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Prof Dr Willem F Lems
Department of Rheumatology
EULAR Centre of Excellence:
VU University medical centre and Reade,
Amsterdam, the Netherlands
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Een terugblik op ASBMR (en ACR) 2013
IWO-meeting Zwolle, 30 November 2013

(poten(ële)
belangenverstrengeling
Geen

Voor
bijeenkomst
mogelijk
relevante

rela(es
met
bedrijven

Eli
Lilly,
Novar(s,
MSD,
Servier,
Will

Pharma,
Takeda

•  Sponsoring
of
onderzoeksgeld

•  Honorarium
of
andere
(ﬁnanciële)

vergoeding

•  Aandeelhouder

•  Andere
rela(e,
namelijk
…

•
Eli
Lilly,
Novar(s,
MSD,
Servier,
Will
Pharma,

Takeda

•Eli
Lilly,
Novar(s,
MSD,
Servier,
Will
Pharma,

Takeda

•-‐

•-‐

Disclosure
belangen
spreker
Prof
Dr
WF
Lems

•  Wat
is
tegenwoordig
de
meest
gestelde
vraag
bij
nascholing

osteoporose?:

wat
te
doen
na
5
jaar
behandeling?

•  Nieuwe
Ontwikkelingen
Diagnos(ek
(VFA,
TBS:
al
besproken)

•  Vergelijkende
Studies
tussen
an(-‐osteoporose
medica(e

•  Botkwaliteit

•  Ontwikkeling
nieuwe
medicamenten

•  Fracture
Outpa(ent
Clinic

•  En
ook:
nieuwtjes
voor
de
prak(serende
osteoporose-‐
deskundige

Meest
gestelde
vraag
bij
nascholing
osteoporose:

wat
te
doen
na
5
jaar
behandeling?

Na
5
jaar
therapie*:

herevalua1e,
inclusief

klinische
risicofactoren

en
DXA

(en
VFA
of
RX
WK
bij

vermoeden
van
nieuwe

wervelbreuk)

Hoog
risico:

-‐ 
T
<-‐2.5
in
femurhals

-‐ 
Nieuwe
fractuur

-‐ 
Erns1ge
secundaire

osteoporose

-‐ 
Glucocor1coïden
≥7.5
mg/d

Laag
risico:

-‐ 
Geen
nieuwe
klinische

risicofactoren

-‐ 
T
>-‐2.5
in
femurhals

Verder

bisfosfonaat
of

andere
medica1e

of
SC,
IV

-‐
Leefs1jladviezen

-‐
Medica1e
staken

Opvolging
na
2-‐3
jaar

of
bij
nieuwe
fracturen

en
inclusief
klinische

risicofactoren,
DXA
(en
VFA

of
RX
WK
bij
vermoeden
van

nieuwe
wervelbreuk)

Herevalua(e
na
5-‐jaar
therapie;
expert
opinion!!!

Aanbevolen

Sterk
aanbevolen

Kan
zinvol
zijn

Gestructureerde
klinische

follow
up

Na
2
jaar
therapie
met

teripara1de/PTH
(1-‐84):

herevalua1e,
inclusief

klinische
risicofactoren

en
DXA

(en
VFA
of
RX
WK
bij

vermoeden
van
nieuwe

wervelbreuk)

Bisfosfonaat
of

raloxifeen

*Bisfosfonaten,
stron(um
ranelaat,
raloxifeen

CBO 2011

HORIZON-‐PFT
Extension
2:

Study
Design

•  3-‐year
interna(onal,
mul(center,
randomized,
double-‐blind
extension
study
enrolled
190

pa(ents
with
PMO
who
had
been
treated
with
ZOL
for
up
to
6
con(nuous
years
in
the
core

and
ﬁrst
extension
studies

*All patients received calcium 1000–1500 mg/d and vitamin D 400–1200 IU/d and follow-up telephone calls every 3 months; Core =
CZOL446H2301; First extension study = CZOL446H2301E1; ZOL = Zoledronic acid;
PMO = Postmenopausal osteoporosis
Core
treatment
assignment
(ZOL 5mg,
N=3889)
(Z6, N=616)
(Z3P3, N=617)
Year
3
(Z6P3, N=95)
(Z9, N=95)
p
1st
dose
q
p
2nd
dose
q
p
3rd
dose
q
p
last
visit
q
Year
7
Year
8
Year
9
Year
6
Core
treatment
assignment
(PBO,
N=3876)
(P3Z3, N=1223)
Ca & Vit D*
Z
=
Zoledronic
acid;
P
=
Placebo

NP4
request
number:
162307

Between-treatment comparison in percentage change in
total hip BMD from Core Study Baseline to Year 9 (ITT)
ITT = Intent-to-treat; BMD = Bone mineral density; Bracketed value is P value, ZOL vs placebo; n = Number of patients with values
at Year 0 and the follow-up visit
NP4
request
number:
162307

0
1
2
3
4
5
6
7
0 0,5 1 1,5 2 2,5 3 3,5 4 4,5 5 5,5 6 6,5 7 7,5 8 8,5 9
Changefrombaseline(%)
Time (years)
Z9
Z6P3
Z9 n = 94 94 94 91 91 92 83 72 67
Z6P3 n = 91 93 93 90 92 92 75 71 68
LS Mean = 0.15 0.29 0.92 0.58 0.55 0.56 1.08 1.71 0.96
Difference
[0.738]
[0.568]
[0.116]
[0.336]
[0.416]
[0.219]
[0.069]
[0.351]
[0.446]
Core Extension-1 Extension-2

Incidence of new Vertebral Morphometric Fractures in the
core study, Years 3-6 and Years 6-9 (ITT)
ITT = Intent-to-treat; Bracketed value is (n/N) n= Number of patients with the event; N = Number of patients in the analysis
population with x-rays; (%)= n/N*100; E2 - relative risk reduction of 40% (95% CI: -144% to 85%). The relative risk reduction
and the lower CI is negative that is quite different from core and extension 1
0
2
4
6
8
10
12
%Patients
ZOL PBO Z6 Z3P3 Z9 Z6P3
10.9%
[310/2853]
3.3%
[92/2822]
3.0%
[14/469]
6.2%
[30/486] 5.3%
[5/95]
3.2%
[3/95]
Morphometric vertebral fractures
Core Extension-1 Extension-2
70%*
(62, 76) 49%†
(26, 95)
*P < 0.001 vs. placebo
†P = 0.035 vs. Z3P3
‡P = 0.461 vs. Z6P3
40%‡
(-144, 85)
NP4
request
number:
162307

Overall
Safety
Results
of
the
Zol-‐Extension
2
Study

Category
Z9, n = 92
n (%)
Z6P3, n = 95
n (%)
Total subjects with any AEs 80 (87.0) 80 (84.2)
Total subjects with any SAEs 24 (26.1) 28 (29.5)
Total deaths 1 (1.1) 5 (5.3)
Total discontinuations due
to AEs
5 (5.4) 8 (8.4)
AE = Adverse event; PMO = Postmenopausal osteoporosis; SAE = Serious adverse event
NP4
request
number:
162307

