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:
– 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
†
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

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
< 50 years
Within expected range for age Z-score > -2.0

Severe (established) T-score < -2.5 with fragility

osteoporosis fracture

Osteoporosis T-score < -2.5

> 50 years
Low bone mass T-score -1.1 to -2.4

Normal T-score > -1.0

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
• 60-year-old woman
• Femoral neck 0.0

T-score = -2.8 -0.5

Femoral neck T-score

-1.0 LOW RISK (<10%)
• Based on age
-1.5
and T-score alone -2.0
= moderate risk -2.5
MODERATE
RISK

• History of fragility -3.0

fracture or prolonged -3.5 HIGH RISK (> 20%)

systemic glucocorticoid -4.0

50 55 60 65 70 75 80 85
use would shift her Age (years)
to high risk

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 Canada 1
• 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
 2010 Guidelines
VFA
• On the left we see a
JB6/23/04;WW5/11/04 IVA/VFA
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 Level 1
prediction independent of BMD alone

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 Level 1
system

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 A
glucocorticoid use

The 2010 CAROC and Canadian FRAX should be used in

Canada since they have been validated in the Canadian A
population

Multiple fractures confer greater risk than a single fracture. In

addition, prior fractures of the hip and vertebra carry greater risk B
than other fracture sites

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 D
validated fracture prediction tool

In both men and women age 50 or older, only the femoral neck T-
score (derived from the NHANES III reference range for Caucasian
D
women) should be used for the calculation of future osteoporotic
fracture risk under the Canadian FRAX and CAROC systems

For purposes of BMD reporting, 2010 CAROC is the preferred national

D
risk assessment system at the present time

All individuals with a T-score of the spine or hip ≤ -2.5 should be

D
considered as having at least moderate risk of osteoporotic fractures
 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
• 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)

Return to main presentation

 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
25
Percent fracture

20

15

10

New Zealand
US Hispanic
Switzerland

United Kingdom

CANADA

Italy

US Black
Germany
US Caucasian

Japan

Hong Kong

US Asian
Sweden

Belgium

Turkey
China
Austria

Argentina

Finland

France

Spain

Lebanon
Return to main presentation Version 3.1 FRAX website (www.sheffield.ac.uk/FRAX).
 2010 Guidelines

Bone Turnover Markers and Fracture

Risk in Postmenopausal Women
4.0
3.5 Serum BAP 3.2
Urinary CTX (1.4-7.4)
3.0
Relative risk

2.5
2.1
1.8 (1.1-4.4)
2.0 (0.8-4.6)

1.5 1.3
1.2 (0.5-3.1)
0.7 (0.5-2.8)
1.0
(0.3-1.8)
0.5
0.0
Q1 Q2 Q3 Q4
Bone marker levels in quartiles

Garnero P, et al. J Bone Miner Res 2000; 15(8):1526-1536.

 2010 Guidelines

Hip Fracture Risk: BMD and BTM

10-year
Prevalence Odds Relative
Risk factor(s) 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

Return to main presentation Johnell O, et al. Osteoporos Int 2002; 13(7):523-526.

 2010 Guidelines

Criteria Used to Assign Levels of

Evidence: Studies of Diagnosis

Level Criteria
i Independent interpretation of test results
ii Independent interpretation of the diagnostic standard

1 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 Non-RCT or cohort study
Before/after study, cohort study with non-contemporaneous
4
controls, case-control study
5 Case series without controls
6 Case report or case series of < 10 patients
RCT = randomized, controlled study
 2010 Guidelines

Criteria Used to Assign Levels of

Evidence: Studies of Prognosis
Level Criteria
i Inception cohort of patients with the condition of interest, but
free of the outcome of interest
ii Reproducible inclusion and exclusion criteria
1 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

Return to main presentation

 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].