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.
Osteoporosis treatment: Medications can help
Osteoporosis treatment may involve medication along with lifestyle change. Get answers to some of the most common questions about osteoporosis treatment.
By Mayo Clinic StaffIf you're undergoing osteoporosis treatment, you're taking a step in the right direction for your bone health. But perhaps you have questions about your therapy. Is the medication you're taking the best one for you? How long will you have to take it? Why does your doctor recommend a weekly pill when your friend takes a pill only once a month?
Which osteoporosis medications are usually tried first?
Bisphosphonates are usually the first choice for osteoporosis treatment. These include:
- Alendronate (Fosamax), a weekly pill
- Risedronate (Actonel), a weekly or monthly pill
- Ibandronate (Boniva), a monthly pill or quarterly intravenous (IV) infusion
- Zoledronic acid (Reclast), an annual IV infusion
Another common osteoporosis medication is denosumab (Prolia, Xgeva). Unrelated to bisphosphonates, denosumab might be used in people who can't take a bisphosphonate, such as some people with reduced kidney function.
Denosumab is delivered by shallow injections, just under the skin, every six months. If you take denosumab, you might have to do so indefinitely unless your doctor transitions you to another medication. Recent research indicates that there could be a high risk of spinal fractures after stopping the drug, so it's important that you take it consistently.
What are common side effects of bisphosphonate pills?
The main side effects of bisphosphonate pills are stomach upset and heartburn. Don't lie down or bend over for 30 to 60 minutes to avoid the medicine washing back up into the esophagus. Most people who follow these tips don't have these side effects.
Bisphosphonate pills aren't absorbed well by the stomach. It may help to take the medication with a tall glass of water on an empty stomach. Don't put anything else into your stomach for 30 to 60 minutes, after which you can eat, drink other liquids and take other medications.
Do intravenous bisphosphonates have advantages over the pill form?
Intravenous forms of bisphosphonates, such as ibandronate and zoledronic acid, don't cause stomach upset. And it may be easier for some people to schedule a quarterly or yearly infusion than to remember to take a weekly or monthly pill.
Intravenous bisphosphonates causes mild flu-like symptoms in some people, but usually only after the first infusion. You can lessen the effect by taking acetaminophen (Tylenol, others) before and after the infusion.
Can osteoporosis medications hurt your bones?
A very rare complication of bisphosphonates and denosumab is a break or crack in the middle of the thighbone. This injury, known as atypical femoral fracture, can cause pain in the thigh or groin that begins subtly and may gradually worsen.
Bisphosphonates and denosumab can also cause osteonecrosis of the jaw, a rare condition in which a section of jawbone is slow to heal or fails to heal, typically after a tooth is pulled or other invasive dental work. This occurs more commonly in people with cancer that involves the bone — who take much larger doses of a bisphosphonate than those typically used for osteoporosis.
Should I take a drug holiday from bisphosphonates?
The risk of developing atypical femoral fracture or osteonecrosis of the jaw tends to increase the longer you take bisphosphonates. So your doctor might suggest that you temporarily stop taking this type of drug. This practice is known as a drug holiday.
However, even if you stop taking the medication, its positive effects can persist. That's because after taking a bisphosphonate for several years, the medicine remains in your bone.
Because of this lingering effect, most experts believe that it's reasonable for people who are doing well during treatment — those who have not broken any bones and are maintaining bone density — to consider taking a holiday from their bisphosphonate after taking it for five years.
Are hormones used to treat osteoporosis?
Estrogen, sometimes paired with progestin, was once commonly used to treat osteoporosis. This treatment can increase the risk of blood clots, endometrial cancer, breast cancer and possibly heart disease. It's now usually reserved for women at high risk of fracture who can't take other osteoporosis drugs.
Women who are considering hormone replacement therapy to reduce menopausal symptoms, such as hot flashes, may factor in increased bone health when weighing the benefits and risks of estrogen treatment. Current recommendations say to use the lowest dose of hormones for the shortest period of time.
Raloxifene (Evista) mimics estrogen's beneficial effects on bone density in postmenopausal women, without some of the risks associated with estrogen. Taking this drug can reduce the risk of some types of breast cancer. Hot flashes are a common side effect. Raloxifene may also increase your risk of blood clots.
