1

Osteoporosis and Fractures The Size of the Problem

Kristina Kristina ÅÅkessonkessonDepartment of OrthopaedicsDepartment of OrthopaedicsMalmMalmöö University HospitalUniversity HospitalLund UniversityLund UniversityMalmMalmöö, Sweden, Sweden

2

A million fragility fractures a year

But can we do more ?

3

Lecture content

•• Definition of OsteoporosisDefinition of Osteoporosis

•• Epidemiology of OsteoporosisEpidemiology of Osteoporosis−− Ageing populationsAgeing populations

−− prevalence and incidence of osteoporotic prevalence and incidence of osteoporotic fractures fractures

−− prevalence of low bone massprevalence of low bone mass

•• Quality of LifeQuality of Life−− morbidity and mortalitymorbidity and mortality

−− pain and limitationspain and limitations

•• Economic burdenEconomic burden

4

“…a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk.”

Definition of osteoporosis

World Health Organization (WHO), 1994

5

normal osteoporotic

Trabecular bone

Bone quality is not the only factor Bone quality is not the only factor ……

6

Bone massBone structureBone quality

Fall Risk Impact offall

Skeletalstrength

Fracture risk

Type of fallEnergy reductionExternal protection

Neuromuscular functionEnvironmental risksAge

Pathogenesis of fragility fractures

7

Lecture content

•• Definition of OsteoporosisDefinition of Osteoporosis

•• Epidemiology of OsteoporosisEpidemiology of Osteoporosis−− Ageing populationsAgeing populations

−− prevalence and incidence of osteoporotic prevalence and incidence of osteoporotic fractures fractures

−− prevalence of low bone massprevalence of low bone mass

•• Quality of LifeQuality of Life−− morbidity and mortalitymorbidity and mortality

−− pain and limitationspain and limitations

•• Economic burdenEconomic burden

8

The ageing population

In Europe, population over 65:In Europe, population over 65:

•• 1212--17 % in 2002 17 % in 2002

•• 2020--25 % by 202525 % by 2025

In western countries

United Nations Statistics Division, Demographic Yearbook 2004

9

Life expectancy in men and womenAge (in years) Life expectancy (in years) in 1999

Male Female

At birth (0) 75.4 80.2

5 71.0 75.7

20 56.2 60.8

30 46.7 51.0

50 27.9 32.0

60 19.4 23.0

70 12.2 15.1

80 7.0 8.7

and life expectancy is increasing Data from the UK

10

The ageing population

In developing countriesIn developing countries

0 0 -- 15 years15 years 30 %30 %

Over 65 yearsOver 65 years 5.5 %5.5 %

But changes are expectedBut changes are expected……

11

Biological age – a factor beyond chronological age

0 1 2 3 4 5 6 7 8

Years after baseline (at age 75) investigation

0,70

0,75

0,80

0,85

0,90

0,95

1,00

Cum

ulat

ive

Pro

porti

on S

urvi

ving

Tertile of biologically oldest

All other women

Higher mortality in women with high biological age

Higher fracture rate in women with high biological age

0 1 2 3 4 5 6 7 8

Years from age 75

0,65

0,70

0,75

0,80

0,85

0,90

0,95

1,00

Cum

ulat

ive

prop

ortio

n w

ith fr

actu

res

All other women

Tertile of biologically oldest

Highest tertile

All other women

N=1044 women 75 years oldGerdhem et al Gerontology 2004; 50:309-14

12

Epidemiology of fractures

•• Incidence and prevalence depend onIncidence and prevalence depend on

•• definition of fracturedefinition of fracture

•• diagnostic method: diagnostic method: −− clinical vs. radiologicalclinical vs. radiological−− quantitative vs. qualitativequantitative vs. qualitative−− morphometric methodmorphometric method

•• study populationstudy population

13

Age- and sex-specific incidence of all limb fractures

Age group

Inci

denc

e pe

r 100

,000

per

son-

year

s

Garraway et al. Mayo Clin Proc 1979; 54:701-7

0

500

1000

1500

2000

2500

3000

3500

4000

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

FemalesMales

14

Fracture and quality of life over the life span

Morbidity

50 60 70 80 90

Colles' fracture

Vertebral fracture

Hip fracture

Age

15

Cooper et al. Trends Endocrinol Metab 1992; 3:224

755535

Men

Forearm

Vertebrae

Hip

Age (years)

