36.4: Bisphosphonates, Calcium Preparations, Vitamin D, and Estrogen Receptor Modulators
By the end of this section, you should be able to:
- 36.4.1 Identify the characteristics of bisphosphates, calcium, vitamin D, and estrogen receptor modulator drugs used to treat osteoporosis.
- 36.4.2 Explain the indications, actions, adverse reactions, and interactions of bisphosphates, calcium, vitamin D, and estrogen receptor modulator drugs used to treat osteoporosis.
- 36.4.3 Describe nursing implications of bisphosphates, calcium, vitamin D, and estrogen receptor modulator drugs used to treat osteoporosis.
- 36.4.4 Explain the client education related to bisphosphates, calcium, vitamin D, and estrogen receptor modulator drugs used to treat osteoporosis.
Bisphosphonates, calcium preparations, vitamin D, and estrogen receptor modulators may seem out of context in this chapter; however, they are included because of their effects on postmenopausal clients who no longer produce sufficient estrogen and are at increased risk of osteopenia and osteoporosis. Osteopenia is a condition in which bone mass is decreased, causing bones to become weaker. Osteoporosis is a condition in which bone mass has decreased to the point that bones become brittle and are much more likely to fracture (Fink, 2019; Zareef & Jackson, 2021; National Institutes of Health, 2022).
(See Thyroid and Parathyroid Disorder Drugs for more information regarding bisphosphonates, calcium preparations, and vitamin D.)
Bisphosphonates
Bisphosphonates are a category of drugs used to prevent and treat osteoporosis in postmenopausal clients. Vitamin D and calcium may be used as an adjunct with bisphosphonate therapy. Weight-bearing exercises, such as walking for 30 minutes several days a week, should be included as part of client education. Routine bone density testing should be scheduled to determine the effectiveness of the drug therapy (Ganesan et al., 2022).
Table 36.16 lists common bisphosphonates and typical routes and dosing for adult clients.
| Drug | Routes and Dosage Ranges |
|---|---|
|
Alendronate
( Fosamax ) |
10 mg orally once daily or 70 mg orally once weekly. |
|
Ibandronate
( Boniva ) |
Oral:
150 mg once monthly.
IV: 3 mg every 3 months. |
|
Risedronate
( Actonel ) |
5 mg orally once daily, or 35 mg once weekly, or 150 mg once monthly. |
|
Zoledronic acid
( Reclast ) |
5 mg IV once every 12 months or 24 months for treatment of osteoporosis. |
Adverse Effects and Contraindications
Adverse effects of bisphosphonates include decreased serum calcium and serum phosphate levels, arthralgia, myalgia, stomach pain, difficulty swallowing, heartburn, and irritation or pain of the esophagus. One major adverse effect from bisphosphonate therapy is osteonecrosis of the jaw (Madhumati & Gonegandla, 2020). The bisphosphonate accumulates in the jaw at a higher rate than in other bones and causes increased new bone formation. As a result, the older bone lacks sufficient blood supply and begins to die or become necrosed. This complication occurs more often in clients with cancer and in those who have invasive dental procedures. Thus, invasive dental procedures should not be performed while a client is receiving bisphosphonates.
Contraindications to bisphosphonates include any esophageal abnormality that prevents adequate and timely emptying of the stomach. Additionally, bisphosphonates should not be used if the client is unable to sit up or stand for at least 30 minutes after taking the medication, to reduce the risk of esophageal irritation. Severe renal insufficiency is another instance where bisphosphonates should not be used.
