Transcript Care Working Group - Osteoporosis Canada

2010 Guidelines
2010 Clinical Practice
Guidelines for the
Diagnosis and Management
of Osteoporosis in Canada
Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].
2010 Guidelines
Fracture Risk Assessment
Section Four
2010 Guidelines
Indications for BMD Testing in Older
Adults (Age > 50 Years)
•
•
All women and men age > 65
Postmenopausal women, and men aged 50 – 64 with clinical risk factors
for fracture:
–
–
–
–
–
–
–
–
–
–
† At
Fragility fracture after age 40
Prolonged glucocorticoid use†
Other high-risk medication use*
Parental hip fracture
Vertebral fracture or osteopenia
identified on X-ray
Current smoking
High alcohol intake
Low body weight (< 60 kg) or major weight loss (>10% of weight at age 25)
Rheumatoid arthritis
Other disorders strongly associated with osteoporosis
least three months cumulative therapy in the previous year at a prednisone-equivalent dose ≥ 7.5 mg daily;
* e.g. aromatase inhibitors, androgen deprivation therapy.
2010 Guidelines
Indications for BMD Testing for
Individuals Under Age 50 Years
•
•
•
•
Fragility fracture
Prolonged use of glucocorticoids*
Use of other high-risk medications†
Hypogonadism or premature
menopause
• Malabsorption syndrome
• Primary hyperparathyroidism
• Other disorders strongly associated with rapid bone
loss and/or fracture
† At
least three months cumulative therapy in the previous year at a prednisone-equivalent dose ≥ 7.5 mg daily;
* e.g. aromatase inhibitors, androgen deprivation therapy.
2010 Guidelines
BMD Reporting Categories
Age
Category
Criteria*
Below expected range for age
Z-score < -2.0
Within expected range for age
Z-score > -2.0
Severe (established)
osteoporosis
T-score < -2.5 with fragility
fracture
Osteoporosis
T-score < -2.5
Low bone mass
T-score -1.1 to -2.4
Normal
T-score > -1.0
< 50 years
> 50 years
Click here for a list of considerations about BMD reporting.
2010 Guidelines
Absolute 10-year Fracture-Risk Tools
• Tools validated in Canada (choice based on
personal preference and convenience)
– CAROC: Joint initiative of the Canadian Association of
Radiologists and Osteoporosis Canada1
– FRAX: Fracture Risk Assessment Tool developed by the
World Health Organization2
• There are large differences in fracture rates from
country to country3-5
– Assessment tools need to be country specific
1. Leslie WD, Berger C, et al. Osteoporosi Int; In press..
2. Leslie WD, Lix LM, et al. Osteoporosi Int; In press.
3. Kanis JA, et al. J Bone Miner Res 2002; 17(7):1237-1244.
4. Melton LJ, III. Endocrinol Metab Clin North Am 2003; 32(1):1-13.
5. Leslie WD, et al. J Bone Miner Res 2010; in press.
2010 Guidelines
10-year Risk Assessment: CAROC
• Semiquantitative method for estimating 10-year
absolute risk of a major osteoporotic fracture* in
postmenopausal women and men over age 50
– Stratified into three zones (Low: < 10%, moderate,
high: > 20%)
• Basal risk category is obtained from age, sex, and
T-score at the femoral neck
* Combined risk for fractures of the proximal femur, vertebra [clinical], forearm, and proximal humerus.
Other fractures attributable to osteoporosis are not reflected; total osteoporotic fracture burden is underestimated
Siminoski K, et al. Can Assoc Radiol J 2005; 56(3):178-188.
2010 Guidelines
10-year Risk Assessment for Women
(CAROC Basal Risk)
Click here for CAROC risk assessment in table format.
Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].
2010 Guidelines
10-year Risk Assessment for Men
(CAROC Basal Risk)
Click here for CAROC risk assessment in table format.
Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].