Eight
Years
of
Denosumab
Treatment
in
Postmenopausal
Women

With
Osteoporosis:
Results
From
the
First
Five
Years
of
the

FREEDOM
Extension

FREEDOM EXTENSION
1 2 3Year 0 5 6 74 8 9 10
1 2 30 5 6 74Year
Denosumab 60 mg
SC Q6M
(N = 3902)
Placebo
SC Q6M
(N = 3906)
Calcium andVitamin D
Long-term
Denosumab
Cross-over
Denosumab
Denosumab 60 mg
SC Q6M
(N = 2343)
Denosumab 60 mg
SC Q6M
(N = 2207)
R
A
N
D
O
M
I
Z
A
T
I
O
N

RESULTS:
Percentage
Change
in
BMD

LS means and 95% confidence intervals. n = number of subjects with values at baseline and the time point of interest.
*P < 0.05 vs FREEDOM baseline; †P < 0.0001 vs FREEDOM baseline and extension baseline.
‡Represents subjects from the FREEDOM DXA substudy.

RESULTS:
Figure
4.
Yearly
Incidence
of

New
Vertebral
Fractures

n = number of subjects
with ≥ 1 fracture.
N = number of
randomized subjects who
remained on study at the
beginning of each period.
*Annualized incidence:
(2-year incidence) / 2.
Lateral radiographs
(lumbar and thoracic)
were not obtained at years
4 and 7 (years 1 and 4 of
the extension).
Placebo Long-term Denosumab Cross-over Denosumab
1/2* 4/5*3
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
YearlyIncidenceof
NewVertebralFractures(%)
Years of Denosumab Treatment
1980
34
1514
25
1496
50
N
n
3691
82
3186
98
3702 3247
35
3453
24
3400
32 107
2.2
3.1 3.1
0.9
0.7
1.1
0.9
1.7 1.7
FREEDOM EXTENSION
2101
58
1614
18
1567
38
4/5* 7/8*6
N
n
3691
82
3186
98
3702 3247
35
3453
24
3400
32 107
2.2
3.1 3.1
0.9
0.7
1.1
1.4
1.1 1.2
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
YearlyIncidenceof
NewVertebralFractures(%)
FREEDOM EXTENSION
1 2 3

RESULTS:
Figure
5.
Yearly
Incidence
of

Nonvertebral
Fractures

n = number of subjects
with ≥ 1 fracture. N =
number of randomized
subjects who remained on
study at the beginning of
each period. Percentages
for nonvertebral fractures
are Kaplan-Meier
estimates.
Placebo Long-term Denosumab Cross-over Denosumab
3.1
2.9
2.52.6
2.1 2.2
1.5
1.2
1.8
1.6
0.7
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
YearlyIncidenceof
NonvertebralFractures(%)
FREEDOM EXTENSION
2343 2244N
n 34 27
2067
34
1867
28
3906
116
3454
83
3902
98
3487
73
3682
75
3688
103
1742
12
1 2 3 4 5 7 86
YearlyIncidenceof
FREEDOM EXTENSION
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
2207 2105N
n 55 41
1965
46
1756
20
3906
116
3454
83
3902
98
3487
73
1646
22
3682
75
3688
103
1 2 3 4 5
3.1
2.9
2.52.6
2.1 2.2
2.5
2.0
2.6
1.2
1.4

RESULTS:
Table
2.
Exposure-‐adjusted

Subject
Incidence
of
Adverse
Events

(Rates
per
100
Subject-‐years)

N = number of subjects who
received ≥ 1 dose of investigational
product. Treatment groups are
based on the original randomized
treatments received in FREEDOM.
Rate = exposure-adjusted subject
incidence per 100 subject-years.
AEs coded using MedDRA v13.0.
ONJ = osteonecrosis of the jaw.
Cumulative ONJ cases: 3 cross-
over, 5 long-term. Cumulative
atypical femoral fracture cases: 1
cross-over, 1 long-term.
Denosumab Extension Study Years 1–5
Cross-over Denosumab Long-term Denosumab
N = 2206 N = 2343
Rate Rate
All AEs 99.7 100.8
Infections 22.3 21.1
Malignancies 1.9 2.0
Eczema 0.9 0.9
Hypocalcemia 0.1 < 0.1
Pancreatitis < 0.1 < 0.1
Serious AEs 10.2 10.7
Infections 1.3 1.4
Cellulitis or erysipelas < 0.1 < 0.1
Fatal AEs 0.7 0.8
ONJ < 0.1 < 0.1
Atypical femoral fracture < 0.1 < 0.1

Further
Reduc(on
in
Nonvertebral
Fracture
Rate
Is
Observed

Following
3
Years
of
Denosumab
Treatment:

Results
With
Up

to
7
Years
in
the
FREEDOM
Extension

S
Ferrari1,
et
al

ASBMR: 1018. Baltimore, MD, USA; October 4–7, 2013

FREEDOM
Extension
Study
Design

Key Inclusion Criteria for the Extension:
•  Completed the FREEDOM study (completed their 3-year visit, did not discontinue
investigational product, and did not miss > 1 dose).
•  Not receiving any other osteoporosis medications.
FREEDOM EXTENSION
1 2 3Year 0 5 6 74 8 9 10
1 2 30 5 6 74Year
R
A
N
D
O
M
I
Z
A
T
I
O
N
DMAb 60 mg
SC Q6M
(N = 3902)
Placebo
SC Q6M
(N = 3906)
Long-term
DMAb
Treatment
Cross-over
DMAb
Treatment
DMAb 60 mg
SC Q6M
(N = 2343)
DMAb 60 mg
SC Q6M
(N = 2207)
Calcium and Vitamin D

n
=
number
of
subjects
who
have
≥
1
nonvertebral
fracture.
Percentages
for
nonvertebral
fractures
are
Kaplan-‐Meier
es1mates.

Yearly Nonvertebral Fracture Incidence
With DMAb Treatment for Up to 7 Years
Long-term
DMAb
Treatment
Long-term DMAb Cross-over DMAb
YearlyIncidenceof
Years of DMAb Treatment
2066 1867
43 47 33 27 31 2746
2207 2105 1964 1755
FREEDOM EXTENSION
Cross-over
DMAb
Treatment
n
N 2343 2343 2343 22432343
N
n 53 40 40 17
YearlyIncidenceof
Years of DMAb Treatment
EXTENSION

Further
reduc(on
in
Nonvertebral
Fracture
Rate
by
denosumab:

7
year
data,
a
new
analysis
(1018).

Klinische
Consequen(es:

Bij
de
afweging
over
wel
of
niet
doorgaan
met
behandelen

na
5
jaar,
zijn
er
nu
gegevens
over
eﬀec(viteit
beschikbaar

over
7-‐8
jaar
over
denosumab.

