Side effects of bisphosphonates

What Are Bisphosphonates?

These drugs are used to treat several conditions associated with bone loss.

Bisphosphonates are a group of drugs used to help prevent and treat bone loss.

They’re prescribed for people with osteopenia (softening of the bones), osteoporosis (brittle and easily broken bones), Paget’s disease, and certain bone cancers.

These drugs work by interfering with the process through which the body breaks down bone tissue.

In some cases, bisphosphonates can halt this process altogether.

The following drugs belong to the bisphosphonate family:

  • Actonel or Altevia (risedronate)
  • Fosamax (alendronate)
  • Boniva (ibandronate)
  • Reclast or Zometa (zoledronic acid)

Reclast and Zometa (zoledronic acid) are administered by intravenous (IV) injection once a year. The other bisphosphonates come in pills, taken orally.

Warnings and Precautions

Don’t take bisphosphonates if you:

  • Are allergic to them
  • Have disorders of the food pipe (esophagus), including tears, holes, narrowing, or difficulty swallowing
  • Have severe kidney disease
  • Can’t sit in an upright position for at least 30 minutes
  • Have low levels of calcium in your bloodstream

To avoid irritation to your stomach and food pipe, you must remain in an upright position for at least 30 minutes after taking a bisphosphonate by mouth.

Boniva requires you to remain upright for 1 hour.

Except for Altevia, all pill forms of bisphosphonates should be taken on an empty stomach before eating breakfast — generally 30 minutes beforehand.

Take Boniva on an empty stomach 1 hour before eating; Altevia should be taken after meals.

Bisphosphonates should be taken with a full glass of water only — no juice, coffee, soda, or flavored beverages.

Always take a bisphosphonate by itself. Wait at least 30 minutes (or 1 hour with Boniva) before taking any other medications or supplements.

Common Side Effects

The most common side effects of bisphosphonates are stomach irritation and heartburn, but these problems are often avoided by taking the medication correctly.

Other common side effects include:

  • Bone or joint pain, or generalized pain
  • Muscle cramps or aches
  • Nausea, constipation, diarrhea, or other stomach discomfort
  • Headache or dizziness
  • Head colds, sinus or throat infections, or the flu
  • Bladder infections
  • Tiredness or trouble sleeping

Drug Interactions

Ask your doctor or pharmacist about bisphosphonates if you’re taking:

  • Calcium in any form, including calcium gluconate, antacids like Citrical (calcium citrate) or Tums (calcium carbonate), or a calcium supplement
  • Iron supplements like FeoSol (ferrous sulfate) or ferrous gluconate
  • Magnesium-containing drugs like Milk of Magnesia (magnesium hydroxide) or Maalox (magnesium with aluminum)
  • Diuretics or “water pills” such as Lasix (furosemide) or Edecrin (ethacrynic acid)
  • Antbiotics like Amphosin and Fungizone (amphotericin B), amikacin, or gentamicin

Side effects for all the bisphosphonates (alendronate, ibandronate, risedronate and zoledronic acid) may include bone, joint or muscle pain. Side effects of the oral tablets may include nausea, difficulty swallowing, heartburn, irritation of the esophagus (tube connecting the throat to the stomach) and gastric ulcer.

When low levels of calcium in the blood are present, bisphosphonates should not be given. Low calcium levels must be corrected or the problem will worsen.

Side effects that can occur in a minority of people shortly after receiving an IV bisphosphonate include flu-like symptoms, fever, headache and pain in muscles or joints. Acetaminophen tablets are recommended after the infusion to reduce any body aches that may occur. These generally stop within two to three days and usually do not happen with future infusions.
Inflammation of the eye (called uveitis) is a rare side effect of all bisphosphonates. Bisphosphonates are not recommended for people with severe kidney disease or low blood calcium. People with certain problems of the esophagus may not be able to take the oral tablets. If you take certain over-the-counter medicines (known as proton pump inhibitors or PPIs) for heartburn, make sure your healthcare provider knows. One of the other medicines used for osteoporosis may be a better choice for you.

