essay on bone cancer

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Types of Bone Cancer

• Surgery for Bone Cancer
• Chemotherapy for Bone Cancer
• Radiation Therapy for Bone Cancer

There are several different types of bone cancer. Most primary bone cancers are in the category of tumors called sarcomas, a kind of cancer that can affect soft tissues such as muscles and nerves as well as bone. Sarcomas have a diverse range of features at the molecular and cellular level. Because of that, not all bone sarcomas respond to the same types of treatment.

Osteosarcoma

Osteosarcoma is the most common type of primary bone cancer, making up about one third of cases. This cancer mainly affects children and young adults between the ages of 10 and 25. Osteosarcoma often starts at the ends of bones, where new tissue forms as children grow, especially in the knees.

Chondrosarcoma

Chondrosarcoma is one of the most common types of primary bone cancer in people over age 50. It forms in cartilage, usually around the pelvis, knees, shoulders, or upper part of the thighs. This cancer makes up about a quarter of all primary bone cancer cases.

Ewing Sarcoma

Ewing sarcoma usually occurs in the middle part of a bone, most often in the hips, ribs, upper arms, and thighs. Like osteosarcoma, this cancer affects mainly children and young adults between the ages of ten and 25. Ewing sarcoma is responsible for about 15 percent of primary bone cancer cases.

Rare Bone Cancers

The following bone cancers are rare and occur primarily in adults:

• Fibrosarcoma usually appears in the knees or hips. It can arise in older patients after radiation therapy for other cancers.
• Giant cell tumors , which usually begin in the knees, affect young adults most frequently and women more often than men.
• Adamantinoma usually occurs in the shin bone.
• Chordoma is found most often in the sacrum, which is the lower part of the spine, also known as the tailbone.

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Primary Bone Cancer

What are bone tumors.

Several different kinds of tumors can grow in bones: primary bone tumors, which form from bone tissue and can be malignant (cancerous) or benign (not cancerous), and metastatic tumors (tumors that develop from cancer cells that formed elsewhere in the body and then spread to the bone). Malignant primary bone tumors (primary bone cancers) are less common than benign primary bone tumors. Both types of primary bone tumors may grow and compress healthy bone tissue, but benign tumors usually do not spread or destroy bone tissue and are rarely a threat to life.

Primary bone cancers are included in the broader category of cancers called sarcomas . (Soft-tissue sarcomas—sarcomas that begin in muscle, fat, fibrous tissue, blood vessels , or other supporting tissue of the body, including synovial sarcoma —are not addressed in this fact sheet.)

Primary bone cancer is rare. It accounts for much less than 1% of all new cancers diagnosed. In 2018, an estimated 3,450 new cases of primary bone cancer will be diagnosed in the United States ( 1 ).

Cancer that metastasizes (spreads) to the bones from other parts of the body is called metastatic (or secondary) bone cancer and is referred to by the organ or tissue in which it began—for example, as breast cancer that has metastasized to the bone. In adults, cancerous tumors that have metastasized to the bone are much more common than primary bone cancer. For example, at the end of 2008, an estimated 280,000 adults ages 18–64 years in the United States were living with metastatic cancer in bones ( 2 ).

Although most types of cancer can spread to the bone, bone metastasis is particularly likely with certain cancers, including breast and prostate cancers. Metastatic tumors in the bone can cause fractures, pain, and abnormally high levels of calcium in the blood, a condition called hypercalcemia .

What are the different types of primary bone cancer?

Types of primary bone cancer are defined by which cells in the bone give rise to them.

Osteosarcoma

Osteosarcoma arises from bone-forming cells called osteoblasts in osteoid tissue (immature bone tissue). This tumor typically occurs in the arm near the shoulder and in the leg near the knee in children, adolescents, and young adults ( 3 ) but can occur in any bone, especially in older adults. It often grows quickly and spreads to other parts of the body, including the lungs. Risk of osteosarcoma is highest among children and adolescents ages 10 and 19. Males are more likely than females to develop osteosarcoma. Among children, osteosarcoma is more common in blacks and other racial/ethnic groups than in whites, but among adults it is more common in whites than in other racial/ethnic groups. People who have Paget disease (a benign bone condition characterized by abnormal development of new bone cells) or a history of radiation to their bones also have an increased risk of developing osteosarcoma.

Chondrosarcoma

Chondrosarcoma begins in cartilaginous tissue. Cartilage is a type of connective tissue that covers the ends of bones and lines the joints. Chondrosarcoma most often forms in the pelvis , upper leg, and shoulder and usually grows slowly, although sometimes it can grow quickly and spread to other parts of the body. Chondrosarcoma occurs mainly in older adults (over age 40). The risk increases with advancing age. A rare type of chondrosarcoma called extraskeletal chondrosarcoma does not form in bone cartilage. Instead, it forms in the soft tissues of the upper part of the arms and legs.

Ewing sarcoma

Ewing sarcoma usually arises in bone but may also rarely arise in soft tissue (muscle, fat, fibrous tissue, blood vessels , or other supporting tissue). Ewing sarcomas typically form in the pelvis, legs, or ribs, but can form in any bone ( 3 ). This tumor often grows quickly and spreads to other parts of the body, including the lungs. The risk of Ewing sarcoma is highest in children and adolescents younger than 19 years of age. Boys are more likely to develop Ewing sarcoma than girls. Ewing sarcoma is much more common in whites than in blacks or Asians.

Chordoma is a very rare tumor that forms in bones of the spine. These tumors usually occur in older adults and typically form at the base of the spine ( sacrum ) and at the base of the skull. About twice as many men as women are diagnosed with chordoma. When they do occur in younger people and children, they are usually found at the base of the skull and in the cervical spine (neck).

Several types of benign bone tumors can, in rare cases, become malignant and spread to other parts of the body ( 4 ). These include giant cell tumor of bone (also called osteoclastoma) and osteoblastoma. Giant cell tumor of bone mostly occurs at the ends of the long bones of the arms and legs, often close to the knee joint ( 5 ). These tumors, which typically occur in young and middle-aged adults, can be locally aggressive , causing destruction of bone. In rare cases they can spread ( metastasize ), often to the lungs. Osteoblastoma replaces normal hard bone tissue with a weaker form called osteoid. This tumor occurs mainly in the spine ( 6 ). It is slow-growing and occurs in young and middle-aged adults. Rare cases of this tumor becoming malignant have been reported.

What are the possible causes of bone cancer?

Although primary bone cancer does not have a clearly defined cause, researchers have identified several factors that increase the likelihood of developing these tumors.