Andere
gegevens
spelen
ook
een
rol:

•  kans
op
bijwerkingen;

•  achtergrond-‐risico:
high
risk
pa(ent?;

•  wens
van
de
pa(ent;

•  Kosten;

•  Lange
termijn
eﬀecten.

A
Longitudinal
Study
of
Skeletal
Histomorphometry
in
Subjects

On
Teripara(de
(TPTD)
or
Zoledronic
Acid
(ZOL),
The
SHOTZ

Study

Objective: To evaluate the biological effects of TPTD and ZOL in
postmenopausal women with osteoporosis, based on histomorphometric indices
and material properties
Study

Design

• A
2-‐year
trial
with
paired
biopsy
design

• Pa(ents
who
completed
1-‐year
randomized
trial
were
eligible
for
1-‐year,

open-‐label,
extension
study

Postmenopausal
women

with
osteoporosis

N
=
19

TPTD

20
μg/d,
SC

n
=
10

Aper
6
and
24
months,
transiliac
crest
bone
biopsies
were
performed
aper
tetracycline

labeling

SC, subcutaneous; TPTD, teriparatide; ZOL, zoledronic acid.
Dempster D, et al. Columbia University, USA. A longitudinal Study of Skeletal Histomorphometry in Subjects On Teriparatide (TPTD) or Zoledronic acid (ZOL), the SHOTZ Study. Abstract
[1020]. Presented at the 2013 Annual Meeting of The American Society for Bone and Mineral Research. October 5, 2013.
ZOL
5
mg/y,

IV
infusion

n
=
9

Assessments

1020

A
longitudinal
study
of
Skeletal
Histomorphometry
in
subjects
On
Teripara(de

(TPTD)
or
Zoledronic
acid
(ZOL),
the
SHOTZ
study.
David

Dempster
et
al.

Objec1ve:
To
test
the
hypothesis
that
BMD
increases
following
denosumab
administra(on,
which
is
seen
despite

low
bone
turnover
markers
and
limited
iliac
crest
tetracycline
labeling,
result
from
a
non-‐remodeling
dependent

mechanism
that
accrues
bone
matrix

The
hypothesis
was
tested
by
examining
the
ﬂuorochrome
labeling
parern
in
proximal
femur
sec(ons
from

ovariectomized
cynomolgus
monkeys
treated
with
denosumab
for
16
months

Dempster D, et al. Columbia University, USA. Continuous Modeling-Based Bone Formation: A Novel Mechanism That Could Explain the Sustained Increases in Hip Bone Mineral Density
(BMD) With Denosumab Treatment. Abstract [LB-MO30]. Presented at the 2013 Annual Meeting of The American Society for Bone and Mineral Research. October 7, 2013.
Mature
ovariectomized
cynomolgus

monkeys
(N
=
34;
age
>9
years)

Vehicle
(n
=
20)

Denosumab

25
mg/kg
(n
=
14)

•  Administra(on
of
ﬂourochrome
labels
was
at
months
6,
12,
and
16

•  Dose
of
denosumab
was
25x
clinical
dose

BMD, bone mineral density.
Continuous Modeling-Based Bone Formation: A Novel Mechanism
That Could Explain the Sustained Increases in Hip Bone Mineral
Density (BMD) With Denosumab Treatment

Figure: Epifluorescent micrograph from denosumab-treated cynomolgus monkeys femur sections
•  Both
the
superior
endocortex
and
the
inferior
periosteal
surface
contained
mul(ple
superimposed
labels
over
smooth

cement
lines
which
open
spanned
months
6
to
16
(see
ﬁgure),
sugges(ng
that
modeling-‐based
bone
forma(on
occurred

con(nuously
during
denosumab
administra(on

•  Signiﬁcant
increase
in
bone
strength
was
due
to
augmenta(on
of
bone
mass,
which
occurred
at
biomechanically
relevant

sites
on
the
superior
and
inferior
aspects
of
the
femur
neck

Source: Dempster D, et al. Presented at the 2013 Annual Meeting of The ASBMR. October 7, 2013.
Dempster D, et al. Columbia University, USA. Continuous Modeling-Based Bone Formation: A Novel Mechanism That Could Explain the Sustained Increases in Hip Bone Mineral Density
(BMD) With Denosumab Treatment. Abstract [LB-MO30]. Presented at the 2013 Annual Meeting of The American Society for Bone and Mineral Research. October 7, 2013.
Continuous Modeling-Based Bone Formation: A Novel Mechanism
That Could Explain the Sustained Increases in Hip Bone Mineral
Density (BMD) With Denosumab Treatment
Results

Objec1ve:
To
determine
the
compara(ve
eﬀects
of
TPTD,
DMAB,
and
combina(on

therapy
(COMBO)
on
peripheral
compartmental
bone
density
and
microarchitecture

Tsai J, et al. Massachusetts General Hospital, USA. Comparative Effects of Teriparatide, Denosumab, and Combination Therapy on Peripheral Compartmental Bone Density and
Microarchitecture: the DATA-HRpQCT Study. Abstract [FR0372]. Presented at the 2013 Annual Meeting of The American Society for Bone and Mineral Research. October 4, 2013.
Postmenopausal

women

age
(51–91)

randomized

(N
=
100)

TPTD

20-‐ug
SC
QD

DMAB

SC
Q6
months

COMBO

12
months

Measurements
at
distal
radius
and

(bia
by
HR-‐pQCT

•  DTot,
DTrab,
DCort

•  Tb.Th,
Tb.Sp,
Tb.N

•  Ct.Th,
Ct.Po

Ct.Th, cortical thickness; Ct.Po, cortical porosity; DMAB, denosumab; DTot, total density; Dtrab, trabecular density; Dcort, cortical density; HR-pQCT,
high-resolution peripheral quantitative computed tomography; QD, once a day; SC, subcutaneous; Tb.TH, trabecular thickness; Tb.Sp, trabecular spacing; Tb.N, trabecular number;
TPTD, teriparatide.
Compara(ve
Eﬀects
of
Teripara(de,
Denosumab,
and

Combina(on
Therapy
on
Peripheral
Compartmental

Bone
Density
and
Microarchitecture:
The
DATA-‐HRpQCT
Study

1019.
The
DATA
Extension
Study:
2
Years
of
Combined
Denosumab
and

Teripara(de
in
Postmenopausal
Women
with
Osteoporosis:
A
Randomized

Controlled
Trial.
Benjamin
Leder
et
al.