Table 36.17 is a drug prototype table for bisphosphonates featuring alendronate. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
Bisphosphonates Mechanism of Action Inhibits normal and abnormal bone resorption |
Drug Dosage
10 mg orally once daily or 70 mg orally once weekly (may vary depending on indication). |
|
Indications
Prevention and treatment of osteoporosis in postmenopausal clients For the treatment of osteoporosis in males, Paget’s disease, and glucocorticoid-induced osteoporosis Therapeutic Effects Increases bone density |
Drug Interactions
Calcium Antacids Aspirin Nonsteroidal anti-inflammatory drugs (NSAIDs) Food Interactions No significant interactions unless food or beverages (except water) are taken within 30 minutes of drug Avoid orange juice for at least 2 hours after taking |
|
Adverse Effects
Decreased serum calcium and serum phosphate levels Arthralgia Myalgia Stomach pain Difficulty swallowing Heartburn Irritation or pain of the esophagus Osteonecrosis of the jaw |
Contraindications
Esophageal abnormalities that prevent adequate and timely emptying of the stomach Inability of client to sit up or stand for at least 30 minutes after taking the medication (to reduce risk of esophageal irritation) Severe renal insufficiency |
Calcium Preparations
Calcium, the most abundant mineral in the body, is necessary for bone development and bone maintenance. In fact, about 98% of the body’s calcium is stored in the bones. Calcium from food and supplements is absorbed by both active transport and passive diffusion across the intestinal mucosa. Vitamin D is essential for calcium absorption and for maintaining adequate calcium levels. Estrogen is also important for maintaining bone health; thus, during menopause when females produce less estrogen, they have a considerable risk of developing osteopenia and osteoporosis (National Institutes of Health, 2022).
Food sources of calcium include dairy, salmon, dark green vegetables (broccoli, kale, spinach), and other foods with high levels of oxalic acid such as sweet potatoes, rhubarb, and beans. Calcium supplements vary widely as to their source and the amount of calcium contained in the tablets (National Institutes of Health, 2022).
Calcium supplements include calcium acetate , calcium citrate , calcium gluconate , and calcium chloride . Calcium supplements used to treat osteoporosis and osteopenia are administered orally; dosages depend on the specific type of calcium supplement being prescribed and the reason for its use. Calcium carbonate and calcium citrate are the two most common forms of calcium used in supplements. Calcium has varying rates of absorption depending on the specific supplement, an individual’s level of stomach acid, and the fat content in a meal eaten when a calcium supplement is taken. The greater the fat content, the less calcium is absorbed. Calcium gluconate and calcium chloride are administered intravenously and used for serious and life-threatening acute hypocalcemia, hyperkalemia, and certain cardiac emergencies. See Fluids and Electrolytes, Vitamins, Minerals, and Alternative Therapies for more information about calcium and Vitamin D.
Adverse Effects and Contraindications
Adverse effects of calcium supplements are usually GI related and include abdominal pain, gas, bloating, constipation, and nausea. Hypercalcemia can lead to poor muscle tone, renal insufficiency, weight loss, fatigue, polyuria, and heart arrhythmias.
Contraindications and precautions are necessary depending on the client’s chronic diseases and other medications being taken. Clients with heart disease and renal disease may need closer monitoring of calcium levels. Calcium supplements generally decrease stomach acid necessary for the metabolism and absorption of other medications. Levothyroxine is one example; it should be taken at least 30 minutes prior to or 2 hours after calcium. So a complete medication history is important in planning calcium supplementation.
Vitamin D
Along with calcium supplements, vitamin D should be taken either as a separate supplement or included in the calcium supplement. The best source of vitamin D is sunlight. The appropriate amount of time for sun exposure is determined by the skin type based on Fitzpatrick’s skin typing, which ranges from I (fair skin that burns easily) to VI (skin that is always tan) (National Institutes of Health, 2022; Sakamoto, 2019; Zareef & Jackson, 2021). The use of sunscreen during sun exposure is controversial as far as the effect on vitamin D; however, the client should take care to avoid sunburn (AIM at Melanoma Foundation, n.d.).
Other sources of vitamin D include fatty fish (such as trout, salmon, tuna, and mackerel) and fish liver oils and fortified foods such as milk and cereals (National Institutes of Health, 2022).
Estrogen Receptor Modulators
Estrogen receptor modulators (ERMs) are not hormones. They are estrogen receptor site agonists or antagonists. ERMs possess some of the positive effects of estrogen and have fewer adverse effects. Raloxifene and toremifene are the drugs discussed in this section.
Raloxifene
Raloxifene is used to prevent and treat postmenopausal osteoporosis by increasing bone density. Contraindications include allergy, pregnancy, and lactation. Caution should be used for clients with a history of deep vein thrombosis and/or smoking because of the risk of clot development. Adverse effects are like those of estrogen and can include skin rash and edema. Raloxifene dosage is 60 mg daily orally.
