Seminar 22-11-2014 Prof. Dr. W.F. Lems - Highlights ASBMR

Congress Highlights ASBMR Houston
2014
1

Welke Bronnen?
1)Eigen aantekeningen/interpretatie (bias!)
2) Website IOF:
http://www.iofbonehealth.org/what-we-do/training-and-education/educational-slide-kits/
congress-highlights-asbmr-houston-2014
§  3)

Congress Highlights ASBMR Houston 2014 3
Welke nieuwe medicamenteuze ontwikkelingen zijn er?
Odanacatib Phase 3 study!
Nieuwe inzichten in diagnostiek?
Controversen?
Tips/wetenswaardigheden voor dagelijkse praktijk

Bone
Resorp*on
by
Osteoclasts

Rodan SB, Duong LT. BoneKey. 2008;5(1):16-24.
Cathepsin K (cat K) is highly expressed in the osteoclast, where it is
localized in the lysosomes and released during bone resorption.
Odanacatib

1147 Odanacatib, Phase III Long-Term Odanacatib
Fracture Trial (LOFT)
§  Women ≥65 years with a BMD T-score ≤−2.5 at the total hip (TH) or
femoral neck (FN) or with a prior radiographic VFx and a T-score ≤
−1.5 at the TH or FN.
Objective To evaluate efficacy and safety of ODN 50 mg once-weekly to reduce
fracture risk in postmenopausal women with osteoporosis.
PARTICIPANTS
§  Participants were randomized to either ODN or placebo (1:1) and received
weekly vitamin D3 and daily calcium supplements to ensure a total daily
calcium intake of ~1200 mg.
INVESTIGATIONS
§  Primary endpoints: new morphometric vertebral (VFx), hip, and clinical non-
vertebral fractures (NVF).
§  Secondary endpoints: safety and tolerability, clinical VFx, spine and hip
BMD, and bone turnover markers.
ANALYSES
BMD: bone mineral density • ODN: odanacatib • VFx: vertebral fracture • NVF: non-vertebral fractures
MICHAEL MCCLUNG, OREGON OSTEOPOROSIS CENTER, USA
Back to TOC

1147 The Phase III Long-Term Odanacatib Fracture Trial
(LOFT)
§  16,713 participants were randomized at 387 centers in 40
countries,
At baseline, mean (SD) age was 72.8 (5.3) years,
57% were Caucasian, 46.5% had a prior VFx, and mean BMD T-
scores were: lumbar spine -2.7, TH -2.4, and FN -2.7.
The study was targeted for obtaining 237 hip fractures.
§  In July 2012, the decision was made to stop the study due to the
occurrence of a high number of hip fractures.
METHODS
BMD: bone mineral density • NVF: non-vertebral fractures • VFx: vertebral fracture • SD: standard deviation
Back to TOC

1147 Odanacatib Anti-Fracture Efficacy (LOFT):
Fracture Data
§  Fracture Reduction:
§  morphometric VFx : - 54%;
§  hip fractures: - 47%
§  nonvertebral fractures: -23%
§  clinical vertebral fractures: -72%
§  (secundaire uitkomstmaat)
RESULTS
BMD: bone mineral density • NVF: non-vertebral fractures • VFx: vertebral fracture
Back to TOC

Vergelijking Fractuurdata?
Een vergelijking tussen verschillende studies is niet
mogelijk/verantwoord, vanwege verschillen in
patientenpopulatie en/of design van de studies.

