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Verslag ASBMR 2009,
IWO
(14 October, Utrecht)
Prof Dr Willem F Lems
Vrije Universiteit medisch centrum,
afdeling reumatolo...
• Combinatietherapie;
• Nieuwe middelen;
• Therapietrouw;
• Denosumab;
• Vertebroplastiek;
• Nederlandse Young Investigato...
Combinatietherapie met PTH en
botresorptieremmer zinvol?
Black, D. M. et al. N Engl J Med 2003;349:1207-1215
Mean Percent Changes in Areal Bone Mineral Density
on Dual-Energy X-Ra...
Black, D. M. et al. N Engl J Med 2003;349:1207-1215
Changes in Markers of Bone Formation (N-Propeptide of Type I Collagen,...
Effects of Once-Yearly Zoledronic Acid 5mg in Combination with
Teriparatide (PTH) on Postmenopausal Women with Osteoporosi...
New Anti-Osteoporotic Drugs?
Disease and Therapy Mediated by the
Calcium-Sensing Receptor
Ronacaleret, A Calcium-Sensing Receptor Antagonist: Results of a 1 Year
Double-Blind, Placebo-Controlled, Dose-Ranging Pha...
Over therapie-trouw
Netelenbos, ASBMR, Denver, 2009
?
Persistance of anti-osteoporotic drugs in daily practice
Most Non-Persistent Patients with Osteoporosis Do Not
Switch to Other Drug Treatments: a 3,5 year market survey
of 240,000...
Reasons for stopping anti-osteoporosis medications among
postmenopausal women. (GLOW).
(Ch Roux, et al, M 352)
• Heel veel data over denosumab!
Denosumab Binds to RANK Ligand Inhibiting
Osteoclast Development, Activation, and Survival
Osteoblasts
Hormones
Growth fac...
Original Article
Steven R. Cummings, M.D., Javier San Martin, M.D., Michael R. McClung, M.D., Ethel
S. Siris, M.D., Richar...
17
FREEDOM Study Design
• International, multicenter, randomized, double-blind,
placebo-controlled study
Key Inclusion Cri...
Primairy Endpoint: Vertebral Fractures
Cummings SR et al. N Engl J Med 2009;361:756-765
RR hip: 0.60; 95% c.i.: 0.37-0.97
RR 0.80; 95% c.i.: 0.67-0.95
Secondairy Outcomes: non-vertebral
fractures and hipfractur...
Percent Changes in Bone Mineral Density and Biochemical Markers of Bone Turnover
Cummings SR et al. N Engl J Med 2009;361:...
Cummings SR et al. N Engl J Med 2009;361:756-765Cummings SR et al. N Engl J Med 2009;361:756-765
Freedom-studie, subanalyse (pre-specified)
bij high-risk patients:
>70 jaar, T<-3, prevalente wervelfractuur
(tenminste 2 ...
Effects of denosumab on bone
histology/histomorphometry:
FREEDOM and STAND studies
•
Reid et al; Saturday 1030 hour
Background
• Anti-resorptive therapies for postmenopausal osteoporosis reduce
bone resorption, increase bone mineral densi...
Subject Incidence of New Vertebral Fracture Through
Month 36 by Baseline CTX Quartiles
n = Number of subjects with spine x...
Subject Incidence of New Vertebral Fracture Through Month 36
by Baseline TRACP5b Quartiles
n = Number of subjects with spi...
Subject Incidence of Nonvertebral Fracture Through
Month 36 by Baseline CTX Quartiles
n = Number of randomized subjects.
C...
Subject Incidence of Nonvertebral Fracture Through
Month 36 by Baseline CTX Quartiles
n = Number of randomized subjects.
C...
Subject Incidence of Nonvertebral Fracture Through
Month 36 by Baseline TRACP5b Quartiles
n = Number of randomized subject...
Effects of Denosumab on Bone Mineral Density and
Biochemical Markers of Bone Turnover: 6 Year Results of a Phase 2 Clinica...
