Preventing Bone Loss in Early Postmenopausal Women A CME Slide Library From the Council on Hormone Education

Preventing Bone Loss in Early Postmenopausal

WomenA CME Slide Library From the

Council on Hormone Education

Preventing Bone Loss in Early Postmenopausal Women

Section 1: Introduction

Section 2: Mechanisms Underlying Menopause-Related Bone Loss

Section 3: Prevalence and Consequences of Bone Loss

Section 4: Predicting Fracture Risk in Postmenopausal Women

Section 5: Prevention of Bone Loss

Section 6: Osteoporosis Therapies and Fracture Prevention

Section 7: Effect of HT on Fracture Prevention

Section 8: Summary and Conclusions

Section 1:

Introduction


10 20 30 40 50 60 70 80

Bone Mass by Age and SexB

on

e M

ass

Age (years)Adapted from Finkelstein JS. Cecil Textbook of Medicine. 21st ed. 1999;1366-73. ©1999 Reprinted with permission from Elsevier.Riggs BL, Melton LJ III. N Engl J Med. 1986;314:1676-86.

Men Women

Menopause-AssociatedBone Loss

Change in Spine and Femoral Neck BMD Versus Years Since Menopause

Pe

rce

nt

per

Ye

ar

Bjarnason NH, et al. Bone. 2002;30:637-42.

-2.5

-2.0

-1.5

-1.0

-0.5

0.0

0.5

1.0

1.5

2 2 to 4 4 to 7 7 to 10 10

Spine Femur

Years Since Menopause

Section 2:

Mechanisms Underlying

Menopause-Related Bone Loss


Osteocytes

Osteoclasts

Reversal

Apoptotic Osteoclasts

Lining Cells

Osteocytes

Activation

Osteocytes

Formation

Osteoblasts

Osteocytes

Resorption

Resting Phase

Osteoclasts

Osteoclasts

Bone Remodeling

Osteoid

Lining Cells

Osteocytes

Preosteoblasts

Estrogen Deficiency Increases Bone Resorption

IL = interleukin; TNF = tumor necrosis factor; M-CSF = macrophage colony-stimulating factor; GM-CSF = granulocyte M-CSF; TGF = transforming growth factor ; RANKL = receptor activator of nuclear factor B ligand; OPG = osteoprotegerin.

IncreasedBone

Resorption

MonocytesMonocytes

IL-6IL-6M-CSFM-CSFIL-11IL-11GM-CSFGM-CSFRANKLRANKL

StromalStromalCells/Pre-Cells/Pre-

osteoblastsosteoblasts Active

Osteoclasts IL-1IL-1 TNFTNF

EarlyOsteoclastProgenitors

OPGOPGTGFTGF

= RANK

M-CSFM-CSF IL-6, IL-1 IL-6, IL-1

TNFTNFRANKLRANKL

Estrogen Decreases Bone Resorption

E = estrogen.

IL-1IL-1 TNFTNF

DecreasedBone

Resorption

IL-6IL-6M-CSFM-CSFIL-11IL-11GM-CSFGM-CSFRANKLRANKL

MonocytesMonocytes

StromalStromalCells/Pre-Cells/Pre-

osteoblastsosteoblasts Active

OsteoclastsEarlyOsteoclastProgenitors

OPGOPGTGFTGF E

E= RANK

E M-CSFM-CSF IL-6, IL-1 IL-6, IL-1

TNFTNFRANKLRANKL

Biochemical Markers Predict Early Menopausal Bone Loss

Women with markers of resorption or formation within the premenopausal range

– Bone loss over 4 years, <1%

Women with markers of resorption or formation above the premenopausal range

– Bone loss over 4 years, 1.5% to 2.5%

Garnero P, et al. J Bone Miner Res. 1999;14:1614-21.

