Bisphosphonates for Paget's disease of bone

Examples

Generic Name	Brand Name
alendronate sodium	Fosamax
pamidronate disodium	Aredia
risedronate sodium	Actonel
tiludronate disodium	Skelid

How It Works

Bisphosphonates decrease the number and activity of bone cells (osteoclasts) to reduce the breakdown of bone tissue. Over time, they may also decrease the activity of other bone cells (osteoblasts) that are building up too much bone.¹ Bone has a more normal structure after bisphosphonate therapy.²

You take alendronate, risedronate, and tiludronate by mouth (orally). Pamidronate is given intravenously.

Why It Is Used

Bisphosphonates first decrease bone tissue breakdown and, later, decrease overproduction of new bone tissue. This leads to more normal bone structure, and then to decreased pain and risk of fracture.

Doctors may use bisphosphonates to treat people with Paget's disease who do not yet have symptoms to help prevent complications. They also use bisphosphonates before surgery to decrease the activity of Paget's disease, so there is less risk of bleeding and complication from the surgery.

How Well It Works

Most often, bisphosphonates are the first medications doctors use to treat Paget's disease and control its symptoms. Newer bisphosphonates—alendronate, risedronate, and tiludronate—have been shown to be more powerful than an older bisphosphonate called etidronate, so they can lead to a longer time without symptoms (remission) at a lower dose of medicine.¹

Bisphosphonates can decrease symptoms such as bone pain, ringing in the ears, dizziness, and numbness or weakness that Paget's disease can cause. Alendronate, risedronate, and tiludronate slow the rate of bone tissue breakdown and increase bone thickness in the small bones of the spine and hip. This reduces the progression of the disease.

Bisphosphonates may take several months to become fully effective. Effects of bisphosphonates tend to last even after the person stops taking the medicine. On occasion, a person may need additional courses of the medicine to treat a return to active disease.

Reduction in laboratory markers such as alkaline phosphatase shows that the medicine is working to reduce the activity of Paget's disease. Some people eventually become resistant to one medicine, so it doesn't work as well to control their symptoms. When this happens, another bisphosphonate or another medicine will usually be effective.²

Side Effects

Side effects of bisphosphonates can include:

• Severe heartburn.
• Belly pain and irritation of the throat (esophagus).
• Upset stomach (nausea).
• Diarrhea, constipation, and increased gas.
• Flu-like symptoms including headache and pain in muscles and joints (especially if you take intravenous medication).
• Increased bone pain. (This tends to be related to the dose of medication used.)

You may limit side effects by taking the medicine on an empty stomach and by drinking a full glass of water with the medicine. Staying upright and not lying down for 30 minutes to 1 hour after you take this medicine may also help limit side effects. Also, do not have any food or beverage (other than water) for 30 minutes after you take the medication.

Serious problems with bone healing, particularly after dental surgery, have been found in some people taking bisphosphonates.³ If you are taking bisphosphonates and need dental surgery, talk with your doctor about the risk of problems with bone healing.

See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)

What To Think About

People generally use oral bisphosphonates for 2 to 6 months.

Taking etidronate longer than 6 months increases the risk of osteoporosis.

Alendronate, risedronate, and tiludronate can cause damage to the throat (esophagus).¹ You should not use them if you have a malfunction of the nerves of the esophagus (achalasia), an inflammation (esophagitis) or narrowing (esophageal stricture) of the esophagus, or a hiatal hernia.

Pamidronate is given intravenously. People who cannot take the medication by mouth have used it successfully.

You should not take these medicines immediately before or just after meals, because food slows the absorption of the medicine. How soon before or after a meal you take the medicine varies with the medication. Talk with your doctor or nurse, and follow instructions carefully.

Take bisphosphonates with water, not milk, because milk also decreases the absorption of the medication.

Your doctor or nurse may suggest that you take calcium and vitamin D supplements while you are taking bisphosphonates. This can help keep your bones strong. Do not take bisphosphonates within 2 hours of taking antacids or medications high in calcium, magnesium, iron, or aluminum (such as Mylanta or Tums).

Bisphosphonates are often used in cycles. They nearly always make Paget's disease inactive, sometimes for years or decades. In some people, however, Paget's disease becomes active again. You use bisphosphonates until pain decreases and lab tests show normal results. Then you take a break from the medicine for about 3 months, or until lab tests show that Paget's disease is active again.⁴

Bisphosphonates are better than calcitonin for slowing or eliminating disease activity.²

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Author:	Shannon Erstad, MBA/MPH	Last Updated September 30, 2005
Medical Review:	Caroline S. Rhoads, MD - Internal Medicine Hanan Bassyouni, MD - Endocrinology and Metabolism
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