Waarde van botmarkers in de dagelijkse praktijk
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Transcript of Waarde van botmarkers in de dagelijkse praktijk
Botmarkers (BTM) in de dagelijkse praktijk
Universitair Medisch Centrum Groningen
Dr. E. van der Veer Maastricht, 23 en 24 november 2012
UMCG
Bone volume Materials properties
Mineralization (adverse effects of fluoride) Organic matrix composition (mutations in type I collagen gene)
Structure Size and shape Internal architecture
Turnover Damage accumulation
(microcracks) Connectivity
Micro-compression of Bone
Ralph Müller
UMCG Seeman et al. NEJM 2006
PINP
BALP
Osteocalcine CTx
Naylor K, Eastell R. Bone Turnover Markers: use in osteoporosis.
Nat Rev Rheumatol. 2012 Jun 5;8(7):379-389
• BTMs are useful for the management of patients with osteoporosis, – for initial clinical assessment – for guiding and monitoring of treatment.
UMCG
–100
–80
–60
–40
–20
0
Baseline 6 12 months
Mea
n ch
ange
(%)
Urine NTx Serum CTx
p<0.001
p<0.001 –40%
–53% –55%
–74% p<0.001
p<0.001
3
p<0.001
Treatment difference 13%
p<0.001
Treatment difference 19%
Alendronate n = 442 429 414 365 449 443 423 382 Risedronate n = 457 449 426 375 459 455 433 387
Alendronate 70 mg OW Risedronate 35 mg OW
–100
–80
–60
–40
–20
0
Baseline 6 12 months 3
BMD (DXA) wordt uitgedrukt in T-score of Z-score. Maat voor de hoeveelheid botmassa
3 2 1 0
-1 -2 -3
BM
D T
-Sco
re
T-score = -2.5 Z-score = -1
20 30 40 50 60 70 80 90
+1 SD 0 -1 SD
Leeftijd (jaren)
UMCG
Lower half of reference interval
Upper half of reference interval
80
NTX/Cr (nmol/mmol creatinine)
Osteoporosis; untreated
NTX/Cr (nmol/mmol creatinine)
Osteoporosis; risedronate
100 10 32 100 10 32
Num
ber o
f pat
ient
s
0
10
20
30
40
50
60
70
Num
ber o
f pat
ient
s 0
10
20
30
40
Eastell JBMR 2005
0 11 62 27% 7 63 28 2%
UMCG
1. The baseline level of bone resorption is related to subsequent fracture risk,
2. The reduction in bone resorption explains, in part, the reduction in the risk of fractures with risedronate,
Placebo
Calcium + vitamin D
Risedronate 5 mg
u CTx T-score u NTx T-score
UMCG
Eastell R , Barton I , Hannon RA , Chines A , Garnero P , Delmas PD Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate.
J Bone Miner Res 2003; 18: 1051– 1056.
Eastell R, Hannon RA, Garnero P, Campbell MJ, Delmas PD Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate. Review of statistical analysis.
J Bone Miner Res 2007; 22: 1656– 1660.
UMCG
0 5
10 15 20 25 30 35
1 2 3 4 5 6 7 8 9 10
66 patients in each groupe
CTx T-score <-1.7 -1 0 +1 +2 >+2.4
% fr
actu
res
In the context of fracture risk for groups: The appropiate risk is that of the group above a specified limit compared to the risk of the general population e.g. Q4/Q1-4
In the context of fracture risk assessment for an individual: The most appropiate relative risk (assuming a normal distribution) is the risk of the individual compared with the risk in the normal population
BTMs in fracture risk prediction
UM
CG
Rhe
umat
olog
y &
Clin
ical
Imm
unol
ogy
BTM " OC: osteocalcin " PINP: product of collagen formation " BALP: necessary for start of mineralization " sCTX: product of collagen degradation
" Z-scores " (BTM value of individual patient – mean BTM value of the matched 10-year-cohort of
reference group) / SD of matched reference cohort
sCTX in males and females of a healthy reference cohort (n=550)
Healthy reference cohort
UMCG
Bisphosphonate calcium & vitamin D
UMCG
% change after start bisphosphonate Follow-up in Z-scores
LSC
LSC = least significant change
UMCG
???
