Bone metabolism L5 Flashcards
What percentage of the bone is organic
40%
Organic components of bone (2)
Type 1 collagen
non-collagenous proteins
Inorganic components of bone (1)
calcium hydroxyapatite
What percentage of bone is inorganic
60%
other word for trabecular bone
cancellous bone/ spongy bone
osteoclasts have multiple
nuclei
Osteoclasts formed from
fusion of monocytes haematopoietic
Where do osteoclasts sit
Adhere strongly on the bone surface
Osteoblasts have how many nuclei
1
mononuclear cell
What are they called when osteoblasts burry themselves alive in the new bone matrix they form
osteocytes
How is new bone first laid down
non-mineralised osteoid
If formation is equal to resorption –>
coupled remodelling
osteoid=
type 1 collagen and proteins
How much bone do we lose in space per month
1%
Mechanisms involved in bone growth and remodelling
PTH
Vitamin D3
Calcitonin
approx how much calcium in the body
1000g
recommended daily calicum intake
1000mg
percentage of calcium in skeleton
99%
Serum conc of calcium
2.25-2.6
Three fractions of calcium in serum
ionised (50%) Protein bound (40%) Complexed calcium (10%)
Ca2+ levels maintained by
PTH
Vitamin D
Calcitonin
Approx how much phosphate in human body
600g
Percentage phosphate in skeleton
85%
major ionic species of phosphate in serum
HPO4-2
three fractions of inorganic phosphate
ionised (55%) Protein bound (10%) Complexed phosphate (35%)
What is phosphate primarily regulated by
PTH
Main route of Vitamin D into body
7-dehydrocholesterol by UV light
1st activation of vitamin D
25-hydroxylation in the liver produces 25(OH)D3
what is 25(OH)D3 ?
The main circulating metabolite of vitamin D with little biological activity
2nd activation of vitamin D
1-hydroxylation in the kidney produces 1,25 (OH)2 vitamin D3
What is 1,25(OH2)vitamin D3
the principal hormonal form of vitamin D and is responsible for most of its biological actions
What does PTH do in regards to vitamin D
it stimulates and regulates 1,25(OH2) vitamin D3 production
What inhibits vitamin D
elevated serum Ca and P
(3) actions of 1,25 (OH2) vitamin D3
- increases calcium and phosphate absorption from the intestines
- Mobilises calcium and phosphate from bone
- Induces marrow monocytes to differentiate into osteoclasts to stimulate bone resorption.
what does 24-hydroxylation effect
25(OH)D3 and 1,25(OH2)D3 catabolism
what is PTH
parathyroid hormone
What structure does PTH have
small polypeptide
84 amino acids
Where and why is PTH secreted?
by the parathyroid gland in response to low plasma Ca2+ levels
Effect of high PTH levels
osteoclastic bone resorption
mobilising calcium
effect of Intermediate-low PTH levels
osteoblastic bone formation
What is the main way through which PTH communicates its effect
predominatly through osteoblasts which communicate with osteoclasts
Other general effects of PTH (3)
- decreased renal calcium excretion
- Increases renal production of 1,25(OH2) D3
- increases blood calcium
What is PTHrp
parathyroid hormone- related protein
What is increased PTHrp production linked with
malignant tumours
What does PTHrp do?
major mediator of hypercalcaemia (raised calcium)
Calcitonin–>
Reduces bone resorption by activating calcitonin receptors expressed by osteoclasts.
Decreased Ca2+ induces–>
PTH secretion
Increased Ca2+ induces
Calcitonin secretion
Oestrogen–>
reduces bone resorption by inhibiting osteoclastogenesis and inhibiting osteoclast function
What expresses oestrogen receptors
osteoblasts and osteoclasts
Androgen–>
decreases bone resorption by directly targeting osteoclasts
Is Androgen used in men or women
Both
Hypercalcaemia=
elevated calcium in circulation
Causes of hypercalcaemia
primary hyperparathyroidism Malignancy Hyperthyroidism immobilisation vitamin D toxicity
Primary hyperparathyroidism=
hypercalcaemic state caused by excessive secretion of PTH
Main cause= solitary adenoma
Symptoms of hyperparathyroidism
at skeletal sites osteitis fibres cystica
What is osteitis fibres cystica
replacement of bone with fibrous tissue
What area of skeleton does hyperparathyroidism effect most (2)
Skull and phalanges
causes of hypocalcaemia
renal failure
vitamin D deficiency
prematurity
what is secondary hyperparathyroidism
physiological response to hypocalcaemia
Cause of osteomalacia and rickets
vitamin D deficiency
malabsorption
renal disease
Lack of sunlight
Features of osteomalacia
diffuse bone pain localised bone pain around hips Muscle weakness Decreased mineralisation ect
Osteoporosis =
net loss of bone mass resorption> formation.
Osteoporosis most common in
post-menopausal women
Osteoporosis treatment
Calcium supplementation hormone replacement therapy bisphosphonates calcitonin Selective estrogen-receptors modulators (SERMs)
Three bisphosphonates
Alendronate, residronate, etridronate
What cells secret calcium
C cells in thyroid
What cells secret PTH
Chief cells
PTH increases calcium travelling to blood from
intestine
bone
kidney
