bone health - osteoporosis and fractures the size …...bone mass and micro-architectural...
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Osteoporosis and Fractures The Size of the Problem
Kristina Kristina ÅÅkessonkessonDepartment of OrthopaedicsDepartment of OrthopaedicsMalmMalmöö University HospitalUniversity HospitalLund UniversityLund UniversityMalmMalmöö, Sweden, Sweden
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A million fragility fractures a year
But can we do more ?
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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
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“…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
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normal osteoporotic
Trabecular bone
Bone quality is not the only factor Bone quality is not the only factor ……
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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
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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
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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
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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……
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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
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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
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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
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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
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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
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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
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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
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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%*)
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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
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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
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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
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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
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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
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Vertebral fractures and mortality
Hasserius et al. Osteoporos Int. 2003; 14:61-8
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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)
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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
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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
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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
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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
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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
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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
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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