Escort Service Call Girls In Sarita Vihar,, 99530°56974 Delhi NCR
Seminar 09-04-2014 Osteoporose en cni
1.
Osteoporosebehandeling
bij
CKD
Joop
van
den
Bergh,
internist-‐endocrinoloog
VieCuri
MC
Noord-‐Limburg
Maastricht
UMC+
UHasselt,
België
2. CBO
guideline
2011
Osteoporose
en
fractuurprevenIe
1. PaIents
at
increased
risk
for
fracture
2. EvaluaIon
of
skeletal
status
(DEXA/VFA)
3. AnI-‐osteoporosis
therapy:
• BMD
T-‐score
≤
-‐2.5
• Vertebral
fracture(s)
3. Studies
of
fracture
risk
associated
with
CKD
Kidney
InternaIonal
2008:
721–731
• High
risk
of
fracture
because
of
low
bone
mineral
density
• Resembles
or
is
higher
than
in
postmenopausal
osteoporosis
4. However
• The
mineral
and
bone
disorder
associated
with
CKD
(CKD–MBD)
is
more
complex
than
osteoporosis
and
the
same
treatments
might
not
be
appropriate.
5.
Renal
osteodystrophy:
a
complex
interplay
of
geneIc,
growth
and
cellular
factors,
some
of
which
inhibit
bone
formaIon,
whereas
others
sImulate
bone
resorpIon
6. Prevalence
of
low,
normal,
and
high
bone
turnover
in
black
and
white
CKD
paIents
on
maintenance
dialysis
JBMR
2011:
1368–1376
Review
of
630
bone
biopsies
10. Bone
turnover
markers:
levels
dependent
on
eGFR
Moorthi
et
al.
Kidney
InternaIonal
2013:886–894
11. Studies
of
imaging
modaliIes
to
assess
fracture
status
in
paIents
with
CKD
that
report
test
diagnosIc
characterisIcs
Kidney
InternaIonal
2008:
721–731
14. HR-‐pQCT
radius
(lei)
and
Ibia
(right)
B
healthy,
post-‐
menopausal
C
predialysis
with
CKD
and
without
fracture
D
predialysis
with
CKD
with
prevalent
fracture
J
Am
Soc
Nephrol
21:
1371–1380,
2010
15. BMD
and
HR-‐pQCT
vs
fracture
predicIon
• while
both
tests
were
able
to
discriminate
fracture
status,
the
addiIon
of
HR
pQCT
measures
to
BMD
by
DXA
did
not
improve
fracture
discriminaIon
ability
Osteoporos
Int
2012:2805–2813
16. LimitaIons
in
clinical
pracIce
• Overlap
in
laboratory
parameters
• Bone
turnover
markers
influenced
by
eGFR
• BMD
/
DEXA
provides
‘only’
2D
density
parameters
• PotenIal
role
of
HRpQCT
needs
to
be
further
studied
• LimitaIons
for
bone
biopsies
(as
gold
standard)
in
clinical
pracIce
• UlImately:
combinaIon
of
mulIple
imaging
techniques
and
biomarkers
that
are
specific
to
each
gender
and
race
in
CKD
to
predict
fracture
risk
17. Considered
together
• Fracture
risk
appears
to
be
higher
than
in
age-‐
and
BMD-‐matched
paIents
without
CKD
• In
predialysis
CKD
without
substanIal
derangements
in
markers
of
mineral
metabolism
BMD
by
DXA
can
be
used
to
diagnose
osteoporosis
Jamal
et
al.
Curr
Rheumatol
Rep
(2012)
14:217–223
18. CBO
guideline
2011
Osteoporose
en
fractuurprevenIe
1. PaIents
at
increased
risk
for
fracture
2. EvaluaIon
of
skeletal
status
(DEXA/VFA)
3. AnI-‐osteoporosis
therapy:
• BMD
T-‐score
≤
-‐2.5
• Vertebral
fracture(s)
26. J
Bone
Miner
Res
1997;12:191–199
Bone
Biopsies
with
tetracycline
double
labelling
Nat.
Rev.
Nephrol.
