Robert Schmidli

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Osteoporosis update

• Robert Schmidli
• John James Medical Centre

2
.. Defined as

• T score lt -2.5
• -1 - -2.5 osteopenia
• Minimal trauma fracture

3
Some statistics

• 25 of Australian women and 17 of men will
  develop osteoporotic fractures
• 42 women aged 50 will sustain a fracture
• Females 3x commoner than males
• More than half of vertebral fractures do not come
  to medical attention

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Pathology

• Disruption of normal architecture
• ? spicules, thinner
• Horizontal struts do not link to other
  structures
• Normal mineralisation (cf osteomalacia)

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Mechanisms

• Low peak bone mass
• Genetics main determinant
• ? Effect of calcium supplementation maintained
  after cessation
• ? bone resorption
• ? bone formation

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Peak bone mass

• Genetics main determinant - 40-80 in twin
  studies
• Effect of diet uncertain - ? sustained

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Pathogenesis
Idiopathic osteoporosis

• Mismatch between resorption and formation
• Secondary osteoporosis
• Age-related
• Menopause

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Mediators of bone loss

• No difference in hormone levels in idiopathic
  osteoporosis cf suitably matched controls
• Parathyroid hormone excess
• Vitamin D deficiency
• Calcitonin - not a major player
• Estrogen ? ? bone resorption
• important in males
• Androgens similar to E2 deficiency in females
• ? Role in females
• Others IL-1, TNF-?, prostaglandins, TGF-? etc

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Risk factors

• Past fracture
• Family history
• Smoking
• Sedentary lifestyle, immobilisation
• Low body weight
• Alcoholism
• Caffeine (large quantities)
• Above-average height
• Low estrogen/androgen levels

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Secondary osteoporosis

• Thyrotoxicosis
• Coeliac disease
• Vitamin D deficiency
• 1? hyperparathyroidism
• Myeloma
• Glucocorticoid excess
• Immobilisation
• Drugs
• Hypogonadism

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Screening tests

• Minimal trauma fracture
• Spine X-ray
• DEXA Dual Energy X-ray Absorptiometry
• Good precision
• Minimal radiation dose
• Ultrasound - calcaneus
• Sound transmission related to bone density
• As good as DEXA to predict hip fracture (n6189)
• Biochemical markers
• Urinary deoxypyridinoline
• Related to BMD overlap between O.P and normal

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History

• Fractures -throughout life
• Loss of height
• Bone pain
• Glucocorticoids
• Bedrest
• Chronic diarrhoea

• Menopause, menarche/libido
• Calcium intake
• Exercise
• Alcohol
• Smoking
• Drugs anticoagulants
• anticonvulsants

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Screening

• Justified if
• The disease is common
• High morbidity, mortality, cost
• Accurate, safe diagnostic test
• Effective treatment

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Examination

• Weight
• Height
• Bony tenderness, deformity
• Liver disease
• Breasts
• Testicular size

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Investigations

• FBE, ESR, LFT
• Calcium, PTH
• 25-OH vit D
• Anti-endomysial Ab, IgA
• Protein electrophoresis
• Thyroid function
• ?Urinary deoxypyridinoline/creat
• DEXA scan
• ?XR lumbar spine

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Treatments

• Exercise
• Calcium
• Vitamin D
• Calcitriol
• Hormone replacement therapy
• Raloxifene
• Bisphosphonates
• Parathyroid hormone

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Exercise

• gt 4 hours/week ? 41lowering of
  risk(prospective Nurses health study, n 61,000
• Weight-bearing exercise acceptable(eg. Walking)
• No evidence that high-intensity exercise better

18
Calcium

• No evidence for fracture prevention
• 1000g (male, premenopausal female) -1500g/day
  (postmenopause) for positive calcium balance
• Protects against bone loss (700 vs 1000mg/day)

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Vitamin D

• Subclinical deficiency common
• Increases with increasing age
• Elevated PTH levels
• Low 25-OHD - may be in lower normal range
• 30 hip patients have histological osteomalacia
• Prevents fractures in elderly women
• Calcium probably also required
• Milk is greatest dietary source

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Calcitriol

• May stimulate bone formation, restore positive
  calcium balance
• ? vertebral and peripheral in one large study
  (pre-existing )
• Not supported by several (smaller) studies
• Requires monitoring hypercalcaemia,
  hypercalciuria

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Hormone replacement

• ? hip, vertebral and other fracture risk (WHI)
• Max protection if started at menopause and
  continued indefinitely
• Progestin - no effect on efficacy
• Low dose may prevent bone loss
• WHI may increased risk of CHD, stroke, VTE,
  breast cancer
• Not recommended for sole prevention or treatment
  of osteoporosis

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Phytoestrogens

• Estrogenic and anti-estrogenic properties
• Most potent found in soy beans, chick peas and
  lentils
• Much weaker than human estrogens
• Review of 74 studies benefits of HRT far
  outweigh plant products
• May increase breast cancer risk

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Bisphosphonates

• Demonstrated antifracture efficacy
• Continued ? BMD over 7 years
• Slow loss BMD if discontinued - better maintained
  than estrogen
• Stop if oesophagitis symptoms
• Etidronate ?osteomalacia
• Pamidronate (IV) inconvenient, SEs

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Zoledronic acid (Zometa)

• No fracture data available
• 5-min infusion
• ?Annual dose
• Expensive

25
Raloxifene

• Selective estrogen receptor modulator
• ? bone density
• ? LDL cholesterol
• No endometrial hyperplasia/vaginal bleeding
• Beneficial effects less than estrogen or
  bisphosphonates
• Tamoxifen some evidence for efficacy

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Parathyroid hormone

• Intermittent administration ? beneficial effect
  on bone
• Given SC daily
• Trials ? spine BMD, ? vertebral
  (?non-vertebral) fractures
• ? Differential effect ? radius BMD
• Osteosarcoma in rats
• FDA approved in US for high risk patients