1. Drugs Affecting Calcium Levels and Bone Mineralization
Chapter 75
Drugs Affecting Calcium Levels and Bone Mineralization 1

2. Calcium Physiology Functions and daily requirements Body stores
Critical to function of the skeletal, nervous, muscular, and cardiovascular systems
Body stores
Bones: More than 98% stored in the bones
Blood: Total serum calcium = 10 mg/dL
Absorption
Occurs 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. Calcium Physiology Parathyroid hormone
Promotes calcium resorption from bone
Promotes tubular reabsorption of calcium that had been filtered by the kidney glomerulus
Promotes activation of vitamin D, and thereby promotes increased absorption of calcium from the intestine 4

5. Calcium Physiology Vitamin D Increases calcium resorption from bone
Decrease calcium excretion by the kidney
Increases calcium absorption from the intestine 5

6. Calcium Physiology Calcitonin
Released from the thyroid gland when calcium levels in the blood rise too high
Lowers calcium levels by inhibiting resorption of calcium from bone and increasing calcium excretion by the kidney
Does not influence calcium absorption 6

7. Hypercalcemia Usually asymptomatic
If symptoms are present: Kidney, gastrointestinal (GI) tract, CNS
Causes
Cancer
Hyperparathyroidism
Vitamin D intoxication
Sarcoidosis
Use of thiazide diuretics 7

8. Hypercalcemia Treatment
Drugs that promote urinary excretion of calcium
Drugs that decrease mobilization of calcium from bone
Drugs that decrease intestinal absorption of calcium
Drugs that form complexes with free calcium in the blood
IV saline
Then diuresis with a loop diuretic 8

9. Hypercalcemia Drugs Edetate disodium Glucocorticoids Calcitonin
Bisphosphonates
Gallium nitrate
Cinacalcet (Sensipar): Suppresses parathyroid hormone (PTH) secretion; used for hypercalcemia associated with hyperparathyroidism 9

10. Hypocalcemia Increases neuromuscular excitability
Clinical presentation
Tetany, convulsions, and spasm of the pharynx
Causes
Deficiency of PTH
Deficiency of vitamin D
Deficiency of calcium
Chronic renal failure
Long-term use of certain medications, such as magnesium-based laxatives, and drugs used to manage osteoporosis (for example, bisphosphonates and denosumab) 10

11. Hypocalcemia Treatment
Intravenous calcium supplementation (calcium gluconate)
Once calcium levels have been restored: Calcium citrate for maintenance
Vitamin D 11

12. Other Disorders Involving Calcium
Rickets (usually children)
Vitamin D deficiency results in reduced calcium absorption
PTH is released
PTH restores serum calcium by promoting calcium resorption from bone, thereby causing bones to soften
Stress on softened bones caused by bearing weight results in deformity
Treatment: Vitamin D replacement therapy 12

13. Other Disorders Involving Calcium
Osteomalacia (adult counterpart of rickets)
Absence of vitamin D
Impaired mineralization of bone
Bowing of the legs
Fractures of the long bones
Kyphosis (“hunchback” curvature of the spine)
Diffuse, dull, aching bone pain
Treatment: Vitamin D replacement therapy 13

14. Other Disorders Involving Calcium
Osteoporosis: Most common disorder of calcium metabolism
Paget’s disease of bone
Increased bone resorption and replacement of resorbed bone with abnormal bone
Pelvis, femur, spine, skull, tibia
Pain, skeletal deformity, fracture
Treatment: Pain management and bisphosphonates to suppress bone resorption 14

15. Other Disorders Involving Calcium
Hypoparathyroidism
Cause: Inadvertent removal of parathyroid glands during surgery on the thyroid gland
Lack of PTH: Hypocalcemia, paresthesias, tetany, skeletal muscle spasm, laryngospasm, convulsions
Treatment: Calcium supplements 15

16. Other Disorders Involving Calcium
Primary hyperparathyroidism
Cause: Usually results from a benign parathyroid adenoma
Increase in PTH secretion: Hypercalcemia and hypophosphatemia
Skeletal muscle weakness, constipation, CNS symptoms, renal calculi, bone abnormalities
Treatment: Surgical resection of parathyroid glands; calcium-lowering drugs – cinacalcet [Sensipar] 16

17. Other Disorders Involving Calcium
Secondary hyperparathyroidism
Cause: Common complication of chronic kidney disease (CKD)
High levels of PTH and disturbances of calcium and phosphorus homeostasis
Treatment
Vitamin D sterol (for example, paricalcitol) and calcium-containing phosphate-binding agents
Cinacalcet [Sensipar]: Can reduce PTH and has a positive effect on calcium and phosphorus levels 17

