Osteoporosis

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Osteoporosis

• Dr Janet Horner
• Leeds Teaching Hospitals NHS Trust

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Overview

• What is osteoporosis?
• Fracture risk?
• Who should we target for DXA?
• Secondary prevention
• Primary prevention
• What treatments are available and who do we treat?

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WHAT IS OSTEOPOROSIS?
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Osteoporotic vertebrae
Healthy vertebrae
Rizzoli R, ed. In Atlas of Postmenopausal
Osteoporosis (First Edition). Science Press, 2004.
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(No Transcript)
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Osteoporosis
Common sites of fracture
Qualitative Definition
a systemic skeletal disease characterised by
low bone mass and microarchitectural
deterioration of bone tissue, with consequent
increase in bone fragility and susceptibility to
fracture
Spine
Neck of femur
Wrist
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WHO definition of osteoporosis

• Based on the measurement of BMD
• The number of SDs from the average BMD in a group
  of 25-year-old women (T-score)
• Normal T-score of -1 SD or more
• Osteopenia T-score between -1 and -2.5 SD
• Osteoporosis T-score below -2.5 SD
• Established osteoporosis T-score below -2.5 SD,
  with one or more associated fragility fractures.

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Z scores

• The number of SDs from the average BMD in an
  group of age-matched women
• Gives indication of severity ie much worse than
  would be expected from age related bone loss
• Z score lt -2.0, consider secondary causes

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Age-related changes in BMD
Attainment of peak bone mass
Consolidation
Age-related bone loss
Menopause
Bone mass
Men
Women
0 10
20 30
40 50
60
Age (years)
Compston JE. Clin Endocrinol 1990 33 653682.
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Consequences of osteoporosis

• Asymptomatic in absence of
• Substantial pain, disability and reduced quality
  of life.
• Women gt50y
• 1 in 3 risk of vertebral
• 1 in 6 risk of hip .
• After a hip fracture - some patients die within a
  year 50 of survivors are incapacitated and 20
  require long-term residential care
• Lifetime risk for woman of dying from hip same
  as risk of dying from breast cancer

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Scale of the problem

• Prevalence
• 1.2M women in England and Wales
• Osteoporosis causes over 180,000 fractures per
  year in men and women in the UK. Cost 1.8B/y in
  UK.
• Total number of fractures is increasing
• 10-20 of women with osteoporosis receive Rx

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FRACTURE RISK? Age and BMD are key risk factors
and currently the only quantifiable risk factors
for fragility fracture
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BMD estimating risk
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Age - estimating risk
Hip
Vertebrae
Wrist
Adapted from Rosen at al JBMR 2004
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risk and BMD and age
Age, yrs
80
70
60
50
Kanis, Osteoporosis International 2001
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Fracture History

• Women with vertebral have
• 3-5 times greater risk of further in next 12
  months
• increased risk of hip
• Women with wrist gt45y after fall from standing
  ht or less associated with doubling of risk of
  further osteoporotic fracture
• 30 of women gt50y with wrist have osteoporosis

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absolute annual risk of osteoporotic fracture

• Age
• T-score
• Fragility gt50y
• Number of additional risk factors
• FH hip
• Current smoker
• Steroid use ever
• Alcohol gt2u/day
• RA

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WHO SHOULD WE TARGET FOR DXA?
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NICE Technology Appraisal TA087 Osteoporosis Jan
2005

• Secondary prevention of osteoporotic fragility
  fracture ( after fall from standing height)
• Postmenopausal women
• not men, not CSO
• Recommendations based on cost and clinical
  effectiveness

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WHO SHOULD WE TARGET FOR DXA?Postmenopausal
women who sustain a fragility fracture and who
are lt 75years
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WHO SHOULD WE TARGET FOR DXA? primary prevention

• Currently RCP case finding strategy
• Untreated hypogonadism (ie HRT refused or
  inappropriate)
• perimenopausal with other risk factors
• premature natural/surgical menopause (lt45y)
• 2y amenorrhoea gt6m and not pregnancy related
• Glucocorticoid use gt3months, patient lt65y (M or
  F)
• Risk of secondary osteoporosis (M or F)
• Malabsorption, Inflammatory bowel disease,
  Chronic liver disease, Hyperparathyroidism,
  Thyrotoxicosis

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WHO SHOULD WE TARGET FOR DXA? primary prevention

• Radiological osteopenia or vertebral deformity (M
  or F)
• Other risk factors
• Family history of osteoporosis / maternal hip
  fracturelt80y
• Smoker
• Alcohol intake gt35u/w (F) , gt50u/w (M)
• Low BMI lt19
• Height loss gt2cm in 1 y

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NICE Osteoporosis - primary prevention

• Cost effectiveness
• No opportunistic screening lt70y

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WHAT TREATMENTS ARE AVAILABLE AND WHO DO WE
TREAT?
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NICE guidelines secondary prevention

• Selection of patients for Rx based on
• inter-related factors, age and BMD
• other age-independent risk factors
• Adequate calcium and vitamin D provided

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NICE guidelines secondary prevention
Bisphosphonate