Was er echt nieuws over
vertebro-kyfoplastieken? (Sa -389)
• R. Pflugmacher
•
Background: Excellent clinical and radiologi...
Original Article
A Randomized Trial of Vertebroplasty for Painful
Osteoporotic Vertebral Fractures
Rachelle Buchbinder, Ph...
Buchbinder R et al. N Engl J Med 2009;361:557-568
Original Article
A Randomized Trial of Vertebroplasty for
Osteoporotic Spinal Fractures
David F. Kallmes, M.D., Bryan A. C...
Secondary Outcome Measures at 1 Month (Intention-to-Treat Analyses)
Kallmes DF et al. N Engl J Med 2009;361:569-579
Scores on Measures of Disability and Pain over a 3-Month Period
Kallmes DF et al. N Engl J Med 2009;361:569-579
397/23/03
EFOS participants
Enrolment
8 European countries
Austria
Denmark
France
Germany
Greece
Ireland
Netherlands
Sweden
Incident fractures during
teriparatide treatment
40
n=72
(4.6%)
n=45
(3.5%)
n=33
(2.8%)
n=138
(8.8%)
OR 0.68 (95% CI 0.47,...
Frequency of back pain
41
Langdahl et al. CTI [in press]
* ***
*p<0.001 compared to baseline (sign test)
Limitation of activities
42
Langdahl et al. CTI [in press]
* ***
*p<0.001 compared to baseline (sign test)
Incidence of fractures during
and after teriparatide treatment
51
(3.5%)
76
(4.8%)
34
(2.7%)
41
(3.0%)
18
(1.6%)
13
(1.3%)...
About Fractures
Effects of antiresorptive treatment of various non-vertebral
fracture outcomes (1242, Mackey D, Cummings S).
• Achtergrond...
Effects of antiresorptive treatment of various non-vertebral
fracture outcomes (1242, Mackey D, Cummings S).
• Treatment e...
Effects of antiresorptive treatment of various non-vertebral
fracture outcomes (1242, Mackey D, Cummings S).
Time Since Prior Fracture is a Risk Modifier for Ten Year
Osteoporotic Fractures: The Manitoba Bone Density
Program(Leslie...
Risico voor nieuwe fractuur
clusteren in de tijd
Maastricht UMC & UHasselt
--- First fracture Subsequent fracture
from men...
• Twee Young Investigators Award!
• Tineke van Geel (Maastricht) en Lilian
van Tuyl (Amsterdam)
5- EN 10-JAARS FRACTUURRISICO:
EEN NOMOGRAM (1022, Van Geel)
• 2372 postmenopausal women, 3 years follow-
up;
• 382 fractu...
1
Lancet 1997
COBRA trial results: 1 year
Change in
disease activity
Arthritis & Rheumatism 2004
COBRA trial results: 4.5 years
P =0.008
0
10
20
30
40
0 1 2 3 4 5
Damage progression (Sharp/va...
Annals of Rheumatic Diseases 2009
COBRA trial results: 11 years
CTX-1 dataset CTX-2 dataset
RANKL:OPG RANKL:OPG
CTX1 CTX2 at 3 mo
ESR at 3 mo ESR at 3 mo
Baseline damage Baseline damage
...
• Dank voor Uw
aandacht!
About FRAX: case finding by the web
www.shef.ac.uk/FRAX/ Kanis, Osteoporosis Int, 2008
Doelstellingen van FRAX
• Berekening van het 10-jaars fractuurrisico
– op basis van gewogen bijdragen van klinische risico...
Voordelen van FRAX
• Wereldwijd bruikbaar, en gratis
beschikbaar via web
• Zinvol voor:
–klinische opsporing van fractuurr...
Beperkingen van FRAX (1)
• Houdt geen rekening met dosiseffect van risico’s
– dosis glucocorticoïden
– tijdstip van en aan...
Beperkingen/aandachtspunten FRAX (2):
– vitamine D deficiëntie
– lichamelijke (in)activiteit
– botmarkers
– medicatie zoal...
