Transcript Care Working Group - Osteoporosis Canada

2010 Guidelines
Case Study #4:
Mr. JM
2010 Guidelines
Case Presentation
• 64-year-old retired firefighter
– Retired nine years ago; now doing contract
carpentry
• Presents for physical examination,
complaining his back has been “worse than
usual” the past three weeks
• On no medications
• Prior smoker (45 pack/year history)
– Quit smoking one year ago
2010 Guidelines
Physical Examination
• Height: 180 cm (5'11")
– Patient recalls being 185.5 cm (6'1")
• Weight: 80 kg (up 5 kg from one year ago)
• Body mass index (BMI): 24.7 kg/m2
– Changes in height and weight can be signs of
vertebral fractures
– Other indicators of vertebral fracture in physical
examination: Rib-pelvis distance and occiput-wall
distance
2010 Guidelines
Risk Factor Assessment
• Family history: none significant
• No history of systemic glucocorticoids or
androgen-deprivation therapy
• No history of secondary causes of osteoporosis
• Historical height loss
• No previous trauma
• Alcohol use: approximately two drinks per week
Click here for a discussion of factors known to increase fracture risk in men.
2010 Guidelines
Why is Osteoporosis Underappreciated
in Men?
•
•
•
•
Men have higher peak bone mass
Slower rate of bone loss
Shorter life expectancy
Greater periosteal bone formation (greater
cross-sectional bone diameter and a
biomechanical advantage since larger bones
have less fracture risk)
Khan AA, et al. CMAJ 2007;176(3):345-348.
2010 Guidelines
Question
• What tests would you consider ordering?
2010 Guidelines
Mr. JM: Diagnostic Testing
• Screening for osteoporosis with dual energy
X-ray absorptiometry (DXA) is indicated,
based on 2010 guideline criteria
– T-score -1.9 at femoral neck
• Lateral thoraco-lumbar spine X-ray is ordered
to rule out vertebral compression deformities
– The radiologist makes note of two vertebrae being
wedge shaped and just meeting the criteria for
vertebral compression fracture
2010 Guidelines
Question
• Given the presence of vertebral fractures, is
further risk assessment necessary before
initiating pharmacologic therapy?
2010 Guidelines
Considerations for Therapy
• The guidelines do recommend that diagnosis
and treatment decisions should be based on a
validated 10-year risk-assessment tool (i.e.,
CAROC or FRAX)
– FRAX predicts 12% risk (moderate)1
• However, the presence of multiple vertebral
fractures in this case place Mr. JM at high risk
– In fact, 10-year assessment tools underestimate
risk in patients with vertebral fractures
1. Leslie WD, Lix LM, et al. Osteoporos Int 2010. In press.
2010 Guidelines
Question
• How would you proceed with therapy for Mr. JM?
2010 Guidelines
Treatment Considerations
• Bloodwork to rule out
secondary causes of osteoporosis
• Assume vitamin D level is low and
start supplementation (with calcium)
• According to the 2010 OC guidelines
– Pharmacotherapy is indicated for a high-risk patient
(see integrated management model)
– Testosterone therapy is not recommended
2010 Guidelines
Mr. JM: Conclusions
• Mr. JM is high risk because of his vertebral
fractures
• In this case, 10-year assessment tools
underestimate risk
• Patients at high risk benefit from
pharmacologic therapy
– Recommended agents for first-line use in men are
alendronate, risedronate, or zoledronic acid
2010 Guidelines
Back-up Material
Additional slides that can be accessed
from hyperlinks on case slides
Case 4 – Mr. JM
2010 Guidelines
Importance of Weight
• In men > 50 years and postmenopausal
women, the following are associated with low
bone mineral density
(BMD) and fractures
– Low body weight (< 60 kg)
– Major weight loss (> 10%
of weight at age 25)