4-Y

ear

Ra

te o

f L

oss

(%

)

-3.5

-3.0

-2.5

-2.0

-1.5

-1.0

-0.5

0.0

0.5

BMD Change: Healthy Postmenopausal Women With Low and High Bone Turnover

BMD = bone mineral density; BAP = bone alkaline phosphatase; PICP = C-terminal propeptide of type I collagen; PINP = N-terminal propeptide of type I collagen; NTX = N-telopeptide breakdown products; CTX = C-telopeptide breakdown products; High turnover = bone marker levels above the upper limit of the premenopausal range .Garnero P, et al. J Bone Miner Res. 1999;14:1614-21. Used with permission.

Low Turnover High Turnover

SerumOsteocalcin

SerumBAP

SerumPICP

SerumPINP

UrinaryNTX

UrinaryCTX

SerumCTX

P = .0016 P = .06 P = .09 P = .01 P = .005 P = .006 P = .0001

Section 3:

Prevalence and Consequences

of Bone Loss


Diagnostic Categories for Osteoporosis in Postmenopausal Women (WHO Criteria)

Normal: T-score above –1

Low bone mass (osteopenia): T-score between –1 and –2.5

Osteoporosis: T-score at or below –2.5

WHO = World Health Organization.WHO Study Group. WHO Technical Report Series. 1994;843:5-6.

Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994) for women 50 years of age.Looker AC, et al. J Bone Miner Res. 1997;12:1761-8.

Prevalence of Low Bone Mass and Osteoporosis in Postmenopausal Women

by Ethnicity

Population

Prevalence of Low Bone Mass

(T-score between –1 and –2.5)

Prevalence of Osteoporosis

(T-score –2.5)

Non-Hispanic white

African American

Mexican American

All ethnic groups (total)

42%

28%

37%

40%

17%

8%

12%

16%

Fracture Risk by Ethnicity in US Women

4 out of 10 white women1

2 out of 10 black women2

1Melton LJ III, et al. J Bone Miner Res. 1992;9:1005-10.2Griffin MR, et al. Am J Epidemiol. 1992;136:1378-85.3Melton LJ III. Endocrinol Metab Clin North Am. 2003;32:1-13.

Lifetime Risk for Fracture, After Age 50 Years

Lower risk in Hispanic women compared with non-Hispanic white; greater than in black women3

Risk for vertebral fracture in Asian women similar to non-Hispanic whites; hip fracture risk is lower3

Section 4:

Predicting Fracture Risk in

Postmenopausal Women


DXA = dual-energy x-ray absorptiometry; QCT = quantitative computed tomography; pQCT = peripheral quantitative computed tomography; QUS = quantitative ultrasonometry; RA = radiographic absorptiometry.American Association of Clinical Endocrinologists. Endocr Pract. 2003;9:544-64.

Prediction of Fracture Risk

All techniques (DXA, QCT, pQCT, QUS, RA, etc) predict fracture risk

Bone loss can best be monitored using DXA of the spine in early postmenopausal women

Predictive Validity of BMC for Fracture

BMC = bone mineral content; CHD = coronary heart disease.WHO Study Group. WHO Technical Report Series. 1994;843:46; Neaton JD, Wentworth D. Arch Intern Med. 1992;152:56-64.

Re

lati

ve

Ris

k

Increasing Total Cholesterol

Decreasing BMC

0

2

4

6

8

10

12

BMC/Hip Fracture

Total Cholesterol/CHD

Quartile 1 Quartile 4Quartile 2 Quartile 3

Comparison to Predictive Validity of Cholesterol for Heart Disease

2.25 3.37

7.21

4.1

1.56 1.631.72

1.570.71 0.65

0.96 0.73

0

2

4

6

8

10

12

14

16

18

Finger Forearm Heel US Heel SXA

Fra

ctu

re R

ate

per

100

P

atie

nt-

Yea

rs ±

95%

CI

<–2.5

–2.5 to –1.0

>–1.0

NORA: All Devices Studied Predicted Fracture Risk

US = ultrasound; SXA = single-energy x-ray absorptiometry.Fractures during 1-year follow-up in 149,524 postmenopausal Caucasian women. Miller PD, et al. J Bone Miner Res. 2002;17:2222-30. Used with permission.

