Drugs For Osteoporosis

Question 1

PTH actions

Answer 1

Acts on cGMP receptors so increases cAMP in bone and renal tubules
In kidneys: inhibits calcium secretion but promotes phosphate excretion to form vit D metabolites
In bones: promotes osteoblast activity which would form RANK ligand stimulating osteoclast formation and osteoclast differentiation
Regulated by levels of calcium (high Ca-> low PTH)and active vit D metabolites (presence inhibits PTH secretion)

Question 2

High PTH levels

Answer 2

Hypercalcemia, hyperphosphotemia, bone resorption

Question 3

Low PTH levels

Answer 3

Increase in bone formation

Question 4

Teriparatide

Answer 4

Decreases levels of PTH for bone formation used for osteoporosis

Question 5

Active metabolites

Answer 5

In the liver: 25hydroxyvitamin D or calcifediol
In the kidneys: 1.25- dihydroxyvitamin D or calcitriol (stimulated formation by FGF23 and PTH) and its synthesis is inhibited by phosphate and VitD metabolites
They increase levels of Ca and Phosphate by increasing their absorption in intestins, bone resorption and decreasing renal excretion.

Question 6

Cholecalciferol D3 and ergocalciferol D2

Answer 6

Absorbed usually from the diet but also can be used as oral supplements

Question 7

Calcitriol

Answer 7

Used for conditions with impaired vitD activation (chronic kidney, liver diseases, hypoparathyroidism) and in secondary hyperparathyroidism where it decreases PTH levels, hypercalcemia and hypercalciuria (correcting hypocalcemia and bone diseases)

Question 8

Doxercalciferol

Answer 8

1alpha-hydroxyvitamin D2 is a prodrug converted in the liver to calcitriol
Taken orally and parenterally fir secondary hyperparathyroidism with chronic liver disease

Question 9

Paricalcitol and calcipotriol

Answer 9

19-nor-1,25-dihydroxyvitamin D2 and calcipotriene respectively are Analogs of calcitriol
Calcipotriene is used for topical treatment of psoriasis

Question 10

Calcitonin

Answer 10

Secreted by thyroid gland taken orally or by nasal spray.
Effects: decrease serum Ca, phosphate by inhibiting bone resorption and renal excretion of these minerals.
Usage: needed in hypercalcemia or paget’s disease, in osteoporosis, increase bone mass reducing spine fractures

Question 11

Estrogens and SERMs

Answer 11

Prevent or delay bone loss in postmenopausal women by inhibiting PTH stimulated bone resorption

Question 12

Glucocorticoids

Answer 12

Inhibit bone mineral maintenance but can cause osteopororsis so not used for a long term

Question 13

Alendronate, etidronate, ibandronate, -dronate, zolidronic acid

Answer 13

Bisphosphonates that act on hydroxyapatite crystal structures to reduce both resorption and formation of bones, affect vitD production, calcium absorption in the GI, inhibit farnesyl synthase playing a role in osteoclast survival, treat paget’s disease and manage hypercalcemia associated malignancies

Question 14

Bisphosphonates usage for osteoporosis and toxicity

Answer 14

Food impairs their absorption
Dosing:
-daily oral dosing of alendronate or risedronate or ibandronate
-weekly oral dosing of alendronate or risedronate
-monthly oral dosing of ibandronate
-quarterly injection dose of ibandronate
-annual infusions of zoledronate
Toxicity: gastric, esophgeal irritation, if used in high doses for hypercalcemia causes renal impairment and osteonecrosis of the jaw

Question 15

Denosumab

Answer 15

RANKL inhibitor taken subcutaneously for 6 months that inhibits formation and activity of osteoclasts and can be used for postmenopausal osteoporosis

Question 16

Cinacalcet

Answer 16

Activates calcium sensing receptors in the parathyroid gland so decreases PTH levels.
Used for oral treatment of hyperparathyroidism, chronic kidney disease, treatment of hypercalcemia in patients with parathyroid carcinoma
Toxicity: hypocalcemia, adynamic bone disease