Bone Pain

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 through 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.

Bone metastases can also be asymptomatic and diagnosed by a bone scan or CAT scan done as part of a disease work-up that is designed to tell if and when a cancer has spread. 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 percent 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 bone fracture as well as prevent spinal cord compression). 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.

If a vertebral bone has fractured with the resulting collapse of the vertebra, a procedure is now available known as kyphoplasty, which reexpands the vertebral bone through injection of a bone cement. This stabilizes the vertebral column, relieves pain, and restores height.

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 in that area. Radiation is especially useful when metastatic lesions are limited to a single part of the body.

Another type of radiation therapy is called radiopharmaceutical therapy. This approach involves injecting a radioactive substance into a vein, such as Quadramet^® (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. This form of radiation is usually used when a patient has painful symptoms in two or more areas of their skeleton.

Both forms of radiation are about 80 percent effective in eliminating or significantly decreasing skeletal or bone pain.

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

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 to 10, will dictate what type of pain medication is used.

• Mild to Moderate Pain (1 to 3) - Nonopioids are the first choice of treatment for mild to moderate pain. This includes medication such as Tylenol® (acetaminophen) or a nonsteriodal antiinflammatory drug, such as ibuprofen.
• Moderate to Severe Pain (4 to 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, dihydrocodiene, oxycodone, propoxyphene, and tramadol. Acetaminophen or a nonsteriodal may be added.
• Severe Pain (7 to 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 nonopioid 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 early onset of pain and/or at regular intervals. Taking pain medication after the pain gets too severe frequently causes the pain to last longer and does not achieve the same level of relief as it would have if it were taken earlier.

Bisphosphonate drugs - Bisphosphonates have become attractive adjuvants for reducing the risk of pathologic fracture caused by metastatic bone lesions and for the treatment of bone pain. Bisphosphonate drugs, such as Zometa^® (zoledronic acid)and Aredia^® (pamidronate injection) 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 prevent or delay 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, or the need for radiation treatments, surgery, or ever-changing chemotherapy treatments.

Most importantly, bisphosphonates significantly reduced the incidence and severity of pain.

Zoledronic acid  has the stronger activity of these two bisphosphonate drugs. In a recent clinical trial, zoledronic acid was shown to be a safe and effective treatment in prostate cancer patients with bone metastases. Compared with a placebo, zoledronic acid 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 zoledronic acid in blastic lesions, in which extra bone has built up, whereas previous trials have only shown activity of bisphosphonates on lytic metastases in which the bone is destroyed.

Both zoledronic acid and pamidronate are administered intravenously, but zoledronic acid provides a more convenient regimen for patients. Zoledronic acid is administered in a dose 10 times lower than pamidronate, resulting in an infusion time that is significantly shorter: 15 minutes versus 2 to 4 hours for pamidronate. In an effort to eliminate the need for intravenous administration, research is aimed at developing oral biphosphonates. At this time, however, there are no oral biphosphonates that are nearly as effective or potent as zoledronic acid.