Mean percent change (SD) from baseline in bone density and
microarchitecture at 12 months at the radius
•  Increase
in
Dcort
was
observed
in
the
COMBO
group
versus
TPTD
group
(P<.01)

•  Cor(cal
porosity
was
increased
more
with
TPTD
(18.0,
36.4%)
than
in
DMAB
(2.9,
18.8%)
and
COMBO
(3.0,

18.7%)

-‐5

0

5

10

15

20

DTot
DTrab
DCort
Tb.Th
Tb.Sp
Tb.N
Ct.Th
Ct.Po

Mean
percent
change
from
the

baseline

HR-‐pQCT

TPTD

DMAB

COMBO

Ct.Th, cortical thickness; Ct.Po, cortical porosity; Dcort, cortical density; DMAB, denosumab; DTot, total density; Dtrab, trabecular density; HR-pQCT,
TPTD, teriparatide.
Compara(ve
Eﬀects
of
Teripara(de,
Denosumab,
and

Combina(on
Therapy
on
Peripheral
Compartmental

Bone
Density
and
Microarchitecture:
The
DATA-‐HRpQCT
Study

Results

Mean percent change (SD) from baseline in bone density and
microarchitecture at 12 months at the tibia
•  In
the
COMBO
group,
increased

DTot
was
observed
at
the
(bia
(3.1,
2.1%)
when
compared
with
the
TPTD

(0.0,
2.3%,
P<.0001)
and
DMAB
groups
(2.2,
2.0%,
P
=
.011)

•  Cor(cal
porosity
increased
more
at
(bia
in
TPTD
(5.6,
10.3%)
than
in
DMAB
(-‐2.0,
10.6%)
and
COMBO
(-‐1.0,

10.0%)

Ct.Th, cortical thickness; Ct.Po, cortical porosity; Dcort, cortical density; DMAB, denosumab; DTot, total density; Dtrab, trabecular density; HR-pQCT,
TPTD, teriparatide.
Compara(ve
Eﬀects
of
Teripara(de,
Denosumab,
and

Combina(on
Therapy
on
Peripheral
Compartmental

Bone
Density
and
Microarchitecture:
The
DATA-‐HRpQCT
Study

Results

Objec1ve:
To
assess
the
12-‐month
eﬀect
of
romosozumab
on
LS
and
TH
BMD,
and
bone
BMC
as

measured
by
QCT
in
postmemopausal
women
(aged
55–85
years)
with
LS,
TH,
or
femoral
neck
T-‐
score
≤-‐2.0
and
≥-‐3.5

Genant HK, et al. USCF & Synarc Inc., USA. Effect of Romosozumab on Lumbar Spine and Hip Volumetric Bone Mineral Density (vBMD) as Assessed by Quantitative Computed
Tomography (QCT). Abstract [1022]. Presented at the 2013 annual meeting of The American Society of Bone and Mineral Research. October 5, 2013.
•  Interna(onal,
randomized,
placebo-‐controlled,
Phase
II
study

•  Subjects
with
baseline
and
≥1
post-‐baseline
QCT
measurements
were
included
in
the

analyses

•  Measurements
were
performed
at
the
“total”
LS
(mean
of
L1
and
L2
en(re
vertebral

bodies)
and
TH
with
QCT

•  Percentage
change
from
baseline
in
integral
and
cor(cal
vBMD
and
BMC
and
trabecular

vBMD
was
evaluated
for
placebo,
20
µg
QD
subcutaneous
TPTD
and
210
mg
QM

romosozumab
at
12
months

Study
design

Par1cipants

Inves1ga1ons

BMC, bone mineral content; LS, lumbar spine; QCT, quantitative computed tomography; TH, total hip; TPTD, teriparatide; vBMD, volumetric bone mineral density.
Eﬀect
of
Romosozumab
on
Lumbar
Spine
and
Hip
Volumetric
Bone
Mineral

Density
(vBMD)
as
Assessed
by
Quan(ta(ve
Computed
Tomography
(QCT)

Effect
of
Romosozumab
on
Lumbar
Spine
and
Hip
Volumetric
Bone
Mineral

Density
(vBMD)
as
Assessed
by
Quan(ta(ve
Computed
Tomography
(QCT)

Results

Percentage change in integral vBMD and BMC from baseline at 12 months
*P<.05 compared with baseline, placebo, and TPTD
BMC
25
20
15
10
5
0
-5
10
7.5
5
2.5
0
-2.5
-5
*
*
*
*
Placebo Teriparatide Romosozumab
Percentagechange
frombaseline
LSmean(96%CI)
Percentagechange
frombaseline
LSmean(95%CI)
“Total” lumbar spine
Total hip
vBMD BMC
vBMD
n = 18 n = 19 n = 9n = 19 n = 9n = 18
n = 27 n = 30 n = 24 n = 27 n = 30 n = 24
vBMD, volumetric bone mineral density; BMC, bone mineral content; LS, lumbar spine; TH, total hip; TPTD, teriparatide.
•  Significant
increases
in

integral
vBMD
and
BMC

were
observed
at
both
the

“total”
LS
and
TH
from

baseline
with

romosozumab
treatment

compared
with
placebo

and
TPTD

•  No
difference
between

TPTD
and
placebo
was

observed
for
TH


•  Trabecular
vBMD
increased
from
baseline
with
romosozumab
and
TPTD
at
both
LS

and
TH
(P<.05
for
both)

–  At
LS,
gains
were
similar
with
both
romosozumab
and
TPTD
(18.3%
vs
20.1%,

respec(vely)

–  At
TH,
gains
were
greater
with
romosozumab
compared
with
TPTD
(10.8%
vs
4.2%,
P<.
05)

•  Cor(cal
vBMD

–  At
LS,
greater
increases
with
romosozumab
(13.7%)
compared
with
TPTD
(5.7%);
P<.0001

–  At
TH,
increases
with
romosozumab
(1.1%),
but
not
with
TPTD
(-‐0.9%)

•  Cor(cal
BMC

–  At
LS,
increases
with
romosozumab
compared
with
TPTD
(23.3%
vs
10.9%,
P<.0001)

– 
At
TH,
increase
with
romosozumab
was
3.4%
compared
with
0.0%
with
TPTD,
P<.05

vBMD, volumetric bone mineral density; BMC, bone mineral content; LS, lumbar spine; TH, total hip; TPTD, teriparatide.
Eﬀect
of
Romosozumab
on
Lumbar
Spine
and
Hip
Volumetric
Bone
Mineral

Density
(vBMD)
as
Assessed
by
Quan(ta(ve
Computed
Tomography
(QCT)

Results

Objec1ve:
To
evaluate
the
effects
of
subcutaneous
blosozumab
treatment
on
non-‐invasive

es(mates
of
spine
and
hip
strength
in
postmenopausal
women
(mean
age,
62
years)
with
low
areal

BMD
(lumbar
spine
T-‐score
of
-‐3.5
to
-‐2.0)

Tony Keaveny, et al. University of California, Berkeley, USA. Effects of Blosozumab on Estimated Spine and Hip Strength in Postmenopausal Women with Low Bone Mineral Density:
Finite Element Analysis of a Phase-II Dosing Study. Abstract [1023]. Presented at the 2013 annual meeting of The American Society of Bone and Mineral Research. October 5, 2013.
Analyses
of
sub-‐group
of
pa(ents
enrolled
in
a
double-‐blind,
placebo-‐controlled,
randomized,

mul(center,
1-‐year
Phase-‐II
dosing
study

•  To
es(mate
spine
and
hip
strength,
finite
element
analyses
were
performed
for
all
pa(ents

who
had
spine
and/or
hip
CTs
at
baseline
and
at
either
24
or
52
weeks,
using
the
VirtuOst

sopware
(O.N.
Diagnos(cs,
Berkeley,
CA)