• Het is niet mogelijk om in het model meerdere secundaire risicofactoren
in te voeren, terwijl soms ook sprake is van mee...
UK: Strategie voor interventie in FRAX-NOGG
• (elderly) women with a prior fragility fracture
should be considered for tre...
NOF richtlijn (VS) interventie
– Postmenopauzale vrouwen en mannen van
50 jaar en ouder met de volgende criteria:
• Zelf g...
Case finding
Risicoscore ≥ 4
DEXA (VFA)
T-score ≥ -1
T-score tussen -1
en -2,5
T-score ≤ -2,5
of
wervelinzakking
Geen beha...
• Dank voor Uw
aandacht!
Seminar 14-10-09 - asbmr 2009
Seminar 14-10-09 - asbmr 2009
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Seminar 14-10-09 - asbmr 2009

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Seminar 14-10-09 - asbmr 2009

  1. 1. Verslag ASBMR 2009, IWO (14 October, Utrecht) Prof Dr Willem F Lems Vrije Universiteit medisch centrum, afdeling reumatologie, Amsterdam
  2. 2. • Combinatietherapie; • Nieuwe middelen; • Therapietrouw; • Denosumab; • Vertebroplastiek; • Nederlandse Young Investigators Award Winners; • FRAX : pro en contra. • NB Soms korte terugblik op zeer recente literatuur!
  3. 3. Combinatietherapie met PTH en botresorptieremmer zinvol?
  4. 4. Black, D. M. et al. N Engl J Med 2003;349:1207-1215 Mean Percent Changes in Areal Bone Mineral Density on Dual-Energy X-Ray Absorptiometry
  5. 5. Black, D. M. et al. N Engl J Med 2003;349:1207-1215 Changes in Markers of Bone Formation (N-Propeptide of Type I Collagen, Panel A) and Bone Resorption (C-Terminal Telopeptide of Type I Collagen, Panel B)
  6. 6. Effects of Once-Yearly Zoledronic Acid 5mg in Combination with Teriparatide (PTH) on Postmenopausal Women with Osteoporosis • In 412 postmenopausal, osteoporotic, women, the combination of ZOL and PTH increased BMD more than either alone. • “Combination therapy could be considered for patients at high risk for hip fractures or those with very low BMD” F Cosman et al; 1025
  7. 7. New Anti-Osteoporotic Drugs?
  8. 8. Disease and Therapy Mediated by the Calcium-Sensing Receptor
  9. 9. Ronacaleret, A Calcium-Sensing Receptor Antagonist: Results of a 1 Year Double-Blind, Placebo-Controlled, Dose-Ranging Phase II Study • 569 postmenopausal women open-label teriparatide (TER) or placebo or one of 4 doses of ronacaleret (RON) (100, 200, 300 or 400mg daily), or alendronate (ALN) (70mg weekly). • The primary endpoint was the % change in lumbar spine (LS) bone mineral density (BMD) at 12 months. • The trial was terminated early due to lack of efficacy following an interim analysis of % change in LS BMD at 6 months. • Ronacaleret (200, 300, 400mg) Spine BMD was significantly different from placebo (1.4-1.9%), while ALN and TER increased LS BMD 4.7% and 9.2%. • At the total hip, RON caused small but statistically significant decreases in BMD at all dose ronacaleret levels, while ALN and TER showed modest gains (2.8%, 2.6%). • RON (200, 300, 400mg) showed median increases in serum CTx >20% starting at month 6, reaching a maximum of 58% at month 10 as compared to TER
  10. 10. Over therapie-trouw
  11. 11. Netelenbos, ASBMR, Denver, 2009 ? Persistance of anti-osteoporotic drugs in daily practice
  12. 12. Most Non-Persistent Patients with Osteoporosis Do Not Switch to Other Drug Treatments: a 3,5 year market survey of 240,000 patients in the Netherlands • After stopping, follow-up of 18 month: only 20% (95% c.i.: 17-25%) switched to other drugs. • “ major failure to adequately treat patients at high risk for fractures in real clinical practice”
  13. 13. Reasons for stopping anti-osteoporosis medications among postmenopausal women. (GLOW). (Ch Roux, et al, M 352)
  14. 14. • Heel veel data over denosumab!