Medicament
Wervelfracturen
Heup

Fracturen

Niet-‐Wervel

Fracturen

Alendronaat
0,55

Risedronaat
0,63

E*dronaat
0,59

Zoledronaat
0,30

Stron*umrane-‐

laat

0,63

Teripara*de
0,36

Denosumab
0,32

Raloxifen
0,60

Ibandronaat
0,50

Odanaca*b
0,46

…………

Fractuurdata Phase III-studies

Fractuurdata
Phase
III-‐studies
Medicament
Wervelfracturen
Heup

Fracturen

Alendronaat
0,55
0.61

Risedronaat
0,63
0,74

E*dronaat
0,59

Zoledronaat
0,30
0,59

Stron*umrane-‐

laat

0,63

Teripara*de
0,36

Denosumab
0,32
0,60

Raloxifen
0,60

Ibandronaat
0,50

Odanaca*b
0,46
0,53

…………

Fractuurdata Phase III-studies

Fractuurdata
Phase
III-‐studies

Medicament
Wervelfracturen
Heup

Fracturen

Niet-‐Wervel

Fracturen

Alendronaat
0,55
0.61
0,84

Risedronaat
0,63
0,74
0,80

E*dronaat
0,59

Zoledronaat
0,30
0,59
0,75

Stron*umrane-‐

laat

0,63

Teripara*de
0,36

Denosumab
0,32
0,60
0,80

Raloxifen
0,60

Ibandronaat
0,50

Odanaca*b
0.46
0,53
0,77

1147 Odanacatib Anti-Fracture Efficacy (LOFT)
The mean increase of BMD after 5 years was:
- 11.5% at the lumbar spine.
- 9.5% at the total hip.
§  The changes of Bone Turn Over Markers: similar compared
with those obtained in phase II studies:
§  Large decrease during the first year for CTX and
progressive increase thereafter.
§  Slight decrease during the first year for P1NP and
progressive increase thereafter.
RESULTS
BMD: bone mineral density • NVF: non-vertebral fractures • VFx: vertebral fracture
Back to TOC

1148 Safety and Tolerability of Odanacatib Therapy in
Postmenopausal Women with Osteoporosis: Results from
the Phase III Long-Term Odanacatib Fracture Trial (LOFT)
§  Participants of LOFT-study
OBJECTIVE Evaluate the SAFETY of ODN 50 mg once-weekly in reducing the
risk of fractures in postmenopausal women with osteoporosis.
PARTICIPANTS
§  Randomized to placebo or ODN; all received 5600IU Vit D weekly and Ca.
INVESTIGATIONS
§  AE of special interest: skin, dental, serious respiratory, delayed fracture
union, atypical femoral fractures, atrial fibrillation/flutter, cardiovascular and
cerebrovascular.
ANALYSES
LOFT: Long-Term Odanacatib Fracture Trial • ODN: Odanacatib • FN: femoral neck • TH: total hip • VFx: vertebral fracture • TH: total hip • FN: femoral neck • Ca:
calcium • VitD: vitamin D• AE: adverse event
SOCRATES PAPAPOULOS, LEIDEN UNIVERSITY MEDICAL CENTER, THE NETHERLANDS Back to TOC

Papapoulos, Loft, 1148 (ASBMR2014)
§  Respiratory infection 1.3% versus 1.5% (NS).
§  Morphea skin lesions 0.1% versus 0.0% (12 versus 3, p=0,04).
§  Systemic sclerosis 0.0% versus 0.0% (2 versus 1) (NS).
§  Atrial fibrillation 1.1% versus 1.0% (NS).
§  ONJ 0 versus 0.
§  Atypical Femur Fracture: 0.1% versus 0.0% (5 versus 0).
§  Cerebrovascular events.
Back to TOC
Odanacatib versus placebo:

-  Morphea waren reden om programma van bacalatib te stoppen
-  Voorbode van sclerodermie?
-  Zeldzame aandoening: 1:100.000?
-  Belangrijkste: na stoppen medicatie verdwenen de huidafwijkingen bij
alle 15 patienten!
-  12 gedurende 50.000 patient jaren observatie!
-  Overalertheid in trial?
-  NB Scleroderma en voorstadia geen exclusiecriterium!
LOFT-study, Papapoulos et al, ASBMR, 2014, 1148

JBMR 2014
Patiente X:
Geen prodromale pijn,
geen periost reactie
T lumbaal -4,4 en heup -3,2
LOFT-study, Papapoulos et al, ASBMR, 2014, 1148

Safety Odanacatib, LOFT-study
§  Fataal CVA: geen verschil op grond van beoordeling
locale principal investigators;
§  Sommige data incompleet volgens Adjucation
Committee: daarna statistisch significant meer fataal
CVA bij odanacatib!
§  Geen onderliggend mechanisme bekend;
§  Nieuwe analyse (verzoek FDA);
§  Wachten op 5 jaarsdata.
§  NB Geen verschil in cardiale events;

