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Chapter 75 Drugs Affecting Calcium Levels and Bone Mineralization Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Calcium Physiology Functions and daily requirements Body stores More than 98% stored in the bones Total serum calcium = 10 mg/dL Absorption Critical to the function of the skeletal, nervous, muscular, and cardiovascular systems Absorption in the small intestine Increased by parathyroid hormone and vitamin D Glucocorticoids decrease absorption Excretion Calcitonin augments calcium elimination Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 2 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 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 3 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 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 4 Hypercalcemia Drugs Furosemide (Lasix) Glucocorticoids Others: calcitonin, bisphosphonates, inorganic phosphates, gallium nitrate Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 5 Hypocalcemia Increases neuromuscular excitability Clinical presentation Causes Tetany, convulsions, and spasm of the pharynx Deficiency of parathyroid hormone (PTH), vitamin D, or calcium Treatment Calcium supplementation (calcium gluconate) Vitamin D Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 6 Other Disorders Involving Calcium Rickets Osteomalacia Paget’s disease of bone Hypoparathyroidism Hyperparathyroidism Primary Secondary Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 7 Drugs for Disorders Involving Calcium Calcium salts Vitamin D Calcitonin-salmon (Calcimar, Miacalcin, Fortical) Bisphosphonates Alendronate, risedronate, ibandronate, tiludronate, etidronate, zoledronate, pamidronate Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 8 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 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 9 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 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 10 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 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 11 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 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 12 Drugs for Hypercalcemia Furosemide Glucocorticoids Gallium nitrate Bisphosphonates Inorganic phosphates Edetate disodium Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 13 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) Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 14 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) Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 15 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) Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 16