Skeletal Metastases

Original Editors - Cassie Ferrett & Rebecaa Porter from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors - Amy Person, Rebecca Porter, Cassandra Ferrett, Elaine Lonnemann, Thomas Mudd, Lucinda hampton, Admin, Selena Horner, Evan Thomas, Wendy Walker, Kim Jackson and Vidya Acharya  

Definition/Description

     Cancer is created in the body when abnormal cells begin to rapidly multiply. These cancer cells can end up traveling to other parts of the body if they enter into the bloodstream and/or lymph vessels. The term 'metastasis' refers to the process in which cancer cells travel to a new place and begin to grow in its new location.

     A cancer is always named for the place that it first formed; this is called its primary site. For instance, if a person has breast cancer that has spread to the bone, it still is labeled as breat cancer and not bone cancer. Cancer that actually originates in the bone is called primary bone cancer and is less common than a bone metastasis.

     The definition of a skeletal metastasis is a cancer of the bone that has originated from another site. Bones are a common site for certain cancers such as breast cancer and prostate cancer. The most common sites for skeletal metastases are the spine (this is the most common site), pelvis, femur, humerus, ribs, and skull.

     Skeletal metastases are common with other cancers. When one gets skeletal metastases, this usually means one has an advanced cancer. “Its prevalence is rising due to higher rate of diagnosis, better systemic treatment, longer lives with the disease and higher disease burden rate”.[4]

    There are two types of bone cells, osteoblast and osteoclast. Osteoblast is the forming of new bone, the tumor signals to the bone to overproduce bone cells. Osteoclast is what dissolves the bone, leaving weakened bones. With osteoclast, you develop osteolytic lesions which are when the bone breaks down. This allows excess calcium to be released into the bloodstream. Osteoblastic or osteolytic changes will be seen in most cancers, sometimes both are seen.

This 3-minute computer-animated video explains the process of cancer spreading to bone and how the cancer affects the bone once it has implanted.

https://www.youtube.com/watch?v=q7b55yQP4g4

                                                                         

Prevalence

• Bone is the third most common site for metastatic cancer
• Skeletal metastasis is much more common than primary bone cancers
• Account for 70% of all malignant bone tumors
• About 10,000 cases of bone metastases are reported each year in the United States
• of these 10,000 cases, 75% caused by tumors in breast, prostate, lung, and kidney
• More than 2 out of 3 breast and prostate cancers that spread to other parts of the body spread to the bone

Characteristics/Clinical Presentation

 The most common symptoms of skeletal metastases include pain, fractures, and anemia. Pain usually is worse at night and may get better with movement, but can become constant and may be worse during activity.[1] Pain is usually localized to the site of metastases, but can refer to areas around the site. Pain usually increases to severe intensity. Weakening of bones due to metastases puts patients at risk for fractures. Fractures can happen with fall, injury, or during everyday activities. Most common are in the long bones of arms and legs and bones of the spine.[1] Tumors in the spine can cause compression on the spinal cord resulting in numbness or tingling in the abdomen and legs, bowel and bladder problems, and difficulty walking. Metastases in the bones producing blood cells in pelvis, ribs, spine, skull, upper arms, and long bones of legs may cause abnormalities in blood cells. Anemia is a common abnormality for patients with skeletal metastases, especially with chemotherapy and radiation therapy. Patients exhibit weakness, fatigue, and shortness of breath. Patients with a white blood cell abnormality are prone to infections; whereas, patients with deviations in platelets counts cause abnormalities in bleeding and clotting.

                                       

Associated Co-morbidities

Any cancer can metastasize into the bone. The most common metastasizing cancers include prostate, breast, kidney, thyroid, and lung. Cancers that have metastasized to other organs or the lymph system are more likely to metastasize to bone. 

Hypercalcemia can present as the cancer weakens the bones. With excessive lysis of the bone, the integrity of the bone is compromised which can lead to pathological fractures. When the bone breaks down, excess calcium is released into the blood which can lead to:

Feeling tired/drowsiness
Trouble thinking clearly
Loss of appetite
Pain
Frequent urination
Increased thirst
Constipation
Nausea
Vomiting
Coma 

Diagnostic Tests/Lab Tests/Lab Values

     If a person has cancer, lab tests and imaging tests may be done to see if the caner has spread to other sites. This is how skeletal metastases are discovered in their early stages. In other situations, symptoms of skeletal metastases may be the first indicator that the cancer has spread. These symptoms include bone pain, fractures, symptoms of spinal cord compression, and/or symptoms of hypercalcemia (these symptoms are explained in more detail under 'Characteristics/Clinical Presentation'). Lab tests and imaging tests are then performed to confirm whether or not a skeletal metastasis is causing these symptoms.

