4. Metabolic bone conditions (Robson) Flashcards
What is used to diagnose metabolic bone conditions?
Serum blood tests
What will serum blood test results show in osteoporosis?
The blood test results will generally show as normal
MAY be slightly low level of calcium and vitamin D
What is osteoporosis?
Reduced bone density occurring from a loss of tissue due to calcium or vitamin D deficiency
Does osteoporosis affect men or women more and why?
Affects women more - women start off with a lower bone mass in life (and then are effected by the menopause due to loss of oestrogen protection)
What is the key investigation used to assess osteoporosis and reduced bone mass?
DEXA scan - used to measure the bone mass - gives you a T or Z score
What does the T score from a DEXA scan take into account?
Number of SDs from a young individual of the same same sex and same ethnicity
What does the Z score from a DEXA scan take into account?
Number of SDs from an individual of the SAME AGE, same sex and same ethnicity
How does the Z score differ from the T score from a DEXA scan?
Z score - takes into account the age of the individual
Where is a DEXA scan used?
Scan where there is lots of trabeculae bone - top of the femur and at the vertebral bodies (especially lumbar vertebrae
What DEXA T score indicates osteoporosis?
T score below 2.5
What is osteopenia and what is this on the DEXA T score?
Reduced bone density but not as severe as osteoporosis
T score between -1 and -2.5
What is a fragility fracture?
A fracture that occurs where someone with a full bone density would not experience a fracture
E.g. a fracture from a trip and the hip bends slightly rather than an actual fall
What is indicated by a fragility fracture?
This indicates that the bones are becoming fragile and are breaking more easily than they should - should send anyone with a fragility fracture for a DEXA scan
What is the prevalence of osteoporosis?
2% at 50 years old
>25% at 80 years old
Why is trabecular bone more prone to osteoporosis?
Has a greater surface area
This type of bone is in locations that has to respond to new stresses and increased levels of mechanical stress
What is the mechanism of osteoporosis?
There is an increase in the rate of resorption of the bone which is not matched by the rate of bone formation - there is less bone
Describe the activity of the osteoclasts and osteoblasts in osteoporosis
Osteoblasts are not as active as the osteoclasts
Where are bone biopsies for osteoporosis taken and why?
Tend to be taken across the iliac crest - this shows cortical bone and trabecular bone and also bone marrow
What does osteoporotic bone look like in a biopsy?
The cortical bone will appear normal - there will be a loss of trabeculae bone centrally
What is the treatment for osteoporosis?
Non-pharmacological treatment: calcium and vitamin D supplements and 30 minutes physical activity at least three times a week
HRT - oestrogen replacement in peri-menopausal women for at least five years
Bisphosphonates
Antibodies
What level of calcium and vitamin D supplement should be provided to osteoporotic patients?
Calcium - 1500mg/day
Vitamin D - 800IU/day
What are bisphosphonates and what are their mechanism of action?
Group of drugs that are absorbed into bone when taken - become incorporated into the bone
Osteoclasts then come to the bone and take the bisphosphonates up along with the bone resorption
The bisphosphonate is taken up into the osteoclast and this promotes their apoptosis - osteoclast activity is inhibited
May also act to modulate signalling to osteoblasts and decrease their production of RANKL - this reduces the signal to osteoclasts and so they cease to proliferate and differentiate
What is the efficacy of bisphosphonates?
Reduce the risk of fragility fractures by 50%
What is the adverse effect of bisphosphonate usage?
Some osteoclasts do not clamp down on the bone that has taken up the bisphosphonate - results in the development of giant osteoclasts free floating in the bone marrow - the osteoclasts do not carry out their role of remodelling and there is necrosis of the bone due to death of osteocytes
SO: major complication is osteonecrosis
How can osteonecrosis be prevented?
Intermittent use of bisphosphonates - take the patient off of these for e.g. six months at a time - gives osteoclasts time to remodel the bone
What is teriparatide and how is it used to treat osteoporosis?
Short term PTH
PTH activates osteoblasts in the short term and osteoclasts in the long term
SO short term PTH ensures that osteoblasts are still activated by osteoclasts are not
What is denosumab?
Relatively new - antibody treatment
Binds to RANKL to prevent it from getting to and activating the osteoclasts
What is osteomalacia?
AKA. Rickets
Insufficient calcium and phosphate to mineralise the new bone osteoid due to deficient vitamin D
Condition of the woven bone
SO - LACK OF BONE MINERALISATION
How does osteomalacia show on a serum blood test?
