Transcript Diaporama ASBMR 2010

CHAPTER I
Osteoporosis:
evaluation of risks
Osteoporosis: evaluation of risks
1
Astronaut : a profession reserved in the future for women?
● Study in 25 astronauts
→ measurement of bone loss
→ back from mission, evaluation of the risk of fracture at hip
Surface BMD at femoral neck
Evolution of fracture risk factor before and
after the flight
after the flight
p = 0,03
p < 0,01
1,1
-3 %
(p = 0,16)
High fracture risk
-6,7 %
(p < 0,01)mean loss rate per month :
1,2
p < 0,0001
1,0
1,0
0,8
Before flight
0,7
After flight
0,6
0,5
Women
(n = 5)
Men
(n = 20)
Risk fact
0,8
men = -1,3 %
women = -0,55 %
0,9
risk
Increasing
Risk increase
Femoral neck BMD (g/cm²)
1,2
0,6
0,4
0,2
0,0
Women
(n = 5)
Men
(n = 20)
 In space, bone loss (femoral neck) is greater in men
 Men are at high risk of hip fracture after returning from their space flight
La Lettre du Rhumatologue
ASBMR 2010 - D’après Ellman R et al., Boston, États-Unis, abstr. 1142, actualisé
Osteoporosis: evaluation of risks
2
Hot flushes: witness of an excessive bone resorption ?
Association between vasomotor flushes and urinary NTX
(multivariate analysis with or without estradiol)
Presence vs absence of
vasomotor flushes
Frequent vs not frequent
vasomotor flushes
Urinary  NTX
p
Urinary  NTX
p
Premenopause
1.017
0.17
0.741
0.61
Perimenopause onset
1.944
 0.0001
3.077
 0.0001
Advanced perimenopause
2.437
0.03
3.625
 0.001
Postmenopause
1.259
0.10
1.909
0.02
Premenopause
0.969
0.23
0.701
0.63
Perimenopause onset
1.784
 0.001
2.827
 0.0001
Advanced perimenopause
2.022
0.07
3.294
0.002
Postmenopause
1.307
0.09
1.748
0.06
Adjustement for estradiol
 Women undergoing perimenopause who experience vasomotor flushes have a high level of bone
resorption
La Lettre du Rhumatologue
ASBMR 2010 - D’après Crandall C et al., Los Angeles, États-Unis, abstr. 1094, actualisé
Osteoporosis: evaluation of risks
3
Relationship between sun tanning and vitamin D levels
● Scottish ANSAViD cohort : 314 women aged 60 to 65 years
● Spectrophometric measurement of face coloration every three months (15 months)
UV dose received over the year
Skin type I
Skin type II
Change of skin coloration over the year (in ITA
individual typology angle])
Skin type III
50
ITA (degrés)
10
8
6
4
2
Skin type I
Skin type II
Skin type III
45
40
35
30
0
Spring
2006
Summer
Autumn
Winter
Spring
2007
Spring
2006
Winter
Automn
Winter
Spring
2007
 For every ITA standard deviation (SD) increase between summer and the following winter, there is a
significant increase of 25(OH)D level of 0.8 nmol/l
 This first longitudinal study suggests that modifications of skin coloration are predictive of
vitamin D levels variations
La Lettre du Rhumatologue
ASBMR 2010 - D’après Macdonald H et al., Aberdeen, Royaume-Uni, abstr. SU0326, actualisé
Osteoporosis: evaluation of risks
4
Synergic effect of a low level of vitamin D and sex hormones
on bone risk in men
● Study based on the MrOS cohort ; DXA data at initial visit and a mean follow-up
of 4.6 years in 1 468 men (median age: 74 years)
Effect on bone loss
Effect on the risk of nonvertebral
fracture
Normal levels (all parameters)
Low vitamin D ( 20 ng/ml)
Low testosterone + low vit. D
Low estradiol and/or elevated SHBG
**
Low estradiol and/or elevated SHBG and low vit.D
*
-0,75
-0,50
-0,25
Bone loss at total hip/year (%)
17 %
NS
19 %
NS
18 %
NS
23 %
1,3 (0.9-1.9)
30 %
1.6 (1.1-2.5)
0
0,5
1
2,5
5 RR
*p = 0,0006 ; **p = 0,007
 Vitamin D insufficiency effects on bone loss and nonvertebral fracture risk are significant in
men who have, at the same time, a low level of estradiol and an elevated level of SHBG
La Lettre du Rhumatologue
ASBMR 2010 - D’après Barrett-Connor E et al., La Jolia, États-Unis, abstr. 1020, actualisé
Osteoporosis: evaluation of risks
5
Is hyponatremia a risk factor of fracture ?