Return to case
1. Papaioannou A, et al. Osteoporos Int 2009; 20(5):703-715.
2. Waugh EJ, et al. Osteoporos Int 2009; 20:1-21.
3. Cummings SR,et al. N Engl J Med 1995; 332(12):767-773.
4. Papaioannou A, et al. Osteoporos Int 2005; 16(5):568-578.
5. Kanis J, et al. Osteoporos Int 1999; 9:45-54.
6. Morin S, et al. Osteoporos Int 2009; 20(3):363-70.
2010 Guidelines
Importance of Height Loss
• Increased risk of vertebral
fracture
– Historical height loss (> 6 cm)1,2
– Measured height loss (> 2 cm)3-5
• Significant height loss should
be investigated by a lateral
thoracic and lumbar spine
X-ray
Return to case
1. Siminoski K, et al. Osteoporos Int 2006; 17(2):290-296.
2. Briot K, et al. CMAJ 2010; 182(6):558-562.
3. Moayyeri A, et al. J Bone Miner Res 2008; 23:425-432.
4. Siminoski K, et al. Osteoporos Int 2005; 16(4):403-410.
5. Kaptoge S, et al. J Bone Miner Res 2004; 19:1982-1993.
2010 Guidelines
Additional Tests for Clinical
Identification of Vertebral Fracture
Test
Rationale
Method
Interpretation
Rib-pelvis
distance1
To identify
lumbar fractures
Measure the
distance
between the
costal margin
and the pelvic
rim on the midaxillary line
< 2 fingerbreadths
is associated with
vertebral fractures
Occiput-to-wall
distance2,3
To help identify
thoracic spine
fractures
Stand straight
with heels and
back against the
wall
> 5 cm raises
suspicion of
vertebral fracture
1. Olszynski WP, et al. BMC Musculoskeletal Disorders 2002; 3:22.
2. Green AD, et al. JAMA 2004; 292(23):2890-2900.
3. Siminoski K, et al. J Bone Miner Res 2001; 16(Suppl):S274.
2010 Guidelines
Rib-Pelvis and Occiput-to-Wall
Distances
4 cm
8 cm
3 cm
Height loss
12 cm
3 FBs
Return to case
2 FBs
8 cm
2010 Guidelines
Risk Factors with Good Evidence
for Low BMD in men
• Advancing age
– Between 50 and 80 years, men have1.5% – 2.5%
decline in hip BMD per year
– BMD at lumbral-sacral spine increases with age (falsely
elevated due to osteophyte formation)
• Smoking
– Current smokers have greater risk of low BMD at the hip
compared to former smokers.
– Highest risk subgroups
• Men > 20 pack years
• Current smokers with low body weight (< 75 kgs)
Papaioannou A, et al. Osteoporosis Int 2009;20:507-518.
2010 Guidelines
Risk Factors with Good Evidence
for Low BMD in Men
• Low weight/weight loss
– BMD at the hip increases roughly 3% – 7% for
every 10 kg weight gain
– Low baseline weight/BMI predicts subsequent bone
loss at the hip
• Physical functional limitations
– Men who can rise from a chair without using arms
have 2% – 4% higher hip BMD than those who
cannot
• Prevalent fracture after 50 years of age
Return to case
Papaioannou A, et al. Osteoporosis Int 2009;20:507-518.
2010 Guidelines
Indications for BMD Testing
•
•
All women and men age > 65
Postmenopausal women, and men aged 50 – 64 with clinical risk factors
for fracture:
–
–
–
–
–
–
–
–
–
–
Return to case
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
Plain Radiographic
Examinations of the Spine
Type
Use(s)
Plain radiographs,
complete
To investigate symptoms such
as back pain or after trauma
Plain radiographs,
limited
Specifically to look for osteoporotic fracturing
Plain radiographs,
incidental
Incidental views of the spine on radiographs
undertaken for other purposes (e.g., lateral chest films)
2010 Guidelines
Other Radiographic
Examinations of the Spine
Type
Use(s)
Incidental to DXA – provides lower-resolution
Vertebral fracture
images of the spine, not subject to projection
assessment (VFA), T4 to L4
distortion
Computed tomography (CT) To clarify subtle or uncertain findings on
of the spine
radiographs
Magnetic resonance
imaging (MRI) of the spine
Radionuclide bone
scanning
Return to case
To examine soft tissues or clarify the
acuteness of spinal fracturing
To look for disease activity or distribution
May also be helpful in diagnosing such
conditions as metastatic disease and
acuteness of injury
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
• Other fractures attributable to osteoporosis are not
reflected; total osteoporotic fracture burden is
underestimated
* Combined risk for fractures of the proximal femur, vertebra [clinical], forearm, and proximal humerus
Siminoski K, et al. Can Assoc Radiol J 2005; 56(3):178-188.
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
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
Papaioannou
Papaioannou
A, A,
et al.
et al.
CMAJ
CMAJ
2010
2010
OctOct
12.12.
[Epub
[Epub
ahead
ahead
of print].