There have been rare reports of osteonecrosis of the jaw with bisphosphonate medicines. Osteonecrosis of the jaw (ONJ) occurs when the jaw bone is exposed and begins to starve from a lack of blood. Most cases of ONJ happen after a dental extraction and is associated with cancer treatments (including radiation), infection, steroid use, or potent antiresorptive medications. While ONJ is associated with these conditions, it also can occur without any identifiable risk factors. The risk of ONJ increases with treatment periods longer than 5 years and is estimated to be between 1 in 10,000 and 1 in 100,000 people on osteoporosis treatment each year. Most patients with ONJ who are taking antiresorptive therapy for osteoporosis can be healed with conservative treatment and often do not require surgery. You may wish to have a dental checkup before starting a bisphosphonate medicine. Good oral hygiene and regular dental care is the best way to lower the risk of ONJ.

There have also been rare reports of unusual fractures of the upper femur (thigh bone) in people taking bisphosphonate medicines for longer periods of time, for example, longer than 5 years. These unusual fractures are different than the type of fracture that happens from untreated osteoporosis, and are usually called “atypical femoral fractures.” If you have been taking bisphosphonate medicines for several years or longer and have an unusual persistent ache or pain in your hip or thigh bone, it’s important to tell your healthcare provider. There have been reports of people having an ache or pain, sometimes for several weeks or even months, before having an unusual break in the thigh bone. There are varying estimates of the risk of developing an atypical femoral fracture, but the risk seems to be around 1 person out of 10,000 people on treatment during the early part of therapy. After many years of treatment, the risk may be higher.

All bisphosphonates can affect how the kidneys work and should not be taken by patients who have poor kidney function or kidney failure. Certain blood tests will be done to check your kidney function before starting these medicines.

Patients taking the oral bisphosphonate tablets should stop taking the drug and contact their healthcare provider immediately if experiencing chest pain, new or worsening heartburn, or difficult or painful swallowing. It is important for patients to report these or other side effects to their healthcare provider.

Bisphosphonates

Bisphosphonates are a group of drugs that can be used to help protect bones against the effects of some cancers and to treat some bone conditions. Sometimes bisphosphonates are called bone strengthening or bone hardening treatments.

Bisphosphonates may be used to treat multiple myeloma and bone metastases.

How bisphosphonates work

Bisphosphonates slow down the action of bone cells (osteoclasts) that dissolve small bits of bones to help remodel them and keep them strong. When cancer spreads to the bone (metastasizes), these cells become overactive, causing the bone to be destroyed faster than it’s rebuilt. When this happens, the damage can cause bones to become thinner and weaker causing:

  • pain in the affected bones
  • high calcium levels in the blood (hypercalcemia)
  • an increased risk of bones breaking (fracturing)

Uses of bisphosphonates

Bisphosphonates slow down the breakdown of bones. They may be used to:

  • reduce bone pain caused by bone metastases or multiple myeloma
  • reduce high levels of calcium in the blood
  • help strengthen bone and reduce the risk of breaks caused by cancer, bone metastases or osteoporosis

Bone pain

Most cancers that affect the bones have started in another part of the body and have spread to the bone. The most common types are breast cancer, prostate cancer and lung cancer. Cancer pain is often linked to bone metastases.

Multiple myeloma is a cancer of abnormal plasma cells (a type of white blood cell) that collect in the bone marrow. These abnormal cells make a substance that leads to bone damage and bone pain.

Hypercalcemia

When bone metastases and multiple myeloma cause bones to break down, calcium moves out of the bones and into the bloodstream. This can cause calcium levels in the blood to rise. A high level of calcium in the blood is called hypercalcemia. This can also cause bones to become weak and fragile so that they break easily.

