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Osteoporosis
What is it?
• Systemic skeletal disease characterised by:
– low bone mass
– microarchitectural deterioration of bone tissue
– resultant increase in fragility and risk of
fracture
national osteoporosis society
Why is it important?
• 1 in 3 women and 1 in 12 men over the age of 50
• Every 3 minutes someone has a fracture due to
osteoporosis
• ~2 million people in the Aus have osteoporosis
• 20,000 hip fractures/yr Aus
• 50,000 wrist fractures UK
• 120,000 spinal fractures UK
• Costs $7.4 billion each year
Bone Components
• Protein matrix of collagen fibres
• Bone mineral;an inorganic calcium compound
hydroxyapatite
• Osteoblasts; synthesise collagen and the control of
mineralisation.
• Osteoclasts; resorb bone by pumping out H+ that dissolves
the hydroxyapatite.
• Osteocytes; direct bone to form in the places where it is
most needed. They may detect mechanical deformation and
mediate the response of the osteoblasts
Idiopathic Osteoporosis
• Type 1
– postmenopausal women
– accelerated loss of trabecular bone
– # vertebral bodies, distal forearm
– Oestrogen inhibits osteoclasts; postmenopause bone is
resorbed faster
Idiopathic Osteoporosis
• Type 2
– women and men >70yrs
– loss of trabecular and cortical bone
– NOF, prox. Humerus, pelvis, prox tibia
Type 2...
• “age related”
• increased breakdown by osteoclasts
• decreased bone formation by osteoblasts
• contribution of:
– decreased oestrogen levels
– Vitamin D deficiency
– secondary Hyperparathyroidism
• Decreased activity
• ?decreased production of insulin-like growth
factors
Secondary Osteoporosis
• Hyperparathyroidism
• Hyperthyroidism
• Hypogonadism
• Cushing’s
• Vit D
– helps Ca+ absorbtion in the intestine. Low Vit D results in decreased plasma Ca+..
This increases PTH secretion -> More Ca+ is resorbed from bone
• Ca+ deficiency
• Malabsorption
•IMMOBILITY
Associated
• Mechanism not always understood
– Rheumatoid Arthritis
– COPD
– ETOH dependance or >3 units/day
– Myeloma
– Chronic Liver Disease
– Diabetes
Other Risk factors
• Female - lower peak bone mass, increased menopausal
bone loss, longer life
• >60years
• FmHx (maternal)
• Caucasian or Asian
• Early menopause
• Prolonged Amenorrhoea at young age
• Low BMI (<19)
• History of fracture
• Smoker
• Sedentary
Medications
• Steroids
– increased bone loss by suppressing osteoblasts
– 2.5% pop age>75
• Phenytoin
• Heparin
• Chemotherapy - letrozole
Presentation
• Either with fracture or case finding
• otherwise asymptomatic
Kinds of Fracture
• “Low trauma fractures”
• “fragility fractures”
• WHO: # caused by injury insufficient to
break normal bone - minimal standing
height, or no trauma at all
Vertebral crush #
•Acute or Chronic
•Asymptomatic in 2/3rds
•Pain
•Kyphosis
•Instability
•Decreased Height
Hip Fracture
•70% mortality at one-year if not fixed
•30% one year mortality
•40% severely disabled at one year
RED FLAG identification
• Investigations
– FBC
– ESR
– LFTs
– U&E
– Ca/Phos/ALP
– Immunoglobulins
– Electrophoresis/BJP
– TFTs
Diagnosis without fracture
• Don’t use XR for diagnosis unless reported as “severe
osteopenia” (then get DXA scan)
• Ultrasound of calcaneus - not useful
DEXA Scan
• Dual-energy X-Ray absorptiometry
• two beams of single energy pass through bone. The denser the bone the
more the beams are attenuated.
• BMD is then compared to a reference range of young adults with
average bone density, this is expressed in standard deviations:
• T scores:
– 0 and -1 SD - within normal range
– -1 and -2.5 SD - osteopenia
– below -2.5SD - osteoporosis (WHO definition)
• a Z score is also calculated. This compares BMD with a reference
range of those the same age.
•only do DXA scan as a “casefinding
strategy, rather than for population
screening”
•it predicts future fracture with high
specificity, but low sensitivity
Treatment -Drugs
• Calcium and vitamin D
• Bisphosphonates.
• Strontium
• Hormone replacement therapy (HRT)
• Selective Estrogen Receptor Modulators
(SERMs)
• Testosterone
• recombinant Parathyroid Hormone
Bisphosphonates.
