Ageing and Metabolic Bone Conditions

Question 1

What happens to bone in osteoporosis, osteomalacia, paget’s?

Answer 1

• osteoporosis = low bone volume
• osteomalacia = abnormal mineralisation
• paget’s = high bone turnover

Question 2

In osteomalacia what are the blood results?

Answer 2

• low calcium
• low phosphate
• high alkaline phosphatase
• • high PTH
• low vitamin D

Question 3

In Paget’s what are the blood results?

Answer 3

• very high alkaline phosphatase

Question 4

In renal failure what are the blood results?

Answer 4

• low calcium
• high phosphate
• high alkaline phosphatase
• high PTH
• low vitamin D

Question 5

In primary hyperparathyroidism what are the blood results?

Answer 5

• high calcium
• low phosphate
• high alkaline phosphatase
• high PTH

Question 6

What is alkaline phosphatase?

Answer 6

• produced by osteoblasts
• marker of active osteoblasts
• also produced by liver

Question 7

What happens in osteoporosis?

Answer 7

• blood results normal
• ratio of matrix to mineral remains the same
• only difference is reduced overall bone amount

Question 8

What happens in osteomalacia?

Answer 8

• low calcium and low phosphate
• increased PTH
• increase in AP as bone broken down

Question 9

What happens in Paget’s?

Answer 9

• everything normal except AP

- osteoblasts producing a lot of new bone

Question 10

Who is at risk of getting osteoporosis?

Answer 10

• aged 40 onwards
• more common in women as have lower bone mass to begin with and bone loss sped up after menopause due to oestrogen loss (oestrogen inhibits RANKL)

Question 11

How is osteoporosis diagnosed?

Answer 11

• DEXA
• expressed as T or Z score
• T = no. of s.d from mean young (30 years)
• Z = no. of s.d. from mean

Question 12

What is osteopenia classified as?

Answer 12

• T scores between -1 and 2.4

Question 13

What is osteoporosis classified as?

Answer 13

T score <2.5

Question 14

What is the mechanism of osteoporosis?

Answer 14

• relative increase in resorption not matched by formation
• loss unevenly distributed
• primarily affects trabecular bone

Question 15

Why is trabecular bone more susceptible to loss in osteoporosis?

Answer 15

• higher turnover than cortical
• greater SA
• in locations that has to respond to new stresses

Question 16

What are the primary areas impacted by osteoporosis?

Answer 16

• vertebral bodies

- femoral neck

Question 17

What are the different possible treatments for osteoporosis?

Answer 17

• calcium supplements
• vitamin D
• hormone replacement therapy
• selective oestrogen receptor modulator (raloxifene)
• bisphosphonates
• teriparatide
• denosumab

Question 18

How do calcium supplements work?

Answer 18

• reduce negative calcium balance

Question 19

How does HRT work?

Answer 19

• first choice in peri-menopausal women

- lasts 5 years

Question 20

How does raloxifene work?

Answer 20

• only works on bone which is an advantage

- anti-oestrogenic for uterus and breast

Question 21

How do bisphosphonates work?

Answer 21

• first line treatment
• drug absorbed onto bone surface and incorporated into matrix
• ends up precipitated onto surface
• osteoclast clamps itself down
• = osteoclast apoptosis
• also signals to osteoblasts to produce new bone and decrease expression of RANKL

Question 22

What are the complications of bisphosphonates?

Answer 22

• giant osteoclasts (accumulate)
• osteonecrosis (dead bone)
• atypical fractures (sub trochanteric and femoral shaft, old osteocytes signal for remodelling)
• SO prevent by not taking for a few months

Question 23

How does teriparatide work?

Answer 23

• recombinant PTH

- intermittent exposure increases osteoblast activity vs. osteoclast

Question 24

How does denosumab work?

Answer 24

• monoclonal antibody
• binds to RANKL acting as decoy receptor
• stops RANKL signalling to osteoclasts to differentiate
• subcutaneous injection every 6 months
• inhibits formation of osteoclasts

Question 25

How does osteomalacia occur?

Answer 25

• insufficient calcium and phosphate to mineralise new bone osteoid
• = softer bones, bend/fracture more easily
• vitamin D deficiency causes

Question 26

What does tetracycline labelling show in osteomalacia?

Answer 26

• low bone turnover state
• some areas no labelling
• some diffuse labelling
• some single line

Question 27

What is the treatment for osteomalacia?

Answer 27

• vitamin D supplements
• dietary (increase calcium)
• sun/UV exposure

Question 28

What foods contain calcium?

Answer 28

• milk, bread, beans, pulses

- dried fruit, green leafy vegetables

Question 29

Who is at risk of Paget’s disease?

Answer 29

• mostly over 80 years
• some 50-80
• otherwise rare

Question 30

What are the 3 phases of Paget’s?

Answer 30

1) Initially increases rate of bone resorption (lots of giant osteoclasts)
2) compensatory phase/proliferative (increased bone formation and accelerated disorganised deposition)
3) sclerotic (woven bone not properly replaced/remodelled and irregular thickened trabeculae)

Question 31

Which bones are affected by Paget’s?

Answer 31

• pelvis
• femur
• vertebra
• skull
• tibia
  (not symmetrical)

Question 32

What is a later complication of Paget’s?

Answer 32

• osteosarcoma

Question 33

What is osteosarcoma?

Answer 33

• most malignant of cancers
• usually in long bone
• often near knee
• can spread rapidly
• to prevent spread = remove affected bone part/limb amputation

Question 34

How is Paget’s treated?

Answer 34

• bisphonate (oral 2-6 months then IV single infusion)
• calcium and vitamin D
• pain management
• surgery

Question 35

What is sclerostosis?

Answer 35

• lack of sclerostin which normally inhibits osteoblasts when osteocytes are healthy
• autosomal recessive
• Van Buchem syndrome

Question 36

How does sclerostosis present?

Answer 36

• excessive height
• resistance to fracture
• endosteal hyperostosis