•  Sta(s(cal
analyses
were
carried
out
using
a
mixed-‐effect
model

Study
design

Postmenopausal
women
with
low
areal
BMD

(n
=
42;
all
receiving
calcium
+
vitamin
D)

Assessments

Placebo

Blosozumab
180
mg

every
4
weeks

Blosozumab
180
mg

every
2
weeks

Blosozumab
270
mg

every
2
weeks

BMD, bone mineral density.
Effects
of
Blosozumab
on
Es(mated
Spine
and
Hip
Strength
in
Postmenopausal

Women
With
Low
Bone
Mineral
Density:
Finite
Element
Analysis
of
a
Phase-‐II

Dosing
Study

Eﬀects
of
Blosozumab
on
Es(mated
Spine
and
Hip
Strength
in
Postmenopausal

Women
With
Low
Bone
Mineral
Density:
Finite
Element
Analysis
of
a
Phase-‐II

Dosing
Study

Results

Change in finite element-estimated spine and hip strength
Percent change from baseline; LS mean (95% CI)
P<.05 at least, as compared with placebo (†) or baseline (*); n = number of patients.
CI, confidence interval.
•  Although
there
was
no
change
in
either
spine
or
hip
strength
from
baseline
in
the
placebo

group,
an
increase
in
both
spine
and
hip
strength
was
observed
at
both
week
24
and
week
52

in
the
treated
groups
(P<.05
at
least)

Placebo

Blosozumab
180
mg

every
4
weeks

Blosozumab
180
mg

every
2
weeks

Blosozumab
270
mg

every
2
weeks

Spine

24
weeks

-‐0.4
(-‐7.1,
6.3)

n
=
10

12.0†*
(5.5,
18.4)

n
=
11

27.5†*
(21.4,
33.7)

n
=
12

29.5†*
(21.3,
37.9)

n
=
7

52
weeks

0.7
(-‐7.0,
8.5)

n
=
7

13.7†*
(6.3,
21.3)

n
=
8

32.0†*
(25.0,
38.5)

n
=
10

37.0†
(26.8,
47.2)

n
=
3

Hip

24
weeks

-‐0.4
(-‐2.3,
1.4)

n
=
11

0.7
(-‐1.1,
2.5)

n
=
12

3.1†*
(
1.3,
4.9)

n
=
12

9.6†*
(7.1,12.1)

n
=
6

52
weeks

0.3
(-‐1.9,
2.4)

n
=
8

1.4*
(-‐0.6,
3.5)

n
=
9

5.4†*
(3.4,
7.4)

n
=
10

12.6†*
(9.3,
15.9)

n
=
3

Tony Keaveny, et al. University of California, Berkeley, USA. Effects of Blosozumab on Estimated Spine and Hip Strength in Postmenopausal Women with Low Bone Mineral Density:
Finite Element Analysis of a Phase-II Dosing Study. Abstract [1023]. Presented at the 2013 annual meeting of The American Society of Bone and Mineral Research. October 5, 2013.

The
Pharmacokine(cs
of
Odanaca(b
50
mg
Are
Not
Affected

by
Severe
Renal
Insufficiency

Objective: To assess the impact of severe renal insufficiency on pharmacokinetics,
pharmacodynamics, and tolerability of odanacatib 50 mg

Stoch A, et al. USA. The Pharmacokinetics of Odanacatib 50 mg are Not Affected by Severe Renal Insufficiency. Abstract [SA0390]. Presented at the 2013 Annual Meeting of The
American Society for Bone and Mineral Research. October 5, 2013.
Open-label, single-dose study;
odanacatib orally administered to
Subjects
(n=13)
with
severe
renal
insufficiency*

(aged
47–79
years)

Healthy
control
(n=12)
subjects**

(aged
40-‐72
years)

Collection of plasma and urine samples (pre-dose and at specified time points over 15 days post-
dose) for analyzing odanacatib concentrations and biomarkers
*Defined as a creatinine clearance of <30 mL/min, **creatinine clearance ≥90 mL/min; both the groups were matched for age, gender, and body mass index.
•  ANCOVA
model
to
determine
odanaca(b
AUC0-‐∞
on
log
scale

•  AUC0-‐∞
GMR
to
determine
pharmacokine(c
similarity
between
2
groups
based
on
the
90%
CI
for
the
GMR

contained
within
the
comparability
bounds
of
(0.40,
2.50)

•  Determina(on
of
Cmax,
Tmax,
and
apparent
terminal
t1/2

•  Analysis
of
serum
NTx
and
urine
NTx/Cr
to
determine
pharmacodynamics
by
linear
mixed
effect
model

•  AEs
analyzed
throughout
the
study

AEs, adverse events; ANCOVA, analysis of covariance; AUC, area under the curve; CI, confidence interval; Cr, creatinine; Cmax, maximum plasma concentration; GMR, geometric mean
ratio; NTx, N-terminal telopeptide; Tmax, time to reach maximum concentration; t1/2, half-life.

The
Pharmacokine(cs
of
Odanaca(b
50
mg
Are
Not
Affected

by
Severe
Renal
Insufficiency

Results

95% CI
-47.30,
-23.38
95% CI
-53.39,
-30.76
95% CI
-65.81,
-51.51
95% CI
-52.83,
-32.08
AEs, adverse events; AUC, area under the curve; CI, confidence interval; Cmax, maximum plasma concentration; Cr, Creatinine; GMR, geometric mean ratio; NS, Non-sgnificant;
NTx, N-terminal telopeptide; t1/2 , half-life.
The
differences
in
serum
NTx
and
urine
NTx
levels
between
the
pa(ents
with
renal
insufficiency
and
healthy-‐
matched
controls
were
non-‐significant
(*P
=
NS)

Serum NTx and urine NTx/Cr values at 168 hours post-dose
Stoch A, et al. USA. The Pharmacokinetics of Odanacatib 50 mg are Not Affected by Severe Renal Insufficiency. Abstract [SA0390]. Presented at the 2013 Annual Meeting of The
American Society for Bone and Mineral Research. October 5, 2013.

Effect of Odanacatib on BMD and Fractures: Results
From Bayesian Univariate and Bivariate Meta-Analyses
Systema(c
review
of

Medline,
EMBASE,

Cochrane
library,

conference
proceedings,

and
bibliographies

31
poten(al
ar(cles

selected

6
ar(cles
on
4
RCT’s

included
(N
=
788)

Objective: Using Bayesian univariate and bivariate meta-analysis, this
systematic review aimed to estimate the efficacy of ODN (50 mg/wk) in current
trials and predicted its efficacy in future trials
Gajic-Veljanoski O, et al. University Health Network, Canada. Effect of odanacatib on BMD and fractures: Results from Bayesian univariate and bivariate meta-analyses. Abstract
[SA0384]. Presented at the 2013 Annual meeting of The American Society for Bone and Mineral Research. October 5, 2013.
BMD, bone marrow density; ODN, odanacatib; RCT, randomized controlled trial.

