Bone Cancer

Bone-Cancer-Stages Osteosarcoma Overview Overview Osteosarcoma is the most common type of cancer of the bone. It is the third most common malignancy in children and adolescents, accounting for approximately 5% of all cancers in these age groups. In children and adolescents, 50% of osteosarcomas arise from the bones around the knee. The cause of most cases of osteosarcoma is unknown although a genetic predisposition is suspected. The main known cause of osteosarcoma is radiation therapy. Osteosarcoma is a relatively frequent complication in survivors of childhood cancers treated with radiation therapy with a latency period of 15-20 years.[1][2] Osteosarcoma originates most frequently in the thigh bone (distal femur), lower leg (proximal tibia) or upper arm (proximal humerus). Symptoms of osteosarcoma depend on the extent of disease, but may include pain, swelling, localized enlargement of the extremity and, occasionally, a bone fracture without trauma. At the time of diagnosis, approximately 80% of patients have localized osteosarcoma and the remainder have metastatic osteosarcoma. Diagnostic Procedures It is imperative that patients with diagnosed or suspected osteosarcoma undergo an evaluation by an orthopedic oncologist who is familiar with surgical management of this disease. Patients should undergo this evaluation prior to an initial biopsy, since an inappropriately performed biopsy may jeopardize a subsequent limb-sparing procedure. There are several methods for diagnosing osteosarcoma. At this time, controversy exists over which of these methods is optimal. Open Incisional Biopsy: An open incisional biopsy involves a wide incision through the skin in order to expose the suspicious mass so that a tissue sample can be removed and analyzed in a laboratory. Complications occur in approximately 16% of patients that receive this type of biopsy. In some cases, these complications could lead to unnecessary amputation. Percutaneous Biopsy: A percutaneous biopsy, is an effective method for making a diagnosis before surgery. Since most patients are currently treated with neoadjuvant chemotherapy, it is important to make the diagnosis prior to surgery. A percutaneous core needle biopsy is a procedure in which a small needle with a hollow core is placed into the suspicious mass and a tissue sample is collected. This procedure uses computed tomography (CT) or fluoroscopy to help guide the biopsy needle.[3] In a recent study of 110 primary bone tumors, a percutaneous biopsy resulted in accurate diagnosis in all but 13 cases. Fine Needle Aspiration Biopsy (FNAB): FNAB is another type of biopsy in which a very fine needle is placed into the mass for the collection of a cell sample, and is less invasive than the percutaneous biopsy. However, an adequate number of cells are difficult to obtain through FNAB, often times resulting in the need for a patient to undergo a repeat biopsy. One study using FNAB resulted in a conclusive diagnosis in only 65% of 40 patients.[4] Other: Additional tests may help determine the extent or stage of osteosarcoma. X-ray examinations commonly detect bone destruction and increased bone formation caused by osteosarcoma. Computed tomography (CT) scans and bone scans using isotopes are recommended as part of the staging process to detect lung and bone metastases, respectively. Staging The process of identifying the extent of the cancer is called staging. Accurately identifying the stage of a cancer helps determine what treatment will be most effective. Staging is particularly important for determining whether a cancer has spread from its original site to other parts of the body. Although there are more sophisticated staging systems for patients with osteosarcoma, it is most convenient to categorize the cancer as localized, metastatic, and recurrent. Localized Osteosarcoma Localized cancers are limited to the bone of origin. In these cases, smaller tumors that are separate from the primary cancer, called “local skip metastases”, may be apparent within the bone, indicating a worse prognosis. Approximately 50% of primary osteosarcomas occur in the upper leg. Of these, 80% arise adjacent to the knee joint in young patients. Other primary sites are the lower leg, upper arm, pelvis, jaw, and ribs. Metastatic Osteosarcoma Metastatic osteosarcoma has spread beyond the primary site of origin. Metastatic disease is diagnosed when staging tests reveal evidence of disease in the lung, other bones, or other distant sites. More than 80% of patients with metastatic osteosarcoma have cancer that has spread to the lung. The second most common site of spread is another bone. Recurrent Osteosarcoma Patients with recurrent osteosarcoma have disease that has recurred after a complete response or have disease that was not eradicated with initial treatment. The most common sites for recurrent osteosarcoma are the lungs and bone. References [1]Bielack SS, Kempf-Bielack B, et al. for the Cooperative German-Austrian-Swiss Osteosarcoma Study Group: Combined modality treatment for osteosarcoma occurring as a second malignant disease. Journal of Clinical Oncology 1999;17:1164-1174. [2]Tabone