Bone Metabolism Flashcards
What is lamellar bone?
It’s mature bone, either of the cortical or trabecular form.
What is woven bone?
Immature bone that is formed in response to damage or may be pathological
What percentage of total bone mass is made up of cancellous/trabecular bone?
20%
What percentage of total bone mass is made up of cortical/compact bone?
80%
How does the collagen organisation differ between lamellar and woven bone?
In woven bone there is random collagen organisation which makes it mechanically weak in comparison to the ordered structure of lamellar bone.
Describe the composition of the extracellular matrix of bone
• 35-40% organic o Type 1 collagen for tensile strength o Proteoglycans for compressive strength o Growth factors, cytokines and osteoid • 60% inorganic o Contains a large amount of calcium hydroxyapatite on top of the collagen fibres • 5% consists solely of water.
What type of collagen is ordinarily present in bone?
Type 1
What are the main organic components of bone matrix?
Type 1 collagen, proteoglycans, growth factors, cytokines and osteoid
What is the main inorganic component of bone matrix?
Calcium hydroxyapatite (on top of collagen fibres)
Which cells secrete sclerostin?
Osteocytes
What is the function of sclerostin?
Inhibits bone formation by osteoblasts
What is the function of osteocytes?
To sense mechanical stress on bone by detecting death and a need for remodelling; in response to stress stop secreting sclerostin (due to action of PTH)
How does calcitonin affect sclerostin production by osteocytes?
Upregulates secretion and therefore inhibits bone formation by osteoblasts
How does PTH affect sclerostin production by osteocytes?
Inhibits sclerostin production in response to mechanical stress; this signals for osteoblasts to deposit bone
What are osteoblasts?
A form of mesenchymal cell which replace (deposit) more bone matrix (osteoid)
What are osteoclasts?
Macrophage-like cells from red bone marrow that work to dissolve and digest the bone matrix
What are osteoprogenitor cells?
Bone marrow stem cells.
What are canaliculi?
These allow chemical communication between osteocytes to decide whether remodelling is required in response to stress
What are osteocyte lacunae?
The ‘pit’ or ‘lake’ in which individual osteocytes sit
Outline the process of bone remodelling
- Osteoclast attached to bone to form a leak-proof seal
- Protein-digesting enzymes break down the collagen fibres
- Acid secreted dissolves the bone minerals
- Bone proteins and minerals (mainly Ca2+) to cross the osteoclast and exitinto the interstitial fluid
- Osteoblasts then fill the lacuna with osteoid, and the osteoid is mineralised approximately a week later
What does serum calcium depend upon?
Intestinal absorption, renal excretion and skeletal mobilisation
What is normal serum calcium?
2.2-2.6mmol/L (8.5-10.5mg/dL)
What is the recommended daily intake of calcium?
500-1,300mg
How is calcium excreted?
Calcium is excreted by kidneys (~200mg/day) and gut (~600-800mg/day in stools)
What are normal serum phosphate levels?
0.8-1.5mmol/L
Which hormones are involved in ‘bone maintenance’?
Vitamin D, oestrogen, progesterone
Which hormones are involved with increased bone degradation?
Calcitonin, PTH, glucocorticoids (steroids)
Outline the effect of PTH on bone metabolism
Low serum calcium stimulates PTH production which then promotes calcium reabsorption from kidney (and phosphate excretion), calcium resorption (osteoblasts PTH receptor –> RANKL –> RANK receptor on osteoclasts) and increased 1,25 dihydroxyvitamin D production (increases calcium absorption from gut)
Outline the effect of calcitonin on bone metabolism
Released when serum calcium is just within the normal range. Causes inhibition of osteoclasts, increases calcium excretion from kidney and inhibits calcium absorption in the gut.
Outline the effect of vitamin D on bone metabolism
Increases calcium absorption in the gut, and increases bone resorption (activates RANKL –> more osteoclast differentiation)
What is the active form of vitamin D?
1,25 dihydroxyvitamin D
Outline the effect of oestrogen on bone metabolism?
Increases calcium absorption from the gut (increases production of 1,25 dihydroxyvitamin D) and inhibits osteoclasts
Outline the effect of glucocorticoids on bone metabolism
Decreases calcium absorption in the gut and increases bone resorption and decreases bone formation (prolonged steroid use can therefore lead to osteoporosis)
Outline the effect of progesterone on bone metabolism
Adding progesterone cream in osteoporosis therapy has shown to increase bone density (mechanism unknown)
What is the role of calcitonin on bone metabolism?
Prevents bone formation by osteoblasts; it up regulates the production of sclerostin by osteocytes
What stimulates the release of PTH?
Low serum calcium levels
What stimulates the secretion of calcitonin?
Serum calcium levels just within the normal range (2.25mmol/L)
What is the normal daily requirement of vitamin D?
400IU/day
Where is 1,25 dihydroxyvitamin D formed?
Kidney, and it’s the active form of vitamin D.
How may vitamin D aid in the production of mineralised bone matrix?
By producing pro-collagen type 1 anad alkaline phosphatase vesicles
