Bone Complications and Cancer

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Bone Complications and Cancer
modified: 9/17/2007
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Bone health is maintained through active processes that are constantly taking place in the bone tissue. Cancer and its treatment may disrupt this activity and compromise bone health. Bone complications occur when cancer spreads to the bones, causing pain, a weakening of the bones that makes them more susceptible to fracture, and/or a dangerously high level of calcium in the blood.

The treatment for cancer-related bone complications depends largely on the particular condition and symptoms, but may include surgery, radiation, pain medication, or, bisphosphonate drugs, which treat hypercalcemia and prevent the weakening of the bones.

The following is a general overview of cancer-related bone complications and their management. Treatment may consist of drug therapy, surgery, radiation, or a combination of these treatment techniques. In some cases, participation in a clinical trial utilizing new, innovative therapies may provide the most promising treatment. Circumstances unique to each patient's situation may influence how these general treatment principles are applied. The information on this website is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision-making process with their treating cancer physician.

Bone Health:

What are the components of bone?
Does bone change?
What factors contribute to bone health?
What diseases affect the bones?
Cancer-Related Bone Complications:

Bone pain
Bone loss
Hypercalcemia
Treatment for Cancer-Related Bone Complications:

Bisphosphonate drugs
Bone Health
Although bone appears to be the most static of all the tissues in the body, it is actually very dynamic and active. In fact, the active processes that constantly take place in bone are critical to maintaining healthy bone. Disruption to bone activity compromises bone health and underlies most bone diseases and complications.

What are the Components of Bone?
Bone is composed of both organic and inorganic materials. The organic components include cells, as well as fibers that are similar to those that make up other connective tissues, such as cartilage. The inorganic minerals are predominantly calcium salts. This combination of organic and inorganic components is what allows bone to be both flexible and strong.

Does Bone Change?
Normal bone is constantly being remodeled, or broken down and rebuilt. Every week, humans recycle 5% to 7% of their bone mass. As much as half a gram of calcium may enter or leave the adult skeleton each day.

This remodeling process serves two primary functions. First, remodeling helps maintain blood calcium levels. Calcium is necessary for many processes in the body, including contraction of muscles, nerve function, blood coagulation, and cell division. Only 1% of the calcium in the body is available in circulation for these functions. The other 99% is locked in the bones. If blood calcium levels drop, calcium must be released from the bones through remodeling in order to maintain important physiological functions that require calcium. Remodeling also serves to reshape the skeleton in response to stressors, such as gravity and weight bearing exercise. This keeps the skeleton strong where it is most needed.

Two types of cells are involved in the remodeling of bone: osteoclasts and osteoblasts. Osteoclasts are the cells that break down bone, converting the calcium salts to a soluble form that passes easily into the blood. Osteoblasts produce the organic fibers on which calcium salts are deposited. In healthy young adults, the activities of these two cell types are balanced so that total bone mass remains constant.

What Factors Contribute to Bone Health?
Adequate dietary intake of calcium is an important factor for maintaining bone health. Without enough calcium, bones cannot properly mineralize. For calcium to be absorbed, vitamin D and magnesium are also necessary.

What are the Diseases that Affect the Bones?
Among the most notable bone diseases are osteoporosis, rickets, and cancer. An imbalance between bone formation and bone resorption underlies nearly every disease that affects the adult skeleton. In osteoporosis, bone is broken down faster than it is rebuilt, resulting in lighter and more porous bones that may not be strong enough to support the body. Rickets is a children's disease in which the bones are inadequately mineralized. As in osteoporosis, the bones are weakened and weight-bearing bones, particularly in the legs and pelvis may fracture or bend.

Cancer can start in the bones or spread to the bones. Both types of bone cancer can compromise bone health by causing increased build-up or excessive breakdown of bone. Additionally, cancer treatment may damage or weaken bones. Most notably, cancer treatments such as hormonal therapies for breast and prostate cancers can cause increased bone loss.

Cancer-Related Bone Complications
Aside from primary bone cancers, the main bone complications that are related to cancer include:

Bone pain
Bone loss
Hypercalcemia
Bone pain: A common cause of bone pain is metastatic cancer. In fact, bone metastases are often diagnosed because the patient experiences pain near the metastases. Bone pain due to metastases may be hard to differentiate from ordinary low back pain or arthritis. The most notable difference is that pain due to bone metastasis is typically more constant, even at night.

To learn more, go to Bone Pain

Bone loss: Bone loss occurs when there is decreased calcification or reduced density of the bones. The result is weak bones that are at increased risk of fracture. Bone loss can occur as part of the normal aging process or as a complication of cancer or cancer treatment. The cancers that most commonly spread to the bones and cause bone loss include multiple myeloma, breast, prostate, lung, kidney, and thyroid cancers. In addition, hormonal therapy for breast and prostate cancer is known to cause bone loss.

To learn more, go to Bone Loss

Hypercalcemia:An increased level of calcium in the bloodstream is called hypercalcemia. This disorder is most commonly caused by cancer and results from the destruction of bone due to metastasis. Hypercalcemia can be a life-threatening condition.

To learn more, go to Hypercalcemia

Treatment for Cancer-Related Bone Complications
The goal of treatment for bone metastases is to relieve pain, prevent the cancer from spreading, and reduce the risk of fracture. Treatment consists of surgery, radiation therapy, pain management and the use of.bisphosphonate drugs. The bisphosphonate drugs can effectively prevent pathological fractures, relieve bone pain from metastases, and decrease bone loss in patients at risk of bone complications from cancer and its treatment.1

Bisphosphonate Drugs

Bisphosphonate drugs can effectively prevent loss of bone that occurs from metastatic lesions, reduce the risk of fractures, and decrease pain. 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.[ 1 ]

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.

