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• Module 7 Medicatie ter preventie van fracturen bij glucocorticoïden
• Uitgangsvraag
• Wanneer en welke medicatie ter preventie van fracturen is bij gebruik van glucocorticoïd
geïndiceerd?
• Prof Dr Willem F Lems 17-11-2021


• Amsterdam University medical centre, location VUmc


• Department of Rheumatology, (EULAR Center of Excellence),


• Amsterdam, the Netherlands
Copyright
Prof. Dr. Willem F Lems
Disclosure:


Willem F. Lems, MD
Company
Speaking Fees/


Advisory Boards
Amgen, Eli Lilly, Merck, Curaphar, Galapagos, Pfizer.
Copyright
Prof. Dr. Willem F Lems
Risk factors for osteoporosis and fractures


in patients with rheumatic diseases
Primary
Osteoporosis
Secondary
Osteoporosis
Copyright
Prof. Dr. Willem F Lems
Glucocorticoids and vertebral fracture
1.4


1.2


1.0


0.8


0.6


0.4


0.2


0


van Staa TP et al. JBMR 2000;15:993-1000
Women
Men
High dose


Medium dose


Low dose


Control
Incidence (%)
<35 40 50 60 70 80 >85
<35 40 50 60 70 80 >85
Age (yrs)
Copyright
Prof. Dr. Willem F Lems
0.0
0.5
1.0
1.5
2.0
PMO GIO PMO GIO
RR
N = 9,681 987 14,551 500
Vertebral fracture Non-vertebral fracture
RR= 0.58 0.48 0.81 0.79
Oral bisphosphonates In postmenopausal women and GIOP
From Kanis et al, Health Tech Assess 2007;11:1-258
Copyright
Prof. Dr. Willem F Lems
Modern GIOP-studies
New drugs are not tested against placebo, but against an active
comparator!
Copyright
Prof. Dr. Willem F Lems
Copyright
Prof. Dr. Willem F Lems
Saag K et al. AR 2009, New Engl J Med 2007


ModernGIOP-studies
Copyright
Prof. Dr. Willem F Lems
% of patients with fractures:


teriparatide versus alendronate in GIOP
alendronate
teriparatide
p=0,004
p=0.007
Saag A & R 2009, New Engl J Med 2007
Copyright
Prof. Dr. Willem F Lems
Effect of Denosumab Compared With Risedronate in


Glucocorticoid-treated Individuals: Results From the 12-month


Primary Analysis of a Randomized, Double-blind, Active-controlled Study
K Saag1, RB Wagman2, P Geusens3, J Adachi4, O Messina5,R Emkey6,
R Chapurlat7, NS Daizadeh2, N Pannacciulli2,WF Lems8
1University of Alabama, Birmingham, AL, USA; 2Amgen Inc., Thousand Oaks, CA, USA;
3Maastricht University, Maastricht, The Netherlands; 4McMaster
EULAR; Madrid, Spain; June 14, 2017; Presentation #OP0010
Accepted for publication Lancet Endocrinology on 27 02 2018
Copyright
Prof. Dr. Willem F Lems
-0,5
1
2,5
4
5,5
-0,5
1
2,5
4
5,5
Lumbar Spine BMD Percentage Change From Baseline
at Months 6 and 12
Glucocorticoid-continuing (GC-C) Glucocorticoid-initiating (GC-I)
BL 6 12 BL 6 12
BMD
Percentage
Change


From
Baseline
BMD
Percentage
Change


From
Baseline
Study Month Study Month
227 211
224 209
128 126
127 119
Risedronate n=
Denosumab n=
n = Number of subjects with observed values at baseline and the time point of interest; *p ≤ 0.002
*
* *
*
Risedronate Denosumab
Copyright
Prof. Dr. Willem F Lems
-0,2
0,6
1,4
2,2
3,0
-0,5
0,4
1,3
2,1
3,0
Total Hip BMD Percentage Change From Baseline at
Month 12
* *
BMD
Percentage
Change


