Calcium Pharmacology

Question 1

Vitamin D Supplementation

Answer 1

• Max: 2,000 IU/Day
• Cholecalciferol (D3)- animal sources
• Ergocalciferol (D2)- Plant sources
• Calcitriol (1,25(OH)2D)- 100 X more potent than vit. D

Question 2

Calcium

Answer 2

Max: 2,500 mg/day
- Adequate Calcium intake = 3 glasses of milk or equivalent
- Calcium Carbonate
- Calcium Citrate
Calcium Phosphate

Question 3

Bisphosphonates

Answer 3

• Bind to bone surface at remodeling sites, ingested by osteoclasts –> causes osteoclast cell death
  Non-N-containing BPs (etidronate): incorporated into ATP producing cytotoxic analog, rarely used
  N-Containing BPs (alendronate, zoledronic acid): inhibit osteoclast mevalonate pathway, blocking prenylation of key regulatory proteins
• Indications: first line for osteoporosis and malignant hypercalcemia

Side Effects: - Upper GI disturbances (oral)

• Flu like syndrome- fever, myalgias (IV)
• MSK pain
• Very rare: iritis, osteonecrosis of the jaw, atypical femoral fractures

Contraindications: - Hypocalcemia

• Swallowing disorders or inability to remain upright after oral dosing
• Significant renal insufficiency

Question 4

Estrogen

Answer 4

• Estrogen alpha mediates most estrogen action on bone
• Reduces bone fractures and hot flushes
• Increases risk of breast and uterine cancers and clot risk

Question 5

Raloxifene

Answer 5

• Reduces bone fractures, breast and uterine cancer
• Increases hot flushes and DVT risk
• Estrogen and Raloxifene increase OPG (osteoprogerin) production which is a decoy rec. for RANKL s/t it doesn’t bind RANk on osteoclasts which block osteoclast activation

Question 6

Denosumab

Answer 6

mAB against RANKL s/t RANKL can’t bind RANK on osteoclasts and cause stimulation

Question 7

Teriparatide

Answer 7

• PTH Therapy
• Stimulates formation of normal bone; low amounts forms trabecular bone, high amounts forms cortical bone
  Indications: severe osteoporosis
  Contraindications: - hx of skeletal malignancies or radiation
• Pre-existing hypercalcemia
• Unexplained elevation in Alk Phos
• Paget’s

Question 8

Medications for Secondary Hyperparathyroid

Answer 8

Vitamin D Analogs: Calcitriol, paracalcitol, doxecalciferol

• Directly decreases PTH secretion because they are or act like 1,25(OH)2D
• Indicated for CKD
• May induce hypercalcemia or increase ectopic calcifications

Calcimimetics: Cinacalect

• Positive allosteric activator of CaSR, directly decreases PTH secretion
• Contraindications: hypocalcemia
• Dose adjustments w/ hepatic failure

Phosphate binders: reduce phosphate absorption in the gut