1. Prevention and Treatment of Osteoporosis
4/27/2017
Prevention and Treatment of Osteoporosis
Jane A. Cauley, DrPH
University of Pittsburgh

2. Osteoporotic Bone Loss
4/27/2017
Osteoporotic Bone Loss
A skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. Bone Strength:
Bone Density: Grams of mineral per area or volume (70% bone strength)
Bone Quality:
Architecture
Turnover
Damage accumulation
Mineralization
Normal Bone
NIH. Consensus Conference Statement. 2000;17(1):1-36.
WHO. Available at:
These figures illustrate the changes in bone architecture at the microscopic level that are characteristic of osteoporosis.
Normal trabecular bone, as shown on the left, appears as a dense network of thick trabeculae with small spaces.
Osteoporotic trabecular bone, on the right, shows clear loss of bone, with large spaces and perforation of the trabecular network (see arrows). These perforations lead to weakened bone, and ultimately to fractures.
This bone loss and architectural damage is relatively rapid in the perimenopausal phase of PMO and has been reported to be rapid in patients initiating chronic glucocorticoid therapy.
Osteoporosis

3. World Health Organization (WHO) Osteoporosis Guidelines
4/27/2017
World Health Organization (WHO) Osteoporosis Guidelines
WHO, Guidelines for Preclinical Evaluation and Clinical Trials in Osteoporosis, 1998.
Speaker’s Notes
It should be noted that these guidelines are based on data from postmenopausal Caucasian women; they may not be applicable to other races or ethnic groups.
Patients with osteopenia may still be at risk for fracture.
There are patients with osteopenia who have fractures already. Many physicians are confused about this phenomenon. For example, a patient having a T-score –2.2 is at significant risk for fracture even though osteopenic.
T-Score

4. Densitometric Diagnosis of Osteoporosis
4/27/2017
Densitometric Diagnosis of Osteoporosis
Age, Gender and Race Differences
Adjust Bone Differences to a STANDARD
T-score
Z-score
Comparison to young normals
What is desirable
Assess fx risk
Comparison to age, gender, race, peers
What is expected
Assess BMD unusually low

5. Both t-scores and z-scores Expressed as Standard Deviation (SD) Scores
4/27/2017
Both t-scores and z-scores Expressed as Standard Deviation (SD) Scores
Calculation Example
t-score = Patient BMD – BMD of Young Normals
1 SD of Young Normals
Example
PT BMD = 0.8 g/cm Mean Young Normals = 1.0
SD= 0.10
t-score = = -2.0
0.10

6. 4/27/2017
Who has osteoporosis?

7. Number of Women age 50+ with Osteoporosis and Low Bone Mass: 2002 – 2020
4/27/2017
# in Millions
America’s Bone Health: The State of Osteoporosis and Low Bone Mass in our Nation. NOF 2002

8. Prevalence of Osteoporosis (Hip BMD) by Age for Caucasian Women
4/27/2017
Prevalence of Osteoporosis (Hip BMD) by Age for Caucasian Women
100%
80%
52%
60%
Prevalence
34%
40%
20%
Looker AC, et al. J Bone Miner Res. 1997;12(11):
20% 4% 0%
50-59
60-69
70-79
80+
Age (Years)

9. Frequency of Hip Fractures worldwide as a ratio of rates observed to those expected for white women in USA
4/27/2017
Cummings and Melton Lancet 2002; 359: 1761

10. Projected Burden of Osteoporotic Hip Fracture Worldwide
4/27/2017
3,250,000
1,000,000
800,000
600,000
400,000
200,000
Cooper et al. Osteo Int 1992; 2:
North America
Europe
Latin America
Asia
1990 = 1.66 million 2050 = 6.26 million

11. Prevalence of Vertebral Fractures by Age
4/27/2017
Prevalence of Vertebral Fractures by Age
Cummings and Melton Lancet 2002; 359: 1761
Age

12. Annual incidence of common diseases
4/27/2017
OSTEOPOROTIC FRACTURES ARE MORE COMMON IN WOMEN THAN HEART ATTACK, STROKE, AND BREAST CANCER COMBINED1-3
2,000,000 *
1,500,000
1,500,000
250,000 hip
Annual incidence of common diseases
250,000 forearm
1,000,000
250,000 other sites **
513,000 †
1. Riggs, B.L., and Melton, L.J. III, Bone 17(5)(Suppl.):505S-511S, 1995
2. Heart and Stroke Facts: 1996 Statistical Supplement, American Heart Association
3. Cancer Facts & Figures—1996, American Cancer Society
This slide demonstrates that the incidence of osteoporotic fracture in women is far greater than the incidence of heart attack, stroke and breast cancer combined. This information couples nicely with the information on the previous slide to further emphasize that osteoporosis should be considered a major health concern among postmenopausal women in the United States. The point is not to suggest that osteoporosis is more important than the other diseases, but rather that it should be managed as routinely as are the other diseases.
500,000
228,000 ‡
750,000 vertebral
184,300
Osteoporotic
Heart Attack
Stroke
Breast Cancer
Fractures
* annual incidence all ages ** annual estimate women 29+
† annual estimate women 30+ ‡ new cases, women all ages