Test	Description
X-rays	Often the first test performed if a person is having symptoms of a skeletal metastasis. Certain cancers are osteolytic and cause the bone to become less dense. Other cancers are osteoblastic and cause the bone to become more dense. X-rays help to show the bone density and can also indicate if there are any fractures in the bone that may have been caused by cancer.
Bone Scan	Shows the entire skeleton and so can help discover metastases that have not caused symptoms yet. Sometimes may not be able to detect osteolytic metastases.
Computed Tomography (CT)	Shows cross-sectional images of the body. Often used if a metastasis is thought to be osteolytic since a bone scan may not show the tumor.
Tumor Markers	Certain cancers release substances called 'tumor markers'. These can be detected through blood tests and higher levels of tumor markers indicate that cancer has spread in the body. However, this test does not help indicate where the cancer has spread.
Other Blood Tests	Cancer can cause increased levels of calcium and alkaline phosphates in the blood. Blood tests can help show if these levels are higher than normal.
Urine Tests	If the bone has become damaged by skeletal metastases, certain substances may be released into the urine.
Magnetic Resonance Imaging (MRI)	Shows cross-sectional images of the body and is useful at looking at the spine and spinal cord. It is the test most often used if a person is experiencing symptoms of spinal cord compression.
Positron Emission Tomography (PET)	Shows the whole body at once and is useful in detecting tumors throughout the body. The scans are not very detailed and so if cancer is thought to be seen, MRI or CT scans are used to have a more thorough scan.
Needle Biopsy	There are two types--fine needle biopsy and core needle biopsy. With fine needle biopsy, a thin needle is inserted and a little bit of fluid and tissue fragments are removed from the tumor. With core needle biopsy, a larger needle is used to remove a small cylinder of tissue. The samples are then looked under a microscope.
Surgical Bone Biopsy	With this test, the bone is cut into and a small part of the tumor is removed and inspected under a microscope.

Etiology/Causes

Metastatic bone cancer starts with a tumor within another organ of the body. Cancer cells that break from the tumor and travel to and through the circulatory or lymph system. Some of these cells have an outer make up that helps to adhere to the bony network of cells. Other cancer cells secrete a substance to change the bone cells for easier attachment or increased growth of the cancer cells that do metastasize in the bone. Once the cancer is within the bone, it either increases production of osteoclasts or osteoblasts. An increase in osteoclasts weakens the bone leading to the increased risk of fracture. An increase in osteoblasts amplifies the production of bone cells causing sclerotic changes in the skeletal system.

Systemic Involvement

As a metastases, skeletal metastases results from cancer in another organ of the body. These cancers could cause symptoms from another system; however, skeletal metastases can also directly lead to other systemic symptoms:
Neurological-spinal lesion, hypercalcemia
Cardiovascular-blood pathology, hypercalcemia
Gastrointestinal-hypercalcemia
Genitourinary-hypercalcemia

Besides the metastases, systemic treatment can produce side effects throughout the body; including blood pathology, nerve damage, kidney damage, and heart damage.

Medical Management (current best evidence)

     Treatments for skeletal metastases can work to shrink and/or slow down the growth of cancer. It can slo help reduce the symptoms that the cancer is causing. However, in most cases treatments do not make the metastases disappear completely. The treatments offered for skeletal metastases are influenced by many factors including:

• the type of cancer
• which bones are affected 
• whether the bones are weak or broken
• previous treatments
• general health

     The following are potential treatment options for skeletal metastases:

Chemotherapy: this is the main treatment used for skeletal metastases and often can help shrink the tumors and reduce the symptoms caused by the cancer. With chemotherapy, anti-cancer drugs are put into the body by mouth or through a vein. These drugs can affect both cancer and normal cells and some side effects of chemotherapy are: loss of hair, loss of appetite, nausea and vomiting, mouth sores, diarrhea, increased chance of infection, problems with bruising and bleeding, and feeling weak or fatigue. 

Hormone Therapy: Some hormones contribute to the growth of cancers. By keeping these hormones from affecting the cancer cells, certain types of cancers can be treated. Hormone therapy has multiple approaches. One approach is to surgically remove the organ producing the hormone. The more common approaches are prescribed drugs that can either keep the hormones from being produced or keep the hormones from affecting the cancer cells. The most common side effect of hormone therapy is hot flashes.

Immunotherapy: With this type of treatment, the immune system is strengthened to help fight the cancer cells. The side effects vary but may include fever, chills, nausea, loss of appetite, rashes, and fatigue.

Radiopharmaceuticals: Drugs that have radioactive elements are injected into the body through a vein. The drugs go into the cancerous bones and work to kill the cancer cells. The main side effect is a lower blood cell count which can increase the risk for infection and bleeding.

Bisphosphonates: Drugs that work to slow down the breakdown of bone (this can be caused by certain skeletal metastases) can be taken by mouth or given through a vein. Benefits of bisphosphonates are that they can help with the following: reduce bone pain, slow down bone damage, lower high blood calcium levles, and decrease risk for broken bones. Common side effects are fatigue, fever, nausea, vominting, anemia, and bone'joint pain. Something to be cautious about is that another side effect is osteonecrosis of the jaw (a portion of the jaw lacks blood supply and dies). It is important to have routine dental check-ups.