T-Score

When Measurement of BMD in Women is Inappropriate

Healthy premenopausal women

Healthy children and adolescents

Women initiating HT for menopausal symptom relief

– Other osteoporosis therapies should not be initiated without BMD measurement

When to Measure BMD in Women

All women 65 years and older Postmenopausal women <65 years of age

– If results might influence decisions about intervention

– One or more risk factors

– History of fracture

– Patient requests measurement

American Association of Clinical Endocrinologists. Endocr Pract. 2003;9:544-64.National Osteoporosis Foundation. Washington, DC: National Osteoporosis Foundation; 2003:1-37.

Risk Factors for Osteoporosis-Related Fractures

Non-modifiable Female sex Advanced age Caucasian race History of fracture as

an adult Family history of

osteoporosis Early or premature

menopause

Modifiable Low BMD Low body weight/BMI Smoking Low calcium intake Vitamin D deficiency Inadequate physical

activity Glucocorticosteroid use Estrogen deficiency High risk for falls

American Association of Clinical Endocrinologists. Endocr Pract. 2003;9:544-64.National Osteoporosis Foundation. Washington, DC: National Osteoporosis Foundation; 2003:1-37.

Who Should Be Offered Intervention?

All women with osteoporosis-related fractures irrespective of BMD

All postmenopausal women with a BMD T-score of –2.5 or lower

Who Should Be Considered for Preventive Intervention?

Patients with levels of BMD above –2.5 with other risk factors, including

– Age

– Glucocorticosteroid use

– Low body weight/BMI

– Smoking

– Family history

– Early or premature menopause

Hui SL, et al. J Clin Invest. 1988;81:1804-9.

For a Given BMD, Fracture Risk Increases With Age

0

20

40

60

80

100

120

140

160

>1.0 0.90-0.99 0.80-0.89 0.70-0.79 0.60-0.69 <0.60Fra

ctu

re R

isk

per

10

00 P

erso

n-Y

ear

s

Bone Mass (g/cm)

Age (years)

80+

75-79

70-74

65-69

60-64

55-5950-5445-49<45

NORA: Osteoporotic Fracture Rate by Age

8.1 8.94 9.0911.94

15.28

20.93

27.94

39.24

0

5

10

15

20

25

30

35

40

45

50–54 55–59 60–64 65–69 70–74 75–79 80–84 85+

Age (years)

Fra

ctu

re R

ate

per

100

0 P

erso

n-Y

ears

*

*Corrected for initial BMDDerived from Siris ES, et al. JAMA. 2001;286:2815-22, and Miller PD, et al. J Bone Miner Res. 2002;17:2222-30.

NORA: Factors Associated With Reduced Risk of Osteoporosis

Siris ES, et al. JAMA. 2001;286:2815-22.

FactorOdds Ratio

(95% CI)

BMI 30 kg/m2

Current estrogen use

Alcohol use (14 drinks/week)

Former estrogen use

Regular exercise

0.16 (0.15–0.17)

0.27 (0.25–0.28)

0.62 (0.54–0.71)

0.77 (0.73–0.80)

0.86 (0.82–0.89)

NORA: Inverse Relationship Between BMD and Fracture Rate

BMD T-scores

Fra

ctu

re R

ate

pe

r 10

00

Pe

rso

n-Y

ea

rs

>1.01.0 to 0.5

0.5 to 0.00.0 to –0.5

–0.5 to –1.0–1.0 to –1.5

–1.5 to –2.0–2.0 to –2.5

–2.5 to –3.0–3.0 to –3.5

< –3.5

Adapted from Siris ES, et al. JAMA. 2001;286:2815-22.