4,000

3,000

2,000

1,000

Women

Forearm

Inci

denc

e pe

r 100

,000

per

son-

year

s

Vertebrae

Hip

55 7535

Osteoporotic fracture incidence

16

Number of osteoporotic fractures worldwide

0

10000

20000

30000

40000

50000

60000

No of incident fx No of prevalent fx

MenWomenTotal

17

Type of Fracture Men Women

Forearm 4.6 20.8Hip 10.7 22.9Spine 8.3 15.1Proximal Humerus 4.1 12.9

Other 22.4 46.4

Remaining lifetime fracture risk (%) in Caucasian population at the age of 50

Johnell et al. Osteoporos Int 2005; 16 Suppl 2:S3-7

18

Prior fracture increase risk for subsequent fracture

Klotzbuecher et al. J Bone Miner Res 2000; 15:721-727

Risk of subsequent fractureRisk of subsequent fractureSite of prior Site of prior fracturefracture

Hip Hip SpineSpine ForearmForearm Minor fractureMinor fracture

HipHip 2.32.3 2.52.5 1.41.4 1.91.9SpineSpine 2.32.3 4.44.4 1.41.4 1.81.8ForearmForearm 1.91.9 1.71.7 3.33.3 2.42.4Minor FractureMinor Fracture 2.02.0 1.91.9 1.81.8 1.91.9

19

Mortality after major types of osteoporotic fracture in men and women

Age-standardized mortality ratioFracture Women Men

Proximal femur 2.2 3.2Vertebral 1.7 2.4Other major 1.9 2.2Other minor 0.8 1.5

5-year prospective cohort study

Center et al. Lancet 1999; 353:878-882

20

Vertebral fractures: grading of severity

Adapted from Genant HK et al. J Bone Miner Res 1993; 8:1137-1148

MiddleAnterior Posterior

Fracture Grade0- Normal

1- Mild(20-25%*)

2- Moderate(26-40%*)

3- Severe(>40%*)

21

Incidence of vertebral fractures in women and men

EPOS Group, J Bone Miner Res 2002; 17:716-24

Age group50-54 55-59 60-64 65-69 70-74 75-79

n pe

r 100

0 pe

rson

-yea

rsV

erte

bral

frac

ture

s

0

10

20

30

40

50men women

The EPOS Study

22

Proportion with vertebral deformity

0

20

40

60

80

100

50-59 60-69 70-79 80-86

Men Women

Per

cent

age

%

Age group

Hasserius et al. Acta Orthop Scand. 2001; 72:273-8

23

Vertebral fracture prevalence

McCloskey MethodO’Neill, J Bone Miner Res 1996; 11:1010

Age (years)

10% 11% 12% 12% 13%

18%

5%8%

10%

13%

17%

25%

0%

5%

10%

15%

20%

25%

30%

50-54 55-60 60-64 65-69 70-75 75-79

Men Women

24A

nnua

l inc

iden

ce

Fracture type

Incidence of fractures

Hip

300,000+

Vertebral(Morphometric)

700,000

300,000+

Wrist0

250,000

500,000

750,000

200,000

Other

Only 30% of morphometric vertebral fractures are “clinically apparent”

Clinicallyapparent

US data

25

Risk for new vertebral fracture following first vertebral fracture

2725 post2725 post--menopausal women, randomized placebomenopausal women, randomized placebo--controlledcontrolled

00

55

1010

1515

Inci

denc

e of

new

ver

tebr

al fr

actu

res

(%)

Number of vertebral fractures at start of study

RR=7.3

RR=5.1

RR=2.6

00 11 ≥≥11 ≥≥22

Lindsay et al. JAMA 2001; 285:320-23

26

Cumulative proportion without fracture

1.0

0.5

Without Vfx

With Vfx

105Years

Hasserius et al. Osteoporos Int. 2003; 14:61-8

Vertebral deformity and the risk of future fracture

Risk increaseHR 2.0

27

Vertebral fractures and mortality

Hasserius et al. Osteoporos Int. 2003; 14:61-8

28

Hip fracture incidence

Melton et al. Calcif Tissue Int 1987; 41:57

500

1000

1400

40 50 60 70 80

500

1000

1400

40 50 60 70 80

Femoral Neck

Men Women

Femoral Neck

IntertrochantericIntertrochanteric

Inci

denc

epe

r 100

,000

per

son-

year

s

Age (years) Age (years)

29

Hip fracture incidenceGeographic variation

Women Men

Lifetime risk (%)

