Vietnam Osteoporosis Workshop, HCMC 2006 RISK FACTORS FOR OSTEOPOROTIC FRACTURE IN THE ELDERLY Tuan...

Vietnam Osteoporosis Workshop, HCMC 2006

RISK FACTORS FOR OSTEOPOROTIC FRACTURE

IN THE ELDERLY

Tuan Van Nguyen and Nguyen Dinh Nguyen

Garvan Institute of Medical Research

Sydney, Australia


Overview

• Background

• Risk factors for fracture risk

• Summary


Background

• Aging population: fastest growing age group

• Osteoporosis and osteoporotic fracture: age-related disorders

• Osteoporosis and osteoporotic fracture:

– Common

– Cause serious disability and excess mortality

– Major economic burden on healthcare system


Incidence of common diseasesA

nn

ua

l in

cid

en

ce

of

co

mm

on

dis

ea

se

s (

x1

00

0)

0

500

1000

1500

2000

Osteoporotic fracture

(all ages)

Heart attack(women 29+)

Stroke(women 30+)

Breast cancer(women all ages)

1 500 000

513 000

228 000184 300

250 000hip

250 000forearm

250 000others

750 000vertebrae

(Sources: Riggs BL et al., 1995; American Heart Foundation, 1998; American Cancer Society, 1998)


Survival probability and fracture

Age (y)

Women Men

Cum

ulat

ive

surv

ival

rat

e

(Soure: Center J, Nguyen TV et al., Lancet 1999;353:878-82)


Burden of Osteoporotic fractures

• Annual cost of all osteoporotic fractures: $20 billion in USA and ~$30 billion on EU1.

• Worldwide direct and indirect cost of hip fracture: US$131.5 billion2.

• Australia: Total health system costs of osteoporosis, $1.9 billion (2000-2001).

(Sources: 1Cummings et al., Lancet 2002;359:1761-67; 2Johnell O, Am J Med 1997;103:20S-26)


A systematic skeleton disease characterized by:

- low bone mass- microarchitectural deterioration of bone tissue- consequent increase in bone fragility and

susceptibility to fracture

Definition of OsteoporosisDefinition of Osteoporosis(WHO)(WHO)

Consensus Development Conference: Diagnosis, Prophylaxis, and Treatment of Osteoporosis, Am J Med 1993;94:646-650. WHO Study Group 1994.

Vietnam Osteoporosis Workshop, HCMC 2006(VN 2006, unpublished data)

Relationship between BMD and Age


Measure of association: Relative risk (RR)

• The ratio of the incidence of disease (fracture) in exposed individuals to that in unexposed individuals.

• In longitudinal studies: the hazards ratio equivalent to relative risk or risk ratio.


Measure of association: Relative risk (RR)

RR > 1: riskRR = 1: no differenceRR < 1: risk

Relative risk (95% confidence interval)

RR (95%CI)

Example:


Bone mineral density: the best predictor of osteoporotic fracture

Study Type of study N Unit RR (95% CI)

Nguyen TV et al., 1993

Cohort 1080 -1SD 2.4 (1.9 - 3.0)

Marshall D et al., 1996

Meta-analysis 11 cohorts -1SD

Any fracture 1.5 (1.4 - 1.6)

Hip 2.6 (2.0 - 3.5)

Vertebrae 2.3 (1.9 - 2.8)

Johnell O el al., 2005

Meta-analysis 29082 -1SD

Any fracture 1.5 (1.4 - 1.6)

Hip 2.0 (1.9 – 2.2)

WOMEN


Bone mineral density: the best predictor of osteoporotic fracture

Study Type of study N Unit RR (95% CI)

Nguyen TV et al., 1993

Cohort 790 -1SD 2.0 (1.5-2.6)

Johnell O el al., 2005

Meta-analysis 9785 -1SD

Any fracture 1.6 (1.4 - 1.8)

Hip 2.4 (1.9 – 3.1)

MEN


Other bone-related risk factors

Outcome/Risk factor Unit RR (95% CI)

Women Men

Hip fracture

Hip strength*

CSMI -1SD 1.8 (1.1-3.2) 1.6 (1.0-2.5)

Section modulus -1SD 1.6 (1.1-5.1) 2.3 (1.4-2.9)

Volumetric BMD** -1SD 2.4 (1.8-3.2) 3.2 (2.0-5.0)

Bone loss* -5%/y 1.4 (1.1-1.8) NA

* Adjusted for femoral neck BMD; **adjusted for age

(Sources: Nguyen TV et al., 2005; Ahlborg H, Nguyen TV et al, 2005; Center J, Nguyen TV et al. 1998 and 2004)


