by Dr. C.H. Weaver M.D. Medical editor, updated 10/2020

Bone pain in patients with cancer is commonly caused by cancer cells that have spread to the bones, called bone metastases. Bone pain is commonly the first symptom of bone metastases and may lead to tests that will confirm the diagnosis. Treatment of bone metastases is intended to relieve the pain, reduce the risk of fracture, and prevent or delay additional bone complications. Treatment options for metastases causing bone pain are directed at relieving the pain and preventing the spread of metastases.

Treatment may consist of pain medications, Xgeva (denosumab) and bisphosphonate drugs like Zometa, Strontium89, radiation therapy, and/or surgery.

  • What causes bone pain?
  • How are bone metastases diagnosed?
  • How is bone pain treated?

What Causes Bone Pain

A common cause of bone pain is metastatic cancer. The spread of cancer from its site of origin to another location in the body is called metastasis. A bone metastases is not a new cancer, but consists of cancer cells from the original cancer, such as breast, prostate, lung, kidney, or thyroid, that have spread to bone.

Cancer cells can spread, or metastasize, through the blood and lymph systems. Bone is one of the most common locations in the body to which cancer metastasizes. Bone metastasis usually occurs by way of the bloodstream. A cancer cell may break away from the original location in the body and travel in the circulatory system until it gets lodged in a small capillary network in bone tissue. Cancer may also spread to bone by erosion from the adjacent cancer, though this occurs less frequently than spread by the bloodstream.

Normal bone is constantly being remodeled, or broken down and rebuilt. Cancer cells that have spread to the bone disrupt this balance between the activity of osteoclasts (cells that break down bone) and osteoblasts (cells that build bone), resulting in either weakened or excessively built-up bone. This damage can either stretch the periosteum (thick membrane that covers bone) or stimulate nerves within the bone, causing pain.

How are Bone Metastases Diagnosed

Bone metastases are usually diagnosed because a patient experiences pain near the metastases and reports this to their doctor. The doctor may then complete an x-ray or a more complicated procedure called a bone scan to confirm that the pain is caused by cancer-related damage to the bones. In a bone scan, low level radioactive particles are injected into a vein. They circulate through the body and some are absorbed into the bones. A high concentration of these radioactive particles on the bone scan results indicates the presence of rapidly growing cancer cells in the bone.

Bone pain may be hard to differentiate from ordinary low back pain or arthritis. Usually the pain due to bone metastasis is fairly constant, even at night. It can be worse in different positions, such as standing, which may compress the cancer in a weight bearing bone. If pain lasts for more than a week or two, doesn’t seem to be going away, and is unlike other pain that may have been experienced, it should be evaluated by a physician.

Bone metastases generally occur in the central parts of the skeleton, although they may be found anywhere in the skeletal system. Common sites for bone metastases are the back, pelvis, upper leg, ribs, upper arm, and skull. More than 90% of all metastases are found in these locations.

How is Bone Pain Treated

The goal of treatment is to relieve the pain reduce the risk of fracture, and prevent or delay additional bone complications from the metastases.

Pain medications

Cancer-related bone pain can be managed with various pain medications. Although most adult cancer patients can have their pain relieved, uncontrolled cancer-related occurs in half of patients, particularly in those who are living at home. Research indicates that most cancer patients are not prescribed enough medication to control their pain.(1,6)

Pain medications may have side effects, including sleepiness, constipation, dizziness, nausea, and vomiting. Relief from pain medications is temporary and the pain may return in a short time; thus, medications are best used at the onset of pain or at regular intervals.

Strontium89

Strontium89 is a radionuclide therapy that has been prescribed for nearly 30 years to alleviate pain caused by bone metastases. Strontium89 delivers radiation directly to the boney cancerous sites to help decrease bone pain and is an established option for the treatment of bone pain associated with cancer. Administered alone or with other cancer therapies, Strontium89 has been shown to provide pain relief from bone metastasis from all types of cancer following a single injection and last 3 months. (4)

  • Strontium89 is not an opioid and is not addictive and can relieve pain for extended periods of time.
  • Strontium89 is administered by a Nuclear Medicine physician or a Radiation Oncologist.
  • When Strontium89 is injected into the vein, it travels to areas of the bone where cancer is present and gives off radiation that destroys cancer cells and can treat multiple areas of the bone affected by cancer while causing minimal risk of damage to surrounding healthy cells.
  • In clinical trials with Strontium89, participants experienced: Bone pain relief within 7 to 20 days after injection that lasted 2 to 5 months. Decreased need for additional pain medications, including opioids.
  • Re-treatment with Strontium89 is possible after 90 days.
  • Strontium89 Patient and Caregiver Support

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Xgeva (denosumab)

Xgeva can effectively prevent loss of bone that occurs from metastatic lesions, reduce the risk of fractures, and decrease pain. Xgeva targets a protein known as the RANK ligand which regulates the activity of osteoclasts (cells that break down bone). Xgeva is more effective than Bisphosphonate medications at delaying or preventing bone complications such as fracture.

Xgeva has been directly compared to the Bisphosphonate drug Zometa in patients with prostate and other cancers with bone metastases. In a pivotal trial that enrolled 1,901 patients with metastatic, hormone-refractory prostate cancer Xgeva and Zometa were directly compared.

The objective of the study was to determine whether the occurrence of bone complications (“skeletal related events”) differed between the two study groups. The bone complications that were evaluated were fracture, radiation to the bone, surgery to the bone, and spinal cord compression.