● Study of the relationship between moderate hyponatremia ( 136 mmol/l) and fracture risk in
the Rotterdam cohort (n = 5 208 subjects, age: > 55 years, follow-up : 7.7 years)
Non vertebral fractures
Number of events
RR (CI95) adjusted
p
Hyponatremia
Normonatremia
93/399 (23.3 %)
833/4 809 (17.3 %)
1.34 (1.08-1.68)
Reference
0.009
23/136 (16.9 %)
269/2 390 (11.3 %)
1.61 (1.00-2.59)
Reference
0.049
95/399 (23.8 %)
787/4 809 (16.4 %)
1.34 (1.03-1.75)
Reference
0.029
Incident and prevalent
vertebral fractures
Hyponatremia
Normonatremia
Recent falls
Hyponatremia
Normonatremia
 Moderated hyponatremia is associated with an increased risk of fractures and falls
La Lettre du Rhumatologue
ASBMR 2010 - D’après Zillikens M et al., Rotterdam, Pays-Bas, abstr. 1092, actualisé
Osteoporosis: evaluation of risks
6
Influence of the abdominal body composition
on the risk of nonvertebral fracture
● Study of the association of abdominal body composition with incident fracture in Mr OS
cohort study (n = 616, median age : 74.2 years) and a case-control group (n = 294)
Relationship between infiltration of adipose
tissue of the lumbar muscle mass and risk of nonvertebral fracture
RR (CI95)
Lumbar spine scannner L4-L5
Nonadjusted
1.05 (0.88-1.26)
+ age, race, center of analysis
1.07 (0.86-1.33)
+ BMI
1.27 (0.99-1.65)
+ BMD at femoral neck
1.29 (1.01-1.65)
+ history of fracture and muscle force (wrist)
1.30 (1.00-1.70)
 Adipose infiltration of the abdominal muscle may increase the risk for nonvertebral fracture
independent of BMD
La Lettre du Rhumatologue
ASBMR 2010 - D’après Sheu Y et al., Pittsburgh, États-Unis, abstr. 1095, actualisé
Osteoporosis: evaluation of risks
7
Simulation
Fall
Standing
-2,5
-5
-7,5
-4,8 %
-10
*
-12,5
-15
-9,5 %
*
Total
0
0%
-10
Trabecular-Cortical
0
-5,9 %
*
-20
-16,5 %
Variation of CMO (%)
0
Total
l l Trochanter-Cortical
Variation of DMOv (%)
Evolution of the resistance (%)
Radiotherapy does not spare the bone…
-10
-20
-30
-15,5 %
-14,0 %
*
*
*
-23,7 %
*p < 0,05
-40
*
● 8 women treated with pelvic radiotherapy at a dose of 50 Gy in 6 weeks (28 fractions)
● Early bone evaluation with FEA and volumetric quantitative analysis at femur
 Pelvic radiotherapy causes rapid and intensive loss of bone resistance, density and bone mineral
content
 The effect observed at 6 weeks is equivalent to 3 years of spontaneous bone loss.
La Lettre du Rhumatologue
ASBMR 2010 - D’après Bateman T et al., Chapel Hill, États-Unis, abstr. SU0040, actualisé
Osteoporosis: evaluation of risks
8
Are rib fractures osteoporotic fractures?
● evaluation on the basis of a prospective cohort : mean follow-up of 13.9 years (8 560 patients-year)
● 699 patients; 67 rib fractures ( 17 of which occurring after a severe trauma) in 56 patients
● Median age at occurrence : 83 years in women, 70 years in men
Risk factors
HR (CI95)
Adjusted for age
History of osteoporotic fracture (yes, no)
1.95 (1,11-3.44)*
History of rib fracture (yes, no)
1.72 (0.91-3.26)
Physical activity practice (yes, no)
0.40 (0.16-0.97)*
Elevated serum-osteocalcin levels
1.72 (1.19-2.47)**
*p < 0,05 ; **p < 0,01
 Age is the main risk factor for rib fracture(s) after, or without, trauma
 After adjustment for age, only prior fracture remains a risk factor for rib fracture(s)
 After adjustement for age, practice of a physical activity an and elevated serum-osteocalcin
levels are protection factors.