MD, Terrier P, Pacquement H, et al. Outcome of radiation-related osteosarcoma after treatment of childhood and adolescent cancer: a study of 23 cases. Journal of Clinical Oncology 1999;17: 2789-2795 [3]Jelinek JS, Murphey MD, Welker JA, et al. Diagnosis of primary bone tumors with image-guided percutaneous biopsy: experience with 110 tumors. Radiology 2002;223:731-737. [4]Dodd LG, Scully SP, Cothran RL, et al. Utility of fine-needle aspiration in the diagnosis of primary osteosarcoma. Diagn Cytopathol 2002;27:350-353. Copyright © 2012 Omni Health Media. All Rights Reserved. Bone Complications and Cancer 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. Copyright © 2012 Omni Health Media. All Rights Reserved. Hypercalcemia Overview An increased level of calcium in the bloodstream is most often a complication of cancer and is referred to as hypercalcemia of malignancy. In its severe form, hypercalcemia may be a life-threatening emergency. Management of hypercalcemia may involve increasing fluid intake, as well as the use of diuretics and bisphosphonate drugs. * What is hypercalcemia? * What causes hypercalcemia? * What are the signs and symptoms of hypercalcemia? * How is hypercalcemia diagnosed? * How is hypercalcemia treated? What is Hypercalcemia? Hypercalcemia is an increased level of calcium in the bloodstream. This disorder is most commonly caused by malignancy (called hypercalcemia of malignancy) or primary hyperparathyroidism. Other causes of elevated calcium are less common and are usually not considered until it has been determined that neither malignancy nor parathyroid disease is present. Hypercalcemia of malignancy occurs in approximately 10% of patients with advanced cancers. The occurrence of hypercalcemia may rise as high as 40% in some types of cancer, including breast, lung and multiple myeloma. What Causes Hypercalcemia? Hypercalcemia of malignancy has many causes. It may be related to the spread of cancer from its site of origin to bones in the body, a process called metastasis. Cancer cells can spread, or metastasize, through the blood and lymph systems. A cancer cell may break away from the original location in the body and travel in the circulatory system until it gets lodged in a small capillary network in bone tissue. Cancer may also spread to bone from the adjacent cancer, though this occurs less frequently than spread by the bloodstream. Bone metastases result in injury to the bone tissue. Although bone appears to be the most static of all the tissues in the body, it is actually very dynamic and active. 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. One important function of bone remodeling is maintenance of blood calcium levels. Calcium is necessary for many processes in the body, including contraction of muscles, nerve function, blood clotting 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. In the case of hypercalcemia, bone metastases cause an imbalance between bone formation and bone resorption, resulting in the release of excess calcium into the blood. What are the Signs and Symptoms of Hypercalcemia? Signs and symptoms of hypercalcemia may include: * Nausea * Fatigue * Vomiting * Lethargy * Stomach pain * Moodiness * Constipation * Irritability * Anorexia * Confusion * Excessive thirst * Extreme muscle weakness * Dry mouth or throat * Irregular heart beat * Frequent urination * Coma These many signs and symptoms are commonly attributed to either the cancer treatment or the malignancy itself and may make it difficult for doctors to detect hypercalcemia of malignancy when it first occurs. This disorder can be severe and difficult to manage. Severe hypercalcemia is a medical emergency requiring immediate treatment. How is Hypercalcemia Diagnosed? Hypercalcemia may be diagnosed with a blood test. Blood calcium levels are tested by taking a small amount of blood from the patient with a needle. The blood is collected in tubes and sent to a lab for evaluation. Normal blood calcium levels range from 8.5 to 10.5 milligrams per deciliter (mg/dl) of blood. The normal range may vary slightly from lab to lab. More than one test may be necessary to determine that blood calcium levels are abnormally high. In a person with cancer, a high blood calcium level is considered a medical emergency and treatment should be started immediately. How is Hypercalcemia Treated? The best treatment for hypercalcemia due to cancer is treatment of the cancer itself. However, since hypercalcemia often occurs in patients whose cancer is advanced or has not responded to treatment, management of hypercalcemia is sometimes necessary. Treatment for hypercalcemia is based on a number of factors, including the condition of the patient and the severity of the hypercalcemia. Increasing fluid intake and the use of diuretics has been standard practice. Most recently, bisphosphonate drugs have become an effective approach. Hydration: One of the primary treatments for hypercalcemia of malignancy is hydration, which may consist of increasing oral fluid intake or intravenous (through a vein) administration of fluids. Hydration helps decrease the calcium level through dilution and causes