Online
October
2013
27. Fracture
outcomes
in
paIents
with
CKD–MBD
• No
clinical
studies
to
assess
fracture
outcomes
in
paIents
with
CKD–MBD
28. Risedronate
in
PaIents
With
Age-‐Related
Reduced
Renal
FuncIon
:
A
Pooled
Analysis
of
Nine
Clinical
Trials
n=301
vs
271
J
Bone
Miner
Res
2005;20:2105–2115.
new
vertebral
fractures
29. Bisphosphonate
use
in
paIents
with
CKD
• Mainly
confined
to
those
with
early
stages
of
the
disease
• Post
hoc
analyses
from
osteoporosis
clinical
trials:
– paIents
with
mild
CKD
(but
normal
Ca,
AF
and
PTH)
have
a
similar
reducIon
in
fractures
to
that
observed
in
paIents
without
CKD
• Histological
findings:
in
only
one
single-‐centre,
observaIonal
study
– in
all
13
paIents
with
CKD
stage
2–4
who
had
taken
bisphosphonates,
bone
biopsies
revealed
adynamic
bone
disease*.
• The
KDIGO
commioee
could
not
idenIfy
any
clinical
trial
that
met
their
minimum
criteria
for
incorporaIon
into
their
consensus
guidelines:
inclusion
of
at
least
50
paIents
and
a
duraIon
of
at
least
6
months.
*Blood
Purif.
2010:293-‐99
31. Acute
Kidney
Injury
and
Bisphosphonate
Use
• Preclinical
and
clinical
observaIons
reveal
that
all
BPs
can
potenIally
cause
acute
tubular
necrosis
• Decline
in
GFR,
coupled
with
decreased
renal
blood
flow,
leads
to
reduced
drug
clearance
and
increased
concentraIon
of
drugs
in
the
renal
medulla
• Mainly
aier
iv
dosing
• In
cancer
paIents
(high
dose
and
co-‐morbidity)
J
Oncology
PracIce
2013:101-‐106
32. Raloxifene
(SERM)
• Raloxifene
is
excreted
via
hepaIc
metabolism,
and
serum
drug
concentraIons
are
about
1.4
Imes
higher
in
paIents
with
CKD
than
in
individuals
with
normal
renal
funcIon
• Aier
1
year
raloxifene,
lumbar
spine
BMD
(trabecular
bone)
significantly
improved,
femoral
neck
BMD
(corIcal
bone)
did
not
change
significantly
• Incidence
of
breast
cancer
is
lowered
by
70%
• However,
raloxifene,
like
oestrogen,
increases
the
risk
of
thromboembolism
Kidney
InternaIonal
2003:2269–2274
33. Denosumab
• MAB
that
targets
the
osteoclast-‐differenIaIon
cytokine
RANKL
– Reducing
the
number
of
osteoclasts
and
bone
formaIon
rates
• Is
not
excreted
by
the
kidney
34. JBMR
2012:
1471
GFR
at
baseline
by
Cockcroi-‐Gault
esImaIon:
• normal
renal
funcIon
(GFR
>80
mL/min/1.73m2)
• mild
CKD
(GFR
50–80
mL/min/1.73m2)
• moderate
CKD
(GFR
30–49
mL/min/1.73m2)
• severe
CKD
(GFR
<30
mL/min/1.73m2)
• kidney
failure
requiring
hemodialysis
35. Denosumab
in
paIents
with
CKD
• None
had
stage
5
CKD
• Fracture
risk
reducIon
and
changes
in
BMD
at
all
sites
were
in
favour
of
DMAb
• The
test
for
treatment
by
subgroup
interacIon
was
not
staIsIcally
significant,
indicaIng
that
treatment
efficacy
did
not
differ
by
kidney
funcIon
JBMR
2011;1829
36. • Denosumab
has
not
been
available
long
enough
to
assess
its
long-‐term
safety
in
paIents
with
CKD–MBD
• Problems
related
to
suppression
of
bone
formaIon
are
likely
to
be
seen
Denosumab
in
paIents
with
CKD
37. Hypocalcemia
aier
denosumab
in
severe
CKD
JBMR
2012:
1471
Calcium
and
vitamin
D
supplementaIon
was
not
iniIally
required
by
the
study
protocol,
but
was
added
during
the
trial
No
subject
who
received
adequate
calcium
and
vitamin
D
supplementaIon
became
hypocalcemic.