• Previous cancer treatment with radiation, chemotherapy, or stem cell transplantation. Osteosarcoma occurs more frequently in people who have had high-dose external radiation therapy (particularly at the location in the body where the radiation was given) or treatment with certain anticancer drugs, particularly alkylating agents ; those treated during childhood are at particular risk. In addition, osteosarcoma develops in a small percentage (approximately 5%) of children undergoing myeloablative hematopoietic stem cell transplantation.
• Certain inherited conditions. A small number of bone cancers are due to hereditary conditions ( 3 ). For example, children who have had hereditary retinoblastoma (an uncommon cancer of the eye) are at a higher risk of developing osteosarcoma, particularly if they are treated with radiation. Members of families with Li-Fraumeni syndrome are at increased risk of osteosarcoma and chondrosarcoma as well as other types of cancer. Additionally, people who have hereditary defects of bones have an increased lifetime risk of developing chondrosarcoma. Childhood chordoma is linked to tuberous sclerosis complex, a genetic disorder in which benign tumors form in the kidneys, brain, eyes, heart, lungs, and skin. Although Ewing sarcoma is not strongly associated with any heredity cancer syndromes or congenital childhood diseases ( 7 , 8 ), accumulating evidence suggests a strong inherited genetic component to Ewing sarcoma risk ( 9 ).
• Certain benign bone conditions. People over age 40 who have Paget disease of bone (a benign condition characterized by abnormal development of new bone cells) are at increased risk of developing osteosarcoma.

What are the symptoms of bone cancer?

Pain is the most common symptom of bone cancer, but not all bone cancers cause pain. Persistent or unusual pain or swelling in or near a bone can be caused by cancer or by other conditions. Other symptoms of bone cancer include a lump (that may feel soft and warm) in the arms, legs, chest, or pelvis; unexplained fever; and a bone that breaks for no known reason. It is important to see a doctor to determine the cause of any bone symptoms.

How is bone cancer diagnosed?

To help diagnose bone cancer, the doctor asks about the patient’s personal and family medical history . The doctor also performs a physical examination and may order laboratory and other diagnostic tests . These tests may include the following:

• A bone scan , which is a test in which a small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it then collects in the bones and is detected by a scanner .
• A computed tomography ( CT or CAT) scan , which is a series of detailed pictures of areas inside the body, taken from different angles, that are created by a computer linked to an x-ray machine.
• A magnetic resonance imaging ( MRI ) procedure , which uses a powerful magnet linked to a computer to create detailed pictures of areas inside the body without using x-rays.
• A positron emission tomography (PET) scan , in which a small amount of radioactive glucose (sugar) is injected into a vein, and a scanner is used to make detailed, computerized pictures of areas inside the body where the glucose is used. Because cancer cells often use more glucose than normal cells, the pictures can be used to find cancer cells in the body.
• An angiogram , which is an x-ray of blood vessels.
• Biopsy (removal of a tissue sample from the bone tumor) to determine whether cancer is present. The surgeon may perform a needle biopsy , an excisional biopsy , or an incisional biopsy . During a needle biopsy, the surgeon makes a small hole in the bone and removes a sample of tissue from the tumor with a needle-like instrument. For excisional biopsy, the surgeon removes an entire lump or suspicious area for diagnosis. In an incisional biopsy, the surgeon cuts into the tumor and removes a sample of tissue. Biopsies are best done by an orthopedic oncologist (a doctor experienced in the treatment of bone cancer) because the placement of the biopsy incision can influence subsequent surgical options. A pathologist (a doctor who identifies disease by studying cells and tissues under a microscope) examines the tissue to determine whether it is cancerous.
• Blood tests to determine the levels of two enzymes called alkaline phosphatase and lactate dehydrogenase . Large amounts of these enzymes may be present in the blood of people with osteosarcoma or Ewing sarcoma . High blood levels of alkaline phosphatase occur when the cells that form bone tissue are very active—when children are growing, when a broken bone is mending, or when a disease or tumor causes production of abnormal bone tissue. Because high levels of alkaline phosphatase are normal in growing children and adolescents, this test is not a reliable indicator of bone cancer.

How is primary bone cancer treated?

Treatment options depend on the type, size, location, and stage of the cancer, as well as the person’s age and general health. Treatment options for bone cancer include surgery , chemotherapy , radiation therapy , cryosurgery , and targeted therapy .

• Surgery is the usual treatment for bone cancer. The surgeon removes the entire tumor with negative margins (that is, no cancer cells are found at the edge of the tissue removed during surgery). The surgeon may also use special surgical techniques to minimize the amount of healthy tissue removed along with the tumor. Dramatic improvements in surgical techniques and preoperative tumor treatment have made it possible for most patients with bone cancer in an arm or leg to avoid radical surgical procedures (that is, removal of the entire limb). However, most patients who undergo limb-sparing surgery need reconstructive surgery to regain limb function ( 3 ).
• Chemotherapy is the use of anticancer drugs to kill cancer cells. Patients who have Ewing sarcoma (newly diagnosed and recurrent ) or newly diagnosed osteosarcoma usually receive a combination of anticancer drugs before undergoing surgery. Chemotherapy is not typically used to treat chondrosarcoma or chordoma ( 3 ).
• Radiation therapy , also called radiotherapy, involves the use of high-energy x-rays to kill cancer cells. This treatment may be used in combination with surgery. It is often used to treat Ewing sarcoma ( 3 ). It may also be used with other treatments for osteosarcoma, chondrosarcoma, and chordoma, particularly when a small amount of cancer remains after surgery. It may also be used for patients who are not having surgery. A radioactive substance that collects in bone, called samarium, is an internal form of radiation therapy that can be used alone or with stem cell transplant to treat osteosarcoma that has come back after treatment in a different bone.
• Cryosurgery is the use of liquid nitrogen to freeze and kill cancer cells. This technique can sometimes be used instead of conventional surgery to destroy tumors in bone ( 10 ).
• Targeted therapy is the use of a drug that is designed to interact with a specific molecule involved in the growth and spread of cancer cells. The monoclonal antibody denosumab (Xgeva®) is a targeted therapy that is approved to treat adults and skeletally mature adolescents with giant cell tumor of bone that cannot be removed with surgery. It prevents the destruction of bone caused by a type of bone cell called an osteoclast.

More information about treatment for specific types of bone cancers can be found in the following PDQ ® cancer treatment summaries:

• Ewing Sarcoma Treatment
• Osteosarcoma and Malignant Fibrous Histiocytoma of Bone Treatment
• Unusual Cancers of Childhood Treatment (section on Chordoma)

What are the side effects of treatment for bone cancer?

People who have been treated for bone cancer have an increased likelihood of developing late effects of treatment as they age. These late effects depend on the type of treatment and the patient’s age at treatment and include physical problems involving the heart, lung, hearing, fertility , and bone; neurological problems; and second cancers ( acute myeloid leukemia , myelodysplastic syndrome , and radiation-induced sarcoma). Treatment of bone tumors with cryosurgery may lead to the destruction of nearby bone tissue and result in fractures, but these effects may not be seen for some time after the initial treatment.

Bone cancer sometimes metastasizes , particularly to the lungs, or can recur (come back), either at the same location or in other bones in the body. People who have had bone cancer should see their doctor regularly and should report any unusual symptoms right away. Follow-up varies for different types and stages of bone cancer. Generally, patients are checked frequently by their doctor and have regular blood tests and x-rays. Regular follow-up care ensures that changes in health are discussed and that problems are treated as soon as possible.