Denosumab: A drug that helps slow down the breakdown of bone; it is injected under the skin every four weeks. Common side effects are nausea, diarrhea, and fatigue.

Bone cement: Bone cement can be injected into a bone to help stabilize and reduce symptoms of pain.

External Radiation Therapy: This is similar to receiving an x-ray except the radiation beams are much more intense. Radiation helps to destroy cancer cells or helps to slow down the growth of tumors. Side effects can be reduced with the right dose and aim of the beam.

Ablation Therapy: Heat, cold, or chemicals may be used to destroy tumors. This is performed by placing a needle or probe directly into the tumor. This treatment is often well tolerated and a person can usually return to their normal activities in a few days.

Surgery: This is done to help reduce a person's symptoms and to help stabilize a weakened bone. Screws, plates, pins, and rods can be used to help keep a bone from staying unstable.       

Physical Therapy Management (current best evidence)  

Strengthening

Balance/Fall Prevention

Splint/Bracing

Assistive Device

Mobility

Pain Management                                            

Differential Diagnosis

Arthritis

Low Back Pain

Traumatic Fracture

Case Reports/ Case Studies

Callan B. Metastatic Hip Tumor in a Middle-Aged Woman.J Orthop Sports Phys Ther. 2016 May;46(5):400. doi: 10.2519/jospt.2016

McGarvey CL. A case report:breast cancer metastasis and implications of bony metastasis on activity and ambulation. Rehabilitation Oncology; 2006: 24- 1.

Reicherter EA. An African American patientwith pathological fractures due to metastatic breast cancer: An evidence-based commentary on patient management. Geriatric Rehabilitation; 2005: 155-168.

Resources  

American Cancer Society

1-800-227-2345

www.cancer.org

National Cancer Institute (NCI)

1-800-4-CANCER (1-800-422-6237)

www.cancer.gov

National Coalition for Cancer Survivorship

1-888-650-9127

www.canceradvocacy.org

CancerCare

1-800-813-HOPE (1-800-813-4673)

www.cancercare.org

Recent Related Research (from Pubmed)

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References

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1. American Cancer Society. Understanding Your Diagnosis. http://www.cancer.org (accessed 21 March 2013).
2. ↑ Zometa. Bone Metastases. http://www.us.zometa.com (accessed 21 March 2013).
3. OncoLink. Bone Metastasis Treatment with Medications. https://www.oncolink.org/cancers/bone/bone-metastases/bone-metastasis-treatment-with-medications (accessed 1 April 2017).
4. Indian Journal of Orthopaedics. Management of skeletal metastases: An orthopaedic surgeon’s guide. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4292329/ (accessed 27 March 2017).
5. Bone Metastasis (Secondary bone tumors) [Internet]. Stritch School of Medicine. [cited 2017Apr4]. Available from: http://www.meddean.luc.edu/Lumen/MedEd/Radio/curriculum/Surgery/Met_bone_list1.htm
6. Society of Interventional Radiology. Nonsurgical Treatments for Metastatic Cancer in Bones. http://www.sirweb.org (accessed 26 March 2013).
7. Tumblr. Scissorthief. http://www.tumblr.com (accessed 23 March 2013).
8. American Academy of Orthopaedic Surgeons. Orthoinfo:Metastatic Bone Disease. http://orthoinfo.aaos.org/topic.cfm?topic=a00093 (accessed 23 March 2013).
9. Kenan S and Mechanick JI. NCBI. Skeletal Metastases. http://www.ncbi.nlm.nih.gov/books/NBK12348/
10. University of Michigan Comprehensive Cancer Center. Bone Metastases Symptoms. http://www.cancer.med.umich.edu/cancertreat/tissue_bone/bonesymptoms.shtml
11. Most Common Tumors to Metastasize to Bone (80% of bone mets). Learning Radiology - Metastatic, Disease, Bone, Osteoblastic, Osteolytic. http://learningradiology.com/archives05/COW%20142-Osteoblastic%20mets/blasticmetscorrect.htm (accessed 05 April 2017)
12. National Cancer Institute at the National Institutes of Health. Symptoms of Hypercalcemia. http://www.cancer.gov/cancertopics/pdq/supportivecare/hypercalcemia/Patient/page2
13. XGEVA. When Cancer Spreads to Bone. http://www.myxgeva.com (accessed 28 March 2013).
14. Cleveland Clinic. Treatments and Procedures. http://my.clevelandclinic.org(accessed 26 March 2013).
15. Prostate Cancer Foundation. Managing Bone Metastases and Pain. http://www.pcf.org (accessed 28 March 2013).
16. Bunting RW, Shea B. Bone metastasis and rehabilitation. Cancer 2001; 92:1020-1028. http://onlinelibrary.wiley.com/doi/10.1002/1097-0142(20010815)92:4%2B%3C1020::AID-CNCR1415%3E3.0.CO;2-I/full