OSTEOPOROSIS Jessica Fraser

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OSTEOPOROSISJessica Fraser
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What is osteoporosis?

• A disease characterised by low bone mass and
  microarchitectural deterioration of bone tissue
• WHO define on basis of BMD (T scores)1
• Occurs as result of increased bone breakdown by
  osteoclasts and decreased bone formation by
  osteoblasts

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Complications and prognosis of osteoporosis

• Fractures (Nb, not all associated with falls).
• Up to 14,000 people die annually as a result of a
  hip fracture2
• 50 of people are unable to live independently
  following a hip fracture
• Chronic back pain

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Fragility Fractures

• A fracture occurring as a result of mechanical
  force that would not ordinarily cause a
  fracture.3
• Fragility fractures occur most commonly in the
  vertebrae, hips and wrists.3

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T- Score

• The number of standard deviations (SD) by which
  the individuals BMD differs from the BMD of an
  average 25 yr old woman.
• Normal T score not less than -1 SD
• Osteopenia T score between -1 SD and -2.5 SD
• Osteoporosis T-score -2.5 or less
• Established osteoporosis T-score below -2.5
  fragility
• Depends on site and method of bone density
  measurement

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Z-Score

• The number of SDs by which an individuals BMD
  differs from the BMD for people of same age3

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How common is osteoporosis/ fragility fractures?

• Recent estimate- 940000 women with OP in England
  and Wales4
• Osteoporotic affect ½ women and 1/5 men gt 50
  yrs
• 60000 hip each year in UK costing 1.73 billion
  per yr

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Risk factors for osteoporosis

• Female sex
• Age gt 60
• Family History
• Caucasian or Asian origin
• Untreated premature menopause
• Low body mass index (lt 19kg/m2)
• Smoking
• Low calcium intake
• Low vit D levels
• Prolonged immobility
• Corticosteroids
• Alcohol gt 3 units/day
• Falls

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Secondary Causes of Osteoporosis

• Endocrine
• Thyrotoxicosis
• Male hypogonadism
• 10 Hyperparathyroidism
• Malabsorptive or nutritional
• Inflammatory bowel disease
• Chronic liver disease
• Coeliac disease
• Anorexia nervosa
• Vitamin D deficiency
• Others
• RA
• Myeloma
• Renal disease

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Diagnosis of Osteoporosis

• BMD measured by axial DXA at 2 sites- Gold
  standard2
• Identify those at risk and refer for DXA scan
• Also refer the following people
• People with thoracic kyphosis
• People with x-ray evidence of osteopenia/
  vertibral deformity
• Postmenopausal women with 2 vertebral
• People lt 65 yrs taking oral corticosteroids for 3
  months or more
• BMD unreliable if taking strontium

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Routine Ix to exclude 2o causes of Osteoporosis

• FBC
• ESR
• LFTs
• U Es
• Bone group
• Serum immunoglobulins and paraproteins, urinary
  Bence-Jones proteins
• TFTs
• Testosterone, gonadotrophins (FSH and LH), sex
  hormone binding globulin in men
• FSH, LH in women

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Management of Osteoporosis

• If there is a long waiting time for DXA,
  treatment may be initiated in women, and if DXA
  normal then stop.1
• Start Rx for postmenopausal women with 2
  vertebral fractures whilst awaiting DXA.3
• Treatment in men is best initiated following
  specialist assessment
• Start treatment when starting glucocorticoids in
  high risk patients
• Exclude 20 causes
• Offer lifestyle advice
• Assess and manage risk of falls
• Drugs

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Drug treatment in women with 1 fragility fracture
(as per draft guidelines from NICE, 2005)

• Consider treatment in following groups
• - 75 yrs or older
• - 65-74 yrs with T score -2.5 or less
• - Postmenopausal women lt 65 yrs with T score of
  -3 or below
• - Postmenopausal women lt 65 yrs with T score lt
  -2.5 1 or more age-independent risk factors

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Bisphosphonates

• Reduce rate of bone turnover
• Alendronate (fosamax)and risedronate (actonel)
• reduces incidence of vertebral and non-vertebral
  fractures
• Available as once daily and once weekly
  preparations
• Etidronate (didronel)
• Reduces incidence of vertebral fractures
• Given in 90 day cycles
• GI side effects
• Osteonecrosis of jaw-rare!
• Should be taken on an empty stomach, standing
  upright for at least 30 mins afterwards

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Strontium Ranelate

• Stimulates bone formation and reduces bone
  resorption
• Reduces both vertebral and non vertebral
  fractures
• Mild GI side effects
• Increased risk of venous thromboembolism
• Take at bedtime at least 2 hrs after food.

