Transcript osteoporosis - WA Centre for Health and Ageing

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
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
national osteoporosis society
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
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Hyperparathyroidism
Hyperthyroidism
Hypogonadism
•IMMOBILITY
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
Associated
• Mechanism not always understood
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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
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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
– -1 and -2.5 SD
– below -2.5SD
- within normal range
- osteopenia
- 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
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Weight loaded exercise
stop smoking
“bone-friendly diet”
decrease ETOH consumption
avoid high doses Vitamin A (ie cod liver
oil!)
• Reduce risk of falls