Osteoporosis: Osteoporosis: Measuring the ProblemMeasuring the Problem

Dr. Tuan V. NguyenDr. Tuan V. NguyenAssociate ProfessorAssociate Professor

Bone and Mineral Research ProgramBone and Mineral Research ProgramGarvan Institute of Medical ResearchGarvan Institute of Medical Research

Sydney, AustraliaSydney, Australia

Measuring osteoporotic Measuring osteoporotic fracturesfractures

• Magnitude of the problem

• Consequences

• Undertreated, underdiagnosed and what to do?

Increase in life expectancyIncrease in life expectancy

22

33

43

55

75

0

10

20

30

40

50

60

70

80

RomanEmpire

Middle Age Mid-19thcentury

Early 1900 Now

Yea

rs

WHO. Human Population: Fundamentals of Growth World Health, 2000.

The ageing of populationThe ageing of population

0

5

10

15

20

25

1996 2001 2011 2021 2031 2041

Per

cent

World Australia

Percent of population aged 65+

ABS and US Bureau of Census, 1996.

Osteoporosis – shift in Osteoporosis – shift in definitionsdefinitions

“Low bone mass, microarchitectural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture risk” (Consensus Development Conference,

1991)

“[…] compromised bone strength predisposing a person to an increased risk of fracture. Bone strength primarily reflects the integration of bone density and bone quality” (NIH Consensus Development Panel on Osteoporosis JAMA 285:785-95; 2001)

Shift in thinkingShift in thinking

BoneQuality

BoneStrength and

ArchitectureTurnover rateDamage accumulationDegree of mineralizationProperties of the collagen/mineral matrix

BoneMineralDensity

Osteoporosis FractureRISK FACTOR OUTCOME

BMD and fractureBMD and fracture

0

2

4

6

8

10

12

14

16

18

<0.40

0.40-

0.45-

0.50-

0.55-

0.60-

0.65-

0.70-

0.75-

0.80-

0.85-

0.90-

0.95-

1.00-

1.05-

1.10-

Femoral neck BMD

Pre

vale

nce

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

10-y

ear

Ris

k o

f F

x

T < 2.5 osteopor

osis

14-year risk of fractures in 14-year risk of fractures in WOMEN aged 60+WOMEN aged 60+

1287women

Osteoporosis 345 (27%)

Non-osteoporosis

942 (73%)

Fx = 137 (40%)

No Fx = 208 (60%)

No Fx = 751 (80%)

Fx = 191 (20%)

42%

14-year risk of fractures in MEN 14-year risk of fractures in MEN aged 60+aged 60+

821 men

Osteoporosis N = 90 (11%)

Non-osteoporosis 731 (89%)

Fx = 27 (30%)

No Fx = 63 (70%)

No Fx = 640 (88%)

Fx = 91 (12%)

23%

Magnitude of the Magnitude of the ProblemProblem

Incidence of all-limb Incidence of all-limb fracturesfractures

0

100

200

300

400

500

0-4 5-14 15-24 25-34 35-44 45-54 55-64 65-74 75-84 85+

Age group

Rate

per

100,0

00 p

op

ula

tio

n

Annual fracture incidence in Annual fracture incidence in Australia Australia 1996-20511996-2051

93.75104.42

115.27125.86

150.74

207.66

0

50

100

150

200

250

2001 2006 2011 2016 2026 2051

1000

Projected annual number of all-limb fractures in Australia aged 35+ (Sanders et al, MJA 1999)

Hip, vertebrae, and Colles Hip, vertebrae, and Colles fracturesfractures

FractureFracture 20062006 20512051

HipHip 20,70020,700 60,00060,000

VertebraeVertebrae 14,50014,500 31,70031,700

CollesColles 11,90011,900 23,00023,000

HumerusHumerus 7,5007,500 16,30016,300

PelvisPelvis 4,1004,100 9,8009,800

Projected annual number of all-limb fractures in Australia aged 35+(Sanders et al, MJA 1999)

Lifetime risk of some Lifetime risk of some diseases - womendiseases - women

Any osteoporotic fracture

Hip fracture

Clinical vertebral fracture

Cancer (any site)*

Breast cancer*

Lung/bronchus*

Coronary heart diseases

Diabetes Mellitus

*, from birth Residual lifetime risk (%)

0 10 20 30 40 50 60 70

1/2

1/6

1/4

2/5

1/8

1/16

1/4

1/3

(from the age of 50)

Lifetime risk of some Lifetime risk of some diseases - mendiseases - men

Any osteoporotic fracture

Hip fracture

Clinical vertebral fracture

Cancer (any site)*

Prostate cancer*

Lung/bronchus*

Coronary heart diseases

Diabetes Mellitus

*, from birth (from the age of 50)

