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Drug Profile

The information on this site is intended to supplement and enhance, not replace, the advice of a physician who is familiar with your medical history. Decisions about your health should always be made ONLY after detailed conversation with your doctor.

Limited Use [what does this mean?]
Generic drug name: alendronate (a LEN dro nate)
Brand name(s): BINOSTO, FOSAMAX
GENERIC: not available FAMILY: Bisphosphonates
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: risedronate (ris ED roe nate)
Brand name(s): ACTONEL, ATELVIA
GENERIC: not available FAMILY: Bisphosphonates
Find the drug label by searching at DailyMed.

Pregnancy and Breast-feeding Warnings [top]

Pregnancy Warning

The bisphosphonates caused fetal harm in animal studies, including interference with bone formation. Because of the potential for serious adverse effects to the fetus, these drugs should not be used by pregnant women.

Breast-feeding Warning

No data are available about the excretion of bisphosphonates in milk. However, since bisphosphonates interfere with bone formation and remain in bones for an extremely long time (years), you should not nurse while taking these drugs.

Safety Warnings For This Drug [top]

Things You Can Do to Prevent Falls

Falls, of course, will increase your chances of a fracture. Ask your doctor to review your continued need for and dose of any drug that causes you to be dizzy or drowsy. Check the list of drugs that can cause falls. Check your home for situations that can lead to falls such as areas that are not well lit or loose rugs on hardwood floors.

DO NOT USE

Alendronate or Risedronate for the Treatment of Glucocorticoid (Steroid)-Induced Osteoporosis

Each year, millions of people are prescribed steroids such as prednisone, prednisolone, or other similar anti-inflammatory steroids for treatment of autoimmune diseases such as lupus, rheumatoid arthritis, asthma, ulcerative colitis, muscle disorders, skin conditions, or other diseases. When the use of these drugs exceeds a very short period of time, osteoporosis can result, because these steroids inhibit the formation of new bone. The way, or mechanism, by which this happens is very different from the mechanism whereby postmenopausal osteoporosis occurs.[1]

Despite this important difference, Merck, seeking to significantly increase its market for this drug, conducted studies to see if alendronate, previously approved for postmenopausal osteoporosis, could also be approved for preventing steroid-induced osteoporosis. The fact that the FDA, unfortunately, approved this new use in 1999 represents a triumph of Merck pressure, with complicity by top FDA officials, over medical evidence and against the recommendation for nonapproval by the FDA physician primarily responsible for reviewing the studies concerning this new indication.[2]

Alendronate improved bone mineral density (BMD) in the spine, although not as much as it does in postmenopausal osteoporosis, and reduced the occurrence of vertebral fractures. Although there was a reduction in vertebral fractures, there was a barely measurable improvement in total height (stature) of only 1.5 millimeters (less than one-sixteenth of an inch.[2] Most disturbingly, it actually increased the total incidence of nonvertebral fractures, such as those of the foot, pelvis, ankle, and hip.[1] The FDA medical officer who opposed this approval correctly described these latter, nonvertebral fractures as more serious, more painful, and more incapacitating than vertebral fractures.[1] Other problems identified in the review included the fact that alendronate causes esophageal ulcers and irritation and, compared to a placebo, increases the risk of abdominal pain. The FDA medical officer concluded, in recommending against approval, that the drug represents “very small returns for the inconvenience and the costs and risks of taking this drug.”[3] A 2018 study that analyzed data from 10 randomized clinical trials showed that when alendronate was used to treat osteoporosis in people with glucocorticoid-induced osteoporosis, there was an increase in bone mineral density of the spine and neck but not a reduced risk of fractures compared with use of a placebo.[4]

What You Can Do to Prevent Osteoporosis

Diet and Exercise

Many women are not at risk of developing hip or other types of fractures. Women who are thin or small-boned, particularly if they are Asian or white, and women who drink more than two alcoholic drinks per day are at higher risk of osteoporosis. Black women, heavy women, and women who get lots of exercise are at a lower risk. There are steps women can take to prevent osteoporosis; for instance, a lot of calcium in the diet from early adulthood and weight-bearing exercise such as jogging, walking, tennis, and bicycling. You should be receiving from 800 to 1,200 milligrams of calcium per day in your diet, depending on your age. Women who are postmenopausal require an average of 1,500 milligrams per day of calcium (see Calcium Content of Some Foods table in Osteoporosis). These two steps (diet and exercise) are enough to prevent osteoporosis in many adults.