  15. 15. Denosumab Binds to RANK Ligand Inhibiting Osteoclast Development, Activation, and Survival Osteoblasts Hormones Growth factors Cytokines Bone Resorption Prevented and Inhibited Osteoclast Precursor Osteoclast Formation Inhibited Osteoclast Function and Survival Inhibited Adapted from Boyle WJ, et al. Nature. 2003;423:337-342. RANK Ligand RANK Denosumab OPG
  16. 16. Original Article Steven R. Cummings, M.D., Javier San Martin, M.D., Michael R. McClung, M.D., Ethel S. Siris, M.D., Richard Eastell, M.D., Ian R. Reid, M.D., Pierre Delmas, M.D., Ph.D., Holly B. Zoog, Ph.D., Matt Austin, M.S., Andrea Wang, M.A., Stepan Kutilek, M.D., Silvano Adami, M.D., Ph.D., Jose Zanchetta, M.D., Cesar Libanati, M.D., Suresh Siddhanti, Ph.D., Claus Christiansen, M.D., for the FREEDOM Trial N Engl J Med Volume 361(8):756-765 August 20, 2009
  17. 17. 17 FREEDOM Study Design • International, multicenter, randomized, double-blind, placebo-controlled study Key Inclusion Criteria: • Postmenopausal women aged 60 to 90 years • T-score < -2.5 and > -4.0 at the lumbar spine or total hip • No severe or > 2 moderate vertebral fractures Primary Endpoint: • New vertebral fractures Secondary Endpoints: • Nonvertebral fractures • Hip fractures R A N D O M I Z A T I O N Placebo n = 3906 Denosumab 60 mg Q6M SC n = 3902 Daily Calcium and Vitamin D Supplementation N = 7808 S C R E E N I N G Months: 0 6 12 18 24 30 36 E N D O F T R E A T M E N T Last dose Cummings S, et al. N Engl J Med. 2009;361:756-765.
  18. 18. Primairy Endpoint: Vertebral Fractures Cummings SR et al. N Engl J Med 2009;361:756-765
  19. 19. RR hip: 0.60; 95% c.i.: 0.37-0.97 RR 0.80; 95% c.i.: 0.67-0.95 Secondairy Outcomes: non-vertebral fractures and hipfractures
  20. 20. Percent Changes in Bone Mineral Density and Biochemical Markers of Bone Turnover Cummings SR et al. N Engl J Med 2009;361:756-765
  21. 21. Cummings SR et al. N Engl J Med 2009;361:756-765Cummings SR et al. N Engl J Med 2009;361:756-765
  22. 22. Freedom-studie, subanalyse (pre-specified) bij high-risk patients: >70 jaar, T<-3, prevalente wervelfractuur (tenminste 2 items) 0 2 4 6 8 10 12 vertebral hip nonvertebral all placebo high risk placebo high risk denosumab -65%, p<0,0001 -48%, p=0,02 NS
  23. 23. Effects of denosumab on bone histology/histomorphometry: FREEDOM and STAND studies • Reid et al; Saturday 1030 hour
  24. 24. Background • Anti-resorptive therapies for postmenopausal osteoporosis reduce bone resorption, increase bone mineral density (BMD), and reduce the risk of fracture. • Whether therapy-associated increases in BMD and reductions in fracture risk are related to the level of bone resorption at baseline is a topic of interest.