La Lettre du Rhumatologue
ASBMR 2010 - D’après Wuermser LA et al., Rochester, États-Unis, abstr. SU0345, actualisé
Osteoporosis: evaluation of risks
9
Analysis of bone resistance in young women with fractures during childhood or adolescence
● Study of bone resistance at wrist and tibia by means of finite element analysis (HRpQCT)
● 95 young women (20.4 years) ; 34 with history of fracture
Finite element analysis at wrist
HR-pQCT wrist
Mean + ET
No fracture
(n = 62)
Fracture
(n = 32)
p
Difference (%)
Stiffness
82,6 + 15,7
74,9 + 14,1
0,022
0,021*
-9,3
Failure head
3 947 + 728
3 603 + 642
0,026
0,024*
-8,7
Apparent modulus
2 030 + 397
1 791 + 478
0,012
0,047*
-11,8
*After adjustment for age, weight, calcium and protren contributioin,, pubertal age,
lsize and physical activity
 Young women reporting childhood fracture have a reduction in bone resistance, suggesting that
fractures during growth reflects persistent fragility in adult
La Lettre du Rhumatologue
ASBMR 2010 - D’après Ferrari (1127)
Osteoporosis: evaluation of risks
10
Diagnosis of vertebral fractures in men is difficult
? ● Comparison of 4 diagnostic methods for vertebral fractures
?
– Method 1: qualitative ABQ
?
– Method 2: semi-quantitative Genant
– Methode 3: semi-quantitative without grade 1 at the thoracic level
– Methode 4: semi-quantitative + expert opinion (adjudication)
Prevalence of Vertebral fractures
according to method
Patients (%)
50
Method comparison
Best concordance
● At patient level
40
– Between methods 1 and 4: 86.49 %
– PABAK score = 0.73
20
● At vertebrae level
10
– Between methods 1 and 4: 87.4 % to
0
98 %
Method 1
Method 2
Method 3
Mehod 4
27.2 %
45-2 %
30.7 %
26.4 %
– PABAK score = 0.86-0.91
 Good concordance between the quantitative method and the semi-quantitative method with expert
opinion
 Results of analysis based only on the height of vertebral body brings out different results
30
La Lettre du Rhumatologue
ASBMR 2010 - D’après Fechtenbaum (1023)
Osteoporosis: evaluation of risks
11
Think to mastocytosis in case of unexplained osteoporosis !
Study of 58 bone biopsies of systemic mastocytosis over 15 years
● 16 patients had bone biopsies for unexplained osteoporosis (11 ♂, 5 ♀, 57 years [37-74]), without
previous clinical sign of systemic mastocytosis
● Important variation of bone densitometry values and microarchitectural parameters were observed.
Nevertheless, increase of eroded surfaces and increase of star volume (deteroriation of bone quality)
were frequent.
BV/TV
z-score
DEXA
1
3
0
2
-1
1
Star volume
-2
-3
T-score Total Hip
T-score lumbar spine
70
0
4
3
1
40
-2
-1
-5
-3
-2
-6
-4
Without fracture
With fracture
-4
Number of
osteoclasts
Toluidine bleue
Tryptase
C-kit
70
60
20
50
0
25
60
2
-1
Eroded
surfaces
30
50
15
10
20
-3
10
-4
0
40
30
20
5
10
0
0
 Diagnosis of systemic mastocytosis shall be kept in mind in case of unexplained osteoporosis with or
without fracture, even if there is no other clinical sign of the disease (cutaneous, organomegaly)
 Transiliac bone biopsy allows the diagnosis and evaluates the cell activity and architectural
parameters
La Lettre du Rhumatologue
ASBMR 2010 - D’après Bouvard B et al., Angers, France, abstr. SU0359, actualisé
Osteoporosis: evaluation of risks
12
Determination of the test screening interval
for the diagnosis of osteoporosis
Delay before onset of osteoporosis
Delay for the onset of osteoporosis following the initial T-scorel
100
Normal BMD
T-score > -1.00
(n = 1 275)
80
Osteopenia
T-score -1.50 à -1.99
(n = 1 485)
60
Osteopenia
T-score -1.01 à -1.49
(n = 1 405)
40
Osteopenia
T-score -2.00 à -2.49
(n = 1 389)
20
0
2
4
6
8
10
12
14
 In women aged >67 years the interval for a DXA for osteoporosis depends on the initial T-score.
