Bone Metastasis Treatment with Medications

Julia Draznin Maltzman, MD and
Updated by Carolyn Vachani, RN, MSN
Last Modified: October 3, 2016

Introduction

Bone metastases are a common complication of advanced cancer. They are most common in breast and prostate cancer. Bone metastases can cause severe pain, bone fractures, life-threatening electrolyte imbalances, and compress nerves (which cause pain and/or weakness). The pain and nerve dysfunction may be difficult to treat and significantly affects quality of life. Bone metastases usually signify advanced, often incurable, disease.

Osteolytic vs. Osteoblastic

Bony metastases are characterized as being either osteolytic or osteoblastic. Osteolytic means that the tumor has caused bone break down or thinning. This usually results in calcium being released from the bone, into the bloodstream. On X-rays these are seen as holes called "lucencies" within the bone. Osteolytic lesions are most commonly seen with a blood cancer called multiple myeloma, however they may be present in patients with other types of cancers, including breast cancer.

Osteoblastic bony lesions, by contrast, are characterized by increased bone production. The tumor somehow signals to the bone to overproduce bone cells and result in rigid, thickened, inflexible bone being formed. Osteoblastic bony lesions are most often seen in prostate cancer.

Most cancers result in either osteolytic or osteoblastic bony changes, but some can lead to both. Breast cancer patients usually develop osteolytic lesions, although at least 15-20 percent can have osteoblastic lesions.

Why the bone?

The bone is a common site of metastasis for many solid tumors including prostate, breast, lung, kidney, stomach, bladder, uterus, thyroid, colon and rectum tumors. Researchers speculate that this may be due to the high blood flow to the bone and bone marrow. Once cancer cells gain access to the blood vessels, they can travel all over the body and usually go where there is the highest flow of blood. Furthermore, tumor cells themselves secrete adhesive molecules that can bind to the bone marrow and bone. This molecular interaction can cause the tumor to signal for increased bone destruction and enhance tumor growth within the bone. Research has shown that the bone is actually a rich source of growth factors. These growth factors signal cells to divide, grow, and mature. As the cancer attacks the bone, these growth factors are released and serve to further stimulate the tumor cells to grow. This results in a self-generating growth loop.

What are the symptoms of bone metastasis?

Keep in mind that the symptoms of bone metastasis be caused by many other conditions. Most people with bone pain do not have bone metastasis. The most common symptom of a bone metastasis is pain. Another common presentation is a bone fracture without any history of trauma. Bone fracture is more common in osteolytic metastases than osteoblastic metastases.

Sometimes people with more advanced disease may develop numbness and tingling sensation in their feet and legs. They may have bowel and bladder dysfunction – either losing continence of urine and/or stool, or severe constipation and urinary retention. Others may report leg weakness and difficulty moving their legs against gravity. This would imply that there is tumor impinging on the spinal cord, compromising the nerves that control these functions. This is called spinal cord compression and is considered an emergency requiring immediate medical attention. A less common presentation of bone metastasis is high levels of calcium in the body. High calcium can cause constipation, which can result in abdominal pain, and with very high calcium levels, confusion and mental status changes can occur.

Diagnosis of Bone Metastasis

Once a patient experiences any of the symptoms of bone metastasis, various tests can be done to find the true cause. In some cases, bone metastasis may be detected before the symptoms arise.

X-rays, bone scans, and MRIs are used to diagnose bone metastases. X-rays are especially helpful in finding osteolytic lesions. These often appear as "holes" or dark spots in the bone on the x-ray film. Unfortunately, bone metastases often do not show up on plain x-rays until they are quite advanced.

By contrast, a bone scan can detect very early bone metastases. This test is done by injecting the patient with a small amount of radio-tracing material in the vein. Special x-rays are taken a short time after the injection. The radiotracer will go to the site of the metastases and will appear as a darker, denser, area on the film. However, because this technique is so sensitive, sometimes infections, arthritis, and old fractures can appear as dark spots on the bone scan and may be difficult to differentiate from a true cancer. Bone scans are also used to follow patients with known bone metastasis. Sometimes CT scan images can show if a cancer has spread to the bone. An MRI is most useful when examining nerve roots suspected of being compressed by tumor or bone fragments due to tumor destruction (called spinal cord compression).

