This document discusses real-world evidence on denosumab for osteoporosis treatment and fracture prevention. It summarizes several studies, including one that found denosumab reduced fracture risk by 38% compared to placebo in over 25,000 postmenopausal women. Another study showed good long-term persistence with denosumab therapy in over 800 patients. Additional studies observed that zoledronic acid can prevent bone loss following denosumab discontinuation, and bisphosphonate treatment after denosumab provides protection against new vertebral fractures.

1. Real world evidence
omtrent denosumab
Antoon van Lierop
IWO Webinar
16 november 2022
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Dr. A van Lierop

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• Sponsoring of onderzoeksgeld
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• Andere relatie, namelijk …
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Disclosure belangen spreker
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Dr. A van Lierop

3. Real world evidence
Randomized controlled trials Real world evidence
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Dr. A van Lierop

4. Real world evidence denosumab
1. Fractuurpreventie
• Lai et al. Osteoporosis International 2022 May 33(5):1155-1164
2. Persistentie
• Boschitsch et al. Osteoporosis International 2022 Jan 33(1):263-272
3. Effect van bisfosfonaten op rebound effect
• Evert-Graber et al. Bone 2022 Oct 163:11498
• Burckhardt et al. J of Bone and Mineral Research 2021 Sep 36(9):1717-1728
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Dr. A van Lierop

5. FREEDOM trial: effect denosumab op fractuur risico
Cummings SR, et al. N Engl J Med. 2009; 361: 756-765
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Dr. A van Lierop

6. FREEDOM extension trial: effect denosumab op fractuur
risico
0,0
1,0
2,0
3,0
4,0
1 2 3 4/5 6 7/8 9/10
0
0
0
0
1
1
1
3,1
3,1
2,2
Years of Study Treatment
Yearly
Incidence
of
New
Vertebral
Fractures,
% Pivotal Phase 3 Fracture Trial Extension Study
Placebo (n=3906) Continued denosumab (n=2343)
1.5
1.2
1.4
1.3
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Dr. A van Lierop

7. Effectiveness of denosumab for fracture prevention in real‑world
postmenopausal women with osteoporosis: a retrospective cohort study
Lai et al. Osteoporosis International 2022 May 33(5):1155-1164
25.059 ptn
13.847 ptn
13.419 ptn
Propensity
score
matching
13.419 ptn
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Dr. A van Lierop

8. Effectiveness of denosumab for fracture prevention in real‑world
postmenopausal women with osteoporosis: a retrospective cohort study
Lai et al. Osteoporosis International 2022 May 33(5):1155-1164
1.0 per 100 vs 1.7 per 100 patientjaren
Risico reductie van 38%
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Dr. A van Lierop

9. Long‑term persistence with denosumab: real‑world data from the
Austrian Osteoporosis Clinic (AOC). A retrospective data analysis
Boschitsch et al. Osteoporosis Int 2022 Jan 33(1):263-272
851 patienten
- 630 intern
- 221 extern
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Dr. A van Lierop

10. Rebound effect denosumab
Bone et al. J Clin Endocrinol Metab, April 2011, 96(4):972–980
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Dr. A van Lierop

11. Effects of zoledronate on bone mineral density and bone turnover after long-term denosumab therapy: Observations in a real-world
setting
Evert-Graber et al. Bone 2022 Oct 163:11498
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Dr. A van Lierop

12. Effects of zoledronate on bone mineral density and bone turnover after long-term denosumab therapy: Observations in a real-world
setting
Evert-Graber et al. Bone 2022 Oct 163:11498
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Dr. A van Lierop

13. Effects of zoledronate on bone mineral density and bone turnover after long-term denosumab therapy: Observations in a real-world
setting
Evert-Graber et al. Bone 2022 Oct 163:11498
Copyright
Dr. A van Lierop

14. Fractures After Denosumab Discontinuation:
A Retrospective Study of 797 Cases
• Gemiddeld 6 injecties
• FU: 26 maanden
• Vooraf 48% bisfosfonaat
• Achteraf 63% bisfosfonaat
• 81 patienten (10%)
• 215 wervelfracturen
Burckhardt et al. JBMR 2021 Sep 36(9):1717-1728
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Dr. A van Lierop

15. Fractures After Denosumab Discontinuation:
A Retrospective Study of 797 Cases
Burckhardt et al. JBMR 2021 Sep 36(9):1717-1728
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Dr. A van Lierop

16. Samenvatting
• Denosumab geeft ook in real world setting adequate fractuur reductie
• Behandeling wordt in merendeel patienten gecontinueerd
• Nabehandeling met zoledoninezuur voorkomt ten delen botverlies tgv
rebound fase
• Nabehandeling met bisfosfonaten geven adequate bescherming tegen
nieuwe wervelfracturen na staken van denosumab
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Dr. A van Lierop

17. Vragen
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Dr. A van Lierop