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


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


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


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


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


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

OdanacatibCollageen degradatie

RANK

OsteoblastWnt signalering

LRP Frizzeld

WntDKK

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



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


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

Perc

enta

ge c

hang

e

from

bas

elin

e

* *

* *

** **

FREEDOM (Years 1-3) Placebo (Calcium + Vitamin D)

Extension (Years 1-5) Denosumab 60 mg Q6M

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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

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RESULTS

CLEMENS BECKER, ROBERT-‐BOSCH-‐KRANKENHAUS, GERMANY Back to TOC


Welke nieuwe medicamenteuze ontwikkelingen zijn er? Nieuwe inzichten in diagnostiek? Controversen? Tips/wetenswaardigheden voor dagelijkse praktijk

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


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§  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


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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

Ferrari et al, Fr 0391

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.

INVESTIGATIONS

§  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.

ANALYSES

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

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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


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

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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

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1014 Effects of Vitamin D and Multimodal Exercise 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)

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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



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

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§  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)

Incide

nce of pa<

ents with hip

fracture

DFRI score

Hip fracture incidence p<0.001

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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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1014 Effects of Vitamin D and Multimodal Exercise 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



Back to TOC

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

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