• gt75years, without need for DEXA scanning
• 65-75years, if osteoporosis confirmed by DEXA (T
  score lt -2.5)
• lt65years
• T score ? - 3.0
• T score -2.5 to -3.0 and age-independent risk
  factor
• FH hip
• medical conditions associated with bone loss -
  IBD, RA, coeliac disease, hyperthyroidism

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NICE guidelines secondary prevention Strontium
ranelate

• Bisphosphonates contraindicated
• renal impairment, oesophageal stricture
• Unable to comply with dosing instructions for
  bisphosphonates
• Unsatisfactory response to bisphosphonates
• 1year of Rx and further fragility fracture or
  loss in BMD
• Intolerant of bisphosphonates

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NICE guidelines secondary prevention
Raloxifene

• Strontium ranelate contraindicated
• OR
• Unsatisfactory response to strontium ranelate
• OR
• Intolerant of strontium ranelate
• Nausea and diarrhoea

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NICE guidelines secondary prevention
Teriparatide

• Women gt65y
• unsatisfactory response to bisphosphonates
• 1year of Rx and further fragility fracture or
  loss in BMD
• AND
• T score -4.0
• OR
• T score -3.0 and gt2 fractures and additional
  age-independent risk factor

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NICE guidelines secondary preventionsummary

• Secondary prevention of osteoporotic fractures in
  postmenopausal women
• Bisphosphonate first line Rx
• Strontium ranelate as second line Rx
• Raloxifene as third line Rx
• Teriparatide in very severe osteoporosis

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NICE Osteoporosis - primary prevention

• Number of additional risk factors and T-score
  determine Rx decisions in women gt70years

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Vertebral Endo Rev 2002 Meta - analysis of
therapies for postmenopausal osteoporosis

• AGENT No of trials RR (patients)
  (95CI)
• Vitamin D 8 (1130) 0.63 (0.45, 0.88)
• Alendronate 8 (9360) 0.52 (0.43, 0.65)
• Risedronate 5 (2604) 0.64 (0.54, 0.77)
• Raloxifene 1(6828) 0.60 (0.5, 0.7)

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Non-vertebral Endo Rev 2002 Meta - analysis of
therapies for postmenopausal osteoporosis

• AGENT No of Trials RR (95CI) (Patients)
• Alendronate 6 (3723) 0.51(0.38,0.69)
• Risedronate 7 (12,958) 0.73(0.61,0.87)

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Teriparatide (NEJM 2001 )n1637

• Daily injections
• Median Rx period 21 months
• Raised spinal BMD by 9 and 13
• 
  (dose dependent)
• Reduced new vertebral fractures by 65
• Reduced non-vertebral fracture risk by 35-40

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Strontium Ranelate (NEJM 2004)

• RCT 1649 PMF with osteoporosis and at least 1
  vertebral
• 2g oral strontium ranelate or placebo for 3y
• Reduced vertebral by 49 at 1yr and 41 over 3y

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Strontium Ranelate (JCEM 2005)

• RCT 5091 PMF with osteoporosis gt74y
• 2g oral strontium ranelate or placebo for 3y
• Reduced non-vertebral by 16 at 3y
• Inadequately powered to look at hip alone
• Post hoc subgroup analysis of elderly high risk
  group did show reduction

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Ibandronate

• BONE study (Chesnut CH, et al. J Bone Miner Res
  20041912419)
• After 3 years treatment with daily ibandronate -
  62 reduction in new vertebral fractures
• MOBILE study(Miller PD, et al. J Bone Miner Res
  200520, 8 1315-1322)
• Once-monthly oral ibandronate (150mg) is at least
  as effective as daily ibandronate at 1 and 2
  years with comparable safety to daily ibandronate

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Ca/vitamin D

• No indication for using Ca and vitD ALONE for
  prevention of further in previously mobile
  elderly
• Record study (Lancet 2005)
• 5292 people gt70y (85 F) who were mobile prior to
  sustaining low trauma
• 800iu vitD or 1000mg Ca or 800iu vitD and
  1000mg Ca or placebo
• End point fragility - 13 of 5292 had new
  fragility
• No difference in incidence between groups

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Other Ca/vitamin D studies

• BMJ 2005
• 3314 PMF gt70y with 1 risk factor for hip
• 1000mg Ca and 800iu D3
• No effect on hip
• NEJM 2006
• WHI 36, 292 PMF 50-79y
• 1000mg Ca and 400iu D3
• Small significant ? BMD
• No effect on hip

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Calcium and vitamin D

• Requirements calcium
• Postmenopausal women 1000mg/day
• Dietary or supplements
• Requirements vitamin D
• Postmenopausal women 800iu or 20ug/day
• Vitamin D concentrations
• Population reference range vs. target range

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Conclusions

• Osteoporosis still unrecognised and under-treated
• Treatment target fracture risk
• Guidance on secondary prevention available
• Guidance on primary prevention awaited
• New agents ibandronate, strontium ranelate,
  teriparatide
• Recent trials of calcium/vitamin D not
  effective Rx
• Risk factor algorithm - aggregating other risk
  factors - predict individual fragility fracture
  risk - awaited
• Optimum age to start Rx ??
• Optimum duration of Rx ??

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10year 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.