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Osteoporosis – detection and treatment. Dr Gill Coombes November 2007. Osteoporosis : Definition (NIH, 2001 ).

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osteoporosis detection and treatment

Osteoporosis –detection and treatment

Dr Gill Coombes

November 2007

osteoporosis definition nih 2001
Osteoporosis : 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.

development of osteoporotic bone
Development of osteoporotic bone

Rizzoli R ed In Atlas of Postmenopausal Osteoporosis (1st edition) Science Press, 2004

age and osteoporotic fractures
Age and Osteoporotic Fractures

4,000

3,000

2,000

1,000

Men

Women

Hip

Hip

Vertebrae

Incidence/100,000 person-years

Vertebrae

Colles'

Colles'

35–39

>85

>85

Age group, year

Cooper C. Epidemiology of Osteoporosis. Chapter 49:IV. Metabolic Bone Diseases. Am Soc for Bone & Min Research 2003.

osteoporosis some facts and figures
Osteoporosis – 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
annual incidence of osteoporotic fractures in england and wales
Annual 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

risk of subsequent fracture after initial vertebral fracture

Women

Men

Risk 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): 214–21.

management of osteoporosis identifying risk factors for osteoporosis
Management of Osteoporosis Identifying Risk Factors for Osteoporosis
  • Previous fragility fracture
  • Corticosteroid use > 3 months
  • Family history, especially maternal hip fracture
  • Medical conditions associated with osteoporosis e.g. RA, coeliac disease, hyperparathyroidism
  • Premature menopause < 45 years old
  • Excess alcohol consumption
  • Low BMI (<19)
  • Smoking
bone density referral guidelines
Bone 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 >65 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 > 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
osteoporosis and cancer treatments
Prostate cancer

Gonadorelin analogues

Breast cancer

Chemotherapy induced ‘menopause’

Tamoxifen in

pre-menopausal women

Aromatase inhibitors

Osteoporosis and cancer treatments
osteoporosis and aromatase inhibitors
Osteoporosis 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
peripheral measurements
Peripheral measurements

Forearm DXA

Heel DXA

Heel ultrasound

ten year probability of fracture age and bmd
Ten 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.

slide17

Kanis JA, Johnell O, Oden A et al. Ten year probabilities of osteoporotic fractures according to BMD and diagnostic thresholds. Osteoporos Int 2001; 12:989–995.

management of osteoporosis identifying risk factors for falling
Management of OsteoporosisIdentifying Risk Factors for Falling
  • Medical conditions

e.g. arrhythmias, postural hypotension

  • Failing vision
  • Sedative drugs
  • Physical environment
investigation of osteoporosis
Investigation of osteoporosis

FBC PV

Igs / electrophoresis BJP

TT glutaminase

Biochemical screen including calcium

TFTs

Testosterone levels in men

? Vitamin D levels

age related changes in bone mass
Age-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: 653–682.

treatment 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

Treatment Options in Osteoporosis
new 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

New Treatment Options in Osteoporosis
bone remodelling cycle
Bone remodelling cycle

Pre-osteoblasts

Monocytes

Osteoblasts

Osteoclasts

Osteocytes

Servier Medical Art

effect of alendronate on risk of fractures

Alendronate n=1022

Placebo n=1005

Effect 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

(p=0.001)

Wrist fractures (p=0.05)

Hip fracture

(p=0.05)

Adapted from: Rizzoli. R: Atlas of Osteoporosis. (Second Edition). Curr Med Group 2005.

effect of risedronate on incidence of new vertebral and non vertebral fractures

Placebo

Risedronate 5 mg/day

Effect 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 non-vertebral fractures (%)

Incidence of new vertebral fractures (%)

16

8

12

6

8

4

4

2

0

0

Vert-MN

Years 0-3

P<0.001

Vert-NA

Years 0-3

P<0.003

Vert-MN

Years 0-3

NS

Vert-NA

Years 0-3

P=0.02

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: 1344–1352.

effect of ibandronate on incidence of vertebral fractures

Daily ibandronate (2.5 mg), n=982

Intermittent ibandronate (20 mg), n=982

Placebo, n=982

Effect 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

*p<0.001 versus placbo

†p<0.0017 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; 19;1241-1249.

strontium has a dual action
Strontium 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. 2001;69:121-129.

strontium increases bone mineral density

Lumbar BMD1 = +14.4 %

Femoral neck BMD1 = +8.3 %

over 3 years

over 3 years

Mean change (%)

Mean change (%)

16

8

*

Protelos®

*

*

Protelos®

12

*

*

*

*

*

4

8

*

*

*

* p<0.001

*

4

placebo

0

placebo

0

- 4

0

6

12

18

24

30

36 Time (mo)

0

6

12

18

24

30

36 Time (mo)

Strontium increases bone mineral density

* p<0.001

1 mean relative change from baseline versus placebo (p<0.001)

Meunier P J et al. N Engl J Med. 2004; 350:459-468.

strontium reduces the risk of vertebral fracture soti

35

30

25

Protelos® 2 g/day

20

placebo

15

10

5

RR=0.59, 95%CI [0.48 ; 0.73] * p<0.001

RR=0.51, 95%CI [0.36 ; 0.74] * p<0.001

0

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; 350:459-468.

strontium ranelate reduces non vertebral fracture risk tropos
Strontium ranelate reduces non-vertebral fracture risk (TROPOS)

19%*

* p=0.031

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

n=2537

n=2555

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.

strontium ranelate reduces hip fracture in patients at higher risk 74 yr old and t score 2 4 tropos
Strontium ranelate reduces hip fracture in patients at higher risk (> 74 yr-old and T-score <-2.4) TROPOS

36%*

n=1977

8

7

Strontium ranelate 2 g/day

n=982

6

Placebo

5

n=995

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.

nice guidelines teriparatide
NICE 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