Aromatase Inhibitor-Related Joint Pain

Aromatase inhibitors (AIs) are used for women with hormone positive breast cancer who have already gone through menopause. After menopause, estrogen is mostly made when androgens (sex hormones made by the adrenal glands) turn into estrogens. This happens in fat cells (and not in the ovaries like it did before menopause). An enzyme called aromatase helps this happen. AIs cause less estrogen in the body.

AIs raise your risk of osteoporosis (when your bones become weak and brittle). They can also cause joint (or muscle) aches and pains. These joint symptoms, often called arthralgias, can affect your quality of life and are often the cause of a woman stopping therapy early.

Joint symptoms often start within the first 3 months on therapy, though some cases can start after 3 months. About 20-50% of women on therapy report this side effect. It can affect the fingers, hands, wrists, elbows, shoulders, knees, and ankles. Carpal tunnel syndrome is a common issue in women with AI-related joint symptoms. Other diagnoses include osteoarthritis, tendonitis, and bursitis.

What causes AI-related joint symptoms?

The cause of AI-related joint symptoms is not well understood. One thought is that the quick drop in estrogen levels may cause joint pain for two reasons:

• This drop may lower how much pain you can handle, allowing the brain to better "detect" joint symptoms that already exist.
• The drop in estrogen causes cytokines (proteins released by the body’s cells) to be released in high levels, which may speed up bone loss and aging, causing pain.

It is hard to prevent this side effect since it is not well understood. The goal is to treat the symptoms to let you have good quality of life while taking your prescribed therapy in full.

Who is at risk of this side effect?

We don’t know who will be affected by AI-related joint pain. Some studies have shown that having had chemotherapy, hormone replacement therapy, taxane chemotherapy (paclitaxel, taxotere) and having had your last menstrual period within 5 years may put you at higher risk. Taking tamoxifen before an AI may lower your chances of having joint symptoms. There may also be a higher risk for those who had joint problems before treatment, like rheumatoid arthritis. Research continues to find factors that could help better predict each woman's risk.

How are joint symptoms treated?

You should talk with your oncology team if you start having joint symptoms. Your care team is there to help you so you can finish your therapy and will help find ways to manage this side effect. It is important to take your medication every day, for as long as it is prescribed. Talk with your team if your side effects are making it hard for you to take your medications as directed.

Medications for treating symptoms

One of the most common symptoms of AIs is swelling of the joints. A medication that decreases this swelling, such as non-steroidal anti-inflammatory drug (NSAID, like ibuprofen) or a coxib (such as celecoxib, or Celebrex), may help with pain relief. These medications have side effects of their own, so you should talk with your team before starting these medications. Other pain-relieving medications, like acetaminophen (Tylenol) and opioids, can be added if you do not get relief or if you cannot tolerate the anti-inflammatory medications.

Switching AIs

Some providers may switch to another AI or tamoxifen when symptoms affect your daily life or if you are thinking about stopping therapy altogether. Before switching, it may be helpful to stop your current therapy for 6 to 8 weeks to be sure that the AI is causing the symptoms.

Supplements and Other Therapies

Vitamin D supplementation may help decrease AI-related arthralgia, although this has not been proven in clinical trials. Some studies have suggested that calcium and bisphosphonate therapy (used to prevent/treat osteoporosis) may also prevent AI-related joint symptoms.

Small studies have found a benefit from acupuncture and exercise. Acupuncture was shown to reduce pain from joint symptoms and improve functioning and wellbeing. Gentle stretching and exercise may also be helpful in reducing symptoms.

AI-related joint symptoms can cause pain and affect your daily quality of life. Researchers continue to look for ways to know who is at the highest risk of getting this side effect and to find therapies to treat it. You should report these symptoms to your care team right away. Your care team will work with you to improve joint symptoms so that you can finish your therapy in full.