the body to eliminate excess calcium through the urine. For mild-to-moderate elevations of calcium, patients are usually directed to increase oral fluid intake. For acute hypercalcemia, hydration with saline is immediately administered intravenously. The rate of hydration is based upon the severity of the hypercalcemia, the severity of dehydration, and the ability of the patient to tolerate rehydration. Diuretics: Sometimes, hypercalcemia of malignancy is treated with a diuretic. The most commonly used diuretic, furosemide (Lasix®), causes the kidneys to produce more urine. As a result, the amount of free water in the body is reduced. Along with an increase in urine volume, furosemide causes loss of calcium, sodium and potassium. Furosemide is well tolerated; however, it is not free of side effects, which may include dehydration, low blood potassium and low blood sodium. Furosemide is available by intravenous administration, as well as oral tablets. The intravenous method of administration is used to achieve an urgent effect. Oral tablets are used for maintenance. Oral tablets of furosemide are administered once or twice a day. Bisphosphonates: 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. There is also evidence that these drugs bind to bone, thereby blocking osteoclastic resorption. 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 treated with a bisphosphonate drug 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 hypercalcemia include Zometa® (zoledronic acid) and Aredia® (pamidronate). Of these two dugs, 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 treatment regimen for patients. 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. Copyright © 2012 Omni Health Media. All Rights Reserved. Bone Loss Overview Bone loss is a weakening of the bones and may be caused by aging, cancer, or cancer treatment. Bone loss may be diagnosed if the results of a test (called a bone scan) indicate weak bones. However, many individuals do not realize they have bone loss until they experience a fracture. Treatment for bone loss may consist of surgery to repair a fracture, radiation to treat cancer in the bones, or drug therapy, including the newer bisphosphonate drugs, which can also prevent bone loss. * What is bone loss? * What causes bone loss? * Does cancer treatment contribute to bone loss? * What are the signs and symptoms of bone loss? * How is bone loss diagnosed? * How can bone loss be prevented? * How can osteoporosis be treated and/or prevented? What is 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. What Causes Bone Loss? Normal bone is constantly being broken down and rebuilt, a process called remodeling. Every week, humans recycle 5% to 7% of their bone mass. Bone loss occurs when there is a disruption to this normal remodeling activity in the form of an increase in the breakdown of bone without a comparable increase in bone building. Bone loss may occur as a result of: * Osteoporosis (a weakening of the bones related to aging and other factors) * Hormonal therapy for the treatment of breast and prostate cancer * Chemotherapy for the treatment of cancer in women * Bone Cancer or Bone Metastases (cancer that has spread to the bones) Does Cancer Treatment Contribute to Bone Loss? Some cancer treatments can increase bone loss. Hormonal therapies administered in the treatment of breast and prostate cancer can leave patients more susceptible to bone loss. Treatment with chemotherapy may also lead to bone loss in some patients. Patients that are diagnosed with early stage breast or prostate cancer often receive long-term treatment with hormonal therapy. The goal of hormonal therapy is to reduce the levels of the hormone estrogen in women and androgens (male sex hormones) in men, since these can stimulate the growth of breast and prostate cancers. However, the sex hormones also play an important role in maintaining healthy bones, and reducing their levels may cause bone loss. Women undergoing hormonal therapy for breast cancer have significant rates of bone loss1 that are at least double those reported during early menopause, a time that women typically experience profound bone loss. For men receiving hormone therapy and orchiectomy (removal of one or both testes) in the treatment of prostate cancer, a loss of hip bone mineral density of up to 9.6% has been reported in the first year after treatment.2 Furthermore, many women who undergo chemotherapy experience ovarian failure after treatment and have increased bone loss as a result.3, 4 What are the Signs and Symptoms of Bone Loss? Bone loss is sometimes called a “silent disease” because it occurs without symptoms. People may not know they have bone loss or low-density bones until they become so weak that a sudden strain, bump, or fall causes a fracture. Fractures can occur in any bone. However, fractures to the hip or spine are particularly troublesome and are often a sign of bone loss. When these bones are healthy, they can withstand significant impact; however, when an individual has low bone-density, even a minor fall may result in a fracture. How is Bone Loss Diagnosed? Bone loss is diagnosed with a bone density scan. DEXA ( Dual Energy X-ray Absortiometry) scanning is the most widely used method for measuring bone mineral density. DEXA scanning rapidly directs x-ray energy, alternating from two different sources, through the bone being examined. Once the x-rays have passed through the bone, their strength is recorded. Bone density or bone loss is calculated from the amount of energy that travels through the bone and is picked up by the detector. The minerals in bone, predominantly calcium, weaken the transmission of the x-rays through the bone. The more dense the bone is, the fewer x-rays get through to the detector. The use of two different x-ray energy sources greatly improves the precision and accuracy of the measurement. How Can Bone Loss be Prevented? 