Osteoporosis

Question 1

Describe the relationship between RANKL, RANK, and OPG in the regulation of osteoclast activation

Answer 1

• activation of osteoclasts requires signaling from osteoblasts
• RANKL expressed on osteoblasts in response to PTH–>RANKL on blasts activate RANK on clast precursors–>promotes differentiation
• OPG is a decoy receptor that bind to RANKL and prevents it from activating RANK

Question 2

how does estrogen inhibit osteoclast function?

Answer 2

increases OPG production

Question 3

Describe the relationship between circulating calcium levels and the release/production of active vitamin D, parathyroid hormone, and calcitonin

Answer 3

Decreased blood calcium–>PTH activated and increases osteoclast activity, increases Ca absorption in kidney, and increases activation of vit D (per kidney), leading to increased intestinal Ca absorption

-calcitonin is a peptide from C cells in thyroid–>when Ca blood levels are high, it decreases plasma calcium by inhibiting osteoclasts–>decreases resorption of bone (salmon calcitonin is used for this effect)

Question 4

Describe the regulation of vitamin D production and its actions on circulating calcium levels and bone

Answer 4

(PTH helps regulate vit D)
chol is skin +UV–>1st vit D version–>liver adds 25-OH–>kidney adds another OH per PTH–>fully activated vit D–>inc. intestinal absorption of Ca

Question 5

Describe the regulation of parathyroid hormone release and its actions on circulating calcium levels and bone

Answer 5

high blood Ca levels–>Ca binds to GPCR–>blocks mRNA and translation and inhibition of PTH secretion
-low blood ca–>inhibition removed from GPCR–>PTH released–> increases osteoclast activity, increases Ca absorption in kidney, increased vit D activation for intestinal absorption

Question 6

What are the RFs for osteoporosis?

Understand that osteoporosis is a silent disease that may require prophylactic treatment in high risk individuals

Answer 6

1. decreased estrogen: woman
2. Ca or Vit D deficiency
3. chronic glucocorticoid def.
4. age–> > 50

Question 7

Distinguish between medications that are anti-resorptive and anabolic

Answer 7

anti-resorptive: HRT, SERMs, salmon calcitonin, bisphosphonates, denosumab

anabolics: teriparatide

Question 8

which drug is no longer recommended as a first line treatment for management in osteoporosis in post-menopausal women?

Answer 8

HRT

Question 9

which drug is 1st line treatment of osteoporosis?

Answer 9

bisphosphonates

Question 10

what side effect of bisphosphonates is extremely rare in pts taking it for osteoporosis. The risk is higher in what patient population?

Answer 10

osteonecrosis of the jaw

cancer pts taking high dose bisphosphonates for their tx

Question 11

what is bisphosphonates major side effect?

Answer 11

GI and esophageal irritation