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Raloxifene

• Selective oestrogen-receptor modulator that binds
  to oestrogen receptors
• Reduces risk of vertebral fractures
• Reduced relative risk of breast Ca
• Side effects
• Hot flushes, leg cramps
• Increased risk of venous thromboembolism

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Calcitonin

• Endogenous polypeptide hormone that inhibits bone
  resorption by osteoclasts
• Side effects
• Local irritation to nose
• Flushing, dizziness, GI symptoms

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Drugs for osteoporosis in postmenopausal women

• Drugs which can be initiated by GP
• Bisphosphonates (alendronate, etidronate,
  risedronate) 1st line1,3
• Strontium ranelate if bisphosphonate
  contraindicated, licenced for postmenopause
• Raloxifene (evista)- 3rd line
• Intranasal calcitonin
• HRT-not licenced
• Teriparatide (a recombinant human parathyroid
  hormone) may be initiated by specialist
• Ca and/or Vit D should be given to all women
  receiving Rx for osteoporosis1
• Continue Rx indefinitely

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Drugs for men with osteoporosis

• Aledronate, 10mg daily (other bisphosphonates not
  licenced)
• Calcium 600mg-1.2g per day
• Vitamin D if dietary intake thought to be
  inadequate
• Little evidence on other drug treatments.

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Corticosteroid induced osteoporosis5

• 350,000 people in UK at risk of developing
  glucocorticoid-induced fractures
• Approx 1 of adults take oral glucocorticoids
• Fracture risk increases rapidly after the onset
  of treatment, and declines rapidly after stopping
• Loss of BMD is greatest in the first few months
  of Rx
• Use lowest dose possible to reduce risk
• Routine DXA for lt65 yrs on 3 months course

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Drug Rx for corticosteroid-induced osteoporosis

• Treat all people taking corticosteroids found to
  have OP and all those over 65
• 3-4 courses of corticosteroids in 12 months
  considered to 3 months continuous Rx
• Rx if T score -1.5 or less
• Bisphosphonate 1st line Rx
• HRTlt 50 yrs
• Alfacalcidol and calcitriol-specialist advice
• Ca and Vit D
• Raloxifene, strontium not studied

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Follow-Up

• If lt 65, no previous on corticosteroids
• T score gt 0, no f.U, unless very high doses
• T score 0 to -1.5 repeat in 1-3 yrs if steroid
  use continues
• Alfacalcidol
• Check Ca and creatinine levels at 1 wk then
  monthly to exclude hypercalcaemia
• Calcitriol
• Check Ca and creatinine levels at 1 month, 3
  months and 6 months, then 6 monthly to exclude
  hypercalcaemia

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Follow-up

• Insufficient evidence for routinely monitoring
  BMD in those on Rx for OP
• Rpt BMD only after 2 yrs if thought to be
  appropriate
• Consider rpt DXA scanning if patient has another
  fragility fracture despite adhering to Rx with
  bisphosphonate for yr. If lt pre-Rx level,
  consider alternative Rx

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Summary

• Osteoporosis is common and has high morbidity and
  mortality
• DXA- most useful Ix
• Several Risk factors/ secondary causes to
  consider
• Drug Rx differ slightly in different groups, but
  bisphosphonates usually 1st line

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Any Questions?
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References

• 1. The national Institute for Health and clinical
  Excellence technology appraisal and quick
  reference guide. Bisphosphonates(alendronate,
  etidronate, risedronate), selective oestrogen
  receptor modulators (raloxifene) and parathyroid
  hormone (teriparatide) for the secondary
  prevention of osteoporotic fragility fractures in
  postmenopausal women (2005)
• 2. National osteoporosis Society
• 3. The Scottish Intercollegiate Guidelines
  Network (SIGN) guideline, Management of
  Osteoporosis 2003
• 4. Stevenson, M et al 2005. A systematic review
  and economic evaluation of alendronate,
  etidronate, raloxifene and teriparatide for the
  prevention and treatment of postmenopausal
  osteoporosis. Health technology asseaament.
  9(22), 1-179
• 5. The Royal College of Physicians guideline,
  Glucocorticoid-induced osteoporosis (2002)