Residual lifetime risk (%)

0 10 20 30 40 50 60

1/3

1/16

1/8

3/7

1/8

1/16

1/3

1/2

Ten-year and lifetimeTen-year and lifetime risk of risk of fracturesfractures

Age free of fracture (y)

(%)

0

10

20

30

40

50

60

60 65 70 75 80 85Age free of fracture (y)

(%)

0

10

20

30

40

50

60

60 65 70 75 80 85

WomenMen

with advancing age with advancing age

10-y risk Lifetime risk

Ten-year and lifetimeTen-year and lifetime risk of risk of fracturesfractures

Osteoporosis T-scores < -2.5

Osteopenia -2.5 < T-scores < -

1.0

NormalT-scores >-1.0

Lif

etim

e ri

sk

Age free-of-fracture (y)

10-

y r

isk

Age free-of-fracture (y)

(%)

0

10

20

30

40

50

60

70

60 65 70 75 80 85

WomenMen

0

10

20

30

40

50

60

70

60 65 70 75 80 850

10

20

30

40

50

60

70

60 65 70 75 80 85

(%)

0

10

20

30

40

50

60

70

60 65 70 75 80 850

10

20

30

40

50

60

70

60 65 70 75 80 850

10

20

30

40

50

60

70

60 65 70 75 80 85

Ten-year and lifetimeTen-year and lifetime risk of any fracture by risk of any fracture by BMD and ageBMD and age

FNBMDFNBMD 10-year risk10-year risk LifetimeLifetime risk risk

(T-score)(T-score) Age free of fracture (y)Age free of fracture (y) Age free of fracture (y)Age free of fracture (y)

6060 7070 8080 6060 7070 8080

WOMENWOMEN

> -1.0 3.6 13.2 13.0 23.4 22.6 13.0

-2.4 to -1.1 25.4 25.3 25.7 55.7 44.3 33.0

-2.5 35.8 40.1 42.3 72.2 64.9 54.8

MEN

> -1.0 9.7 7.6 15.1 25.1 18.4 15.1

-2.4 to -1.1 9.3 9.7 10.3 35.3 25.7 23.7

-2.5 30.0 29.8 29.2 56.4 44.8 36.5

Consequences of Consequences of Osteoporotic FracturesOsteoporotic Fractures

Survival probability in thoseSurvival probability in thosewith and without fracturewith and without fracture

Time to follow-up (year)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Cu

mm

ula

tive

su

rviv

al p

rop

ort

ion

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Non-fracture

Any fracture

B Men

Time to follow-up (year)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Cu

mm

ula

tive

su

rviv

al p

rop

ort

ion

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Non-fracture

Any fracture

A Women

Nguyen et al, 2005

Risk of death from hip Risk of death from hip fracturefracture

50-year old women: Lifetime risk of mortality from: Hip Fracture: 2.8% Breast Cancer: 2.8% Endometrial Cancer: 0.7%

Cummings et al. Arch Intern Med 1989; 149: 2445-8

Impact of hip fracturesImpact of hip fractures

25% die within 6 months (*)25% die within 6 months (*) 60% have restricted mobility (*)60% have restricted mobility (*) 25% remain functionally more 25% remain functionally more

dependentdependent Cardiac (8%) and pumonary Cardiac (8%) and pumonary

complication (4%)complication (4%) Transient heart attacksTransient heart attacks Non-union and avancular necrosisNon-union and avancular necrosis

(*) Data from the Dubbo Osteoporosis Epidemiology Study

Impact of vertebral Impact of vertebral fracturesfractures

Symptomatic fx : Lifetime risk 1/4 Symptomatic fx : Lifetime risk 1/4 women, 1/8 men women, 1/8 men

Asymptomatic fx prevalence: 20-30%Asymptomatic fx prevalence: 20-30%

Back pain, functional limitationBack pain, functional limitation Rib-against-pelvis (RAP) syndromeRib-against-pelvis (RAP) syndrome Costoiliac impingement syndromeCostoiliac impingement syndrome Decrease vital lung capacityDecrease vital lung capacity

Pongchaiyakul C et al, J Bone Miner Res 2005

Asymptomatic vertebral Asymptomatic vertebral fracture increases risk of fracture increases risk of

subsequent fracturessubsequent fractures300 m+w

234 No V #66 V #

29 Fx 37 no fx 54 Fx 180 no fx

44% 23%

Pongchaiyakul C et al, J Bone Miner Res 2005

Asymptomatic vertebral Asymptomatic vertebral fracture increases risk of fracture increases risk of

deathdeath300 m+w

234 No V #66 V #

20 deaths 46 survived 25 deaths 209 survived

30% 11%

Pongchaiyakul C et al, J Bone Miner Res 2005

Impact of wrist fractureImpact of wrist fracture

More common in women in their More common in women in their 50s50s

Post-traumatic arthritisPost-traumatic arthritis Account for 39% of all physical Account for 39% of all physical

therapy sessionstherapy sessions Reduced daily living activiesReduced daily living activies