Age group vs. < 50 (y)

50 55 60 65 70 75 80 85

Rel

ativ

e ri

sk (

95%

CI)

0.8

1.0

1.2

1.4

1.6

1.8

2.0

MEN

Age group vs. < 50 (y)

50 55 60 65 70 75 80 85

Rel

ativ

e ri

sk (

95%

CI)

0.8

1.0

1.2

1.4

1.6

1.8

2.0

WOMEN (n=29188) (n=9875)

(Adapted from Johnell O el al., JBMR 2005;20:1185-94)

Association between age and fracture


BMD: primary predictor of fracture but not good discriminator

Femoral neck BMD (g/cm2)

0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6

Non-fractureAny fracture

RR =2.4 (95%CI: 1.9 - 3.0)

> 80% overlapping

(Calculation based on Nguyen TV et al., BMJ, 1993;307:1111-15)


Prior fracture

Outcome Gender RR (95% CI)* Increment (%)

Any fracture Men 2.04 (1.67-2.48) 104

Women 1.73 (1.59-1.88) 73

Osteoporotic fx Men 1.91 (1.50-2.43) 91

Women 1.74 (1.57-1.92) 74

Hip fracture Men 1.97 (1.12-3.48) 97

Women 1.56 (1.23-1.98) 56

(Kanis J et al., Bone 2004;35:375-82)

Results from meta-analysis

*RRs were adjusted for BMD


Fall and fall-related factors Risk factor/Outcome Gender RR (95% CI)* Increment (%)

Fall

Hip fracture Men 2.0 (1.0-4.2) 100

Women 2.0 (1.3-3.2) 100

Postural sway (+1SD)

Osteoporotic fx Men Sex combined

Women 1.90 (1.63-2.21) 90


Women 1.6 (1.4-1.8) 60

Quadriceps strength (-1SD)

Osteoporotic fx Men Sex combined

Women 1.83 (1.49-2.24) 83


Women 2.6 (1.9-3.6) 160

(Nguyen TV el al., BMJ 1993;307:1111-5; Nguyen ND et al., JBMR 2005; 20:1921-8))



Corticosteroids use

Outcome Gender RR (95% CI) Increment (%)

Any fracture Men 1.67 (1.10-2.51) 67

Women 1.39 (1.18-1.64) 39


Women 1.42 (1.18-1.70) 42

Hip fracture Men 2.62 (0.91-7.51) 162

Women 2.07 (1.38-3.10) 107

(Kanis J et al., JBMR 2004;19:893-99)

Results from meta-analysis


Lifestyle: Smoking

Outcome Gender RR (95% CI) Increment (%)

Any fracture Men 1.27 (1.07-1.51) 27

Women 1.18 (1.10-1.26) 18


Women 1.15 (1.07-1.25) 15

Hip fracture Men 1.42 (1.18-1.72) 42

Women 1.38 (1.15-1.65) 38

(Kanis J et al., Osteoporos Int 2005;16:155-62)

Association between smoking and fracture Results from meta-analysis

Although the magnitude of the association was modest, but the impact of smoking on the community with high prevalence of smoking could be significant


Lifestyle: Alcohol consumption

Outcome Level (U/d) RR (95% CI)* Increment (%)

Any fracture >2 1.24 (1.06-1.45) 24

>3 1.34 (1.11-1.62) 34

>4 1.51 (1.19-1.93) 51

Osteoporotic fx >2 1.36 (1.13-1.63) 36

>3 1.53 (1.23-1.91) 53

>4 1.64 (1.24-2.17) 64

Hip fracture >2 1.70 (1.20-2.42) 70

>3 2.05 (1.35-3.11) 105

>4 2.39 (1.39-4.09) 139

(Kanis J et al., Bone 2004;35:1029-37))

Results from meta-analysis (men and women combined)

*RRs were adjusted for BMD1U/d ~ 8g pure alcohol


Family history of fracture

Parental history Outcome RR (95% CI)* Increment (%)

Any fracture Any fracture 1.18 (1.07-1.31) 18

Osteoporotic fx 1.22 (1.08-1.38) 22

Hip fracture 1.63 (1.24-2.13) 63

Hip fracture Any fracture 1.41 (1.17-1.71) 42

Osteoporotic fx 1.54 (1.25-1.88) 54

Hip fracture 2.28 (1.48-3.15) 128

(Kanis J et al., Bone 2004;35:1029-1037)

Results from meta-analysis (men and women combined)



