Bone Metastasis

What are?

Bone metastases are a frequent complication of advanced malignancies. Following the lung and liver, bone is one of the most common sites of metastasization for most cancers.

Bone metastases can occur in any part of the skeleton, but most commonly they involve the pelvis, spine, skull, legs and arms. The effect of skeletal involvement is variable and depends on a number of factors, including the number and location of lesions. Direct complications of bone involvement include pain and pathological fractures. With rare exceptions, metastatic bone cancer cannot be cured. However, different treatment options can help the cancer patient manage pain and other symptoms.

Causes

Metastases occur when cancer cells, through the blood or lymphatic stream, migrate from the site of the primary tumor to other organs or tissues, taking root and giving rise to new neoplastic formations. In some cases, these cells reach the bones, where they begin to proliferate.

A bone metastasis can represent the first sign of a neoplasm or it can occur years after the treatment of the primitive tumor.

Note . Bone metastases are more common than primitive bone tumors, especially in adults.

Osteolitic and Osteoblastic Metastases

Under normal conditions, the bone undergoes continuous remodeling: the osteoclasts mediate resorption (demolish the bone tissue), while osteoblasts are responsible for bone deposition (they build bone tissue). The dysregulation of these processes by tumor cells leads to two different phenotypes:

  • Osteolytic bone metastases : characterized by the destruction of normal bone in a particular area; it is the most common damage in tumors that have spread from the lung, thyroid, kidney and colon.
  • Osteoblastic bone metastases : the deposition of new tissue occurs in response to the spread of cancer. The process causes abnormal growth, where the bone structure is weak and deformed. It is most often found in prostate, bladder and stomach cancers.

This distinction is not absolute; many patients with bone metastases have both osteolytic and osteoblastic lesions.

In both types of lesions, dysregulation of the normal bone remodeling process leads to malformation of the bones. The bones thus altered are not able to withstand normal mechanical stresses and are exposed to pathological fractures, compression and instability.

Symptoms

Bone metastases can cause a wide range of symptoms, which can compromise quality of life or shorten patient survival. Some tumors more easily metastasize to the bones: breast, lung, prostate, thyroid and kidney.

Signs and symptoms of bone metastases include:

  • Bone pain (most common symptom);
  • Fractures. Bones weakened by the neoplastic process break more easily. A fracture after a minor injury is a possible sign of bone metastasis.
  • Anemia. Reduced red blood cell production is a common blood abnormality in patients with bone metastases.

In addition to these local effects, osteolytic metastases can cause hypercalcemia (increased levels of calcium in the blood). Other effects of bone metastases may include: spinal cord compression, decreased mobility, urinary and fecal incontinence. Patients with metastases located in the bones of the spine may develop damage to the nervous system, which can lead to paralysis and loss of use of the legs and / or arms.

Diagnosis

In some cases, a bone metastasis is discovered before or at the same time as the primary tumor. Doctors can determine the site of origin of the disease by characterizing the type of cancer cells that make up the metastases. Importantly, many cancer patients present with bone and joint pain as a side effect of some chemotherapy regimens.

Anamnesis and physical examination

The first approach is aimed at understanding the patient's general health status. If your doctor suspects that a bone metastasis is responsible for the symptoms, it collects information about previous medical conditions and their management. After the anamnesis, a physical examination is performed, concentrated above all on the painful areas.

Diagnostic imaging

After medical history and physical examination, the doctor acquires a series of radiographic images of the suspect region. The examination allows to determine if a primitive tumor has given rise to metastases and the possible degree of bone involvement. Other imaging techniques help establish the severity of the lesions: bone scintigraphy is useful for determining whether other bones, in addition to those in which the symptoms are concentrated, are affected by metastasis; in some cases, positron emission tomography (PET), computed tomography (CT) and / or magnetic resonance imaging (MRI) may be indicated, especially in cases where the spine or pelvis may be involved.

Blood and urine tests

Cancer patients should be evaluated regularly with a complete blood count, as red cell deficiency (anemia) is often found in metastatic bone disease. Furthermore, the alteration of some blood chemistry parameters (electrolytes, calcium and alkaline phosphatase) may be indicative. In particular, in patients with metastases, blood tests can detect protein markers of bone loss and higher levels of calcium in the blood. Urinalysis can show the presence of blood in patients with renal carcinoma, while thyroid function tests and the evaluation of tumor markers - such as CEA (carcino-embryonic antigen), CA-125 (Cancer Antigen 125) and PSA ( prostate specific antigen) - may be altered in patients with specific tumors.

Bone biopsy

The doctor must determine whether the metastasis results from a primary bone tumor (sarcoma) or from a neoplasm that began in another location. A bone biopsy involves taking a sample of tissue, to be analyzed to characterize the tumor cells and define this aspect.

