Osteoporosis Flashcards
What cells secrete parathyroid hormone? What does it do?
Chief cells of parathyroid gland.
Acts to increase the concentration of calcium in the blood
What is calcitonin and where is it produced?
Parafollicular C cells of the thyroid.
Prevents hypercalcaemia by directly inhibiting osteoclast activity, thereby reducing calcium mobilization and release from the skeleton.
Draw a diagram to explain the release of PTH and its interaction with calcium
See notes: Secretion of parathyroid hormone occurs in response to low serum calcium through negative feedback. Calcium-sensing receptors located on parathyroid cells are activated when calcium is low. Also stimulated by an increase in serum phosphate (increased phosphate causes formation of a complex with serum calcium, forming calcium phosphate, which reduces stimulation of calcium sensitive receptors, triggering release of PTH)
What effect does PTH have?
It activates 25-hydroxyvitamin D-1 alpha-hydroxylase, the enzyme that converts 25-hydroxyvitamin D3 to the active form of vitamin D (1,25(OH)2D3), resulting in a marked elevation of plasma levels of vitamin D (calcitriol).
PTH also stimulates the renal absorption of calcium and inhibits the reabsorption of phosphate, causing phosphate diuresis.
What effect does Vitamin D have?
1,25(OH)2D3 increases dietary calcium absorption in the small intestine and increases osteoblast activity, resulting in stimulation of osteoclast-mediated resorption.
Vit D plays an important role in differentiation of the promyelocyte to the osteoclast precursor to mature osteoclast, through osteoblast generated osteoclast differentiation factor.
These effects of vitamin D provide bone calcium for the plasma and also cause bone resorption coupled with formation as part of the bone remodeling process.
Thus, vitamin D strengthens bone and repairs microfractures that may have occurred during bone usage.
The result is calcium mobilization by the skeleton into the plasma compartment by the action of vitamin D hormone and PTH.
Where in the kidney do PTH and vit D work and what do they do?
In the distal renal tubule they act in concert to produce virtually complete reabsorption of the filtered load of calcium
Why is phosphorus important?
Phosphate accounts for more than 50% of bone mineral mass.
Osteoblasts are unique among all other cell types in that they create a mineral trap (calcium phosphate) in bone matrix after it has been deposited.
This trap depletes the ECF around the osteoblast of both calcium and phosphorus, and if the local concentration of phosphate is too low, osteoblasts become phosphorus starved.
How is phosphate homeostasis maintained?
Intestinal absorption, renal excretion, balance of phosphate exchange in and out of cells and hormonal regulation.
What effect does PT have on phosphate excretion?
It promotes it (through the inhibition of brush border membrane Na-Pi cotransport activity)
What effect does Vit D or Insulin have on phosphate excretion?
It is decreased. Phosphate is reabsorbed through stimulation of brush border membrane Na-Pi cotransport and inhibition of the phophaturic action of PTH.
Vit D also regulates intestinal absorption by stimulating the same transporter in the upper SI
What effect does Vit D deficiency have on Pi?
Increased Pi renal excretion and decreased intesting Pi and calcium absorption, resulting in a severe loss of both calcium and phosphate from bone because of enhanced PTH activty resuling in loss of bone mineral and osteomalacia
This is in contrast to osteoporosis by calcium defiency
What is the mechanism by which Vit D induces bone resorption?
There is a Vit D receptor expressed in osteoblasts and regulates the expression of several genes in the this cell. These genes include bone matrix proetins osteocalcin and osteopontin which are upregulated by vit d (in addition to type 1 collaagen which is repressed).
Vit D and PTH induce the expression of RANK on osteoclast proenitors and mature osteoclasts which promotes osteoclast differentiation and increases osteoclast activity
What is the role of Osteoblasts?
BLASTS BUILD
Synthesise and secrete the organic matrix.
Active osteoblasts are found on the surface of newly forming bone.
