1. Drugs Affecting Calcium Levels and Bone Mineralization1

2. Calcium Physiology Functions and daily requirements Body stores
Critical to the function of the skeletal, nervous, muscular, and cardiovascular systems
Body stores
More than 98% stored in the bones
Total serum calcium = 10 mg/dL
Absorption
Absorption in the small intestine
Increased by parathyroid hormone and vitamin D
Glucocorticoids decrease absorption
Excretion
Calcitonin augments calcium elimination 2

3. Calcium Physiology Regulation of calcium levels
Absorption from the small intestine
Excretion by the kidney
Resorption in bone
Regulated by
Parathyroid hormone
Vitamin D
Calcitonin 3

4. Hypercalcemia Usually asymptomatic
If symptoms present: often involve the kidneys
Causes
Cancer
Hyperparathyroidism
Treatment
Promote urinary excretion
Decrease mobilization from bone
Decrease intestinal absorption
IV saline 4

5. Hypercalcemia Drugs Furosemide (Lasix) Glucocorticoids
Others: calcitonin, bisphosphonates, inorganic phosphates, gallium nitrate 5

6. Hypocalcemia Increases neuromuscular excitability
Clinical presentation
Tetany, convulsions, and spasm of the pharynx
Causes
Deficiency of parathyroid hormone (PTH), vitamin D, or calcium
Treatment
Calcium supplementation (calcium gluconate)
Vitamin D 6

7. Other Disorders Involving Calcium
Rickets
Osteomalacia
Paget’s disease of bone
Hypoparathyroidism
Hyperparathyroidism
Primary
Secondary 7

8. Drugs for Disorders Involving Calcium
Calcium salts
Vitamin D
Calcitonin-salmon (Calcimar, Miacalcin, Fortical)
Bisphosphonates
Alendronate, risedronate, ibandronate, tiludronate, etidronate, zoledronate, pamidronate 8

9. Raloxifene (Evista) Selective estrogen receptor modulator (SERM)
Structurally similar to estrogen and binds to estrogen receptors
Therapeutic uses
Osteoporosis and breast cancer
May decrease risk of cardiovascular events
Adverse effects
Venous thromboembolism, fetal harm, hot flashes 9

10. Teriparatide (Forteo)
Form of parathyroid hormone (PTH)
Produced by recombinant DNA
Only drug that increases bone formation
Generally well tolerated
Nausea, headache, back pain, leg cramps 10

11. Denosumab
Approved in 2010
First-in-class RANKL inhibitor with two indications:
treatment of osteoporosis in postmenopausal women at high risk for fractures
prevention of skeletal-related events (see below) in patients with bone metastases from solid tumors

12. Cinacalcet (Sensipar)
Calcimimetic drug
Approved for primary hyperparathyroidism and secondary hyperparathyroidism (caused by chronic kidney disease [CKD])
Somehow increases the sensitivity of calcium-sensing receptors to activation by extracellular calcium
PTH secretion suppressed 12

13. Drugs for Hypercalcemia
Furosemide
Glucocorticoids
Gallium nitrate
Bisphosphonates
Inorganic phosphates
Edetate disodium 13

14. Osteoporosis Most common disorder of calcium metabolism
Low bone mass and increased bone fragility
Primary prevention
Calcium, vitamin D, lifestyle
Diagnosis
Measuring bone mineral density (BMD)
Dual-energy x-ray absorptiometry (DEXA) 14

15. Treating Osteoporosis in Women
Antiresorptive therapy: drugs that reduce bone resorption
Estrogen (Premarin)
Raloxifene (Evista)
Bisphosphonates
Alendronate (Fosamax)
Risedronate (Actonel)
Ibandronate (Boniva)
Calcitonin-salmon nasal spray (Miacalcin)
Drugs that promote bone formation
Teriparatide (Forteo) 15

16. Treating Osteoporosis in Men
Antiresorptive therapy: drugs that reduce bone resorption
Not much research available on treatment of men
Four drugs approved
Bisphosphonates
Alendronate (Fosamax)
Risedronate (Actonel)
Teriparatide (Forteo)
Zoledronate (Reclast) 16