It is of 1 year if T≤-2, of 5 years if -1≤ T <-2, and of 10 years if T>-1
La Lettre du Rhumatologue
ASBMR 2010 - D’après Gourlay M et al., Chapel Hill, États-Unis, abstr. 1130, actualisé
Osteoporosis: evaluation of risks
13
Osteoporosis and fracture risk within 10 years in early menopausal women
● 12-years follow-up of the MENOS cohort, composed of recent menopausal French
women (n = 713, median age 54 + 4 years) who were never treated
Pronostic value of the absence of osteoporosis risk and/or
fracture at12 years according toT-score threshold
T-score value at initial and final visits
Initial
Percentage
60
50.2
50
47,8
20
41
36.4
40
30
T-score < -2.5
(spine or femoral neck)
Final
28.8
21
15.8
22,3
10
0
Normal
Osteopenia Osteoporosis Osteoporosis
or fracture
T-score < -2.5
(spine or femoral neck or
fracture)
Predictive factor
at baseline
Lumbar
espine
Femoral
Minimum
neck
Lumbar
spine
Femoral
Minimum
neck
Threshold at
initial visit
T = -1.5
T = -1.4
T = -1.9
T = -0.9
T = -1
T = -1.5
Positive
predictive value
(%)
46.7
43.6
54
42.3
42.4
49
Negative
predictive value
(%)
90
90
90
90
90
90
 Nearly one third of recent menopausal women will develop osteoporosis within the following 10 years
 Women with a T-score > -1.5 have a 90 % probability of avoiding osteoporosis and/or low energy fractures
within the next following years
La Lettre du Rhumatologue
ASBMR 2010 - D’après Pouilles (FR0321)
Osteoporosis: evaluation of risks
14
Validity of FRAX® for the prediction of major osteoporosis fractures
● OPUS study (1 504 women), median age: 65.7 years
● Follow-up: 6 years, 60 major osteoporotic fracture
Predictive value of FRAX® at 6 years
RR
(CI95)
C-statistic
(CI95)
Age
1.28 (1.06-1.54)
0.58 (0.51-0.66)
Femoral neck BMD
1.20 (1.05-1.38)
0.55 (0.48-0.63)
History of personal fracture
1.69 (1.28-2.23)
0.63 (0.57-0.69)
Models
ROC curves
1
0,8
0,6
0,4
0,2
Age + femoral neck BMD
+ history of fracture
1.50 (1.22-1.83)
FRAX® without femoral neck BMD
1.18 (1.03-1.35)
0.59 (0.51-0.67)
FRAX® with femoral neck BMD
1.22 (1.07-1.39)
0.58 (0.51-0.65)
0.65 (0.57-0.73)
0,0
0
0,2
0,4
0,6
0,8
1
Age
Femoral deck BMD+ age + fracture
antecedent
FRAX® with
Femoral deck BMD
FRAX® without BMD
BMD
 FRAX® predicts major osteoporotic fractures but when the femoral neck BMD value and history of
fracture are known, the prediction of the fracture risk is not improved
La Lettre du Rhumatologue
ASBMR 2010 - D’après Briot K et al., Paris, France, abstr. 1131, actualisé
Osteoporosis: evaluation of risks
15
Does serial BMD measurement allow the prediction of fracture risk after
discontinuation of bisphosphonate treatment?
● During the FLEX study, in the placebo arm the risk of new fractures was 21% at 5 years
(109 NVF and 28 clinical VF in 94 women)
40
p according to tendency = 0,001
33,1
30
22,8
20
8,8
10
0
-3,8 à -2,1
-2,1 à -1,5
-1,5 à 0,1
»Total hip » T-score variation in tertile at 1 year
Patients with fractures (%)
Patients with fractures (%)
Initial « total hip » T-score in tertile
40
p according to tendency = 0,81
30
20,4
20
20,3
15,4
10
0
-9,2 à -2,3
-2,3 à -0,3
-0,3 à 8,6
Percentage
 Total hip BMD after a first therapeutic sequence allows the prediction of fracture risk at 5
years
 On the other hand, repeat BMD measurements at 1 year and at 2 years do not allow the
prediction of fracture risk
La Lettre du Rhumatologue
ASBMR 2010 - D’après Bauer (1098)
Osteoporosis: evaluation of risks
16
FRAX® or FICTION : what was the FRAX® value the day before the fracture ?