Fracture Rate

BMD Distribution

0

10

20

30

40

50

60

# Fractures

NORA: Fracture Rate vs Number of Fractures by T-Score

BMD T-scores

Fra

ctu

re R

ate

pe

r 10

00

Pe

rso

n-Y

ea

rsN

um

be

r of F

ractu

res

>1.01.0 to 0.5

0.5 to 0.00.0 to –0.5

–0.5 to –1.0–1.0 to –1.5

–1.5 to –2.0–2.0 to –2.5

–2.5 to –3.0–3.0 to –3.5

< –3.5

Adapted from Siris ES, et al. JAMA. 2001;286:2815-22.

Fracture Rate

BMD Distribution

0

10

20

30

40

50

60

0

50

100

150

200

250

300

350

400

450

Patient A

Patient B

Gomberg BR, et al. IEEE Trans Med Imaging. 2000;19:166-74.

Bone Quality: Contribution of Bone Micro-Architecture

Two Patients With Similar BMD, Dissimilar Micro-Architecture

Bone Quality: Contribution of Bone Micro-Architecture continued

0

0.2

0.4

0.6

0.8

1

Re

lati

ve

Va

lue

Surface Density Curve Density Surface/Curve Erosion Index

Most plate-like Most rod-like

60-Year-Old Male 68-Year-Old Female 53-Year-Old Female 74-Year-Old Female

Dis

tal R

adiu

s S

pec

imen

s

Gomberg BR, et al. IEEE Trans Med Imaging. 2000;19:166-74.

Section 5:

Prevention of Bone Loss


Calcium Supplementation Alone Does Not Prevent Early Postmenopausal Bone Loss

Ch

ang

e in

BM

D A

fter

2 Y

ears

(%

)

-4

-3

-2

-1

0

Placebo(n = 14)

Calcium supplementation = 500 mg/day.*P < .01 vs baseline.Dawson-Hughes B, et al. N Engl J Med. 1990;323:878-83.

CalciumCitrate(n = 25)

CalciumCarbonate

(n = 28)

-4

-3

-2

-1

0

Placebo(n = 11)

CalciumCitrate(n = 24)

CalciumCarbonate

(n = 23)

* **

Spine Femoral Neck

FDA-Approved for the Prevention of Bone Loss

Estrogen

Bisphosphonates

– Alendronate

– Risedronate

Raloxifene

Blue area represents placebo-treated population of oophorectomized women.Lindsay R, et al. Lancet. 1976;1:1038-41.

Met

acar

pal

Bo

ne

Min

eral

Co

nte

nt

(mg

/mm

)

Years

At Oophorectomy

3 Years After Oophorectomy

6 Years After Oophorectomy

44

42

40

38

36

34

0 2 4 6 8 10 12 14 16

Effect of Delayed Initiation of HT on Bone Loss

-4

-3

-2

-1

0

1

2

3

4

Baseline 6 Mo 12 Mo 18 Mo 24 Mo

CEE 0.625/MPA 2.5 mg/dayCEE 0.45/MPA 2.5 mg/dayCEE 0.45/MPA 1.5 mg/dayCEE 0.3/MPA 1.5 mg/dayPlacebo

-4

-3

-2

-1

0

1

2

3

4

Baseline 6 Mo 12 Mo 18 Mo 24 Mo

Me

an

Ch

an

ge

Fro

m B

as

eli

ne

(%

)

CEE 0.625 mg/dayCEE 0.45 mg/day

CEE 0.3 mg/dayPlacebo

CEE CEE/MPA

Changes in Spine BMD With HT

Intent-to-treat population only; Women’s HOPE = Women’s Heart, Osteoporosis, Progestin, Estrogen; CEE = conjugated equine estrogens; MPA = medroxyprogesterone acetate.Lindsay R, et al. JAMA. 2002;287:2668-76. Used with permission.

