilization Others
Hyperthyroidism
HypogonadismCushing Syndrome
Glucocorticoids
ImmunosuppresslyAnticonvulsants
Rheumatoid A.
DiabetesTumors
(Myeloma, etc.)
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BMD and risk of fracture
1
For a cumulative dose of 13.9 g of prednisone (Van Staa
et al, 2002)
2
General Practice Research Database3 From Marshall D et al, BMJ, 1996;312:1254-1259
Estimated
BMD Decreases1Spine
-
0.5 SD
3.0
1.5
Hip
-
0.4 SD
2.2
1.4
Relative Risk of Fracture
GIOP2 Postmen. OP3
For the same change in BMD, glucocorticoid-treated patients
may be at higher risk of fracture
Van Staa
TP et al, Osteoporos
Int, 2002;13:777-787
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Management of glucocorticoid-induced osteoporosisGuidelines
ACR, 2001
UK, 1998
a.
Patients about to start a long term
(>3 months) GC treatmentGeneral measures
Yes
Yes
(smoking cessation-alcohol reduction)
(exercise)Initiate calcium plus vitamin D
Yes
YesDXA evaluation to consider BP
Yes
Yes
T-score Cut-off to start BP -
-1.5
GC dose
5 mg /d
Not specified
b. Patients already taking GC treatmentGeneral measures
Yes
Yes
(smoking cessation-alcohol reduction)(exercise)
Initiate calcium plus vitamin D
Yes
Yes
DXA evaluation to consider BP
Yes
Yes
T-score Cut-off to start BP -1
-1.5
GC dose
5mg/d
Not specified
ACR: American
College
of
Rheumatology, UK: National Osteoporosis
Society
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What FurtherStudies Should
be Done?
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Further Studies
PTH, Calcium, phosphate, 25-hydroxy-
vitamin D CBC Serum creatinine Alkaline phosphatase, aminotransferases TSH
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Does she have osteoporosis?
What should be done?
Non Pharmacological Approaches
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Non Pharmacological Approaches to
the Prevention
of
Postmenopausal Osteoporosis Adequate intake of dietary calcium &protein Regular physical activity
Avoid tobacco
Minimize risk of falls
Recommend hip protectors in those
prone to falls
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Surgeon General Report 2004
Calcium has been singled out as a majorpublic health concern today not only because itis a critical nutrient for bone but also because of
national surveys that suggest that the average
calcium intake of individuals is far below the
levels recommended for optimal bone health
U.S. Department of Health and Human Services. Bone Health and Osteoporosis:A report of the Surgeon General. 2004;115
The Majority of Americans Are Not
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The Majority of Americans Are NotReceiving Adequate Levels of Vitamin D
*Percent consuming adequate intake or abovefrom diet + supplements significantly differentfrom diet alone; P70 yNHANES = National Health and NutritionExamination Survey.
Consequences of Vitamin D
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Consequences of Vitamin DInsufficiency
1.
Holick MF. Curr Opin Endocrinol Diabetes. 2002;9:8798.
2. Lips P. Endocr Rev. 2001;22:477501.
Calcium absorption1
When vitamin D status is sufficient, absorption of
dietary calcium is approximately 30% to 40%.As vitamin D status declines, absorption of dietary
calcium declines to about 10% to 15%.
PTH
Low levels of vitamin D lead to increased release
of PTH,2
which increases bone resorption and
decreases bone mass.
Sources of Vitamin D
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Sources of Vitamin D
Sunlight exposure Major source of vitamin D.1,2 Vitamin D production is affected by season, duration of exposure,
sunscreen use, and skin pigmentation.2
Endogenous production
Skin and kidneys form and process vitamin D4; this may decrease
with age.2
Dietary intake
Minor source of vitamin D.2
Vitamin D is rare in foods other than fatty fish and fortified foodproducts, such as milk and breakfast cereals.3,4
1.
Holick MF. J Cell Biochem. 2003;88:296303.2.
Holick MF. Osteoporos Int. 1998;8(suppl 2):S24S29.
3. Lips P.Adv in Nutr Res. 1994:151165..
What is the Optimal Intake of Vitamin
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Defining the Upper Limit of Vitamin D
Intake:
There is limited information regardingdoses of vitamin D associated withacute toxicity, although intermittent(yearly or twice yearly) single doses
of vitamin D as high as 600,000 IUhave been given without reports of
toxicity.
What is the Optimal Intake of Vitamin
D?
I ib i f C l i
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Important contribution of Calcium (Osteoporosis Studies)
All studies that formed the basis of
osteoporosis indications for risedronate,
alendronate, ibandronate, teriparatide,
raloxifene and calcitonin required calcium
supplementation in the study design
Sunyecz JA et al. Journal of Womens Health 2005;14(2):180-192
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Future Monitoring
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DXA for Monitoring Therapy
Slow response time.
Increased signal to noise ratio.
GarneroGarnero
P &P & DelmasDelmas
PD,PD, Curr
Opin
Rheumatol, 2004;16:428-434
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DXA for Monitoring Therapy
Decreases in BMD while on therapy do not
always indicate treatment failure. Some who lose BMD the first year, gain
during the second year regression tothe mean.
Even when BMD declines during therapy,
fracture risk may decrease.
Bi h i l k f b
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Biochemical markers of bone
turnoverFormation
markers
Osteocalcin
Bone
specific
alkaline
phosphatase Procollagen type-1N-propeptide
Procollagen
type-1
C-propeptide
Resorption
markers
Hydroxyproline
Hydroxylysine
Pyridinoline
Deoxypyridinoline
Bone
sialoprotein
Acid phosphatase
Tartrate-resistant
acid
phosphatase
Type-1 collagen
telopeptides (CTX, NTX)
A i ti b t BMD
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Association between BMD,
resorption markers and fracture risk
0
1
2
3
4
5
low hip BMD high CTX low
hip BMD
+ high CTX
2.7
2.2
4.8
R
iskofhipfracture
(oddsratio)
Garnero
P et al, J Bone
Miner Res, 1996;11:1531-1538
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2 Years later
Her T-score is -2.9.
She is oligomenorrheic and having hotflashes. Her FSH on day 3 of the menstrual cycleis 42.
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Does she have osteoporosis?
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Does she need drug therapy?
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Osteoporosis Therapy
D d i t i
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Drugs used in osteoporosis
treatment
HRT
SERM/Raloxifene
Calcitonin
Bisphosphonates
- Alendronate
- Risedronate
- Ibandronate
-
Zoledronic
Acid
Parathyroid hormone (PTH)
Anti-fracture Efficacy of Therapeutic Agents
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Anti fracture Efficacy of Therapeutic Agents
Drug Vertebralfractures Non-vertebralfractures (hip)
Alendronate,Risedronate + + + + +
Ibandronate +++ -
Zoledronic
Acid +++ -
HRT + + +
PTH + + + + +Raloxifene + + + 0
Calcitonin +Adapted from Delmas PD, Lancet, 2002;359:2018-2026
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Conclusions
In premenopausal women, low bone mass
alone is not adequate to establish adiagnosis of osteoporosis.
Low BMD in premenopausal women mayresult from low peak bone mass oraccelerated bone loss.
Premenopausal women with low BMDdeserve careful follow up.
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Conclusions
Bone density testing is appropriate in
premenopausal women with history of afragility fracture or known secondarycause of osteoporosis
Adequate calcium and vitamin D intakeare fundamental components ofosteoporosis therapy.
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