Bone Mineral Homeostasis

Question 1

PTH hormone Rx

Answer 1

Teriparatide (hPTH 1-34) — increases bone formation w/o resorption stimulation – and hPTH (1-84)

Question 2

Calcitonin and MOA and uses

Answer 2

Synthetic hCT and Calcimar/Miacalcin (salmon)

• dec osteoclast ruffled border SA = dec bone resorption, dec kidney Ca reabsorption, 1,25 Vit D (opposes PTH)
• uses: HyperCa, Pagets, Osteoporosis

Question 3

Vit D agents

Answer 3

• • Calcitriol (1, 25) –>
• • Cholecalciferol (25) / cholecalciferol D3 –> stays in lipid stores
• • Ergosterol –> similar to cholesterol
• • Dihydrotachysterol (DHT) –> osteoporosis! needs high doses
• • Paricalcitol –> reduces PTH secretion

Question 4

Bisphosphonates “dronates”

Answer 4

• • 1st gen: Etidronate
• • 2nd gen: alendronate, pamidronate, ibandronate
• • 3rd gen: risedronate, tiludronate, zoledronate

MOA: x bone resorption,

Uses: paget’s (EAR), osteoporosis (A?), xcancer tx induced bone loss (Z and P)

Question 5

Cinacalcet + MOA

Answer 5

Calcium sensing receptor mimetrics

MOA: bind CaSR = x PTH at lower [Ca] ie for hypercalcemia/hyperparathyroidism

Question 6

Flouride MOA

Answer 6

F- binds calcium, replaces hydroxyapetite with flouroapetite –> can be used to prevent blood clotting and osteoporosis

+ mottled enamel / resistance to tooth decay

Question 7

Calcium Sensing Receptor – cell types, MOA,

Answer 7

• Parafollicular thyroid, Parathyroid + Kidney, osteoblast, hematopoietic cells in BM, GI mucosa
• Activation: phospholipase C/incDAG and IP3
• Inhibition: adenylate cyclase, suppresses cAMP

Question 8

Raloxifene

Answer 8

SERM (Selective estrogen receptor modulator) approved for ostoporosis — estrogen benefits w/out chance of br cancer

Question 9

Denosumab

Answer 9

• – Monoclonal Ab to RANKL = xOsteoclast formation

- – increases bone mass in breast and prostate cancer

Question 10

FGF23

Answer 10

x 1, 25 OH D3 = opposes PTH in kidney
Decreases phosphate reabsorption in prox tubule

produced by osteoclasts and blasts in bone

Question 11

Calcitriol MOA and uses

Answer 11

• • inc synthesis of Calbindin
• • Inc Ca and PO4 absorption in small intestine

– Uses: prophylaxis/cure of nutritional rickets, tx metabolic rickets/osteomalacia, tx hypoPTH, osteoporosis prevention

Question 12

Bisphosphonate SE’s

Answer 12

• • Osteonecrosis of Jaw
• • swelling/loosening of teeth
• • surgical correction makes lesions worse
• • often complicated by infection
• • more potent with 3rd generation drugs! = more potent

Question 13

Rx for reversing lymphoma induced hyperCa?

Answer 13

Glucocorticoids
- x Ca uptake in intestine
-

Question 14

Plicamycin

Answer 14

Antibiotic used for Paget’s dz and hyperCa

seldom used now

Question 15

Strontium Ranelate

Answer 15

Blocks Differentiation of Ostoeclasts / promotes apoptosis
+ promotes bone formation

= increases bone mineral density/decreases fracture