18. Drugs for Disorders Involving Calcium
Calcium salts
Oral
Mild hypocalcemia, dietary supplements
PMS
Colorectal adenoma
Adverse effects: Hypercalcemia
Drug interactions: Corticosteroids, tetracycline, fluoroquinolone, thyroid hormone, phenytoin, bisphosphonates, loop diuretics, thiazide diuretics 18

19. Drugs for Disorders Involving Calcium
Calcium salts (Cont.)
Parenteral: Calcium chloride and calcium gluconate
Adverse effects: Highly irritating; do not give IM; can cause IV extravasation
Drug interaction: Digoxin 19

20. Drugs for Disorders Involving Calcium
Vitamin D
Important regulator of calcium and phosphorus homeostasis
Health benefits
Vitamin D deficiency
Activation of vitamin D
Vitamin D as a hormone 20

21. Drugs for Disorders Involving Calcium
Vitamin D toxicity
Early symptoms: Weakness, fatigue, nausea, vomiting, anorexia, abdominal cramping, constipation
Later symptoms: Kidney function is affected, resulting in polyuria, nocturia, and proteinuria
Neurologic: Seizures, confusion, ataxia
Cardiac dysrhythmia
Coma
Calcium deposition in soft tissues
Decalcification of bone 21

22. Drugs for Disorders Involving Calcium
Calcium salts
Vitamin D
Calcitonin-salmon [Calcimar, Miacalcin, Fortical]
Bisphosphonates
Alendronate, risedronate, ibandronate, tiludronate, etidronate, zoledronate, pamidronate 22

23. Drugs for Disorders Involving Calcium
Vitamin D
Ergocalciferol [Calciferol Drops, Drisdol]
Cholecalciferol (Vitamin D3)
Calcitriol (1,25-Dihydroxy-D3) 
Doxercalciferol [Hectorol]
Paricalcitol [Zemplar]
Calcitonin-salmon 23

24. Drugs for Disorders Involving Calcium
Calcitonin
Inhibits the activity of osteoclasts
Decreases bone resorption
Inhibits tubular resorption of calcium
Increases calcium excretion
Therapeutic uses: Osteoporosis, Paget’s disease, hypercalcemia
Adverse effects 24

25. Drugs for Disorders Involving Calcium
Bisphosphonates
Structural analogs of pyrophosphate
Incorporate into bone: Inhibit bone resorption by decreasing activity of osteoclasts
Indications: Postmenopausal osteoporosis, osteoporosis in men, glucocorticoid-induced osteoporosis, Paget’s disease of bone, hypercalcemia of malignancy
May also help prevent and treat bone metastases in patients with cancer
Adverse effects: May include ocular inflammation, osteonecrosis of the jaw (ONJ), atypical femur fractures, atrial fibrillation (A-fib) 25

26. Bisphosphonates Alendronate [Fosamax, Fosamax Plus D]
Most widely used oral bisphosphonate
Uses: Postmenopausal osteoporosis, male osteoporosis, glucocorticoid-induced osteoporosis, Paget’s disease of bone
Oral bioavailability: Poor
Adverse effects: Generally safe; esophageal ulceration, atypical femoral fracture, esophageal cancer, musculoskeletal pain, ocular problems, ONJ, hyperparathyroidism, A-fib 26

27. Bisphosphonates Risedronate [Actonel]
Uses: Postmenopausal osteoporosis, male osteoporosis, glucocorticoid-induced osteoporosis, Paget’s disease of bone
Adverse effects: Arthralgia, diarrhea, headache, rash, nausea, flulike syndrome, esophagitis, atypical femoral fractures, ocular problems, musculoskeletal pain 27

28. Bisphosphonates Ibandronate [Boniva]
Uses: Prevention and treatment of postmenopausal osteoporosis
Dosing: Once a month or once every 3 months
Adverse effects: GI effects, including esophagitis, dyspepsia, abdominal pain; ocular inflammation; atypical fractures; ONJ; renal damage if IV administered too rapidly 28

29. Bisphosphonates Tiludronate [Skelid] Use: Paget’s disease of bone
Adverse effects: Nausea, diarrhea, dyspepsia, esophagitis, ocular problems, musculoskeletal pain, possibly esophageal cancer, chest pain, edema, paresthesias, hyperparathyroidism, vomiting, flatulence 29

30. Selective Estrogen Receptor Modulator (SERM)
Raloxifene [Evista]
Structurally similar to estrogen and binds to estrogen receptors
Comparison to estrogen
Therapeutic uses
Osteoporosis
Breast cancer
Adverse effects
Thromboembolic events, such as deep vein thrombosis (DVT), pulmonary embolism, and stroke, and fetal harm 30

31. Teriparatide [Forteo]
Form of PTH
Produced by recombinant DNA
Only drug that increases bone formation
Generally well tolerated
Nausea, headache, back pain, leg cramps 31

32. Denosumab [Prolia, Xgeva]
First-in-class RANKL inhibitor with three indications:
Osteoporosis in postmenopausal women and in men at high risk for fractures
Bone loss in women and men receiving certain anticancer therapy
Prevention of skeletal-related events in patients with bone metastases from solid tumors
RANKL, Receptor activator of nuclear factor kappa-B ligand.