There are no blood tests that are currently used to diagnose a bone metastasis. There are, however, a number of blood tests that may suggest the presence of bone lesions, but the diagnosis rests with the combination of radiology testing, clinical picture (symptoms), and the type of cancer (is it one that travels to bone?). For example, elevated levels of calcium can be related to bone metastasis, but these lab tests alone cannot prove their presence.

Treatment

The best treatment for bone metastasis is the treatment of the primary cancer. Therapies may include chemotherapy, hormone therapy, radiation therapy, immunotherapy, or treatment with monoclonal antibodies. Pain is often treated with narcotics and other pain medications, such as non-steroidal anti-inflammatory agents. Physical therapy may be helpful and surgery may have an important role if the cancer resulted in a fracture of the bone. 

Bisphosphonates

Bisphosphonates are a category of medications that decrease pain from bone metastasis and help make bones stronger. Bisphosphonates are a man-made version of a naturally occurring compound called pyrophosphate that prevents bone breakdown. They are a class of medications widely used to treat or prevent osteoporosis and to treat other bone diseases (such as Paget's Disease), as well as in the treatment of elevated blood calcium. These medications suppress bone breakdown caused by cells called osteoclasts, and, can indirectly stimulate the bone forming cells called osteoblasts to make new bone. Strengthening bone and relieving bone pain has made bisphosphonates a good treatment for cancer that has spread to the bone.

However, treatment of bone metastases is not curative. There is increasing evidence that bisphosphonates can prevent bone complications in some metastatic cancers and may even improve survival in some cancers. Most researchers agree that these medications are more helpful in osteolytic lesions and less so in osteoblastic metastasis in terms of bone restoration and health, but the bisphosphonates are able to alleviate pain associated with both types of lesions.

Bisphosphonates can be given either orally (by mouth) or intravenously (IV), however in oncology care it is generally given by IV. The two most commonly used in oncology are pamidronate (Aredia) and zoledronic acid (Zometa). Their side effect profile is fairly mild and includes a flu-like reaction during the first 48 hours after the infusion, nausea, low calcium levels, kidney impairment, and osteonecrosis of the jaw with long-term use. Patients with kidney problems may not be candidates for this therapy.

Studies have found that bisphosphonates can reduce the risk of developing bone or other metastasis and improve survival in post-menopausal women with early stage breast cancer. These medications continue to be studied in the prevention of bone metastases.

Denosumab

In addition to bisphosphonates, osteoclast inhibition can also be achieved with a medication called denosumab (XGEVA). This medication works a little differently – it is a type of targeted therapy (monoclonal antibody) and works by targeting a specific protein that is necessary for bone destruction to occur. By inhibiting this protein, called RANKL, denosumab inhibits the breakdown of bone and, in turn, reduces the chance of developing a fracture in the affected bone. Denosumab is given as an injection under the skin (subcutaneous, SQ) every 4 weeks. This medication has side effects similar to the bisphosphonates, though it has a higher likelihood of causing low blood calcium, so patients are asked to take calcium and vitamin D supplements while on this treatment.

The Future

Skeletal metastases remain one of the more debilitating problems for cancer patients. Research is ongoing to identify the molecular mechanisms that result in both osteolytic and osteoblastic bone lesions.

References

American Cancer Society. Understanding Bone Metastasis. 2012. Found at: http://www.cancer.org/treatment/understandingyourdiagnosis/bonemetastasis/bone-metastasis-treating-systemic-treatments

Gnant M, Mlineritsch B, Schippinger W et al.: Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med. 360(7),679–691 (2009).

Henry DH, Costa L, Goldwasser F, et al. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol. 2011;29(9):1125-32.

Tan, WW, et al. Bone Health and Breast Cancer Management Overview of Bone Health in Breast Cancer. Emedicine.com May 25, 2016.

The Lancet. Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. 2015. 366(10001):1353-1361.

Van Poznak CH, Temin S, Yee GC, et al. American Society of Clinical Oncology executive summary of the clinical practice guideline update on the role of bone-modifying agents in metastatic breast cancer. J Clin Oncol. 2011;29(9):1221-7.

West, H. Denosumab for prevention of skeletal-related events in patients with bone metastases from solid tumors: incremental benefit, debatable value. J Clin Oncol. 2011;29(9):1095-8.


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