Morphine, Bone Pain, and Bone Loss in Metastatic Breast Cancer

When breast cancer spreads to the bones — called bone metastasis — it often causes bone pain as well as bone loss. Morphine is a common treatment for cancer-caused bone pain, but has been linked to inflammation, bone loss, and increased bone pain. A study has uncovered how morphine causes this.

The research was published on June 15, 2023, by the journal PAIN. Read “Morphine-induced osteolysis and hypersensitivity is mediated through toll-like receptor-4 in a murine model of metastatic breast cancer.”

If breast cancer becomes metastatic, meaning it spreads to parts of the body away from the breast, it often spreads to the bones. More than 50% of people who develop metastatic breast cancer have bone metastases.

Bone pain is a common side effect when breast cancer is in the bones. This type of pain is usually treated with opioid medicines, including morphine, and in many cases the dose is increased over time because people become resistant to its effects. Opioids are also highly addictive, especially when used to manage pain for a long time.

Bone loss is also a common side effect of bone metastasis, which also causes pain and increases the risk of breaking a bone.

Although morphine is used to treat bone pain caused by breast cancer that has spread to the bones, it also has been shown to cause more bone pain and loss, as well as inflammation. In this study, the researchers wanted to figure out how morphine worsened these conditions it’s supposed to be treating.

This study looked at cells in the lab and in mice that had cells from metastatic breast cancer tumors implanted in their bones. The animals also had morphine pumps implanted for pain control.

The researchers looked at how morphine interacted with two types of receptors:

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  Mu opioid receptors, which are on the surfaces of some nerve cells and bind to opioids, are responsible for controlling pain perception, among other things.

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  Toll-like receptor 4s (TLR4), which are on the surfaces of some immune cells and bind to foreign molecules, usually increase in number when the body has to deal with a disease like cancer.

In both the mouse and lab parts of the study, the researchers found that when morphine interacted with TLR4s, it started processes that increased both inflammation and the activity of cells called osteoclasts, cells that break down bone. These processes led to more bone loss and more severe bone pain. When the researchers blocked TLR4s, morphine didn’t increase bone loss or bone pain.

When morphine interacted with the mu opioid receptor, it didn’t cause more bone pain or bone loss.

“We believe that morphine is acting through toll-like receptor 4 to increase the number of osteoclasts that are produced and the activity of those osteoclasts,” senior author Todd Vanderah, PhD, said in a statement. Dr. Vanderah is director of the University of Arizona Health Sciences Comprehensive Pain and Addiction Center and professor and head of the Department of Pharmacology at the University of Arizona College of Medicine. He explained that as osteoclasts break down more bone, pain levels rise. “In the bigger picture, chronic opiates may start enhancing bone loss in any inflammatory condition — if somebody has an activated immune system because of cancer or arthritis, for example.”

Dr. Vanderah said that more research is needed to better understand how opioids interact with opioid receptors, as well as other types of receptors, in the body, which, he hopes, can lead to better treatments for pain.

Treating and managing pain are an important part of any cancer treatment plan, especially metastatic breast cancer.

If you’ve been diagnosed with metastatic breast cancer that has spread to the bones, you may want to talk to your doctor about this study.

There are a number of pain management options available to you; opioids are just one option. If morphine or another opioid are making any bone pain you have worse, and also causing more bone loss, you and your doctor can discuss other options that may be a good fit for your situation.