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.5 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 How Can Osteoporosis be Treated and/or Prevented? Osteoporosis is a weakening of the bones related to aging and other factors. Although there is no cure for osteoporosis, a number of medications have been approved by the FDA to prevent and/or treat osteoporosis in postmenopausal women. * Bisphosphonate drugs * Miacalcin® * Forteo® (teriparatide) * Evista® (raloxifene) * Hormone Replacement Therapy (HRT) Bisphosphonate Drugs: Bisphosphonate drugs treat osteoporosis by decreasing the rate of bone resorption. Resorption is an activity that takes place in normal bone remodeling. In osteoporosis, resorption occurs faster than new bone formation. Fosamax® is approved as a treatment for osteoporosis in men and is approved for treatment of glucocorticoid (steroid)-induced osteoporosis in men and women. Actonel® is approved for prevention and treatment of glucocorticoid-induced osteoporosis in men and women. Boniva® (ibandronate) is approved for the treatment and prevention of osteoporosis in postmenopausal women. Boniva® is available for oral (by mouth) administration Miacalcin® (calcitonin): Calcitonin is a natural hormone that increases the deposition of calcium in the bones. Calcitonin is the active ingredient in Miacalcin®, which has been shown to prevent bone loss in postmenopausal women with reduced bone mass.6 Forteo® (teriparatide): Forteo® is a form of parathyroid hormone that increases bone formation. It is approved for the treatment of osteoporosis. Forteo® is approved for the treatment of osteoporosis in men and postmenopausal women who are at high risk for a fracture. Evista® (raloxifene): Evista® is a type of hormonal therapy called a selective estrogen receptor modulator (SERM). It is approved for the prevention of osteoporosis in postmenopausal women and has been evaluated in the prevention of breast cancer. Hormone Replacement Therapy (HRT): HRT has been shown to prevent bone loss in postmenopausal women. Examples of HRT include: * Estrogens (brand names, such as Climara®, Estrace®, Estraderm®, Estratab®, Menostar™, Ogen®, Ortho-Est®, Premarin®, Vivelle®, and others) * Estrogens and Progestins (brand names, such as Activella™, FemHrt®, Premphase®, Prempro®, and others) References 1) Sverrisdottir A, Fornander T, Jacobsson H, et al. Bone mineral density among premenopausal women with early breast cancer in a randomized trial of adjuvant endocrine therapy. J Clin Oncol. 2004 Sep 15;22(18):3694-9. 2) Eriksson S, Eriksson A, Stege R et al. Bone mineral density in patients with prostatic cancer treated with orchidectomy and with estrogens. Calcif Tissue Int. 1995;57:97–99. 3) Shapiro CL, Manola J, Leboff M. Ovarian failure after adjuvant chemotherapy is associated with rapid bone loss in women with early-stage breast cancer. J Clin Oncol. 2001;19:3306–3311. 4) Saarto T, Blomqvist C, Valimaki M et al. Chemical castration induced by adjuvant cyclophosphamide, methotrexate, and fluorouracil chemotherapy causes rapid bone loss that is reduced by clodronate: a randomized study in premenopausal breast cancer patients. J Clin Oncol. 1997;15:1341–1347. 5) 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. 6) Ellerington MC; Hillard TC; Whitcroft SI, et al. Intranasal salmon calcitonin for the prevention and treatment of postmenopausal osteoporosis. Calcif Tissue Int. 1996 Jul;59(1):6-11. Copyright © 2012 Omni Health Media. All Rights Reserved. Bone Pain Overview Bone pain in patients with cancer is commonly caused by cancer cells that have spread to the bones, called bone metastases. Bone pain is commonly the first symptom of bone metastases and may lead to tests that will confirm the diagnosis. Treatment for bone pain is intended to relieve the pain, treat fractures, reduce the risk of fracture, and prevent or delay additional bone complications. Treatment options include pain medications, bisphosphonate drugs, radiation therapy, and/or surgery. * What causes bone pain? * How are bone metastases diagnosed? * How is bone pain treated? What Causes Bone Pain? A common cause of bone pain is metastatic cancer. The spread of cancer from its site of origin to another location in the body is called metastasis. A bone metastases is not a new cancer, but consists of cancer cells from the original cancer, such as breast, prostate, lung, kidney, or