Download Case Study #2 - Osteoporosis Canada

2010 Guidelines
Case Study #2:
Mrs. BR
2010 Guidelines
Case Presentation
• 65-year-old woman
• Natural menopause at age 50
• 10-year history of hypertension (currently
treated and controlled)
• Presents for periodic health examination
2010 Guidelines
Physical Examination
• Height: 160 cm (5'3")
– 1 cm less than self-reported historic peak height
•
•
•
•
Weight: 63.5 kg (140 lbs.)
Body mass index (BMI): 24.8 kg/m2
Blood Pressure: 136 / 84 mmHg
Physical examination is unremarkable
2010 Guidelines
Medications
• Perindopril 8 mg once daily (OD)
• Multivitamin (for adults over 50)
2010 Guidelines
Screening and Risk Assessment
• Mrs. BR meets the 2010 guideline criteria for
screening using dual energy X-ray absorptiometry
(DXA)
– All women and men age > 65
• Current recommendations are to use one of these
validated tools to assess 10-year risk of osteoporotic
fractures
– CAROC developed by The Canadian Association of
Radiologist and Osteoporosis Canada
– FRAX Fracture Risk Assessment Tool developed by The
World Health Organization
2010 Guidelines
Ms. BR: Risk Factor Assessment
• No hormone treatment
• No personal fracture history
• Positive family history: Hip fracture in her mother at
age 75 (fell in own home; ended up in personalcare home)
• Non smoker
• No history of systemic steroid use
• No history of rheumatoid arthritis
• No potential secondary causes of osteoporosis
• Alcohol use: < 3 drinks/day
2010 Guidelines
Question
• What is the impact of family history of hip
fracture on risk assessment?
2010 Guidelines
CAROC: Using Age, Sex, and BMD to
Estimate 10-year Risk of Fracture
– Femoral neck:
-2.3
– Spine: -2.2
0.0
Femoral neck T-score
• Age: 65
• BMD T-score:
-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
Age (years)
Mrs. BR is at moderate risk of fractures using the CAROC model
85
2010 Guidelines
Impact of Family History of Hip Fracture
on CAROC Risk Assessment
• The CAROC risk-assessment tool does not
include family history of hip fracture among its
variables
• Family history is one of the potential additional
factors that can be considered in decisionmaking if the patient is at moderate risk
2010 Guidelines
Impact of Family History of Hip Fracture
on FRAX Risk Assessment
• FRAX does include a family history of hip
fracture as one of its variables
• The presence or absence of this risk factor
dramatically changes the 10-year absolute-risk
calculation (see next two slides)
2010 Guidelines
FRAX Risk Calculation for Mrs. BR,
with Family History of Hip Fracture
2010 Guidelines
FRAX Risk Calculation for Mrs. BR, Hypothetical
Situation Without Family History of Hip Fracture
2010 Guidelines
Impact of Family History of Hip Fracture
on FRAX Risk Assessment
• For a person like Mrs. BR, the family history of
parental hip fracture increases her absolute
10-year risk of major osteoporotic fractures by
9.0%
• This has potential major implications for
treatment
• In Mrs. BR's case, this factor moved her from
the lower end to the higher end of the
moderate-risk range using FRAX
2010 Guidelines
Question
• What laboratory tests are recommended for
patients with a diagnosis of osteoporosis?
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
Treatment Considerations
for Moderate-risk Individuals
• The 2010 guidelines’ integrated management
model recommends consideration of:
– Additional clinical risk factors to refine assessment
– Lateral thoracolumbar X-ray (T4-L4) or vertebral
fracture analysis (VFA) to aid in decision-making by
identifying vertebral fractures
2010 Guidelines
Vitamin D, Calcium and Other
Nonpharmacologic Interventions
• The 2010 guidelines have new
recommendations for vitamin D and calcium
intake
• Optimal treatment strategies can also include
other lifestyle interventions (e.g., physical
activity, nutrition)
2010 Guidelines
Mrs. BR: To Treat or Not to Treat
• Decision whether or not to treat patients at
moderate risk with pharmacologic therapy also
involves
– Discussion of benefits (e.g., fracture risk reduction)