From
Baseline
BMD
Percentage
Change


From
Baseline
n = Number of subjects with observed values at baseline and the time point of interest; *p ≤ 0.001
BL 6 BL 6 12
Study Month Study Month
Risedronate n=
Denosumab n=
12
215
217
128
119
Glucocorticoid-continuing (GC-C) Glucocorticoid-initiating (GC-I)
Risedronate Denosumab
Copyright
Prof. Dr. Willem F Lems
GIOP
Copyright
Prof. Dr. Willem F Lems
14
Guidelines for Management of Glucocorticoid-Induced Osteoporosis.
Weinstein RS. N
Copyright
Prof. Dr. Willem F Lems
• GIOP is most common form of secondary osteoporosis;
• GCs are associated with elevated vertebral and non-vertebral fracture risk;
• Effective antiosteoporotic drug treatment is available!
• Are GC-treated patients optimal protected with anti-osteoporotic drugs?
• Urgent Need for Guidelines that help Clinicians to Prevent Fractures in their GC-treated
patients: but are all guidelines the same/comparable?
Copyright
Prof. Dr. Willem F Lems
Copyright
Prof. Dr. Willem F Lems
% of individuals > 50 years, using > 7.5 mg prednsione per day
and bone sparing drugs, in the Netherlands: around 30%!
Copyright
Prof. Dr. Willem F Lems
Copyright
Prof. Dr. Willem F Lems
Copyright
Prof. Dr. Willem F Lems
Aanbeveling 1: algemene maatregelen
Copyright
Prof. Dr. Willem F Lems
Really New!
• Overweeg direct te starten met parenterale medicatie (denosumab,
teriparatide of zoledroninezuur) bij:


• patiënten van 50 jaar en ouder die behandeld worden met ≥ 7,5 mg
prednison per dag gedurende 3 maanden en


• die een zeer hoog fractuurrisico hebben, bijvoorbeeld in geval van
een of meerdere risicofactoren:


– leeftijd ≥ 75 jaar;


– een recente (< 2 jaar) niet-wervelfractuur;


– een wervelfractuur graad 2, bevestigd met beeldvorming (minimaal ≥ 25%
hoogteverlies)


– een lage T-score (≤-2.0) in heup en/of wervelkolom;


– hoge dosis glucocorticoïden (≥ 15 mg per dag gedurende tenminste 3 maanden);


– een ernstige activiteit van de onderliggende ziekte.
Copyright
Prof. Dr. Willem F Lems
Alendronaat, Risedronaat
Zolendronaat, Denosumab of
Teriparatide
≥ 40jr
Prednison: ≥ 2,5 mg


en < 7,5 mg
neen
Wervelfractuur ≥ gr2
en/of BMD* ≤ -2
ja
Geef leefstijl en valpreventie adviezen, start zo nodig Ca/D3
Lab
DXA+VFA
Prednison < -2,5
mg (elke leeftijd)
< 40jr
Prednison: ≥ 7,5 mg


40-50 jr
Recente fractuur (≤ 1 jaar) of
klinische WF (≥ gr 2)
≥ 50jr
Indien :


Leeftijd ≥ 75 jaar of


Recente fractuur of≥ gr 2 of


T-score ≤-2 of ≥


≥ 15 mg per dag of


Hoge ziekte-activiteit
Bijwerkingen


of


Therapie falen
Prednison: stop


DXA+VFA
Indien:


T≤-2.5 of


Wervelfractuur ≥ gr 2 of


Fractuur afgelopen 2 jr
Therapie door
Behandelschema patienten met Glucocorticoiden ≥ 3 maanden
Therapie


Therapie 2e
lijn


Van wervelkolom of totale heup of heuphals
neen ja
Copyright
Prof. Dr. Willem F Lems
• Guidelines differ in GC dose/duration and BMD-treshold before
starting anti-osteoporotic treatment;


• Implementation of guidelines might be inhibited by complexity
and accelerated by simplicity and the use of clinically relevant
features.


• Life-Style factores, including exercise therapy, is important!


• In GC-treated patients with high fracture risk, starting with
second-line drugs (teriparatide, zoledronic acid or denosumab)
might be attractive.
Copyright
Prof. Dr. Willem F Lems
Learning goals 1. In 50+ patienten met ≥7,5 mg prednison per dag gedurende
tenminste 3 maanden, direct starten met anti-osteoporose
medicatie/orale bisfosfonaten (zonder DXA/VFA);


2. Idem, als er hoog fractuurrisico is: direct starten met
denosumab, teriparatide of zoledronaat;


3. 40-50 jaar en ≥7,5 mg prednison gedurende tenminste 3
maanden, en recente niet-wervelfractuur of klinische
wervelfractuur: direct starten orale bisfosfonaten (zonder
DXA/VFA)


4. Overige: 40+ en ≥2,5 mg prednison diagnostische DXA,
behandelen als T< -2 of wervelfractuur graad 2;


5. Stop prednison: DXA/VFA en een T-score > -2,5,


geen wervelfractuur en geen recente niet-wervelfractuur.
Content
Er is nog steeds onderbehandeling van GIOP, dit vraagt om actie van de
voorschrijvend arts!
Copyright
Prof. Dr. Willem F Lems
Thank you for your attention! Questions?? Or
wf.lems@amsterdamumc.nl
Copyright
Prof. Dr. Willem F Lems
IWO 25 jaar (1996-2021)
1995
Copyright
Prof. Dr. Willem F Lems
27
“Not only Glucocorticoids, but also the underlying disease might
have a negative effect on bone strength! (drug/disease confounding)
RA Disease Activity Bone Strength
Glucocorticoids
Courtesy of Maarten Boers
Secondary Osteoporosis: RA, SLE, Vasculitis, COPD, Inflammatory Bowel
Disease, etc
Copyright
Prof. Dr. Willem F Lems