thyroid, that have spread to bone. Cancer cells can spread, or metastasize, through the blood and lymph systems. Bone is one of the most common locations in the body to which cancer metastasizes. Bone metastasis usually occurs by way of the bloodstream. A cancer cell may break away from the original location in the body and travel in the circulatory system until it gets lodged in a small capillary network in bone tissue. Cancer may also spread to bone by erosion from the adjacent cancer, though this occurs less frequently than spread by the bloodstream. The pain occurs with bone cancer because the cancer disrupts the balance of normal cellular activity in the bones, causing damage to the bone tissue. Normal bone is constantly being remodeled, or broken down and rebuilt. Cancer cells that have spread to the bone disrupt this balance between the activity of osteoclasts (cells that break down bone) and osteoblasts (cells that build bone), resulting in either weakened or excessively built-up bone. This damage can either stretch the periosteum (thick membrane that covers bone) or stimulate nerves within the bone, causing pain. How are Bone Metastases Diagnosed? Bone metastases are usually diagnosed because the patient experiences pain near the metastases and reports this to their doctor. The doctor may then complete an x-ray or a more complicated procedure called a bone scan to confirm that the pain is caused by cancer-related damage to the bones. In a bone scan, low level radioactive particles are injected into a vein. They circulate through the body and some are absorbed into the bones. A high concentration of these radioactive particles on the bone scan results indicates the presence of rapidly growing cancer cells in the bone. Bone pain may be hard to differentiate from ordinary low back pain or arthritis. Usually the pain due to bone metastasis is fairly constant, even at night. It can be worse in different positions, such as standing, which may compress the cancer in a weight bearing bone. If pain lasts for more than a week or two, doesn’t seem to be going away, and is unlike other pain that may have been experienced, it should be evaluated by a physician. Bone metastases generally occur in the central parts of the skeleton, although they may be found anywhere in the skeletal system. Common sites for bone metastases are the back, pelvis, upper leg, ribs, upper arm, and skull. More than 90% of all metastases are found in these locations. How is Bone Pain Treated? The goal of treatment for bone pain caused by bone metastases is to relieve the pain, treat fractures, reduce the risk of fracture, and prevent or delay additional bone complications. Treatment options for bone metastases include pain medications, bisphosphonate drugs, radiation therapy, and/or surgery. Pain medications: Cancer-related bone pain can be managed with various pain medications. Despite the claim that 90% of adult cancer patients’ pain can be relieved, uncontrolled cancer-related pain is still a concern, particularly for patients who are living at home. Research presented at the 2003 Annual Meeting of the Oncology Nursing Society indicates that most cancer patients are not prescribed enough medication to control their pain.1 The World Health Organization recommendations for relief of cancer pain indicate that the severity of a patient’s pain, rated on a scale of 1-10, will dictate what type of pain medication is used.2 * Mild to Moderate Pain (1-3): Non-opioids are the first choice of treatment for mild to moderate pain. This includes medication such as acetaminophen (Tylenol®) or a non-steroidal anti-inflammatory drug (NSAID), such as ibuprofen. * Moderate to Severe Pain (4-6) Patients with moderate to severe pain who have not responded to the first step should receive an opioid. These medications may include codeine, hydrocodone, dilhydrocodiene, oxycodone, propoxyphene, and tramadol. Acetaminophen or a NSAID may be added. * Severe Pain (7-10) Patients with severe pain or patients whose pain has not been relieved by the previous recommendations will usually receive a stronger opioid. Opioids for severe pain may include morphine, oxycodone, hydromorphone, methadone, levophanol, or fentanyl. A non-opioid medication such as aspirin, acetaminophen, or ibuprofen may be added in some cases. Pain medications may have side effects, including sleepiness, constipation, dizziness, nausea, and vomiting. Relief from pain medications is temporary and the pain may return in a short time; thus, medications are best used at the onset of pain or at regular intervals. 