- ODN efficacy for preventing hip fracture seems to be slightly
higher compared with ZOL and Dmab (although there is no
head-to-head study).
- Safety profile is satisfying, but the real impact in clinical
practice of the rare AE described should be evaluated.
- PMO requires a long-term strategy, therefore several drugs
with different mechanisms of action (including ODN), are
required.
-GI AE may occur with bisphosphonates, requiring a switch to
another drug such as ODN.
Opinie
Dr Michael Mc Clung, Oregon, US

-Safety profile is generally clean; ODN will make a valuable
contribution to our osteoporosis armamentarium;
- Significant differences favoring placebo for fatal stroke and
AFF, although small numbers.
- IOF committee: “further adjudication efforts may nullify
the increase in fatal stroke”.
Opinie
Prof Dr Socrates Papaoulos

Cathepsine K
Osteoclast
Odanacatib
Collageen degradatie
RANK
Osteoblast
Wnt signalering
LRP Frizzeld
Wnt
DKK
Osteocyt
RANKL
Denosumab Anti-sclerostin
rhPTH (1-34) and (1-84)
Sclerostine
pre-‐
osteoclast

pre-‐
osteoblast

RANKL Sclerostine
Lems, Geusens, Current Opinion
Rheumatology, 2014

Phase II 419 postmenopausal
women
Age : 55-85 yrs
LS T –score <-2.0 and >-3.5
Bmab 180 mg Q4W
N=31
Bmab 180 mg Q2W
N=30
Bmab 270 mg Q2W
N=30
Placebo
N=29
52 weeks of
treatments 52 weeks follow up
1151 Effect of Blosozumab on Bone Mineral Density: 52-
Week Follow-up of a Phase 2 Study of Postmenopausal
Women with Low Bone Mineral Density
Congress
Highlights
ASBMR
Houston
2014
21
OBJECTIVE 52-week follow-up data from the Phase 2 study.
BMAB: Blosozumab • FN: femoral neck • LS: lumbar spine
CHARLES
BENSON,
ELI
LILLY
AND
COMPANY,
USA

Back to TOC

1151 Effect of Blosozumab on Bone Mineral Density: 52-
Week Follow-up of a Phase 2 Study of Postmenopausal
Women with Low Bone Mineral Density
BMAB: Blosozumab • BMD: bone mineral density • FN: femoral neck • TH: total hip
CHARLES BENSON, ELI LILLY AND COMPANY, USA
Back to TOC

Percentage Change from Baseline in Bone Mineral Density.
McClung MR et al. N Engl J Med 2014;370:412-420

1152 Effects of 2 Years of Treatment With Romosozumab
Followed by 1 Year of Denosumab or Placebo in
Postmenopausal Women With Low Bone Mineral Density
419 postmenopausal women
Age : 55-85 years
LS, TH or FN T –score <-2.0 and >-3.5

Romo 70 mg
QM

Romo 210
mg QM

1 year extension
Re-randomization 1:1

Dmab 60 mg
Q6M
PLACEBO

Romo 140
mg QM

Romo 140
mg Q3M PLACEBO
1 year extension
Re-randomization 1:1
Dmab 60 mg
Q6M PLACEBO
Romo 210
mg Q3M
BMD: bone mineral density • DMAb: denosumab • FN: femoral neck • LS: lumbar spine • Romo: romosozumab • TH: total hip
MR MCCLUNG, OREGON OSTEOPOROSIS CENTER, USA Back to TOC

1152 Effects of 2 Years of Treatment With Romosozumab
Followed by 1 Year of Denosumab or Placebo in
Postmenopausal Women With Low Bone Mineral Density
RESULTS
BMD: bone mineral density • DMAb: denosumab • Romo: romosozumab • P1NP: procollagen type I N-terminal propeptide • CTX: C-terminal telopeptide of type I
collagen • Pbo: placebo • LS: lumbar spine • TH: total hip
MR MCCLUNG, OREGON OSTEOPOROSIS CENTER, USA Back to TOC

1047 Denosumab Restores Cortical Bone Loss at the Distal
Radius Associated With Aging and Reduces Wrist Fracture Risk:
Analyses From the FREEDOM Extension Cross-over Group
§  BMD changes of distal radius during FREEDOM study and the 5-year
extension
RESULTS
BMD: bone mineral density • EXT: extension • Pbo: placebo
JOHN P. BILEZIKIAN, COLUMBIA UNIVERSITY, USA
+1.5%
2
1
0
1
-2
0 1 2 3 1 2 3 5
Study Year
Percentagechange
frombaseline
*
*
* *
**
**
FREEDOM (Years 1-3)
Placebo (Calcium + Vitamin D)
Extension (Years 1-5)
Denosumab 60 mg Q6M
Back to TOC