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• Review Article
• Open access
• Published: 16 March 2021

Review of a new bone tumor therapy strategy based on bifunctional biomaterials

• Jinfeng Liao 1 ,
• Ruxia Han 1 ,
• Yongzhi Wu 1 &
• Zhiyong Qian 1  

Bone Research volume  9 , Article number:  18 ( 2021 ) Cite this article

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• Bone cancer

Bone tumors, especially those in osteosarcoma, usually occur in adolescents. The standard clinical treatment includes chemotherapy, surgical therapy, and radiation therapy. Unfortunately, surgical resection often fails to completely remove the tumor, which is the main cause of postoperative recurrence and metastasis, resulting in a high mortality rate. Moreover, bone tumors often invade large areas of bone, which cannot repair itself, and causes a serious effect on the quality of life of patients. Thus, bone tumor therapy and bone regeneration are challenging in the clinic. Herein, this review presents the recent developments in bifunctional biomaterials to achieve a new strategy for bone tumor therapy. The selected bifunctional materials include 3D-printed scaffolds, nano/microparticle-containing scaffolds, hydrogels, and bone-targeting nanomaterials. Numerous related studies on bifunctional biomaterials combining tumor photothermal therapy with enhanced bone regeneration were reviewed. Finally, a perspective on the future development of biomaterials for tumor therapy and bone tissue engineering is discussed. This review will provide a useful reference for bone tumor-related disease and the field of complex diseases to combine tumor therapy and tissue engineering.

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Introduction.

Bone tumors involve the invasion of tumors into bone tissue and are classified as either primary tumors or metastatic tumors. Osteosarcoma is a well-known primary malignant bone tumor that often occurs in children and adolescents. It has been reported that this disease has become the second leading cause of tumor-related death in young teenagers. 1 The majority of patients die from lung metastases. Its annual incidence worldwide is ~1–3 cases per million. 2 The clinical signs of osteosarcoma are not obvious without spontaneous fracture or severe pain early on. Therefore, this disease is not easily diagnosed, but the tumors grow quickly. As a result, osteosarcoma causes a large bone defect and limitations in motion and can metastasize to the lungs. 3 The etiology of osteosarcoma is still not clear. 4 To date, the most common clinical treatment methods for bone tumors include chemotherapy, wide surgical resection, and radiotherapy. 5 However, osteosarcoma is not sensitive to radiotherapy and is prone to chemotherapy resistance. Surgical resection often fails to completely remove the tumor, which is the main cause of postoperative recurrence and metastasis. Moreover, osteosarcoma invades large areas of bone, which cannot repair itself, and has serious effects on the quality of life of patients. 6 The 5-year survival rate of patients with osteosarcoma is ~60%. 7 Unfortunately, advances in osteosarcoma treatment have reached a plateau over the past 40 years. 8

Metastatic bone tumors start somewhere else in the body and then spread to bone tissue at a later stage. Bone tissue is one of the most common metastatic sites, and certain cancers, such as breast, prostate, colon, and lung cancer, are closely related to bone metastasis. 9 , 10 , 11 , 12 , 13 Bone metastasis results from tumor cells migrating and adhering to the bone, thus interfering with the balance of bone formation and bone resorption. Osteosarcoma and bone metastasis share some similarities, 14 but metastatic bone tumors exist in the later stage of the tumor. The primary tumor is usually diagnosed before it metastasizes to the bone after treatment. In tumor-induced bone defects, metastatic bone tumors and osteosarcoma share similar tumor niches and microenvironments. Innovative and efficient therapeutic strategies are urgently needed to solve the problems in the treatment of bone tumors. 15

Along with the development of bionanotechnology, new innovative treatment options have been designed for bone tumor therapy. Bone tumor therapy combines the complex issues of tumor therapy and bone regeneration, which demand functional biomaterials for treatment. It is challenging to design novel strategies with the dual capabilities of both preventing tumor recurrence and supporting bone formation, demanding an interdisciplinary research background. 16 , 17 Many researchers worldwide have focused their efforts on solving these bone tumor treatment problems. Although they are only in the early stages of development, new treatment methods have brought great hope to finding a cure for bone tumors.

Traditional postoperative bone tumor treatment is chemotherapy. However, these chemical drugs can lead to systemic side effects such as liver dysfunction, heart toxicity, and bone marrow suppression. The development of new supplementary or alternative tumor treatment methods based on biomaterials can avoid these side effects by selective delivery. 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 Specifically, photothermal therapy is an emerging treatment method that converts near-infrared (NIR) light into localized thermal energy to destroy tumor tissue. 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 Photothermal therapy is based on nanomaterials with strong NIR absorption, such as gold nanoparticles, 36 , 37 , 38 , 39 , 40 , 41 carbon nanomaterials, 42 , 43 magnetic nanoparticles, 44 , 45 , 46 , 47 , 48 and copper nanomaterials. 49 , 50 Photothermal therapy is suitable for localized tumor therapy due to the concentrated irradiation region of the laser and its ability to limit the deep penetration of heat without damaging other organs or tissues. 51 , 52 , 53 , 54 , 55 With its rapid development, photothermal therapy is a potential supplement to preclinical and clinical tumor therapy. For example, photothermal therapy based on gold nanoshells has shown a great therapeutic effect in clinical trials for prostate tumor therapy. 56 , 57 Photothermal therapy is a suitable candidate method for bone tumor treatment, and related studies have focused on it.

Due to the offensive spreading of tumors into bone, bone metabolism becomes unbalanced. Healthy bone tissue is resorbed and invaded by the tumor, leading to bone defects. After tumor therapy, these bone defects become the next issue of concern. Bone tissue engineering is a fascinating field that gives hope to bone regeneration. The biomaterial scaffolds developed for bone tissue regeneration include nanofibers, 3D-printed scaffolds, hydrogels, microspheres, and nanoparticles. 58 , 59 , 60 , 61 , 62 , 63 , 64 Bioactivity, biocompatibility, and biodegradability are critical concerns in scaffold design, playing an important role in bone regeneration. 65 , 66 , 67 , 68 In particular, the key parameters of porosity, stiffness, and viscoelasticity can regulate cell adhesion, cell proliferation, and osteogenesis differentiation. 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 Scaffolds provide cells with sustainable regenerative factors, provide physical and biological support, and mobilize stem cells to regenerate the defect cavity. 77 , 78 , 79 , 80 , 81 , 82 Bifunctional scaffolds have been designed in recent years, thanks to the tireless work of researchers, for tumor photothermal therapy and bone repair. These scaffolds are capable of simultaneously providing tumor therapy and enhanced bone regeneration, a useful “two birds, one stone” strategy. Figure 1 shows a bone tumor that was killed by bifunctional biomaterials through either local or systemic administration. The locally administered bifunctional scaffolds (such as 3D-printed scaffolds, nano/microparticle-containing scaffolds, and hydrogels) were inserted into the bone defect area for tumor photothermal therapy and, subsequently, improved bone repair. The systemically administered nanoparticles penetrated blood vessels to target the bone tissues for tumor treatment and to inhibit bone reabsorption. Some representative examples of bifunctional biomaterials were summerized and listed in Table 1 .

