Understanding Bone Metastases

Cancer that has developed in one place can spread and invade other parts of the body. This process of spreading is called metastasizing. If a tumor spreads to the bone, it is called bone metastasis.

Cancer cells that have metastasized to the bone can damage the bone and cause symptoms. Various treatments are available to control the symptoms and the spread of bone metastases. To better understand what happens in metastasis, it helps to know the anatomy of the bones.

Bone Basics

Bone is a type of connective tissue made up of minerals, such as calcium and phosphate, and the protein collagen. The outer layer of bone is called the cortex. The spongy center of bone is called bone marrow.

Bone is a dynamic tissue that constantly repairs and renews itself through a process called remodeling. There are two kinds of cells involved in this process:

• Osteoblasts are bone-forming cells

• Osteoclasts are cells that break down, or reabsorb, bone

Here are some of the functions that bones have in the body:

• The skeleton provides structural support.

• Bones store and release, as needed, minerals that the body needs to function, such as calcium.

• Bone marrow produces and stores blood cells. These include red blood cells, white blood cells, and platelets. Red blood cells transport oxygen from the lungs to the rest of the body. White blood cells fight infections. Platelets help the blood clot.

When cancer cells invade the bone, any or all of the functions of the bone may be affected.

How Cancer Spreads to the Bone

When cancer cells break free from a cancerous tumor, they can travel through the bloodstream or lymph vessels to other parts of the body. Cancer cells can lodge in an organ at a distant location and establish a new tumor. The original tumor that cells break away from is called the primary tumor. The new tumor that the traveling cells create is called the secondary tumor. Secondary tumors in the bone are called bone metastases.

Different types of tumors seem to prefer to spread to particular sites in the body. For example, many types of cancer commonly spread to the bone. The bone is a common site of metastasis for these cancers:

• Breast

• Kidney

• Lung

• Prostate

• Thyroid

Bone metastases are not the same as cancer that starts in the bone. Cancer that starts in the bone is called primary bone cancer. There are different types of primary bone cancers, such as osteosarcoma. A tumor that has metastasized to bone is not made of bone cells. Bone metastases are made up of abnormal cancer cells that arise from the original tumor site. For example, lung cancer that spreads to the bone is made of lung cancer cells. In this case, the bone metastasis would be called metastatic lung cancer.

Cancer cells that spread to the bone commonly lodge in these places:

• Limbs

• Pelvis

• Rib cage

• Skull

• Spine

Cancer cells that spread to bone can cause damage in these two ways:

• The tumor may eat away areas of bone. That creates holes called osteolytic lesions. This process can make bones fragile and weak so that they break or fracture easily. These areas may be painful.

• The tumor may stimulate bone to form and build up abnormally. These areas of new bone are called osteosclerotic or osteoblastic lesions. They are weak and unstable and may break or collapse. They can also be painful.

Symptoms of Bone Metastases

Bone metastases can cause these symptoms:

• Bone pain. Pain is the most common symptom of bone metastasis. It's usually the first symptom that people notice. At first, the pain may come and go. It tends to be worse at night or with bed rest. Eventually, the pain may increase and become severe. Not all pain indicates metastasis. The doctor can help distinguish between pain from metastasis and aches and pains from other sources.

• Fragile bones. Bone metastasis can weaken bones, putting them at risk for breaking. In some cases, a fracture is the first sign of bone metastasis. The long bones of the arms and legs and the bones of the spine are the most common sites of fracture. A sudden pain in the middle of the back may indicate a compressive cancerous bone fracture.

• Numbness or weakness in the legs, trouble urinating or having a bowel movement, or numbness in the abdomen. These are all signs that the spinal cord or spinal nerves may be compressed. When cancer metastasizes to the spine, it can squeeze the spinal cord. The pressure on the spinal cord may cause these symptoms, as well as back pain. If you have these symptoms, you should tell a doctor or nurse right away. If untreated, they can cause paralysis.

• Loss of appetite, nausea, thirst, constipation, tiredness, or confusion. These are all signs that there may be high levels of calcium in the blood. Bone metastases can cause calcium to be released from the bones and into the bloodstream. This condition is called hypercalcemia. If you have these symptoms, you should tell a doctor or nurse right away. If untreated, they may cause a coma.

• Other symptoms. If bone metastasis affects the bone marrow, people may have other symptoms related to decreased blood cell counts. For instance, red blood cell levels may drop, causing anemia. Signs of anemia are tiredness, weakness, and shortness of breath. If white blood cells are affected, people may develop infections. Signs of infection include fevers, chills, fatigue, or pain. If the number of platelets drops, bruising or abnormal bleeding may occur.

It is important for people to discuss any of these symptoms with their doctor. Detecting and treating bone metastases early can help reduce complications.

How Doctors Find and Diagnose Bone Metastasis

In some cases, a doctor may find bone metastasis before a person has symptoms. In some cancers, where bone metastasis is common, the doctor may order tests to make sure the cancer has not spread to the bones before recommending treatment. When a person has symptoms of bone metastasis, doctors can do these tests to find the cause:

• Bone scan

• Computed tomography (CT) scan

• Lab tests

• Magnetic resonance imaging (MRI) scan

• X-rays

Each of these tests is described below:

Bone scan. A bone scan can usually detect bone metastasis earlier than an X-ray can. Because the scan looks at the entire skeleton, it also allows the doctor to monitor the health of all the bones in the body, including how they are responding to treatment.