UMCG
UMCG
UMCG
Osteoporose
25OHvitD en Botmarkers meten
3 – 6 mnd botmarkers herhalen
Daling tot onder gemiddelde waarde gezonde vrouwen, 25OHvitD en botmarkers jaarlijks meten
Geen goede daling, compliantie navragen evt dosering aanpassen? ander geneesmiddel overwegen?
Start behandeling
Na 5 jaar evaluatie behandeling
Behandeling stoppen
Botmarkers meten
Behandeling voortzetten
Botmarkers jaarlijks meten
UMCG
#
6
Ca+D
* p<0.05 from baseline # p<0.05 from placebo Watts et al, OI, 2007
#
#
UMCG
Ca+D
* p<0.05 from baseline # p<0.05 from placebo Watts et al, OI, 2007
#
# # #
UMCG
Alendronate
Urine NTx Mean Percentage Change
Bone NEJM 2004
UMCG
Alendronate
BALP Mean Percentage Change
Bone NEJM 2004
Naylor K, Eastell R. Bone turnover markers: use in osteoporosis. Nat Rev Rheumatol. 2012 Jun 5;8(7):379-389
• BTMs are useful for the management of patients with osteoporosis, – for initial clinical assessment – for guiding and monitoring of treatment.
• BTM levels respond rapidly to both anabolic and antiresorptive treatments
BTMs in monitoring of osteoporosis treatment
Vasikaran 2011
BTMs in monitoring of osteoporosis treatment
Naylor K, Eastell R. Bone turnover markers: use in osteoporosis. Nat Rev Rheumatol. 2012 Jun 5;8(7):379-389
• BTMs are useful for the management of patients with osteoporosis, – for initial clinical assessment – for guiding and monitoring of treatment.
• BTM levels respond rapidly to both anabolic and antiresorptive treatments
• BTMs are also poten.ally useful as surrogate biomarkers for fracture.
UMCG
0 5
10 15 20 25 30 35
1 2 3 4 5 6 7 8 9 10
66 patients in each groupe
CTx T-score <-1.7 -1 0 +1 +2 >+2.4
% fr
actu
res
BTMs in fracture risk prediction
uCTX T-score > 2.0 SD
BMD T-score < -2.5 SD
Naylor K, Eastell R. Bone turnover markers: use in osteoporosis. Nat Rev Rheumatol. 2012 Jun 5;8(7):379-389
• BTMs are useful for the management of patients with osteoporosis, – for initial clinical assessment – for guiding and monitoring of treatment.
• BTM levels respond rapidly to both anabolic and antiresorptive treatments
• BTMs are also potentially useful as surrogate biomarkers for fracture.
• BTMs can indentify patients with high bone turnover and rapid bone loss – to determine possible causes of secondary osteoporosis
BTM in secondary osteoporosis
Disease Specific BTM findings
Primary Hyperparathyroidism increased BTM (depend disease severity) Thyroid disease Diabetes Paget disease of bone high BTM Myeloma high BTM Rheum Arthritis increased BTM (depend disease severity) Bechterew disease increased BTM (depend disease severity)
Crohn's disease Malabsorption vit D and Ca2+ , increased BTM
Chronic Kidney disease impaired renal function, increased BTM
UM
CG
Rhe
umat
olog
y &
Clin
ical
Imm
unol
ogy
Ankylosing Spondylitis
" Increased bone formation " Syndesmophytes " Joint ankylosis
" Increased bone resorption " Osteoporosis " Vertebral fractures
NORMAL
OSTEOPOROSIS
UM
CG
Rhe
umat
olog
y &
Clin
ical
Imm
unol
ogy
Ankylosing Spondylitis
" AS " bone formation " bone resorption
" Detection of osteoporosis is difficult in patients with advanced AS " overestimation of lumbar spine BMD by the
presence of syndesmophytes, ligament calcifications, and fusion of facet joints
Naylor K, Eastell R. Bone turnover markers: use in osteoporosis. Nat Rev Rheumatol. 2012 Jun 5;8(7):379-389
• BTMs are useful for the management of patients with osteoporosis, – for initial clinical assessment – for guiding and monitoring of treatment.
• BTM levels respond rapidly to both anabolic and antiresorptive treatments
• BTMs are also potentially useful as surrogate biomarkers for fracture.
• BTMs can indentify patients with high bone turnover and rapid bone loss – to determine possible causes of secondary osteoporosis
• BTM changes can also be used for understanding the mechanism of action of drugs in development and identifying the correct dose.
• Appropriate reference intervals should be used for the optimum interpretation of results.