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
Return to case
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
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
Return to case
2010 Guidelines
Recommended Biochemical Tests for Patients
Being Assessed for Osteoporosis
•
•
•
•
•
•
Calcium, corrected for albumin
Complete blood count
Creatinine
Alkaline phosphatase
Thyroid stimulating hormone (TSH)
Serum protein electrophoresis for patients with
vertebral fractures
• 25-hydroxy vitamin D (25-OH-D)*
* Should be measured after three to four months of adequate supplementation
and should not be repeated if an optimal level ≥ 75 nmol/L is achieved.
2010 Guidelines
Tests for Potential Secondary Causes
In patients with
Persistently elevated serum
calcium
Multiple or atypical vertebral
fractures
Symptoms/signs of
malabsorption or non
response to vitamin D
therapy
Condition /
Disease
Hyperparathyroidism PTH
Multiple myeloma
Protein electrophoresis
Immunoelectrophoresis
Celiac disease
Antibodies associated
with gluten enteropathy
Signs and symptoms of
Hypogonadism
androgen deficiency (in men)
History of kidney stones
Return to case
Test
Hypercalciuria
Testosterone
(bioavailable or total)
Serum prolactin
24-hour urine for
calcium
2010 Guidelines
Recommended Vitamin D
Supplementation
Group
Recommended
Vitamin D
Intake (D3)
Adults < 50 without osteoporosis or conditions
affecting vitamin D absorption
400 – 1000 IU daily
(10 mcg to 25 mcg
daily)
Adults > 50 or high risk for adverse outcomes from
vitamin D insufficiency (e.g., recurrent fractures or
osteoporosis and comorbid conditions that affect
vitamin D absorption)
800 – 2000 IU daily
(20 mcg to 50 mcg
daily)
Hanley DA, et al. CMAJ 2010; 182:E610-E618.
2010 Guidelines
Vitamin D: Optimal Levels
• To most consistently
improve clinical
outcomes such as
fracture risk, an optimal
serum level of 25hydroxy vitamin D is
probably > 75 nmol/L
– For most Canadians,
supplementation is
needed to achieve this
level
Hanley DA, et al. CMAJ 2010; 182:E610-E618.
2010 Guidelines
When to Measure Serum 25-OH-D
• In situations where deficiency is suspected or
where levels would affect response to therapy
– Individuals with impaired intestinal absorption
– Patients with osteoporosis requiring pharmacotherapy
• Should be checked no sooner than three months
after commencing standard-dose supplementation
in osteoporosis
• Monitoring of routine supplement use and routine
screening of otherwise healthy individuals are not
necessary
Hanley DA, et al. CMAJ 2010; 182:E610-E618.