Kanis et al, J Bone Miner Res. 2002; 17:1237

0 5 10 15 20 25 30

TurkeyChina

HungaryChina (HK)

PortugalGreece

SpainFinlandFranceJapan

CanadaUK

GermanyNetherlands

USADenmarkAustralia

ItalyIceland

SwitzerlandNorwaySweden

Lifetime risk (%)

0 2 4 6 8 10 12 14

TurkeyChina

HungaryChina (HK)

PortugalGreece

SpainFinlandFranceJapan

CanadaUK

GermanyNetherlands

USADenmarkAustralia

ItalyIceland

SwitzerlandNorwaySweden

30

Incidence of hip fractures in women and men

Elffors et al, Osteoporos Int. 1994; 4:253

SevilleCreta

RomePort

MadridToulouse

ParisSiena

parmaIstanbul

AnkaraRural Turkey

Inci

denc

e/10

'000

0

10

20

30

40

50

60men women

The Medos Study

31

Projected to reach 3.250 million in Asia by 2050

Adapted from Cooper et al, Osteoporos Int. 1992; 2:285-9

Estimated number of hip fractures: (1000s)

1950 2050

600

3250

1950 2050

668

400

1950 2050

742

378

1950 2050

10

0

629

Projected number of osteoporotic hip fractures worldwide

Total number ofhip fractures:

1950 = 1.66 million2050 = 6.26 million

32

Distal radius fractures•• The most common fracture in women at middle The most common fracture in women at middle

ageage

•• Incidence increase begins just after menopause in Incidence increase begins just after menopause in womenwomen

•• The most common fracture in men below age 70 The most common fracture in men below age 70 yearsyears

Fracture incidence - women

Forearm Vertebral Prox Humerus Ankle Hip

45-49 50-54 55-59 60-64 65-69 70-740,00

1,00

2,00

3,00

4,00

5,00

6,00

inci

denc

e / 1

000

pers

on y

rs

Fracture incidence - men

Forearm Vertebral Prox Humerus Ankle Hip

45-49 50-54 55-59 60-64 65-69 70-740,00

1,00

2,00

3,00

4,00

5,00

6,00

inci

denc

e / 1

000

pers

on y

rs

Holmberg et al, Osteoporos Int. 2006; 7:1065-77

33

Distal radius fractures

•• It is estimated that It is estimated that 16.6% of women16.6% of women and and 2.9% of men2.9% of men will suffer a distal radius will suffer a distal radius fracture from the age of 50 years in the fracture from the age of 50 years in the UKUK

•• Only Only 50% report good functional outcome50% report good functional outcomeat 6 months and up to at 6 months and up to 30% of individuals 30% of individuals may suffer some longmay suffer some long--term complicationsterm complications

O'Neill et al. Osteoporos Int 2001; 12:555-558

34

Proximal humerus fracture

•• Estimated that fractures of the proximal part of Estimated that fractures of the proximal part of the humerus account for 4the humerus account for 4--8 % of all fractures8 % of all fractures

•• In persons over 40, fractures of the proximal In persons over 40, fractures of the proximal humerus account for 76% of all fractures of the humerus account for 76% of all fractures of the humerushumerus

•• Data suggest that fracture of the proximal Data suggest that fracture of the proximal humerus is the third most common fracture over humerus is the third most common fracture over age 65age 65

•• Fractures of the proximal humerus have shown a Fractures of the proximal humerus have shown a pattern of increase similar to other common pattern of increase similar to other common fragility fractures fragility fractures

35

Epidemiology of low bone mass

Prevalence depends on:Prevalence depends on:

•• definition of low bone mass (WHO)definition of low bone mass (WHO)

•• densitometry technique (DXA)densitometry technique (DXA)

•• skeletal siteskeletal site

•• study populationstudy population

36

WHO criteria for osteoporosis

Kanis et al. J Bone Miner Res 1994; 9:1137-41

T-score: Difference expressed as standard deviation compared to young reference population

T-score

Normal - 1.0 and above

Osteopaenia - 1.0 to - 2.5

Osteoporosis - 2.5 and below

Severe (established) osteoporosis

- 2.5 and below, plus one or more osteoporotic fracture(s)

37

Prevalence of osteoporosis in men and women by gender-specific scores

Schuit et al. Bone 2004; 34:195

55-59

60-64

65-69

70-74

75-79

80-84 85

+

55-59

60-64

65-69

70-74

75-79

80-84 85

+

Pre

vale

nce

(%)

