Bone Pain

• 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 the original cancer, such as breast, prostate, lung, kidney, or thyroid that has 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 metastases usually occur by way of the blood stream. 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 blood stream.

How are bone metastases diagnosed?

Bone metastases are usually diagnosed because the patient experiences pain near the metastases. The pain is caused by lesions, or injury to the bone tissue by the cancer that can either stretch the periosteum (thick membrane that covers bone) or stimulate nerves within the bone. 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).

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 up, 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 for bone pain caused by bone metastases is palliative, to relieve pain and reduce the risk of fracture. Treatment may consist of surgery, radiation therapy, pain medications, and/or bisphosphonate drugs.

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.

Radiation Therapy: 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.

Another type of radiation therapy is called radiopharmaceutical therapy. This approach involves injecting into a vein a radioactive substance such as strontium-89. 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 relieve symptoms. Two possible side effects of radiopharmaceutical therapy are decreased blood counts with increased risk of bleeding, and rarely, leukemia.

Pain Medications: Bone pain that results from metastases can be managed with various pain medications. Despite the claim that 90% of adult cancer patients’ pain can be relieved, uncontrolled cancer related pain is still a concern, particularly for patients who are living at home. Recent research presented at the 2003 Oncology Nurses Society annual meeting indicates that most cancer patients are under-prescribed.

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.

• 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-steriodal anti-inflammatory drug, 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 nonsteriodal 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.

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 they are best used at the onset of pain or at regular intervals.

Bisphosphonate Drugs: Bisphosphonates have become attractive adjuvants for reducing the risk of pathological fracture caused by metastatic bone lesions and for the treatment of bone pain. Bisphosphonate drugs, such as Zometa® and Aredia® and work by inhibiting cells in the bone called osteoclasts, which resorb or break down bone tissue. This action effectively prevents the loss of bone that occurs from metastatic lesions.

Bisphosphonates effectively for prevent or delay of bone destruction and related pain. This activity has been demonstrated by clinical trials in multiple myeloma and breast cancer patients. In trials comparing treatment with chemotherapy plus bisphosphonates to chemotherapy alone, patients receiving bisphosphonates were less likely to experience complications related to cancerous involvement of the bone such as fractures.

Additionally, patients receiving bisphosphonates lived longer and had a lesser need for radiation and surgical treatment than those patients not receiving bisphosphonates. Most importantly, bisphosphonates significantly reduced the incidence and severity of pain.

Zometa® demonstrates the strongest activity of these two bisphosphonate drugs. In a recent clinical trial, Zometa® was shown to be a safe and effective treatment in prostate cancer patients with bone metastases. Compared to placebo, Zometa® significantly reduced the proportion of patients who experienced skeletal complications, extended the time to first skeletal complication, and significantly reduced the risk of skeletal complications over the course of this 15-month study. These results are notable because they show activity of Zometa® in blastic lesions, in which extra bone has built up, whereas previous trials have only shown activity of bisphosphonates on metastases in which the bone is weakened.

Both Zometa® and Aredia® are administered intravenously, but Zometa® provides a more convenient regimen for patients. Zometa® is administered in a dose ten times lower than Aredia®, resulting in an infusion time that is significantly shorter: 15 minutes versus 2-4 hours for Aredia®. In an effort to eliminate the need for intravenous administration, research is aimed at developing oral biphosphonates.

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