2010 Guidelines
Risk Assessment with CAROC:
Important Additional Risk Factors
• Factors that increase CAROC
basal risk by one category
(i.e., from low to moderate or
moderate to high)
– Fragility fracture after age 40*1,2
– Recent prolonged systemic
glucocorticoid use**2
* Hip fracture, vertebral fracture, or multiple fracture events should be considered high risk
** >3 months use in the prior year at a prednisone-equivalent dose ≥ 7.5 mg daily
1. Siminoski K, et al. Can Assoc Radiol J 2005; 56(3):178-188.
2. Kanis JA, et al. J Bone Miner Res 2004; 19(6):893-899.
2010 Guidelines
Example of Adjusting Basal Risk:
Based on Additional Risk Factors
•
0.0
Femoral neck T-score
• 60-year-old woman
• Femoral neck
T-score = -2.8
• Based on age
and T-score alone
= moderate risk
History of fragility
fracture or prolonged
systemic glucocorticoid
use would shift her
to high risk
-0.5
-1.0
LOW RISK (<10%)
-1.5
-2.0
MODERATE
RISK
-2.5
-3.0
HIGH RISK (> 20%)
-3.5
-4.0
50
55
60
65
70
75
80
85
Age (years)
Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].
2010 Guidelines
Risk Assessment Using FRAX
• Uses age, sex, BMD, and clinical risk factors to
calculate 10-year fracture risk*
– BMD must be femoral neck
– FRAX also computes 10-year probability of hip fracture
alone
• This system has been validated for use in Canada1
• There is an online FRAX calculator with detailed
instructions at: www.shef.ac.uk/FRAX
* composite of hip, vertebra, forearm, and humerus
1. Leslie WD, et al. Osteoporos Int; In press.
2010 Guidelines
FRAX Tool: On-line Calculator
www.shef.ac.uk/FRAX.
2010 Guidelines
FRAX Clinical Risk Factors
•
•
•
•
•
•
Parental hip fracture
Prior fracture
Glucocorticoid use
Current smoking
High alcohol intake
Rheumatoid arthritis
2010 Guidelines
Absolute Fracture Risk Tools
• Calculate risk for treatment-naïve patients only
• Cannot be used to monitor response to
therapy
• Using CAROC or FRAX in a patient on therapy only
reflects the theoretical risk of a hypothetical patient
who is treatment naïve and does not reflect the risk
reduction associated with therapy
2010 Guidelines
Laboratory assessment:
Bone Turnover Markers (BTMs)
• The value of bone turnover markers (BTMs) in
estimating future risk of fracture in individual
patients needs further research
• As a result, BTMs have not yet been integrated
in current fracture-risk assessment systems
Brown JP, et al. Clin Biochem 2009; 42(10-11):929-42.
2010 Guidelines
VFA Recognition and Reporting
• VFA is a scanning and
software option on bone
densitometers
• A fracture detected by
vertebral fracture
assessment (VFA) or
radiograph should be
considered a prior fracture
under the FRAX or
CAROC system
VFA
JB6/23/04;WW5/11/04 IVA/VFA
2010 Guidelines
• On the left we see a
normal lateral VFA
(vertebral fracture
assessment) showing
no vertebral fracture
as high as we can
see (T6).
• On the right, we see
a lateral VFA with a
wedge fracture of
T12
2010 Guidelines
Impact of Prior Vertebral Fracture
on Risk Assessment
• Unequivocal vertebral fractures unrelated to
trauma are associated with a five-fold
increased risk for recurrent vertebral fractures
• A fracture detected from VFA or radiograph
alone should be considered a prior fracture
under the FRAX or CAROC system
2010 Guidelines
Fracture Risk Assessment after Age 50:
Summary Statements
Statement
Strength
Clinical risk factors (especially age, prior fragility fracture
and prolonged glucocorticoid exposure) enhance fracture
prediction independent of BMD alone
Level 1
The Canadian FRAX tool and CAROC are well calibrated for
prediction of major osteoporotic fracture risk
Level 1
The CAROC model shows a high overall degree of
concordance in risk categorization with the Canadian FRAX
system
Level 1
Click here for a summary of the grading system for levels of evidence.