Facts About This Drug [top]

Alendronate (FOSAMAX) and risedronate (ACTONEL) belong to a class of drugs called bisphosphonates, which are used to treat and prevent osteoporosis in postmenopausal women and to increase bone mass in men with osteoporosis. They also are approved for treatment of a bone disease known as Paget's disease.

Bisphosphonates also are approved to treat and prevent osteoporosis caused by prolonged use of corticosteroids, such as prednisone (DELTASONE) or prednisolone (PRELONE), which is known as...

Alendronate (FOSAMAX) and risedronate (ACTONEL) belong to a class of drugs called bisphosphonates, which are used to treat and prevent osteoporosis in postmenopausal women and to increase bone mass in men with osteoporosis. They also are approved for treatment of a bone disease known as Paget's disease.

Bisphosphonates also are approved to treat and prevent osteoporosis caused by prolonged use of corticosteroids, such as prednisone (DELTASONE) or prednisolone (PRELONE), which is known as glucocorticoid-induced osteoporosis. However, they should not be used for this purpose (see the "DO NOT USE" warning box above). Therefore, we have designated these drugs as Limited Use.

Bisphosphonates inhibit activity of the bone cells that break down and reabsorb bone. The breakdown and creation of bone are linked, and because of that, these drugs decrease bone turnover (synthesis and breakdown).

Alendronate and risedronate are not indicated for use in children. The safety and effectiveness of bisphosphonates in children under the age of 18 years is not known. Bisphosphonates should not be used in pregnant or breast-feeding women.[5] Bisphosphonates are not to be used in premenopausal women or by people with mild osteoporosis or severe kidney problems. The drugs should not be given to people with dementia or those who are otherwise unable to follow the instructions on how to take the medication.

For Paget's disease, alendronate is given daily for six months. If a relapse occurs, alendronate is sometimes resumed. Risedronate is given for two months and repeated if necessary.

Alendronate

Alendronate has been shown to reduce the risk of hip fracture by 1% in women who had previously experienced at least one vertebral fracture; 2% of women taking a placebo had hip fractures versus 1% of women taking alendronate, a 50% relative reduction. Vertebral fracture is a spinal fracture that may or may not be symptomatic. Most (more than 85%) of the women who took the placebo in three-year clinical trials did not have a fracture of any type. Fewer studies have been done on men taking alendronate.

A study looking at patients using alendronate for up to 10 years has left many questions unanswered. Three groups of postmenopausal women were studied:

  1. Those who had taken alendronate for five years, followed by a placebo for five years;
  2. Those who had taken 5 milligrams (mg) per day for 10 years; and
  3. Those who had taken 10 mg per day for 10 years.

The main study endpoint was bone mineral density (BMD) at the lumbar spine — not fractures, although fractures also were studied.[6]

Although there were greater increases in BMD with the larger, 10-mg dose, taken for 10 years, this increase was not associated with a lower fracture rate.

Women who had discontinued the drug after five years had about the same number of vertebral fractures as those taking 10 mg for five years. (New "fractures" were defined by examining radiographs and measuring loss of height of the vertebrae.) The loss in height was only very slightly less in the 10-mg group than in the discontinuation group (less than 0.1 inch less loss over the five-year period). As noted in the drug profile for raloxifene (EVISTA), improvements in BMD and fracture reduction are not clearly related; that appears here as well. Yet, women often are treated based on BMD alone.

An accompanying commentary to the 10-year trial raised concerns about what happens to bone structure with continuing increases in BMD. There is evidence from animal studies that with prolonged alendronate use, bones become more brittle and susceptible to fracture. Unfortunately, it is currently unknown at what point that occurs in people. The commentary stated that it was not known how long women should stay on alendronate or how long benefits might last after the drug is stopped.[7]

A more recent study concluded that for many women, discontinuation of alendronate after five years for up to five more years does not significantly increase fracture risk. The product labeling for alendronate now states that optimal duration of use of the drug has not been determined and that for patients at low risk of fracture, drug discontinuation after three to five years of use should be considered. However, women at high risk of clinical vertebral fractures, such as those with previous vertebral fracture or very low BMD, may benefit by continuing treatment beyond five years.[8]