Osteoporosis

A loss of bone mass (or bone density) is called osteoporosis. This condition causes bone to become weak and more likely to break. Some cancer treatments, such as long-term corticosteroid use, hormonal therapies and some chemotherapy drugs can increase the risk of osteoporosis. Osteoporosis can also happen because of factors not related to cancer. Bisphosphonates may be used to prevent and treat osteoporosis.

Types of bisphosphonates

The type of bisphosphonate used can depend on the type of cancer being treated. Common bisphosphonates used to treat bone metastases and multiple myeloma include:

  • clodronate (Bonefos) given by mouth or by an intravenous (IV) infusion (through a vein)
  • pamidronate (Aredia) given by an IV infusion
  • zoledronic acid (Zometa) given by an IV infusion

Bisphosphonates used to prevent and treat osteoporosis include alendronate (Fosamax), risedronate (Actonel) and etidronate (Didrocal, Didronel).

Taking bisphosphonates

Bisphosphonates can be taken as pills or by an IV infusion.

Pills are usually taken once or twice per day on an empty stomach.

IV infusions are usually given every 3 to 4 weeks. They can take anywhere from 15 minutes to 4 hours, depending on which bisphosphonate is given. They can be given at the hospital or at home by a homecare nurse.

Follow-up after bisphosphonates

Follow-up when bisphosphonates are given includes:

  • checking to see if bone pain has lessened
  • blood chemistry tests to check how the kidney is working and calcium level
  • a bone density scan

Side effects

Side effects can happen with any type of treatment, but everyone’s experience is different. Some people have many side effects. Other people have few or none at all.

If you develop side effects, they can happen any time during, immediately after or a few days or weeks after bisphosphonate therapy. Most side effects go away on their own or can be treated, but some side effects may last a long time or become permanent.

Side effects of bisphosphonate therapy will depend mainly on the type of bisphosphonate, the dose, how the drug is given and your overall health. Tell your healthcare team if you have these side effects or others you think might be from bisphosphonates. The sooner you tell them of any problems, the sooner they can suggest ways to help you deal with them.

The following are some side effects of bisphosphonate therapy.

Fatigue

Fatigue is a general lack of energy and tiredness that can happen during bisphosphonate therapy. Fatigue makes a person feel more tired than usual and can interfere with daily activities and sleep. It tends to be worse when you are also having other treatments, such as chemotherapy or radiation therapy.

Increased bone pain

Sometimes bone pain can temporarily become worse when you first take bisphosphonates. This side effect is often temporary. You may be given stronger pain relievers until this side effect goes away.

Digestive problems

Digestive problems can happen, especially when the bisphosphonate is taken as pills. Digestive problems include:

  • nausea and vomiting
  • heartburn
  • abdominal cramps or pain
  • diarrhea

Flu-like symptoms

Flu-like symptoms can happen shortly after bisphosphonates are given. They include fever, chills, muscle and joint aches or pain and headaches. These side effects do not usually happen and are often temporary. They are more likely to happen after bisphosphonates are given by an IV infusion.

Low calcium levels

Bisphosphonates can lower blood calcium to below normal levels. This side effect does not usually happen and is often temporary. Calcium levels in the blood are often checked when you are given bisphosphonates.

Change in how the kidney works

Bisphosphonates can affect how the kidney works. It does not often cause any symptoms. Blood tests to check the kidney are done while you are taking bisphosphonates.

Osteonecrosis

Osteonecrosis is the death of bone caused by poor blood supply to the area. Osteonecrosis of the jaw bone underneath the teeth is a rare side effect of some bisphosphonates if they are taken for over a year. It is sometimes seen when a tooth is pulled in someone who is taking bisphosphonates. Osteonecrosis is not usually seen in people who take bisphosphonates as pills.

Osteonecrosis can cause loosening of the teeth and tooth loss and infection or open sores of the jaw bone that don’t heal. These sores are often hard to treat.

You may be advised by your doctor to get a dental check-up and have tooth or jaw problems treated before starting to take bisphosphonates. Maintaining good oral hygiene, making sure your dentures are well fitted and having regular dental check-ups might help prevent osteonecrosis of the jaw.

