1. 골절 예방의 중요성과 비척추골절 예방 효과
정 호 연 경희대학교 동서신의학 병원

2. Annual Incidence in the US x 1000
Osteoporotic Fractures in Women: Comparison With Other Diseases
Vertebral Fx: 70 만건
Hip Fx: 30 만건
Wrist Fx: 25 만건
기타: 25 만건
2000
1500
Annual Incidence in the US x 1000
1000
500
Osteoporotic
Fractures
Heart
Attack
Stroke
Breast
Cancer
1Osteoporosis Fast Facts. National Osteoporosis Foundation National Institutes of Health. Healthy Heart Handbook for Women Statistical Information on Women and Women’s Health. US Department of Health and Human Services

4. (5713 women aged between 50 and 85 years)
Estimated prevalence of female osteoporosis, measured at the fermoral neck, by age band
Data from UK
(5713 women aged between 50 and 85 years)
Br J Radiol 75:736, 2002

5. NHANES, source: NOF, 2002

6. Osteoporosis - An Epidemic Yet to Come
Europe, USA,
Oceania, Russia
Asia, Middle East
Lat America, Africa
3500
Hip Fractures in Asia
Hip fracture incidence (HK): 300%  over 30 years
In 2050, more than 50% of hip fractures will occur in Asia
3000
2500
Hip Fractures, x1000
2000
1990
2025
1500
2050
1000
500
Men
Women
Men
Women

7. All fractures are associated with morbidity
Unable to carry out at least one independent
activity of daily living
80%
One year after an hip fracture:
Patients (%)
Unable to walk
independently
40%
Permanent
disability
Death within
one year
30%
20%
Cooper C, Am J Med, 1997;103(2A):12S-17S

9. Mortality Following Hip and Vertebral Fractures
Years after fracture
Source: Cooper Am J Med 103(2A):12S-19S

14. FALLS AND FRACTURE
The incidence of wrist fracture is parallel to the incidence of falls in women. Winner et al, Br med J 1989
The nature of the fall determines the type of fracture.
Nevitt et al, JAGS 1993
forward: wrist
sideways: hip
1/3 of people > 65 years old fall each year
6% of falls result in fracture
1% are associated with hip fracture (90% of hip fractures are associated with falls). Tinetti et al, N Engl J Med 1997

15. Number of Baseline Vertebral Fractures
The Fracture Cascade
Overall, 20% fractured again within the year following a new fracture
Risk of fracture increased with the number of baseline fractures 30 * 25 20
% of Patients 15 10 5
Overall 1 2+
Number of Baseline Vertebral Fractures
*p<0.05, vs patients with no prevalent vertebral fractures (12-fold increased risk).
Lindsay R, et al. JAMA. 2001;285:

16. NON VERTEBRAL FRACTURE IS A RISK FACTOR FOR OTHER FRACTURES
N = 2548 placebo patients
Prior NON VERT FRACTURE
Yes No
Subsequent NON VERT Fracture
Subsequent VERT Fracture

17. Increased risk of subsequent fracture following an initial fracture
A Medline search was performed using the search terms “osteoporosis” and “fractures” to identify all articles in English from January 1966 up to September 1999.
A total of 3576 articles were identified and performed a statistical synthesis of the risk of future fracture, given a history of prior fracture.
JBMR 15:721, 2000

18. Risk factors for proximal humerus fracture
Related to
Femoral neck BMD
Calcaneal SOS
Maternal history of hip fracture
History of falls
Number of physical activities
Static balance
Ankle or foot pain
1.4 ( )
1.3 ( )
1.8 ( )
1.1 to 3.0 ( )
1.4 to 2.2 ( )
1.8 ( )
1.4 ( )
Osteoporosis + -
Fall Risk Score
Low
High
Incidence per 1000 woman-years
5.1
3.8
5.3
12.1
Lee et al, JBMR 2002

19. INDIVIDUAL RISK ASSESSMENT ROTTERDAM STUDY
Age (per 5 years)
Gender (female)
Height (5cm class)
Use of walking aid (yes/no)
Current cigarette smoking (yes/no)
BMD (0.05g/cm²)
OR (95% CI)
1.8 ( )
2.6 ( )
1.5 ( )
2.7 ( )
2.2 ( )
1.5 ( )
Point 6 9 4 10 8
Burger et al Bone 1999

20. INDIVIDUAL RISK ASSESSMENT
Black et al, Osteoporos Int 2001

21. Risk factors used in the calculation of 10-year risk of fracture
Femoral neck T-score
Age
Previous low trauma fracture
Low BMI
Ever steroid exposure
Family history of hip fracture
Current cigarette smoking
High alcohol intake (> 2 units/day)*
*1 unit = 8 gm alcohol ~ ½ pt. beer ~ glass wine
Kanis JA et al, Bone, 2002;30:
Kanis JA et al, Osteoporos Int, 2005;16:

22. Hierarchy of clinical evidence
EBM and osteoporosis
Decision
making

23. Magnitude of effect on vertebral fractures
Summary of meta-analyses of therapies for postmenopausal osteoporosis. Endocrine Rev 2002; 23:570–8. ( without WHI data of hormone therapy)

24. Magnitude of effect on nonvertebral fractures
Summary of meta-analyses of therapies for postmenopausal osteoporosis. Endocrine Rev 2002; 23:570–8. ( without WHI data of hormone therapy)