Treatment

To determine the best treatment plan, doctors must consider a number of factors. Often, the choice between treatment options depends on where the bone metastases developed and their extent.

Unfortunately, in many cases, at the time of diagnosis the cancer has already progressed to the point where more sites are involved. As a result, treatment is often focused on symptom management and is not intended to be curative.

Depending on these factors, the treatment of bone metastases often involves a complete approach that may include one or more of the following approaches:

  • Treating the primitive tumor;
  • Reduce the extent of metastases;
  • Manage pain and damage to bone structure.

The most common treatment options for bone metastases include surgery to stabilize weak or broken bone, radiation therapy and some drugs to control pain and prevent further spread of the disease.

drugs

Drug treatment options for patients with bone metastases include:

  • Anti-resorbing drugs : they are commonly used to treat people with osteoporosis, but they can also help patients with bone metastases. These drugs can strengthen bones, reducing pathological fractures and pain. Anti-resorbing drugs can also decrease the risk of developing bone metastases in other sites. Therapy can cause temporary pain and kidney problems. In rare cases, anti-reabsorbent drugs increase the risk of avascular osteonecrosis.
  • Drugs to control pain : painkillers, such as ibuprofen or morphine, can control the symptoms caused by bone metastases.
  • Chemotherapy : involves the use of drugs to stop the proliferation of cancer cells. The effect of chemotherapy is systemic, so it affects the entire organism and also damages healthy cells. For this reason the therapeutic regimen is carried out in cycles that provide for periods of rest. Chemotherapy drugs are administered orally, intravenously or intramuscularly. The side effects depend on the duration of the treatment and the dose used; may include fatigue, hair loss, nausea and vomiting.
  • Hormone therapy : some types of cancer are sensitive to hormones, such as estrogens, which can stimulate the proliferation of neoplastic cells. Hormone therapy therefore aims to limit the effects of hormones on disease progression. Treatment may involve taking drugs that suppress the production of the hormones responsible or block their interaction with cancer cells. The therapy presents side effects similar to menopause (in women), related to hormonal fluctuations, including hot flushes, anemia and loss of sexual desire.
  • Bisphosphonates : these drugs can be used to stabilize bone mass and slow down the degenerative process of metastases. Bisphosphonates are also useful for the treatment of pain and hypercalcaemia. The oral form is generally well tolerated, but long-term therapy may involve several side effects, such as: arthralgia and osteonecrosis of the jaw.

Radiotherapy

Radiation therapy involves the destruction of tumor cells by administering high-energy radiation, directed to the metastatic tumor and adjacent tissue. The treatment allows to control the progression of the disease and to prevent pathological fractures. Depending on how many areas are affected by metastasis, one or more bones may be the target of radiotherapy treatment.

Treatment may be an option if the condition causes pain that cannot be controlled effectively with pain medication. Depending on the situation, the radiotherapy regimen may include the administration of one or more doses, for a specific period of time. The side effects depend on the site to be treated. In general, radiotherapy causes fatigue, mild skin reactions, stomach upset and diarrhea. The primary goal of treatment is to relieve pain, producing minimal side effects. Even if the different tumors respond in a variable way to radiation, in general, it is unlikely that radiotherapy will be curative; therefore, the doctor must balance the potential benefits and risks of the treatment for each patient. In the case of multiple bone metastases, radiopharmaceuticals can be administered intravenously. Once in the body, the radioactive particles travel to the areas of bone metastasis and selectively produce their effect.

Surgical treatment

The goals of surgical treatment for bone metastases are to relieve pain and restore skeletal strength. Surgical procedures can help stabilize a bone at risk of breaking or repairing a fracture.

  • Surgery to stabilize the bone. If the bone is weakened and at risk of fracture, due to bone metastasis, surgeons can stabilize it using orthopedic fixation devices, such as metal plates, pins and nails. The procedure can relieve pain and improve the function and mobility of the treated area. In some cases, bone cement is inserted into the defect created by the tumor. This gives strength to structures that cannot be easily stabilized with fixation devices, such as the pelvic bones and the spine. This procedure can also reduce pain due to bone metastases.
  • Surgery to repair a broken bone. If bone metastases have caused a fracture, surgeons can repair the injured bone. This operation involves the use of metal plates, nails and screws to stabilize the bone. Another option is prosthetic replacement of bone segments.

Conclusions

The response to treatment depends on:

  • Position and extent of metastases;
  • Pain intensity;
  • Number of painful sites;
  • Seat of the primitive tumor;
  • Type of lesions (osteolytic vs. osteoblastic);

Bone metastases are usually not curable. However, advances in surgical techniques, as well as the use of medical radiation and appropriate pharmacological therapies, have greatly improved the quality of life of the cancer patient with bone metastases.

The identification and early therapy of a metastatic tumor correlate with a more favorable clinical outcome.

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