1011 Phase 2 Randomized, Double Blind, Placebo
Controlled Trial of Anti-Myostatin Antibody LY2495655 in
Older Fallers With Low Muscle Strength
§  OBJECTIVE To test whether the anti-myostatin monoclonal antibody
LY2495655 (LY) could increase appendicular lean body mass (aLBM)
and improve physical performance in elderly fallers with low muscle
strength.
Clemens Becker, Robert-Bosch-Krankenhaus, Germany

1011 Phase 2 Randomized, Double Blind, Placebo
Controlled Trial of Anti-Myostatin Antibody LY2495655
in Older Fallers With Low Muscle Strength
§  Subjects randomized (N=201) aged ≥75 yrs, with ≥1 fall in
past year, low hand grip strength (≤37 kg [men]; ≤21 kg
[women]) and low performance on a 5-time chair stand
(5XCS) test without arms (≥12 s).
PARTICIPANTS
§  LY 315 mg or placebo (pbo) was administered as 3 SC
injections of 1.5 mL every 4 weeks for 20 weeks, followed by
a 16 week observational period.
INVESTIGATIONS
§  Primary objective: assess the change from baseline to 6
months for aLBM for LY compared to pbo.
ANALYSES
aLBM: appendicular lean body mass • sc: subcutaneous
CLEMENS BECKER, ROBERT-BOSCH-KRANKENHAUS, GERMANY Back to TOC

1011
Phase
2
Randomized,
Double
Blind,
Placebo
Controlled

Trial
of
An*-‐Myosta*n
An*body
LY2495655
in
Older
Fallers

With
Low
Muscle
Strength

Congress Highlights ASBMR Houston
2014
30
RESULTS
CLEMENS
BECKER,
ROBERT-‐BOSCH-‐KRANKENHAUS,
GERMANY
Back to TOC

Controversen?

SYMP2 Biochemical Markers Are of Practical Value
in the Routine Management of Osteoporosis
§  Bone turnover markers (BTM) should be measured after an
overnight fast (circadian rhythm).
§  The most relevant markers are CTX for bone resorption and
P1NP for bone formation.
§  Short- and long-term CVs are satisfying and permit their use in
clinical practice.
§  Cost is reasonable and the measurements may be repeated.
TECHNICAL
ASPECTS
§  In the evaluation of an unrecognized bone disease for
assessing the likelihood of fracture.
§  The combination BTM+BMD improves the prediction of
fracture risk.
IN PRACTICE
THEY SHOULD
BE MEASURED
AT BASELINE
BMD: bone mineral density • BTM: bone turnover marker • CV: coefficient of variation • LSC: least significant change • P1NP: procollagen type 1 N-terminal propeptide
• CTX: C-terminal telopeptide of type 1 collagen
FOR THE MOTION WILLIAM FRAZER, UK
Back to TOC

§  Evaluating bone response to antiresorptive therapy:
there is a strong correlation between the decrease of
BTM (inhibitors of bone resorption) and the level of anti-
fracture efficacy.
§  Persistence of high levels of BTM on treatment
requires the search for:
§  Myeloma
§  Fracture
§  Poor compliance
§  Excessive alcohol consumption
THEY ALSO
SHOULD BE
MEASURED
FOR
ASSESSING
TREATMENT
RESPONSE
FOR
BMD: bone mineral density • P1NP: procollagen type 1 N-terminal propeptide • BTM: bone turnover marker
FOR THE MOTION WILLIAM FRAZER, UK
Back to TOC