2010 Guidelines
Recommended Calcium Intake
• From diet and supplements
combined: 1200 mg daily
– Several different types of calcium
supplements are available
• Evidence shows a benefit of
calcium on reduction of fracture
risk1
• Concerns about serious adverse effects with highdose supplementation2-4
Return to case
1. Tang BM, et al. Lancet 2007; 370(9588):657-666.
2. Bolland MJ, et al. J Clin Endocrinol Metab 2010; 95(3):1174-1181.
3. Bolland MJ, et al. BMJ 2008; 336(7638):262-266.
4 Reid IR, et al. Osteoporos Int 2008; 19(8):1119-1123.
2010 Guidelines
Agents Recommended First-line for
Fracture Prevention in Men
• Alendronate
• Risedronate
• Zoledronic acid
Return to case
2010 Guidelines
Integrated Approach to Management of
Patients Who Are at Risk for Fracture
Encourage basic bone health for all individuals over age 50, including regular active weight-bearing exercise, calcium
(diet and supplementation) 1200 mg daily, vitamin D 800-2000 IU (20-50µg) daily and fall-prevention strategies
Age < 50 yr
• Fragility fractures
• Use of high-risk
medications
• Hypogonadism
• Malabsorption syndromes
• Chronic inflammatory
conditions
• Primary
hyperparathyroidism
• Other disorders strongly
associated with rapid bone
loss or fractures
Age 50-64 yr
• Fragility fracture after age 40
• Prolonged use of glucocorticoids or other
high-risk medications
• Parental hip fracture
• Vertebral fracture or osteopenia identified
on radiography
• High alcohol intake or current smoking
• Low body weight (< 60 kg) or major weight
loss (> 10% of body weight at age 25)
• Other disorders strongly associated with
osteoporosis
Initial BMD Testing
Age > 65 yr
• All men and women
2010 Guidelines
Integrated Approach, Continued
Initial BMD Testing
Assessment of fracture risk
Low risk
(10-year fracture risk < 10%)
Moderate risk
(10-year fracture risk 10%-20%)
Unlikely to benefit from
pharmacotherapy
Reassess in 5 yr
Lateral thoracolumbar
radiography (T4-L4) or vertebral
fracture assessment may aid in
decision-making by identifying
vertebral fractures
Factors warranting
consideration of pharmacologic
therapy…
High risk
(10-year fracture risk > 20% or
prior fragility fracture of hip or
spine or > 1 fragility fracture)
Always
consider
patient
preference
Good evidence of
benefit from
pharmacotherapy
2010 Guidelines
Integrated Approach, Continued
Initial BMD Testing
Assessment of fracture risk
Low risk
(10-year fracture risk < 10%)
Moderate risk
(10-year fracture risk 10%-20%)
Unlikely to benefit from
pharmacotherapy
Reassess in 5 yr
Lateral thoracolumbar
radiography (T4-L4) or vertebral
fracture assessment may aid in
decision-making by identifying
vertebral fractures
Factors warranting
consideration of pharmacologic
therapy…
High risk
(10-year fracture risk > 20% or
prior fragility fracture of hip or
spine or > 1 fragility fracture)
Always
consider
patient
preference
Good evidence of
benefit from
pharmacotherapy
2010 Guidelines
Integrated Approach, Continued
Initial BMD Testing
Assessment of fracture risk
Low risk
(10-year fracture risk < 10%)
Moderate risk
(10-year fracture risk 10%-20%)
Unlikely to benefit from
pharmacotherapy
Reassess in 5 yr
Lateral thoracolumbar
radiography (T4-L4) or vertebral
fracture assessment may aid in
decision-making by identifying
vertebral fractures
Factors warranting
consideration of pharmacologic
therapy…
High risk
(10-year fracture risk > 20% or
prior fragility fracture of hip or
spine or > 1 fragility fracture)
Always
consider
patient
preference
Good evidence of
benefit from
pharmacotherapy
2010 Guidelines
Integrated Approach,
Continued
Moderate risk
(10-year fracture risk 10%-20%)
Lateral thoracolumbar radiography (T4-L4) or vertebral
fracture assessment may aid in decision-making by identifying
vertebral fractures
•
•
Repeat BMD in
1-3 yr and
reassess risk
•
•
•
•
•
•
•
Factors warranting consideration of pharmacologic therapy:
Additional vertebral fracture(s) (by vertebral fracture assessment or
lateral spine radiograph)
Previous wrist fracture in individuals aged > 65 or those with
T-score < -2.5
Lumbar spine T-score much lower than femoral neck T-score
Rapid bone loss
Men undergoing androgen-deprivation therapy for prostate cancer
Women undergoing aromatase inhibitor therapy for breast cancer
Long-term or repeated use of systemic glucocorticoids (oral or
parenteral) not meeting conventional criteria for recent prolonged
use
Recurrent falls (> 2 in the past 12 mo)
Other disorders strongly associated with osteoporosis, rapid bone
loss or fractures
Good
evidence
of benefit
from
pharmacotherapy
2010 Guidelines
Integrated Approach,
Continued
Moderate risk
(10-year fracture risk 10%-20%)
Lateral thoracolumbar radiography (T4-L4) or vertebral fracture assessment may aid in decision-making by identifying vertebral fractures
Repeat BMD in
1-3 yr and
reassess risk
Return to case
Factors warranting consideration of pharmacotherapy:
• Additional vertebral fracture(s) (by vertebral fracture
assessment or lateral spine radiograph)
• Previous wrist fracture in individuals aged > 65 or those with
T-score < -2.5
• Lumbar spine T-score much lower than femoral neck T- score
• Rapid bone loss
• Men on ADT for prostate cancer
• Women on AI for breast cancer
• Long-term or repeated use of systemic glucocorticoids (oral
or parenteral) not meeting conventional criteria for recent
prolonged use
• Recurrent falls (> 2 in the past 12 mo)
• Other disorders strongly associated with osteoporosis, rapid
bone loss or fractures
Good
evidence
of benefit
from
pharmacotherapy
2010 Guidelines
Testosterone in Men: Summary
Statement and Recommendation
Statement
Testosterone maintains BMD in hypogonadal men but has
not been shown to reduce the risk of fractures
Recommendation
Testosterone is not recommended for the treatment of
osteoporosis in men
Return to case
Strength
Level 2
Grade
B