  • Patients treated with Xgeva remained free of bone complications longer than patients treated with Zometa. Median time to first on-study bone complication was 20.7 months among patients treated with Xgeva compared with 17.1 months among patients treated with Zometa. Xgeva also reduced the rate of multiple bone complications.
  • Overall survival and time to cancer progression were similar among patients treated with Zometa and patients treated with Xgeva.
  • Osteonecrosis of the jaw (an uncommon but serious side effect) occurred in 2.3% of patients treated with Xgeva and 1.3% of patients treated with Zometa. This difference between study groups was not statistically significant, suggesting that it could have occurred by chance alone. (5)

Surgery and Radiation

Surgery: When there is an immediate or significant risk of fracture, surgery may be necessary to stabilize the weakened bone. Metal rods, plates, screws, wires, nails, or pins may be surgically inserted to strengthen or provide structure to the bone damaged by metastasis.

For metastatic lesions that do not represent an immediate risk of fracture, radiation is effective for reducing bone pain and progression of the cancer. Radiation is especially useful when metastatic lesions are limited to a single area.

One type of radiation therapy is called radiopharmaceutical therapy. This approach involves the injection of a radioactive substance, such as strontium-89, into a vein. This substance is attracted to areas of bone that contain cancer. Providing radiation directly to the bone in this way destroys active cancer cells in the bone and can relieve symptoms. Two possible side effects of radiopharmaceutical therapy are decreased blood counts with increased risk of bleeding, and rarely, leukemia.

Bisphosphonate Drugs

Bisphosphonate drugs can effectively prevent loss of bone that occurs from metastatic lesions, reduce the risk of fractures, and decrease pain but have largely been replaced by Xgeva and Strontium89. Bisphosphonate drugs work by inhibiting bone resorption, or breakdown. Bone is constantly being “remodeled” by two types of cells: osteoclasts, which break down bone; and osteoblasts, which rebuild bone. Although the exact process by which bisphosphonates work is not completely understood, it is thought that bisphosphonates inhibit osteoclasts and induce apoptosis (cell death) in these cells, thereby reducing bone loss. There is also evidence that these drugs bind to bone, thereby blocking osteoclasts from breaking down bone.

Cancer cells release various factors that stimulate osteoclastic activity, causing increased breakdown of bone. By inhibiting osteoclasts, bisphosphonate drugs effectively reduce the detrimental impact that cancer cells have on bone density. An analysis of the results from 30 clinical trials demonstrates that patients with bone metastases treated with a bisphosphonate had a delayed time to skeletal fractures, a reduced need for radiation therapy to treat bone metastasis, a reduction in hypercalcemia (high blood levels of calcium), and a reduction in the need for orthopedic surgery.(3)

Bisphosphonate drugs that are FDA-approved for the treatment of cancer-related skeletal complications include Zometa® (zoledronic acid) and Aredia® (pamidronate). Of these two drugs, Zometa® appears to demonstrate the strongest activity. An added benefit of Zometa® is that it is administered in a dose ten times lower than Aredia®, which considerably reduces the administration time from several hours to 15 minutes, resulting in a more convenient regimen for patients.

How Does Your Doctor Measure Pain?

The World Health Organization recommendations for relief of cancer pain indicate that the severity of a patient’s pain, rated on a scale of 1-10, will dictate what type of pain medication is used.(2)

  • Mild to Moderate Pain (1-3): Non-opioids are the first choice of treatment for mild to moderate pain. This includes medication such as acetaminophen (Tylenol®) or a non-steroidal anti-inflammatory drug (NSAID), such as ibuprofen.
  • Moderate to Severe Pain (4-6) Patients with moderate to severe pain who have not responded to the first step should receive an opioid. These medications may include codeine, hydrocodone, dilhydrocodiene, oxycodone, propoxyphene, and tramadol. Acetaminophen or a NSAID may be added.
  • Severe Pain (7-10) Patients with severe pain or patients whose pain has not been relieved by the previous recommendations will usually receive a stronger opioid. Opioids for severe pain may include morphine, oxycodone, hydromorphone, methadone, levophanol, or fentanyl. A non-opioid medication such as aspirin, acetaminophen, or ibuprofen may be added in some cases.
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References:

  1. Oncology Nursing Society. ONS Position Paper on Pain. Pittsburgh PA ; 2002.
  2. Chen H, Wilkie D, Huang H. Opiod Prescritption for Cancer Pain Management. Proceedings form the 2003 Annual Meeting of the Oncology Nursing Society. Abstract #147.
  3. Ross JR, Saunders Y, Edmonds PM, et al. Systematic Review of Role of Bisphosphonates on Skeletal Morbidity in Metastatic Cancer. British Medical Journal 2003; 327:469-471.
  4. Nilsson S, Strang P, Ginman C, et al. Palliation of Bone Pain in Prostate Cancer Using Chemotherapy and Stontium-89. A Randomized Phase II Study. Journal of Pain and Symptom Management. 2005; 29: 352-357.
  5. Fizazi K, Carducci MA, Smith MR et al. A randomized phase III trial of denosumab versus zoledronic acid in patients with bone metastases from castration-resistant prostate cancer. Presented at the 2010 annual meeting of the American Society of Clinical Oncology. June 4-8, 2010. Chicago, IL. Abstract LBA 4507.
  6. dx.doi.org/10.3344/kjp.2013.26.3.223

†In the same study, after a single injection of Strontium89, 14.3% of participants (6/42) had a reduction in pain score and analgesic score to zero, compared with 6.8% of participants (3/44) taking placebo at 1 month, 13.2% of participants (5/38) had a reduction in pain score and analgesic score to zero compared with 8.6% of participants (3/35) taking placebo at 2 months, and 15.2% of participants (5/33) had a reduction in pain score and analgesic score to zero compared with 5.9% of participants (2/34) taking placebo at 3 months.