Last Updated on January 9, 2024
Bone metastasis or metastatic bone disease is said to occur when cancer cells from other parts of the body spread to the bone. After lung and liver, bone is considered to be the third most common organ involved in metastases. In breast cancer, the bone is the second most common site for metastases.
Metastases in the bone need early detection and aggressive management.
What is Bone Metastasis?
The term metastasis refers to the spread of the cancer cells from their original or primary site to a different location in the body. It must be stressed that local invasive growth is not considered metastases but local spread or expansion of the tumor.
Bone metastasis is also called metastatic bone cancer or secondary bone cancer [cancer that originates primarily in the bone is primary bone cancer). Typically bone metastasis originates in other tissues and then spreads to the bone though some primary bone tumors can metastasize to other bone.
What Are Malignancies that Spread to Bone
Following malignancies commonly spread to the bones
Prostate cancer has the highest risk for bone metastasis followed by lung, renal, or breast cancer.
Mechanism of Metastasis
Metastasis is the process by which cancer cells migrate throughout the body. Cells need to break away from the primary tumor and form a tumor at some other place in the body [secondary tumor].
Metastasis in Greek means displacement. It is one of the three hallmarks of malignant tumors.
Different tumors have different capacity to metastasize.
The cancer cells break away from the main tumor and enter the bloodstream or lymphatic system. Then they can be carried to any part like bones, brain, liver, lymph nodes, and lungs among other tissues.
Each tissue has a specific milieu where the cancer cells can grow. However, to break and grow at some other place, the cells must become exposed to environmental stresses, including a lack of oxygen or nutrients, a low pH, and mediators of the inflammatory response. These pressures can select tumor cells with the capability of growth despite these conditions.
The metastatic cells first climb over/around neighboring cells and crawl until they hit a blockage called the basal lamina or basement membrane.
To cross this, the cells make use of digestive enzyme matrix metalloproteases. After crossing the basal lamina, they squeeze between vessel lining cells and float through the circulatory system until they find a suitable location to settle and re-enter the tissues. The cells can then begin to grow in this new location, forming a new tumor.
A malignant cell that has gained access is not always successful in forming a secondary tumor. It could be killed by
- the immune system
- gets damaged
- gets stuck in blood vessels
- gets stuck in the lymphatic system.
Moreover, the cell may not be able to survive once it leaves its colony or primary tumor.
Routes of Bone Metastasis/ Pathophysiology
Three primary paths of tumor spread can result in bone metastases
- Hematogenous or through blood circulation
- Lymphatic system
- Transcoelomic – Through the body wall into the abdominal and chest cavities
The hematogenous route system is the primary route of spread.
The lymphatic vessels are the main route for spread to the local lymph nodes. From there again, the hematogenous route is taken.
Approximately, 3% of all cancers are of unknown primary origin. In some of these cases, a primary tumor may appear later.
The metastatic spread to the bone is hematogenous. Therefore, bony metastasis affects vascularised parts, especially the axial skeleton.
However local invasion from soft tissue tumors is also possible.
The following bones are most commonly involved in the metastases
- Rib cage
Some cancers have a predilection for certain regions
- Lung and breast cancers metastasize preferably in the thoracic region [via Azygos vein and Batson plexus]
- Prostate – Lumbosacral spine, pelvis [via pelvic plexus]
during spread, interactions occur between the receptors on the tumor cells (like CXCR4, RANKL) and the stromal cells of the bone leading to the release of growth factors, cytokines (IL-6, IL-8), and angiogenic factors (VEGF). This causes tumor growth.
Types of Bone Metastasis
Depending on whether the tumor cells destroy the bone or form new bone.
- Osteolytic Lesions: These tumors cause osteolysis or destruction of bone making it fragile and risk the fracture occurrence.
- Osteoblastic Lesions: The tumor cells cause bone formation but the built-up bone is abnormal and is hard and brittle. Again it increases the risk of fractures.
- Mixed Type: Has both characteristics
Bone metastasis from prostate cancer is osteoblastic. Those from the breast, lung, and kidney are osteolytic. Breast cancer metastasis are mixed type.
Depending on the Distribution Type
- Single bone lesion
- Oligometastatic disease
- Multiple bone metastases
- Visceral plus bone
Presentation and Evaluation of Bone Metastasis
Bone metastasis may not lead to any symptoms initially. As the tumor grows in size, it weakens bone and exerts pressure on the surrounding structures leading to various kinds of presenting symptoms that may vary with the location and the tissue involved. These presentations are called skeletal-related events and are as follows
- Bone pain: It is the most frequent symptom. n the spine it may present as back pain. Often the patient may attribute it to the trauma and the unsuspecting clinician may treat it that way too. However, the pain and bony tenderness that does not improve within a reasonable period should be investigated further. The pain is usually localized and progressively worsens. There might be worsening of pain during loading [walking in case of limbs].
- Spinal cord compression: Bone metastases may cause nerve root compression or spinal cord compression in the spine. Spinal compression is an emergency and occurs due to the collapse of the involved vertebra(e). The suggestive symptoms may be back pain, limb weakness, sensory loss, bladder and bowel dysfunction etc.
- Fractures: Bone metastases cause bone destruction. Increased destruction of bone increases the risk of impending pathological fracture.
