1. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 75 Drugs Affecting Calcium Levels and Bone Mineralization

2. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.2 Calcium Physiology  Functions and daily requirements  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

3. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.3 Calcium Physiology  Regulation of calcium levels  Absorption from the small intestine  Excretion by the kidney  Resorption in bone  Regulated by Parathyroid hormone Parathyroid hormone Vitamin D Vitamin D Calcitonin Calcitonin

4. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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

5. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.5 Hypercalcemia  Drugs  Furosemide (Lasix)  Glucocorticoids  Others: calcitonin, bisphosphonates, inorganic phosphates, gallium nitrate

6. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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

7. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.7 Other Disorders Involving Calcium  Rickets  Osteomalacia  Paget’s disease of bone  Hypoparathyroidism  Hyperparathyroidism  Primary  Secondary

8. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.8 Drugs for Disorders Involving Calcium  Calcium salts  Vitamin D  Calcitonin-salmon (Calcimar, Miacalcin, Fortical)  Bisphosphonates  Alendronate, risedronate, ibandronate, tiludronate, etidronate, zoledronate, pamidronate

9. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.9 Raloxifene (Evista)  Selective estrogen receptor modulator (SERM)  Structurally similar to estrogen and binds to estrogen receptors  Therapeutic uses Osteoporosis and breast cancer Osteoporosis and breast cancer May decrease risk of cardiovascular events May decrease risk of cardiovascular events  Adverse effects Venous thromboembolism, fetal harm, hot flashes Venous thromboembolism, fetal harm, hot flashes

10. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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

11. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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

13. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.13 Drugs for Hypercalcemia  Furosemide  Glucocorticoids  Gallium nitrate  Bisphosphonates  Inorganic phosphates  Edetate disodium

14. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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)

15. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.15 Treating Osteoporosis in Women  Antiresorptive therapy: drugs that reduce bone resorption  Estrogen (Premarin)  Raloxifene (Evista)  Bisphosphonates Alendronate (Fosamax) Alendronate (Fosamax) Risedronate (Actonel) Risedronate (Actonel) Ibandronate (Boniva) Ibandronate (Boniva)  Calcitonin-salmon nasal spray (Miacalcin)  Drugs that promote bone formation  Teriparatide (Forteo)

16. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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) Alendronate (Fosamax) Risedronate (Actonel) Risedronate (Actonel) Teriparatide (Forteo) Teriparatide (Forteo) Zoledronate (Reclast) Zoledronate (Reclast)