fracture risk assessment: from basics to baffling
TRANSCRIPT
Fracture risk assessment:
From Basics to Baffling
William D Leslie MD FRCPC MSc CCD
By the end of this session
attendees shall be able to:
• Understand how and why fracture risk
assessment has changed over the past decade
• Understand how recent advances in fracture risk
assessment enhance the quality of patient care
1. Leslie WD, et al. Osteoporos Int 2010; 21:1317‐1322.
2. Burge J, et al. J Bone Miner Res 2007; 22:465-475.
3. Public Health Agency of Canada. 2009.
4. Canadian Cancer Society/National Cancer Institute of Canada. 2007.
22,30019,50022,200
21,200
Hip
31,100
Wrist
9,800
Pelvic
39,500
Other
37,000
Vertebral
0
20,000
40,000
60,000
80,000
100,000
120,000
140,000
160,000
Osteoporotic
Fractures
Heart
Attack
Stroke Breast
Cancer
Ann
ual I
ncid
ence
of C
omm
on D
isea
ses
138,600
Incidence of Osteoporotic Fracture, Heart Attack,
Stroke and Breast Cancer in Canadian Women
3 41,2
3
*
* Canadian hip fractures from (1). Non-hip fractures extrapolated from (2).
Fragility Fracture: Definition
• A fracture occurring
spontaneously or
following minor
trauma such as a fall
from standing height
or less1,2
– Excluding face/head,
hand, ankle, and foot
fractures
1. Kanis JA, et al. Osteoporos Int 2001; 12(5):417-427.
2. Bessette L, et al. Osteoporos Int 2008; 19:79-86.
Consequences of Fracture
• Increased risk of
– Hospitalization1
– Institutionalization2
– Death3-5
– Subsequent fracture6-8
– Decreased quality of life9-12
– Economic burden on
healthcare system2
1. Papaioannou A, et al. Osteoporos Int 2001; 12(10):870-874.2. Wiktorowicz ME, et al. Osteoporos Int 2001; 12(4):271-278.3. Ioannidis G, et al. CMAJ 2009; 181(5):265-271.4. Papaioannou A, et al. J SOGC 2000; 22(8):591-597.5. Tosteson AN, et al. Osteoporos Int 2007; 18(11):1463-1472.6. Papaioannou A, et al. J SOGC 2000; 22(8):591-597.
7. Colon-Emeric C, et al. Osteoporos Int 2003; 14:879-893.8. Lindsay R, et al. JAMA 2001; 285:320-323.9. Sawka AM, et al. Osteoporos Int 2005; 16:1836-1840.10. Cranney A, et al. J Rheumatol 2005; 32(12):2393-2399.11. Pasco JA, et al. Osteoporos Int 2005; 16(12):2046-2052.12. Papaioannou A, et al. Osteoporos Int 2009; 20(5):703-715.
Death 1st Year Post Fractureadjusted for age, comorbidity, home care/PCH status
0
0.5
1
1.5
2
2.5
3
3.5
Women Men
RR
fo
r D
ea
th
Hip Spine Humerus Wrist Other
Morin S. Osteoporo Int. 2010.
N=49,197
Incident fractures
N=21,067
Incident fractures
Post-fracture Care Gap:
Comparison with Heart Attack
~15%
~80%
0
20
40
60
80
100
Anti-osteoporosis medication post fracture
Beta-blockers post heart attack
% o
f p
ati
en
ts b
ein
g t
rea
ted
1. Bessette L, et al. Osteoporos Int 2008; 19:79-86.
2. Austin PC, et al. CMAJ 2008; 179(9):901-908.
Percentage of individuals who received OP medication 1 year following
major fracture in Canada, 2000–2001 to 2014–2015
0.0
5.0
10.0
15.0
20.0
25.0
30.0P
erc
en
tage
(%)
Fiscal Year
Females - new OP medication prescription Males - new OP medication prescription
Results for Canada
“Up to” 26.1% in Women and 16.9% in Men
Increase up to 2008–2009 (p for trend <0.0001)
Followed by a Decline to 2014–2015 (p for trend <0.0001)
Morin SN et al. ASBMR 2018.
Women Men
Results for Canada
Brown JP. Can Family Physician 2014.
