Secondary Hormonal Regulators of Bone Mineral Homeostasis

Question 1

Which are the Secondary Hormonal Regulators of Bone Mineral Homeostasis?

Answer 1

Calcitonin
Glucocorticoids
Estrogens

Question 2

What are the characteristics of Calcitonin?

Answer 2

● Has opposite effects of PTH (want to keep Ca in bone) or excrete Ca in the urine in order to lower
serum Ca levels
● Acts directly on osteoclast calcitonin receptors to produce a rapid and profound decrease in ruffled
border surface on the osteoclast thus decreasing resorption
● Secreted by C­cells of thyroid gland (these cells lie between the follicular cells which synthesize T3 and T4)
● Available from salmon “ Calcimar® ”
o Salmon calcitonin has longer DOA (~60 min) and is 50 X more potent than human calcitonin
● In bone-Inhibits bone resorption by action on osteoclasts described above
● In kidney :
● Uses:
o “Pharmacological” doses: increases excretion of PO 4 and increases Ca excretion (opposite to the actions of vitamin D).
o Physiological doses: increases excretion of PO 4 and decreases renal excretion of Ca
Treatment of:
o Hypercalcemia (but bisphosphonates are the preferred agents)
o Paget’s disease (s.c .50 units 3 times a week, after initial therapy at 100 units/day s.c.)
Pagets disease = Uncontrolled OC activity = increased bone resorption = hypercalcemia and disorganized hyper­remodeling of bone
o Osteoporosis

Question 3

What are the characteristics of Glucocorticoids?

Answer 3

● MOA:
o Antagonize Vit D­ stimulated intestinal transport of calcium
o Stimulate renal Ca excretion
o Increase PTH ­stimulated bone resorption
o Block bone formation (inhibit collagen formation; several other mechanisms)
o Augment osteoclast recruitment
o Decreases OPG release
o Inhibit the release of growth hormone (GH) – chronic high levels or at “pharmacological” doses
● Low physiological levels of cortisol are actually needed for osteoblast differentiation, nonetheless the net effects of glucocorticoids, especially high serum levels (“pharmacological doses”) of glucocorticoids favor osteclastic actions and therefore lead to increased bone break­down (also remember that chronic high serum levels of cortisol decrease the release of growth hormone (GH) from the pituitary).

Question 4

What are the characteristics of Estrogens?

Answer 4

● Have opposite effects of glucocorticoids on bone
● *Estrogen causes apoptosis of OC’s
● Estrogens increase Vit D binding globulin to protect Vit D from degradation
● Estrogens decrease the release of certain cytokines (e.g. IL­1, IL­6, TNF) from osteoblasts that normally recruit osteoclasts and aid in activating osteoclasts.
● Estrogens increase the release of the decoy molecule OPG which can bind RANK ligand located on the outer membrane of osteoblasts (and thus prevent the activation of osteoclasts by preventing RANK ligand from binding to RANK (the receptor) on osteoclasts.
● Stimulate osteoblast proliferation