Transcript Case Study #1 - Osteoporosis Canada

2010 Guidelines
Case Study #1
Mrs. DT
2010 Guidelines
Case Presentation
• Age 59: nine years post-menopause with treated
osteoporosis
• Has always enjoyed excellent health with no
past medical or surgical history
• Comes in for her periodic health exam—
concerned about calcium and cardiovascular risk
2010 Guidelines
Physical Examination
• Height = 154 cm (60.5 in.)
• Weight = 55.5 kg (122 lbs.)
• No significant changes in height, weight,
posture, or gait from previous visits
– Changes in height and weight can be signs
of vertebral fractures
2010 Guidelines
Medications
• Risedronate 35 mg weekly
for past six years
• Calcium 600 mg + vitamin D
400 IU (single-tablet supplement)
2010 Guidelines
History of Osteoporosis:
T-scores and Treatment Decisions
Age BMD T-scores Action taken
53
Spine: -1.8
Femoral neck: -2.4
Ruled out secondary causes of osteoporosis
Initiated risedronate 35 mg weekly
Educated on importance of dietary calcium
Initiated calcium 1500 mg daily
Initiated vitamin D 400 IU daily
2010 Guidelines
Current Risk Factor Assessment
•
•
•
•
•
•
•
Non-smoker, no regular alcohol consumption
No previous history of fracture
No parental history of hip fracture
No history of systemic glucocorticoid use
No comorbidities
Diet rich in calcium (1200 mg daily from foods)
High caffeine intake
2010 Guidelines
Question
• Were the diagnosis and treatment initiation in
line with today's guideline recommendations?
2010 Guidelines
Reflections on the
Decision-making Process
• Previous diagnosis and treatment decisions
were largely based on bone density T-scores
• 2010 osteoporosis guidelines advocate making
decisions based on an assessment of overall
10-year fracture risk
• Tools endorsed: CAROC and FRAX
• Current recommendations for:
– Calcium: 1200 mg from diet and supplement combined
– Vitamin D: 800 – 2000 IU daily for age over 50
2010 Guidelines
Should This Patient Have Been Receiving
Treatment? FRAX 10-year Risk Assessment
Age BMD
53
FRAX-calculated 10-year risk
Spine: -1.8
6.0% for major osteoporotic fracture
Femoral neck: -2.4
2010 Guidelines
FRAX Calculation of Original Risk
(Age 53 – Six Years Ago)
2010 Guidelines
Mrs. DT: Reflection on Diagnosis
• Six years ago, the diagnosis and therapy were
appropriate, given the low BMD at the femoral
neck (-2.4) and two minor risk factors (weight
< 57kg, high caffeine intake)
• With today's tools (e.g., CAROC, FRAX),
however, Mrs. DT would have been low risk
– Treatment would not have been recommended
under the current system
2010 Guidelines
Question
• Would you consider using a risk-assessment
tool to check Mrs. DT's current level of risk on
treatment?
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
• One could use these tools to assess what the risk might
be for a woman like Mrs. DT who had never been
treated
2010 Guidelines
FRAX Calculation of Risk for a Woman Like
Mrs. DT, but Who Had Never Been Treated
2010 Guidelines
Question
• What would you do in this case?
• Would you continue or discontinue treatment
with risedronate?
– Discuss the rationale for your decision
2010 Guidelines
Mrs. DT: Conclusions
• Diagnosis and treatment decisions should now be based on
10-year assessment of risk using a validated tool
– Patients at low risk (10-year risk < 10%) should not be
receiving treatment
• Her current risk level is not known:
– 10-year absolute risk tools were developed to assess patients
who are treatment naive
• Mrs. DT currently gets adequate calcium from her diet
(~1200 mg daily)
– Calcium supplementation should be stopped
– Vitamin D supplementation should continue
2010 Guidelines
Back-up Material
Additional slides that can be accessed
from hyperlinks on case slides
Case 1 – Mrs. DT
2010 Guidelines
Potential Risks of Calcium
Supplementation
• High-dose calcium supplementation has been
associated with
– Renal calculi in older women
– Cardiovascular events in older women
– Prostate cancer in older men
Return to case
1. Bolland MJ, et al. J Clin Endocrinol Metab 2010; 95(3):1174-1181.
2. Bolland MJ, et al. BMJ 2008; 336(7638):262-266.
3. Reid IR, et al. Osteoporos Int 2008; 19(8):1119-1123.
2010 Guidelines
Importance of Weight
• In men > 50 years and in postmenopausal
women, the following are associated with low
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
First Line Therapies with Evidence for Fracture
Prevention in Postmenopausal Women*
Bone
formation
therapy
Antiresorptive therapy
Type of
Fracture
Bisphosphonates
Raloxifene
Hormone
therapy
(Estrogen)**
Teriparatide
Alendronate
Risedronate
Zoledronic
acid
Denosumab
Vertebral







Hip




-

-
Nonvertebral+




-


Return to case
* For postmenopausal women,  indicates first line therapies and Grade A recommendation. For men requiring treatment,
alendronate, risedronate, and zoledronic acid can be used as first line therapies for prevention of fractures [Grade D].
+ In clinical trials, non-vertebral fractures are a composite endpoint including hip, femur, pelvis, tibia, humerus, radius, and clavicle.
** Hormone therapy (estrogen) can be used as first line therapy in women with menopausal symptoms.
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 Women
(CAROC Basal Risk)
Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].
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
Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].
2010 Guidelines
10-year Risk Assessment for Men
(CAROC Basal Risk)
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 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
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: Online Calculator
www.shef.ac.uk/FRAX.
2010 Guidelines
FRAX Clinical Risk Factors
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Parental hip fracture
Prior fracture
Glucocorticoid use
Current smoking
High alcohol intake
Rheumatoid arthritis
Return to case
2010 Guidelines
Recommended Vitamin D
Supplementation
Recommended
Vitamin D
Intake (D3)
Group
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; Jul 26. [epub before print].
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
Return to case
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
high-dose 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.