§  Poor short-term and long-term precision as compared with
DXA.
§  Need for standardization between laboratories and a defined
reference standard.
TECHNICAL
ASPECT
§  3 studies with 3 different treatments (RLX, RIS, IBN)
showed BTM not helpful for improving compliance.
§  Prediction was less than that compared with BMD at the hip
measured by DXA .
§  Combination BTM+BMD improves only slightly the prediction
of fracture.
PREDICTION
OF FRACTURE
BMD: bone mineral density • BTM: Bone turnover markers • DXA: Dual-energy X-ray absorptiometry • RR: relative risk • SD: standard deviation • P1NP: procollagen
type 1 N-terminal propeptide • CTX: C-terminal telopeptide of type 1 collagen
AGAINST THE MOTION DOUGLAS BAUER, USA
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SYMP3 ASBMR-NOF Task Force on Treat to Target
for Osteoporosis Treatment
§  Appealing because it sets a goal to be achieved by patients
and physicians.
§  Similar to dogma in hypertension, diabetes , reumatoid
arthritis and gout, where target levels have been identified.
CONCEPT OF
TREAT TO
TARGET
§  Bone density: Which site? T-score or g/cm2?
§  Bone turnover markers: Which BTM? Different targets for
different agents?
§  Combinations BTM and BMD?
§  Fracture risk tool (FRAX)?
WHAT IS THE
OSTEOPOROSIS
TARGET?
BTM: bone turnover marker • BMD: bone mineral density
STEVEN CUMMINGS, FELICIA COSMAN, E. MICHAEL LEWIECKI
Back to TOC

SYMP3 ASBMR-NOF Task Force on Goals for
Osteoporosis Treatment
§  Often osteoporosis therapies cannot bring a patient to
reach a defined target
§  If BMD is the target, fracture risk may be different at same
BMD in a patient on therapy as compared to not on therapy
§  Bone turnover markers: resorption and formation markers
behave differently with different therapies
§  FRAX was not designed to be used with patients on therapy
CONCERNS
BMD: bone mineral density • BTM: bone turnover marker
Back to TOC

SYMP3 ASBMR-NOF Task Force on Goals for
Osteoporosis Treatment
§  “Treat to target” for osteoporosis patients is not ready now
for the clinic.
§  With more data regarding risk of fracture at defined targets
(on and off therapy) and more therapies able to help
patients achieve the defined targets, we may be able to
develop this in the future.
CONCLUSION
Back to TOC

Controversen?

1077 Intestinal Calcium Absorption Decreases
Dramatically After Gastric Bypass Surgery, Despite
Optimization of Vitamin D Status
§  33 obese men and women (body mass index 45 ± 7 kg/m2).
§  Serum 25-hydroxyvitamin D [25(OH)D] levels repleted and
maintained at ≥30 ng/mL, before and after Roux Y Gastric Bypass
(RYGB) surgery.
§  Total daily Ca intake of 1200 mg was maintained with individually-
dosed Ca citrate supplements.
INVESTIG
ATIONS
§  Report here the first 22 participants’ pre- and post-op data.
§  Fractional Ca absorption was determined pre-op and 6 months
post-op, with a dual stable isotope method.
ANALYS
ES
Ca: calcium • DXA: dual-energy X-ray absorptiometry • RYGB: roux-en-Y gastric bypass surgery
ANNE SCHAFER, UNIVERSITY OF CALIFORNIA, SAN FRANCISCO AND THE SAN FRANCISCO VA MEDICAL
CENTER, USA
Back to TOC

BMD: bone mineral density • BMI: body mass index • Ca: calcium • RYGB: roux-en-Y gastric bypass surgery • PTH: parathyroid hormone • IGF: insulin growth factor •
P1NP: procollagen type 1 N-terminal propeptide • CTX: C-terminal telopeptide of type 1 collagen
CENTER, USA
Fractional Ca absorption and other parameters, before and after RYGB
Variables Pre-op 6 months Post-op p-value
Weight (kg) 127 ± 19 93 ± 15 ≤0.001
BMI (kg/m2) 45 ± 8 33 ± 6 ≤0.001
Fractional Ca absorption 0.33 ± 0.14 0.07 ± 0.04 ≤0.001
25(OH)D (ng/mL) 41 ± 10 38 ± 13 0.21
24-hour urinary Ca (mg) 145 ± 96 105 ± 77 0.02
Serum Ca (mg) 9.2 ± 0.3 9.2 ± 0.3 0.55
PTH (pg/mL) 47 ± 3 53 ± 21 0.04
Estradiol (pg/mL) 51 ± 24 57 ± 35 0.68
IGF-1 (ng/mL) 129 ± 46 134 ± 56 0.94
IGFBP-3 (ng/mL) 4220 ± 840 3785 ± 753 ≤0.01
P1NP (ng/mL) 0.276 ± 0.119 0.999 ± 0.344 ≤0.001
Total hip areal BMD (g/cm2) 1.158 ± 0.149 1.112 ± 0.115 ≤0.01
Femoral neck BMD (g/cm2) 0.967 ± 0.142 0.929 ± 0.117 ≤0.001
Back to TOC