Bifunctional biomaterials include ( a ) local treatment scaffolds (such as 3D-printed scaffolds, nano/microparticle-containing scaffolds, and hydrogels) and ( b ) systemic treatment nanoparticles (such as bone-targeting nanoparticles) for tumor photothermal therapy and bone regeneration

This review provides details of the recent developments in the use of bifunctional biomaterials to achieve bone tumor therapy. The new strategies in bifunctional biomaterial preparation and treatment methods are presented in the main text. Bone tumor therapy by bifunctional biomaterials is an important development direction for bone tissue engineering. 83 Moreover, bifunctional biomaterials will play a vital role in the therapy of complex diseases, which combine tumor therapy and tissue engineering (including bone tissue engineering, skin tissue engineering, adipose tissue engineering, etc.).

A new strategy for tumor therapy and bone regeneration

The rapid proliferation and invasion of osteosarcoma cancer cells is still the main reason why the survival rate of osteosarcoma patients has not improved in decades. Therefore, there has become an urgent need to explore new ways to treat osteosarcoma. Biomaterials for bone tumor therapy need to possess two functions: killing tumor cells and helping bone regeneration. For administration, we divided the bifunctional biomaterials into local treatment and systemic treatment options. The local bifunctional biomaterials for bone tumor therapy concentrate mainly on 3D-printed scaffolds, nano/microparticle-containing scaffolds and hydrogels. The representative systemic treatment biomaterial is bone-targeting nanoparticles for bone tumor therapy. Therefore, in this section, we present and discuss recent research on these strategies for tumor therapy and bone regeneration.

Local treatment

3d-printed scaffolds.

The new, innovative technology of 3D printing was first proposed by Prof. Ely Sachs. 84 Through its rapid development, 3D printing is now widely applied in the field of tissue engineering. 85 , 86 , 87 , 88 The bioactive ions in 3D-printed scaffolds, such as Ca 2+ , P 5+ , Si 4+ , Mg 2+ , Fe 3+ , and Mn 4+ , can improve osteogenic activity. 89 , 90 , 91 , 92 , 93 , 94 , 95 In only a few years, a series of 3D-printed bifunctional ceramic scaffolds for tumor therapy and bone repair have been developed. Some outstanding work in this field has been done by Chengtie Wu’s group. 96 , 97 For example, a 3D-printed scaffold modified with a Ca-P/polydopamine nanolayer was formulated by their group. 98 The polydopamine nanoparticles used on the surface can cause hyperthermia to kill MDA-MB-231 tumors in nude mice. Additionally, this scaffold can release Ca and P in a sustainable manner to induce femoral defect regeneration. Moreover, a high-strength 3D bioscaffold with Fe-CaSiO 3 was designed and prepared for tumor therapy and bone repair (Fig. 2 ). 99 The 3D-printed Fe-CaSiO 3 scaffold possessed the high compressive strength of 126 MPa, contributing to the high inherent mechanical properties of Fe. The high mechanical strength of this scaffold meets the load-bearing application requirements of human bone. Fe nanoparticles not only can provide photothermal therapy due to localized surface plasmon resonance but also can promote H 2 O 2 decomposition to generate reactive oxygen species (ROS). Thus, synergistic photothermal and ROS therapies can enhance Saos-2 bone tumor inhibition. Furthermore, large bone defects in the legs of rabbits were repaired by an Fe-CaSiO 3 scaffold. Recently, β-tricalcium phosphate 3D-printed scaffolds (TCP-PDLLA-LB) modified with LaB 6 micro-nanoparticles/poly(D,L-lactide) were fabricated for tumor photothermal therapy and bone repair. 100 Lanthanum and boron, as a “bone-seeking” element and a trace element, respectively, are bioactive, and their complex LaB 6 possesses NIR photothermal conversion properties. Therefore, the bone tumors were significantly suppressed by photothermal therapy. Regardless of NIR laser irradiation, TCP-PDLLA-LB 3D-printed scaffolds effectively assisted in new bone formation.

3D printing of Fe-CaSiO 3 composite scaffolds for tumor therapy and bone regeneration. a The fabrication of Fe-CaSiO 3 composite scaffolds for short-term tumor therapy and long-term bone regeneration. b Infrared (IR) radiation thermal images of tumor-bearing mice after irradiation with an 808 nm laser for 600 s. The photographs of the tumors from the six groups are from day 15. c Micro-CT images ( a – c ) and histological analysis ( d – f ) of the bone defects in the CaSiO 3 , Fe, and Fe-CaSiO 3 (30CS) groups postsurgery in a rabbit critical-sized femoral defect model. The statistical analysis of the defects ( g , h ) and histomorphometric measurements of in vivo osteogenesis ( i ) in the CaSiO 3 , Fe, and 30CS groups 8 weeks post surgery. Reprinted with permission from ref. 99 © 2018, Nature Publishing Group

In a recent example, a larnite/C 3D-printed scaffold showed an excellent photothermal effect, killing MNNG/HOS human osteosarcoma cells and inhibiting tumor growth in nude mice. 101 Additionally, the multifunctional 3D-printed scaffold enhanced bone formation in a rat calvarial defect model. In another related study, an “all-in-one” 3D-printed biomaterial coloaded with calcium peroxide (CaO 2 ) and iron oxide (Fe 3 O 4 ) nanoparticles was used to solve the abovementioned dilemma in osteosarcoma therapy. 102 The CaO 2 produced sufficient H 2 O 2 in the acidic tumor environment, and the Fe 3 O 4 nanoparticles generated toxic ROS via a Fenton-like catalytic reaction. Along with magnetic hyperthermia, these two agents can produce a synergistic effect in MNNG/HOS osteosarcoma tumor-bearing BALB/c in nude mice. Importantly, the CaO 2 nanoparticles released calcium ions to improve bone regeneration in SD rats cervical defects.

In the orthopedic field, there have been clinical trials in recent years in which 3D-printed personalized titanium plates were applied to bone defects. 103 Inspired by their utility and encouraging clinical outcomes, Mao et al. designed and fabricated titanium plates via computer-aided design and computer-aided manufacturing techniques customized and fixed to the patients’ bone defects after the tumor was removed. 104 Twelve patients with osteosarcoma had their bone tumor tissues surgically removed and were then treated with microwave-induced hyperthermia to kill the residual tumor cells. Subsequently, allograft bone and poly(methyl methacrylate) (PMMA) cement were applied to fill the bone defect. Finally, the 3D-printed personalized plate was fixed to strengthen the bone segment. Hyperthermia and 3D plate therapy improved the clinical outcomes in terms of the mean maximum flexion of the affected knees and the Musculoskeletal Tumor Society score.