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IWO Meeting 17 November 2021 - Prof. Dr. Willem F Lems

  • 1. • Module 7 Medicatie ter preventie van fracturen bij glucocorticoïden • Uitgangsvraag • Wanneer en welke medicatie ter preventie van fracturen is bij gebruik van glucocorticoïd geïndiceerd? • Prof Dr Willem F Lems 17-11-2021 • Amsterdam University medical centre, location VUmc • Department of Rheumatology, (EULAR Center of Excellence), • Amsterdam, the Netherlands Copyright Prof. Dr. Willem F Lems
  • 2. Disclosure: 
 Willem F. Lems, MD Company Speaking Fees/ 
 Advisory Boards Amgen, Eli Lilly, Merck, Curaphar, Galapagos, Pfizer. Copyright Prof. Dr. Willem F Lems
  • 3. Risk factors for osteoporosis and fractures 
 in patients with rheumatic diseases Primary Osteoporosis Secondary Osteoporosis Copyright Prof. Dr. Willem F Lems
  • 4. Glucocorticoids and vertebral fracture 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0 van Staa TP et al. JBMR 2000;15:993-1000 Women Men High dose Medium dose Low dose Control Incidence (%) <35 40 50 60 70 80 >85 <35 40 50 60 70 80 >85 Age (yrs) Copyright Prof. Dr. Willem F Lems
  • 5. 0.0 0.5 1.0 1.5 2.0 PMO GIO PMO GIO RR N = 9,681 987 14,551 500 Vertebral fracture Non-vertebral fracture RR= 0.58 0.48 0.81 0.79 Oral bisphosphonates In postmenopausal women and GIOP From Kanis et al, Health Tech Assess 2007;11:1-258 Copyright Prof. Dr. Willem F Lems
  • 6. Modern GIOP-studies New drugs are not tested against placebo, but against an active comparator! Copyright Prof. Dr. Willem F Lems
  • 8. Saag K et al. AR 2009, New Engl J Med 2007 ModernGIOP-studies Copyright Prof. Dr. Willem F Lems
  • 9. % of patients with fractures: 
 teriparatide versus alendronate in GIOP alendronate teriparatide p=0,004 p=0.007 Saag A & R 2009, New Engl J Med 2007 Copyright Prof. Dr. Willem F Lems
  • 10. Effect of Denosumab Compared With Risedronate in 
 Glucocorticoid-treated Individuals: Results From the 12-month 
 Primary Analysis of a Randomized, Double-blind, Active-controlled Study K Saag1, RB Wagman2, P Geusens3, J Adachi4, O Messina5,R Emkey6, R Chapurlat7, NS Daizadeh2, N Pannacciulli2,WF Lems8 1University of Alabama, Birmingham, AL, USA; 2Amgen Inc., Thousand Oaks, CA, USA; 3Maastricht University, Maastricht, The Netherlands; 4McMaster EULAR; Madrid, Spain; June 14, 2017; Presentation #OP0010 Accepted for publication Lancet Endocrinology on 27 02 2018 Copyright Prof. Dr. Willem F Lems
  • 11. -0,5 1 2,5 4 5,5 -0,5 1 2,5 4 5,5 Lumbar Spine BMD Percentage Change From Baseline at Months 6 and 12 Glucocorticoid-continuing (GC-C) Glucocorticoid-initiating (GC-I) BL 6 12 BL 6 12 BMD Percentage Change From Baseline BMD Percentage Change From Baseline Study Month Study Month 227 211 224 209 128 126 127 119 Risedronate n= Denosumab n= n = Number of subjects with observed values at baseline and the time point of interest; *p ≤ 0.002 * * * * Risedronate Denosumab Copyright Prof. Dr. Willem F Lems
  • 12. -0,2 0,6 1,4 2,2 3,0 -0,5 0,4 1,3 2,1 3,0 Total Hip BMD Percentage Change From Baseline at Month 12 * * BMD Percentage Change From Baseline BMD Percentage Change From Baseline n = Number of subjects with observed values at baseline and the time point of interest; *p ≤ 0.001 BL 6 BL 6 12 Study Month Study Month Risedronate n= Denosumab n= 12 215 217 128 119 Glucocorticoid-continuing (GC-C) Glucocorticoid-initiating (GC-I) Risedronate Denosumab Copyright Prof. Dr. Willem F Lems
  • 14. 14 Guidelines for Management of Glucocorticoid-Induced Osteoporosis. Weinstein RS. N Copyright Prof. Dr. Willem F Lems