How do osteoporosis medications work?
Throughout your life, healthy bones continuously break down and rebuild. As you age — especially after menopause — bones break down more quickly. Because bone rebuilding cannot keep pace, bones deteriorate and become weaker.
Most osteoporosis medications work by reducing the rate at which your bones break down. Some work by speeding up the bone-building process. Either mechanism strengthens bone and reduces your risk of fractures.
Which drugs help speed up the bone-building process?
Bone-building drugs include:
- Teriparatide (Forteo)
- Abaloparatide (Tymlos)
- Romosozumab (Evenity)
These types of drugs are typically reserved for people who have very low bone density, who have had fractures or whose osteoporosis is caused by steroid medication.
Teriparatide and abaloparatide require daily injections. Studies in laboratory rats found an increase in the risk of bone cancer, so these medications are not used in people at high risk of bone cancer. So far, an increase in bone cancer has not been found in people who have taken these medications.
Romosozumab is given as a monthly injection at your doctor's office. It is a new drug and less is known about long-term side effects, but it is not given to people who have recently had a stroke or heart attack. Treatment stops after 12 monthly doses.
These bone-building drugs can be taken for only one or two years and the benefits begin disappearing quickly after you stop. To protect the bone that's been built up, you'll need to start taking a bone-stabilizing medication such as a bisphosphonate.
Can medication alone successfully treat osteoporosis?
Don't rely entirely on medication as the only treatment for your osteoporosis. These practices also are important:
- Exercise. Weight-bearing physical activity and exercises that improve balance and posture can strengthen bones and reduce the chance of a fracture. The more active and fit you are as you age, the less likely you are to fall and break a bone.
- Good nutrition. Eat a healthy diet and make certain that you're getting enough calcium and vitamin D.
- Quit smoking. Smoking cigarettes speeds up bone loss.
- Limit alcohol. If you choose to drink alcohol, do so in moderation. For healthy women, that means up to one drink a day. For healthy men, it would be up to two drinks a day.
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Aug. 24, 2022
- Osteoporosis: In-depth. National Institute of Arthritis and Musculoskeletal and Skin Diseases. //www.niams.nih.gov/health-topics/osteoporosis/advanced. Accessed June 9, 2020.
- Goldman L, et al., eds. Osteoporosis. In: Goldman-Cecil Medicine. 26th ed. Elsevier; 2020. //www.clinicalkey.com. Accessed June 9, 2020.
- Eastell R, et al. Pharmacological management of osteoporosis in postmenopausal women: An Endocrine Society clinical practice guideline. Journal of Endocrinology and Metabolism. 2019; doi:10.1210/jc2009-00221.
- Ferri FF. Osteoporosis. In: Ferri's Clinical Advisor 2020. Elsevier; 2020. //www.clinicalkey.com. Accessed June 9, 2020.
- Rosen HN, et al. Overview of the management of osteoporosis in postmenopausal women. //www.uptodate.com/contents/search. Accessed June 9, 2020.
- Rosen HN. Risks of bisphosphonate therapy in patients with osteoporosis. //www.uptodate.com/contents/search. Accessed June 9, 2020.
- Bone HG, et al. 10 years of denosumab treatment in postmenopausal women with osteoporosis: Results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes and Endocrinology. 2017; doi:10.1016/S2213-8587(17)30138-9.
- Kearns AE (expert opinion). Mayo Clinic. June 15, 2020.
See more In-depth
See also
- Ankylosing spondylitis: Am I at risk of osteoporosis?
- Anorexia nervosa
- Back pain
- Bone density test
- Bone health tips
- Calcium
- Timing calcium supplements
- Celiac disease
- CT scan
- Exercising with osteoporosis
- Fall prevention
- High-protein diets
- Male hypogonadism
- Osteoporosis
- Risks of osteoporosis drugs
- Osteoporosis: How long must I take bisphosphonates?
- Osteoporosis rehabilitation
- Spinal compression fracture
- Symptom Checker
- Ultrasound
.