bone density drugs

osteoid is (organic/inorganic), while hydroxyapatite is (organic/inorganic)

• osteoid = organic

• hydroxyapatite = inorganic

5 steps of bone remodeling cycle

1. activation

2. resorption

3. reversal

4. formation

5. termination

______ and ______ are critical mineral ions essential for bone structure and function

• calcium and phosphate

glucocorticoid-induced osteoporosis

• decreased calcium absorption

• increased renal calcium excretion

• decreased osteoblast formation and survival

• increased RANKL-mediated osteoclast activation

what do antiresorptive drugs do?

• decrease osteoclast-mediated bone resorption

what are the 2 classes of bisphosphonates?

• non-nitrogen containing (1st gen)

• nitrogen-containing (2nd + 3rd gen)

indications for bisphosphonates

• osteoporosis

• Paget disease

• hypercalcemia of malignancy

Which of the following bisphosphonates is non-nitrogen containing, first generation, and less potent?

a) alendronate

b) Zoledronic acid

c) etidronate

d) pamidronate

c) etidronate

non-nitrogen containing (first gen) bisphosphonates MOA

• form toxic ATP analogs

  • induce apoptosis by inhibiting ATP dependent cellular processes in osteoclasts

nitrogen containing (2/3 gen) bisphosphonates MOA

• bind hydroxyapatite

• inhibit farnesyl pyrophosphate synthase (FFPS) → impaired cholesterol synthesis in osteoclast

• induce osteoclast apoptosis + inhibit bone resorption

bisphosphonate administration counseling

• take on empty stomach

• full water of glass

• remain upright for 30-60 minutes

bisphosphonate ade

• esophagitis, GERD, ulcers

• osteonecrosis of the ja w(ONJ)
  atypical femur fractures

• nephrotoxicity

• hypocalcemia

bisphosphonate contraindications

• esophageal disorders

• roux-en-Y gastric bypass

• CKD

• inability to remain upright

how does calcium, iron, and antacids affect bisphosphonates?

• decrease absorption

how do NSAIDS affect bisphosphonates?

• increased GI toxicity

low risk patients should stop bisphosphonates after ______ years ( ____ years if on IV)

vs

high risk patients should stop bisphosphonates after ______ years ( ____ years if on IV)

• low risk = after 5 years; 3 on IV

• high risk = after 10 years; 6 on IV

bisphosphonates may be restarted ______ years after a drug holiday

• 3-5 years

which of the following is the most potent?

a) ibandronate

b) zoledronic acid

c) risedronate

d) alendronate

b) zoledronic acid

which of the following is used for postmenopausal osteoporosis?

a) ibandronate

b) zoledronic acid

c) risedronate

d) alendronate

a) ibandronate

which of the following is used as 1st line for osteoporosis?

a) ibandronate

b) zoledronic acid

c) risedronate

d) alendronate

d) alendronate

which of the following causes flu-like symptoms (IV)?

a) risedronate

b) zoledronic acid

c) ibandronate

d) alendronate

c) ibandronate

which of the following does NOT reduce hip fracture risk?

a) risedronate

b) zoledronic acid

c) ibandronate

d) alendronate

e) all of the above

c) ibandronate

which of the following is used as an annual IV dose for osteoporosis, which is the best for adherence issues?

a) etidronate

b) zoledronic acid

c) alendronate

d) risedronate

b) zoledronic acid

which of the following is used primarily in oncology settings (IV only)?

a) etidronate

b) zoledronic acid

c) alendronate

d) pamidronate

d) pamidronate

what type of drug is denosumab? what are its effects?

• RANKL Inhibitor

  • human monoclonal antibody against RANKL

• increases bone mineral density

• decrease fracture risk

Denosumab ADE

• hypocalcemia

• ONJ (osteonecrosis of jaw)

• rebound fractures if stopped

• diarrhea / nausea

• anemia or thrombocytopenia

• fatigue

• atypical femur fractures

selective estrogen receptor modulators (SERMS) / estrogen agonists MOA

• upregulate OPG

• downregulate RANKL

• decreases pro-inflammatory cytokines

• increases osteoblast survival

calcitonin drug administration options

• nasal spray or injection

calcitonin MOA

• weak antiresorptive effect

  • directly inhibits osteoclast activity through calcitonin receptors on osteoclasts without impairing osteoblast collagen

calcitonin indications

• hypercalcemia

• Paget disease

• osteoporosis

calcitonin effectiveness may decline due to ______ over time

• receptor downregulation

calcitonin ADR

• hypocalcemia

• hypersensitivity reactions - salmon-derived products

• rhinitis / epistaxis

• malignant neoplasm

calcitriol MOA

• active form of vitamin D → binds to VDR

  • increased absorption of calcium + phosphate

  • decreased PTH

paricalcitol MOA

• selective vitamin D receptor activator

  • suppresses PTH

doxercalciferol MOA

• vitamin D2 analog prodrug

  • VDR activation + decreased PTH

ergocalciferol (vitamin D2) MOA

• converted to active vitamin D

  • increased calcium + phosphate absorption

cholecalciferol (vitamin D3) MOA

• converted in liver/kidney → calcitriol

Calcifediol MOA

• 25-hydroxyvitamin D3 that bypasses hepatic activation

  • converted in kidney → calcitriol

calcitriol and vitamin D analog uses

• rickets

• hypoparathyroidism

• secondary hyperparathyroidism

• osteoporosis

CI with calcitriol and vitamin D analogs

• hypercalcemia

• vitamin D toxicity

T/F: Paricalcitol has a lower hypercalcemia risk than calcitriol

• true

which of the following does NOT need renal activation?