1014 Effects of Vitamin D and Multimodal Exercise
on Prevention of Injurious Falls in Older Finnish
Women
§  Two-year randomized (double-blind for vitamin D) placebo-
controlled intervention trial.
STUDY DESIGN
§  409 Finnish home-dwelling women aged 70-80 years (median
age=74 y.o.).
§  At least one fall during the previous year.
§  No Vit D supplements, no regular exercise.
STUDY
POPULA
TION
§  20 µg vitamin D (800 IU)/day + exercise (D+Ex+).
§  20 µg vitamin D (800 IU)/day + no exercise (D+Ex-).
§  Placebo + exercise (D-Ex+).
§  Placebo + no exercise (D-Ex-).
TREATMENT
GROUPS
EX: exercice • D: VitaminD
KIRSTI UUSI-RASI, UKK INSTITUTE FOR HEALTH PROMOTION RESEARCH, FINLAND
Back to TOC

on Prevention of Injurious Falls in Older Women
§  25OHD levels improved from 65 nmol/L to 94 nmol/L in
Vitamin D treated groups.
§  There was no difference in the rate of all falls between
groups.
§  D+Ex+ and D-Ex+ groups had less injurious falls requiring
medical care compared with the reference group (D-Ex-).RESULTS
D: vitamin D • EX: exercice
Measurement D+Ex+ D-Ex+ D+Ex_
Rate of injurious falls compared to D-Ex- 0.28
(0.1-0.76)
0.17
(0.05-0.59)
0.84
(0.41-1.71)
Back to TOC

1012 Fall Risk Assessment Predicts Fall Related
Osteoporotic and Hip Fracture in Older Women and
Men
§  From the Senior Alert register, 128,596 older patients (82.4 ±
7.8 years, 59.6% women) identified who had a fall risk
assessment using the Downton Fall Risk Index (DFRI) at
baseline.
METHODS
§  The predictive role of DFRI was calculated using a Cox
proportional hazards model with age, sex, height, weight,
and prevalent osteoporotic fracture as covariates, taking
time to outcome or end of study into account.
STATISTICAL
ANALYSIS
DFRI: Downton Fall Risk Index
MARTIN NILSSON, CENTRE FOR BONE AND ARTHRITIS RESEARCH AT THE SAHLGRENSKA ACADEMY, SWEDEN Back to TOC

Men
THE DOWNTON
FALL RISK
INDEX (DFRI)¹
¹ modified from Downton JH. Falls in the elderly. London: Edward Arnold, 1993: 128-30.
MARTIN NILSSON, CENTRE FOR BONE AND ARTHRITIS RESEARCH AT THE SAHLGRENSKA ACADEMY, SWEDEN
Items Score
Known previous falls
No 0
Yes 1
Medications
None 0
Medications (sedatives, diuretics, antidepressants, antiparkinsonians,
antihypertensives)
1
Sensory deficits
None 0
Impairments (visual, hearing, limb) 1
Mental state
Oriented 0
Confused (cognitively impaired) 1
Gait
Normal, safe with walking aids, unable 0
Unsafe (with/without walking aids) 1
Back to TOC

Men
§  During the follow up 6,699 patients suffered an osteoporotic
fracture, among those, 2,557 had a hip fracture.
§  DFRI independently predicted osteoporotic fracture (HR
1.06) and hip fracture (HR 1.14).
RESULTS
DFRI: Downton Fall Risk Index • HR: hazard ratio
MARTIN NILSSON, CENTRE FOR BONE AND ARTHRITIS RESEARCH AT THE SAHLGRENSKA ACADEMY, SWEDEN
0,00%

0,50%

1,00%

1,50%

2,00%

2,50%

3,00%

3,50%

Low
(0-‐1)
High
(7-‐11)

