calcium and bone Flashcards
vitamin D: recall the synthesis of vitamin D, the role of vitamin D and its metabolites in calcium regulation; recall the clinical features of vitamin D deficiency, including predisposing factors; recall how renal dysfunction leads to bone disease; explain the mechanism and effects of vitamin D excess
definition of vitamin D deficiency
lack of minerlisation in bone
effect of vitamin D deficiency
softening of bone, bone deformaties and pain; severe proximal myopathy
vitamin D deficiency in children
rickets (bowing of legs)
vitamin D deficiency in adults
osteomalacia
features of primary hyperparathyroidism
high Ca2+, low PO43-, high (unsuppressed PTH) as autonomous
treatment of primary hyperparathyroidism
parathyroidectomy
features of secondary hyperparathyroidism
low Ca2+ as vitamin D deficiency, so PTH increases to try to normalise serum Ca2+
4 biochemical findings in vitamin D deficiency
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)
why is plasma [PO43-] low in vitamin D deficiency
reduced gut absorption
when might plasma [Ca2+] be normal in vitamin D deficiency
if secondary hyperparathyroidism has developed (high PTH)
treatment of vitamin D deficiency in patients with normal renal function
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
what is ergocalciferol
25 hydroxy vitamin D2
what is cholecalciferol
25 hydroxy vitamin D3
treatment of vitamin D deficiency in patients with renal failure
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)
what can vitamin D excess (intoxication) lead to and why
hypercalcaemia and hypercalcuria due to increased intestinal absorption of Ca2+
2 causes of vitamin D excess
excessive treatment with active metabolites of vitamin D (e.g. alfacalcidol), granulomatous diseases
examples of granulomatous diseases which cause vitamin D excess
sarcoidosis, leprosy, TB
how do granulomatous diseases cause vitamin D excess
macrophages produce 1a hydroxylase to convert 25(OH) D to active metabolite 1,25 (OH)2 D
how much of body Ca2+ is stored in bone
> 95%
what consists of 35% of bone mass
organic components (osteoid unmineralised bone), mostly made up of type 1 collagen fibres (95%)
what consists of other 65% of bone mass
inorganic mineral component (calcium hydroxyapatite crystals fill space between collagen fibrils)
bone remodelling: what do osteoblasts do
synthesise osteoid and participate in minerasilation/calcification of osteoid (bone formation)
bone remodelling: what do osteoclasts do
release lysosomal enzymes which break down bone (bone resorption)
how do osteoclasts differentiate
RANKL expressed on osteoblast surface -> binds to RANK-R on osteoclast precursor to stimulate osteoclast formation and activity
what 2 other receptors do osteoblasts express as well as RANK-R and why
PTH and calcitriol (1,25 (OH)2 vit D) to regulate balance between bone formation and resorption
2 sections of bone and where present
cortical on outside, trabecular on inside
what is cortical bone
hard
what is trabecular bone
network of bony bars, making it spongy
pattern and contents of bone sections, and consequence
lamellar (collagen fibrils laid down in alternating orientations so is mechanically strong)
characteristics of woven bone
disorganised collagen fibrils so weaker
effect of vitamin D deficiency on bone
inadequate materialisation of newly formed bone matrix (osteoid)
name of vitamin D deficiency effect on bone in children
rickets
what does rickets affect
cartilage of epiphysial growth plates and bone
consequences of rickets
skeletal abnormalities (e.g. bowing of legs) and pain, growth retardation, increased fracture risk
name of vitamin D deficiency effect on bone in adults
osteomalacia
what does osteomalacia affect and when
bone after epiphysial closure
consequences of osteomalacia
skeletal pain, increased fracture risk, proximal myopathy
why does vitamin D deficiency increase fracture risk
normal stresses on abnormal bone cause insufficiency (stress) fractures (looser zones)
what sign when walking is typical of vitamin D deficiency
waddling gait
what causes primary hyperparathyroidism and consequence
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
what causes secondary hyperparathyroidism and consequence
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)
what causes tertiary hyperparathyroidism and consequence
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
how does renal failure cause vascular calcification
decreased renal function -> low PO43- excretion -> high plasma [PO43-]
how does renal failure cause hypocalcaemia (2 pathways)
decreased renal function -> low calcitriol -> low Ca2+ absorption; decreased renal function -> low PO43- excretion -> high plasma [PO43-]
how does hypocalcaemia lead to osteitis fibrosa cystica
decreases bone mineralisation and increases [PTH], increasing bone resorption
what is osteitis fibrosa cystica and cause
rare hyperparathyroid bone disease, caused by excess osteoclastic bone resorption secondary to high PTH
how does osteitis fibrosa cystica show on x-ray
“brown tumours” (radiolucent bone lesions) due to excess PTH and therefore osteoclast resorption to liberate Ca2+
3 ways osteitis fibrosa cystica is treated
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)
how is hyperphosphataemia in osteitis fibrosa cystica treated
low phosphate diet, phosphate binders to reduce GI phosphate absorption