2010 Guidelines
Recommendations for Fracture Risk
Assessment
Recommendation
Grade
Absolute fracture risk assessment should be based on
established factors including age, BMD, prior fragility fracture, and
glucocorticoid use
A
The 2010 CAROC and Canadian FRAX should be used in
Canada since they have been validated in the Canadian
population
A
Multiple fractures confer greater risk than a single fracture. In
addition, prior fractures of the hip and vertebra carry greater risk
than other fracture sites
B
Click here for a summary of the grading system for levels of evidence.
2010 Guidelines
Recommendations for Fracture Risk
Assessment (Cont'd)
Recommendation
Grade
Initiation of pharmacologic treatment for osteoporosis should be
predicated on an assessment of absolute fracture risk using a
validated fracture prediction tool
D
In both men and women age 50 or older, only the femoral neck T-score
(derived from the NHANES III reference range for Caucasian women)
should be used for the calculation of future osteoporotic fracture risk
under the Canadian FRAX and CAROC systems
D
For purposes of BMD reporting, 2010 CAROC is the preferred national
risk assessment system at the present time
D
All individuals with a T-score of the spine or hip ≤ -2.5 should be
considered as having at least moderate risk of osteoporotic fractures
D
2010 Guidelines
Back-up Material
Additional slides that can be accessed from
hyperlinks on core slides
Section Four – Fracture Risk Assessment
2010 Guidelines
Disorders Associated with Osteoporosis
and Increased Fracture Risk
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•
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•
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•
•
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Primary hyperparathyroidism
Type I diabetes
Osteogenesis imperfecta
Untreated long-standing hyperthyroidism, hypogonadism, or
premature menopause (< 45 years)
Cushing’s disease
Chronic malnutrition or malabsorption
Chronic liver disease
Chronic obstructive pulmonary disease (COPD)
Chronic inflammatory conditions (e.g., rheumatoid arthritis [RA],
inflammatory bowel disease)
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2010 Guidelines
Considerations for BMD Reporting
• T-score is the number of standard deviations
that BMD is above or below the mean normal
peak BMD for young white women (NHANES
III for hip measurements)
• Z-score is the number of standard deviations
that BMD is above or below the mean normal
BMD for sex, age, and (if references are
available) race/ethnicity
2010 Guidelines
Considerations for BMD Reporting (Cont'd)
• Osteoporosis cannot be diagnosed by BMD alone
below age 50
• BMD reporting is based upon lowest value for lumbar
spine (minimum two vertebral levels), total hip, and
femoral neck
– If either the lumbar spine or hip is invalid, then the forearm
should be scanned and the distal one-third region reported
• Fracture risk assessment under the FRAX / CAROC
system is based upon the femoral neck
T-score only
Return to main presentation
2010 Guidelines
Variations in Estimated FRAX 10-Year
Fracture Probabilities According to Country
10-Year Major Fracture Probability
Canada Age 65 years,
prior fracture with femoral neck T-score -2.5
30
Female
Male
Percent fracture
25
20
15
10
Turkey
China
Lebanon
Spain
US Black
New Zealand
France
US Asian
US Hispanic
Germany
Finland
Hong Kong
Argentina
Italy
Japan
Belgium
CANADA
United Kingdom
Austria
US Caucasian
Sweden
0
Switzerland
5
10-Year Hip Fracture Probability
Version 3.1 FRAX website (www.sheffield.ac.uk/FRAX).
Age 65 years, prior fracture with femoral neck T-score -2.5
Return to main presentation
2010 Guidelines
Bone Turnover Markers and Fracture
Risk in Postmenopausal Women
Relative risk
4.0
3.5
Serum BAP
3.0
Urinary CTX
3.2
(1.4-7.4)
2.5
2.1
(1.1-4.4)
1.8
(0.8-4.6)
2.0
1.5
0.7
(0.3-1.8)
1.0
1.3
1.2 (0.5-3.1)
(0.5-2.8)
0.5
0.0
Q1
Q2
Q3
Bone marker levels in quartiles
Q4
Garnero P, et al. J Bone Miner Res 2000; 15(8):1526-1536.
