Title: Osteoporosis detection and treatment
1Osteoporosis detection and treatment
- Dr Gill Coombes
- November 2007
2Osteoporosis Definition (NIH, 2001)
-
- A skeletal disorder characterised by compromised
bone strength predisposing a person to an
increased risk of fracture. Bone strength
primarily reflects integration of bone density
and bone quality.
3Development of osteoporotic bone
Rizzoli R ed In Atlas of Postmenopausal
Osteoporosis (1st edition) Science Press, 2004
4Age and Osteoporotic Fractures
4,000 3,000 2,000 1,000
Men
Women
Hip
Hip
Vertebrae
Incidence/100,000 person-years
Vertebrae
Colles'
Colles'
3539
gt85
gt85
Age group, year
Cooper C. Epidemiology of Osteoporosis. Chapter
49IV. Metabolic Bone Diseases. Am Soc for Bone
Min Research 2003.
5Osteoporosis Some facts and figures
- 1 in 2 women and 1 in 5 men aged 50 will suffer a
fragility fracture in their remaining lifetime - There are 20 million people aged 50 years and
over in the UK. By 2020 this will have increased
to 25 million. - The lifetime risk of fracture in women at age 50
is greater than the risk of breast cancer or
cardiovascular disease
6Annual Incidence of Osteoporotic fractures in
England and Wales
- 180,000 Symptomatic osteoporotic fractures
- 70,000 Hip fractures
- 25,000 Vertebral fractures
- 41,000 Wrist fractures
- Estimated total cost of treating osteoporotic
fractures in postmenopausal women - 1.5 to 1.8 billion in 2000
- 2.1 billion in 2010
7Risk of subsequent fracture after initial
vertebral fracture
100 80 60 40 20 0
Cumulative incidence ()
0
1
2
3
4
5
6
7
8
9
10
Years following vertebral fracture
Melton LJ 3rd, et al. Osteoporos Int. 1999
10(3) 21421.
8Management of Osteoporosis Identifying Risk
Factors for Osteoporosis
- Previous fragility fracture
- Corticosteroid use gt 3 months
- Family history, especially maternal hip fracture
- Medical conditions associated with osteoporosis
e.g. RA, coeliac disease, hyperparathyroidism - Premature menopause lt 45 years old
- Excess alcohol consumption
- Low BMI (lt19)
- Smoking
9Bone density referral guidelines
- REASON FOR REFERRAL
- Corticosteroid therapy any dose for more than
three months. However, patients of any age who
have had a minimal trauma fracture or patients
gt65 treat without a scan. - Minimal trauma fracture eg wrist, vertebra,
hip, pelvis. If known vertebral fracture, please
state which vertebra. - Early menopause before 45 years, or prolonged
amenorrhoea gt 1 year scan when patient reaches
50 years of age. - Other diseases or treatments associated with
osteoporosis - Please specify ..
- Family History of osteoporosis in first degree
relative, particularly maternal hip fracture. - Significant radiological osteopenia
- Patients with proven osteoporosis who discontinue
HRT and who are not on other OP treatment. Scan
12 months after stopping
10Osteoporosis and cancer treatments
- Prostate cancer
- Gonadorelin analogues
- Breast cancer
- Chemotherapy induced menopause
- Tamoxifen in
- pre-menopausal women
- Aromatase inhibitors
11Osteoporosis and aromatase inhibitors
- All aromatase inhibitors cause bone loss
- (anastrazole, letrozole and exemestane)
- and are associated with increased fracture risk
- Bone loss is most rapid in the first 6-12 months
(approx 3) after changing from tamoxifen - Bone loss then slows eg 4-5 overall at 2 years
- Consider DXA scan at time of switching from
tamoxifen to aromatase inhibitor especially if
other risk factors present
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13Lumbar Spine DXA Results
14DXA Results
15Peripheral measurements
- Forearm DXA
- Heel DXA
- Heel ultrasound
16Ten year probability of fracture age and BMD
Age (yrs) T-score
1 0 -1 -2 -3
-4
50 2.4 3.8 5.9 9.2 14.1 21.3 60 3.2
5.1 8.2 13.0 20.2 30.6 70 4.3
7.1 11.5 18.3 28.4 42.3 80 4.6 7.7 12.7
20.5 31.8 46.4
Kanis et al. Osteoporosis Int 2001 12 989-95.
17Kanis JA, Johnell O, Oden A et al. Ten year
probabilities of osteoporotic fractures according
to BMD and diagnostic thresholds. Osteoporos Int
2001 12989995.
18Management of OsteoporosisIdentifying Risk
Factors for Falling
- Medical conditions
- e.g. arrhythmias, postural hypotension
- Failing vision
- Sedative drugs
- Physical environment
19Osteoporotic vertebral fractures
20Investigation of osteoporosis
- FBC PV
- Igs / electrophoresis BJP
- TT glutaminase
- Biochemical screen including calcium
- TFTs
- Testosterone levels in men
- ? Vitamin D levels
21Age-related changes in bone mass
Attainment of peak bone mass
Consolidation
Age-related bone loss
Menopause
Bone mass
Men
Fracture threshold
Women
0 10
20 30
40 50
60
Age (years)
Compston JE. Clin Endocrinol 1990 33 653682.