0

20

40

60

80

100Normal BMD Osteopaenia Osteoporosis

Men Women

38

Prevalence of osteoporosis in women at different skeletal sites

Melton et al. J Bone Miner Res 1995; 10:175

0

10

20

30

40

50

60

50-59 60-69 70-79 80+ age 50+

Spine Hip Mid-radius Any site

T-score ≤ -2.5

Pre

vale

nce

(%)

Age (years)

39

Prevalence of osteoporosis at the femoral neck in Caucasian women

Kanis et al, Calcif Tissue Int 2001; 69:218

Age (years)

0%

10%

20%

30%

40%

50%

50-54 55-59 60-64 65-69 70-74 75-79 80-84

(Sweden)

Pre

vale

nce

40

50%

4% 6%

33%

47%

0%

10%

20%

30%

40%

Female cut off points Male cut off points

OsteopaeniaT-score -1 to -2.5

OsteoporosisT-score ≤ -2.5

Prevalence of low bone mass in male Caucasians aged 50 years and older

Looker et al. J Bone Miner Res 1997; 12:1761Melton et al. J Bone Miner Res 1998; 13:1915

Pre

vale

nce

Femoral Neck

41

Bone density is not the only factor of fracture risk …

Bone massBone structureBone quality

Fall Risk Impact offall

Skeletalstrength

Fracture risk

Type of fallEnergy reductionExternal protection

Neuromuscular functionEnvironmental risksAge

42

Osteoporotic fracture and BMD

Fractures per 1,000 person-years Number of fractures

1.0 0.5 0.0 -0.5 -1.0 -1.5 -2.0 -2.5 -3.0 -3.5

Fracture rate

Women with fractures

0

10

20

30

40

50

0

100

200

300

400

Siris et al. Arch Intern Med. 2004; 164:1108-1112

43

T-score (SD)-3 -2 -1 0 1

0

10

20

Fracture probability (%)

50

60

70

80

Age (years) Women

Ten-year probability of hip fracture in Sweden

44

0

5

10

15

50 55 60 65 70 75 80 85-2.5

Age

Ten-year probability of hip fracture in women at T–score = –2.5

45

Fracture risk – multifactorial

The relative importance of risk factors

0

0.5

1

50 60 70 75 80 85 >90 Age

BMD independent factors

BMD dependent factors

46

Fracture risk – multifactorial

The relative importance of risk factors

0

0.5

1

50 60 70 75 80 85 >90 Age

BMD independent factors

BMD dependent factors

Vertebral fractures

47

Fracture risk – multifactorial

The relative importance of risk factors

0

0.5

1

50 60 70 75 80 85 >90 Age

BMD independent factors

BMD dependent factors

Non- vertebral fractures

48

Fracture risk is…

•• highest in the oldest populationhighest in the oldest population

•• highest in womenhighest in women

•• highest in those with previous fracturehighest in those with previous fracture

•• high in those with low bone densityhigh in those with low bone density

•• high in very thin peoplehigh in very thin people

•• high in those with comorbidityhigh in those with comorbidity

•• high in those on steroid treatmenthigh in those on steroid treatment

•• high in those who smokehigh in those who smoke

49

Lecture content•• Definition of OsteoporosisDefinition of Osteoporosis

•• Epidemiology of OsteoporosisEpidemiology of Osteoporosis−− ageing populationsageing populations

−− prevalence and incidence of osteoporotic prevalence and incidence of osteoporotic fractures fractures

−− prevalence of low bone massprevalence of low bone mass

•• Quality of LifeQuality of Life−− morbidity and mortalitymorbidity and mortality

−− pain and limitationspain and limitations

•• Economic burdenEconomic burden

50

0

10

20

30

40

50

60

70 years 80 years

ActiveCity-livingCountry-living

%

Ringsberg et al. Gerontology 2001; 47:15-20

City-livingwomen

Active women have fewer fragility fractures and better quality of life

51

All fractures are associated with morbidity

Cooper. Am J Med. 1997; 103(2A):12s-19s

40%

Unable to walk independently

30%

Permanentdisability

20%

Death within one year

80%

One year after a hip

fracture:

Pa t

i ent

s ( %

)

Unable to carry out at least one independent activity of daily living

52

Morbidity after vertebral fractures

•• Back painBack pain

•• Loss of heightLoss of height

•• Deformity (kyphosis, protuberant abdomen)Deformity (kyphosis, protuberant abdomen)

•• Reduced pulmonary functionReduced pulmonary function

•• Diminished quality of lifeDiminished quality of life–– loss of selfloss of self--esteem, distorted body imageesteem, distorted body image

–– dependence on sleeping tablets, sleep disordersdependence on sleeping tablets, sleep disorders

–– depressiondepression

–– loss of independenceloss of independence

53

Vertebral fractures restrict daily activities

Adapted from Ross PD et al.