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.3 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 Radiation therapy: For metastatic lesions that do not represent an immediate risk of fracture, radiation is effective for reducing bone pain and progression of the cancer. Radiation is especially useful when metastatic lesions are limited to a single area. One type of radiation therapy is called radiopharmaceutical therapy. This approach involves the injection of a radioactive substance, such as strontium-89, into a vein. This substance is attracted to areas of bone that contain cancer. Providing radiation directly to the bone in this way destroys active cancer cells in the bone and can relieve symptoms. Two possible side effects of radiopharmaceutical therapy are decreased blood counts with increased risk of bleeding, and rarely, leukemia. Surgery: When there is an immediate or significant risk of fracture, surgery may be necessary to stabilize the weakened bone. Metal rods, plates, screws, wires, nails, or pins may be surgically inserted to strengthen or provide structure to the bone damaged by metastasis. References [1]Oncology Nursing Society. ONS Position Paper on Pain. Pittsburgh PA ; 2002. [2]Chen H, Wilkie D, Huang H. Opiod Prescritption for Cancer Pain Management. Proceedings form the 2003 Annual Meeting of the Oncology Nursing Society. Abstract #147. [3]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. Copyright © 2012 Omni Health Media. All Rights Reserved. Bone Metastases Overview The spread of cancer from its site of origin to another location in the body is called metastasis. Cancer cells can spread, or metastasize, through the blood and lymph systems. Bone metastases usually occur by way of the bloodstream. A cancer cell may break away from the original location in the body and travel in the circulatory system until it gets lodged in a small capillary network in bone tissue. Cancer may also spread to bone by erosion from the adjacent cancer, though this occurs less frequently than spread by the bloodstream. Bone is one of the most common locations in the body to which cancer metastasizes. The major cancer types that tend to metastasize to bone include multiple myeloma, breast, prostate, lung, kidney, and thyroid cancers. Bone metastases may cause pain, may make the bones more susceptible to fractures, and may cause increased levels of calcium in the blood. Bone metastases result in lesions or injury to the bone tissue. There are two types of lesions: lytic lesions, which destroy bone material; and blastic lesions, which fill the bone with extra cells. Normal bone is constantly being remodeled, or broken down and rebuilt. Cancer cells that have spread to the bone disrupt the balance between the activity of osteoclasts (cells that break down bone) and osteoblasts (cells that build bone). Bone metastases generally occur in the central parts of the skeleton, although they may be found anywhere in the skeletal system. Common sites for bone metastases include the back, pelvis, upper leg, ribs, upper arm, and skull. More than 90% of all metastases are found in these locations. Complications Associated with Bone Metastases Complications that are associated with bone metastases include pain, bone loss, hypercalcemia, and decreased blood cell production. Pain: A common complication, and often the initial symptom of bone metastases, is bone pain. The thick membrane that covers each bone, called the periosteum, has many nerves, making it a highly sensitive tissue. Damage or pressure to this tissue caused by bone metastases may result in a great deal of pain. Bone pain can be debilitating to the point that it compromises a patient’s ability to manage normal day-to-day activities. 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. Learn more about the management of 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 in the leg or hip bones can be a serious condition because these are major weight-bearing bones and fractures in these areas are often debilitating. Learn more about the management of Bone loss Hypercalcemia: An increased level of calcium in the bloodstream is called hypercalcemia. This disorder results from the destruction of bone associated with metastases. Hypercalcemia can be a life-threatening condition. Symptoms of hypercalcemia may include: Nausea Fatigue Vomiting Lethargy Stomach Pain Moodiness Constipation Irritability Anorexia Confusion Excessive thirst Extreme muscle weakness Dry mouth or throat Irregular heart beat Frequent urination Coma These many signs and symptoms make it difficult for doctors to correctly diagnose hypercalcemia. Consequently, they are commonly attributed to either the cancer treatment or the malignancy itself. This disorder can be severe and difficult to manage. Severe hypercalcemia is a medical emergency requiring immediate treatment. Learn more about the management of Hypercalcemia Decreased blood cell production: Bone metastases can also cause a decrease in blood cell production. The multiplication of cancer cells in the bone marrow eventually crowds out and suppresses the normal production of blood cells. This may cause a significant decrease in red blood cells, platelets, and white blood cells, which can cause anemia, abnormal bleeding, and neutropenia, respectively. Anemia decreases the body’s ability to transport oxygen to the body’s organs. Anemia may cause patients to experience tiredness, fatigue, shortness of breath, and/or a reduced tolerance to activity. Neutropenia, or the depletion of white blood cells, compromises the immune system and makes patients more susceptible to infection. Learn more about low blood counts Copyright © 2012 Omni Health Media. All Rights Reserved.