Seminair 22-11-2014 - Prof. dr. P. Geusens- Osteoporose en Mortaliteit

Prof. Dr. P. Geusens
Osteoporosis
and
mortality
Prof
Dr
Piet
Geusens
Reumatoloog
en
Revalida8earts
MUMC
&
UHasselt

MUMC
&
UHasselt
Arras,
France
OLL
Maastricht
2012

Only
post-‐mortem
fractures:
a
long
way
to
go
MUMC
&
UHasselt
Arras,
France

Mortality
aJer
fractures
MUMC
&
UHasselt
Arras,
France

• What
are
causes
of
mortality?
• How
much
the
risk
of
mortality
is
increased
aJer
fracture,
and
why?
• Mul8-‐outcome
compe8ng
risk
analysis
(re-‐fracture
+
mortality)
• Can
we
influence
post-‐fracture
mortality?
MUMC
&
UHasselt

www.index.mundi
Death rate Europe (/1000)
Nl: 8.4
Be: 10.6
MUMC
&
UHasselt

MUMC
&
UHasselt

MUMC
&
UHasselt
WHO website
ASDR: age-specic death rate

MUMC
&
UHasselt
WHO website

IS
THE
RISK
OF
MORTALITY
INCREASED
AFTER
FRACTURE?

Independent
effects
of
vertebral
deformity
(yes/no)
and
femoral
neck
BMD
T
score
(osteoporosis;
low/normal)
on
mortality
(bars).
Pongchaiyakul, J Bone Miner Res 2005;20:1349

Cumula8ve
mortality
over
5
years
WOMEN
0.8
0.6
0.4
0.2
Center JR et al., Lancet 1999, 353:878
MEN
Age
Dubbo Population Australia
Vertebral/Major Fractures
Proximal Femur Fractures
Vertebrall#
Survival probability
1.0
0.8
0.6
0.4
0.2
0
60 65 70 75 80 85
Age
Survival probability
1.0
0
Hip#
60 65 70 75 80 85
Population

Kaplan–Meier
survival
analysis
in
males
and
females
with
a
fragility
hip
fracture
in
2004–2005
Women
Men
Diamantopoulos, Clinical Interventions in Aging 2013:8 817
MUMC
&
UHasselt

Mortality
following
hip
fracture
compared
with
general
popula8on
values
Abrahamson, Osteoporos Int (2009) 20:1633

Mortality
aJer
second
HFx
stra8fied
according
to
sex
compared
with
the
mortality
of
the
background
popula8on
MUMC
&
UHasselt

Kaplan-‐Meier
survival
curves
for
women
with
osteoporo8c
fractures
aged
60–74
yr
(A),
aged
75+
yr
(B).
MUMC&UHasselt
Center, JCEM, 2011,1006

Standardized
mortality
ra8o
among
2901
Olmsted
County,
MN,
USA,
residents
following
a
fracture
due
to
no
more
than
moderate
trauma
in
1989–1991,
adjusted
for
age,
by
fracture
site,
and
sex
Melton, Osteoporos Int. 2013 May ; 24(5): 1689

Bliuc, JAMA, February 4, 2009—Vol 301

MUMC
&
UHasselt
Cameron, JBMR, 2010, pp 866

Adjusted*
hazard
ra8os
of
death
among
par8cipants
with
incident
hip
fracture
and
death
Ionnaidis, CMAJ 2009

Fractures and mortality: literature review of prospective studies
Population/cohort studies Osteoporosis cohort
Prevalent vertebral fracture
A. Leboime et al. / Joint Bone Spine 77 (2010) S107

Paiern
of
mortality
in
the
general
popula8on
and
following
hip
fracture
MUMC
&
UHasselt
Kanis, Bone 32 (2003) 468

MULTI-‐OUTCOME
COMPETING
RISK
ANALYSIS
(RE-‐FRACTURE
+
MORTALITY)

• Mul8-‐outcome
compe8ng
risk
analysis
– Compe88ef
risicomodel
• CBO
2011
• Opsporingsbeleid
– Case
finding
• Opvolging
– Follow
up

Cumula8ve
incidences
of
refracture
and
mortality
following
ini8al
osteoporo8c
fracture
MUMC
&
UHasselt
Bliuc, JBMR, 2013, pp 2317

Schema8c
illustra8on
of
various
outcome
states
during
8me-‐to
event
analysis
of
fracture
Leslie, Osteoporos Int (2013) 24:681

Competing risk model in cancer patients
Mutis, Leukemia , 2010, 1388
Effect of HA-1 disparity on all outcome
parameters, depending on the aGVHD
status. All curves estimated in a competing
risks framework; the four panels arise from
fitting a competing risk model on each of
the four subgroups separately (that is, four
univariate analyses without further model
assumptions apart from the competing
risks framework).
RFS: relapse-free survival;
NRM: non-relapse-related mortality.
MUMC
&
UHasselt