  25. 25. Subject Incidence of New Vertebral Fracture Through Month 36 by Baseline CTX Quartiles n = Number of subjects with spine x-ray at baseline and ≥ 1 postbaseline visit. Baseline CTX Quartiles (ng/mL) ncidence Through Month 36 (%) 0 2 4 6 8 10 12 14 Cochran-Armitage trend test among denosumab groups; P = 0.01 891 898 895 914n < 0.381 0.381-0.536 0.537-0.717 ≥ 0.718 IncidenceThroughMonth35(%) Placebo Denosumab 86% 884 917 937 887 3.1% P = 0.0002 55% 6.9% 1.4% P < 0.0001 9.9% 4.9% 1.8% P = 0.0002 64% 6.7% 3.2% P = 0.0009 51%
  26. 26. Subject Incidence of New Vertebral Fracture Through Month 36 by Baseline TRACP5b Quartiles n = Number of subjects with spine x-ray at baseline and ≥ 1 postbaseline visit. Placebo Denosumab Baseline TRACP5b Quartiles (IU/L) < 3.424 3.424-4.352 4.353-5.478 ≥ 5.479 0 2 4 6 8 10 881 878 891 940n Cochran-Armitage trend test among denosumab groups; P = 0.16 7.9% 3.2% P < 0.0001 59% 906 919 918 871 6.7% 2.1% P < 0.0001 70% 7.3% 1.7% P < 0.0001 76% 6.5% 2.4% P < 0.0001 62% IncidenceThroughMonth35(%)
  27. 27. Subject Incidence of Nonvertebral Fracture Through Month 36 by Baseline CTX Quartiles n = Number of randomized subjects. Cochran-Armitage trend test among denosumab groups; P = 0.09 Baseline CTX Quartiles (ng/mL)) dence Through Month 36 (%) 0 2 4 6 8 10 11 7.5% P = 0.89 9.7% P = 0.06 7.5% 7.2% P = 0.37 P = 0.06 7.2% 7.3% 6.7% 5.2% 2% 26% 15% 30% 937 944 950 951 938 972 966 936n < 0.381 0.381-0.536 0.537-0.717 ≥ 0.718 IncidenceThroughMonth36(%) Placebo Denosumab
  28. 28. Subject Incidence of Nonvertebral Fracture Through Month 36 by Baseline CTX Quartiles n = Number of randomized subjects. Cochran-Armitage trend test among denosumab groups; P = 0.09 Baseline CTX Quartiles (ng/mL)) dence Through Month 36 (%) 0 2 4 6 8 10 11 7.5% P = 0.89 9.7% P = 0.06 7.5% 7.2% P = 0.37 P = 0.06 7.2% 7.3% 6.7% 5.2% 2% 26% 15% 30% 937 944 950 951 938 972 966 936n < 0.381 0.381-0.536 0.537-0.717 ≥ 0.718 IncidenceThroughMonth36(%) Placebo Denosumab
  29. 29. Subject Incidence of Nonvertebral Fracture Through Month 36 by Baseline TRACP5b Quartiles n = Number of randomized subjects. Cochran-Armitage trend test among denosumab groups; P = 0.43 Baseline TRACP5b Quartiles (IU/L) IncidenceThroughMonth36(%) 0 2 4 6 8 10 11 7.4% P = 0.22 8.1% P = 0.62 6.8% 9.4% P= 0.16 P = 0.01 6.0% 8.9% 5.4% 6.1% 20% 8% 24% 35% 934 959 926 968 939 955 984 910n < 3.424 3.424-4.352 4.353-5.478 ≥ 5.479 Placebo Denosumab
  30. 30. Effects of Denosumab on Bone Mineral Density and Biochemical Markers of Bone Turnover: 6 Year Results of a Phase 2 Clinical Trial P Miller
  31. 31. Was er echt nieuws over vertebro-kyfoplastieken? (Sa -389) • R. Pflugmacher • Background: Excellent clinical and radiological results could be achieved in patients with osteoporotic fractures treated with Balloon- Kyphoplasty. Only a few articles report on the clinical and radiological outcome in comparison to a non surgical treatment. Purpose: To evaluate the long-term outcomes of 126 patients with 239 osteoporotic vertebral fractures, located in the thoracic and lumbar spine, treated with Balloon Kyphoplasty and compared with a conservatively treated control group. Study design: A prospective follow-up was performed in all patients. Patients who refused surgical treatment served as