25. Magnitude of therapy effect on fracture risk reduction5

26. 여성호르몬에 대한 장점과 위험성 Estrogen + progestin Estrogen only Benefit (RR)
(WHI, JAMA 288:321, 2002)
Estrogen only
(WHI, JAMA 291:1701, 2004)
Benefit
(RR)
Colon Ca: 0.63 ( )
Hip fx: 0.66 ( )
Colon Ca: 1.08 ( )
Hip fx:0.61( )
Risk
Breast Ca: 1.26( )
CHD: 1.29 ( )
Stroke: 1.41( )
PE: 2.13 ( )
Bresat Ca:0.77( )
CHD: 0.91:( )
PE:1.34 ( )
Stroke: 1.39( )

27. 폐경후 골다공증 치료에서 새로운 약제의 비교 PTH Strontium Ibandronate Zoledro nate 투여방법SC PO IV
투여 용량
20 mg
2 g
2.5 mg
150 mg
3 mg
5 mg
사용법 매일
q 1개월
q 3개월
q 1년 LS
BMD
+9.7%
( 18 개월 )
+14.4% (8.1%)
( 3년 )
+6.5%
+6.6%
( 2년 )
+6.3% + FN
+2.8%
+8.3%
>3% 척추
골절율
- 65%
- 41%
- 62%
-70%
비척추
- 53%
- 19%
- 69%
(고위험군)
-25%
대퇴골
36%
-40% 특징
FDA 공인
골생성 촉진제
골생성 촉진
골흡수 감소 사용
편리성
1년 간격 치료 기타
고 비용
간헐적 용법
골밀도 과대평가
위장관 장애
근육통 발열

28. How can we evaluate anti-fracture efficacy of Osteoporosis?
EMEA
ITT analysis over 3-years required
Most studies have focused on prevention of vertebral fractures
Non-vertebral fractures: often subgroup analysis
European Agency for the Evaluation of Medicinal Products (EMEA)
The gold standard for demonstration of anti-fracture
efficacy in osteoporosis trials is the primary predetermined
analysis of the intention to treat (ITT)
population; this is highlighted by the requirement of
fracture prevention efficacy in trials of at least 3-year
duration for registration of new therapies
The majority of these trials have focused on the prevention
of vertebral fracture, with assessment of efficacy in the
prevention of non-vertebral fracture relying largely on
the analysis of subgroups. The use of subgroup analyses
to demonstrate efficacy of a new treatment is not
in line with recognized scientific standards and should
be interpreted with caution.

29. New ITT and meta-analysis regarding non-vertebral antifracture efficacy
Inclusion:
3-year clinical trials of ITT populations that met regulatory registration criteria
Boonen S et al. Osteoporos Int 2005; 16:

30. Trials Included in the ITT Analysis Characteristics and Results
Drug
Trial
Age
Prevalent #
Total N
Length
nv#incidence PBO
nv#incidence Active
P-value
ARR
ALN
Libermann 64
21%
994 3J
10.7%
8.5% NA
2.2%
FIT VFA 71
100%
2027
14.7%
11.9%
0.06
2.8%
FIT CFV 68 0%
4432 4J
13.3%
11.8%
0.13
1.5%
RIS
VERT-MN
98%
812
16.0%
10.9%
5.1%
VERT-NA 69
78%
1627
8.4%
5.2%
0.02
3.2%
HIP 78
30%
9331
11.2%
9.4%
0.03
1.8%
RAL
MORE 66
37%
6828
9.3%
Strontium
TROPOS 77
34%
4932
12.9%
0.04
1.7%
SOTI
1442
16.9%
15.6%
1.3%
IBN
BONE
94%
2929
8.2%
9.1%/ 8.9%
-0.9/-0.7%
Calcitonin
PROOF
79%
620 5J
15.7%
14.6%
1.1%
Boonen S et al. Osteoporos Int 2005; 16:

31. Anti-nonvertebral fracture efficacy of alendronate and risedronate in ITT

32. Funnel Plot of Six Trials with Alendronate and Risedronate
ALN
10.000
9000
8000
Results of meta-analysis were significant for:
Alendronate (RR=0.86; 95% CI ) and
Risedronate (RR=0.81; 95% CI )
demonstrating non-vertebral anti-fracture efficacy
7000
6000
Sample size
5000
4000
3000
2000
1000
0.0
0.5
1.0
1.5
2.0
Relative risk
Boonen S et al. Osteoporos Int 2005; 16:

33. Non-Vertebral Fracture Incidence by Treatment
Libermann
FIT VFA
FIT CFV
VERT-MN
VERT-NA
HIP
MORE
TROPOS
SOTI
BONE
PROOF
Alendronate
Risedronate * *
Raloxifene *
Strontium
Ibandronate
Calcitonin
0.5
1.0
1.5 RR
Boonen S et al. Osteoporos Int 2005; 16:

34. Fractures incidence (%)
Effects of Treatments on Non-vertebral fractures * * *
Fractures incidence (%)
FIT 1, FIT 2 : The studies for Alendronate
VERT-MN, VERT-NA, HIP : The studies for Risedronate
MORE : The study for Raloxifene
BONE : The study for Ibandronate
TROPOS : The study for Strontium *
placebo
(No head to head studies)
* p < 0.05
Anti-osteoporotic agent

35. Summary of ITT- and Meta-analysis on Non-Vertebral Fractures
Out of 11 clinical trials meeting criteria for review
3 showed significant results within the trial
2x Risedronate
1x Strontium-ranelate
Results of meta-analysis of Alendronate and
Risedronate showed that both are comparably
Efficacious in preventing non-vertebral fractures
Boonen S et al. Osteoporos Int 2005; 16:

36. Need for Complete Fracture Protection
Devastating impact of osteoporosis in terms of morbidity and mortality
Identify individuals most at risk of sustaining vertebral and non-vertebral fractures
Treat to reduce the risk of both vertebral and non-vertebral fractures