No vertebral fractures over the last four years

People with vertebral fractures have greater pain, disability and healthcare utilisation, on average, than those without fracture

05

1015202530354045

Odd

s rat

io

Back pain Difficulty with>3 daily

activities

>3 activitiesaffected dueto back pain

Medicalconsultation

1 #2 #3 #

54

All vertebral fractures are clinically important

Nevitt et al. Arch Intern Med 2000; 160:77-85

No incident fracture

Clinical fracture

Radiographicfracture

050

100150200250300350400

Mea

n nu

mbe

r of d

ays

Moderate Back Pain Severe Back Pain

No incident fracture

Radiographicfracture

Clinical fracture

0

25

50

75

100

Per

cent

age

(%) o

f pat

ient

s

Limited Activity Bed Rest

55

Loss of function

50%

Mortality20%

Regained functional capacity

30%

Sernbo 1993

Outcome after hip fractureThe situation one year after fracture

Sernbo et al. Osteoporos Int. 1993; 3:148-53

56

Improvement in quality of life after surgery for hip fracture

Cranney et al. J Rheumatol. 2005; 32:2393-9

SF-36 at baseline and3, 6, and 9 monthsafter surgery

57

Optimal fracture treatment –a prerequisite for maintaining quality of life

58

Lecture content•• Definition of OsteoporosisDefinition of Osteoporosis

•• Epidemiology of OsteoporosisEpidemiology of Osteoporosis−− aging populationsaging populations

−− prevalence and incidence of osteoporotic prevalence and incidence of osteoporotic fractures fractures

−− prevalence of low bone massprevalence of low bone mass

•• Quality of LifeQuality of Life−− morbidity and mortalitymorbidity and mortality

−− pain and limitationspain and limitations

•• Economic burdenEconomic burden

59

Cost of osteoporosis in the United States

Ray et al. J Bone Miner Res 1997; 12:24-35

Total annual cost

$13.8Billion

$3.9(28%)

$1.3(10%)

$8.6(62%)

Hospitalization

Outpatient

Nursing Home

60

Economic impact of osteoporosis

Annual direct costDisease Prevalence including hospitalization

(millions) (US$ billion)

Cardiovascular 4.6 20.3disease

Asthma 15 7.5Osteoporosis 10 13.8

Information supplied by National Heart, Lung & Blood Institute,National Osteoporosis Foundation, American Heart Association

Annual economic cost of treating fractures in the USA is similarAnnual economic cost of treating fractures in the USA is similar to to that of treating cardiovascular disease and asthmathat of treating cardiovascular disease and asthma

61

Osteoporotic fractures:comparison with other diseases

1996 new cases,all ages184 300

750 000 vertebral

250 000 other sites

250 000forearm

250 000hip

0

500

1000

1500

2000

Osteoporotic fractures

Heartattack

Stroke Breastcancer

Ann

ual i

ncid

ence

x 1

000

1 500 000

annual incidenceall ages

513 000

annual estimatewomen 29+

228 000

annual estimatewomen 30+

American Heart Association, 1996American Cancer Society, 1996Riggs & Melton Bone, 1995; 17:505S-511S

62

The burden of osteoporosisLecture summary

•• Epidemiology of osteoporosisEpidemiology of osteoporosis−− Prevalence and incidence of osteoporotic fractures is high and Prevalence and incidence of osteoporotic fractures is high and

increases exponentially with ageincreases exponentially with age

•• Quality of LifeQuality of Life−− Morbidity and mortality are significantly increased after fractuMorbidity and mortality are significantly increased after fracturesres−− Osteoporotic fractures result in pain and reduced quality of lifOsteoporotic fractures result in pain and reduced quality of life e

•• Economic costs are hugeEconomic costs are huge−− In comparison with other diseases, osteoporosis is very common In comparison with other diseases, osteoporosis is very common

Osteoporosis = important public health problemOsteoporosis = important public health problem

3030--50% of women and 1550% of women and 15--30% of men will suffer an osteoporotic fracture30% of men will suffer an osteoporotic fracture