What is bone metastasis? Why do cancers spread to bone, and how is it treated?

Cancer cells that leave the primary tumor and enter the bloodstream or lymph vessels can reach almost every tissue in the body. Bones are a frequently favored site for these cells to settle and grow.

A bone metastasis is an area of bone containing cancer that has spread from elsewhere

Cancer can spread to any bone, but metastases are most often found in bones near the center of the body. The spine is the most commonly affected site. Others include the hip bone, upper leg bone, upper arm bone, ribs and skull.

Cancer is rarely cured once it spreads to bones or other body parts. Nevertheless, it can be treated to relieve pain and shrink, stop or slow its growth.

What problems can bone metastases cause?

Bone supports the body. Bones consist of fibrous tissue called matrix and networks of minerals within the matrix, such as calcium, which give bone strength and hardness. Osteoblasts and osteoclasts are the 2 main types of bone cells.

Knowing a little about these 2 cell types may help you understand how bone metastases grow and how some medicines work in treating them. Osteoblasts form new bone, while osteoclasts dissolve or break down old bone. When both function properly, new bone forms as old bone dissolves. This helps keep bones strong.

Cancer cells can affect bones by interfering with both osteoblasts and osteoclasts

What do lytic and sclerotic mean?

Usually, cancer cells release substances that overactivate osteoclasts . This causes bone breakdown without new bone formation, weakening the bones. The holes that develop when parts of bone dissolve are called osteolytic or lytic lesions . Lytic lesions are so weak that they can cause the bone to break easily.

Sometimes cancer cells release substances that overactivate osteoblasts. This leads to new bone formation, called sclerosis . Areas where this occurs are called osteoblastic or blastic lesions. Although these rough areas are harder, the bone’s structure is abnormal, and these areas break more easily than normal bone.

Bone metastases can cause other problems too

If cancer spreads to spinal bones, it may press on the spinal cord. Untreated, this can cause nerve damage leading to paralysis.

When cancer cells destroy bone, calcium is released from the bone into the bloodstream. This can lead to hypercalcemia (high blood calcium levels).

Why do cancers metastasize to bones?

Cancer cells must undergo many changes to spread elsewhere in the body:

1. They must leave the primary tumor and enter the bloodstream or lymph system, which can carry them to another body part.
2. At some point, they must attach to a blood or lymph vessel wall and pass through it toward a new organ.
3. They must then grow and develop at the new location.
4. Throughout this process, cancer cells must avoid attacks from the body’s immune system.

After all these steps, the cells forming a new tumor may no longer be exactly the same as those in the original tumor, but they still receive the same name. For example, breast cancer spreading to bone is “metastatic breast cancer”, not bone cancer.

- Related topic: Breast cancer metastasis symptoms—what should you look for?

What is the difference between primary bone cancer and bone metastasis?

Some cancers begin in bone rather than spreading there from elsewhere. Cancers beginning in bone are called primary bone cancers (osteosarcoma) . These cancers differ greatly from bone metastases. Bone metastases are more common than primary bone cancers, especially in adults.

How are bone metastases treated?

There are 2 basic treatment types for bone metastases: systemic (traveling throughout the body) and local (regional) treatments. One or both may be used depending on the size and location of the tumor that has spread to bone.

The most commonly used systemic treatment for bone metastases: bisphosphonates

Bisphosphonates are the most commonly preferred group of medicines for cancer that has spread to bone. They work by slowing osteoclasts’ bone-dissolving activity.

In cancers that have metastasized to bone, bisphosphonates have the following effects:

• Reducing bone pain
• Slowing cancer-related bone damage
• Lowering high blood calcium levels (hypercalcemia)
• Reducing fracture risk
• Bisphosphonates tend to work better in lytic bone metastases, where osteoclasts are overactive. They do not work well for blastic metastases, where bones become denser and osteoblastic activity is high. Lytic and blastic metastases are distinguished through imaging such as CT or magnetic resonance.

