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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