As osteoblast secretes matrix, which is then mineralized, the cell becomes an osteocyte
What is the role of Osteoclasts?
CLASTS CLEAVE
Carry out resorption of bone.
RANK ligand is expressed on the surface of osteoblast progenitors. RANK ligand binds to the RANK receptor on osteoclast progenitors, stimulating osteoclast differentiation and activation.
Both PTH and vitamin D increase osteoclast number and activity, whereas oestrogen decreases osteoclast number and activity by this indirect mechanism.
Calcitonin, in contrast, binds to its receptor on the basal surface of osteoclasts and directly inhibits osteoclast function
Describe the basic model of bone remodeling
The cycle of bone remodeling is carried out by the basic multicellular unit (BMU), which consists of a group of osteoclasts and osteoblasts. In cortical bone, the BMUs tunnel through the tissue, whereas in cancellous bone, they move across the trabecular surface. The process of bone remodeling is initiated by contraction of the lining cells and the recruitment of osteoclast precursors. These precursors fuse to form multinucleated, active osteoclasts that mediate bone resorption. Osteoclasts adhere to bone and subsequently remove it by acidification and proteolytic digestion. As the BMU advances, osteoclasts leave the resorption site and osteoblasts move in to cover the excavated area and begin the process of new bone formation by secreting osteoid, which eventually is mineralized into new bone. After osteoid mineralization, osteoblasts flatten and form a layer of lining cells over new bone.
What are the 3 subdivisions of pain producing structures in the back?
Mechanical, systemic and referred with mechanical being the most common (97%)
What are mechanical causes of pain in the back?
Mechanical is pain that is elicited with spinal motion and decreases with rest
Lumbar strain (disruption of muscle fibres at various points in belly or musculotendinous junction)/sprain (stretch of >1 spinal ligaments
Degenerative disc (increases flexion) and/or facets (increases extension)
Herniated nucleus pulposus (radiation to leg greater than back)
Spinal stenosis
Spondyloslysis and/or spondyloisthesis (lower back with occasional radiation to post thigh
Compresion fracture (may occur without hx- evaluate for osteoporosis etc)
What are the sytemic causes of pain in the back?
Much less common than mechanical but these warrant work up and referrel
Infection
Malignancy
Inflammatory spondyloarthropathy (ie ankylosing spondylitis)
Connective tissue disorder
What are the referred causes of pain in the back?
Aortic aneurysm Acute pancreatitis Acute pyelonephritis Renal colic Peptic ulcer disease UTI Billiary colic disease (problems with gall bladder)
What are some red flags with regards to back pain?
Age > 50 years History of cancer Temperature > 37.8°C Constant pain—day and night Weight loss Significant trauma Features of spondyloarthropathy Neurological deficit Drug or alcohol abuse Use of anticoagulants Use of corticosteroids No improvement over 1 month
Possible cauda-equina syndrome
• saddle anaesthesia
• recent onset bladder dysfunction
What does the nature of the pain indicate in back pain?
aching throbbing pain = inflammation, e.g. sacroiliitis
deep aching diffuse pain = referred pain, e.g. dysmenorrhoea
superficial steady diffuse pain = local pain, e.g. muscular strain
boring deep pain = bone disease, e.g. neoplasia, Paget’s disease
intense sharp or stabbing (superimposed on a dull ache) = radicular pain, e.g. sciatica
What functions does bone remodelling serve?
- To repair microdamage within the skeleton to maintain skeletal strength
- To supply calcium from the skeleton to maintain serum calcium
What are the acute demands for calcium?
What are the chronic demands for calcium?
Acute demands for calcium involve osteoclast-mediated resorption as well as calcium transport by osteocytes
Chronic demands for calcium result in secondary hyperparathyroidism, increased bone remodelling and overall loss of bone tissue.
What regulates bone remodelling?
Several circulating hormones including: oestrogens, androgens, Vit D and PTH and some locally produced growth factors (IGF-1, IGH2, TGF bea, interleukins)