Bayesian
univariate
meta-‐analyses:
Eﬃcacy
of
ODN
on
BMD
or
all
fractures
(1-‐3
yrs)

Eﬀect
of
Odanaca1b
on
BMD
and
Fractures:
Results

From
Bayesian
Univariate
and
Bivariate
Meta-‐Analyses

0 2 4 6 8 10
1.0
0.8
0.6
0.4
0.2
0.0
Density
Mean Difference in LS BMD (% Change): ODN 1-3 Years
De Villiers 2012
Brixen 2013
Nakamura 2013
Eisman 2011
POOLED MD
FUTURE MD
1.0
0.8
0.6
0.4
0.2
0.0
0 2 4 6 8 10
De Villiers 2012
Nakamura 2013
Eisman 2011
Brixen 2013
POOLED MD
FUTURE MD
0.0 0.5 1.0 1.5 2.0 2.5 3.0
6
5
4
3
2
1
0
De Villiers 2012
Brixen 2013
Eisman 2011
POPULATION OR
FUTURE OR
1.0
0.8
0.6
0.4
0.2
0.0
0 2 4 6 8 10
De Villiers 2012
Nakamura 2013
Eisman 2011
Brixen 2013
POOLED MD
FUTURE MD
Density
Mean Difference in TH BMD (% Change): ODN 1-3 Years
Density
Odds Ratio-All Fracture: ODN 2-3 years
Density
Mean Difference in FN BMD (% Change): ODN 1-3 Years
BMD, bone marrow density; ODN, odanacatib.
Gajic-Veljanoski O, et al. University Health Network, Canada. Effect of odanacatib on BMD and fractures: Results from Bayesian univariate and bivariate meta-analyses. Abstract
[SA0384]. Presented at the 2013 Annual meeting of The American Society for Bone and Mineral Research. October 5, 2013.

How
to
TREAT
pa(ents
with
atypical
fractures?

1079

Histology
of
Atypical
Femoral
Fractures.
Jorg
Schilcher*1,

1080
Effect of Teriparatide on Healing of Incomplete Atypical Femur Fractures.
Angela M. Cheung* et al

Histology
of
Atypical
Femoral
Fractures

Results

Histological
observa1ons

Fracture
gap
(X)

Amorphous
material
(+)

Thin
layer
of
amorphous

material
between
intact

bone
and
fragment

(lamellar
bone
tend
to

loosen);
white
arrows

Resorp(on
cavi(es

near
the
fracture
(black

arrows
)

Adapted from Schilcher J, et al. Presented at the 2013 Annual Meeting of The ASBMR. October 7, 2013.
Schilcher
J,
et
al.
Linköping
University,
Sweden.
Histology
of
Atypical
Femoral
Fractures.
Abstract
[1079].
Presented
at
the
2013
Annual
Mee(ng
of
The
American
Society
for
Bone
and
Mineral
Research.

October
7,
2013.

Effect
of
Teripara(de
on
Healing
of
Incomplete
Atypical

Femur
Fractures

Objec1ve:
To
evaluate
the
efficacy
of
teripara(de
in
pa(ents
with
incomplete
AFFs

AFF, atypical femur fracture; ASBMR, American Society for Bone and Mineral Research; CT, computed tomography.
Cheung AM, et al. University Health Network-University of Toronto, CANADA. Effect of Teriparatide on Healing of Incomplete Atypical Femur Fractures. Abstract [1080]. Presented at the
2013 Annual Meeting of The American Society for Bone and Mineral Research. October 7, 2013.
• Pa(ents
from
the
larger
Ontario
AFF
cohort
study
(N
=
22)
who
sa(sfied
the

criteria
for
the
defini(on
of
AFF
according
to
the
ASBMR
Task
Force
Par(cipants

• Fracture
healing
evaluated
by
CT
scans
and
plain
radiographs

• Measurement
of
depth
of
the
lucency
line
through
the
cortex
and
degree

of
extension
around
the
circumference
every
6
months
up
to
2
years

• Capture
of
progression/regression
of
fracture
line
up
to
last
follow-‐up

Inves(ga(ons

• Descrip(ve
sta(s(cs
Sta(s(cal
analysis

Eﬀect
of
Teripara(de
on
Healing
of
Incomplete
Atypical
Femur
Fractures

Results

25(OH)D, 25-hydroxyvitamin D; AFF, atypical femur fracture; BMD, bone mineral density; BMI, body mass index; FN, femoral neck; LS, lumbar spine; PTH, parathyroid hormone;
TH, total hip; TPD, teriparatide.
•  All
pa(ents
were
postmenopausal
women
(mean
age
65.9
years;
range
26.0–80.8
years)
with
normal

ionized
calcium
and
intact
PTH

•  Mean
BMI
=
28.4
kg/cm2
and
mean
serum
25(OH)
D
=
110
nmol/L

•  77%
(n
=
17)
had
bilateral
AFFs
(12
complete
AFF
and
5
bilateral
incomplete
AFF)
and
23%

(n
=
5)
had
unilateral
incomplete
AFF

•  Mean
BMD
T-‐scores
at
diagnosis
were

–  LS:
-‐
1.76

–  TH:
-‐
1.16

–  FN:
-‐
1.78

•  Average
length
of
bisphosphonate
use
was
12
years

At
diagnosis

•  Average
dura(on
of
TPD
was
18.8
months

•  3
pa(ents
had
prophylac(c
surgical
repair

•  15
pa(ents
had
19
incomplete
AFFs
(2
healed,
5
healing,
and
12
stable
AFFs)

•  Worsening
of
fracture
was
not
observed
in
any
pa(ent

•  New
lucency
lines
in
the
same
femur
as
their
original
AFFs
developed
in
4
pa(ents

Aner
TPD
treatment

Cheung AM, et al. University Health Network-University of Toronto, CANADA. Effect of Teriparatide on Healing of Incomplete Atypical Femur Fractures. Abstract [1080]. Presented at the
2013 Annual Meeting of The American Society for Bone and Mineral Research. October 7, 2013.