● Study on the value of FRAX® before the fracture in hospitalized patients
– Department of Orthopedics (Paris, France) [n = 242, 85 %, median age: 75.2 years]
→ According to the FRAX® threshold applied, 25 to 60 % of patients would not be detected
– Emergency Department (Maastricht, The Netherlands) [n = 482, 75 % of women, 50-90
years]
Patients that would be treated according to the value of FRAX® + BMD
(recommandations of the NOGG)
Before fracture
70
60
50
40
30
20
10
0
50
After fracture
Treatment required for
17.1 % of patients and not
required for 82.9 %
60
70
80
90 Age
70
60
50
40
30
20
10
0
50
Treatment required for
30 % of patients and not
required for 70 %
60
70
80
90 Age
 With FRAX®, the majority of patients hospitalized for osteoporotic major fractures would have been
considered as presenting a weak fracture risk
La Lettre du Rhumatologue
ASBMR 2010 - D’après Briot (SA345) et Van Geel (FR0322)
Osteoporosis: evaluation of risks
17
FRAX® value in treated osteoporotic women
● Comparison of the predictive value of FRAX® for hip and major osteoporotic fractures in
●
currently, previously and non treated women
Canadian Manitoba cohort (n = 35 764) ; follow-up : 5.3 years
Predictive value of FRAX®
FRAX® with BMD
AUC(CI95)
FRAX® without BMD
AUC(CI95)
Non treated 65 + 10 years (n = 12 450)
0.66 (0.64-0.68)
0.63 (0.61-0.65)
Treated (MPR > 80 %) 66.6 + 9.7 years (n = 9 712)
0.64 (0.62-0.66)
0.67 (0,65-0.69)
Treated (MPR < 80 %) 66.7 + 10 ans (n = 9 216)
0.71 (0.70-0.73)
0.69 (0,67-0.71)
Previous treatment 63.4 + 8.2 years(n = 4 476)
0.69 (0.64-0.74)
0.67 (0.62-0.72)
 In this population, FRAX® continues to predict the fracture risk in female patients currently treated
or having been treated
La Lettre du Rhumatologue
ASBMR 2010 - D’après Leslie (1199)
Osteoporosis: evaluation of risks
18
Prediction of the risk of clinical vertebral fractures in men by means of finite elements analysis
● MrOS cohort (n = 3 500, age : > 65 years) : 63 men with clinical vertebral fractures and
●
242 controls ; mean follow/up: 6.5 years
Modeling by finite elements of the L1 vertebra (QCT)
Multivariate analysis of the risk of clinical
vertebral fracture (RR, IC95)
0,9 (0,6-1,4)
Volume density (g/cm³)
9,4 (5,1-17,4)
Resistance (N)
8,5 (4,5-16,2)
Relationship PHI
(charge/resistance)
2,9 (2,2-4,0)
Resistancee
1
1
Volume density,
resistance or PHI
Surface BMD
(ASC = 0,76)
Sensibility
Femoral neck BMD (g/cm²)
Volume density
Ajustement for age,
BMI, lumbar spine BMD
Sensibility
Variables (for all diminution
of 1 SD)
ROC Curves
0,82 (< 0,04)
0
0
1
Specificity
0,83 (< 0,02)
0
0
1
Specificity
 Vertebral resistance measured by finite elements analysis improves the prediction of clinical
vertebral fractures in men aged >65 years
La Lettre du Rhumatologue
ASBMR 2010 - D’après Keaveny (1022)
Osteoporosis: evaluation of risks
19
Association between low vitamin D concentration and mortality risk in humans
● MrOS Swedish cohort (n = 3 014, age : 70-80 years)
● 6-year follow-up; 382 deaths
Death risk
(IC95)
Global mortality
1,28 (1,15-1,43)
Global mortality after adjustment
1,20 (1,07-1,34)
Cancer mortality
1,33 (1,11-1,59)
Cardiovascular accident mortality
1,25 (1,04-1,50)
3
2,5
2
1,5
1
0,5
*Ajustement on age, IMC, comorbidities and quallity of life scores
0
0
25
50
75 100 125 150
Risk at 2 years
Men of 75 years)
Deaths for 100 patients-years
For each SD reduction of 25(OH)D
concentration
Mortality risk according to vitamin D level
Deaths for 100 patients-years
Multivariate analysis of the death risk
(follow-up 4,5 years)
12
3 years
10
8
6
4
6 years
2
25(OH)D
0
0
25
50
75 100 125 150
Comparison of risk
at 6 years and at 3 years
 A low vitamin D concentration at visit 1 is significantly associated to an increase of the mortality
risk; this increase seems to decrease with time
La Lettre du Rhumatologue
ASBMR 2010 - D’après Johansson (1019)