• Block mineralisation and
osteoclastic bone resorption
• 2nd and 3rd generation
have more anti-resorptive
properties
 cyclic Etidronate (1st gen)
- needs to be cyclical to
stop osteomalacia
developing, (2/52
etidronate, 10/52 calcium)
Side Effects
 not in renal failure!
 Jaw osteonecrosis
 Upper GI side effects
 must be taken upright and stay sitting or standing
without food or drink for 30+ mins
Bisphosphonates...
 Alendronate (2nd gen) - can cause oesophageal
ulceration. Most data is from daily dosing, but current
recommendations are for weekly
 Risedronate. (3rd gen) - cylic side chain
 Ibandronate (not yet available here) - iv preparation or
once monthy oral tablet. Evidence not direct
 Zolendronic Acid - once yearly infusion. NO evidence for
osteoporosis - high risk of Osteonecrosis
Reduce vertebral and non-vertebral, including hip
Strontium
• Sachet drink - daily
• side effects - diarrhoea and headache
Reduce vertebral and non-vertebral, including hip
Other treatment
• SERMs
– (selective oestrogen receptor modulators)
– Raloxifene
– decreases risk of ER+ve breast cancer
– Increases risk of DVT/PE
– Used mainly if intolerant of bisphosphonates
– reduces risk of vertebral fractures only
• Teriparatide
– recombinant 1-34 parathyroid hormone
– sc daily injection
– Reduce vertebral and non-vertebral, but NOT
hip
– EXPENSIVE!
• HRT
– risk outweighs benefits?
– Young women with high risk of fracture and
symtomatic menopause
Vitamin D and Calcium
• Contentious preventative treatment
• 2 french nursing home studies demonstrate
decrease in fractures
• primary care randomised study from York
shows no change (BMJ 30th April 05)
• Aberdeen study shows similar results
(Lancet 28th April 05)
• However - ALL other agents were trialled
whilst taking both Calcium and Vit D
Non-pharmacological
• Weight loaded exercise
• stop smoking
• “bone-friendly diet”
• decrease ETOH consumption
• avoid high doses Vitamin A (ie cod liver
oil!)
• Reduce risk of falls
osteoporosis - E-Ageing

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osteoporosis - E-Ageing

  • 2. What is it? • Systemic skeletal disease characterised by: – low bone mass – microarchitectural deterioration of bone tissue – resultant increase in fragility and risk of fracture
  • 3. national osteoporosis society Why is it important? • 1 in 3 women and 1 in 12 men over the age of 50 • Every 3 minutes someone has a fracture due to osteoporosis • ~2 million people in the Aus have osteoporosis • 20,000 hip fractures/yr Aus • 50,000 wrist fractures UK • 120,000 spinal fractures UK • Costs $7.4 billion each year
  • 4. Bone Components • Protein matrix of collagen fibres • Bone mineral;an inorganic calcium compound hydroxyapatite
  • 5. • Osteoblasts; synthesise collagen and the control of mineralisation. • Osteoclasts; resorb bone by pumping out H+ that dissolves the hydroxyapatite. • Osteocytes; direct bone to form in the places where it is most needed. They may detect mechanical deformation and mediate the response of the osteoblasts
  • 6. Idiopathic Osteoporosis • Type 1 – postmenopausal women – accelerated loss of trabecular bone – # vertebral bodies, distal forearm – Oestrogen inhibits osteoclasts; postmenopause bone is resorbed faster
  • 7. Idiopathic Osteoporosis • Type 2 – women and men >70yrs – loss of trabecular and cortical bone – NOF, prox. Humerus, pelvis, prox tibia
  • 8. Type 2... • “age related” • increased breakdown by osteoclasts • decreased bone formation by osteoblasts • contribution of: – decreased oestrogen levels – Vitamin D deficiency – secondary Hyperparathyroidism • Decreased activity • ?decreased production of insulin-like growth factors
  • 9. Secondary Osteoporosis • Hyperparathyroidism • Hyperthyroidism • Hypogonadism • Cushing’s • Vit D – helps Ca+ absorbtion in the intestine. Low Vit D results in decreased plasma Ca+.. This increases PTH secretion -> More Ca+ is resorbed from bone • Ca+ deficiency • Malabsorption •IMMOBILITY
  • 10. Associated • Mechanism not always understood – Rheumatoid Arthritis – COPD – ETOH dependance or >3 units/day – Myeloma – Chronic Liver Disease – Diabetes
  • 11. Other Risk factors • Female - lower peak bone mass, increased menopausal bone loss, longer life • >60years • FmHx (maternal) • Caucasian or Asian • Early menopause • Prolonged Amenorrhoea at young age • Low BMI (<19) • History of fracture • Smoker • Sedentary
  • 12. Medications • Steroids – increased bone loss by suppressing osteoblasts – 2.5% pop age>75 • Phenytoin • Heparin • Chemotherapy - letrozole
  • 13.