Once-‐Weekly
Teripara(de
Reduces
Vertebral
Fracture

Risk—Subgroup
Analysis
From
the
Teripara(de
Once-‐Weekly

Eﬃcacy
Research
(TOWER)
Trial,
542
Japanese

pa(ents
(RCT)

Results

BMD, bone mineral density; eGFR, estimated glomerular filtration rate; RR, relative risk; SD, standard deviation.
•  2.7%
teripara1de
subjects
and
13.2%
placebo
subjects
had
incident
vertebral
fracture

•  RR
for
incident
vertebral
fracture
was
0.20
(P<.001)

•  Incident
vertebral
fractures
were
not
observed
in
subgroups
of
pa(ents
with
no
prevalent
vertebral

fractures,
with
vertebral
deformity
of
grade
0
to
2,
and
with
lumbar
BMD
≥−2.5
SD
in
the
teripara(de

group

Subgroup
of
pa1ents
RR
P
value

<75
years
0.06
.007

≥75
years
0.32
.015

1
vertebral
fracture
0.08
.015

≥2
vertebral
fractures
0.29
.009

Grade
3
deformity
0.26
.003

Lumbar
BMD
<−2.5
SD
0.25
.035

eGFR
>70
mL/min/1.73
m2
0.13
.001

eGFR
<70
mL/min/1.73
m2
0.31
.004

Sugimoto T, et al. Shimane University School of Medicine, Japan. Once-weekly Teriparatide Reduces Vertebral Fracture Risk − Subgroup Analysis from the Teriparatide Once Weekly
Efficacy Research (TOWER) Trial. Abstract [FR0376]. Presented at the 2013 Annual Meeting of The American Society for Bone and Mineral Research. October 4, 2013.

Objec1ve:
To
iden(fy
predictors
of
re-‐fracture
amongst
a
specialist-‐managed

popula(on

Ca + D, calcium and vitamin
Study
design

• 7-‐year
follow-‐up
study

Par1cipants

• 212
subjects
who
were
treated
for
an
incident
osteoporo(c
fracture
(most
of
them
non-‐
vertebral,
non-‐hip)
for
at
least
4
years
(about
75%
were
put
on
bisphosphonates;
25%
on

Ca+D)

Inves1ga1ons

• Anthropometric,
clinical,
and
technical
data
were
documented
every
6
months

• Predictors
of
re-‐fracture
were
iden(ﬁed
by
logis(c
regression
analyses
before
and
aper

adjustment
for
poten(al
confounders

Ganda K, et al. Concord Hospital, Australia. Predictors of Re-fracture in Patients Managed within a Fracture Liaison Service: A 7-year Prospective Study. Abstract [SU0331]. Presented at
the 2013 annual meeting of The American Society of Bone and Mineral Research. October 6, 2013.
Predictors
of
Re-‐Fracture
in
Pa(ents
Managed
Within
a

Fracture
Liaison
Service:
A
7-‐Year
Prospec(ve
Study

Predictors
of
Re-‐Fracture
in
Pa(ents
Managed
Within
a

Fracture
Liaison
Service:
A
7-‐Year
Prospec(ve
Study

Results

•  The
mean
dura(on
of
the
follow-‐up
was
5.57
years
(4.02–7.51),
at
baseline,
mean
age
72.4
years,

mean
total
hip
T-‐score
-‐1.2

•  79%
female
and
38%
had
prevalent
fractures
at
the
(me
of
index
fracture

•  24%
of
the
treated
subjects
had
re-‐fracture
during
the
study
(most
new
fractures
being
non-‐
vertebral,
non-‐hip),
and
in
a
group
of
similar
composi(on
the
re-‐fracture
rates
were
35%
to
46%

over
2
to
6
years

•  In
unadjusted
analyses,
predictors
of
re-‐fracture
were

–  Female
gender

–  Use
of
oral

glucocor(coid

–  Signiﬁcant
comorbidi(es
(>3)

–  Gastro-‐esophageal
reﬂux

–  Cardiovascular
disease

–  Body
weight,
<66.4
kg

–  Total
hip
T-‐score,
<-‐1.65
SD

–  Previous
falls

–  Maternal
history
of
hip
fracture

–  >2
prevalent
fractures

–  Sunlight
<30
min/d

SD, standard deviation; kg, kilogram.
Ganda K, et al. Concord Hospital, Australia. Predictors of Re-fracture in Patients Managed within a Fracture Liaison Service: A 7-year Prospective Study. Abstract [SU0331].
Presented at the 2013 annual meeting of The American Society of Bone and Mineral Research. October 6, 2013.

Predictors
of
Re-‐Fracture
in
Pa(ents
Managed
Within
a
Fracture
Liaison
Service:
A

7-‐Year
Prospec(ve
Study

Results

•  Aper
adjus(ng
for
confounders,
the
following
factors
remained
signiﬁcantly
associated
with

re-‐fracture

–  Female
gender
(OR
7.3,
95%
CI
1.6–33.8,
P
=
.01)

–  Comorbidity
(OR
4.1,
95%
CI
1.9–9.1,
P<.01)

–  Total
hip
T-‐score
<
–1.65
(OR
3.9,
95%
CI
1.8–8.3,
P<.01)

–  ≥1
fall
within
the
last
year
(OR
2.2,
95%
CI
1.0–4.8,
P
=
.04)

•  Prevalent
fracture
status
and
age
were
not
associated
with
re-‐fracture

•  MPR
below
0.50
was
the
strongest
predictor
of
re-‐fracture.

CI, confidence interval; MPR, medication possession rate; OR, odds ratio; SD, standard deviation.
Ganda K, et al. Concord Hospital, Australia. Predictors of Re-fracture in Patients Managed within a Fracture Liaison Service: A 7-year Prospective Study. Abstract [SU0331].
Presented at the 2013 annual meeting of The American Society of Bone and Mineral Research. October 6, 2013.

•  E-‐Consult
na
fracture:
medica(e
4.7%
ervoor,
5.9%

erna
(ns).
Lee
et
al,
SU
392.

•  System
based
interven(on
aper
fracture:
BMD

tes(ng
van
5%
naar
43.5%.
Bunta
et
al,
SU
391.

•  75.000
clinical
fractures
in
the
Netherlands
in
2010,

•  107.000
in
2025….
(SCOPE,
IOF
2013)

•  62-‐jarige
vrouw,
maakt
zich
zorgen
over
osteoporose,
omdat
haar
moeder

een
heupfractuur
had.

•  Ze
doet
regelma(g
aan
lichaamsbeweging,
neemt
1200
mg
aan

calciumsupplementen
per
dag
en
een
dieet
met
naar
scha‰ng
1040
mg

calcium
per
dag;

•  Ze
maakt
zich
zorgen
om
haar
cardiovasculaire
risico.

•  Wat
adviseert
U
haar?

•  Wie
(her)kent
deze
vrouw?

Bolland et al, BMJ 2008

New Engl J Med 2013
Areas of uncertainty: cardiovascular risk, differences between products in
skeletal benefits and side effects, and requirements in premenopausal
women, men and non caucasians.