- Hypercalcemia: This is found in up to 30 percent of cases of osteolytic bone metastases due to increased bone resorption. It is attributed to the release of parathyroid hormone-related protein by tumor cells that stimulate osteoclasts. [read more about osteoclasts]. Hypercalcemia may present as
- Abdominal pain,
- Mental changes
- Anemia: This may occur due to infiltration of the bone marrow with metastatic tumor cells. In late stages, pancytopenia [decrease in production of all types of blood cells by bone marrow]
Physical examination may reveal a normal-looking area or swelling over the region depending on how much bone is involved. There would be tenderness in the involved region of the bone’
Overlying skin changes may include dilated veins, dimpling, or wounds.
Diagnostic Work Up and Evaluation
These are the initial imaging of choice though these are known to miss lesion till 30-50 percent bone mineral is lost at the site of the disease or the lesion is about 1-2 cms.
Thus plain X-rays are not very sensitive in the detection of bone metastasis especially when these are subtle lesions.
Computed tomography is more sensitive in both osteolytic and sclerotic lesions. It can also be used to stage tumors as it can mark cortical breach early and preoperative planning.
MRI is highly sensitive and specific (95%, 90%) in the detection of bone metastasis. It is also useful to detect marrow involvement before the development of osteoblastic lesions.
Also called skeletal scintigraphy, the bone scan is the most commonly used radionuclide imaging. The 99mTc-MDP scan is the most commonly used. The radionuclide 99mTc-Methyl diphosphonate is injected and its uptake is noted by different regions on plain images. Thus, it can scan the whole skeleton. It is quite sensitive and can aid in early diagnosis.
Bone scans, however, may not readily differentiate between benign and malignant bone lesions. These are also not very good in the detection of pure lytic-type of lesions.
Single-photon emission computed tomography uses 99mTc-MDP radioisotope too to detect the update but generates 3D images and has higher specificity.
Positron emission tomography is uses radiotracers 18F FDG (Fludeoxyglucose) or 18FNaF for the detection of skeletal metastases. The latter is more sensitive and specific.
- Positron emission tomography helps evaluate response to chemotherapy and treatment guidance.
- Complete blood count
- May show anemia, decreased platelet etc
- Metabolic panel
- Serum calcium levels
- Alkaline phosphatase
Biopsy confirms the malignancy and can be done in many ways
- CT guided biopsy
- Open biopsy
- Joint aspiration in intraarticular tumors
It is used in vascular or huge tumors to identify the feeder vessel or embolize it preoperatively.
Treatment of Bone Metastasis
Approach to Treatment
A multimodal approach using surgery, chemotherapy, radiation therapy, and other feasible options [hormone therapies] is considered in treatment of bone metastasis.
Treatment choice generally depends on the type of primary cancer, the size, and location of the metastasis, the patient’s age and general health, and the types of treatments used previously.
The treatment options currently available are rarely able to cure metastatic cancer.
The aim of the treatment in bone metastasis is
- Pain relief
- Preservation/restoration of the function
- Local tumor control
- Skeletal stabilization
Pain Control Drugs
One or more drugs in combination can be given
- Steroids (glucocorticoids)
Osteoclast Inhibitor Drugs
These are known to decrease bone destruction, decrease bone pain, and are associated with lowering the death rate as well. These drugs may reduce risk of new bone metastasis.
Bisphosphonates are typically more effective in osteolytic lesions. Recent studies suggest that bisphosphonates may inhibit the progression of bone metastases.
Zoledronic acid is currently one of the most potent bisphosphonates used.
Bone-targeted radiopharmaceutical therapy
Radiopharmaceuticals use low levels of radioactive materials that have a strong affinity for bones. These agents are – strontium-89, alpha-emitting radium-223 etc.
This therapy helps to treat the pain associated with osteoblastic bone metastasis. However, they can adversely affect the bone marrow and hamper the production of blood cells. The clinical response may take 1-2 weeks.
Systemic chemotherapy for primary tumors, where possible, can also lead to a reduction of tumor size and spread. Chemotherapy involves use of anticancer medications, steroids, hormonal agonist or antagonists [in some tumors] to kill the tumor.
Local radiation is an important form of treatment in providing pain relief in bone metastasis. Radiation has also a role in postoperative tumor management.
The standard approach is external beam radiation. Stereotactic body radiotherapy (SBRT) use it may be indicated in some spinal bone metastasis. Up to 30 percent of patients achieve complete pain relief whereas partial relief is observed in as high as 80 percent.
Surgery is done either for the removal of tumors or fixation of pathological fractures or to carry out amputation in case of unsalvageable limbs. In case of the joint is destroyed by a tumor or needs to be taken out, endoprosthesis or arthrodesis is considered.
Palliative surgery like debulking of the tumor is also done in selected cases.
Pathological fractures are fixed with suitable implants. Bone cement may be used to augment the bone when it is severely weakened.
Prophylactic or stabilization surgery is done in cases where there is an impending fracture. In spine , decompression and fixation can be considered where required.
- Loftus LS, Edwards-Bennett S, Sokol GH. Systemic therapy for bone metastases. Cancer Control. 2012;19(2):145–153. [Link]
- Biermann JS, Holt GE, Lewis VO, Schwartz HS, Yaszemski MJ. Metastatic bone disease: diagnosis, evaluation, and treatment. J Bone Joint Surg Am. 2009 Jun;91(6):1518-30. [Link]