Incidence
of
pa<ents
with
hip

fracture

DFRI
score

Hip
fracture
incidence

p<0.001

Back to TOC

Congress
Highlights
ASBMR
Houston
2014
54

Wie behandelen?
50-plussers met recente fractuur en T-score , -2.5;
Maar ook
-  Ouderen met heupfractuur;
-  Patienten na een bovenarmsfractuur, klinische wervelfractuur, bekkenfractuur
met een T-score in range osteopenie.
-

1045 Bisphosphonate Drug Holiday and Fracture
Risk
§  28,620 women cohort including:
§  59.8% persistent BP users.
§  40.2% drug holiday subjects.
§  The Drug Holiday group had:
§  Fewer comorbidities.
§  Higher baseline T-scores.
§  Lower fracture and fall risk scores.
RESULTS
BP: Biphosphonate • HR: hazard ratio • RR: rate ratio • CI: confidence interval
ANNETTE ADAMS, KAISER PERMANENTE SOUTHERN CALIFORNIA, USA
Unadjusted Fracture Risk for Drug
Holiday compared to Persistent users
(Rate Ratio)
RR (95% CI)
Any osteoporosis-related fractures 0.87 (0.81-0.94)
Hip fracture 1.0 (0.9-1.2)
Adjusted Fracture
Risk (Hazard Ratio)
HR (95% CI)
Fracture risk 0.90 (0.80–1.00)
Hip fracture risk 0.84 (0.68–1.03)
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§  Zijn de IWO-avonden altijd op woensdag en in Utrecht?
§  Bijna altijd.
§  Volgend jaar is de ECTS in Rotterdam, en is er eenmalig een IWO-
avond met ECTS-topsprekers: dinsdag 28 april 2015.

1003 Direct Transformation of Chondrocytes to Bone
and Vessel Cells in Patients with Osteoarthritis (OA)
Hypertrophic chondrocytes, distributed in
pairs, transforming in osteocyte-like cells.
They are able to produce type I Collagen,
Osterix and MEPB. Bone-like islands can be
identified inside cartilage, far from
subchondral areas. Some chondrocytes are
positive for VEGF and α-SMA, suggesting
that they can participate in angiogenesis,
accelerating the osteosclerotic process.
α-SMA: alpha- smoth muscle actin • VEGF: vascular endothelium growth factor
YAN JING, BAYLOR COLLEGE OF DENTISTRY, USA
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on Prevention of Injurious Falls in Older Women
§  Exercise training twice a week for 12 months, and once a week
for subsequent 12 months.
§  Monthly fall diaries.
§  Functional lower limb strength, dynamic balance and mobility
assessed at
6-month interval.
PROTOCOL
D: vitamin D • EX: exercice
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1045 Bisphosphonate Drug Holiday and Fracture
Risk
§  Women who undertake a holiday from BP use are not at greater risk of
osteoporosis-related fragility fractures, nor hip fractures specifically, than are
women who continue to use BPs persistently.
AUTHOR’S
CONCLUSION
§  The Drug Holiday group seems to be more healthy than the persistent
group. This could be one of the reasons for their drug use interruption.
People with more severe osteoporosis tend to be more persistent.
§  This makes the conclusions of the authors risky, since it can give the idea
that the BP treatment does not change the risk of fractures.
CLINICAL
IMPACT FROM
REVIEWER’S
PERSPECTIVE
BP: Biphosphonate
ANNETTE ADAMS, KAISER PERMANENTE SOUTHERN CALIFORNIA, USA
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SYMP3 ASBMR-NOF Task Force on Treat to Target
for Osteoporosis Treatment
§  Appealing because it sets a goal to be achieved by patients
and physicians.
§  Similar to dogma in hypertension, diabetes , reumatoid
arthritis and gout, where target levels have been identified.
CONCEPT OF
TREAT TO
TARGET
§  Bone density: Which site? T-score or g/cm2?
§  Bone turnover markers: Which BTM? Different targets for
different agents?
§  Combinations BTM and BMD?
§  Fracture risk tool (FRAX)?
WHAT IS THE
OSTEOPOROSIS
TARGET?
BTM: bone turnover marker • BMD: bone mineral density
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Seminar 22-11-2014 Prof. Dr. W.F. Lems - Highlights ASBMR

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