control. Patient sample: 90 patients (37 males and 53 females) with 187 osteoporotic vertebral fractures were treated with Balloon Kyphoplasty, 36 (12 males and 24 females) with 52 vertebral fractures served as controls. We were able to have a 2 year follow up in 78 patients with 168 vertebrae treated with Balloon Kyphoplasty and 32 patients with 45 vertebral fractures treated conservatively. Outcome measures: Clinical and radiological results were measured prospectively in all patients. Methods: Symptomatic levels were identified by correlating the clinical presentation with conventional radiographs, CT and / or MRI. During the 2 year follow-up reduction in pain was determined. The effects on pain symptoms were measured on a self-reported Visual analog Scale (VAS) and the Oswestry score was documented to assess disability. Radiographic scans were performed pre- and postoperatively and after 3, 6, 12 and 24 months. The vertebral height and kyphosis angle were measured to assess the restoration of the sagittal alignment. Results: The median pain scores (VAS) improved significantly from pre- to post-intervention as did the Oswestry Disability Score (p<0.001), in the conservative group no significant changes could be documented. Balloon Kyphoplasty led to a significantly vertebral height restoration and correction of kyphotic deformity in the long-term (p<0.05), in the conservative group significant further height loss and increase of kyphosis could be documented (p<0.001). There were significantly fewer patients with new vertebral fractures of the thoracic and lumbar spine, after 24-months, in the kyphoplasty group (15 patients, 4 male, 11 female, 19.2%) than in the control group (13 patients, 3 male, 9 female, 40.6%). Conclusion: Balloon Kyphoplasty as an addition to medical treatment leads to a statistically significant reduction of pain status and improvement of physical function. Further, Balloon Kyphoplasty reduces occurrence of new vertebral fractures and prevents a height loss and increase of kyphotic deformity in the long term. Disclosures: None
  32. 32. Original Article A Randomized Trial of Vertebroplasty for Painful Osteoporotic Vertebral Fractures Rachelle Buchbinder, Ph.D., Richard H. Osborne, Ph.D., Peter R. Ebeling, M.D., John D. Wark, Ph.D., Peter Mitchell, M.Med., Chris Wriedt, M.B., B.S., Stephen Graves, D. Phil., Margaret P. Staples, Ph.D., and Bridie Murphy, B.Sc. N Engl J Med Volume 361(6):557-568 August 6, 2009
  33. 33. Buchbinder R et al. N Engl J Med 2009;361:557-568
  34. 34. Original Article A Randomized Trial of Vertebroplasty for Osteoporotic Spinal Fractures David F. Kallmes, M.D., Bryan A. Comstock, M.S., Patrick J. Heagerty, Ph.D., Judith A. Turner, Ph.D., David J. Wilson, F.R.C.R., Terry H. Diamond, F.R.A.C.P., Richard Edwards, F.R.C.R., Leigh A. Gray, M.S., Lydia Stout, B.S., Sara Owen, M.Sc., William Hollingworth, Ph.D., Basavaraj Ghdoke, M.D., Deborah J. Annesley-Williams, F.R.C.R., Stuart H. Ralston, F.R.C.P., and Jeffrey G. Jarvik, M.D., M.P.H. N Engl J Med Volume 361(6):569-579 August 6, 2009
  35. 35. Secondary Outcome Measures at 1 Month (Intention-to-Treat Analyses) Kallmes DF et al. N Engl J Med 2009;361:569-579
  36. 36. Scores on Measures of Disability and Pain over a 3-Month Period Kallmes DF et al. N Engl J Med 2009;361:569-579
