Week 1 - B - Biochemistry (1) - Osteoporosis, Osteomalacia and Ricket's Flashcards
What is the quantitative defect of bone characterized by reduced bone mineral density and increased porosity known as? (ie the bone is of normal quality however there is just not enough it) What can this conditions increase the risk of?
Osteoporosis is a quantitative defect of bone (normal quality but not enough) characterised by reduced bone mineral density and increased porosity
This condition can leads to fragility of the bone and increased fracture risk with fractures occurring after minimal or no trauma
Which sex is osteoporosis more common in? What are the 4 common sites for fracture in osteoporosis?
Osteoporosis is more common in females
Common Fracture sites
* Neck of femur
* Vertebral body
* Hip
* Humeral neck
What are the different risk factors for osteoporosis?
Risk factors =
- shattered Steroid use long term
- Hyperthyroidism,
- hyperparathyroidism,
- hypercalcuria
- Alcohol and tobacco use
- Thin BMI
- Testosterone low
- Early menopause
- Renal or liver failure
- Erosive / inflammatory bone disease (eg myeloma or RA)
- Dietary decreased calcium
What is the most widely used method of assessing bone mineral density? What is the normal standard deviation for bone mineral density?
Using a DEXA bone scan is the most widely used method of assessing a patients bone mineral density
Normal bone mineral density is within 1 standard deviation below the young adult mean * (T score > -1)
What is the condition known as that is the intermediate stage between normal bone mineral density and osteoporosis? What is the bone mineral densities for this condition and for osteoporosis from DEXA scan?
Osteopenia is the intermediate stages between normal BMD and osteoporosis
* Osteopenia - greater than 1 but less than 2.5 standard deviations below the young adult mean (T-score -1 to -2.5)
* Osteoporosis - greater than 2.5 standard deviations from the young adult mean (T-score -2.5 o worse)
What are the two types of osteoporosis?
Type 1 - post menopausal osteoporosis
Type 2 - Osteoprosis of old age
Describe Type 1 osteoporosis Which types of fractures tend to predominate in this group?
Type 1 osteoporosis - post-menopasual osteoporosis is associated with an exacerbated loss of bone in the post-menopasual period
It is associated with Colle’s fractures and vertebral insufficiency fractures
Describe Type 2 osteoporosis Which conditions may it occur secondary to? Which type of fractures occur in this age group?
Type 2 osteoporosis - osteoporosis of old age - decline in bone density in old age - can occur secondary to conditions such as
- * Steroid use
- * Hyperthryroidism/hyperparathyroidism, hyperacluria
- * Alcohol and tobacco use
- * Chronic disease eg renal/liver failure,,
- malignancy,
- rheumatoid
Femoral neck and vertebral fractures predominate this group
Can treatment of osteoporosis reverse the bone mineral loss?
Unfortunately once osteoporosis is diagnosed, no treatments can increase bone mineral density.
Treatments aim to slow any further deterioration and hopefully decrease the risk of subsequent fracture
What lifestyle measures should be done to maximise peak bone mineral density? - therefore reducing osteoporosis risk when bone mineral density starts to decrease
* Quit smoking and reduce alcohol consumption
* Carry out weight bearing exercise
* Calcium and vitamin D rich diet
* Healthy levels of sunlight exposure
What is the recommended minimum daily calcium intake? What is prescribed to somebody who does not receive their recommended calcium intake or who are not exposed to much sunlight?
Recommended minimum daily calcium intake is 700 mg/day
If a person’s calcium intake is inadequate prescribe vitamin D and calcium
What does the T-score need to be to give the first line drug treatment for osteoporosis? What is the 1st line drug treatment? - which drug can be given if the patient is intolerant
T-score needs to be -2.5 or less to receive 1st line drug treatment
Oral biphosphonates - specifically alendronic acid (aldendronate) is first line
(if intolerant, can try risendronic acid - risedronate)
How should biphosphonates be taken? What side effects are important to know?
Patient should take the oral biphosphonates with plenty of water will remaining upright for >30 minutes and wait 30 minutes before eating or other drugs (usually in the morning then)
Biphosphonates can cause
- * Esophageal ulcers
- * GI upset
- * Also hypocalcaemia/tired
- * Rarely - osteonecrosis of the jaw and atypical fractures (usually of the femur)
How do biphosphonates work?
Bisphosphonates bind to the surfaces of the bones and slow down the bone resorbing action of the osteoclasts (bone-eroding cells).
This allows the osteoblasts (bone-building cells) to work more effectively.
Biphosphonates reduce osteoclast resorption
If the patients are not suitable for oral biphosphonates, what is the second line drug treatment and via which route?
Second line drug treatment is zolendronic acid It is a once yearly IV infusion for 3 years
If biphosphonates are not tolerated or contraindicated, what drug can be given as third line? How does this drug work and how is it given?
Denosumab is a monoclonal antibody given subcutaneously that inhibits osteoclast activity by targeting the RANK ligand It is given subcutaneously every 6 months (twice yearly)
When is DENOSUMAB recommended as 1st line treatment for osteoporosis?
Denosumab subcutaneous injection (every 6 months) is recommended as
• 1st line in patients with severe renal impairment (eGFR<35ml/min) (Bisphosphonates should be avoided in patients with moderate to severe renal impairment. (Calculated creatinine clearance <35ml/minute for alendronate, <30ml/minute for risedronate))
Is HRT used as treatment for osteoporosis in post menopasual women? What is the drug that acts similarly to HRT that can also be given? (selective oesotrogen receptor modulator)
Consider prescribing hormone replacement therapy (HRT) to women who have a premature menopause (menopause before 40 years of age)
- not used as a first line treatment to treat osteoprosisi however
Raloxifene (an oestrogen receptor modulator) can also be considered
What are the important side effects of HRT? What side effect does raloxifene share?
HRT increases the risk of breast cancer and endometrial cancer and DVT
Raloxifene also increases the risk of DVT
What is the qualitative defect of bone known as where there is abnormal softening of bone?
This is known as osteomalacia - nromal quantity of bone, abnormal quality
Deficiencies in which electrolytes are key for the development of osteomalacia? What do these deficiencies cause?
Inadequate amounts of calcium/vit D/phosphorus leads to an abnormal softening of bone due to deficient mineralisation of osteoid (immature bone)
What is ostemalacia known as when it arises in children? (prior to fusion of the epiphyses and therefore during bone growth)
Osteomalacia that arises in children is known as Ricket’s disease
What is the principle cause of the deficiencies of calcium / vit D / phosophorus that may lead to osteomalacia?
Insufficient calcium absorption from the intestine because of lack of dietary calcium or
a deficiency or a resistance to the action of vitamin D or
Phosphate deficiency caused by increased renal loss - eg renal osteodystrophy
Name some other causes of osteomalacia?
* Malnutrition (low calcium and vit D)
* Malabsorption - low vit D
* Lack of sunlight exposure - no vitamin D activation
* Hypophosphateaemia - re-feeding syndrome, alchol abuse, renal osteodystrophy
* Long term anticonvulsant use
* Vitamin D resistant rickets