Nano/microparticle-containing scaffolds

Nano/microparticle-containing scaffolds usually refer to inorganic-organic hybrid scaffolds. Particle-containing bifunctional hybrid scaffolds are the desired design for bone tumor therapy. 105 , 106 , 107 Microspheres composed of calcium phosphate-phosphorylated adenosine were prepared with high doxorubicin (DOX) loading for bone tumor therapy. 108 The pH-sensitive properties of microspheres presented a positive therapeutic effect on subcutaneous 143B osteosarcoma tumors in rats. Additionally, the hybrid microspheres can release active molecules to promote osteogenic differentiation in vitro. The study showed the potential application of calcium phosphate-phosphorylated adenosine microspheres for tumor inhibition and bone repair.

Additionally, a multifunctional magnetic mesoporous calcium silicate/chitosan (MCSC) porous scaffold that consisted of M-type ferrite particles (SrFe 12 O 19 ), mesoporous calcium silicate (CaSiO 3 ), and chitosan was prepared. 109 The SrFe 12 O 19 particles improved the photothermal efficacy with DOX-induced chemotherapy to reduce bone tumors. The MCSC hybrid scaffold upregulated indicators for osteogenesis. The data indicated that the MCSC hybrid scaffold promoted human bone marrow stromal cells to differentiate into osteogenic cells. In another study by the same author, 110 fabricated SrFe 12 O 19 nanoparticles containing bioglass/chitosan scaffolds also showed good bone repair of calvarial defects in rats.

Organic and inorganic materials are typically combined for complex disease in bone tumor treatment. Inorganic biomaterials, including nHA, TCP, bioglass, and bioceramics supply nutrients for tumor-defective bone repair. In a recent study, 111 the surface of beta-tricalcium phosphate bioceramic (β-TCP) materials was coated with carbon aerogel, which was developed for MNNG/HOS osteosarcoma tumor therapy. The carbon aerogel coating particularly enhanced the roughness and surface area of β-TCP, resulting in good bone regeneration in a calvarial defect model.

Breast cancer-induced bone metastasis is shown to cause cancer recurrence and local bone defects. A multifunctional magnetic chitosan matrix incorporating Fe 3 O 4 nanoparticles and GdPO 4 nanorods was utilized for breast tumor therapy and bone defect regeneration. 112 The Fe 3 O 4 nanoparticles in the scaffold supplied a high temperature through photothermal effects every other day for 14 days to avoid postoperative cancer recurrence in MDA-MB-231 tumor-bearing mice. Additionally, the GdPO 4 nanorods became orderly arranged in the scaffold and acted as a new bioactive component to induce M2 polarization of macrophages for enhanced stabilizing angiogenesis in the calvarial defect.

Another scaffold was developed from Fe 3 O 4 magnetic nanoparticles containing PMMA bone cement with mechanical support, magnetic photothermal ablation, and bone repair features (Fig. 3 ). 113 The liquid phase of these PMMA-Fe 3 O 4 scaffolds can be accurately injected into the bone defect area. Once PMMA-Fe 3 O 4 solidifies, an alternating magnetic field was used for the thermal ablation of the bone tumor. The fast phase transition of the PMMA-Fe 3 O 4 scaffold prevented the leakage of Fe 3 O 4 nanoparticles, which were nonbiodegradable during the long recovery period. Fortunately, good mechanical support is useful for physical function reconstruction. To simulate the clinical characteristics of the bone tumor, the therapeutic efficacy of the PMMA-Fe 3 O 4 scaffold was evaluated in the tibia a tumor-bearing rabbit. The excellent heating performance provided a good VX2 tibial plateau tumor ablation outcome. The PMMA-Fe 3 O 4 scaffold was shown to be a promising and minimally invasive agent with great clinical translation potential for the treatment of bone tumors.

PMMA-Fe 3 O 4 for magnetic ablation of bone tumors and bone repair. a PMMA powder, b Fe 3 O 4 nanoparticles, c MMA monomer, and d injectable PMMA-6% Fe 3 O 4 . e Low-magnification SEM image of polymerized PMMA. The scale bar is 50 μm. f High-magnification SEM image of polymerized PMMA. The scale bar is 20 μm. g Low-magnification SEM image of polymerized PMMA-6% Fe 3 O 4 . The scale bar is 50 μm. h High-magnification SEM image of polymerized PMMA-6% Fe 2 O 3 . The scale bar is 20 μm. i Thermal images of rabbit legs in the PMMA-6% Fe 3 O 4 –H group and Tumor-H group. j Enhanced MRI images and coronal reconstructed CT images at each follow-up time point (red arrow: bone destruction and swelling of soft tissue, blue arrow: cortical bone of upper tibial plateau, yellow arrow: area of bone resorption and new bone formation). Reprinted with permission from ref. 113 © 2019, Ivyspring International Publisher

Another very smart strategy is to simultaneously integrate photothermal therapy and bioactivity for bone regeneration into a single material. Bismuth (Bi)-doped bioglass provides photoinduced hyperthermia and enhanced remineralized bone tissue. 114 The high photothermal conversion of Bi was first reported in this study. The photothermal effects were controlled by managing the radiative and nonradiative processes. Under NIR light, Bi hybrid bioglass can efficiently kill bone tumors. Moreover, Bi promotes the proliferation, differentiation, and mineralization of osteogenic cells.

Titanium is widely used in the clinical application of dental implants and is also a good choice for bone tumor therapy applications. Zheng et al. 115 prepared a hydrogenated black TiO 2 (abbreviated as H-TiO 2 ) coating with a hierarchical porous topography on a titanium implant. The H-TiO 2 coating surface has photothermal abilities and can induce necrosis of Saos-2 bone tumor cells. Considering that the micro/nanostructures on the implant improved the osteogenic differentiation of BMSCs, it is promising to hypothesize that BMSCs can migrate to the implant surface for bone defect regeneration. Further in vivo demonstrations of the of defect repair results are needed.

Hydrogels are very large meshes that can contain water and have similar properties to the extracellular matrix. Hydrogels possess a highly porous structure, good biocompatibility, biodegradability, and a capability to load growth factors, leading to good bone defect repair. 116 , 117 , 118 , 119 Thus, hydrogels are good candidates for bone repair. Several studies have shown potential for the use of hydrogels in bone tissue regeneration. For bone tumor therapy, the hydrogel needs to also be capable of treating tumors. It is highly advised to administer drugs or ingredients into the resected tumor area. 120 , 121 Hydrogels can provide sustainable drug release for tumor illumination. 122 , 123 , 124 , 125 Some hydrogels integrate interior antitumor activity with localized delivery in one system. 126 Localized cancer treatment by hydrogels can replace the need for systemic chemotherapy administered intravenously or orally. 127 , 128 , 129 , 130 With the development of multifunctional hydrogels, their applications are not limited to tissue repair but also extend to tumor cure and bone repair.

The ideal hydrogel system requires favorable parameters with good biocompatibility, a porous structure, adhesion to the cavity, good mechanical properties, and injectability. 131 Among them, an injectable hydrogel can fill or match irregular defects with a mild gelation process in a minimally invasive manner. 132 , 133 , 134 , 135 Recently, an injectable hydrogel was formed via a Schiff base reaction between the amino group of chitosan and the aldehyde groups of oxidized sodium alginate. 136 As shown in Fig. 4 , a hydrogel was mixed with nanohydroxyapatite (n-HA) to induce bone repair in the joint bone of a rabbit. Moreover, n-HA was decorated with polydopamine and cisplatin, which can supply photothermal therapy and chemotherapy to treat 4T1 breast tumor-bearing mice.