Low calcium Low phosphate High ATP High PTH Low vitamin D
How do osteomalacia and osteoporosis differ from each other?
Osteoporosis - decreased total bone mass but normal ratio of the matrix to mineral i.e. matrix to bone
Osteomalacia - decreased ratio of mineral to matrix i.e. higher level of matrix compared to relative levels of bone
What is the most common presentation of osteomalacia?
Bow legs - genu varum
Is osteomalacia more damaging in adults or children and why?
More damaging in children - their epiphyseal growth plates are still open and these widen lengthways (top to bottom) - more deforming
What are pseudofractures in osteomalacia?
In adults
Where there is new bone formation e.g. bone remodelling - mineralisation does not occur - psuedofractures - regions of unmineralised bone
How does osteomalacia appear in a bone biopsy?
Normal bone - has less than 20% unmineralised bone
Osteomalacia - see wide streams of unmineralised osteoid casing the mineralised osteoid
What is the treatment for osteomalacia?
Vitamin D supplements - may be required for the rest of their life
Dietary increase in calcium
Increased sun or UV exposure
Give five food groups high in calcium
Milk Bread Beans and pulses Dried fruit Green leafy veg
How much sun exposure should an individual have to get sufficient levels of vitamin D?
15 minutes of sun on the hands and face 2-3 times a week
What is Paget’s disease?
Condition where the normal cycle of bone renewal and repair is disrupted
What are the three stages of Paget’s disease?
Describe these
Initial phase - increased rate of bone resorption - large number of giant osteoclasts
Compensatory/proliferative phase - increased bone formation - accelerated deposition in disorganised manner (making woven bone very quickly in an attempt to compensate for the increased resorption
Burnt out phase - bone hypercellularity and hyper-vascular bone marrow
What are the bones commonly affected in Paget’s disease?
Pelvis Femur Vertebrae Skull Tibia
Does Paget’s disease tend to be unilateral or bilateral?
Unilateral
What is the relation of osteosarcoma and Paget’s disease?
Osteosarcoma is a rare complication of Paget’s disease - often occurs in the young
Occurs due to the giant osteoclasts and rapid proliferation
What is the treatment for Paget’s disease?
Bisphosphonates - work directly on the osteoclasts to slow bone resorption
Calcium and vitamin D supplements
Pain management
Surgery
What is slerostosis?
This is a condition where there is an absence or reduced production of sclerostin
What is the rationale for providing calcium supplements to patients with osteoporosis?
Calcium supplements will bring the serum calcium levels to the range in which they are required
This will cause PTH levels to fall (due to release of calcitonin)
PTH stimulates activity of osteoclasts and so:
PTH levels fall - reduced activity of osteoclasts and reduced bone resorption - decreases onset of osteoporosis
What is the rationale for providing vitamin D supplementation to patients with osteoporosis?
1,25-hydroxyvitamin D (active form) increases calcium absorption in the gut
This will result in falling PTH levels due to release of calcitonin - reduced osteclast activity
Function of bisphosphonates x2
Inhibition of osteoclast activity
Inhibition of RANKL production from osteoclasts
Bisphonates have action on what cell type?
Osteoclasts
PTH - short term action is on which cells?
Osteoblasts
PTH - long term action is on which cells?
Osteoclasts
Teriparatide has action on which cells
Teriparatide - short term PTH
Acts of osteoblasts
Cause of osteomalacia?
Insufficient calcium and phosphate levels
Technical term for bow legs is?
Genu Varum
In normal bone - what is the percentage of unmineralised osteoid?
<20%
In osteomalacia, what is the percentage of unmineralised none?
> 20%
Three stages of Paget’s disease are?
Initial
Compensatory/proliferative
Burn out
Main feature of initial stage in Paget’s disease is?
Increased bone resorption via giant osteoclasts
Main feature in compensatory/proliferative stage of Paget’s disease is? x2
Increased bone formation
Deposition of bone in disorganised manner
Main feature of burnt out phase in Paget’s disease is? x3
Sclerosis
Cement lines - prominent
Bone marrow replaced with fibrovascular connective tissue
What is Van Buchem syndrome?
Reduced production of sclerostin
Sclerostin is secreted from which cells?
Osteocytes
Consequence of Van Buchem syndrome is?
Hyperactivity of osteoblasts
Inheritance of Van Buchem syndrome is?
Autosomal recessive
