Bone Mineral Homeostasis Flashcards
How is the production of PTH regulated?
PTH is stimulated by phosphate but suppressed by calcium and vitamin D (1,25(OH)2D).
The production of FGF23 is stimulated by what?
Vitamin D and phosphate
How is the production of vitamin D regulated?
Vitamin D is stimulated by PTH and inhibited by FGF23.
Describe the mechanisms contributing to BMH?
PTH and Vitamin D increase the input of calcium and phosphorus from bone into the serum and stimulate bone formation. Vitamin D also increases calcium and phosphate absorption from the gut.
Vitamin D decreases excretion of calcium and phosphorus, whereas PTH reduces calcium but increases phosphorus excretion. FGF23 reduces serum phosphate.
What is the mechanism of parathyroid hormone?
Calcium limits production of PTH. It also has a vitamin D receptor and CYP27B1, that produces vitamin D, which also suppress PTH production.
What are pharmacokinetics and features of PTH
Clearance is rapid with a short half life. Most of the clearance occurs in the liver and kidney. PTH increases the activity of osteoclasts. PTH binds to RANKL which increases the number and activity of osteoclasts. PTH also inhibits production of sclerostin (a protein that blocks osteoblasts)
Where does vitamin D2 and D3 come from?
D2: comes only from the diet
D3: comes from the skin or the diet.
Describe the metabolism process of vitamin D
25-hydroxylation of vitamin D to 25-hydroxylationvitamin D. 25(OH)D is metabolized to the active hormone 1,25(OH)2D in the kidney.
What is the mechanism of action of vitamin D?
Its a potent stimulant of intestinal calcium and phosphate transport and bone resorption. It can also induce RANKL in osteoblasts.
What is the mechanism of action FIbroblast growth factor 23?
Inhibits production of vitamin D and phosphate reabsorption.
Explain the role of calcitonin in regulating BMH?
Secreted by the parafollicular cells of the mammalian thyroid. Acts on bone and kidney by lowering serum calcium and phosphate by reducing reabsorption.
What is the MOA of glucocorticoids and oestrogens in BMH?
Glucocorticoids: antagonize vitamin D intestinal calcium transport. Stimulating renal calcium excretion, bone formation is blocked.
Oestrogens: Reduces bone-resorbing action of PTH. Increases vitamin D due to decreased serum calcium and phosphate and increased PTH.
What is the MOA of bisphosphonates?
They inhibits vitamin D production and inhibits intestinal calcium transport. Also inhibits cell growth.
What should we watch out and counsel for in bisphosphonates?
High doses cause gastric and esophageal irritation. Take the drug with a full glass of water and sit upright for 30 minutes. Can also cause osteonecrosis.
What is the MOA of Denosumab?
It binds and prevents the action of RANKL. This will inhibit osteoclast formation and activity. Used for postmenopausal osteoporosis.
