189b/190b - Calcium, Parathyroid, Bone Flashcards
What is the most common cause of outpatint hypercalcemia?
Hyperparathyroidism
(Benign, solitary parathyroid adenoma = most common cause of primary hyperparathyroidism)
MOA: denosumab
What is it used for?
Human monoclonal antibody against RANKL
Tx for:
- Osteoporosis
- Bone metastases
List 3 things that promote Ca2+ excretion in the kidney
- Loop diuretics (Bumetanide, Ethacrynic acid, Furosemide, Torsemide)
- Dietary protein
- Glucocorticoids
Describe the pathogenesis fo Ricketts/Osteomalacia
Serum Ca2+ is preserved at the expense of bone
- Chronic low vitamin D
- -> Decreased Ca2+ absorption, reabsorption
- -> Low Ca2+
- -> PTH release
- -> Bone resorption, Ca2+ absorption/reabsorption, PO4 excretion
How does long term glucocorticoid use affect the bone?
List 5 mechanisms
Decreaed bone density -> osteoporosis
- Increased PTH (increased resorption)
- Increased renal excretion of calcium
- Decreased intestinal absorption of calcium
- Decreased gonadal steroids (less estrogen)
- Decreased protein synthesis in bone
What 3 deficiencies can lead to Ricketts/Osteomalacia?
- Vitamin D (most common)
- Ca2+
- Phosphate
What is the MOA of raloxifene?
What tissues are effected?
Raloxifine = SERM (selective estrogen response modulator)
- In the bone:
- Acts like estrogen = anti-resorptive
- In the mammary gland:
- Acts against estrogen = decreased breast cancer risk
Prevent and treat ostteoprorsis, reduce risk of bresat cancer
What is the major stimulus that causes osteoclast precursors to mature?
RANKL
- Secreted by osteoblasts (negative feedback!)
- Binds to RANK on osteoclasts and precursors
- Causes precursor differentiation
- Causes mature osteoclast activation
Describe the action of PTH on the bone if exposure is:
- Continuous:
- Intermittent:
- Continuous: Bone resorption
- Increases RANKL expression
- Intermittent: Bone formation
- Decreased osteoblast apoptosis
- Increased osteoblast differntiation
- Suppression of sclerostin
- Sclerostin inhibits wnt signaling
- Leads to activation of osteoblast differentiation and decreased apoptosis
Teriparatide = PTH analog that can be used as tx for osteoporosis
Which bones in the body are made up of trabecular bone?
Axial skeleton
Hips
Ankles
**These locations have the highest turnover => greatest risk of osteoporosis**
Long bones are appendicular bones (corticol bone)
Which bone is most susceptible to fracture in…
- Osteoporosis:
- Hyperparathyroidism:
- Osteoporosis: Trabecular bone (axial skeleton, hip, ankle)
- This is the higher turnover bone in general; most likely place where osteoblasts will fail to keep up
- Hyperparathyroidism: Cortical bone (long bones)
- Usually lower turnover, but in respose to PTH osteoclasts will burrow/tunnel into the bone (?)
What is the major director of intestinal Ca2+ absorption?
Vitamin D (calcitriol)
What cell secretes sclerostin?
What is the effect?
Osteocytes secrete sclerostin
- Inhibits wnt signaling -> decreased osteoblast differentiation
- Normally, wnt causes osteoblast differentiation
Inhibiting sclerostin -> increasing bone formation
How do you correct a serum calcium measurement?
Corrected calcium = total measured calcium + [(4-albumin) x 0.8]
Low albumin = low total serum calcium, but normal free (ionized) calcium
How does dietary protein intake affect calcium homeostasis?
Increased dietary protein = increased Ca2+ excretion
-> decreased serum Ca2+
What are the most common cells in bone?
Osteocytes
(Mature osteoblasts)