Risedronate

Risedronate, like alendronate, is associated with a modestly favorable effect on the risk of vertebral fracture. The absolute reduction in the risk of a new vertebral fracture in women taking risedronate is 5% (compared with women taking an inactive placebo). The most benefit was seen in women with two or more vertebral fractures before they started taking risedronate.[9]

A published study sponsored by risedronate manufacturer Procter & Gamble suggests that risedronate may reduce the risk of hip fracture, the most serious consequence of osteoporosis, in elderly women with low BMD by about 1% (the same result as alendronate).[10] However, this study has been criticized on a number of grounds, including the fact that follow-up information was not available for 3,324 of the 9,331 women in the study.[11] This could have biased the results in favor of risedronate by leaving out women who eventually had fractures.

Risedronate is retained in bones for many years, but its long-term effects remain uncertain. Concern exists because some bisphosphonates increase the occurrence of spontaneous fractures in animals.[12] The product labeling for risedronate now states that optimal duration of use of the drug has not been determined and that for patients at low risk of fracture, drug discontinuation after three to five years of use should be considered.

Adverse effects

Since alendronate came on the market, there have been reports of serious adverse effects associated with its use, including several cases of bone, joint and muscle pain.

Other common adverse effects include stomach pain, nausea, indigestion, constipation and diarrhea.[13] Rare adverse effects include changes in vision.[14] Bisphosphonates are retained in bones for many years, even after patients stop taking them.[15],[16] Uncertainty exists as to when therapy should begin and how long it should continue, as well as the impact on nonspinal fractures for those with low risk.[17]

Reports of very rare allergic and skin reactions (including hive-like swelling under the skin, especially around the face and mouth [angioedema], generalized rash and severe blistering of the skin) have been associated with risedronate since it has been on the market.

Osteonecrosis of the jaw

Severe musculoskeletal pain and death of the bone tissue of the jaw (osteonecrosis) also have been reported.[18] The typical signs and symptoms of osteonecrosis of the jaw include pain, swelling or infection of the gums; loosening of the teeth; poor healing of the gums; numbness or a feeling of heaviness in the jaw; drainage; and exposed bone. Patients with the least serious form of this condition may not show any symptoms, but in the most serious cases, some patients may require the removal of sections of the jaw.

An Annals of Internal Medicine review of medical literature shows that there have been hundreds of reported cases of osteonecrosis of the jaw linked to drugs commonly used to treat osteoporosis. According to the review, osteonecrosis was more common in the lower jaw than the upper jaw. More than half of all cases (60%) occurred after dentoalveolar surgery (such as tooth extraction) to treat infections, and the remaining 40% were probably related to infection, denture trauma or other physical trauma occurring in the absence of dental surgery.

The authors of the review stated, "The concern is that with more women aging and taking bisphosphonates for longer periods of time, more cases of osteonecrosis may develop even in patients receiving alendronate or ibandronate [BONIVA] therapy."[19]

Ninety-four percent of the patients who developed osteonecrosis of the jaw were those with cancers such as multiple myeloma, as well as patients with cancers that have spread to the bone and patients who are receiving intravenous bisphosphonates. The remaining cases were in people using oral bisphosphonates such as alendronate or risedronate.

Osteonecrosis of the external ear canal

In November 2015, the Food and Drug Administration (FDA) updated the drug product label of alendronate to include a warning about reports of osteonecrosis of the external ear canal. In December 2015, the Medicines and Healthcare Regulatory Agency (MHRA), a regulatory agency in the U.K., also issued an update that osteonecrosis of the external ear canal has been reported rarely with bisphosphonate use. Signs of osteonecrosis of the external ear canal may include ear pain, ear discharge and ear infection. [20]

Interactions with other drugs

Emerging evidence suggests a possible harmful interaction between nonsteroidal anti-inflammatory drugs and bisphosphonates. The combination can result in an increased risk of ulcers and other gastrointestinal adverse effects. Read more in the July 2010 Worst Pills, Best Pills News.

In 2020, an article in Medicine reported two cases of increased bleeding in patients treated with warfarin who start taking alendronate.[21] The patients had marked increases in their levels of anticoagulation within 24 hours of starting the alendronate.