and risks (e.g., adverse events) of treatment
– Assessment of patient preferences and health
priorities to come up with an "individualized
intervention threshold"
2010 Guidelines
Mrs. BR: Conclusions
• Diagnosis and treatment decisions should be based
on 10-year assessment of risk using a validated tool
– Mrs. BR is moderate risk using both the CAROC and FRAX
tools
• Patients at moderate risk (10-year risk 10% – 20%)
may benefit from pharmacologic therapy
– Decision of whether to initiate treatment can be made after a
discussion of benefits and risks with the patient
• Mrs. BR’s fear of hip fracture leads her to decide to
initiate therapy
2010 Guidelines
Back-up Material
Additional slides that can be accessed
from hyperlinks on case slides
Case 2 – Mrs. BR
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
Importance of Weight
• In men > 50 years and 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
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
Papaioannou
A, etA,al.etCMAJ
al. CMAJ
20102010
Oct Oct
12. [Epub
12. [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: Online Calculator
www.shef.ac.uk/FRAX.
2010 Guidelines
FRAX Clinical Risk Factors
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•
•
•
•
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Parental hip fracture
Prior fracture
Glucocorticoid use
Current smoking
High alcohol intake
Rheumatoid arthritis
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
Factors that Warrant Consideration for
Pharmacological Therapy in Moderate Risk Patients
•
•
•
•
•
•
•
•
•
Additional vertebral fracture(s) (> 25% height loss with end-plate
disruption) identified on VFA or lateral spine X-ray
Previous wrist fracture in individuals > 65 or those with T-score < -2.5
Lumbar spine T-score much lower than femoral neck T-score
Rapid bone loss
Men on androgen deprivation therapy for prostate cancer
Women on aromatase inhibitor therapy for breast cancer
Long-term or repeated systemic glucocorticoid use (oral or parenteral)
that does not meet the conventional criteria for recent prolonged
systemic glucocorticoid use (i.e., > 3 months cumulative during the
preceding year at a prednisone equivalent dose > 7.5 mg daily)
Recurrent falls defined as falling 2 or more times in the past 12 months
Other disorders strongly associated with osteoporosis, rapid bone loss or
fractures
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
Chronic inflammatory conditions (e.g., rheumatoid arthritis
inflammatory bowel disease)
Return to case
2010 Guidelines
VFA Recognition and Reporting
• VFA is a scanning and
software option on bone
densitometers
• A fracture detected by
VFA or radiograph
should be considered a
prior fracture under the
FRAX or CAROC
system
Return to case
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
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.
2010 Guidelines
Summary Statement for Other
Nonpharmacologic Therapies
Statement
Strength
Weight bearing, balance, and strengthening exercises can
improve outcomes in individuals with osteoporosis
Level 2
Exercise-focused interventions improve balance and reduce
falls in community-dwelling older people
Level 2
Hip protectors may reduce the risk of hip fractures in longterm care residents; however adherence with their use may
pose a challenge for the older adult
Level 2
Return to case
2010 Guidelines
First Line Therapies with Evidence for Fracture
Prevention in Postmenopausal Women*
Bone
formation
therapy
Antiresorptive therapy
Type of
Fracture
Bisphosphonates
Raloxifene
Risedronate
Zoledronic
acid
Denosumab
Alendronate
Hormone
therapy
(Estrogen)**
Vertebral







Hip




-

-
Nonvertebral+




-


Teriparatide
* 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
Adverse Events of Osteoporosis Therapies
• Consult individual product monographs for
adverse event information for approved
therapies (click on drug names below to link to
online resources)
– Bisphosphonates: alendronate, risedronate,
zoledronic acid
– Calcitonin
– Denosumab
– Raloxifene
– Teriparatide
Return to case