Osteoporosis

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Osteoporosis
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Osteoporosis is characterized by reduced bone
strength
Osteoporosis is a skeletal disorder
characterized by compromised bone strength
predisposing a person to an increased risk of
fracture.1
Normal2
Osteoporosis2
1. Consensus Development Conference, JAMA 2001
285 785-95 2. Dempster DW et al, JBMR 1986 1
15-21.
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Total fracture incidence in Southern Tasmania by
age and gender
Fracture incidence ( pa)

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Risk factors for osteoporosis

• Female
• Low body weight
• Smoking
• Corticosteroids
• Coeliac disease
• Milk avoidance
• Physical inactivity
• Early menopause/menstrual irregularity
• Mild vitamin D deficiency

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Bone density is the only accurate way of
identifying osteoporosis
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Relationship between bone density and
fractures
Adapted from Marshall et al, BMJ , 1996
3121254-59 Hans et al, Lancet, 1996 348511-4.
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• Risk factors for fracture that are independent of
  DXA
• Ultrasound measurement of BMD
• Bone turnover markers
• Family history of fracture (esp. hip)
• Previous fracture (esp. vertebral)
• Femoral neck axis length (hip only)
• Corticosteroids (all fractures)
• Fall risk (quadriceps strength, postural sway)

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Primary prevention 1 Peak bone mass 1. Physical
activity 2. Adequate calcium intake 3. Delay
smoking uptake 4. Prevent eating disorders 5.
Adequate sunlight exposure 6. Breastfed child 7.
No smoking by mother during pregnancy 8. Adequate
diet during pregnancy
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Primary prevention 2 the menopause 1. Hormone
replacement therapy 2. Adequate calcium intake 3.
Stop smoking 4. Consider thiazide diuretic if
hypertensive 5. Restrict salt intake 6. Adequate
sunlight exposure 7. Physical activity 8. Alcohol
in moderation
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Primary prevention 3 the elderly 1. Calcium and
vitamin D supplementation 2. Physical activity 3.
Falls prevention 4. External hip protectors
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When to Initiate Treatment

• Prevalent spinal fracture and BMD in osteoporotic
  (T score lt -2.5) or osteopenic (T score between
  -1 to -2.5) range - TREAT
• Prevalent non spine fracture and BMD in
  osteoporotic range - TREAT
• Low BMD (T score lt -2.5) but no fracture - TREAT
• Osteopenia (T score -1 to -2.5) but no fracture -
  NNT not favourable for treatment
• Clinical risk factors for fractures and falls -
  more data needed

Fracture Summit, MJA, 2002
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Mode of Action of Osteoporosis Therapies

• Anti-Resorptive
• Calcium
• Vitamin D
• Calcitonin
• Bisphosphonates
• Oestrogen
• SERMs
• Strontium ranelate
• Denosumab

• Formation Stimulating
• Anabolic steroids
• PTH
• Strontium Ranelate

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Risedronate and microarchitecture
Placebo
Risedronate
Dufresne et a. ,2002
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Clinical Trial Milestones Teriparatide Improves
Skeletal Architecture
Source Patient 1124 B3D-MC-GHAC - UCSF Jiang
2003
Review Hong Ren 11-19-02 WPDF global kit
LX200308c (Li Xie) 090403
Reviewer Memo
Jiang UCSF
Baseline
Follow-up
Female, age 65 Duration of therapy 637 days
(approx 21 months) BMD Change ?Lumbar Spine
7.4 (group mean 9.7 7.4) ?Total Hip
5.2 (group mean 2.6 4.9)
Patient treated with teriparatide 20µg
Jiang et al Vol 18 JBMR 2003
Slide Modified on 10/22/2002 125503 PM
SL10 Rev 147on 9/4/2003 81122 AM SL24
Rev 72 on 9/25/2003 63858 PM SL1 Rev 128
Memo ACR 2002changed title, references, added
new notes 16Jul03added to history set, modified
notes and title 06Aug03 - MR
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PROTOS - Evidence on Bone Architecture and Bone
Strength
Cortical Thickness 18 Trabecular Number
14 Trabecular Separation -16
3D-micro CT images courtesy of Y. Jiang,
University of California, VAMC, San Francisco,
CA, USA and H.K. Genant, Synarc, Inc, San
Francisco, CA, USA.
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How Long to Treat For?

• Optimal duration of therapy unclear
• Studies with bisphosphonates suggest after 5 yrs
  therapy, treatment may be stopped and BMD
  maintained for several yrs
• If treatment stopped, monitor bone loss and/or
  bone turnover markers

Fracture Summit, MJA, 2002
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Treatment ranking

• First line treatments
• Alendronate, Risedronate, Strontium ranelate,
  Parathyroid hormone, ibandronate, zolendronate,
  denosumab
• Second line treatments
• Raloxifene, HRT
• Third line treatments
• Calcitriol, etidronate, calcium and Vitamin D