In a bone scan, the patient is given an injection of a low amount of radioactive material. The amount is much lower than that used in radiation therapy. The radioactive substance is attracted to diseased bone cells throughout the body. Diseased bone can appear on the bone scan image as darker, dense areas. Conditions other than metastasis, such as arthritis, infections, or previous fractures that have healed, may also be picked up on a bone scan, although the patterns they produce are often different from those produced by cancer. Additional tests can help distinguish among these other conditions.

Computed tomography (CT) scan. The CT scan provides X-ray images to look at cross sections of organs and bones in the body. Whereas an X-ray results in only one perspective per image, the CT scanner takes many pictures as it rotates around the body. A computer combines the images into one picture to show if cancer has spread to the bones.

Laboratory tests. Bone metastasis can cause a number of substances to be released into the blood in amounts that are higher than normal. Two such substances are calcium and an enzyme called alkaline phosphatase. Blood tests for these substances can help diagnose bone metastasis. Doctors can also measure the levels of these chemicals over time to monitor a person's response to treatment. Elevated levels of these substances can indicate other medical conditions besides metastasis.

Magnetic resonance imaging (MRI). An MRI scan uses radio waves and strong magnets instead of X-rays to provide pictures of bones and tissues. It is particularly useful in looking at the spine.

X-rays. Radiographic examination, called X-rays, can show where in the skeleton the cancer has spread. X-rays also show the general size and shape of the tumor or tumors. It's common for more than one bone metastasis to be found.

How Bone Metastasis Is Treated

In addition to treating the cancer, these treatment options are available for bone metastasis:

• Bisphosphonates

• Denosumab

• Radiation therapy

• Chemotherapy, targeted therapies, and hormone therapy

• Surgery

• Other treatments, including physical therapy and drugs 

Each of these treatments is described below:

Bisphosphonates. These are drugs that slow the abnormal bone destruction and formation caused by bone metastases. They are used to:

• Decrease the risk for fractures

• Reduce bone pain

• Lower high blood calcium levels

• Slow bone damage caused by metastases

Different types of bisphosphonates are available. Here are some of them:

• Didronel (etidronate)

• Aredia (pamidronate)

• Zometa (zoledronate)

Each has somewhat different effects. Bisphosphonates in cancer treatment are usually given through an intravenous (IV) line since the oral forms are not well absorbed and can irritate the gastrointestinal tract. The side effects of bisphosphonates are usually mild and do not last long. Here are some of the common side effects:

• Tiredness

• Nausea

• Vomiting

• Lack of appetite

• Bone pain

Early studies with bisphosphonates focused on the use of the drugs in people with breast cancer, prostate cancer, and multiple myeloma. Researchers are examining bisphosphonates in treating bone metastases from other types of cancer. Researchers are also looking at whether bisphosphonates can prevent the development or recurrence of bone metastases.

Denosumab (Xgeva). Like bisphosphonates, denosumab can help prevent bone pain and broken bones. But this medication works differently than the bisphosphonates. It blocks a protein called RANKL that turns on the cells involved in bone breakdown. Taken by injection every four weeks, denosumab may cause side effects such as tiredness, nausea, diarrhea, and problems with the jaw bone.

Radiation therapy. Radiation is useful in easing pain and killing tumor cells in the bone metastases. It may be used to prevent a fracture. It can also treat spinal cord compression.

Radiation therapy uses high-energy ionizing radiation to injure or destroy cancer cells. Typically radiation is administered once a day in 10 treatments over a two-week period. Full effects of this treatment may take two to three weeks to occur. Side effects of radiation may include skin changes in the area being treated and, rarely, a temporary increase in symptoms of bone metastasis.

Another type of radiation is called radiopharmaceutical therapy. This approach involves injecting a radioactive substance such as strontium-89 or samarium-153 into a vein. This substance is attracted to areas of bone containing cancer. Providing radiation directly to the bone in this way destroys active cancer cells in the bone and can ease symptoms. It is especially useful if many bones are involved. Two important side effects are decreased blood counts with increased risk for bleeding, and, rarely, leukemia.

Chemotherapy, targeted therapies, and hormone therapy. Chemotherapy drugs are used to kill cancer cells throughout the body. They may be taken orally or given intravenously. Newer biologic or molecularly-targeted agents have fewer side effects, and may be easier to tolerate. Hormone therapy uses drugs to prevent hormones from forming or acting on cells to promote cancer growth. The goals of either of these treatments in people with bone metastases are to control the tumor's growth, reduce pain, and reduce the risk for skeletal fractures.

Surgery. Surgery for bone metastases is done to prevent or treat a bone fracture. It can involve removing most of the tumor or stabilizing the bone to prevent or manage a fracture, or both. Metal rods, plates, screws, wires, or pins may be surgically inserted to strengthen or provide structure to the bone damaged by metastasis.

Other therapies. Other treatments for bone metastases and their symptoms include physical therapy and drug and nondrug approaches to control pain. Many different drugs or combinations of drugs can be used to treat pain from bone metastases. The principal drug type used to treat bone metastases is a nonsteroidal anti-inflammatory agent. They stop prostaglandins, the substances that seem to be responsible for much of the bone pain. It is important to take these medicines with food or milk to protect the stomach. Nondrug approaches to managing pain include the use of heat and cold, relaxation techniques, and therapeutic beds or mattresses.

Clinical trials are exploring the ways to better manage bone metastases.