How to take these drugs

Bisphosphonates such as alendronate and risedronate can irritate the esophagus (the tube that connects the mouth and stomach), causing ulcers and bleeding. Because of this, the drugs must be taken with water on an empty stomach. Patients should stay upright for at least half an hour after each dose to ensure that the tablet does not get stuck in the esophagus before reaching the stomach. Also, to get the maximum absorption of the drug, patients should not eat or drink anything but water during this half-hour period.

Studies show ...

There have been multiple case reports of synovitis (inflammation and pain in a joint) associated with alendronic acid, used in alendronate, and one published case report of myalgia (muscle pain) and arthritis. A comparison of the patients receiving alendronic acid with the patients receiving a placebo during clinical trials found that bone, joint or muscle pain occurred in about 4% of the patients treated with alendronic acid and in about 2.5% of the patients treated with placebo.[22]

A July 15, 2008, New York Times article discussed a study documenting growing evidence for the long-held concern that long-term use of bisphosphonates can actually make bones brittle and more likely to fracture. Although the evidence is far from conclusive, emerging reports of a unique type of fracture in patients receiving bisphosphonates for many years point toward the drug as a possible culprit.[23]

In September 2011, the Center for Adverse Reactions Monitoring in New Zealand reported that as of June 30, 2011, it had received reports of eye inflammatory effects associated with bisphosphonate drugs.[24]

In December 2020, the Journal of the American Medical Association Network Open published a systematic review showing that bisphosphonate therapy did not lead to an improvement in hip fracture rates when the medication was used for more than five years .[25]

Regulatory actions surrounding bisphosphonates

2004: The FDA updated the adverse reaction section of the product label for alendronate to include post-marketing reports of bone, joint and muscle pain.[26]

2006: The FDA required manufacturers of bisphosphonates to add information about severe musculoskeletal pain and osteonecrosis to the adverse reaction section of their product labels.[18]

2008: The FDA issued an alert to highlight the possibility of severe and sometimes incapacitating bone, joint and muscle pain in patients taking bisphosphonates. The alert informed health care professionals that they should consider whether bisphosphonate use might be responsible for severe musculoskeletal pain in patients.[27]

In January, the FDA issued an early communication of an ongoing safety review concerning the association of atrial fibrillation with the use of bisphosphonates. The agency had reviewed some safety data and requested additional data to further evaluate this risk.[28]

In November, the FDA issued an update to the review of atrial fibrillation associated with bisphosphonate use, saying:

The occurrence of atrial fibrillation was rare within each study, with most studies containing two or fewer events. Across all studies, no clear association between overall bisphosphonate exposure and the rate of serious or non-serious atrial fibrillation was observed. Additionally, increasing dose or duration of bisphosphonate therapy was not associated with an increased rate of atrial fibrillation.[29]

2010: The FDA issued information relating to bisphosphonate use and a risk of atypical subtrochanteric femur (leg) fractures. The FDA stated that the data it reviewed did not show a clear connection between bisphosphonate use and this risk. The agency said it would continue to gather more information and evaluate the issue further.[30]

In October, the FDA issued another advisory relating to bisphosphonate use and a risk of leg fractures. It required that this information be added to the "Warnings and Precautions" section of the drug product labels and that a Medication Guide be given to patients when they pick up or refill their bisphosphonate prescriptions.[31]

Alendronate and risedronate are two of a limited number of drugs for which the FDA requires an FDA-approved Medication Guide be dispensed when the prescription is filled or refilled.

2011: The FDA released information regarding whether the use of oral bisphosphonate drugs is associated with a potential increased risk of cancer of the esophagus. The agency stated that it was conducting an ongoing review of data and, so far, had not concluded that a risk was present. The agency said that it would continue to update the public when more information became available.[32]

In September, Public Citizen testified before the FDA's Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee. The testimony stated that given the effects of underreported rare stress fractures, osteonecrosis of the jaw and other serious risks, bisphosphonates should be restricted to patients who would actually benefit from them. The testimony contended that bisphosphonates have not been shown to decrease fracture risk in postmenopausal women with osteopenia (decreased bone density that is less severe than that seen with osteoporosis) and all patients remaining on these drugs beyond five years.