  • 15. • GIOP is most common form of secondary osteoporosis; • GCs are associated with elevated vertebral and non-vertebral fracture risk; • Effective antiosteoporotic drug treatment is available! • Are GC-treated patients optimal protected with anti-osteoporotic drugs? • Urgent Need for Guidelines that help Clinicians to Prevent Fractures in their GC-treated patients: but are all guidelines the same/comparable? Copyright Prof. Dr. Willem F Lems
  • 17. % of individuals > 50 years, using > 7.5 mg prednsione per day and bone sparing drugs, in the Netherlands: around 30%! Copyright Prof. Dr. Willem F Lems
  • 20. Aanbeveling 1: algemene maatregelen Copyright Prof. Dr. Willem F Lems
  • 21. Really New! • Overweeg direct te starten met parenterale medicatie (denosumab, teriparatide of zoledroninezuur) bij: • patiënten van 50 jaar en ouder die behandeld worden met ≥ 7,5 mg prednison per dag gedurende 3 maanden en • die een zeer hoog fractuurrisico hebben, bijvoorbeeld in geval van een of meerdere risicofactoren: – leeftijd ≥ 75 jaar; – een recente (< 2 jaar) niet-wervelfractuur; – een wervelfractuur graad 2, bevestigd met beeldvorming (minimaal ≥ 25% hoogteverlies) – een lage T-score (≤-2.0) in heup en/of wervelkolom; – hoge dosis glucocorticoïden (≥ 15 mg per dag gedurende tenminste 3 maanden); – een ernstige activiteit van de onderliggende ziekte. Copyright Prof. Dr. Willem F Lems
  • 22. Alendronaat, Risedronaat Zolendronaat, Denosumab of Teriparatide ≥ 40jr Prednison: ≥ 2,5 mg en < 7,5 mg neen Wervelfractuur ≥ gr2 en/of BMD* ≤ -2 ja Geef leefstijl en valpreventie adviezen, start zo nodig Ca/D3 Lab DXA+VFA Prednison < -2,5 mg (elke leeftijd) < 40jr Prednison: ≥ 7,5 mg 40-50 jr Recente fractuur (≤ 1 jaar) of klinische WF (≥ gr 2) ≥ 50jr Indien : Leeftijd ≥ 75 jaar of Recente fractuur of≥ gr 2 of T-score ≤-2 of ≥ ≥ 15 mg per dag of Hoge ziekte-activiteit Bijwerkingen of Therapie falen Prednison: stop DXA+VFA Indien: T≤-2.5 of Wervelfractuur ≥ gr 2 of Fractuur afgelopen 2 jr Therapie door Behandelschema patienten met Glucocorticoiden ≥ 3 maanden Therapie Therapie 2e lijn Van wervelkolom of totale heup of heuphals neen ja Copyright Prof. Dr. Willem F Lems
  • 23. • Guidelines differ in GC dose/duration and BMD-treshold before starting anti-osteoporotic treatment; • Implementation of guidelines might be inhibited by complexity and accelerated by simplicity and the use of clinically relevant features. • Life-Style factores, including exercise therapy, is important! • In GC-treated patients with high fracture risk, starting with second-line drugs (teriparatide, zoledronic acid or denosumab) might be attractive. Copyright Prof. Dr. Willem F Lems
  • 24. Learning goals 1. In 50+ patienten met ≥7,5 mg prednison per dag gedurende tenminste 3 maanden, direct starten met anti-osteoporose medicatie/orale bisfosfonaten (zonder DXA/VFA); 2. Idem, als er hoog fractuurrisico is: direct starten met denosumab, teriparatide of zoledronaat; 3. 40-50 jaar en ≥7,5 mg prednison gedurende tenminste 3 maanden, en recente niet-wervelfractuur of klinische wervelfractuur: direct starten orale bisfosfonaten (zonder DXA/VFA) 4. Overige: 40+ en ≥2,5 mg prednison diagnostische DXA, behandelen als T< -2 of wervelfractuur graad 2; 5. Stop prednison: DXA/VFA en een T-score > -2,5, geen wervelfractuur en geen recente niet-wervelfractuur. Content Er is nog steeds onderbehandeling van GIOP, dit vraagt om actie van de voorschrijvend arts! Copyright Prof. Dr. Willem F Lems
  • 25. Thank you for your attention! Questions?? Or wf.lems@amsterdamumc.nl Copyright Prof. Dr. Willem F Lems
  • 26. IWO 25 jaar (1996-2021) 1995 Copyright Prof. Dr. Willem F Lems
  • 27. 27 “Not only Glucocorticoids, but also the underlying disease might have a negative effect on bone strength! (drug/disease confounding) RA Disease Activity Bone Strength Glucocorticoids Courtesy of Maarten Boers Secondary Osteoporosis: RA, SLE, Vasculitis, COPD, Inflammatory Bowel Disease, etc Copyright Prof. Dr. Willem F Lems