2010 Guidelines
Hip Fracture Risk: BMD and BTM
Risk factor(s)
10-year
Prevalence Odds Relative
probability
(%)
ratio
Risk
(%)
Average
100
1.0
18.0
Low BMD
56
2.8
1.4
23.6
Prior fracture
39
3.5
1.77
28.8
High CTX
23
2.4
1.82
29.5
Low BMD + prior fracture
23
4.1
2.39
36.3
Low BMD + high CTX
16
4.1
2.74
40.1
Prior fracture + high CTX
12
5.3
3.50
47.3
All of the above
7
5.8
4.43
54.5
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Johnell O, et al. Osteoporos Int 2002; 13(7):523-526.
2010 Guidelines
Criteria Used to Assign Levels of
Evidence: Studies of Diagnosis
Level
1
Criteria
i
Independent interpretation of test results
ii
Independent interpretation of the diagnostic standard
iii Selection of people suspected, but not known to have the
disorder
iv Reproducible description of the test and diagnostic standard
v
At least 50 people with and 50 people without the disorder
2
Meets four of the Level 1 criteria
3
Meets two of the Level 1 criteria
4
Meets one or two of the Level 1 criteria
2010 Guidelines
Criteria Used to Assign Levels of Evidence:
Studies of Treatment and Intervention
Level Criteria
1+
Systematic overview of meta-analysis of RCTs
1
One RCT with adequate power
2+
Systematic overview or meta-analysis of Level 2 RCTs
2
RCT that does not meet Level 1 criteria
3
5
Non-RCT or cohort study
Before/after study, cohort study with non-contemporaneous
controls, case-control study
Case series without controls
6
Case report or case series of < 10 patients
4
RCT = randomized, controlled study
2010 Guidelines
Criteria Used to Assign Levels of
Evidence: Studies of Prognosis
Level
Criteria
i
ii
1
Inception cohort of patients with the condition of interest, but
free of the outcome of interest
Reproducible inclusion and exclusion criteria
iii Follow-up of at least 80% of participants
iv Statistical adjustment for confounders
v
Reproducible description of the outcome measures
2
Meets criterion i and three of the other four Level 1 criteria
3
Meets criterion i and two of the other four Level 1 criteria
4
Meets criterion i and one of the other four Level 1 criteria
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2010 Guidelines
Criteria Used to Assign
Grades of Recommendation
Level
Criteria
A
Need supportive level 1 or 1+ evidence plus consensus*
B
Need supportive level 2 or 2+ evidence plus consensus*
C
Need supportive level 3 evidence plus consensus
D
Any lower level of evidence supported by consensus
* As appropriate level of evidence was necessary, but not sufficient to assign
a grade in recommendation; consensus was required in addition.
Return to main presentation
2010 Guidelines
10-year Risk Assessment for Women
(CAROC Basal Risk)
Age
Low Risk
Moderate Risk
High Risk
50
above -2.5
-2.5 to -3.8
below -3.8
55
above -2.5
-2.5 to -3.8
below -3.8
60
above -2.3
-2.3 to -3.7
below -3.7
65
above -1.9
-1.9 to -3.5
below -3.5
70
above -1.7
-1.7 to -3.2
below -3.2
75
above -1.2
-1.2 to -2.9
below -2.9
80
above -0.5
-0.5 to -2.6
below -2.6
85
above +0.1
+0.1 to -2.2
below -2.2
Return to main presentation
Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].
2010 Guidelines
10-year Risk Assessment for Men
(CAROC Basal Risk)
Age
Low Risk
Moderate Risk
High Risk
50
above -2.5
-2.5 to -3.9
below -3.9
55
above -2.5
-2.5 to -3.9
below -3.9
60
above -2.5
-2.5 to -3.7
below -3.7
65
above -2.4
-2.4 to -3.7
below -3.7
70
above -2.3
-2.3 to -3.7
below -3.7
75
above -2.3
-2.3 to -3.8
below -3.8
80
above -2.1
-2.1 to -3.8
below -3.8
85
above -2.0
-2.0 to -3.8
below -3.8
Return to main presentation
Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].