Table 36.18 is a drug prototype table for estrogen receptor modulators featuring raloxifene . It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
Estrogen receptor modulator Mechanism of Action Binds to estrogen receptors with either activation of estrogenic pathways (agonism) or blockade of estrogenic pathways (antagonism) |
Drug Dosage
60 mg orally once daily. Supplemental calcium and/or vitamin D should be added to the diet if daily intake is inadequate. |
|
Indications
Prevention and treatment of osteoporosis in postmenopausal clients Therapeutic Effects Increases bone density |
Drug Interactions
Cholestyramine Warfarin Systemic estrogens Use with caution with certain other highly protein-bound drugs such as diazepam, diazoxide, and lidocaine Food Interactions No significant interactions |
|
Adverse Effects
Venous thromboembolism Skin rash Edema Hot flashes Leg cramps Nausea Arthralgia Rhinitis |
Contraindications
Allergy Pregnancy and lactation History of deep vein thrombosis, pulmonary embolism, or retinal vein thrombosis and/or smoking because of the risk of clot development |
FDA Black Box Warning
Raloxifene
Raloxifene may cause increased risk of venous thromboembolism and death from stroke in clients with a history of venous thrombosis, documented coronary heart disease, or at increased risk for major coronary events.
Toremifene
Toremifene is used to treat clients who have estrogen receptor–positive advanced breast cancer. Toremifene works by binding to estrogen receptors, which prevents cancer cells from developing. Contraindications include allergy to the drug, pregnancy and lactation, and hypercalcemia. Caution must be used in prescribing toremifene to clients with renal or hepatic dysfunction or bone marrow suppression. Adverse effects are like menopausal symptoms, which were discussed in Review of the Female Reproductive System.
Table 36.19 is a drug prototype table for estrogen receptor modulators featuring toremifene . It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
Estrogen receptor modulator Mechanism of Action Binds to estrogen receptors, which prevents cancer cells from developing |
Drug Dosage
60 mg orally once daily. Supplemental calcium and/or vitamin D should be added to the diet if daily intake is inadequate. |
|
Indications
Treatment for female clients who have estrogen receptor–positive advanced breast cancer Therapeutic Effects Prevents cancer cells from growing and spreading |
Drug Interactions
Thiazide diuretics Drugs that prolong QT interval (quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide) Strong CYP3A4 enzyme inducers, such as dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital, St. John’s wort Food Interactions Grapefruit or grapefruit juice |
|
Adverse Effects
Venous thromboembolism Hot flashes Nausea and vomiting Fatigue Depression Lethargy Anorexia Arthritis Pulmonary embolism Myocardial infarction |
Contraindications
Allergy Pregnancy and lactation Prolonged QT interval Renal or hepatic impairment |
FDA Black Box Warning
Toremifene
Toremifene may cause QT prolongation, which could result in a type of ventricular tachycardia called torsade de pointes, which may result in syncope, seizure, and/or death.
Nursing Implications
The nurse should do the following for clients who are taking bisphosphonates, calcium preparations, vitamin D, or estrogen receptor modulators:
- Perform a physical assessment and determine the reason for the specific drug therapy.
- Assess past medical history and family history for osteoporosis, hypocalcemia, and vitamin D deficiency.
- Assess the client’s ability to understand and follow medication regimen.
- Determine pregnancy and lactation status.
- Assess smoking history and use of alcohol.
- Obtain necessary diagnostic and laboratory testing, such as bone density, calcium and vitamin D levels, and electrocardiogram.
- Assess diet and exercise patterns.
- Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.
Client Teaching Guidelines
The client taking a bisphosphonate, calcium, vitamin D, or an estrogen receptor modulator should:
- Understand the medication’s purpose, side effects, contraindications, precautions, and any signs and symptoms to report that require immediate attention.
- Know how to manage the side effects of the specific drug therapy.
- Know the medication dosage and route and be able to self-administer correctly (e.g., drink at least 6–8 ounces of water with bisphosphonate and remain standing or sitting upright for 30 minutes after taking the medication).
- Maintain weight-bearing exercise of 30 minutes 3–5 times weekly to increase bone strength.
- Include foods high in calcium in diet: leafy green vegetables, salmon, dairy, sweet potatoes, rhubarb, and beans.
- Understand drug, food, or herbal interactions with the specific medication.
- Verbalize the importance of follow-up appointments and diagnostic testing to manage the medication regimen.
The client taking a bisphosphonate, calcium, vitamin D, or an estrogen receptor modulator should not:
- Take bisphosphonates at the same time as other medications or supplements.
- Take calcium supplements with a high-fat meal.