Before You Use This Drug [top]

Do not use if you have or have had:

  • frequent heartburn
  • reflux disease
  • hiatal hernia
  • throat problems
  • difficulty swallowing
  • ulcers
  • kidney problems
  • sensitivity to alendronate or risedronate
  • pregnancy or are breast-feeding
  • low calcium levels or vitamin D deficiency
  • inability to sit or stand for 30 minutes

Tell your doctor if you have or have had:

  • allergies
  • Crohn’s disease
  • dental disease
  • pain of the bone tissue of the jaw
  • cancer
  • anemia
  • blood clotting disorder

Tell your doctor about any other drugs you take, including aspirin, herbs, vitamins, and other nonprescription products.

When You Use This Drug [top]

  • Get regular, preferably weight-bearing exercise, such as bicycling, jogging, tennis, or walking.
  • Eat a diet adequate in calcium. You may need to take a calcium supplement. If you do not live in a sunny climate, you may need to take vitamin D, particularly during the winter or if you do not go outdoors.
  • Prevent falls by using handrails on stairs, adequate lighting, and avoiding throw rugs and electric cords in your path. Use proper lifting techniques.
  • Avoid alcohol and sedatives, which increase the risk of falls and fractures.
  • Stop smoking, which increases the risk of osteoporosis.
  • If a relative or friend takes alendronate at an institution, check that the timing and method for taking alendronate (as described below) is correct and followed closely.

How to Use This Drug [top]

  • On arising or soon after, sit or stand, then swallow tablet with a full six- to eight-ounce glass of plain water. Do not chew or suck on tablets. Take on an empty stomach. Wait at least 30 minutes before taking any food, beverage (including mineral water, coffee, tea, or orange juice), or medication. Do not take any other medications or dietary supplements during this time.
  • Stay upright, standing or sitting, for at least 30 minutes after a dose of alendronate.
  • If you miss a daily dose, skip it. If you miss a weekly dose, take it the morning after you remember. Do not take double doses.
  • Do not take at bedtime or before getting up for the day.
  • Wait at least one-half hour after taking alendronate before taking any calcium supplement. A good practice is to take calcium with the evening meal.
  • Do not share your medication with others.
  • Take the drug at the same time(s) each day.
  • Store tablets at room temperature with lid on tightly. Do not store in the bathroom. Do not expose to heat, moisture, or strong light. Keep out of reach of children.

Interactions with Other Drugs [top]

The following drugs, biologics (e.g., vaccines, therapeutic antibodies), or foods are listed in Evaluations of Drug Interactions 2003 as causing “highly clinically significant” or “clinically significant” interactions when used together with any of the drugs in this section. In some sections with multiple drugs, the interaction may have been reported for one but not all drugs in this section, but we include the interaction because the drugs in this section are similar to one another. We have also included potentially serious interactions listed in the drug’s FDA-approved professional package insert or in published medical journal articles. There may be other drugs, especially those in the families of drugs listed below, that also will react with this drug to cause severe adverse effects. Make sure to tell your doctor and pharmacist the drugs you are taking and tell them if you are taking any of these interacting drugs:

antacids, calcium supplements, iron supplements, NAPROSYN, naproxen, sodium bicarbonate, TUMS, zinc carbonate, zinc sulfate.

Be especially careful of taking aspirin- and salicylate-containing products. Beware that aspirin is one of the ingredients in many combination drug products and may increase adverse reactions. Read your drug labels and/or ask your pharmacist. Examples include: aspirin, ECOTRIN, EMPIRIN.

Adverse Effects [top]

Call your doctor immediately if you experience:

  • abdominal pain
  • abnormal bleeding
  • heartburn
  • nausea or vomiting
  • muscle pain
  • skin rash
  • swallowing difficulty
  • throat irritated or painful
  • heavy jaw feeling
  • loosening of a tooth
  • pain, swelling or numbness in the mouth or jaw

Call your doctor if these symptoms continue:

  • abdomen feels full or bloated
  • constipation
  • diarrhea
  • gas
  • headache
  • nausea
  • tastes altered
  • vision changes

Signs of overdose:

  • upset stomach
  • heartburn
  • esophagitis
  • gastritis
  • ulcer

If you suspect an overdose, call this number to contact your poison control center: (800) 222-1222.

Periodic Tests[top]

Ask your doctor which of these tests should be done periodically while you are taking this drug:

bone mineral density

  • alkaline phosphatase level in serum
  • calcium and creatinine serum levels
  • urinary hydroxyproline
  • urinary collagen (N-telopeptide, type 1)

last reviewed April 30, 2021