4. Metabolic bone conditions (Robson)

Question 1

What is used to diagnose metabolic bone conditions?

Answer 1

Serum blood tests

Question 2

What will serum blood test results show in osteoporosis?

Answer 2

The blood test results will generally show as normal

MAY be slightly low level of calcium and vitamin D

Question 3

What is osteoporosis?

Answer 3

Reduced bone density occurring from a loss of tissue due to calcium or vitamin D deficiency

Question 4

Does osteoporosis affect men or women more and why?

Answer 4

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)

Question 5

What is the key investigation used to assess osteoporosis and reduced bone mass?

Answer 5

DEXA scan - used to measure the bone mass - gives you a T or Z score

Question 6

What does the T score from a DEXA scan take into account?

Answer 6

Number of SDs from a young individual of the same same sex and same ethnicity

Question 7

What does the Z score from a DEXA scan take into account?

Answer 7

Number of SDs from an individual of the SAME AGE, same sex and same ethnicity

Question 8

How does the Z score differ from the T score from a DEXA scan?

Answer 8

Z score - takes into account the age of the individual

Question 9

Where is a DEXA scan used?

Answer 9

Scan where there is lots of trabeculae bone - top of the femur and at the vertebral bodies (especially lumbar vertebrae

Question 10

What DEXA T score indicates osteoporosis?

Answer 10

T score below 2.5

Question 11

What is osteopenia and what is this on the DEXA T score?

Answer 11

Reduced bone density but not as severe as osteoporosis

T score between -1 and -2.5

Question 12

What is a fragility fracture?

Answer 12

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

Question 13

What is indicated by a fragility fracture?

Answer 13

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

Question 14

What is the prevalence of osteoporosis?

Answer 14

2% at 50 years old

>25% at 80 years old

Question 15

Why is trabecular bone more prone to osteoporosis?

Answer 15

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

Question 16

What is the mechanism of osteoporosis?

Answer 16

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

Question 17

Describe the activity of the osteoclasts and osteoblasts in osteoporosis

Answer 17

Osteoblasts are not as active as the osteoclasts

Question 18

Where are bone biopsies for osteoporosis taken and why?

Answer 18

Tend to be taken across the iliac crest - this shows cortical bone and trabecular bone and also bone marrow

Question 19

What does osteoporotic bone look like in a biopsy?

Answer 19

The cortical bone will appear normal - there will be a loss of trabeculae bone centrally

Question 20

What is the treatment for osteoporosis?

Answer 20

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

Question 21

What level of calcium and vitamin D supplement should be provided to osteoporotic patients?

Answer 21

Calcium - 1500mg/day

Vitamin D - 800IU/day

Question 22

What are bisphosphonates and what are their mechanism of action?

Answer 22

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

Question 23

What is the efficacy of bisphosphonates?

Answer 23

Reduce the risk of fragility fractures by 50%

Question 24

What is the adverse effect of bisphosphonate usage?

Answer 24

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

Question 25

How can osteonecrosis be prevented?

Answer 25

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

Question 26

What is teriparatide and how is it used to treat osteoporosis?

Answer 26

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

Question 27

What is denosumab?

Answer 27

Relatively new - antibody treatment Binds to RANKL to prevent it from getting to and activating the osteoclasts

Question 28

What is osteomalacia?

Answer 28

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

Question 29

How does osteomalacia show on a serum blood test?

Answer 29

``` Low calcium Low phosphate High ATP High PTH Low vitamin D ```

Question 30

How do osteomalacia and osteoporosis differ from each other?

Answer 30

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

Question 31

What is the most common presentation of osteomalacia?

Answer 31

Bow legs - genu varum

Question 32

Is osteomalacia more damaging in adults or children and why?

Answer 32

More damaging in children - their epiphyseal growth plates are still open and these widen lengthways (top to bottom) - more deforming

Question 33

What are pseudofractures in osteomalacia?

Answer 33

In adults Where there is new bone formation e.g. bone remodelling - mineralisation does not occur - psuedofractures - regions of unmineralised bone

Question 34

How does osteomalacia appear in a bone biopsy?

Answer 34

Normal bone - has less than 20% unmineralised bone | Osteomalacia - see wide streams of unmineralised osteoid casing the mineralised osteoid

Question 35

What is the treatment for osteomalacia?

Answer 35

Vitamin D supplements - may be required for the rest of their life Dietary increase in calcium Increased sun or UV exposure

Question 36

Give five food groups high in calcium

Answer 36

``` Milk Bread Beans and pulses Dried fruit Green leafy veg ```

Question 37

How much sun exposure should an individual have to get sufficient levels of vitamin D?

Answer 37

15 minutes of sun on the hands and face 2-3 times a week

Question 38

What is Paget's disease?

Answer 38

Condition where the normal cycle of bone renewal and repair is disrupted

Question 39

What are the three stages of Paget's disease? Describe these

Answer 39

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

Question 40

What are the bones commonly affected in Paget's disease?

Answer 40

``` Pelvis Femur Vertebrae Skull Tibia ```

Question 41

Does Paget's disease tend to be unilateral or bilateral?

Answer 41

Unilateral

Question 42

What is the relation of osteosarcoma and Paget's disease?

Answer 42

Osteosarcoma is a rare complication of Paget's disease - often occurs in the young Occurs due to the giant osteoclasts and rapid proliferation

Question 43

What is the treatment for Paget's disease?

Answer 43

Bisphosphonates - work directly on the osteoclasts to slow bone resorption Calcium and vitamin D supplements Pain management Surgery

Question 44

What is slerostosis?

Answer 44

This is a condition where there is an absence or reduced production of sclerostin

Question 45

What is the rationale for providing calcium supplements to patients with osteoporosis?

Answer 45

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

Question 46

What is the rationale for providing vitamin D supplementation to patients with osteoporosis?

Answer 46

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

Question 47

Function of bisphosphonates x2

Answer 47

Inhibition of osteoclast activity | Inhibition of RANKL production from osteoclasts

Question 48

Bisphonates have action on what cell type?

Answer 48

Osteoclasts

Question 49

PTH - short term action is on which cells?

Answer 49

Osteoblasts

Question 50

PTH - long term action is on which cells?

Answer 50

Osteoclasts

Question 51

Teriparatide has action on which cells

Answer 51

Teriparatide - short term PTH | Acts of osteoblasts

Question 52

Cause of osteomalacia?

Answer 52

Insufficient calcium and phosphate levels

Question 53

Technical term for bow legs is?

Answer 53

Genu Varum

Question 54

In normal bone - what is the percentage of unmineralised osteoid?

Answer 54

<20%

Question 55

In osteomalacia, what is the percentage of unmineralised none?

Answer 55

>20%

Question 56

Three stages of Paget's disease are?

Answer 56

Initial Compensatory/proliferative Burn out

Question 57

Main feature of initial stage in Paget's disease is?

Answer 57

Increased bone resorption via giant osteoclasts

Question 58

Main feature in compensatory/proliferative stage of Paget's disease is? x2

Answer 58

Increased bone formation | Deposition of bone in disorganised manner

Question 59

Main feature of burnt out phase in Paget's disease is? x3

Answer 59

Sclerosis Cement lines - prominent Bone marrow replaced with fibrovascular connective tissue

Question 60

What is Van Buchem syndrome?

Answer 60

Reduced production of sclerostin

Question 61

Sclerostin is secreted from which cells?

Answer 61

Osteocytes

Question 62

Consequence of Van Buchem syndrome is?

Answer 62

Hyperactivity of osteoblasts

Question 63

Inheritance of Van Buchem syndrome is?

Answer 63

Autosomal recessive