Information about specific cancer drugs

Details on specific drugs change regularly. Find out more about sources of drug information and where to get details on specific drugs.

How to take bisphosphonate tablets

Bisphosphonates are taken either once a day, once a week (on the same day of the week), or once a month (on the same day of the month), depending on the one prescribed. Most people take their bisphosphonate first thing in the morning before they eat or drink anything. If you take a bisphosphonate with food, or drinks other than water, only a small amount of the medicine is absorbed.

You need to wait between 30 minutes and 2 hours before eating or drinking anything (other than water). The information leaflet that comes with your tablets will tell you exactly how long you should wait.

You need to swallow the tablet with a full glass of water and sit upright for 30 minutes afterwards. This is because bisphosphonates can irritate the upper part of your gullet (oesophagus – the tube that takes food and drink from your mouth to your stomach).

When taking bisphosphonates

Some important considerations are:

  • What to do if you forget to take your tablets.
  • Have regular dental check-ups.
  • What to do if you have heartburn or difficulty swallowing.
  • Take calcium and vitamin D tablets.
  • Do not take certain other medicines.

What to do if you forget to take your tablets

  • If you are taking a once-a-day bisphosphonate: skip the missed tablet for that day and continue taking them as usual the next day.
  • If you are taking a once-a-week bisphosphonate: take the missed tablet when you remember and take the next tablet when it is normally taken. Do not take more than two tablets on the same day.
  • If you are taking a once-a-month bisphosphonate and you are due to take your tablet within the next seven days then do not take another tablet. Take another tablet on the day you are next due to take one.
  • If you are taking a once-a-month bisphosphonate and you are due to take your next tablet in more than seven days then take the tablet when you remember (in the morning). Do not take two tablets within the same week.

Regular dental check-ups

You must tell your dentist if you are taking a bisphosphonate. You will need to have regular dental check-ups. Also it is advisable to have a dental check-up before starting a bisphosphonate. This is because there is a very small chance that you will get a condition called osteonecrosis of the jaw. In this rare condition the jawbone does not receive enough blood and the bone starts to weaken and die. It is usually painful, but not always. In most people, this goes away after they have stopped taking their medicine.

Heartburn or difficulty swallowing

Bisphosphonates can sometimes cause difficulty swallowing, pain when you swallow, chest pain, or new/worsened heartburn. You must stop taking the bisphosphonate and speak with your doctor if you have any of these problems. Your doctor may consider prescribing a different bisphosphonate or a different type of medicine to help prevent broken bones (fractures).

Calcium and vitamin D

You need calcium and vitamin D to make bone. Many doctors will usually also prescribe calcium and vitamin D if you take a bisphosphonate. This is in order to make sure there is enough calcium and vitamin D in your body. There are quite a few calcium and vitamin D preparations. They include: a chewable tablet, an effervescent tablet, or a sachet. They can be prescribed as a combination of the two, just calcium, or just vitamin D. Your doctor will advise which one is right for you. Your doctor will ask about your diet. If you are already having enough calcium in your diet, you should not take calcium supplements as well. This is because too much calcium may be harmful for you. Calcium and vitamin D are normally taken every day (at a different time to the bisphosphonate).

Taking other medicines

Bisphosphonates sometimes react with other medicines that you may take. So, make sure your doctor knows of any other medicines that you are taking, including ones that you have bought rather than been prescribed. Always check with your pharmacist before you buy any painkillers from the pharmacy or supermarket. Some painkillers – for example, ibuprofen and aspirin – can irritate your gullet (oesophagus) if you take them with a bisphosphonate.

What are the possible side-effects?

The most common side-effects of bisphosphonates are feeling sick (nausea), indigestion and heartburn (dyspepsia), tummy (abdominal) pain, diarrhoea or constipation. These side-effects usually happen in the first month of treatment but usually go away after this.

