Osteoporosis: Scope of the Problem

Elaine DennisonMRC Lifecourse Epidemiology Unit, University of Southampton

Outline

• Public and personal burden of osteopotic fracture

• Geographic trends • Temporal trends• Strategies to reduce burden

0 1000 AD 2000 AD1000 BC

400 BCHippocrates

of Kos

700 ADSaxon

tomb, Wells

1825 ADSir AstleyCooper

1850 ADOsteoporosis

1950 2016199019801970

1948Albright

1963SPA

1976HRT

1987DXA

1990–2016 WHOCalcium, fluoridebisphosphonatesSERMs, PTH, Sr,Dmab, Scl-ab, ODN, FRAX

1940 1960

Osteoporosis: Three Millennia

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

Osteoporosis in Europe

Impact of Osteoporosis-Related Fractures in Europe

Hip Spine Wrist

Lifetime risk (%)Women 14 11 13Men 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

400 -

300 -

200 -

100 -

0 -

Men Women

= Hip fracture

= Radiographic vertebral fracture

= Clinical vertebral fracture

Inci

denc

e pe

r 10,

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

Fracture frequency in clinical practice POSSIBLE, EU study

Freemantle N et al Arch Osteop 2010; 5: 61-72

Number of days in hospital, rehabilitation centre or nursing home for patients with a fracture of the spine, hip

or non-spine/non-hip

617392

120

1306 1252

398

38054083

1103

0

500

1000

1500

2000

2500

3000

3500

4000

4500

Hospital Rehabilitation centre Nursing home

No

of d

ays

Spine fracture Hip fracture Non-spine, non-hip fracture

Ioannidis G et al Osteoporosis Int 2013; 24: 59-67GLOW cohort

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

HipWrist

• 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): 136Kanis JA et al. Arch Osteop 2013; 8 (1-2): 137

Treatment gap (%)

0

20

40

60

80

100

Spain

IrelandH

ungaryG

reeceP

ortugalFranceLuxem

bourgS

loveniaB

elgiumS

lovakiaA

ustriaD

enmark

UK

ItalyN

etherlandsFinlandS

weden

Czech R

epublicG

ermany

Poland

Rom

aniaLatviaE

stoniaLithuaniaB

ulgariaE

U27

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): 136Kanis JA et al. Arch Osteop 2013; 8 (1-2): 137

Worldwide variation in hip fracture incidenceMen and Women

   

Low (<150/100,000)Moderate (150-250)High (>250) Kanis JA et al. Osteop Int 2012; 23: 2239-56

Geographic variation in hip fracture incidence: Europe

Arden N et al (2000)

Correlates:

• Latitude

• Sunlight

• Activity

• BMI

• Height

• Fall risk

• Not BMD

Geographic variation in hip fracture incidenceUSA; 1984-87

Jacobsen SJ et al JAMA 1990; 264: 500-502

Ecological correlates of hip fractureUSA

• 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

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

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

Rela

tive

rate

of f

ract

ure

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

Rela

tive

rate

of f

ract

ure

Index of Multiple Deprivation Category

Hip

Men

Women

0.90.920.940.960.98

11.021.041.061.08

1.1

1 2 3 4 5

Rela

tive

rate

of f

ract

ure

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

Rela

tive

rate

of f

ract

ure

Index of Multiple Deprivation Category

Vertebral

Men

Women

Curtis E et al. Bone 2016; 87: 19-26

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

Childhood fracture incidence and ethnicityUK: 1988-2012

Moon R et al. Bone 2016; 85: 9-14

Prevalence of Vertebral Deformity EVOS

25

20

15

10

5

0

Pre

vale

nce

(%)

Age (years)

O'Neill et al, J Bone Min Res 1996; 11: 1010-18

50 55 60 65 70 75

MenWomen

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%+

Distribution of Vertebral Fractures

0102030405060708090

100

T4 T5 T6 T7 T8 T9T10 T11 T1

2 L1 L2 L3 L4

Ismail et al, J Bone Min Res (1999)

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

Frac

ture

/100

,000

p-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)

Outcome of Vertebral Fracture

Incidentvertebralfractures

Clinical attention

Hospitalization1-3%

40%

100%

Cooper et al J Bone Min Res 1992; 7: 221-7

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 205074

2

378

1990 2050

100

629Total number of

hip fractures:1990 = 1.66 million 2050 = 6.26 million

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]

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

Trends in hip fracture incidence in CanadaAge-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

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

Ave

rage

yea

rly c

hang

e in

the

inci

denc

e of

hip

frac

ture

s

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

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

Japan 02-06Japan 86-01

Singapore 92-98 Singapore 60-91Hong Kong 85-01Hong Kong 66-85

New Zealand 89-98 New Zealand 79-89Australia 89-00

Canada 92-01 Canada 76-85

Spain 88-02Hungary 93-03

Switzerland 91-00Austria 94-06Germany 95-04

Netherlands 93-02 Netherlands 86-93UK 92-98 UK 78-85

UK 68-78Finland 92-03

Finland 70-97Denmark 87-97

Sweden 92-95Sweden 50-92

Norway 79-99

-10 -5 0 5 10% Annual Change

Secular Trends in Hip Fracture Worldwide

Europe

N. America

Oceania

Asia

USA (Rochester) 28-72USA (Rochester) 72-92USA (Rochester) 80-06 USA (Framingham) 48-96

Cooper C et al Osteop Int 2011; 22: 1277-87

Secular trends in hip fracture

Effects of:

• Age

• Period

• Birth-cohort

Risk factors during adult life

Bone mass(g/Ca)

Age (yr)

1500 -

1000 -

500 -

0 -

0 20 40 60 80 100

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

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

Bone massTarget those with a low

bone density

Bone massMove 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.

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 fracture11.8x

Rel

ativ

e ris

k

Relative risk for a second hip fracture increases

one year after a hip fracture2.2x

“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

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

With thanks to all at Southampton