Cumula8ve
incidences
of
refracture
and
mortality
following
ini8al
osteoporo8c
fracture
Kaplan-‐Meyer
At 5 yrs:
26% died
24% re-fracture
At 5 yrs:
37% died
20% re-fracture
MUMC
&
UHasselt

Stacked
graph
of
cumula8ve
incidences
of
refracture,
mortality
following
ini8al
osteoporo8c
fracture,
and
mortality
following
refracture
MUMC
&
UHasselt

Stacked
graph
of
cumula8ve
incidences
of
refracture
and
mortality
aJer
one
osteoporo8c
fracture
and
aJer
refracture
compared
with
an
age-‐matched
general
popula8on
alive, no fracture
refracture and alive
excess deaths after refracture
excess deaths after initial fracture
expected mortality
Bliuc, JCEM, 2014

Stacked
graph
of
cumula8ve
incidences
of
mortality
following
ini8al
osteoporo8c
fracture
in
black
and
following
refracture
MUMC
&
UHasselt

Pa8ents
with
hip
fracture:
risk
of
subsequent
fracture
and
mortality
Re-fracture risk Mortality Re-fracture risk
in all in survivers
azMaastricht
&
UHasselt
Von Friessendorf, JBMR, 2008

Mortality
and
fractures
aJer
ini8al
hip
or
hand/foot
fracture
Maastricht
model
1st Hip
n=469 Died,
56%
8%
9%
27%
no
2nd
fracture
Fracture
+
died
Fracture
+
alive
Alive,
no
2nd
fracture
Absolute
fracture
risk
during
survival:
39%
20%
Maastricht
UMC
UHasselt
Huntjens, Osteoporos Int (2010) 21:2075

WHY
IS
THE
RISK
OF
MORTALITY
INCREASED
AFTER
FRACTURE?

Absolute
mortality
rates
and
age-‐adjusted
standardized
mortality
ra8os
according
to
BMD
and
ini8al
fracture
type
Bliuc, JBMR, 2014
MUMC
&
UHasselt

Popula8on-‐aiributable
risk/frac8on
(PAR/
PAF)
PAR
• 18%
in
women
and
25%
in
men,
similar
for
all
types
of
ini8al
NVNH
fracture
– Bliuc,
JCEM,
2014
• a
minority
of
deaths
following
hospitaliza8on
for
vertebral
fracture
are
aiributable
to
the
fracture
itself
– Kanis,
OI,
2004
PAF
• mortality
associated
with
hip
fracture
during
the
first
two
years
contributed
in
men
4.2%
and
in
women
5.1%
to
the
total
popula8on
mortality
(cigarie
smoking
and
high
blood
pressure
contributed
to
8%
and
7%)
– Omsland,
Bone,
2014

Excess
deaths
over
5
years
in
Dubbo
popula8on
by
sex
and
age-‐group
For all fracture patients, 9·5% of deaths were listed as
directly due to fracture, almost all of which were of the
hip. The other causes of death for the fracture patients
included causes secondary to cancer (21·9%), cardiac
disease (33·3%), and stroke (18·1%),
Center, Lancet, 1999

11% of deaths in women and >30% of deaths in men could be attributed to
low-trauma fractures
Bliuc, JBMR, 2014

Survival
with
Kaplan-‐Meier
analysis
during
22-‐yr
follow-‐up
MUMC
&
UHasselt
Von Friessendorf, JBMR, 2008

Black, JBMR, 2014

Prevalence
of
cardiovascular
risk
factors
and
diabetes
mellitus
type
2
according
to
the
center
classifica8on
Wyers, BioMed Research International, 2014

azMaastricht
&
UHasselt

Kristensen, Medical Care, 2014

Kaplan–Meier
survival
analysis
aJer
hip
fracture
I—independent community ambulator
II—community ambulatory with cane
Group Ia: previous vertebral fracture at the time of hip fracture
Group Ib: no vertebral fracture at the time of hip fracture
Ha, J Bone Miner Metab, 2014
MUMC
&
UHasselt

Frost, Bone, 2011
MUMC
&
UHasselt

The main causes of the excess mortality in the first 9 months were:
- infections (HR: 6.66, 95% CI 1.95–22.77, p<.002) for females
- cardiac disease (HR: 2.68, 95% CI 1.39–5.15, p<.003) for both males and
females.
Bisphosphonate use was associated with a reduction in mortality after hip
fracture (p<.002).
MUMC
&
UHasselt
Cameron, JBMR, 2010, pp 866

HR
for
mortality
by
number
of
dysmobility
condi8ons
and
age
Looker, OI, 2014
MUMC
&
UHasselt

Shortt, J Orthop Trauma 2005;19:396
MUMC
&
UHasselt

Pre-‐opera8ve
indicators
for
mortality
following
hip
fracture
surgery
MUMC
&
UHasselt
Smith, Age and Ageing 2014; 43: 464

CAN
WE
INFLUENCE
POST-‐FRACTURE
MORTALITY?

