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.

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