The formation of a bifunctional OSA-CS-PHA-DDP hydrogel and its bioapplication in tumor therapy and bone regeneration. Reprinted with permission from ref. 136 © 2019, Wiley-VCH

In another study, an in situ UV-crosslinked gelatin methacryloyl hydrogel-encapsulated liposome was formed for the local release of gemcitabine. 137 Drug release lasts for 4 days in vitro, resulting in excellent inhibition of osteosarcoma in BALB/c mice bearing MG63 tumors. Thermosensitive hydrogels are also popular for localized drug release. For example, thermosensitive poly(L-lactide-co-glycolide)-poly(ethylene glycol)-poly(L-lactide-co-glycolide) (abbreviated as PLGA-PEG-PLGA) hydrogels were used to load DOX, methotrexate and cisplatin for localized drug delivery. 138 Synergistic cytotoxic effects were found in the multiple drug-loaded hydrogels against osteosarcoma in vitro and in vivo. Furthermore, localized treatment caused no obvious harm to normal tissues.

A nanohydroxyapatite hybrid reduced graphene oxide (nHA-rGO) hydrogel was developed for tumor-related bone defects. 105 The nHA-rGO hydrogel killed almost all MG-63 osteosarcoma cells via photothermal therapy. Additionally, this hydrogel promoted bone regeneration by stimulating osteoblast mineralization and collagen deposition in a rat cranial defect model.

Systemic treatment

In recent years, there has been strong growth in nanotechnology in the fields of biology, medicine, and pharmaceuticals. Nanosized drug-based delivery platforms have been extensively studied and used for the treatment of osteosarcoma. Various nanoparticles have emerged as effective drug delivery systems in osteosarcoma treatment. Osteosarcoma tumor-invaded bone destruction contributes to an imbalance between bone reabsorption by osteoclasts and bone reconstruction by osteoblasts. Bone reabsorption promotes bone destruction and tumor metastasis processes. 139 , 140 Moreover, a vicious cycle exists in osteolytic metastasis with bidirectional interactions between osteoclasts and tumor cells. 9 Due to the low blood flow in the bone (0.05–0.20 mL·min −1 per gram) 141 and blood–bone marrow barrier, targeted delivery of anticancer agents is highly recommended for bone tumor therapy. Moreover, a targeted delivery strategy shows great potential to solve systemic toxic effects and multidrug resistance, which are longstanding problems with the standard cancer chemotherapy treatment. 142 , 143

Bone-modifying agents with a high affinity for bone are used for active bone targeting, including alendronate, 144 , 145 , 146 zoledronic acid, 147 , 148 , 149 aspartic acid, 150 denosumab, 151 and aptamers. 152 , 153 Nanomaterials and their drug delivery systems have unique advantages for the treatment of bone tumors. 154 , 155 , 156 , 157 , 158 Because bone is composed of organic matrices and inorganic minerals that are assembled at the nanoscale, and nanomaterials can assimilate into the bone microenvironment to heal diseased bone. 159 , 160 Furthermore, targeted delivery systems based on nanotechnology can improve the treatment efficiency of bone tumors. 161 , 162

Bisphosphonate molecules can specifically bind to the bone hydroxyapatite matrix via the chelation of calcium ions, which negatively influence osteoclast activity. 163 , 164 In the 1960s, bisphosphonate was the first molecule to be identified as being able to target bone. Multifunctional melanin-like nanoparticles based on alendronate-anchored polydopamine nanoparticle hybrid Fe were reported for the bone-targeted photothermal and chemotherapy of malignant bone tumors. 165 Alendronate possesses a high affinity for nanohydroxyapatite, resulting in targeted accumulation in the osteolytic bone site. The 7-ethyl-10-hydroxycamptothecin contained within the nanoparticles assisted with the cotherapy for efficient regression of the bone tumor. Additionally, carbon dots (CDs) synthesized from alendronate have strong binding activity for calcium-deficient hydroxyapatite. 166 Alendronate-based CDs (Alen-CDs) showed enhanced bone targeting in the bone structures of zebrafish and rat femurs compared to nitrogen-doped CDs using ethylenediamine (Alen-EDA-CDs). These results were attributed to the bisphosphonate group on the surface of the CDs even after carbonization. Recently, gold nanorods encapsulated in mesoporous silica nanoparticles conjugated with zoledronic acid (Au@MSNs-ZOL) were prepared for bone-targeted assisted inhibition of the proliferation of osteoclast-like cells and the promotion of osteogenic differentiation (Fig. 5 ). 167 The targeted photothermal therapy was enhanced to cure breast tumor bone metastasis in the hindlimbs of nude mice. This Au@MSNs-ZOL nanosystem was capable of curing the tumor, relieving pain, and inhibiting bone reabsorption for breast cancer bone metastasis treatment.

Bone-targeted nanoplatform combining zoledronate and photothermal therapy to treat breast cancer bone metastasis. Top: Timeline of the treatment schedule. A breast cancer bone metastasis mouse model was established by direct injection of MDA-MB-231 cells into the left hindlimbs of nude mice. Nanoparticles and NIR irradiation were administered as indicated. a Images of tumor-bearing nude mice recorded at the end of treatment (day 35). b TUNEL fluorescence detected in the tumor slices. c CT images of the tibias from different angles and micrographs of H&E-stained tibias (right). Reprinted with permission from ref. 167 © 2019, ACS Publications

Although bisphosphonates are widely used as clinical drugs in metastatic bone tumor treatment, they may cause adverse effects such as atypical femoral fractures and esophageal cancer after long-term use. 168 In a recent study by Cheng Yiyun’s group, 169 phytic acid (PA)-capped platinum (Pt) nanoparticles were developed for bone-targeting therapy. PA is a natural compound that contains six phosphate groups, indicating its high bone-targeting capability. In addition, PA shows an inherent anticancer ability, which can be combined with the Pt nanoparticle photothermal therapy. An in situ bone tumor model was established by engrafting PC-9-Luc cells in the tibias of nude mice, which can be detected by imaging the luminescence of the tumor regions. After PA/Pt nanosystem treatment, PA led to an enhancement of the PA/Pt nanoparticles at the tumor site. Additionally, PA/Pt nanoparticle-associated cotherapy inhibited tumor invasion.

Discussion and perspective

From the review on the recent development of bifunctional biomaterials in bone tumor therapy, a promising new strategy was introduced. According to the method of administration, bifunctional biomaterials can be divided into those delivered by local or systemic administration. Locally administered biomaterials mainly include 3D-printed scaffolds, nano/microparticle-containing scaffolds, and hydrogels. The representative systemically administered biomaterial is bone-targeting nanoparticles. A similarity and difference exist between these two types of biomaterials. The similarity is that a localized photothermal effect is used to kill tumor cells to prevent recurrence early on. The difference lies in the mechanism of bone repair. Locally administered scaffolds can be designed to match the bone defect area, and active molecules can be carried into the scaffold to stimulate bone regeneration. Systemically administered nanoparticles target bone tissues to inhibit bone reabsorption. The former is an example of positive regulation of bone regeneration, and the latter represents negative regulation of bone reabsorption. Although their mechanisms of bone repair are different, their outcomes in bone tumor therapy are similar.