Other common side-effects are joint, and/or muscle pain (usually not severe). This pain can happen a few days or a few months after you first start treatment. This pain normally goes away after you stop taking a bisphosphonate. A full list of possible side-effects (each of which will only happen to a few people) is included in the leaflet which comes with the medicine.

Less commonly some people experience more serious side-effects to their gullet (oesophagus). The oesophagus is the upper part of the digestive system, the food pipe that carries food and drink from your mouth to your stomach. Sometimes bisphosphonates can cause inflammation or ulcers of the oesophagus, or a narrowing of the oesophagus. Taking the medicine carefully according to the instructions makes these side-effects less likely. As mentioned above, if you develop any symptoms such as difficulty or pain swallowing, worsening heartburn, or chest pain, you should stop the tablets and see your doctor. There have been very rare reports of bisphosphonates possibly causing cancer of the oesophagus but there is no definite evidence for this currently.

A rare side-effect is osteonecrosis of the jaw. This occurs when the jawbone does not receive enough blood, and the bone starts to weaken and die. You must stop taking bisphosphonates if this happens.

These medicines sometimes react with other medicines that you may take. So, make sure your doctor knows of any other medicines that you are taking, including ones that you have bought rather than been prescribed.

Can I buy bisphosphonates?

You cannot buy bisphosphonates. They are only available from your chemist, with a doctor’s prescription.

Who cannot take bisphosphonates?

You cannot take a bisphosphonate if:

  • You have low calcium levels in your blood (hypocalcaemia).
  • You have uncorrected vitamin D deficiency.
  • You are pregnant or breastfeeding.
  • Your kidneys do not work very well.
  • You cannot sit upright or stand for 30 minutes after you have taken the tablet.
  • You have structural problems with your gullet (oesophagus) which slows down the length of time it takes for the bisphosphonate to reach your stomach. Examples of these include: a narrowing of the oesophagus, or Barrett’s oesophagus.

In addition, you may not be able to take a bisphosphonate if you have a recent history of tummy problems such as stomach ulcers, duodenal ulcers or inflammation of the upper gut.

How to use the Yellow Card Scheme

If you think you have had a side-effect to one of your medicines you can report this on the Yellow Card Scheme. You can do this online at www.mhra.gov.uk/yellowcard.

The Yellow Card Scheme is used to make pharmacists, doctors and nurses aware of any new side-effects that medicines or any other healthcare products may have caused. If you wish to report a side-effect, you will need to provide basic information about:

  • The side-effect.
  • The name of the medicine which you think caused it.
  • The person who had the side-effect.
  • Your contact details as the reporter of the side-effect.

It is helpful if you have your medication – and/or the leaflet that came with it – with you while you fill out the report.

Bisphosphonates are a family of drugs used to treat osteoporosis. There are four bisphosphonates currently approved for use in Canada: alendronate (Fosamax ®), etidronate (Didrocal ®), risedronate (Actonel ®) and zoledronic acid (Aclasta®). Also available are: Actonel DR™, Fosavance® (Fosamax® with vitamin D) and several generic versions.

How do they work?

Bisphosphonates bind to the surfaces of the bones and slow down the bone resorping action of the osteoclasts (bone-eroding cells). This allows the osteoblasts (bone-building cells) to work more effectively.

How effective are they?

All four bisphosphonates increase bone density and reduce the risk of fractures of the spine (vertebral fractures). Alendronate, risedronate and zoledronic acid have also been shown to reduce the risk of hip fractures and fractures of other bones.

Who can take them?

Bisphosphonates are used to treat osteoporosis in: postmenopausal women and in men; and in men and women of any age who are using steroid medications.

How are they taken?

There are very specific instructions about how bisphosphonates must be taken. Following the directions will allow your body to absorb the drug properly and may help you avoid side effects. Because calcium interferes with the absorption of bisphosphonates, calcium supplements must be taken at other times of the day. See table below.

Are there side effects?