a) calcitriol

b) calcifediol

c) doxercalciderol

d) paricalcitol

a) calcitriol

which of the following requires hepatic activation?

a) paricalcitol

b) doxercalciferol

c) cholecalciferol

d) calcifediol

b) doxercalciferol

which of the following requires renal activation?

a) calcitriol

b) doxercalciferol

c) cholecalciferol

d) calcifediol

c) cholecalciferol

T/F: Ergocalciferol is more potent than vitamin D3

• false

  • less potent

what is the preferred supplement form?

a) calcitriol

b) ergocalciferol (vitamin D2)

c) cholecalciferol (vitamin D3)

d) calcifediol

c) cholecalciferol (vitamin D3)

cinacalcet MOA

• calcimimetic / calcium-sensing receptor modulator

  • positive allosteric modulator of calcium-sensing receptor (CaSR) on parathyroid gland

    • increases sensitivity to Ca

    • decreases PTH secretion

etelcalcetide MOA

• calcimimetic / calcium-sensing receptor modulator

  • direct agonist calcium-sensing receptor (CaSR)

    • decreases PTH secretion

calcimimetic / calcium-sensing receptor modulators are useful for…

• secondary hyperparathyroidism

major ADR of calcimimetic / calcium-sensing receptor modulator

• qt prolongation

• hypocalcemia

• GI symptoms

Drug interactions with calcimimetic / calcium-sensing receptor modulator

• cyp3a4 inhibitos + cyp2d6 substrates

cinacalcet administration form

• oral agent

etelcalcetide administration form

• IV administration (post-demodialysis)

is cinacalcet or etelcalcetide more potent

• etelcalcetide

how are parathyroid hormone (PTH) Analogs administered?

• all administered SQ QD

parathyroid hormone (PTH) Analogs MOA

• intermittent, pulsatile administration increases the maturation and activity of osteoblasts while decreasing their apoptosis

parathyroid hormone (PTH) Analogs ADR

• possible osteosarcoma

parathyroid hormone (PTH) Analogs should limit therapy to ___ years

• 2 years

what ty[pe of drug is romosozumab ? MOA?

• sclerostin inhibitor

  • inhibits sclerostin (Osteocyte-derived glycoprotein)

what is the dual effect of sclerostin inhibitors

• increased bone formation

• decrease bone resorption

sclerostin inhibitors should limit use to ____

• 12 months

Teriparatide MOA

• recombinant PTH analog

  • stimulates osteoblast activity > osetoclasts

abaloparatide MOA

• analog of PTH-related peptide (PTHrP)

  • activates PTH-1 receptor = increased osteoblast activity

which of the following is anabolic (builds bone) ?

a) teriparatide

b) abaloparatide

c) romozozumab

a) teriparatide

SATA: which of the following have a drug interaction with digoxin?

a) teriparatide

b) abaloparatide

c) romozozumab

a) teriparatide

b) abaloparatide

Burosumab MOA

• anti-FGF23 antibody

what needs to be done before starting Burosumab therapy?

• oral phosphate and/or active vitamin D should be discontinued for at least 1 week

anti-FGF23 (Ex. Burosumab) indication

• hypophosphatemia

• tumor-induced osteomalacia

Burosumab ADR

• vitamin D deficiency

• GI effects

• tooth cavities/infection

• HA

• injection reaction

Process increased by continuous PTH exposure

• resorption

First-line osteoporosis drugs that bind hydroxyapatite

• bisphosphonates

. Protein inhibited by Romosozumab

• sclerostin

Condition caused by long-term bisphosphonate use affecting the jaw

• osteonecrosis jaw

Selective vitamin D receptor activator used in CKD

• paricalcitol

Major fracture type NOT reduced by Ibandronate

• hip

Thyroid Hormone that decreases bone resorption

• calcitonin

Organ responsible for activating vitamin D to calcitriol

• kidney

PTH analog used for severe osteoporosis

• teriparatide

Positive allosteric modulator of calcium sensing receptor (CaSR) on parathyroid gland

• cinacalcet

Protein that binds RANKL and prevents osteoclast activation

• osteoprotegerin

Drug that inhibits sclerostin

• romosozumab

. Rebound complication seen after stopping Denosumab

• vertebral fractures

Active form of vitamin D

• calcitriol

IV calcimimetic given post-dialysis

• etelcalcetide

Major adverse effect of vitamin D toxicity

• hypercalcemia

Drug used annually IV for osteoporosis

• zoledronic acid

Condition treated by Burosumab involving low phosphate

• hypophosphatemia

Non-nitrogen bisphosphonate that forms toxic ATP analogs in osteoclasts

• etidronate

Drug class that increases risk of venous thromboembolism

• SERMS

Orally administered antiresorptive drug that requires patients to remain upright after dosing

• alendronate

Hormone that increases serum calcium

• parathyroid

Drug class that mimics calcium at the parathyroid gland

• calcimimetics

Key enzyme inhibited by nitrogen-containing bisphosphonates

• FPPS

Monoclonal antibody that inhibits RANKL

• denosumab

Electrolyte decreased by calcimimetics

• calcium

Boxed warning associated with PTH analogs

• osteosarcoma

Hormone that promotes phosphate excretion

FGF23