• “…all Canadians,
wherever they live,
have the right to
effective bone care
and fracture
prevention programs”
Key Changes from 20021 to 20102
• Increased focus on the importance of
fragility fractures
• Increased focus on the care gap that
exists in the identification and
treatment of high-risk individuals
1. Brown JP, Josse RG. CMAJ 2002; 167(10 Suppl):S1-34.
2. Papaioannou A, et al. CMAJ 2010.
No. of fractures
No
. of
frac
ture
s
0
100
200
300
400
500
Most Fragility Fractures in Older Women Occur
with Low Bone Mass ("Osteopenia")
> 0.0 0.0to -0.5
-0.5to -1.0
-1.0to -1.5
-1.5to -2.0
-2.0to -2.5
-2.5to -3.0
-3.0to -3.5
≤ -3.5 Normal Osteo-penia
Osteo-porosis
WHO categoryHip T-score
60
50
40
30
20
10
0
Fracture rate
Frac
ture
rat
e, p
er
10
00
pe
rso
n-y
ear
s
Cranney A, et al. CMAJ 2007; 177(6):575-580.
Treatment initiation:High risk fracture = vertebral, hip, multiple
Leslie WD et al. Bone 2018.
5%
71%
23%
5%
71%
19%
0%
25%
50%
75%
100%
Normal Osteopenia Osteoporosis
Ost
eo
po
rosi
s tr
ea
tme
nt
No fracture High-risk Fracture
95% CI bars
2010 Guidelines
Assessment of fracture risk
Moderate riskLow risk High risk10 year fracture risk > 20% or
prior fragility fracture of hip or spine or > 1 fragility fracture)
Good evidence of benefit from
pharmacotherapy
Initial BMD Testing
10-year MOF Risk Assessment
CAROC 2010FRAX Canada
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
– Three zones (low: < 10%, moderate, high: > 20%)
• Considers two additional risk factors
– Fragility fracture after age 40
– Recent prolonged systemic glucocorticoid use (at
least 3 m last year prednisone > 7.5 mg daily)
Siminoski K, et al. Can Assoc Radiol J 2005; 56(3):178-188.
* Fractures of the thigh bone, vertebra, forearm, and shoulder
Example: 65 year old woman
• Femoral neck
T-score = -2.8
• Based on age and
T-score alone =
moderate risk
Adapted from Siminoski K, et al. Can Assoc Radiol J 2005; 56(3):178-188.
Example: 65 year old woman
• Femoral neck
T-score = -2.8
• Based on age and
T-score alone =
moderate risk
• History of fragility
fracture or prolonged
systemic glucocorticoid
use would shift her
to high risk
Adapted from Siminoski K, et al. Can Assoc Radiol J 2005; 56(3):178-188.
CAROC: Women ≠ Men
A. Papaioannou et al. CMAJ 2010;182:1864-73B. Lentle et al. CARJ 62:243-250, 2011
MenWomen
Canadian FRAX Went Live July 2010
10-year Risk Assessment: FRAX
Leslie WD, et al. J Bone Miner Res 2010.Leslie WD, et al. Osteoporos Int 2010.Fraser L. Osteoporos Int 2010.
10-Year Major Fracture Probability
0
5
10
15
20
25
30
Sw
ed
en
Sw
itze
rla
nd
US
Ca
uca
sia
n
Au
str
ia
Un
ite
d K
ing
do
m
CA
NA
DA
Be
lgiu
m
Ja
pa
n
Ita
ly
Arg
en
tin
a
Ho
ng
Ko
ng
Fin
lan
d
Ge
rma
ny
US
His
pa
nic
US
Asia
n
Fra
nce
Ne
w Z
ea
lan
d
US
Bla
ck
Sp
ain
Le
ba
no
n
Ch
ina
Tu
rke
y
Pe
rce
nt fr
actu
re
Female Male
Age 65 years, prior fracture with femoral neck T-score -2.5
10-Year Hip Fracture Probability
0
2
4
6
8
10
12
Sw
ed
en
Au
str
ia
Be
lgiu
m
Sw
itze
rla
nd
Ita
ly
Un
ite
d K
ing
do
m
Arg
en
tin
a
US
Ca
uca
sia
n
Ho
ng
Ko
ng
Ge
rma
ny
Fin
lan
d
CA
NA
DA
Fra
nce
Ne
w Z
ea
lan
d
Ja
pa
n
Sp
ain
US
His
pa
nic
US
Asia
n
Le
ba
no
n
Ch
ina
US
Bla
ck
Tu
rke
y
Pe
rce
nt fr
actu
re
Female Male
Age 65 years, prior fracture with femoral neck T-score -2.5
Canadian FRAX uses:
• 2005 national hip fracture data
• 2004 national mortality data
• Estimates non-hip fractures from hip fractures
• Predictions validated in >45,000 Canadians
The site and reference technology is DXA
at the femoral neck. T-scores are based
on the NHANES reference values for
women aged 20-29 years. The same
absolute values are used in men.
