Prof. Elaine Dennison's presentation from Osteoporosis 2016: Scope Of The Problem. Find out more at: https://nos.org.uk/conference

1. Osteoporosis: Scope of the
Problem
Elaine Dennison
MRC Lifecourse Epidemiology Unit, University of Southampton

2. Outline
• Public and personal burden of osteopotic
fracture
• Geographic trends
• Temporal trends
• Strategies to reduce burden

3. 0 1000 AD 2000 AD1000 BC
400 BC
Hippocrates
of Kos
700 AD
Saxon
tomb, Wells
1825 AD
Sir Astley
Cooper
1850 AD
Osteoporosis
1950 2016199019801970
1948
Albright
1963
SPA
1976
HRT
1987
DXA
1990–2016 WHO
Calcium, fluoride
bisphosphonates
SERMs, PTH, Sr,
Dmab, Scl-ab,
ODN, FRAX
1940 1960
Osteoporosis: Three Millennia

4. Normal Bone Osteoporosis
WHO Definition of Osteoporosis; 1994
A disorder characterised by low bone mass and
microarchitectural deterioration of bone tissue
leading to an increased risk of fracture

5. Osteoporosis in Europe

6. Impact of Osteoporosis-Related
Fractures in Europe
Hip Spine Wrist
Lifetime risk (%)
Women 14 11 13
Men 3 4 2
Cases/yr 615k 516m 560k
Hospitalisation (%) 100 1-2 5
Relative survival 0.83 0.82 1.00
All sites combined: n=3.5m; cost ~ 39 billion Euros
Hernlund E et al Arch Osteop 2013; 8(1-2): 136

7. 400 -
300 -
200 -
100 -
0 -
Men Women
= Hip fracture
= Radiographic vertebral fracture
= Clinical vertebral fracture
Incidenceper10,000/year
Age group Age group
50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+
400 -
300 -
200 -
100 -
0 -
50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+
= Forearm fracture
Sambrook P, Cooper C. Lancet 2006; 367: 2010-18
Incidence of Osteoporotic Fractures

8. Fracture frequency in clinical practice
POSSIBLE, EU study
Freemantle N et al Arch Osteop 2010; 5: 61-72

9. Number of days in hospital, rehabilitation centre or
nursing home for patients with a fracture of the spine, hip
or non-spine/non-hip
617
392
120
1306 1252
398
3805
4083
1103
0
500
1000
1500
2000
2500
3000
3500
4000
4500
Hospital Rehabilitationcentre Nursinghome
Noofdays
Spinefracture Hipfracture Non-spine,non-hipfracture
Ioannidis G et al Osteoporosis Int 2013; 24: 59-67
GLOW cohort

10. Survival after osteoporotic fracture
Cooper et al, Am J Epidemiol 1993; 137: 1001-5
0.6
0.7
0.8
0.9
1
1.1
0 1 2 3 4 5
Time since fracture (years)
Survival
(%) Vertebral
Hip
Wrist

11. • Monetary burden:
– Direct costs of treating incident fracture
• 26 billion Euros
– Long-term fracture care
• 11 billion Euros
– Prevention
• 2 billion Euros
• Costs by fracture site:
– Hip 55%
– Vertebral 5%
– Wrist 1%
– Other fractures 38%
Costs of Fracture: EU27, 2010
Hernlund E et al. Arch Osteop 2013; 8 (1-2): 136
Kanis JA et al. Arch Osteop 2013; 8 (1-2): 137

12. Treatment gap (%)
0
20
40
60
80
100
Spain
Ireland
Hungary
Greece
Portugal
France
Luxembourg
Slovenia
Belgium
Slovakia
Austria
Denmark
UK
Italy
Netherlands
Finland
Sweden
CzechRepublic
Germany
Poland
Romania
Latvia
Estonia
Lithuania
Bulgaria
EU27
Moderate
High
Very high
Proportion of women at high risk that are untreated (treatment
gap) in 2010 ranked by country and score
Hernlund E et al. Arch Osteop 2013; 8 (1-2): 136
Kanis JA et al. Arch Osteop 2013; 8 (1-2): 137

13. Worldwide variation in hip fracture incidence
Men and Women
Low (<150/100,000)
Moderate (150-250)
High (>250) Kanis JA et al. Osteop Int 2012; 23: 2239-56

14. Geographic variation in hip fracture incidence: Europe
Arden N et al (2000)
Correlates:
• Latitude
• Sunlight
• Activity
• BMI
• Height
• Fall risk
• Not BMD

