Download Care Working Group - Osteoporosis Canada

2010 Guidelines
Case Study #3:
Mrs. SP
2010 Guidelines
Case Presentation
• 73-year-old woman presenting for a physical
examination
• History of low-trauma Colles' fracture (11 years ago)
• BMD from three years ago
– Spine -3.6; Hip -2.0
• No prescription medications
– Takes a multivitamin daily plus a calcium tablet
• Looks and feels healthy and well
2010 Guidelines
Physical Examination
•
•
•
•
Weight: 55 kg (121 lbs.)
Height: 157 cm (5’2”)
Body Mass Index (BMI): 22.3 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
Question
• Should Mrs. SP be treated with pharmacologic
therapy for osteoporosis?
2010 Guidelines
Investigations
• Mrs. SP should have her 10-year risk of
fracture assessed
– Prior DXA done, in accordance with Osteoporosis
Canada guideline indications for use
– CAROC and FRAX are the risk assessment tools
validated for use in Canada
• She has been taking multivitamin with
vitamin D and calcium (800 IU and 500 mg)
– Consider assessing serum 25-OH-D
2010 Guidelines
Calculating Absolute
10-year Fracture Risk: FRAX Tool
Click here to
see her
CAROC
assessment
Mrs. SP is at moderate risk of fractures using the FRAX model
2010 Guidelines
Treatment Considerations
• Counselling should be provided on benefits of
vitamin D and calcium, as well as
nonpharmacologic interventions (e.g., exercise)
• The 2010 Osteoporosis Canada guidelines algorithm
recommends assessment of additional risk factors
among moderate-risk patients
2010 Guidelines
Question
• What additional risk factors may aid in
decision-making for Mrs. SP?
2010 Guidelines
Assessment of Other Risk Factors
• Low spine T-score (-3.6):
– Lumbar spine BMD is not considered
in the initial risk assessment for
either CAROC or FRAX, and fracture
risk is slightly underestimated when
the lumbar spine T-score is much lower than the
hip T-score1
– A lumbar spine T-score much lower than femoral
neck T-score is one of the factors warranting
consideration of pharmacologic therapy in those at
moderate risk1
1. Leslie WD, Lix LM, et al. Osteoporos Int 2010. In press.
2010 Guidelines
Communicating the Benefits, Risks,
and Harms of Therapy
• There are several agents with level 1
evidence for fracture prevention in menopausal
women
• Counsel patients about these benefits as well as
potential adverse events
• Osteoporosis treatment is indefinite; counsel on
importance of adherence
2010 Guidelines
Question
• How should you approach monitoring for a
patient like Mrs. SP?
2010 Guidelines
Considerations for Monitoring
• Rationale for monitoring: To identify
individuals with continued bone mineral
density (BMD) loss, despite appropriate
osteoporosis treatment
• Aspects of monitoring
– Serial BMD measurements
– Assessment of adherence
2010 Guidelines
Mrs. SP: Follow-up (What if...?)
• Mrs. SP presents to your office two years after
being on therapy for follow-up of a vertebral
compression fracture diagnosis made in the
emergency room a short while ago
– She assures you she is always adherent to therapy
• Is this considered a treatment failure?
– Consider referral to specialist
2010 Guidelines
Mrs. SP: Conclusions
• Diagnosis and treatment decisions should start
with the 10-year assessment of risk using a
validated tool
– Mrs. SP is moderate risk using FRAX (10-year risk: 15%)
– Additional clinical risk factors should be considered when
making a treatment decisions
• For monitoring, repeat BMD every one to three
years, with a decrease in testing once therapy is
shown to be effective
2010 Guidelines
Back-up Material
Additional slides that can be accessed
from hyperlinks on case slides
Case C – Mrs. SP
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
Additional Tests for Clinical
Identification of Vertebral Fracture
Test
Rationale
Method
Interpretation
Rib-pelvis
distance1
To identify
lumbar
fractures
Measure the
< 2 fingerbreadths is
distance between associated with
the costal margin vertebral fractures
and the pelvic rim
on the mid-axillary
line
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
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
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
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, 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: Online 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
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 case
Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].
2010 Guidelines
Summary Statement for Other
Nonpharmacologic Therapies
Statement
Strength
Exercises for individuals with osteoporosis should include
weight bearing, balance, and strengthening exercises
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 compliance with their use may
pose a challenge for the older adult
Level 2
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
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+