Can we decrease the risk of fractures?
A shocking question before 1990
Watts, NEJM, 1990, 73
MUMC
&
UHasselt

Agents
for
the
preven8on
of
fragility
fractures
compared
against
placebo
(combined
direct
and
indirect
es8mates).
Murad, JCEM, 2012, 1871
Network meta-analysis of 116 trials (139,647 patients;
median age, 64 yr; 86% females)

Can we decrease mortality after fractures?
A shocking question now?
MUMC
&
UHasselt

• 2.6%
of
incident
fractures
would
be
prevented
if
no
women
had
heart
disease
• 7.2%
of
incident
fractures
would
be
prevented
if
no
women
had
osteoarthri8s
• 1.5%
of
incident
fractures
would
be
prevented
if
no
women
had
COPD
• 0.4%
of
incident
fractures
would
be
prevented
if
no
women
had
mul8ple
sclerosis
and
0.4%
of
incident
fractures
would
be
prevented
if
no
women
had
Parkinson's
disease.
Dennison, Bone 50 (2012) 1288

5-‐year
mortality
rate
aJer
fracture
and
in
the
general
popula8on
according
to
femoral
neck
T-‐score
stra8fied
according
to
age
(>75
and
≤
75
years)
and
gender
(women
and
men)
Bliuc, JBMR, 2014
MUMC
&
UHasselt

Survival
rate
of
pa8ents
with
interval
from
injury
to
surgery
of
>5
and
≤5
days
MUMC
&
UHasselt
Li et al. Journal of Orthopaedic Surgery and Research 2014, 9:37

Hip
fracture
mortality
MUMC
&
UHasselt
Thomas, Bone Joint J 2014;96-B:373

Mortality
aJer
recent
hip
fracture
MUMC
&
UHasselt
Lyles, N Engl J Med 2007;357:1799-

HR
for
reduc8ons
in
death
by
8ming
of
first
study
drug
infusion
MUMC
&
UHasselt
Erikson, Bone Miner Res 2009;24:1308

Sattui, Nat. Rev. Endocrinol. 2014,10, 592

MUMC
&
UHasselt
Sattui, Nat. Rev. Endocrinol. 2014,10, 592

Kaplan-‐Meier
survival
curves
according
to
osteoporosis
medica8on
for
women
with
osteoporo8c
fractures
aged
60–74
yr
(A),
aged
75
yr
(B).
MUMC&UHasselt
Center, JCEM, 2011,1006

Mortality
incidence
within
2
years
aJer
baseline
fracture
between
the
interven8on
and
pre-‐interven8on
group
Before–after impact analysis in consecutive patients
older than 50 years who were admitted
In the same hospital with a NVF during 2 periods:
1/ pre-intervention group (n = 1,920, enrolled in 1999–
2001)
2/ intervention group (n = 1,335, enrolled in 2004–
2006).
Hazard ratio’s were calculated by multivariable Cox regression
analysis with adjustment for age, sex and baseline fracture location
Huntjens, Injury, Int. J. Care Injured 42S (2011) S39
MUMC
&
UHasselt

Cumula8ve
survival
rate
with
mortality
as
the
event
for
the
pa8ents
in
the
FLS
group
(black
line)
and
the
no-‐FLS
group
(gray
line).
Hospital with (MUMC) and without FLS (VieCuri)
Years 2005-2006
Huntjens, J Bone Joint Surg Am. 2014;96:e29(1-8)
MUMC
&
UHasselt

Mechanisms
of
decreased
post-‐fracture
mortality
• Decrease
of
subsequent
fracture
risk?
– Explains
only
8%
of
zoledronate
effect
• Treatment
of
secondary
osteoporosis,
other
metabolic
bone
diseases
and
co-‐morbidi8es?
• Adequate
calcium
and
vitamin
D
supply?
• …..?
MUMC
&
UHasselt

Conclusions
• The
risk
of
mortality
is
increased
aJer
fracture
• Mul8-‐outcome
compe8ng
risk
analysis
(re-‐fracture
+
mortality)
is
the
analysis
of
choice
• We
probably
can
influence
post-‐fracture
mortality:
– Decrease
of
subsequent
fracture
risk
– Treatment
of
secondary
osteoporosis,
other
metabolic
bone
diseases
and
co-‐morbidi8es
– Adequate
calcium
and
vitamin
D
supply
– And
…..
MUMC
&
UHasselt

It’s
8me
now,
Have
a
good
and
safe
WE
and
winter
holidays
MUMC
&
UHasselt

Seminair 22-11-2014 - Prof. dr. P. Geusens- Osteoporose en Mortaliteit

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Seminair 22-11-2014 - Prof. dr. P. Geusens- Osteoporose en Mortaliteit