38. Hypocalcemia
• Increased
risk
of
post-‐denosumab
and
iv
bisphophonate
hypocalcaemia
in
renal
impairment
may
result
from
sudden
inhibiIon
of
the
high
bone
turnover
that
occurs
in
secondary
hyperparathyroidism
• Is
preventable
with
adequate
calcium
and
vitamin
D
supplementaIon
• Measurement
of
serum
calcium
levels
at
8–14
days
post-‐denosumab
may
be
useful
to
allow
Imely
detecIon
of
hypocalcaemia
and
insItuIon
of
early
treatment
Intern
Med
J.
2013
Nov;43(11):1243-‐6
39. Bone
turnover
and
BMD
aier
disconInuaIon
of
Denosumab
JCEM
2011:972–980
41. HD
paIents
• TeriparaIde
improved
BMD
with
adynamic
bone
disease,
although
no
staIsIcal
significance
• PaIents
with
osteiIs
fibrosa,
ibandronate
did
not
improve
BMD
while
cinacalcet
reduced
BMD
Am
J
Nephrol
2012;36:238–244
42. Cinacalcet
Effect
on
Risk
of
Fractures
Cunningham J, et al. Kidney Int. 2005;68:1793-1800.
Week
Event-FreeProbability
0 4 8 12 16 20 24 28 32 36 40 44 48 52
0.75
0.95
1.00
n = 487Placebo
n = 697Cinacalcet
Placebo
Cinacalcet
0.90
0.85
0.80
470 445 419 404 367 314 136 132 120 117 112 109383
656 614 574 554 485 392 132 131 125 115 110 106513
P = 0.04
Pooled analysis of safety data from 4 similarly designed randomized, double-blind, placebo-
controlled trials
All patients received standard care with phosphate binders and vitamin D, if prescribed.
43. Risk
of
Hip
Fracture
May
be
Greater
Aier
Parathyroidectomy
1,0
1,7
0,0
0,2
0,4
0,6
0,8
1,0
1,2
1,4
1,6
1,8
2,0
No
Parathyroidectomy
Parathyroidectomy
Adjusted
Odds
Ra;o
for
Hip
Fracture
Jadoul
M,
et
al.
Kidney
Int.
2006;70:1358-‐1366.
Dialysis
Outcomes
Prac;ce
PaBerns
Study
analysis
of
8,978
pa;ents
on
hemodialysis
with
and
without
a
history
of
parathyroidectomy
(2002-‐2004)
P
=
0.02
44. TeriparaIde
• Recombinant
PTH
(1-‐34)
– Anabolic
effect
• Small
observaIonal
studies
suggest
that
teriparaIde
might
be
beneficial
in
paIents
with
CKD–MBD
– who
have
adynamic
bone
disease
– who
have
undergone
parathyroidectomy
45. Conclusions
• PaIents
with
CKD
– Have
a
high
risk
of
fracture
owing
to
their
low
BMD
– ConvenIonal
medicaIons
for
osteoporosis
are
effecIve
at
reducing
fracture
rates
in
stage
3
CKD
and
normal
PTH,
Ca
and
phosphate
measurements
– In
stage
4–5
CKD,
or
those
with
abnormal
PTH
and
mineral
values,
the
available
data
are
insufficient
to
determine
whether
these
commonly
used
medicaIons
are
effecIve
against
fractures
46. Conclusions
• Alendronate,
risedronate
• Zoledronate
(iv)
• Denosumab
• Raloxifene
• TeriparaIde
• Cinacalcet
• Not
recommended
CrCl
<
30
(some
data
for
risedronate
if
CrCl
15-‐30)
• Contra-‐indicated
CrCl
<
35
• Might
be
useful
in
hypercalcemia
• Risk
of
hypocalcemia
CrCl
<
30,
risky
for
low
bone
turnover,
• No
concerns,
in
HD
beneficial
effects;
the
best
current
choice
in
women
with
CKD
without
VTE
problems
• Benefit
in
low
PTH
en
low
BMD
• Possible
effect
on
fractures
in
SHPT
