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Bisphosphonates

Bisphosphonates

Definition

Bisphosphonates are a class of drugs that lower calcium levels in the blood and can slow down bone loss that results from cancer or other causes.

Purpose

Bisphosphonates are used to slow down the loss of bone that results from multiple myeloma or from breast cancer that has spread, or metastasized, to the bones. These cancers cause bone to dissolve, in a process called resorption. This results in bone weakness and fractures. Bisphosphonates can prevent the holes that form in the bones from multiple myeloma. They can ease bone pain caused by cancer. They also help to prevent bone fractures and compression of the spinal cord, as well as the high calcium levels in the blood (hypercalcemia ) caused by bone loss. Hypercalcemia can cause kidney failure and death. Bisphosphonates may help prevent breast cancer from spreading to the bones and other organs. Clinical trials are evaluating bisphosphonates for the treatment of bone metastases from other types of cancers.

Description

The most commonly used bisphosphonates are pamidronate disodium (APD; brand name Aredia) and etidronate disodium (EHDP; brand name Didronel). Both drugs are approved by the U.S. Food and Drug Administration. These drugs are classified as antihypercalcemics, meaning that they can lower blood calcium levels. They also are classified as bone resorption inhibitors, meaning that they can prevent bone from dissolving.

Other bisphosphonates include cladronate and alendronate. Cladronate is used less frequently because it is not completely absorbed by the digestive system and can cause stomach upset. Zoledronate and ibandronate are new, much more powerful bisphosphonates that are being evaluated, but are not yet available for routine use.

For cancer treatment, bisphosphonates may be used in conjunction with chemotherapy . Treatment with bisphosphonates may be accompanied by the injection of fluids into a vein (intravenous) so that large amounts of urine are excreted.

Recommended dosage

Pamidronate and etidronate are solutions that are injected into a vein. For the treatment of hypercalcemia, 30-90 mg of pamidronate are injected over a period of 2-24 hours. For the treatment of bone metastases from breast cancer, 90 mg are injected over a two-hour period every 3-4 weeks. For multiple myeloma, the 90-mg injection is over a four-hour period once a month. The usual dosage of etidronate is 7.5 mg per kg (3.4 mg per pound) of body weight, injected over two hours, for two or more days. The treatment may be repeated after at least one week off.

Etidronate also may be taken as a tablet, with water, on an empty stomach. The usual dosage for the treatment of hypercalcemia is 20 mg per kg (9.1 mg per pound) of body weight per day for 30 days. The maximum length of treatment usually is 90 days, but the treatment may be repeated after at least 90 days off of the drug. Cladronate is also taken as a pill.

Precautions

The amount of calcium in the diet may be important when taking bisphosphonates. Too much calcium in the diet may prevent absorption of oral etidronate. However, it is important to consume adequate amounts of calcium and vitamin D.

Other medical problems that may affect the use of bisphosphonates include:

  • heart problems that may be aggravated by fluid retention
  • kidney disease that could result in high levels of bisphosphonate in the blood
  • intestinal problems or bowel disease, because etidronate can cause diarrhea
  • bone fractures, particularly of the arm or leg, since etidronate can increase the risk of fractures

Bisphosphonates may cause allergic reactions in some individuals. Children may experience temporary changes in bone growth while being treated with etidronate and they should not take pamidronate. Older individuals may suffer from fluid retention if bisphosphonates are given with large amounts of fluid. Bisphosphonates should not be taken during pregnancy. It is not known whether these drugs pass into breast milk.

Side effects

Although bisphosphonates usually are well tolerated, some patients may experience side effects. The most common side effects include:

  • fatigue
  • fever
  • nausea
  • vomiting
  • abdominal cramps
  • low red blood cell levels (anemia)
  • bone or joint pain
  • muscle stiffness or pain
  • pain or swelling at the site of injection or in the vein

However, some of these symptoms may result from the cancer or from other treatments for the cancer. A mild pain reliever can reduce or prevent the muscle and joint pain. Bisphosphonates that are taken by mouth can cause irritation and ulcers in the esophagus (the tube between the mouth and the stomach).

Additional side effects that may occur with pamidronate, particularly at dosages above 60 mg, include:

  • chills
  • confusion
  • muscle spasms
  • sore throat
  • constipation
  • decreased appetite

Additional side effects that may occur with etidronate include:

  • decreased levels of magnesium and phosphorus in the blood
  • diarrhea
  • bone fracture, particularly of the thigh
  • increases in test results for kidney function
  • hives, skin rash, or itching (rare)
  • swelling of the arms, legs, face, lips, tongue, or throat (rare)
  • loss or altered sense of taste (with drug injection)

Interactions

Substances that may interact or interfere with bisphosphonates include:

  • mineral supplements, antacids, or other substances containing calcium, iron, magnesium, or aluminum, particularly if taken within two hours of taking etidronate
  • substances containing vitamin D

Margaret Alic, Ph.D.

KEY TERMS

Antihypercalcemic

Drug that lowers the levels of calcium in the blood.

Hypercalcemia

High levels of calcium in the blood.

Metastasis

Spread of cancer from its point of origin to other parts of the body.

Resorption

Dissolving of bone, as with multiple myeloma or bone metastases from other cancers.

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bisphosphonates

bisphosphonates (bis-fos-fŏ-nayts) pl. n. a group of drugs that inhibit the resorption of bone by blocking the action of osteoclasts. Bisphosphonates are used in the treatment of Paget's disease and hypercalcaemia due to cancer and in the treatment and prevention of postmenopausal osteoporosis. They include disodium etidronate (Didronel), pamidronate (Aredia), alendronic acid (Fosamax), and clodronate (Bonefos, Loron).

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