calcium and bone

Question 1

definition of vitamin D deficiency

Answer 1

lack of minerlisation in bone

Question 2

effect of vitamin D deficiency

Answer 2

softening of bone, bone deformaties and pain; severe proximal myopathy

Question 3

vitamin D deficiency in children

Answer 3

rickets (bowing of legs)

Question 4

vitamin D deficiency in adults

Answer 4

osteomalacia

Question 5

features of primary hyperparathyroidism

Answer 5

high Ca2+, low PO43-, high (unsuppressed PTH) as autonomous

Question 6

treatment of primary hyperparathyroidism

Answer 6

parathyroidectomy

Question 7

features of secondary hyperparathyroidism

Answer 7

low Ca2+ as vitamin D deficiency, so PTH increases to try to normalise serum Ca2+

Question 8

4 biochemical findings in vitamin D deficiency

Answer 8

plasma [25(OH)D3] usually low (don’t measure active vitamin D as too difficult), plasma [Ca2+] low, plasma [PO43-] low, [PTH] high (secondary hyperparathyroidism)

Question 9

why is plasma [PO43-] low in vitamin D deficiency

Answer 9

reduced gut absorption

Question 10

when might plasma [Ca2+] be normal in vitamin D deficiency

Answer 10

if secondary hyperparathyroidism has developed (high PTH)

Question 11

treatment of vitamin D deficiency in patients with normal renal function

Answer 11

give 25 hydroxy vitamin D (25 (OH) D) -> patient converts to 1,25 dihydroxy vitamin D (1,25 (OH)2 D) via 1a hydroxylase; ergocalciferol and cholecalciferol

Question 12

what is ergocalciferol

Answer 12

25 hydroxy vitamin D2

Question 13

what is cholecalciferol

Answer 13

25 hydroxy vitamin D3

Question 14

treatment of vitamin D deficiency in patients with renal failure

Answer 14

inadequate 1a hydroxylation, so can’t activate 25 hydroxyl vitamin D preparations to form active vitamin D, so must give alfacalcidol (1a hydroxycholecalciferol which allows active vitamin D)

Question 15

what can vitamin D excess (intoxication) lead to and why

Answer 15

hypercalcaemia and hypercalcuria due to increased intestinal absorption of Ca2+

Question 16

2 causes of vitamin D excess

Answer 16

excessive treatment with active metabolites of vitamin D (e.g. alfacalcidol), granulomatous diseases

Question 17

examples of granulomatous diseases which cause vitamin D excess

Answer 17

sarcoidosis, leprosy, TB

Question 18

how do granulomatous diseases cause vitamin D excess

Answer 18

macrophages produce 1a hydroxylase to convert 25(OH) D to active metabolite 1,25 (OH)2 D

Question 19

how much of body Ca2+ is stored in bone

Answer 19

> 95%

Question 20

what consists of 35% of bone mass

Answer 20

organic components (osteoid unmineralised bone), mostly made up of type 1 collagen fibres (95%)

Question 21

what consists of other 65% of bone mass

Answer 21

inorganic mineral component (calcium hydroxyapatite crystals fill space between collagen fibrils)

Question 22

bone remodelling: what do osteoblasts do

Answer 22

synthesise osteoid and participate in minerasilation/calcification of osteoid (bone formation)

Question 23

bone remodelling: what do osteoclasts do

Answer 23

release lysosomal enzymes which break down bone (bone resorption)

Question 24

how do osteoclasts differentiate

Answer 24

RANKL expressed on osteoblast surface -> binds to RANK-R on osteoclast precursor to stimulate osteoclast formation and activity

Question 25

what 2 other receptors do osteoblasts express as well as RANK-R and why

Answer 25

PTH and calcitriol (1,25 (OH)2 vit D) to regulate balance between bone formation and resorption

Question 26

2 sections of bone and where present

Answer 26

cortical on outside, trabecular on inside

Question 27

what is cortical bone

Answer 27

hard

Question 28

what is trabecular bone

Answer 28

network of bony bars, making it spongy

Question 29

pattern and contents of bone sections, and consequence

Answer 29

lamellar (collagen fibrils laid down in alternating orientations so is mechanically strong)

Question 30

characteristics of woven bone

Answer 30

disorganised collagen fibrils so weaker

Question 31

effect of vitamin D deficiency on bone

Answer 31

inadequate materialisation of newly formed bone matrix (osteoid)

Question 32

name of vitamin D deficiency effect on bone in children

Answer 32

rickets

Question 33

what does rickets affect

Answer 33

cartilage of epiphysial growth plates and bone

Question 34

consequences of rickets

Answer 34

skeletal abnormalities (e.g. bowing of legs) and pain, growth retardation, increased fracture risk

Question 35

name of vitamin D deficiency effect on bone in adults

Answer 35

osteomalacia

Question 36

what does osteomalacia affect and when

Answer 36

bone after epiphysial closure

Question 37

consequences of osteomalacia

Answer 37

skeletal pain, increased fracture risk, proximal myopathy

Question 38

why does vitamin D deficiency increase fracture risk

Answer 38

normal stresses on abnormal bone cause insufficiency (stress) fractures (looser zones)

Question 39

what sign when walking is typical of vitamin D deficiency

Answer 39

waddling gait

Question 40

what causes primary hyperparathyroidism and consequence

Answer 40

problem with gland i.e. adenoma of parathyroids, so excess autonomous release PTH so high plasma [Ca2+] (by increased bone resorption, increased kidney absorption, make vitamin D active); associated with hypercalcaemia and normal kidney function

Question 41

what causes secondary hyperparathyroidism and consequence

Answer 41

renal failure (when can’t a-hydroxylate to form active vitamin D) or vitamin D deficiency, so low or normal plasma [Ca2+] and high PTH (normal physiological response)

Question 42

what causes tertiary hyperparathyroidism and consequence

Answer 42

chronic kidney failure so can’t make active vitamin D, so get secondary hyperparathyroidism with excess PTH secretion; overtime, autonomous parathyroids as excess PTH so high plasma [Ca2+]; associated with hypercalcaemia

Question 43

how does renal failure cause vascular calcification

Answer 43

decreased renal function -> low PO43- excretion -> high plasma [PO43-]

Question 44

how does renal failure cause hypocalcaemia (2 pathways)

Answer 44

decreased renal function -> low calcitriol -> low Ca2+ absorption; decreased renal function -> low PO43- excretion -> high plasma [PO43-]

Question 45

how does hypocalcaemia lead to osteitis fibrosa cystica

Answer 45

decreases bone mineralisation and increases [PTH], increasing bone resorption

Question 46

what is osteitis fibrosa cystica and cause

Answer 46

rare hyperparathyroid bone disease, caused by excess osteoclastic bone resorption secondary to high PTH

Question 47

how does osteitis fibrosa cystica show on x-ray

Answer 47

“brown tumours” (radiolucent bone lesions) due to excess PTH and therefore osteoclast resorption to liberate Ca2+

Question 48

3 ways osteitis fibrosa cystica is treated

Answer 48

must reduce hyperphosphataemia, alphacalcidol (calcitriol analogues but active, as cannot activate it themselves as kidney dysfunction), parathyroidectomy in tertiary hyperparathyroidism (indicated for hypercalcaemia and/or hyperparathyroid bone disease)

Question 49

how is hyperphosphataemia in osteitis fibrosa cystica treated

Answer 49

low phosphate diet, phosphate binders to reduce GI phosphate absorption