Transcript ADVANCES IN DIAGNOSIS & TREATMENT OF OSTEOPOROSIS

ADVANCES IN DIAGNOSIS &
TREATMENT OF
OSTEOPOROSIS
Jerry Tenenbaum MD FRCPC
Professor of Medicine:University of Toronto
Mount Sinai Hospital
DISCLOSURES
SPEAKER ON OCCASION FOR
1. P&G
2. Pfizer
3. Merck
4. Novartis
GOAL
Review advances in the diagnosis and
treatment of osteoporosis
OBJECTIVES
1. Show the impact of osteoporosis on the
health of the elderly
2. Advise on screening and diagnosis of
osteoporosis
3. Outline evidence-based treatment
Osteoporosis
Osteoporosis is defined as a skeletal
disorder characterized by compromised
bone strength predisposing to an
increased risk of fracture.
NIH Consensus Development Conference, March 2000
Normal Bone
Osteoporotic Bone
Vertebral Fracture Cascade
THE HUMAN COST
Downward Spiral
Definition of a Fragility Fracture
A fragility fracture is one that results
from mechanical forces that would
not ordinarily cause fracture in a
healthy young adult.
This is quantified as forces
equivalent to a fall from a standing
height or less.
Osteoporosis
8 million Osteoporotic Women and 2.5 million Osteoporotic Men in USA
Expected to increase by about 40% by 2020 1
Estimated Direct costs in 2001 = $ 11.6 - 17.1 billion annually 1
Based on relative older Canadian population 2 &
Australian estimates of 7:1 ratio for Indirect to direct costs 3
 $6 - $40 million every single day in Canada
Mortality increased 2-3 fold in women and women
after all types of Osteoporotic fractures 4
1 Surgeon-Generals
Report
and US census data
3 Access Economics, 4 Center 1999
2 Canadian
Prevalence of VCF’s
Lifetime prevalence in Caucasians:
15% in women
5-9% in men
Higher than risk of breast cancer
Osteoporotic fractures, Cardiovascular events &
Breast cancer
in osteoporotic postmenopausal women
120
Events
per 1000
women-yr
100
80
MORE study
placebo arm
over 3 years
60
40
20
0
Prior spine fracture (1627)
No prior spine fracture (938)
from Silverman et al, 2004
J Am Geriatr Soc 52:1543-8
Fracture and Mortality Risk
SITE
Vertebrae
INCREASE IN
MORTALITY RISK
8.6
Hip
6.7
Any Clinical Fracture
2.2
Each year, one in three Ontarians over the age
of 65 will take a serious tumble that may land
them in hospital with a broken hip. One in three
of those who do break their hip will die within
a year. Two thirds will experience dementia-like
symptoms. Most will never see home again.
Osteoporosis-associated
Mortality
Age-standardised mortality risk
increased 2-3 fold
after all types of osteoporotic fracture
Women
2.2
Men
3.2
Vertebral
1.7
2.4
Other major
1.9
2.2
Proximal femur
Center et al, Lancet 1999
“THE CARE GAP”
IN OSTEOPOROSIS
Despite the introduction of methods to
identify those with osteoporosis and
despite effective treatment, a large
‘care gap’ continues to exist for these
patients.
THE TIP OF THE ICEBERG
ASSESSMENT
MANAGEMENT
Recommendations for Bone
Mineral Density Reporting in
Canada.
Siminoski K, Leslie WD, Brown JP, Frame H, Hodsman A,
Josse RG, Khan A, Lentle BC, Levesque J, Lyons DJ, Tarulli G
Can Assoc Radiol J 2005; 56: 178-188
2002 Definitions: BMD Results
Status 1, 2
T-score
Normal
+2.5 to −1.0, inclusive
Osteopenia
Between −1.0 and −2.5
Osteoporosis
≤−2.5
Severe osteoporosis
≤−2.5 + fragility fracture
1. Kanis JA, et al. J Bone Miner Res 1994;9:1137-1141.
2. WHO, Geneva 1994.
ABOUT
T-SCORES?
Advantages
Disadvantages
Unitless
Depends on site measured
Basis for the majority of
osteoporosis guidelines
Simplicity
Depends on technology
Depends on reference
database—population mean
and standard deviation
Only includes BMD
information and not additional
risk factors
Adapted from Faulkner K. Osteoporos Int 2005;16(4):347-52.
BMD PREDICTS FRACTURES
Fracture Risk
vs. BMD
At Different Ages
Hui et al. J Clin Invest 1988; 81:1804-9
Risk of Fractures Over 10 Years in Women
AGE
T-Score
= -1.0
T-Score
= -2.5
50
6%
11 %
60
8%
16 %
70
12 %
23 %
80
13 %
26 %
Proposed Change
Previous OSC guidelines advised intervention
based on WHO category as a marker of relative
fracture risk.