13. Lifetime Fracture Risk in 50 Year Old Caucasian Men&Women
4/27/2017
Lifetime Fracture Risk in 50 Year Old Caucasian Men&Women
Women (%)
Men (%)
Hip
17.5
6.0
Spine
15.6
5.0
Wrist
16.0
2.5
Any of above
39.7%
13.1%
Black Women : 6%; Black men 3%
Melton LJ et al. JBMR 1992; 7:

14. Five Year Fracture Risk in white women at various ages and t-scores
4/27/2017
Cummings SR et al JAMA 2002;288: 1889

15. Five Year Fracture Risk in white women at various ages and t-scores
4/27/2017
Cummings SR et al JAMA 2002;288: 1889

16. Five Year Fracture Risk in white women at various ages and t-scores
4/27/2017
Five Year Fracture Risk in white women at various ages and t-scores
Cummings SR et al JAMA 2002;288: 1889

17. Lifetime Risk Of Hip Fracture for White women by Age and T-score

18. What are the consequences of osteoporosis?
Mortality
Morbidity
Economic

19. One Year Mortality After a Hip Fracture+
4/27/2017
One Year Mortality After a Hip Fracture+
% Mortality
(972 Patients; 19% Male)
Keene GS et al. Br Med J 1993;307:
Age at fracture

20. 4/27/2017
Increased Mortality associated with Radiographic Vertebral Fractures Study of Osteoporotic Fractures (SOF) 50 40 30
Mortality (1000 Person-Years) 20 10 1 2 3 4 ³5
Number of Vertebral Fractures
N=9575
Kado DM, et al.Arch Intern Med.1999;159:
p for trend <.001

21. Morbidity: Recovery to Pre-fracture Status One Year After Hip Fracture
60.0%
48.5%
51.5%
40.0%
Walking
Physical ADL’s
Recovered Not Recovered
Magaziner et al. J Geront 1990; 45: M101-7

22. SOF Incident Vertebral Fractures Are Associated with Back Pain and Disability
4/27/2017
Back Disability
Back Pain *
60%
55%
60% *
50%
50%
44% * *
38%
40%
36%
40%
% With Back Disability
% With Back Disability
30%
30%
22%
20%
17%
20%
Nevitt et al. Annals Int Med;7:4.
* p<0.01 vs No new deformity, adj age, BMI, strength, smoking, HRT, other fxs, dx osteoporosis
10%
10% 0% 0% No 1
2 or No 1
2 or
More
More

23. Economic Burden of Osteoporotic Fractures in the US
4/27/2017
Economic Burden of Osteoporotic Fractures in the US
Osteoporotic fractures account for:
~$20 billion in direct medical costs
547,000 hospital admissions
4.6 million hospital bed days
~2.5 million physician visits
>180,000 nursing home admissions
Projected direct costs of osteoporosis by 2040: ~$50 billion
Cummings and Melton Lancet 2002; 359: 1761

24. OVERVIEW OF RISK FACTORS

25. Pathogenesis of Osteoporotic Fractures
4/27/2017
Pathogenesis of Osteoporotic Fractures
Other Risk Factors
Aging
Menopause
Genetics
Decreased Bone Mass
Low Peak Bone Mass
Genetics
Low Bone Density
Figure reprinted from National Osteoporosis Foundation, Physician’s Guide to Prevention and Treatment of Osteoporosis. Modified from Riggs BL, Melton LJ: Etiology, Diagnosis and Management. New York: Raven Press; 1988.
Poor Bone Quality
Propensity to Fall
Fractures

26. PREVALENT VERTEBRAL FRACTURE INCREASES RISK OF SUBSEQUENT FRACTURE
4/27/2017
PREVALENT VERTEBRAL FRACTURE INCREASES RISK OF SUBSEQUENT FRACTURE
Study Follow-Up R.R. of Subsequent Fracture
(Years) Vertebral Hip
Hawaii
Mayo
SOF
MORE
Risedronate studies
1. Ross PD, et al. Ann Intern Med. 1991;114: Kotowicz MA, et al. J Bone Miner Res. 1994;9: Black DM, et al. J Bone Miner Res. 1999;14: Ettinger B, et al. JAMA. 1999;282: Lindsay R, et al. JAMA. 2001;285:

27. BONE DENSITY PREDICTS FRACTURE RISK (META-ANALYSIS)
11 prospective cohort studies 90,000 person-years observation
>2,000 fractures
Age-adjusted relative risk
for 1 SD decrease in BMD
Hip Vertebral
Site
Fracture Fracture
Distal radius
Proximal radius
Calcaneus
Spine
Femoral neck
Marshall D et al, BMJ 1996;312:1254