  37. 37. 397/23/03 EFOS participants Enrolment 8 European countries Austria Denmark France Germany Greece Ireland Netherlands Sweden
  38. 38. Incident fractures during teriparatide treatment 40 n=72 (4.6%) n=45 (3.5%) n=33 (2.8%) n=138 (8.8%) OR 0.68 (95% CI 0.47, 0.98)a** OR 0.53 (95% CI 0.35, 0.82)a* a Adjusted model by age, prior bisphosphonate use, and a history of fracture in the last 12 months before starting teriparatide *p<0.05, **p<0.005 Langdahl et al. CTI [in press]
  39. 39. Frequency of back pain 41 Langdahl et al. CTI [in press] * *** *p<0.001 compared to baseline (sign test)
  40. 40. Limitation of activities 42 Langdahl et al. CTI [in press] * *** *p<0.001 compared to baseline (sign test)
  41. 41. Incidence of fractures during and after teriparatide treatment 51 (3.5%) 76 (4.8%) 34 (2.7%) 41 (3.0%) 18 (1.6%) 13 (1.3%) OR 0.71 (95% CI: 0.50, 1.00; p=0.051) OR 0.61 (95% CI: 0.41, 0.90; p=0.012) OR 0.54 (95% CI: 0.36, 0.82; p=0.004) OR 0.33 (95% CI: 0.19, 0.55; p<0.001) OR 0.26 (95% CI: 0.14, 0.47; p<0.001) 43
  42. 42. About Fractures
  43. 43. Effects of antiresorptive treatment of various non-vertebral fracture outcomes (1242, Mackey D, Cummings S). • Achtergrond: verschillende definities voor non- vertebral fractures in RCTs; • Data van FIT (alendronaat), HORIZON (zoledronaat), PEARL (lasoxifen); • 17.098 postmenopausal osteoporotic women, 1.892 non-vertebral fractures;
  44. 44. Effects of antiresorptive treatment of various non-vertebral fracture outcomes (1242, Mackey D, Cummings S). • Treatment effect vergelijkbaar voor high-trauma versus low trauma: 0.70 (0.52-0.96) versus 0.76 (0.69-0.84); • Non vertebral 6 versus all nonvertebral fractures: 0.69 (0.61-0.77) versus 0.78 (0.69- 0.89); • Excluding finger and toe fractures versus all nonvertebral fractures: 0.73 (0.67-0.81) versus 0.75 (0.68-0.82)
  45. 45. Effects of antiresorptive treatment of various non-vertebral fracture outcomes (1242, Mackey D, Cummings S).
  46. 46. Time Since Prior Fracture is a Risk Modifier for Ten Year Osteoporotic Fractures: The Manitoba Bone Density Program(Leslie, 1093)
  47. 47. Risico voor nieuwe fractuur clusteren in de tijd Maastricht UMC & UHasselt --- First fracture Subsequent fracture from menopause on from 1st fracture on Van Geel, ARD, 2009
  48. 48. • Twee Young Investigators Award! • Tineke van Geel (Maastricht) en Lilian van Tuyl (Amsterdam)
  49. 49. 5- EN 10-JAARS FRACTUURRISICO: EEN NOMOGRAM (1022, Van Geel) • 2372 postmenopausal women, 3 years follow- up; • 382 fractures (16,1%); • Age: 1,09 per 5 years; • Low BMD: 1,23 per SD; • Prior Fracture 3.27 for fracture within last 5 years; • Prior Fracture 1.97 for fracture > 5 years ago;
  50. 50. 1 Lancet 1997 COBRA trial results: 1 year Change in disease activity
  51. 51. Arthritis & Rheumatism 2004 COBRA trial results: 4.5 years P =0.008 0 10 20 30 40 0 1 2 3 4 5 Damage progression (Sharp/van der Heijde) Years COBRACOBRA SSZSSZ
  52. 52. Annals of Rheumatic Diseases 2009 COBRA trial results: 11 years
  53. 53. CTX-1 dataset CTX-2 dataset RANKL:OPG RANKL:OPG CTX1 CTX2 at 3 mo ESR at 3 mo ESR at 3 mo Baseline damage Baseline damage RF R2 = 42% R2 = 46% Best prediction models based on baseline AND follow-up measurements
  54. 54. • Dank voor Uw aandacht!