The Women’s HOPE Study

*Adherent participants only (n = 641, age 45 to 64 years). All active treatment groups significant vs placebo; no significant differences were found among active treatment groups.PEPI = Postmenopausal Estrogen/Progestin Interventions; MP = micronized progesterone.Writing Group for the PEPI Trial. JAMA. 1996;276:1389-96. Used with permission.

Different Progestin Regimens Do Not Modify the Impact of Estrogen on BMD

Ch

an

ge

Fro

m B

ase

line

(%

)*

Baseline 12 Months 36 Months-6

-4

-2

0

2

4

6

Baseline 12 Months 36 Months-6

-4

-2

0

2

4

6

Spine Hip

CEE/MP (cyclic)Placebo

CEE Only

CEE/MPA (cyclic)

CEE/MPA (continuous)

The PEPI Trial

Bone Loss Is UncommonWith HT Use

Among Adherent Women in the PEPI Trial

Only 3% of HT users lost >2% inspinal BMD in the first 12 months vs 41% using placebo

Only 1% of HT users lost >2% in spinal BMD after 12 to 36 months vs 16% using placebo

Greendale GA, et al. Arch Intern Med. 2000;160:3065-71.

Section 6:

Osteoporosis Therapies and

Fracture Prevention


FDA-Approved for the Treatment of Osteoporosis

Bisphosphonates

– Alendronate

– Ibandronate*

– Risedronate

Calcitonin

Raloxifene

Teriparatide

*Approved, but not available in the US as of 2/11/04.

Meta-Analysis of Osteoporosis Therapies: Spine BMD

HT (2 year)

Alendronate, 5 mg (2 or 3 year)

Alendronate, 10–40 mg (2–4 year)

Risedronate, 5 mg (1.5–3 year)

Raloxifene, 60 mg (2–3 year)

Calcitonin* (1–5 year)

Calcium (2 year)

*Doses ranged from 250 to 2800 IU per week; predominantly nasal delivery.Cranney A, et al. Endocr Rev. 2002;23:570-8; Endocrine Rev. 2002;23:496-578.

Weighted Mean Difference ± 95% CI (% change in BMD)

0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0

HT (2 year)

Alendronate, 5 mg (2 year)

Alendronate, 10–40 mg (2 year)

Risedronate, 5 mg (1.5–3 year)

Raloxifene, 60 mg (2–3 year)

Calcitonin*

Calcium

-1.0 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0


*Doses ranged from 350 to 800 IU per week; predominantly nasal delivery.Cranney A, et al. Endocr Rev. 2002;23:570-8; Endocrine Rev. 2002;23:496-578.

Meta-Analysis of Osteoporosis Therapies: Total Hip BMD

HT (2 year)

Alendronate, 5 mg (2 year)

Alendronate, 10–40 mg (2–4 year)

Risedronate, 5 mg (1.5 year)

Raloxifene, 60 mg (1 year)

Calcitonin*

Calcium

-1.0 0.0 1.0 2.0 3.0 4.0 5.0 6.0


*Doses ranged from 350 to 800 IU per week; predominantly nasal delivery.Cranney A, et al. Endocr Rev. 2002;23:570-8. Endocrine Rev. 2002;23:496-578.

Meta-Analysis of Osteoporosis Therapies: Forearm BMD

-4

-2

0

2

4

6

8

0 12 24 36 48 60

-4

-2

0

2

4

6

8

0 12 24 36 48 60

Effect of Treatment and Discontinuation on BMD in Older Postmenopausal Women

Ch

ang

e F

rom

Bas

elin

e (%

)

*P < .05 compared with baseline measure.†P < .05 compared with placebo group.Gallagher JC, et al. J Clin Endocrinol Metab. 2002;87:4914-23. Copyright 2002, The Endocrine Society.

Spine BMD Femoral Neck BMD

MonthTreatment Follow-up

Ch

ang

e F

rom

Bas

elin

e (%

)


Placebo HT

*†

*†*†

*

-4

-2

0

2

4

6

8

0 12 24 36

-2

0

2

4

6

8

10

12

0 12 24 36

Effect of Treatment and Discontinuation on BMD in Older Postmenopausal Women

continued

Mea

n C

han

ge

in B

MD

(%

)

Greenspan SL, et al. Ann Intern Med. 2002;137:875-83. Used with permission.