Now propose that an individual’s 10-year
absolute fracture risk, rather than BMD alone,
be used for fracture risk categorization
5-STEPS IN
TREATING OSTEOPOROSIS
STEPS 1 and 2
Begin with the table appropriate for
the patient’s sex
Identify the row that is closest to
the patient's age
CATEGORIZATION BASED ON 10-YEAR
FRACTURE RISK
Absolute fracture risk in 10 years:
low:
<10%
moderate: 10-20%
high:
>20%
USING LOWEST T-SCORE TO FIND 10-YEAR
FRACTURE RISK - WOMEN
WOMEN
0.0
LOWEST T-Score
-0.5
Low Risk
-1.0
Moderate Risk
-1.5
-2.0
-2.5
-3.0
High Risk
-3.5
-4.0
-4.5
50
55
60
65
70
AGE (years)
75
80
85
5-STEPS IN
TREATING OSTEOPOROSIS
STEP 3
Determine the preliminary fracture risk
category by using the lowest T-score
from the recommended skeletal sites
5-STEPS IN
TREATING OSTEOPOROSIS
STEP 4
Evaluate clinical factors that may move
the patient into an even higher fracture
risk category
USING LOWEST T-SCORE TO FIND 10-YEAR
FRACTURE RISK - MEN
MEN
LOWEST T-Score
0.0
-0.5
-1.0
Low Risk
-1.5
-2.0
Moderate Risk
-2.5
-3.0
-3.5
High Risk
-4.0
-4.5
50
55
60
65
70
AGE (years)
75
80
85
Additional Clinical Factors
Certain clinical factors increase fracture
risk independent of BMD.
The most important are:
– Fragility fractures after age 40 (especially
vertebral compression fractures)
– Systemic glucocorticoid therapy >3 months
duration.
Additional Risk Factors
Each factor effectively increases risk
categorization to the next level:
– from low risk to moderate risk, or
– from moderate risk to high risk
When both factors are present the
patient should be considered at high
risk regardless of the BMD result.
5-STEPS IN
TREATING OSTEOPOROSIS
STEP 5
Determine the individual’s final
absolute fracture risk category.
CASE EXAMPLE
Woman – age 52
- t is -2.6
Fracture Risk Category?
CASE EXAMPLE
WOMEN
0.0
LOWEST T-Score
-0.5
Low Risk
-1.0
Moderate Risk
Low Risk
-1.5
Moderate Risk
-2.0
-2.5
-3.0
High Risk
-3.5
High Risk
-4.0
-4.5
50
55
60
65
70
AGE (years)
75
80
85
CASE EXAMPLE
WOMEN
AGE
LOW
<10%
10-YEAR RISK
MODERATE
10 to 20%
50
55
60
65
70
75
80
85
>-2.3
>-1.9
>-1.4
>-1.0
>-0.8
>-0.7
>-0.6
>-0.7
-2.2-2.2
to -3.9
-3.9
1.9 to -3.4
-1.4 to -3.0
-1.0 to -2.6
-0.8 to -2.2
-0.7 to -2.1
-0.6 to -2.0
-0.7 to -2.2
HIGH
>20%
<-3.9
<-3.4
<-3.0
<-2.6
<-2.2
<-2.1
<-2.0
<-2.2
CASE EXAMPLE
Fracture Risk Category
Moderate Risk
CASE EXAMPLE
Fracture Risk Category
Moderate Risk
If Fragility Fracture History
High Risk
CASE EXAMPLE
70 year-old man
BMD done because of strong family
history of osteoporosis (mother fractured hip, sister
has OP)
Lowest T-score –2.7 in total hip
USING LOWEST T-SCORE TO FIND 10-YEAR
FRACTURE RISK - MEN
MEN
LOWEST T-Score
0.0
-0.5
-1.0
Low Risk
-1.5
-2.0
Moderate Risk
-2.5
-3.0
X
-3.5
High Risk
-4.0
-4.5
50
55
60
65
70
AGE (years)
75
80
85
CASE EXAMPLE
Fracture Risk Category
Moderate Risk
OTHER ISSUES FOR THIS 70
YEAR OLD MALE
Chest x-ray – mild loss of vertebral height
at T4, T5
What if he had had polymyalgia
rheumatica at age 69 and was on
prednisone 10 mg./day?