33. Denosumab [Prolia, Xgeva]
Adverse effects
Hypocalcemia
Serious infections
Dermatologic reactions
Osteonecrosis of the jaw

34. Cinacalcet [Sensipar]
Calcimimetic drug
Approved for primary hyperparathyroidism and secondary hyperparathyroidism (caused by CKD)
Increases the sensitivity of calcium-sensing receptors to activation by extracellular calcium
Suppresses PTH secretion 34

35. Cinacalcet [Sensipar]
Adverse effects: Nausea, vomiting, diarrhea, hypocalcemia
Interactions
Monitoring 35

36. Drugs for Hypercalcemia
Furosemide
Glucocorticoids
Gallium nitrate
Bisphosphonates
Inorganic phosphates
Edetate disodium 36

37. Osteoporosis Most common disorder of calcium metabolism
Low bone mass and increased bone fragility
Primary prevention
Calcium, vitamin D, lifestyle
Diagnosis
Measurement of bone mineral density (BMD)
Dual-energy x-ray absorptiometry (DEXA) 37

38. Treating Osteoporosis in Women
Agents that decrease bone resorption: Estrogen, raloxifene, bisphosphonates, calcitonin, denosumab; sufficient calcium and vitamin D are important
Agent that promotes bone formation: Teriparatide (Forteo)
Agents that reduce fractures: Teriparatide, denosumab, zoledronate 38

39. Treating Osteoporosis in Men
Five drugs have been approved for osteoporosis treatment in men:
Alendronate [Fosamax]
Risedronate [Actonel]
Zoledronate [Reclast]
Teriparatide [Forteo]
Denosumab [Prolia] 39

40. Case Study
A nurse has been asked to present a talk on drug therapy for osteoporosis to a group of adults. When preparing the talk, what should the nurse include for the mechanism of action and the adverse effects of the bisphosphonates?
Bisphosphonates help decrease the breakdown of the microstructure of bone. Side effects of bisphosphonates include stomach pain, difficulty swallowing, esophageal inflammation, esophageal reflux, and ulcer formation. 40

41. Case Study
What information should the nurse include to reduce adverse effects of bisphosphonates?
To reduce adverse effects of bisphosphonates, the patient should avoid using aspirin, nonsteroidal anti-inflammatory agents, and antacids when taking bisphosphonates. In addition, the patient should not sit or lie down for 30 minutes after taking the bisphosphonate. 41

42. Case Study
Along with the use of drugs for the treatment of osteoporosis, what other measures can help prevent the development of osteoporosis?
The nurse should inform the group that adequate calcium and vitamin D intake, as well as not smoking, avoiding alcohol, and performing weight-bearing exercises, can prevent the development of osteoporosis. 42

43. Question 1
The nurse should advise patients who are taking calcium to avoid consumption of which food?
A. Spinach
B. Lettuce
C. Tomatoes
D. Squash
Answer: A
Rationale: Calcium absorption is reduced by consumption of foods containing oxalic acid (spinach, rhubarb, Swiss chard, and beets) and phytic acid (bran and whole-grain cereals).

44. Question 2
A patient with hyperparathyroidism has a calcium level of 13.2 mg/dL. What medication does the nurse anticipate being prescribed?
A. Alendronate [Fosamax]
B. Calcium acetate [PhosLo]
C. Salmon calcitonin [Calcimar]
D. Raloxifene [Evista]
Answer: C
Rationale: Salmon calcitonin is administered for hypercalcemia related to hyperparathyroidism. Calcium levels are lowered by inhibition of bone resorption and increased excretion of calcium by the kidneys.

45. Question 3
When preparing to administer intravenous calcium chloride, the nurse should do what?
A. Warm the solution to body temperature.
B. Inject 5 mL over 1 minute.
C. Increase the calcium chloride dose if the patient is also taking digoxin.
D. Evaluate the patient for an increase in tetany as an indication that the drug is exerting its therapeutic effect.
Answer: A
Rationale: Calcium solutions should be warmed to body temperature before IV dosing. Perform IV injections of calcium chloride slowly (0.5 to 2 mL/min). Parenteral calcium may cause severe bradycardia in patients taking digoxin; infuse calcium slowly and cautiously in these patients. Evaluate the patient for reductions in tetany, muscle spasm, laryngospasm, paresthesias, and other symptoms of severe hypocalcemia.