  55. 55. About FRAX: case finding by the web www.shef.ac.uk/FRAX/ Kanis, Osteoporosis Int, 2008
  56. 56. Doelstellingen van FRAX • Berekening van het 10-jaars fractuurrisico – op basis van gewogen bijdragen van klinische risicofactoren voor osteoporose en fracturen – met en zonder resultaten van botdichtheidmeting • Bijdrage tot het bepalen van afkappunten voor: – indicatie voor botmeting – starten van medicamenteuze behandeling – Wat is de plaatsbepaling in de dagelijkse praktijk?
  57. 57. Voordelen van FRAX • Wereldwijd bruikbaar, en gratis beschikbaar via web • Zinvol voor: –klinische opsporing van fractuurrisico –geeft patient en arts inzicht in absoluut fractuurrisico; –kan belangrijk zijn bij beslissing omtrent behandeling.
  58. 58. Beperkingen van FRAX (1) • Houdt geen rekening met dosiseffect van risico’s – dosis glucocorticoïden – tijdstip van en aantal voorafgaande fracturen • Wervelfracturen tellen niet mee; • Valrisico niet meegenomen; • Enkel toepasbaar bij onbehandelde patiënten; • BMD: enkel femurhals • Geen consensus/recommendation omtrent indicaties therapie – wel beschikbaar via rechtstreekse link met NOGG (UK)
  59. 59. Beperkingen/aandachtspunten FRAX (2): – vitamine D deficiëntie – lichamelijke (in)activiteit – botmarkers – medicatie zoals anti-epileptica, aromatase remmers en androgeen deprivatie therapie – Het lijkt logisch met betrouwbaarheidsintervallen te werken wanneer fractuurrisico wordt berekend op basis van risicofactoren, dit is echter niet in het model geïmplementeerd.
  60. 60. • Het is niet mogelijk om in het model meerdere secundaire risicofactoren in te voeren, terwijl soms ook sprake is van meer dan een oorzaken van secundaire osteoporose; Bij de FRAX calculator veranderd het fractuurrisico niet wanneer secundaire osteoporose wordt aangevinkt, en ook een BMD waarde wordt ingevuld. “dit wordt verklaard doordat BMD het risico van secundaire osteoporose teniet doet” • FRAX geeft alleen de mogelijkheid om heuphals BMD in te voeren, terwijl met name een lage BMD in de lumbale wervelkolom geassocieerd is met een verhoogd risico op wervelfracturen. Enkele beperkingen/aandachtspunten FRAX (3):
  61. 61. UK: Strategie voor interventie in FRAX-NOGG • (elderly) women with a prior fragility fracture should be considered for treatment without the need for further assessment • In men with or without a fragility fracture and in women without a previous fragility fracture, management strategy should be based on the assessment of the ten year probability of a major osteoporotic fracture (clinical spine, hip, forearm or humerus).
  62. 62. NOF richtlijn (VS) interventie – Postmenopauzale vrouwen en mannen van 50 jaar en ouder met de volgende criteria: • Zelf gerapporteerde heup of wervelfractuur na het 20e levensjaar • Heuphals of wervel T-score ≤−2.5 • Heuphals T-score tussen −1 en −2.5 SD met een 10-jaars heup fractuur risico ≥3% of 4-fractuur risico ≥20% Dawson-Hughes B et al., Osteoporos Int 2009. webfirst
  63. 63. Case finding Risicoscore ≥ 4 DEXA (VFA) T-score ≥ -1 T-score tussen -1 en -2,5 T-score ≤ -2,5 of wervelinzakking Geen behandeling Bereken FRAX risico indien geen VFA of Wervelfoto VFA of Wervelfoto Behandelen Wervelinzakking Nee Ja Behandelen Bereken FRAX risico NOGG Geen behandeling NOGG Behandelen
  64. 64. • Dank voor Uw aandacht!

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