Dietary and Supplemental Calcium Intake and the Risk
of Mortality in Older Men: the MrOS Study n=5697
Results

*Adjusted for age, energy intake and calcium supplement use;
** Adjusted for age, ethnicity, education, BMI, walking speed, total energy intake, health habits, calcium supplements use, clinical center.
RH, risk hazard; SD, standard deviation.
•  Mean
age
(±SD),
74
±
6
years

•  Mean
dietary
calcium
intake,
1142
±
590
mg/d

•  Calcium
supplements
use,
65%
of
pa(ents

•  Men
with
higher
intake
were
older,
thinner,
berer
educated,
more
likely
to
be
Caucasian,
less
likely

to
smoke,
and
had
higher
gait
speed
compared
with
those
with
lower
total
calcium
intake
(P
trend

<.05
for
all)

At
baseline

•  2022
men
died,
of
which
687
deaths
were
due
to
cardiovascular
disease

–  Aper
par(al
adjustment*,
total
mortality
(RH
=
1.19,
CI:
1.02,
1.39)
was
higher
in
pa(ents

with
lowest
quar(le
of
total
calcium
intake
(<621
mg/d)
compared
with
pa(ents
in

highest
quar(le
(>1565
mg/d)

–  Aper
complete
adjustment**,
dietary
and
supplemental
calcium
intake
were
not

associated
with
total
or
cardiovascular
mortality
(see
the
ﬁgure
on
the
next
slide)

During
10-‐year
follow-‐up

Bauer D, et al. San Francisco, USA. Dietary and Supplemental Calcium Intake and the Risk of Mortality in Older Men: the MrOS Study. Abstract [1001]. Presented at the 2013 Annual
Meeting of The American Society for Bone and Mineral Research. October 4, 2013.

Dietary and Supplemental Calcium Intake and the Risk
of Mortality in Older Men: the MrOS Study
Results

•  Calcium
intake
was
not
associated
with
total
or
cardiovascular
mortality
(P
trend
=
0.51,
0.79,
respec(vely)

•  Intake
of
calcium
supplements
was
also
not
associated
with
total
(RH
=
1.06,
CI:
0.96,
1.18)
or

cardiovascular
mortality
(RH
=
1.00,
CI:
0.83,
1.20)

*Adjusted for age, ethnicity, education, BMI, walking speed, total energy intake, health habits, calcium supplement use, and clinical center.
BMI, body mass index; RH, risk hazard.
0
0.9
1.2
0.6
0.3
1.5
1.8
1.04
1.064
0.97
0.953
1
1.017
11
Q1: <681 Q2: 681-<1000 Q3: 1000-<1565 Q4: >1565
Quartiles of total calcium intake, mg/d
Mortalityhazardratios*(95%Cl)
Referent
Total Mortality
Cardiovascular
Mortality
Bauer D, et al. San Francisco, USA. Dietary and Supplemental Calcium Intake and the Risk of Mortality in Older Men: the MrOS Study. Abstract [1001]. Presented at the 2013 Annual
Meeting of The American Society for Bone and Mineral Research. October 4, 2013.

Original Article
Vitamin D–Binding Protein and Vitamin D Status of
Black Americans and White Americans
Camille E. Powe, M.D., Michele K. Evans, M.D., Julia Wenger, M.P.H., Alan B.
Zonderman, Ph.D., Anders H. Berg, M.D., Ph.D., Michael Nalls, Ph.D., Hector Tamez,
M.D., M.P.H., Dongsheng Zhang, Ph.D., Ishir Bhan, M.D., M.P.H., S. Ananth
Karumanchi, M.D., Neil R. Powe, M.D., M.P.H., M.B.A., and Ravi Thadhani, M.D.,
M.P.H.
N Engl J Med
Volume 369(21):1991-2000
November 21, 2013

Levels of Total 25-Hydroxyvitamin D and Vitamin D–Binding Protein in Community-Dwelling
White and Black Study Participants (n=904 and 1181).
Powe CE et al. N Engl J Med
2013;369:1991-2000

Variant Vitamin D–Binding Proteins and Bioavailable 25-Hydroxyvitamin D.
Powe CE et al. N Engl J Med 2013;369:1991-2000

Total and Bioavailable 25-Hydroxyvitamin D Levels among Homozygous Blacks and Whites
with Similar Parathyroid Hormone Levels.
Powe CE et al. N Engl J Med 2013;369:1991-2000

A
Randomized,
Double-‐Blind,
Placebo-‐Controlled
Trial
of
Alendronate

Treatment
for
Fibrous
Dysplasia
of
Bone

Objec1ve:
To
evaluate
the
efficacy
of
oral
alendronate
in
the
treatment
of
FD

Boyce A, et al. Children’s National Medical Center, USA. A Randomized, Double-blind, Placebo-controlled Trial of Alendronate Treatment for Fibrous Dysplasia of Bone. Abstract
[SA0036]. Presented at the 2013 Annual Meeting of The American Society for Bone and Mineral Research. October 5, 2013.
•  Randomized,
double-‐blind,
placebo-‐controlled
trial

Study
design

BMD, bone mineral density; FD, fibrous dysplasia.
•  40
subjects
with
FD
(children
[n
=
15;
median
age
10,
range
6-‐16]
and
adults

[n
=
23;
median
age
40,
range
20-‐57])
enrolled

Par1cipants

•  Drug
or
placebo
for
6
months,
followed
by
6
months
off,
6
months
on
again,
and
6

months
off

•  Dosage:
40
mg/d
for
subjects
weighing
>50
kg,
20
mg
for
those
weighing
30
to
50
kg,
and

10
mg
for
those
weighing
20
to
30
kg

Treatment

•  Primary
end
point:
Change
from
baseline
in
N-‐telopep(de
and
osteocalcin
at
18
months

•  Secondary
end
points:
Effects
on
pain
and
BMD
at
FD
and
non-‐FD
sites

End
points

A
Randomized,
Double-‐Blind,
Trial
of
Alendronate

Treatment
for
Fibrous
Dysplasia
of
Bone

Results

Wisconsin Brief Pain Questionnaire
10
8
6
4
2
0
0 6 12 18 24
Alendronate
Placebo
Treatment Period
PainScore
Months on Treatment
There was no significant change in pain between the alendronate and placebo groups

A
Randomized,
Double-‐Blind,
Trial
of
Alendronate

Treatment
for
Fibrous
Dysplasia
of
Bone

Results

•  Aper
18
months,
alendronate
decreased
N-‐telopep(de
(P
=
.001),
with
no
change

in
osteocalcin
(P
=
.7)

•  BMD
increased
in
non-‐FD
sites
(P
=
.003);

•  there
was
no
diﬀerence
at
the
FD
sites
(aﬀected
femora
or
humeri)

-‐  Fractures
were
observed
in
3
pa(ents
from
the
alendronate
group

-‐  and
3
from
the
placebo
group

FD, fibrous dysplasia.

SA0077

Varia(on
in
Bone
Turnover
Markers
in
Professional
Sport
Players
During

Training
is
Mediated
by
Changes
in
Scleros(n
Levels.
Ranuccio
Nu(*1
et
al.

University
of
Siena,
Italy,
University
of
Siena,
Italy,
Medical
Staﬀ
Siena
Football
Club,

Italy

Before
Training
Before
Start
Season
Mid
Season

CTX
1,48
0,91
1,01

Bone
AF
12,1
17,5
15,8

Scleros(n

30.6
26.0

Dank
voor
Uw
aandacht!

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