Osteoporosis. What is it? Systemic skeletal disease characterised by: –low bone mass –microarchitectural deterioration of bone tissue –resultant increase.

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