-


* 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.
Return to case
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
2010 Guidelines
Recommendations for
Duration of Therapy
Recommendation
Grade
Individuals at high risk for fracture should continue osteoporosis
therapy without a drug holiday
D
• Evidence supporting recommendations for duration of
treatment is limited
• Data for the above recommendation come from the
FLEX study (long-term alendronate treatment)1 and
the risedronate discontinuation study2
Return to case
1. Black DM, et al. JAMA 2006; 296(24):2927-2938.
2. Watts NB, et al. Osteoporos Int 2008; 19(3):365-372.
2010 Guidelines
Importance of Adherence
in Treatment Success
• The expectation is that treated
patients will experience
anti-fracture benefits similar to
those reported in clinical trials
• Suboptimal adherence reduces
or eliminates anti-fracture
benefits1-3
1. Silverman S. et al. Rheum Dis Clin North Am 2006; 32(4):721-731.
2. McCombs JS, et al. Maturitas 2004; 48(3):271-287.
3. Gold DT, et al. Curr Osteoporos Rep 2006; 4(1):21-27.
2010 Guidelines
Poor Adherence Leaves Patients At
Higher Risk of Fracture
Probability of fracture
0.12
0.11
0.10
0.09
50% adherence leaves
patients at approximately
the same fracture risk
as no therapy
0.08
0.07
0.00
0.10
0.20
0.30
0.40
0.50
0.60
0.70
0.80
0.90
1.00
MPR
Siris E, et al. Mayo Clin Proc 2006; 81:1013-22.
2010 Guidelines
Types and Rates of Nonadherence
in Osteoporosis Therapy
• Types of non-adherence1-3
– Frequently missed doses
– Failing to take the medication correctly to optimize
absorption and action
– Discontinuation of therapy
• Reported one-year adherence rates:
25% – 50%1,3
– Marginally better with less frequent dosing
regimens
1. Silverman S. et al. Rheum Dis Clin North Am 2006; 32(4):721-731.
2. McCombs JS, et al. Maturitas 2004; 48(3):271-287.
3. Gold DT, et al. Curr Osteoporos Rep 2006; 4(1):21-27.
2010 Guidelines
Approaches for Optimizing Adherence
•
•
•
•
•
Reminders
Patient information
Counselling
Simplification of the dosing regimen
Self-monitoring
Return to case
2010 Guidelines
Interpretation of
Serial BMD Measurements
• Measurement error must be considered when
interpreting serial BMD assessments
– Each centre should determine its precision error in order to
estimate the least significant change (LSC)1
• Continued BMD loss exceeding the LSC may reflect
– Poor adherence to therapy
– Failure to respond to therapy
– Previously unrecognized secondary causes of osteoporosis
• Most anti-osteoporosis therapies do not cause large
BMD increases2
– Stable BMD is consistent with successful treatment
1. Baim S, et al. J Clin Densitom 2005; 8(4):371-378.
2. Chen P, et al. J Bone Miner Res 2009; 24(3):495-502.
2010 Guidelines
Recommendations for Frequency of
BMD Testing
• Usually repeated every 1 – 3 years, with a
decrease in testing once therapy is shown to
be effective
• In those at low risk without additional risk
factors for rapid BMD loss, a longer testing
interval (5 – 10 years) may be sufficient
Return to case
2010 Guidelines
When to Refer to Specialist Care:
General
• Fracture on first-line therapy with optimal
adherence
• Significant loss on follow-up BMD on first-line
therapy with optimal adherence
• Intolerance of first- and second-line agents
2010 Guidelines
When to Refer to Specialist Care:
Special Populations
•
Referrals to physicians with an interest or
expertise in osteoporosis
– Secondary causes of osteoporosis outside the comfort
zone of the individual primary care physician
– Patients with extremely low BMD
•
Referrals to other specialists
– Complex individuals with multiple comorbidities, such as
those with frequent falling, Alzheimer’s disease, stroke,
and Parkinson’s disease
Return to case