CASE EXAMPLE
Fracture Risk Category
Moderate Risk
If Fragility Fracture History,
Corticosteroid use
High Risk
Endorsements
Canadian Association of Nuclear Medicine
Canadian Association of Radiologists
Canadian Rheumatology Association
International Society of Clinical Densitometry
Society of Obstetricians and Gynecologists of Canada
Canadian Society of Endocrinology and Metabolism
Canadian Orthopedic Association
College of Family Physicians of Canada
Osteoporosis Prevention and
Treatment
Hormonal Replacement
SERM
Bisphosphonates
Treatment
choice
Strontium
PTH
Vitamin D
Life Style
20
40
60
80
Age
Antifracture efficacy of antiosteoporotic agents
Incident vertebral fractures
Relative risk
Incident nonvertebral fractures
Relative risk
RR ± 95% CI
RLX 60 (MORE)*
RLX 60 (MORE)**
RLX 60, 120
(MORE)***
ALN 5/10 (FIT1)*
ALN 5/10 (FIT1)*
ALN 5/10 (FIT2)**
ALN 5/10 (FIT2)**
RIS 5 (VERT-NA)*
RIS 5 (VERT-NA)*
RIS 5 (VERT-MN)*
RIS 5 (VERT-MN)*
RIS 2.5/5 (Hip Study)***
CT 200 (PROOF)*
CT 200 (PROOF)*
Teriparatide 20µg*
Teriparatide 20µg*
Strontium ranelate
(SOTI)*
Strontium ranelate
(SOTI)*
Strontium ranelate
(SOTI +TROPOS)**
Strontium ranelate
(TROPOS)***
0.2
0.6
1.0
* with prev vert fracture(s) ** without prev vert fractures
0.2
0.6
1.0
*** with or without prev verfractures
Updated from Delmas, Lancet 2002
Medications Available for
Post-Menopausal Osteoporosis
Actonel® (risedronate sodium tablets) (1/day;1/wk; 1/mo)
Didrocal® (etidronate sodium tablets)
Fosamax® (alendronate sodium tablets) 1day/1/wk; Fosovance)
Aclasta ® (zolendronate IV)
Estrogen (some use)
Evista® (raloxifene HCl)
Miacalcin® (calcitonin salmon) Nasal Spray
Forteo (Teriparatide) (sc)
Consult with your physician to determine what medication may
be best for you
Lumbar spine fracture rate
(fractures/100 patient-years)
Bisphosphonates — Cyclical
Etidronate
50
43
40
30
18
20
10
0
Placebo (n = 20)
•
•
•
Etidronate (n = 20)
3-year RCT, 66 subjects
High risk subgroup: reduction in fracture rate with etidronate, p = 0.023
No statistically significant effect at nonvertebral sites
p=NS
Storm T. N Engl J Med 1990;322:1265.
Cumulative Hip Fracture
Incidence
80 fractures
n= 21,615
0.58
% of cohort with a hip fracture
alendronate
0.50
0.40
29 fractures
n = 12,215
0.30
risedronate
0.20
0.10
0.00
Baseline
↓ 46%*
↓ 43%*
Adjusted Relative Rate
Reduction at Month 6
p = 0.02
95% CI: 9% - 68%
Adjusted Relative Rate
Reduction at Month 12
p = 0.01
95% CI: 13% - 63%
Month 6
Month 12
Silverman SL. Osteoporos Int 2007 Jan;18(1):25-34. Epub 2006 Nov 15.
Osteoporosis in Men
Has Its Time Come?
HEADLINES
7.8.07
HIP FRACTURES
MORBIDITY AND MORTALITY
“One-third of all hip fractures occur in men and are
associated with as much illness and increased risk
of death as those that occur in women .”
“The average 50-year-old Caucasian man has a 13
per cent chance of having a fracture related to
osteoporosis sometime in his remaining lifetime. A
60-year-old Caucasian man has a 29 per cent
chance.”
Dr. John Schousboe, Minneapolis 2007
Male Osteoporosis: Morbidity and
Mortality
As compared to women, while lifetime
fracture risk may be less,
– Men have higher rates of morbidity and
mortality due to fractures
– Men are twice as likely to die in hospital after
a hip fracture
– Men have a higher mortality rate than women
one year after a hip fracture
Cooper C, et al. Osteoporos Int 1992;2:285-9; Singer BR, et al. J Bone Joint Surg
Br 1998;80:243-8; Center JR, et al. The Lancet 1999;353:878-82; Forsen L, et al.
Osteoporos Int 1999;10:73-8; Johnell O., et al. Calcif Tissue Int 2001;69:182-4;
Amin S. Curr Osteoporos Rep 2003;1:71-7; Campion JM, et al. Am Fam Phys
GLUCOCORTICOIDS and BONE
Have a reflex! SGC > 3 mo > 7.5 mg./day
-Ca, vitamin D, bisphosphonate
Bone density evaluation?
Back injuries. If you think that golf is for wimps, consider
this: A golf swing puts a higher compressive load on the
low back (8 times body weight) than running (3 times) or
even rowing (7 times). That’s why a single swing can
produce a herniated disc or even a compression fracture
of one of the vertebral bodies. Although these injuries
are extremely painful and can be quite serious, they are
rare. Muscle strains, however, are quite common
because of the twisting that is required for a good swing.
The “modern” swing, with its inverted-C follow-through,
may make for longer drives than the “classic” swing but it
also produces more torque — and more injuries (see
Golf injuries above).
Harvard Men’s Health Watch Aug 2004
SUMMARY
REDUCING THE ‘CARE GAP’
Assess bone health in woman >50 and in
men > 60.
Evaluate risk factors; evaluate BMD
Consider preventative approach to
reduction of fracture risk (the way you
think of hypertension and MI and stroke)
Treat and monitor