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 personal-
care 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
• Age: 65 0.0
-0.5

Femoral neck T-score

• BMD T-score: -1.0 LOW RISK (<10%)

-1.5
– Femoral neck: -2.0
-2.3 -2.5
MODERATE
RISK

– Spine: -2.2 -3.0

HIGH RISK (> 20%)
-3.5
-4.0
50 55 60 65 70 75 80 85
Age (years)

Mrs. BR is at moderate risk of fractures using the CAROC model

 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 decision-
making 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 calciu
m 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:
– 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
Return to case * 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)

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.
Return to case 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
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.
Return to case 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, A,
et et
al.al.
CMAJ
CMAJ
2010
2010
Oct
Oct
12.12.
[Epub
[Epub
ahead
ahead
of of
print].
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.

Return to case 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

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 Age 50-64 yr Age > 65 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
•Fragility fracture after age 40 •All men and women
•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


Integrated Approach, Continued
Low risk
(10-year fracture risk < 10%)
Unlikely to benefit from
pharmacotherapy
Reassess in 5 yr
2010 Guidelines
Initial BMD Testing
Assessment of fracture risk
Moderate risk High risk
(10-year fracture risk 10%-20%) (10-year fracture risk > 20% or
prior fragility fracture of hip or
spine or > 1 fragility fracture)
Lateral thoracolumbar
radiography (T4-L4) or vertebral Always
fracture assessment may aid in consider
decision-making by identifying patient
vertebral fractures preference
Factors warranting Good evidence of
consideration of pharmacologic benefit from
therapy… pharmacotherapy

Integrated Approach, Continued
Low risk
(10-year fracture risk < 10%)
Unlikely to benefit from
pharmacotherapy
Reassess in 5 yr
2010 Guidelines
Initial BMD Testing
Assessment of fracture risk
Moderate risk High risk
(10-year fracture risk 10%-20%) (10-year fracture risk > 20% or
prior fragility fracture of hip or
spine or > 1 fragility fracture)
Lateral thoracolumbar
radiography (T4-L4) or vertebral Always
fracture assessment may aid in consider
decision-making by identifying patient
vertebral fractures preference
Factors warranting Good evidence of
consideration of pharmacologic benefit from
therapy… pharmacotherapy

Integrated Approach, Continued
Low risk
(10-year fracture risk < 10%)
Unlikely to benefit from
pharmacotherapy
Reassess in 5 yr
2010 Guidelines
Initial BMD Testing
Assessment of fracture risk
Moderate risk High risk
(10-year fracture risk 10%-20%) (10-year fracture risk > 20% or
prior fragility fracture of hip or
spine or > 1 fragility fracture)
Lateral thoracolumbar
radiography (T4-L4) or vertebral Always
fracture assessment may aid in consider
decision-making by identifying patient
vertebral fractures preference
Factors warranting Good evidence of
consideration of pharmacologic benefit from
therapy… pharmacotherapy
 2010 Guidelines

Integrated Approach, Moderate risk

(10-year fracture risk 10%-20%)
Continued
Lateral thoracolumbar radiography (T4-L4) or vertebral
fracture assessment may aid in decision-making by
identifying vertebral fractures
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 Good
•Rapid bone loss evidence
Repeat BMD in
•Men undergoing androgen-deprivation therapy for prostate cancer of benefit
1-3 yr and
•Women undergoing aromatase inhibitor therapy for breast cancer from
reassess risk
•Long-term or repeated use of systemic glucocorticoids (oral or pharmaco-
therapy
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
 2010 Guidelines

Integrated Approach, Moderate risk

(10-year fracture risk 10%-20%)
Continued
Lateral thoracolumbar radiography (T4-L4) or vertebral fracture assessment may aid in decision-making by identifying vertebral fractures

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 Good
evidence
Repeat BMD in •Rapid bone loss
of benefit
1-3 yr and •Men on ADT for prostate cancer from
reassess risk •Women on AI for breast cancer pharmaco-
•Long-term or repeated use of systemic glucocorticoids therapy
(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
Return to case
 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

Recommended
Group Vitamin D
Intake (D3)

400 –1000 IU daily

Adults < 50 without osteoporosis or conditions
(10 mcg to 25 mcg
affecting vitamin D absorption
daily)

Adults > 50 or high risk for adverse outcomes from

800 – 2000 IU daily
vitamin D insufficiency (e.g., recurrent fractures or
(20 mcg to 50 mcg
osteoporosis and comorbid conditions that affect
daily)
vitamin D absorption)

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 25-
hydroxy 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
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.
Return to case 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

Level 2
improve outcomes in individuals with osteoporosis

Exercise-focused interventions improve balance and reduce

Level 2
falls in community-dwelling older people

Hip protectors may reduce the risk of hip fractures in long-

term care residents; however adherence with their use may Level 2
pose a challenge for the older adult

Return to case
 2010 Guidelines

First Line Therapies with Evidence for Fracture

Prevention in Postmenopausal Women*
Bone
Antiresorptive therapy formation
therapy
Type of
Bisphosphonates
Fracture Hormone
Zoledronic Denosumab Raloxifene therapy Teriparatide
Alendronate Risedronate (Estrogen)**
acid

Vertebral       

Hip     -  -

Non-
vertebral+     -  

* 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

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