Lumbar Spine Femoral Neck


Mea

n C

han

ge

in B

MD

(%

)


Placebo/Placebo CEE/Placebo Alendronate/Placebo

Section 7:

Effect of HT on Fracture

Prevention


Years

Fra

ctu

re-F

ree

Su

rviv

al

P < .05; prospective trial of women aged 45 to 58 yrs in which 21 wrist fractures were documented; HT = 2 mg oral estradiol + 10 days of 1 mg norethisterone.Reprinted from Mosekilde L, et al. Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women—results of the Danish Osteoporosis Prevention Study. Maturitas. 2000;36:181-93. © 2000, with permission from Elsevier Science.

HT(n = 502)

No HT(n = 504)

1.00

0.99

0.98

0.97

0.960 1 2 3 4 5 6

Danish Osteoporosis Prevention Study: Fracture-Free Survival in Early

Postmenopausal WomenWrist Fracture

0.1 1.0 10.0

Meta-Analysis of Osteoporosis Therapies: Nonvertebral Fractures

HT* (n = 20,494)

Alendronate, 5 mg (n = 8603)

Alendronate, 10–40 mg (n = 3723)

Risedronate, 2.5–5 mg (n = 12,958)

Raloxifene, 60 mg (n = 6961)

Calcitonin† (n = 6961)

Calcium (n = 222)

Relative Risk (95% CI)*Includes the Women’s Health Initiative (WHI) trial.†Estimate from the Prevent Recurrence of Osteoporotic Fractures (PROOF) trial.Cranney A, et al. Endocr Rev. 2002;23:570-8. Endocrine Rev. 2002;23:495-578; Rosen C. Presentation for ASBMR at NIH Scientific Workshop: Menopausal Hormone Therapy, October 23-24, 2002. Available at: http://www4.od.nih.gov/orwh/htslides/rosen2.ppt. Accessed 1/18/03.

Women’s Health Initiative (WHI) Trial

WHI: Baseline Prevalence of Osteoporosis (WHO) by DXA Femoral Neck T-scores

Normal(>–1.0)

Low Bone Mass(–1.0 to –2.4)

E+P Placebo

P = .29

Cauley JA. Available at: http://www.fda.gov/ohrms/dockets/ac/cder03.html#EndocrinologicMetabolicDrugs. Accessed 1/7/04.

In 6% of Participants (n = 1024)

32%

58%

10%

35%

53%

12%

Osteoporosis(–2.5 )

-1

0

1

2

3

4

5

6

7

0 1 2 3

-1

0

1

2

3

4

5

6

7

0 1 2 3

PlaceboHT

-1

0

1

2

3

4

5

6

7

0 1 2 3

WHI Results: Mean Change in BMD During 3 Years of E+P

Follow-up (years)

Cauley JA, et al. JAMA. 2003;290:1729-38.

Mea

n C

han

ge

in B

MD

F

rom

Bas

elin

e (%

)

Total Hip Spine

In 6% of Participants (n = 1024)

0.5 1.0 2.0

WHI Results: Fracture Outcomes

Hip

Vertebral

Lower Arm/Wrist

Total

Hazard Ratio

95% nCI

95% aCI

Adjusted confidence interval reported only for hip fracture.Cauley JA, et al. JAMA. 2003;290:1729-38.

0

50

100

150

200

Total Fractures

WHI Results: Effect of E+P in Preventing Fractures

0

20

40

60

80

Hip ClinicalVertebral

Wrist/LowerArm

Nu

mb

er o

f F

ract

ure

s/Y

ear

in 1

0,00

0 W

om

en

Placebo E+P

Number of Fractures/Year in 10,000 Women

Type of FractureCauley JA, et al. JAMA. 2003;290:1729-38.

need to align bars...

