Drugs Affecting Calcium Levels and Bone Mineralization 1

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

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

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

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

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

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

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

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

Drugs for Hypercalcemia Furosemide Glucocorticoids Gallium nitrate Bisphosphonates Inorganic phosphates Edetate disodium 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) 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) 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) 16