For further development, there are three possible directions for bifunctional biomaterials for tumor therapy, and bone repair may arise. First, NIR-II window-responsive biomaterials for photothermal therapy have been developed for deep tumor treatment, as mild photothermal effects can effectively protect bone tissue. For example, a recent study reported the use of bifunctional CDs combined with WS 2 to cure osteosarcoma under laser irradiation at 1 064 nm. 170 Even when covered with a chicken breast with a thickness of 10 mm, the deep bone tumor was able to be killed. Moreover, mild photothermal effects (~43 °C) reported in recent studies can not only greatly enhance the proliferation of MSCs but also promote osteogenesis. 171 , 172 , 173 , 174 , 175 This is good news for bone tumor therapy. The mild photothermal effect was shown to stimulate and accelerate in vitro and in vivo osteogenesis. 170 , 176 Second, future treatment strategies for bone tumor therapy may not be limited to photothermal therapy and chemotherapy combined with biomaterials, and other therapeutic strategies, such as radiochemotherapy and gas therapy, may also be potential methods to treat malignant bone tumors. 171 , 172 Third, scaffolds developed in the future may need to be multifunctional, considering infection along with tumor therapy and bone regeneration. 177 , 178 During tumor surgery, bleeding and soft tissue defects need to be considered. As shown in Fig. 6 , a nanohydroxyapatite/graphene oxide/chitosan (nHA/GO/CS) scaffold was designed to inhibit osteosarcoma growth with mild photothermal therapy and mildly high temperature (~42 °C) to promote the osteogenesis of hBMSCs. 179 Furthermore, this scaffold showed a good hemostatic effect that can improve soft tissue regeneration.

Schematic illustration of the nanohydroxyapatite/graphene oxide/chitosan (nHA/GO/CS) scaffold for osteosarcoma treatment under photothermal therapy and the promotion of tissue regeneration. Reprinted with permission from ref. 179 © 2020, RSC Publishing

New strategies based on bifunctional biomaterials for bone tumor therapy have the potential to extend to the treatment of other types of tumors (such as melanoma, oral tumors, and breast tumors), as well as damaged neighboring normal tissues. Melanoma treatment requires the complicated removal of tumor tissue and cutaneous defect repair. 173 , 174 , 175 Oral tumors simultaneously destroy the facial bone. In clinical treatment, doctors remove oral tumor tissues along with the surrounding jawbone then collect the patient’s fibula and use it to replace the jawbone with vascular anastomosis. Breast tumor treatment involves curing the residual tumor after surgical resection and breast defect regeneration. 180 Thus, the treatment of breast tumors relates to tumor therapy and adipose tissue engineering. In the latest study by Huang’s group, a bifunctional 3D-printed dopamine-modified alginate scaffold was used to kill breast tumors and fill the defective breast area. 23 Researchers found a favorable photothermal effect from this scaffold to illuminate breast tumors. Additionally, the modulus of the scaffold was similar to that of normal breast tissue, and the scaffold enhanced the proliferation of breast epithelial cells. This method design can be used as a potential strategy for the prevention of breast tumor recurrence after surgery and adipose tissue repair. Future research should be focused on tumor therapy and tissue engineering for other complex diseases.

Although the use of bifunctional biomaterials for bone tumor therapy is developing rapidly, there is still a long way to go. The bifunctional biomaterial strategy further shows great potential for the treatment of complex diseases combined with tumor and tissue defects. Great confidence in researchers and clinicians will push this new strategy forward to solve clinical problems.

This review highlights the recent development of bifunctional biomaterials for bone tumor therapy. A new strategy based on bifunctional biomaterials can inhibit tumor growth in the early treatment period and enhance bone repair in the late treatment period. Photothermal therapy for tumor treatment has a short duration, but bone regeneration takes a long time. With the benefits of locally administered (3D-printed scaffolds, nano/microparticle-containing scaffolds, and hydrogels) and systemically administered (bone-targeting nanoparticles) bifunctional biomaterials, the survival rate of bone tumor patients has great potential to increase. Bifunctional biomaterial treatment may provide new hope for future clinical bone tumor therapy while improving patient quality of life and decreasing mortality.

Siclari, V. A. & Qin, L. Targeting the osteosarcoma cancer stem cell. J. Orthop. Surg. Res. 5 , 78 (2010).

Article   PubMed   PubMed Central   Google Scholar  

Kansara, M., Teng, M. W., Smyth, M. J. & Thomas, D. M. Translational biology of osteosarcoma. Nat. Rev. Cancer 14 , 722–735 (2014).

Article   CAS   PubMed   Google Scholar  

Chen, D. et al. Super enhancer inbibitors suppress MYC driven transcriptional amplification and tumor progression in osteosarcoma. Bone Res. 6 , 11 (2018).

Article   PubMed   PubMed Central   CAS   Google Scholar  

Gianferante, D. M., Mirabello, L. & Savage, S. A. Germline and somatic genetics of osteosarcoma-connecting aetiology, biology and therapy. Nat. Rev. Endocrinol. 13 , 480–491 (2017).

Bosma, S. E., Wong, K. C., Paul, L., Gerbers, J. G. & Jutte, P. C. A cadaveric comparative study on the surgical accuracy of freehand, computer navigation, and patient-specific instruments in joint-preserving bone tumor resection. Sarcoma 11 , 4065846 (2018).

Google Scholar  

Friesenbichler, J. et al. Clinical experience with the artificial bone graft substitute Calcibon used following curettage of benign and low-grade malignant bone tumors. Sci. Rep. 7 , 1736 (2017).

Anderson, M. E. Update on survival in osteosarcoma. Orthop. Clin. N. Am. 47 , 283–292 (2016).

Article   Google Scholar  

Ballatori, S. E. & Hinds, P. W. Osteosarcoma: prognosis plateau warrants retinoblastma pathway targeted therapy. Signal Transduct. Target. Ther. 1 , 16001 (2016).

Mundy, G. R. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat. Rev. Cancer 2 , 584–593 (2002).

Weilbaecher, K. N., Guise, T. A. & McCauley, L. K. Cancer to bone: a fatal attraction. Nat. Rev. Cancer 11 , 411–425 (2011).

Article   CAS   PubMed   PubMed Central   Google Scholar  

Thibaudeau, L. et al. A tissue-engineered human xenograft model of human breast cancer metastasis to bone. Dis. Models Mech. 7 , 299–309 (2014).

Article   CAS   Google Scholar  

Kuchimaru, T. et al. A reliable murine model for bone matastasis by injecting cancer cells through caudal arteries. Nat. Commun. 9 , 2981 (2018).