22Management of Osteoporosis Lifestyle Measures
23Treatment Options in Osteoporosis
- Antiresorptive drugs
- HRT
- Bisphosphonates
- etidronate
- alendronate
- risedronate
- ibandronate
-
- SERMs
- raloxifene
- Calcitonin
- Anabolic drugs
- PTH (teriparatide)
- Dual Action Bone Agents (DABAs)
- Strontium ranelate
24New Treatment Options in Osteoporosis
- Antiresorptive drugs
- HRT
- Bisphosphonates
- etidronate
- alendronate
- risedronate
- ibandronate
- zoledronate
- SERMs
- raloxifene
- Calcitonin
- Anabolic drugs
- PTH analogues
- Forsteo (teriparatide)
- Preotact
- Dual Action Bone Agents (DABAs)
- Strontium ranelate
25Bone remodelling cycle
Pre-osteoblasts
Monocytes
Osteoblasts
Osteoclasts
Osteocytes
Servier Medical Art
26Effect of alendronate on risk of fractures
RR 0.53 ( 95 Cl 0.41 0.68 )
18
16
14
12
Patients with new fractures after 3 years of
treatment ()
10
8
RR 0.52 ( 95 Cl 0.31 0.87 )
6
RR 0.49 ( 95 Cl 0.23 0.99 )
4
2
0
Vertebral fractures (p0.001)
Wrist fractures (p0.05)
Hip fracture (p0.05)
Adapted from Rizzoli. R Atlas of Osteoporosis.
(Second Edition). Curr Med Group 2005.
27Effect of risedronate on incidence of new
vertebral and non-vertebral fractures
RR 0.67 ( 95 Cl 0.44-1.04)
RR 0.51 ( 95 Cl 0.36 0.73 )
34
18
32
16
28
14
RR 0.61 ( 95 Cl 0.39 0.94 )
RR 0.59 ( 95 Cl 0.43 0.82 )
24
12
20
10
Incidence of new vertebral fractures ()
Incidence of new non-vertebral fractures ()
16
8
12
6
8
4
4
2
0
0
Vert-MN Years 0-3 Plt0.001
Vert-NA Years 0-3 Plt0.003
Vert-MN Years 0-3 NS
Vert-NA Years 0-3 P0.02
Vert-MN results adapted from Reginster, J.-Y.,
Minne, H.W. et al.Osteoporosis International
2000 11.83-91.Vert-NA results adapted from
Harris ST, Watts NB, Genant HK et al. JAMA 1999
282 13441352.
28Effect of ibandronate on incidence of vertebral
fractures
12
RR 0.50 ( 95 Cl 0.34 0.74)
10
RR 0.38 ( 95 Cl 0.25 0.59)
8
RR 0.44 ( 95 Cl 0.26 0.73 )
Fracture incidence ()
6
RR 0.39 ( 95 Cl 0.23 0.67 )
RR 0.42 ( 95 Cl 0.17 1.02 )
4
2
0
Year 1
Year 2
Year 3
plt0.001 versus placbo plt0.0017 versus placbo
Adapted from Rizzoli. R Atlas of Osteoporosis.
(Second Edition). Curr Med Group 2005.Reproduced
with permission from Chestnut CH 3rd, Skag A,
Christiansen C J Bone Miner Res 2004
191241-1249.
29Strontium has a dual action
FORMATION
RESORPTION
Strontium
Pre-OB
Pre-OC
REPLICATION
Strontium
DIFFERENTIATION
OB
OB
OB
Strontium
OC
BONE FORMING ACTIVITY
BONE RESORBING ACTIVITY
Bone
Ref 2 Marie PJ et al. Calcif Tissue Int.
200169121-129.
30Strontium increases bone mineral density
plt0.001
1 mean relative change from baseline versus
placebo (plt0.001)
Meunier P J et al. N Engl J Med. 2004
350459-468.
31 Strontium reduces the risk of vertebral fracture
(SOTI)
- 41
Patients ()
NNT 9
- 49
0-3 years
First year
Meunier P J et al. N Engl J Med. 2004
350459-468.
32Strontium ranelate reduces non-vertebral fracture
risk (TROPOS)
19
p0.031
12
10
8
patients with OP-related major non-vertebral
fractures over 3 years
95 Cl 0.66-0.98
6
4
2
0
Placebo
Strontium ranelate
n2537
n2555
1. Reginster JY, Seeman E, De Vernejoul MC, et
al. J Clin Endocrinol Metab 2005 90(5)
2816-2822. 2. Reginster JY, Hoszowski K, Roces
Varela A et al. Bone 2003 32(5) S94.
33Strontium ranelate reduces hip fracture in
patients at higher risk (gt 74 yr-old and T-score
lt-2.4) TROPOS
36
n1977
8
Strontium ranelate 2 g/day
7
n982
6
Placebo
n995
5
Patients ()
4
3
2
1
0
0-3 years
ITT, over 3 years RR 0.64 95 CI 0.412
0.997 p 0.046
1. Reginster JY, Seeman E, De Vernejoul MC, et
al. J Clin Endocrinol Metab 2005 90(5)2816-2822.
34NICE guidelines - Teriparatide
- Secondary prevention of osteoporotic
- fragility fractures in women aged 65 year and
over who have had an unsatisfactory response to
bisphosphonates and - Have an extremely low BMD (T score -4) or
- Have a very low BMD (T score -3) with more than
2 fractures plus 1 or more additional age
independent risk factor
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