Nonhormonal Agents Affecting Bone Mineral Homeostasis

Question 1

Which are the Nonhormonal Agents Affecting Bone Mineral Homeostasis?

Answer 1

BISPHOSPHONATES (aka Diphosphonates ) - they are analogs of pyrophosphate
Mithramycin (aka Plicamycin)
Thiazides
Fluoride

Question 2

What are the characteristics of Mithramycin (aka Plicamycin)?

Answer 2

● Originally used as cancer therapy(used at 1/10 th the dose that is used to treat cancer)
● MOA: Inhibits function of OCs
o Binds to DNA and inhibits formation of mRNA = impaired OC function due to decreased protein synthesis
o Also has chelating activity
● Used to treat:
o Hypercalcemia
o Paget’s disease
o Used as a last resort when bisphoshonates and calcitonin are not efficacious, since
mithramycin is significantly more toxic
o Most serious adverse effect is thrombocytopenia leading to hemorrhage;
also toxic to the liver and kidney

Question 3

What are the characteristics of Thiazides?

Answer 3

● Only class of diuretics that increase reabsorption of Ca in kidney ;serum Ca levels increase
● MOA: enhances PTH effect in kidney to reduce renal elimination of Ca
● Uses: treatment of hypercalcuria

Question 4

What are the characteristics of Fluorides?

Answer 4

MOA: May act to stabilize hydroxyapatite crystal:
F­ can replace OH­ in hydroxyapatite crystals and this appears to prevent resorption of bone With adequate Ca, fluoride therapy can result in bone stimulation ( may activate OBs )
Prolonged, chronic exposure can cause problems:
Crippling fluorosis = thickening of the cortex of long bones or bony outgrowths