Bisphosphonates have been shown to prevent or delay bone destruction and related pain in clinical trials involving patients with bone metastases related to:

Breast cancer
Prostate cancer
Lung cancer
Multiple myeloma
Renal cell carcinoma
Breast cancer: Bisphosphonate therapy has been shown to prevent or delay bone destruction and related pain in women with breast cancer that has spread to the bone. In a large clinical trial, a total of 751 women with metastatic breast cancer were randomly assigned to receive the bisphosphonate drug, Aredia®, or placebo (inactive substitute). The results showed that 64% of women who received the placebo had significant bone damage, compared with only 51% of those who received the bisphosphonate. The average time to the occurrence of the first bone complication was 13 months in the bisphosphonate group, compared to only 7 months in the placebo group. Furthermore, women who did not receive the bisphosphonate experienced significantly more pain and received more pain medications.2

Learn more at the Breast Cancer Information Center

Prostate cancer: Zometa® has been shown to be a safe and effective treatment in prostate cancer patients with bone metastases. Zometa® significantly reduces the proportion of patients who experience skeletal complications, extends the time to first skeletal complication, and reduces the risk of skeletal complications.3

Zometa® also appears to benefit patients with prostate cancer undergoing androgen deprivation therapy, or “hormonal therapy”. Hormonal therapy in the treatment of prostate cancer has been shown to cause bone loss.4

Researchers from Massachusetts General Hospital and 5 other medical institutions conducted a clinical trial evaluating Zometa® in patients with localized prostate cancer being treated with androgen deprivation therapy. This study included 106 men who were randomly selected to receive either Zometa® or a placebo for one year. Bone mineral density in the spine, hips, and legs increased among patients who were treated with Zometa® and decreased in patients who received placebo.5

Learn more at the Prostate Cancer Information Center

Lung cancer: Zometa® is a safe and effective treatment for bone metastases associated with lung cancer. In a clinical trial, 773 patients with lung cancer were randomly assigned to receive Zometa® or placebo via a 15-minute infusion every 3 weeks for 21 months. Results from the two groups were directly compared and showed that the number of patients experiencing at least one skeletal-related event was lower among those who were treated with Zometa® (39%) than patients who received placebo (46%). The patients who received Zometa® went nearly 3 months longer without developing a skeletal-related event and also experienced fewer skeletal-related events.6

Learn more at the Non-Small Cell Lung Cancer Information Center

Multiple myeloma: A major complication suffered by patients with multiple myeloma is destruction of the bones, causing fractures and pain. A comparison of treatment with chemotherapy plus the bisphosphonate drug Aredia® to chemotherapy alone showed that patients who received the bisphosphonate had fewer bone fractures and decreased pain. In addition, some patients lived longer.7

Research indicates that Zometa® is as effective as Aredia®. Among 1,648 patients with multiple myeloma or advanced breast cancer who had at least one bone lesion, pain and the use of pain medication was decreased with both treatments. However, patients who received Zometa® experienced significantly less need for radiation therapy to treat bone complications.8

Learn more at the Multiple Myeloma Information Center

Renal cell carcinoma: Researchers from Pennsylvania have reported that Zometa® improves outcomes and reduces skeletal-related events in patients with renal cell carcinoma and associated bone metastases. The researchers analyzed data from 74 patients with renal cell carcinoma who were involved in a larger trial that involved patients with other types of cancers. Patients with renal cell carcinoma may be at a greater risk for developing skeletal-related events than patients with other types of solid cancers. The proportion of patients with renal cell carcinoma was nearly twofold greater than the proportion of patients in the entire population (44% vs. 74%).

The patients were treated with Zometa® or placebo (inactive substitute) and compared for the development of skeletal-related events, which included bone fracture, spinal cord compression, or the need for radiation or surgery for the treatment of bone metastasis.

Patients treated with Zometa® had a 61% reduced risk of developing a skeletal-related event than those who received a placebo. Also, the patients who received Zometa® had less cancer progression in their bones and lived longer.9

Learn more at the Kidney (Renal Cell) Cancer Information Center

References
1) 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.

2) Lipton A, Theriault RL, Hortobagyi GN, et al. Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: Long term follow-up of two randomized, placebo-controlled trials. Cancer 2000; 88(5):1082-1090.

3) Saad F, Gleason D, Murray R, et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. Journal of the National Cancer Institute 2002; 94:1458-1468.

4) Higano C, Shields A, Wood N, et al. Bone mineral density in patients with prostate cancer without bone metastases treated with intermittent androgen suppression. Urology 2004;64(6):1182-6.

5) Smith MR, Eastham J, Gleason DM, et al. Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer. Journal of Urology 2003; 169:2008-2012.

6) Rosen LS, Gordon D, Tchekmedyian NS , et al. Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: A randomized, Phase III, double-blind, placebo-controlled trial. Cancer 2004;100(12):2613-21.

7) Berenson JR, Lichtenstein A, Porter L, et al. Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Myeloma Aredia Study Group. Journal of Clincal Oncology 1998;16(2):593-602.

8) Rosen LS, Gordon D, Kaminski M, et al. Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial. Cancer J. 2001; 7(5):377-387.

9) Lipton A, Zheng M, Seaman J. Zoledronic acid delays the onset of skeletal-related events and progression of skeletal disease in patients with advanced renal cell carcinoma. Cancer 2003; 98(5):962-969.

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