Osteoporosis, osteomalacia and Paget's disease

Question 1

In what state are Ca2+, PO4 3-, Alkaline phosphatase, PTH and active Vit D in osteoporosis?

Answer 1

All are at normal levels

- the matrix/mineral ratio is normal but the overall amount of bone is reduced

Question 2

What is a T score?

Answer 2

Number of standard deviations from the mean BMD of a young (30) person of the same gender + ethnicity
- used more often than z score

Question 3

What is a z score

Answer 3

Number of standard deviations from the mean BMD of a person of the same age, gender + ethnicity

Question 4

What is a normal bone mineral density score? What score indicates osteopenia, and what indicates osteoporosis?

Answer 4

Normal: -1 –> +4
Osteopenia: -2.5 –> -1
Osteoporosis: = -2.5

Question 5

What kind of bones are more susceptible to osteoporosis?

Answer 5

Bones with a high proportion of trabecular bone –> vertebral bodies, femoral neck

Question 6

Explain the pathogenesis of osteoporosis.

Answer 6

• relative increase in bone resorption (not matched by formation)
• bone is mineralised as normal, there is just less bone
• bone loss is not evenly distributed

Question 7

If a person is >75 and has a low trauma fracture, what action should be taken?

Answer 7

Give bisphosphonates, calcium and vit D

Question 8

If a person is 50-75 and has a low trauma fracture, what action should be taken?

Answer 8

Refer for a DEXA scan

Question 9

If a person is 65-75 and DEXA gives a T score < -2.5, what action should be taken?

Answer 9

Give bisphosphonates, calcium and vit D

Question 10

If a person is 50-75 and DEXA gives a T score >-2.5, what action should be taken?

Answer 10

Give calcium and vit D

Question 11

If a person is 50-65 and DEXA gives a T score < -3.2, what action should be taken?

Answer 11

Bisphosphonates, calcium and vitamin D

Question 12

If a person is 50-65 and DEXA gives a T score -2.5 –> -3.2 + clinical risk factor(s), what action should be taken?

Answer 12

Bisphosphonates, calcium and vitamin D

Question 13

Apart from Bisphosphonates, calcium and vitamin D, what other treatments can be given for osteoporosis?

Answer 13

• HRT (oestrogen replacement for post-menopausal; lasts ~5 years
• Raloixfene: selective oestrogen receptor modulator
• Teriparatide
• Denosumab

Question 14

What is the MOA of bisphosphonates?

Answer 14

• Potent inhibitors of bone resorption - osteoclasts will not attach where bisphosphonates are present
• if osteoclasts do absorb bisphosphonates this will cause apoptosis
• increase OPG production + reduce RANKL production = reduce osteoclast differentiation

Question 15

What complications are associated with bisphosphonates?

Answer 15

• giant osteoclasts
• osteonecrosis of the jaw (due to inhibition of osteoclasts)
• atypical fractures –> subtrochanteric + femoral shaft
• -> old osteocytes signal for remodelling but fewer good osteoclasts

Question 16

What is the MOA of teriparatide?

Answer 16

• Intermittent exposure to PTH will activate osteoclasts, but exposure is not long enough to activate osteoclasts
• will not increase bone mass dramatically

Question 17

What is the MOA of denosumab?

Answer 17

• subcutaneous injection every 6 months

- inhibits osteoclasts formation –> by binding to RANKL

Question 18

In what state are Ca2+, PO4 3-, Alkaline phosphatase, PTH and active Vit D in osteomalacia?

Answer 18

Ca2+: decreased
PO4 3-: decreased
Alkaline phosphatase: increased 
PTH: increased
active vit D: decreased

Question 19

Why does osteomalacia occur?

Answer 19

Usually a result of vitamin D deficiency

Question 20

What is the main difference between osteomalacia in children and adults?

Answer 20

Children: more deformities as epiphyseal growth plate is open

Adult: less deformities epiphyseal growth plate is closed

Question 21

What will imaging of osteomalacia?

Answer 21

pseudo fractures, areas of unmineralised bone

Question 22

How can tetracycline used to diagnose osteomalacia?

Answer 22

give 2 pulses of tetracycline each for 3 days and each pulse is 10 days apart
Normal result: 2 distinct lines
Mild/moderate osteomalacia: diffuse or single labelling
Severe osteomalacia: no labelling –> no mineralisation taking place

Question 23

What is the treatment for osteomalacia?

Answer 23

1. vitamin D
2. increase Ca2+ (dietary)
3. sun or UV exposure

Question 24

What are the 3 phases of Paget’s disease?

Answer 24

1. Initiation phase:
   - increased bone resorption
   - large number of giant osteoclasts
2. compensatory/proliferation phased (mixed)
   - increased bone formation
   - accelerated deposition in disorganised manner
3. Burnt out phase
   - bone hypercellularity may diminish = dense pagetic bone
   - hypervascular bone marrow
   - irregularly thickened trabeculae
   - prominent cement lines
   - bone marrow replaced by fibrovascular connective tissue

Question 25

What bones are typically affected in Paget’s disease?

Answer 25

pelvis, femur, vertebrae, skull, tibia

Question 26

What is a late complication of Paget’s that mostly occurs in young people?

Answer 26

Osteosarcoma –> rare (1%)

- among most malignant of cancers

Question 27

What is used to treat Paget’s disease?

Answer 27

Bisphosphonates 
calcium + vit D
pain management 
surgery 
calcitonin

Question 28

What is Sclerostosis?

Answer 28

Also known as Van Buchem Syndrome

• caused by the absence/ reduced production of sclerostin
• autosomal recessive
• endosteal hyperostosis
• resistant to fracture
• excessive height

Question 29

In what state are Ca2+, PO4 3-, Alkaline phosphatase, PTH and active Vit D in Paget’s?

Answer 29

alkaline phosphatase is v high, everything else is normal

Question 30

In what state are Ca2+, PO4 3-, Alkaline phosphatase, PTH and active Vit D in renal failure?

Answer 30

Ca2+: reduced
PO4 3-: increased 
Alkaline phosphatase: normal/high 
PTH: increased 
active vit D: decreased

Question 31

In what state are Ca2+, PO4 3-, Alkaline phosphatase, PTH and active Vit D in primary hyperthyroidism?

Answer 31

Ca2+: increased
PO4 3-: reduced
Alkaline phosphatase: normal/high 
PTH: increased 
active vit D: normal