Melton LJ, J Bone Miner Res 2003

Utility loss associated with Utility loss associated with fracturefracture

0.00

0.10

0.20

0.30

0.40

0.50

Hip Tibiaand

fibula

Vertebra Ribs Pelvis Humerus Clavicle,sternum

Distalforearm

First year

Subsequent year

Under-treated & Under-Under-treated & Under-diagnosisdiagnosis

What the experts say? What the experts say? ““All women and men with a history of All women and men with a history of

fragility fractures should be considered fragility fractures should be considered for treatment of osteoporosis to reduce for treatment of osteoporosis to reduce their risk of future fracturetheir risk of future fracture.” (.” (Seeman Seeman and Eisman, MJA 2004and Eisman, MJA 2004))

““Initiate therapy to reduce fracture Initiate therapy to reduce fracture risk in postmenopausal women with risk in postmenopausal women with BMD T-scores by DXA below -2 in the BMD T-scores by DXA below -2 in the absence of risk factors and in women absence of risk factors and in women with T-scores below -1.5 if one or more with T-scores below -1.5 if one or more risk factors are presentrisk factors are present.” (.” (NOF 2003NOF 2003))

What the experts say? What the experts say?

““Recommend BMD testing to Recommend BMD testing to postmenopausal women who have postmenopausal women who have suffered a fragility fracture to confirm suffered a fragility fracture to confirm the diagnosis and determine disease the diagnosis and determine disease severityseverity.” (.” (NOF 2003NOF 2003))

Levels of treatment in Levels of treatment in fractured women in primary fractured women in primary

care settingscare settings

27.9

12.5

8.5 8.3

2.2

7.2

12.3

0.00

5.00

10.00

15.00

20.00

25.00

30.00

Any R

xHRT

Bispho

spho

nate

s

Calcitr

iol

Raloxif

ene

Calcium

only

Calcium

+ o

ther

Rx

Per

cen

t

Eisman JA, et al, J Bone Miner Res 2004

N = 20,248

Level of treatment in Level of treatment in outpatientsoutpatients

157 low-trauma fx

No prior fx: 81

Prior fx: 76

BMD:

35 (45%)

Any Rx:

14 (18%)

BMD:

18 (22%)

Any Rx:

3 (10%)

Bliuc D, et al, Osteoporosis Int 2004

Level of treatment – Level of treatment – experience in the USexperience in the US

502 hospitalised hip-fracture patients:502 hospitalised hip-fracture patients: only 14% had BMD scansonly 14% had BMD scans 13% received calcium and/or vitamin D13% received calcium and/or vitamin D 18% received HRT, calcitonin, or 18% received HRT, calcitonin, or

bisphosphonates.bisphosphonates.

Harrington JT, et al. Arthritis Rheum 2002; 47: 651-654

Risk factor modifications Risk factor modifications for fracturefor fracture

InterventionIntervention Estimated Estimated change in change in

fx riskfx risk

Bisphosphonates, HRT, Bisphosphonates, HRT, SERMsSERMs

~30-50%~30-50%

Quit smokingQuit smoking -38%-38%

Treat impaired visionTreat impaired vision -50%-50%

Stop sedativesStop sedatives -40%-40%

Hip protectorsHip protectors -50%?-50%?

SummarySummary

In individuals aged 60+: 25% women and In individuals aged 60+: 25% women and 11% men a11% men are osteoporosis (eg low BMD)re osteoporosis (eg low BMD)

Lifetime risk of fracture (from the age of Lifetime risk of fracture (from the age of 50): 1/3 men and 1/2 women.50): 1/3 men and 1/2 women.

With the presence of osteoporosis, With the presence of osteoporosis, lifetime risk increase to 1/2 men and lifetime risk increase to 1/2 men and 7/10 women7/10 women

SummarySummary

Fracture, particularly hip fracture, is a Fracture, particularly hip fracture, is a serious public health problem in the serious public health problem in the elderly.elderly.

Increase mortality risk, reduced quality Increase mortality risk, reduced quality of life, incurred health care costsof life, incurred health care costs

Osteoporosis is both under-treated and Osteoporosis is both under-treated and under-diagnosed.under-diagnosed.