15. Geographic variation in hip fracture incidence
USA; 1984-87
Jacobsen SJ et al JAMA 1990; 264: 500-502

16. Ecological correlates of hip fracture
USA
• Significant relationship:
– Latitude (higher in South)
– Water hardness (-ve)
– Sunlight hours in January (-ve)
– Poverty level
– Rural land use
– Fluoridated water
• Non-significant relationship:
– Activity level, cigarette smoking, alcohol consumption,
Scandinavian heritage, obesity
Jacobsen SJ et al JAMA 1990; 264: 500-502

17. Regional variation in fragility fracture (spine, hip, wrist, rib, pelvis, and
humerus) incidence in men and women aged 50+ years within UK
CPRD; 1988-2012. Relative rates of fracture are displayed in comparison to London.
Curtis E et al. Bone 2016; 87: 19-26

18. Fragility fracture incidence and index of multiple
deprivation (IMD); UK, 1988-2012
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1 2 3 4 5
Relativerateoffracture
Index of Multiple Deprivation Category
Fragility
Men
Women
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1 2 3 4 5
Relativerateoffracture
Index of Multiple Deprivation Category
Hip
Men
Women
0.9
0.92
0.94
0.96
0.98
1
1.02
1.04
1.06
1.08
1.1
1 2 3 4 5
Relativerateoffracture
Index of Multiple Deprivation Category
Radius/Ulna
Men
Women
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1 2 3 4 5
Relativerateoffracture
Index of Multiple Deprivation Category
Vertebral
Men
Women
Curtis E et al. Bone 2016; 87: 19-26

19. Regional variation in childhood fracture incidence within UK.
Relative rate of fractures for each sex compared to that observed in Greater London
BOYS GIRLS
Referent
Low <1.50
Medium 1.50-1.64
High ≥ 1.65
Relative Rate
Moon R et al. Bone 2016; 85: 9-14

20. Childhood fracture incidence and ethnicity
UK: 1988-2012
Moon R et al. Bone 2016; 85: 9-14

21. Prevalence of Vertebral Deformity
EVOS
25
20
15
10
5
0
Prevalence(%)
Age (years)
O'Neill et al, J Bone Min Res 1996; 11: 1010-18
50 55 60 65 70 75
Men
Women

22. Grade 1 ~
20-25%
Shape
Normal Endplate Wedge Crush
% change
in shape
These
changes in
shape are
often
combined
Vertebral fracture: Semi-quantitative grading
Genant HK, et al. J Bone Miner Res. 1996;11(7):984–96.
Grade 2 ~
25-40%
Grade 3
40%+

23. Distribution of Vertebral Fractures
0
10
20
30
40
50
60
70
80
90
100
T4
T5
T6
T7
T8
T9
T10
T11
T12
L1
L2
L3
L4
Ismail et al, J Bone Min Res (1999)

24. Incidence of Vertebral Fracture
Age (years)
MEN WOMEN
Morphometric
<50 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+
0
1000
2000
3000
4000
5000
Fracture/100,000p-y
EPOS (morph)
EPOS (sq)
Roch, MN (est)
Japan
Roch, MN (morph)
<50 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+
0
1000
2000
3000
4000
5000
Cooper C et al. ASBMR Primer (2006)

25. Outcome of Vertebral Fracture
Incident
vertebral
fractures
Clinical attention
Hospitalization1-3%
40%
100%
Cooper et al J Bone Min Res 1992; 7: 221-7

26. Global projections for hip fracture
Adapted from Cooper C, et al. Osteoporosis Int 1992;2:285-289
Estimated no of hip fractures: (1000s)
Projected to
reach 3.250
million in
Asia by 2050
1990 2050
600
3250
1990 2050
668
400
1990 2050742
378
1990 2050
100
629
Total number of
hip fractures:
1990 = 1.66 million
2050 = 6.26 million

27. Age-adjusted incidence rate for hip fracture
Rochester, MN; 1928-2006
Melton LJ et al Osteop Int 2009; 20: 687-694
HR per 10yr interval = 0.8 [0.6 -0.9]

28. Segments Annual Change, % (95% CI)
Both sexes 1985-1996 -1.2 (-1.3 to -1.0)
1996-2005 -2.4 (-2.6 to -2.1)
Males 1985-1996 -0.8 (-1.1 to -0.5)
1996-2005 -2.0 (-2.4 to -1.6)
Females 1985-1996 -1.3 (-1.5 to -1.1)
1996-2005 -2.4 (-2.6 to -2.2)
Leslie WD et al JAMA 2009; 302: 883-9
Trends in hip fracture incidence: Canada, 1985-
2005

29. Trends in hip fracture incidence in Canada
Age-period-cohort analysis
• Hip fracture incidence 1985-2005
• Age-period-cohort model
• Declining rates in each 5-yr period
• -12% women; -7% men
• Significant birth cohort effects
• men and women (p<0.0001)
Jean S et al J Bone Min Res 2013; 28: 1283-9