These medicines can lower calcium levels and therefore cannot be given to someone whose calcium is already low. They should also be used cautiously in people with kidney damage.

- Related topic: Cancer and dental treatment! What should people taking bone-protective medicines consider?

How frequently and at what dose should bisphosphonates be used?

In January 2017, the respected scientific journal JAMAreported research suggesting that giving the bisphosphonate zoledronic acid less frequently might not increase skeletal event risk, such as fractures or paralysis from spinal cord compression, in cancer patients.

Intravenously administered zoledronic acid significantly reduces pain and skeletal-related events but also has side effects such as kidney toxicity and reduced blood calcium. Research has therefore long sought the most appropriate dosing interval for this important medicine.

Study

The study included breast and prostate cancer patients with bone metastases and multiple myeloma patients, 1822 in total. Half received intravenous zoledronic acid every 4 weeks, while the others received it every 12 weeks.

Patients were monitored for skeletal-related events such as fractures, spinal cord compression, and the need for radiation or surgery to bone. A total of 795 patients completed the study.

Over 2 years, in the 4-week dosing group, 260 patients (% 29.5), and in the 12-week group, 253 patients (% 28.6), experienced at least 1 skeletal-related event. There was ultimately no significant difference between groups in the percentage of these events.

There was also no significant difference in pain scores, performance status scores, jaw osteonecrosis frequency or kidney dysfunction between the 4-week and 12-week dosing groups.

RANK ligand inhibitor: denosumab

Denosumab is another medicine that can prevent cancer spread in bone. Like bisphosphonates, it inhibits osteoclast activity but does so differently through a substance called RANK ligand.

The protein known as RANK ligand has been shown to play an important role in bone destruction. Denosumab is a monoclonal antibody medicine that prevents bone destruction by targeting RANK ligand.

Although it has side effects similar to bisphosphonates, this medicine is safe to give to patients with kidney problems.

Local treatments for bone metastases

Local treatments, including radiation therapy, surgery and other techniques such as cementing, target a single area rather than the whole body.

Local treatments may help when cancer has spread to only one or a few bones and needs immediate treatment because of fractures, spinal cord compression and paralysis resulting from vertebral fractures, or severe pain that painkillers may not adequately relieve.

Radiotherapy (radiation treatment)

When cancer has spread to a certain extent in bones, radiation may be used to help relieve symptoms such as pain. Irradiating bone before it becomes too weak may help prevent a later fracture.

Special types of radiation therapy can focus radiation more precisely to reduce certain side effects. These include 3-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT). For more information, see our radiotherapy page .

Radiotherapy for bone metastases may be given in 1 or 2 large doses, or in smaller amounts over 5 to 10 treatments, resulting in a somewhat larger total dose. Both schedules offer similar pain relief. The greatest advantage of 1 or 2 doses is fewer hospital visits for treatment. Longer treatment has the advantage of a lower likelihood of pain recurring.

Stereotactic body radiation therapy (SBRT): This is a highly specialized radiotherapy method delivering high radiation doses. Rather than small amounts daily over several weeks, SBRT delivers highly focused, high-dose beams over one or a few days. Beams are directed at the tumor from different angles.

Bone cementing

Another option to strengthen and/or stabilize bone is injections of a quick-setting bone cement or glue called PMMA (polymethyl methacrylate).

When PMMA is injected into spinal bone, the procedure is called vertebroplasty . This helps stabilize the bone and relieves pain in most people. Vertebroplasty often reduces pain immediately and can be performed as an outpatient procedure. It is most often preferred for spinal bone involvement in multiple myeloma.

Surgery

Surgery for a bone metastasis is performed to prevent fractures, relieve symptoms and/or stabilize the bone.

Bone metastases may weaken bones, causing fractures or making existing fractures harder to heal. Surgery may place screws, rods, pins, plates, cages or other devices to make bones more stable and help prevent fractures. If the bone has already broken, surgery can often relieve pain quickly and help patients return to normal activities.