Osteoporosis Dexa Score

8/12/2019 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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Osteoporosis Dexa Score

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