• Without CAROC risk factors: 13% - moderate risk
• History of fragility fracture: 21% - high risk
• Systemic glucocorticoids: 21% - high risk
FRAX vs Updated 2010 CAROC
CaMos
0%
10%
20%
30%
Full FRAX CanFRAX
10-y
ear
Fra
ctu
res
Low (0-9) Moderate (10-19) High (20+)
2010 CAROC
Same risk category 90% of cases
Leslie WD and the FRAX Working Group. Osteoporos Int 2010.
Canadian
FRAX
FRAX
Lite
First Line Therapies with Grade A
Evidence for Fracture Prevention
Type of
Fracture
Antiresorptive therapy
Bone
formation
therapy
Bisphosphonates
Denosumab Raloxifene
Hormone
therapy
(Estrogen)
TeriparatideAlendronate Risedronate
Zoledronic
acid
Vertebral
Hip - -
Non-
vertebral+ -
Papaioannou A, et al. CMAJ 2010 Oct 12.
Importance of Prior Major Fracture:Re-fracture in 40,062 women and 17,721 men
Morin SN et al. ASBMR 2018.
Fracture Risk Assessment
Other Factors that Warrant Consideration for Pharmacological Therapy?E.G. LATERAL THORACOLUMBAR IMAGING TO IDENTIFY VERTEBRAL FRACTURES
High Risk10-year fracture risk > 20%
orPrior fragility fracture of hip or SPINE
orMore than one fragility fracture
Good evidence of benefit from pharmacotherapy
Importance of Vertebral Fractures
2010 Guidelines
Papaioannou A, et al. CMAJ 2010.
Case Finding with VFA
VFA VFA
Proportions Dispensed Medication
By VFA Results & Risk Category
Diff 25.9%
Diff 25.2%
Diff 9.1%
Schousboe JT et al. ASBMR 2018.
To Treat or Not to Treat?
• 70 year old woman:
• Breast cancer starting AI therapy
• Low Bone Mass / Osteopenic
• FRAX MOF 31%
Follow Up
• 72 year old woman:
• Breast cancer on AI therapy for 2 years
• No anti-osteoporosis tx
• Low Bone Mass / Osteopenic
• FRAX MOF 7.3%
Prior fracture: fell on the ice, injured wrists, x-ray no fracture
Parental hip fracture: adopted
Glucocorticoids: in conjunction with adjuvant breast chemotx
Rheumatoid arthritis: now indicates fibromyalgia
79 year old woman• Left “wrist” fracture age 55
• fell while curling
• Right radius/ulna fracture age
• stepped off curb
• Type 2 diabetes
• since age 50
• Father hip fracture
• age 102
FRAX Canada without BMD:
• no risk factors: 17%
+ prior fracture: 28%
+ prior fracture + parent hip fracture: 44%
+ prior fracture + RA (diabetes proxy): 38%
X
X
79 year old woman• Left “wrist” fracture age 55
• fell while curling
• Right radius/ulna fracture age
• stepped off curb
• Type 2 diabetes
• since age 50
• Father hip fracture
• age 102
FRAX Canada with BMD (femur neck T-score -2.2):
• no risk factors: 16%
+ prior fracture: 23%
+ prior fracture + parent hip fracture: 39%
+ prior fracture + RA (diabetes proxy): 29%
X
X
79 year old woman• Left “wrist” fracture age 55
• fell while curling
• Right radius/ulna fracture age
• stepped off curb
• Type 2 diabetes
• since age 50
• Father hip fracture
• age 102
CAROC with BMD (femur neck T-score -2.2):
• no risk factors: moderate risk
+ prior fracture: high risk
X
XX
VFA CT
Chest
x-ray
When in doubt….
FRAX vs CAROC: Summary
FRAX:
• Quantitative
• More risk factors
• Computer based
• Widely used in 2018
• Does not include falls and other risk factors
• Requires clinical judgment
CAROC:
• Semi-quantitative
• Simpler
• Table / graphic based
• Widely used in 2010
• Does not include falls and other risk factors
• Requires clinical judgment
Concluding Thoughts
• Osteoporosis is much more than DXA
• We have good tools to improve post fracture care