30. Reversal of the hip fracture secular trend
in Belgian women
-
-
-
-
-
-
Hiligsmann et al. Arthritis Care Res 2012; Jan 11 [epub]
Reginster et al. Bull World Health Organ 2001; 79: 942-6
+2.1%
-1.1%
1984-1996 2000-2007
Averageyearlychangeinthe
incidenceofhipfractures

31. Age- and gender-specific incidence of cervical and
trochanteric fractures in Tottori, Japan; 1986-2006
Hagino H et al. Osteoporos Int 2009; 20: 543-8

32. Change in age-specific incidence of hip fracture in
Beijing, China from 1990-1992 to 2002-2006
*
Xia W et al. J Bone Min Res 2012; 27: 125-9

33. Japan02-06
Japan86-01
Singapore 92-98
Singapore 60-91
Hong Kong 85-01
Hong Kong 66-85
New Zealand 89-98
New Zealand 79-89
Australia 89-00
Canada 92-01
Canada 76-85
Spain88-02
Hungary93-03
Switzerland 91-00
Austria 94-06
Germany95-04
Netherlands 93-02
Netherlands 86-93
UK 92-98 UK 78-85
UK 68-78
Finland 92-03
Finland 70-97
Denmark 87-97
Sweden92-95
Sweden50-92
Norway79-99
-10 -5 0 5 10
% Annual Change
Secular Trends in Hip Fracture Worldwide
Europe
N. America
Oceania
Asia
USA (Rochester) 28-72USA (Rochester) 72-92
USA (Rochester) 80-06 USA (Framingham) 48-96
Cooper C et al Osteop Int 2011; 22: 1277-

34. Secular trends in hip fracture
Effects of:
• Age
• Period
• Birth-cohort

35. Risk factors during adult life
Bone mass
(g/Ca)
Age (yr)
1500 -
1000 -
500 -
0 -
0 20 40 60 80 100

36. Risk factors during adult life
• Potential contribution
• Obesity
• Physical inactivity
• Vitamin D insufficiency
• Increasingly frail elderly population
• Risk assessment by DXA and pharmacotherapy
• Less likely contribution
• Dietary calcium intake
• Cigarette smoking
• Alcohol consumption
• Estrogen use

37. Risk factors during development,
childhood and adolescence
Bone mass
(g/Ca)
Age (yr)
1500 -
1000 -
500 -
0 -
0 20 40 60 80 100
Peak bone mass

38. Bone mass
Target those with a low
bone density
Bone mass
Move entire distribution by
intervening in everyone
Mean
-1SD +1SD
Preventive strategies: High-risk approach
Cooper C, et al. Trends Endocrinol Metab 1992;3:224–9.

39. Fracture risk after hip fracture decreases
with time
Ryg J et al. J Bone Miner Res 2009; 24: 1299-1307.
Relative risk for a second hip fracture increases
one month after a hip fracture
11.8x
Relativerisk
Relative risk for a second hip fracture increases
one year after a hip fracture
2.2x

40. “CAPTURE THE FRACTURE” IOF Campaign www.iofbonehealth.org
A global campaign facilitating the implementation of
coordinator-based, post-fracture models of care for
secondary fracture prevention
1 STANDARD LEVEL 1 BRONZE LEVEL 2 SILVER LEVEL 3 GOLD
Patient
Identification
Standard
Fracture patients within the scope of the institution
(inpatient and/or outpatient facility) are identified
to enable delivery of secondary fracture prevention.
Clinical fracture patients
are being identified but no
patient tracking system
exists to evaluate
percentage of patients that
are identified versus those
that are not.
Clinical fracture patients
are being identified and a
patient tracking system
exists to evaluate
percentage of patients
that are identified versus
those that are not.
Clinical fracture patients
are being identified and a
patient tracking system
exists to evaluate
percentage of patients that
are identified versus those
that are not. The quality
of data capture has been
subject to independent
review.
• Best Practice Framework
• 14 standards (Identification; follow-up;
risk assessment; treatment decision)
• 3 levels of achievement
Akesson K et al Osteoporosis Int 2013; 24: 2135-52

41. Conclusions
• Increasing recognition of burden from non-hip, non-vertebral fractures
• Geographic variation and incidence trends in hip fracture evaluated between
1928 and the present day
• Wide geographic variation in age-adjusted incidence persists for hip (but not
vertebral) fracture in most recent studies
• Age-adjusted rates appear to be reaching a plateau, or have even begun to
decline, in North America, northern Europe and Oceania, but rates continue
to rise in Oriental populations
• Age, period and cohort effects point at determinants throughout the life-
course eg. maternal vitamin D status
• Secondary prevention of fracture an urgent priority

42. With thanks to all at Southampton