The most common side effects are nausea, abdominal pain and loose bowel movements. Bone, joint and/or muscle pain has been reported in patients taking bisphosphonates; such reports have been infrequent. There is a small risk of ulcers in the esophagus with both alendronate and risedronate, especially if taken incorrectly. The most common side effects of zoledronic acid, which usually only last a day or two, are fever, pain in the muscles, bones or joints, and headache. There have been rare cases of kidney dysfunction following infusions of zoledronic acid. In the vast majority of cases, this has been reversible.

In very rare cases, alendronate, risedronate and zoledronic acid have been linked to a breakdown of the jaw bone (called osteonecrosis of the jaw) following dental surgery such as dental extractions. Rare cases of atypical fractures of the femoral (thigh) bone have been reported with bisphosphonates. Notify your physician if you experience pain in the groin or thigh that is present for a few weeks.

How to take a bisphosphonate

Frequency Time of day Instructions
Alendronate (Fosamax®),
10 mg (treatment)
every day first thing in morning, at least 1/2 hour before eating Take with 250ml (8 oz) plain water. Stay upright (don’t bend or lie down) for the first 1/2 hour AND until after the first food of the day
Alendronate
(Fosamax®)
70 mg
(Fosavance®)
70 mg + 2800 IU vitamin D or
70 mg + 5600 IU vitamin D
once a week same as above same as above
Etidronate (Didrocal®)
400 mg
The white etidronate tablet is taken daily for two weeks followed by a blue calcium tablet taken daily for an additional 10 weeks Take the white etidronate tablet (first two weeks) mid morning, mid afternoon or evening (at least two hours before and after eating)Take the blue calcium tablet (next 10 weeks) with food Take the white etidronate tablet with a full glass of water. Do not eat or take any additional supplements or vitamins for 2 hours before or after taking etidronate.Take the blue calcium tablet with food.
Risedronate (Actonel®)
5 mg
every day first thing in morning, at least 1/2 hour before eating Take with a full glass of water. Stay upright (don’t bend or lie down) for the first 1/2 hour AND until after the first food of the day
Risedronate (Actonel®)
35 mg
once a week same as above same as above
(ActonelDR™) 35 mg (DR=delayed release) once a week Take first thing in morning WITH breakfast Take with full glass of water. Stay upright (don’t bend or lie down) for the first 1/2 hour
Risedronate (Actonel®)
150 mg
once a month first thing in morning, at least 1/2 hour before eating Take with a full glass of water. Stay upright (don’t bend or lie down) for the first 1/2 hour AND until after the first food of the day
Zoledronic acid (Aclasta®)
5 mg
once a year not applicable Given as a 15-minute intravenous (IV) infusion by a certified healthcare professional

General cancer information

It is important to keep your mouth clean. Talk to your doctor about any mouth problems during treatment.

Important information

When you’re taking bisphosphonate tablets or capsules, you should follow the instructions your doctor or pharmacist gives you.

Food and drink

Take the tablets or capsules on an empty stomach, or they won’t be absorbed well. Some people find it easiest to take them first thing in the morning and wait at least an hour before eating anything or having any milk.

Drink plenty of fluids to help protect your kidneys. Ask your doctor or nurse about how much they recommend you drink each day.

Other medicines

Bisphosphonates can interact with other drugs you are taking. This includes some painkillers such as non steroidal anti inflammatory drugs (NSAIDs) and antibiotics. Check with your doctor or pharmacist before taking any new medicines.

As bisphosphonates can lower the level of calcium in the blood, your doctor might prescribe you daily calcium and vitamin D supplements. This is only if your calcium level isn’t too high. Vitamin D helps the body absorb calcium.

Pregnancy and Contraception

This treatment might harm a baby developing in the womb. It is important not to become pregnant or father a child while you’re having treatment. Talk to your doctor or nurse about effective contraception before starting treatment.

More information

Find your drug on our cancer drug A-Z list to get more information, including side effects.

Read more about:

Bisphosphonates: Safety and Efficacy in the Treatment and Prevention of Osteoporosis

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