  • 14. Presentation • Either with fracture or case finding • otherwise asymptomatic
  • 15. Kinds of Fracture • “Low trauma fractures” • “fragility fractures” • WHO: # caused by injury insufficient to break normal bone - minimal standing height, or no trauma at all
  • 16.
  • 17. Vertebral crush # •Acute or Chronic •Asymptomatic in 2/3rds •Pain •Kyphosis •Instability •Decreased Height
  • 18. Hip Fracture •70% mortality at one-year if not fixed •30% one year mortality •40% severely disabled at one year
  • 19.
  • 20. RED FLAG identification • Investigations – FBC – ESR – LFTs – U&E – Ca/Phos/ALP – Immunoglobulins – Electrophoresis/BJP – TFTs
  • 21. Diagnosis without fracture • Don’t use XR for diagnosis unless reported as “severe osteopenia” (then get DXA scan) • Ultrasound of calcaneus - not useful
  • 22. DEXA Scan • Dual-energy X-Ray absorptiometry • two beams of single energy pass through bone. The denser the bone the more the beams are attenuated. • BMD is then compared to a reference range of young adults with average bone density, this is expressed in standard deviations: • T scores: – 0 and -1 SD - within normal range – -1 and -2.5 SD - osteopenia – below -2.5SD - osteoporosis (WHO definition) • a Z score is also calculated. This compares BMD with a reference range of those the same age.
  • 23. •only do DXA scan as a “casefinding strategy, rather than for population screening” •it predicts future fracture with high specificity, but low sensitivity
  • 24. Treatment -Drugs • Calcium and vitamin D • Bisphosphonates. • Strontium • Hormone replacement therapy (HRT) • Selective Estrogen Receptor Modulators (SERMs) • Testosterone • recombinant Parathyroid Hormone
  • 25. Bisphosphonates. • Block mineralisation and osteoclastic bone resorption • 2nd and 3rd generation have more anti-resorptive properties  cyclic Etidronate (1st gen) - needs to be cyclical to stop osteomalacia developing, (2/52 etidronate, 10/52 calcium)
  • 26. Side Effects  not in renal failure!  Jaw osteonecrosis  Upper GI side effects  must be taken upright and stay sitting or standing without food or drink for 30+ mins
  • 27. Bisphosphonates...  Alendronate (2nd gen) - can cause oesophageal ulceration. Most data is from daily dosing, but current recommendations are for weekly  Risedronate. (3rd gen) - cylic side chain  Ibandronate (not yet available here) - iv preparation or once monthy oral tablet. Evidence not direct  Zolendronic Acid - once yearly infusion. NO evidence for osteoporosis - high risk of Osteonecrosis Reduce vertebral and non-vertebral, including hip
  • 28. Strontium • Sachet drink - daily • side effects - diarrhoea and headache Reduce vertebral and non-vertebral, including hip
  • 29. Other treatment • SERMs – (selective oestrogen receptor modulators) – Raloxifene – decreases risk of ER+ve breast cancer – Increases risk of DVT/PE – Used mainly if intolerant of bisphosphonates – reduces risk of vertebral fractures only
  • 30. • Teriparatide – recombinant 1-34 parathyroid hormone – sc daily injection – Reduce vertebral and non-vertebral, but NOT hip – EXPENSIVE!
  • 31. • HRT – risk outweighs benefits? – Young women with high risk of fracture and symtomatic menopause
  • 32. Vitamin D and Calcium • Contentious preventative treatment • 2 french nursing home studies demonstrate decrease in fractures • primary care randomised study from York shows no change (BMJ 30th April 05) • Aberdeen study shows similar results (Lancet 28th April 05) • However - ALL other agents were trialled whilst taking both Calcium and Vit D
  • 33. Non-pharmacological • Weight loaded exercise • stop smoking • “bone-friendly diet” • decrease ETOH consumption • avoid high doses Vitamin A (ie cod liver oil!) • Reduce risk of falls