0.00

0.01

0.02

0.03

0 1 2 3 4 5 6 7

WHI Results: Effect of E+P on Risk of Hip Fracture

Kaplan-Meier Estimate

Time (year)

Cu

mu

lati

ve H

azar

dfo

r H

ip F

ract

ure

HR = 0.6795% nCl = 0.47–0.9695% aCI = 0.41–1.10

Placebo

E+P

Cauley JA, et al. JAMA. 2003;290:1729-38.

0.0

0.1

0.2

0.3

0.4

0.5

0 1 2 3 4 5 6 7

WHI Results: Effect of E+P on Risk of Lower Arm/Wrist Fracture

Adjusted confidence interval not reported.Cauley JA, et al. JAMA. 2003;290:1729-38.


Time (year)

Cu

mu

lati

ve H

azar

d f

or

Lo

wer

Arm

/Wri

st F

ract

ure

HR = 0.7195% nCl = 0.59–0.85

Placebo

E+P

0.0

0.1

0.2

0.3

0 1 2 3 4 5 6 7

WHI Results: Effect of E+P on Risk of Vertebral Fracture



Time (year)

Cu

mu

lati

ve H

azar

d

for

Ver

teb

ral F

ract

ure

HR = 0.6595% nCl = 0.46–0.92

Placebo

E+P

0.00

0.05

0.10

0.15

0 1 2 3 4 5 6 7

Cu

mu

lati

ve H

azar

dfo

r T

ota

l Fra

ctu

re

Time (year)

WHI Results: Effect of E+P on Risk of Total Fracture


HR = 0.7695% nCl = 0.69–0.83

Placebo

E+P


1Cauley JA, et al. JAMA. 2003;290:1729-38.2Black DM, et al. Osteoporosis Int. 2001;12:519-28.

WHI: Summary Fracture Risk Score

WHI Investigators1 developed a summary fracture risk score guided by the methods used to develop the FRACTURE Index2

Predictive validity of FRACTURE Index has been shown2

Validity of WHI fracture risk score not established

– WHI reported fracture risk score showed moderate predictive strength for hip fracture1

1Cauley JA, et al. JAMA. 2003;290:1729-38.2Black DM, et al. Osteoporosis Int. 2001;12:519-28.

WHI: Summary Fracture Risk Scorecontinued

Differences between FRACTURE Index and WHI risk score1,2

– WHI score includes age, prior fracture after age 55 years, current smoking, and BMI 22.4 kg/m2

– FRACTURE Index includes age, prior fracture after age 50 years, maternal hip fracture after age 50 years, weight 125 lbs, current smoking, use of arms to stand from a chair, and total hip BMD (if available)

HR for Global Index: Stratified by Fracture Risk Scores

Highest

Middle

Lowest

Hazard Ratio (95% nCI)

Fracture Risk*

0.5 1.0 2.0

*Stratified by tertiles of summary fracture risk scores; the WHI Global Index measure and WHI Fracture Risk Score have not been validated.Cauley JA, et al. JAMA. 2003;290:1729-38.

Summary: WHI Results and Considerations

CEE/MPA significantly decreased the risk of hip fractures, vertebral fractures, and all other fractures in a population not specifically selected for being at increased risk of fracture1

This benefit has not been demonstrated in a similarly low-risk population with any other osteoporosis therapy

1Cauley JA, et al. JAMA. 2003;290:1729-38.

Section 8:

Summary and Conclusions


Summary:Prevention of Early Bone Loss

Bone loss is most rapid in the years immediately following menopause

Women treated with HT to relieve menopausal symptoms do not need another antiresorptive agent

HT is the only therapy that has been demonstrated to prevent fractures in women whose risk for osteoporosis is unknown

Documents

Preventing Bone Loss in Early Postmenopausal Women A CME Slide Library From the Council on Hormone Education