Bone formation Flashcards
(24 cards)
What is a KEY developmental difference between osteoclasts and osteoblasts?
Osteoblasts are derived from pluripotent mesenchymal cells known as “osteoprogenitor cells”
vs
Osteoclasts are derived from hematopoietic precursors… along the same lines as monocytes and macrophages thus think of them as “eaters of bone and multinucleated!”
What are two important ways that osteoblasts activate osteoclast differentiation from osteoclast precursor?
1) RANK ligand on osteoblast can bind RANK receptor on osteoclast
2) Osteoblasts (or stromal cells) secrete a cytokine known as “macrophage colony-stimulating factor” or M-CSF which induces hematopoietic stem cells to differentiate along the lines of a macrophage aka an osteoclast in this case
What acts to prevent over stimulation via osteoblasts RANK Ligand?
Osteoprotegrin acts like a soluble RANK receptor, so it binds up the RANK ligand so it doesn’t bind the real RANK receptor to differentiate more osteoclasts
What are osteocytes?
osteoblasts that got surrounded by newly deposited matrix… recall osteblasts deposit osteoid which needs to be mineralized by mostly calcium and phosphates to turn into “bone”
What is osteoporosis?
Clinical syndrome caused by a decrease in bone mass (or decreased bone mineral density)… However, the bone that does remain is histologically normal
How could menopause initiate osteoporosis?
Estrogen normally inhibits bone resorption by inhibiting osteoclasts. In the absence of estrogen there is increased IL-1, IL-6, and TNF levels which increase expression of both RANK receptor and RANK ligand resulting in increased osteoclast activity!
How do glucocorticoids induce osteoporosis?
they reduce osteoblast function and number
they decrease sex hormone production
they increase bone resorption (indirectly)
What are some secondary causes of osteoporosis?
- hypogonadism (in men and women)
- cushing’s syndrome (increases endogenous glucocorticoids)
- hyperparathyroidism
- multiple myeloma
- hypercalciuria (if kidneys are excreting too much Ca2+)
- osteomalacia (rickets in kids) via vitamin D deficiency
What is a common fracture in those with osteoporosis?
Vertebral body compression fracture! (also hip and wrist are also common)
What kind of imaging does I use to diagnose osteoporosis?
measure bone density via DEXA densitometry measurements
What criteria need to be met to diagnoz osteoporosis?
1) T-score more than 2.5 standard deviations below the mean for young normals
OR
2) fragility fracture regardless of T-score! (like breaking a bone by falling on ice)
What are 3 ways to PREVENT osteoporosis?
1) adequate calcium and vit D intake
2) avoid hypogonadism (estrogen in men and women is the important player here… recall its effects on to limit activity of osteoclasts)
3) weight bearing exercise
What are 5 treatments for osteoporosis?
1) Raloxifene (selective estrogen receptor modulator)
2) Bisphosphonates
3) Teriparatide (synthetic parathyroid hormone)
4) Denosumab
5) Calcitonin
What does Raloxifene work to help with osteoporosis?
only acts on certain estrogen receptors to increase bone density and decrease fracture risk without trophic effects on breast or uterus (does still worsen hot flashes and increase risk of thromboembolic disease)
How does bisphosphonates work?
Potent inhibitors of osteoclast activity! as well as induce osteoclast apoptosis!
Promotes significant increase in bone density and decreases fracture risk by about 50% (overuse can cause osteonecrosis of mandible)
Teriparatide (synthetic parathryoid hormone)
when used INTERMITTENTLY it acts as a potent stimulator of osteoblasts more than osteoclasts
increases bone mass and decreases fracture risk
Denosumab on osteoporosis
Monoclonal antibody against RANK-L thus is binds RANK-L and prevents it from binding the RANK receptor on the osteoclast. Thus it prevents osteoclast activation!
Calictonin on osteoporosis
Only slows bone less, doesn’t restore bone
What causes osteomalacia?
some form of Vit. D deficiency or resistance:
-inadequate sunlight
-malabsorption in GI
-renal failure
-vitamin D receptor defect
OR
phosphate deficiency
Why does a decreased Vitamin D deficiency even matter?
Without activated form of vitamin D, there is decreased absorption of calcium in the GI tract… as serum calcium starts to fall parathyroid hormone will increase and calcium will start to pull from the calcium reserve within bones
Elevated PTH levels will maintain serum calcium at the cost of phosphaturia causing hypophosphatemia and inadequate bone mineralization/decreased bone density
What is the treatment for osteomalacia?
NOT the same as osteoporosis! JUST treat underlying disorder by replacing calcium and phosphorous or Vit D…
What is Paget’s Disease?
Hyperactive osteoclasts… Osteoblasts try to keep up but they don’t lay down “good osteoid” so you end up with thick, abnormal bones
What are some clinical manifestations of pagets?
Bone PAIN and Bowing... Fractures Arthritis Osteosarcoma, giant cell tumors Excessive bleeding with orthopedic surgery (do to increased vascularization)
What is the best treatment for Pagets?
Bisphosphonates are very effective