Genetic factor: COLIA1 and VDR genes and fracture

Genes Outcome RR (95% CI)* Increment (%)

Meta-analysis*

COLIA1 (vs. SS) Any fracture

Ss genotype 1.26 (1.09-1.46) 26

ss genotype 1.78 (1.30-2.43) 78

Ss genotype Vert. fracture 1.37 (1.15 (1.64)

37

ss genotype 2.48 (1.49-3.65) 148

Observational study**

COLIA1 (TT) Hip fracture 3.8 (1.4-10.8) 280

VDR (CC) Hip fracture 2.6 (1.2-5.3) 160

(*Mann V and Ralston SH, Bone 2003;32:711-17; **Nguyen TV et al., JCEM 2005; 90:6575-9)



-Medication: Corticosteroids

Modifiable risk factors Non-modifiable risk factors

Fracture

- Bone-related factors: BMD, bone strength indice…- Fall and fall-related factors- Prior fracture - Lifestyle: smoking, alcohol

- Advancing age- Family history- Genetics

Intervention strategies

Identify high-risk group


Association between risk factors and fracture risk: summary

Relative risk (95% CI)

0.8 1 1.5 2 4 5 6 83 10 0.8 1 1.5 2 4 5 6 83 10

BMD (-1SD)

CSMI (-1SD)

Volumetric BMD (-1SD)

Bone loss (-5%)

Prior fracture

Corticorsteroid use

Smoking

Alcohol consumption

Fall in the last 12 mo

Body sway (+1SD)

Quadriceps strength

Age (+1SD)

Family history of fx

COLIA1 ss genotype

VDR CC genotype

Relative risk (95% CI)

Hip fracture Any fracture


RR of risk factors for fracture

• Measure of population risk (as a group), but not for an individual patient useful in the investigation of etiological relationships.

• Uninformative in clinical decision making, because it obscures the background risk of the outcome interest in the study population.

• How to translate into individual patient’s interests?

• Moving towards ABSOLUTE RISK


Residual lifetime risk of fractures (unadjusted and adjusted for competing risk of death)

5 10 15 20 25 30 35 40 45 50

Men, death-adjusted

Men, unadjusted

Women, unadjusted

Women, death-adjusted

Years of risk from age 50

Cu

mu

lati

ve r

isk

of

frac

ture

(%

)

0

10

20

30

40

50

60

70 (68)

(54)

(50)

(32)

Source: Nguyen et al. 2006, unpublished data


Points 0 10 20 30 40 50 60 70 80 90 100

Age (years)55 60 65 70 75 80 85 90 95 100

FNBMD T-scores4 3 2 1 0 -1 -2 -3 -4 -5 -6

Prior fracture(at age >50 yrs)0 2

1 3

Number of falls (past 12 mo)0 2

1 3

Total Points 0 20 40 60 80 100 120 140 160 180

5-year risk0.01 0.05 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9

10-year risk0.05 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 0.99

Nomogram for predicting fracture in Women

16 65145

100

The risk for this woman sustaining any fracture within next 5 years = 25%

10 years = 45%

A woman of 75 yrs old,Femoral neck BMD T-score = -2.5

Had a fracture when she was 67 yrsHad a fall last year

What is the probability for her sustaining a fracture within the next 5

and 10 years?


Points 0 10 20 30 40 50 60 70 80 90 100

Age (years)

55 60 65 70 75 80 85 90 95 100

FNBMD T-scores4 3 2 1 0 -1 -2 -3 -4 -5 -6

Prior fracture(at age >50 yrs)0 2

1 >=3

Number of falls (past 12 mo)0 2

1 3

Total Points 0 20 40 60 80 100 120 140 160 180

5-year risk0.01 0.05 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9

10-year risk0.01 0.05 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 0.99

Nomogram for predicting fracture in Men


Key messages• Osteoporotic fracture is a multifactorial event

• No single best predictor

• BMD is the best predictor but not good discriminator

• Interaction between risk factors

• Measure of the association:

– Relative risk scale population risk

– Absolute risk scale individual risk more clinical relevant


Lời Cảm tạ

• Chúng tôi xin chân thành cám ơn Công ty Dược phẩm Bridge Healthcare, Australia là nhà tài trợ cho hội thảo.


Thank you!


BMD and the prediction of Osteoporosis and Incident fracture

Osteoporosis Fracture

(Source: Nguyen TV et al, Osteoporos Int 2004;15:49-55)

Vietnam Osteoporosis Workshop, HCMC 2006 RISK FACTORS FOR OSTEOPOROTIC FRACTURE IN THE ELDERLY Tuan...

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