Adjei, I. M., Sharma, B., Peetla, C. & Labhasetwar, V. Inhibition of bone loss with surface-modulated, drug-loaded nanoparticles in an intraosseous model of prostate cancer. J. Control. Release 232 , 83–92 (2016).

Cortini, M., Baldini, N. & Avnet, S. New advances in the study of bone tumors: a lesson from the 3D environment. Front. Physiol. 10 , 814 (2019).

Ando, K. et al. Current therapeutic strategies and novel approaches in osteosarcoma. Cancers 5 , 591–616 (2013).

Liu, Y., Yu, Q., Chang, J. & Wu, C. Nanobiomaterials: from 0D to 3D for tumor therapy and tissue engineering. Nanoscale 11 , 13678–13708 (2019).

Xue, Y. et al. Engineering a biodegradable multifunctional antibacterial bioactive nanosystem for enhancing tumor photothermo-chemotherapy and bone regeneration. ACS Nano 14 , 442–453 (2020).

Fan, D., Tian, Y. & Liu, Z. Injectable hydrogels for localized caner therapy. Front. Chem. 7 , 675 (2019).

Zhao, M. et al. Codelivery of paclitaxel and temozolomide through a photopolymerizable hydrogel prevents glioblastoma recurrence after surgical resection. J. Control. Release 309 , 72–81 (2019).

Liao, J. et al. Physical-, chemical-, and biological-responsive nanomedicine for cancer therapy. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol . 12 , e1581 (2020).

Shao, J. et al. Black-phosphorus-incorporated hydrogel as a sprayable and biodegradable photothermal platform for postsurgical treatment of cancer. Adv. Sci. 5 , 1700848 (2018).

Du, C. et al. Efficient suppression of liver metastasis cancers by paclitaxel loaded nanoparticles in PDLLA-PEG-PDLLA thermosensitive hydrogel composites. J. Biomed. Nanotechnol. 13 , 1545–1556 (2017).

luo, Y. et al. 3D printing of hydrogel scaffolds for future application in photothermal therapy of breast cancer and tissue repair. Acta Biomater. 92 , 37–47 (2019).

Darge, H. F. et al. Locailized controlled release of bevacizumab and doxorubicin by thermo-sensitive hydrogel for normalization of tumor vasculature and to enhance the efficacy of chemotherapy. Int. J. Pharm. 572 , 118799 (2019).

Qu, Y. et al. A biodegradable thermo-responsive hybrid hydrogel: therapeutic applications in preventing the post-operative recurrence of breast cancer. NPG Asia Mater. 7 , e207 (2015).

Wang, H. et al. Biocompatible iodine-starch-alginate hydrogel for tumor photothermal therapy. ACS Biomater. Sci. Eng. 5 , 3654–3662 (2019).

Chu, K. F. & Dupuy, D. E. Thermal ablation of tumours: biological mechanisms and advances in therapy. Nat. Rev. Cancer 14 , 199–208 (2014).

Liu, Y., Bhattarai, P., Dai, Z. & Chen, X. Photothermal therapy and photoacoustic imaging via nanotheranostics in fighting cancer. Chem. Soc. Rev. 48 , 2053–2108 (2019).

Wang, Z. et al. Construction of Bi/phthalocyanine manganese nanocomposite for trimodal imaging directed photodynamic and photothermal therapy mediated by 808 nm light. Biomaterials 28 , 119569 (2010).

Chen, Q. et al. Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy. Nat. Commun. 7 , 13193 (2016).

Zhang, W. et al. A hydrogenated black TiO 2 coating with excellent effects for photothermal of bone tumor and bone regeneration. Mater. Sci. Eng. C. 102 , 458–470 (2019).

Liu, Y. et al. Preparation of therapeutic-laden konjac hydrogel for tumor combination therapy. Chem. Eng. J. 375 , 122048 (2019).

Liao, J. et al. Polymer hybrid magnetic nanocapsules encapsulating IR820 and PTX for external magnetic field-guided tumor targeting and multifunctional theranostics. Nanoscale 9 , 2479–2491 (2017).

Zhang, B., Xu, C., Sun, C. & Yu, C. Polyphosphoester-based nanocarrier for combined radio-photothermal therapy of breast cancer. ACS Biomater. Sci. Eng. 5 , 1868–1877 (2019).

Hu, L. et al. Oxygen-generating hybrid polymeric nanoparticles with encapsulated doxorubicin and chlorin e6 for trimodal imaging-guided combined chemo-photodynamic therapy. Theranostics 8 , 1558–1574 (2018).

Mahmoodzadeh, F., Abbasian, M., Jaymand, M., Salehi, R. & Bagherzadh-Khajehmarjan, E. A novel gold-based stimuli-responsive theranostic nanomedicine for chemophotothermal therapy of solid tumors. Mater. Sci. Eng. C. 93 , 880–889 (2018).

Liao, J. et al. Magnetic/gold core-shell hybrid particles for targeting and imaging-guided photothermal cancer therapy. J. Biomed. Nanotechnol. 15 , 2072–2089 (2019).

Volsi, A. V. et al. Near-infrared light responsive folate targeted gold nanorods for combined photothermal-chemotherapy of osteosarcoma. ACS Appl. Mater. Interfaces 9 , 14453–14469 (2017).

Yang, S., Zhou, L., Su, Y., Zhang, R. & Dong, C.-M. One-pot photoreduction to prepare NIR-absorbing plasmonic gold nanoparticles tethered by amphiphilic polypeptide copolymer for synergistic photothermal-chemotherapy. Chin. Chem. Lett. 30 , 187–191 (2019).

Liao, J. et al. Combined cancer photothermal-chemotherapy based on doxorubicin/gold nanorod-loaded polymersomes. Theranostics 5 , 345–356 (2015).

Yang, X. et al. Gold-small interfering RNA as optically responsive nanostructures for cancer theranostics. J. Biomed. Nanotechnol. 14 , 809–828 (2018).

Li, Q. et al. Graphene-nanoparticle-based self-healing hydrogel in preventing postoperative recurrence of breast cancer. ACS Biomater. Sci. Eng. 5 , 768–779 (2019).

Shi, J., Kantoff, P. W., Wooster, R. & Farokhzad, O. C. Cancer nanomedicine: progress, challenges and opportunities. Nat. Rev. Cancer 17 , 20–37 (2017).

Guo, X. et al. External magnetic field-enhanced chemo-photothermal combination tumor therapy via iron oxide nanoparticles. ACS Appl. Mater. Interfaces 9 , 16581–16593 (2017).

Zhang, J. et al. Multifunctional ferritin nanoparticles as theranostics for imaging-guided tumor phototherapy. J. Biomed. Nanotechnol. 15 , 1546–1555 (2019).

Farzin, A., Hassan, S., Emadi, R., Etesami, S. A. & Ai, J. Comparative evaluation of magnetic hyperthermia performance and biocompatibility of magnetite and novel Fe-doped hardystonite nanoparticles for potential bone cancer therapy. Mater. Sci. Eng. C. 98 , 930–938 (2019).

Du, Y., Liu, X., Liang, Q., Liang, X.-J. & Tian, J. Optimization and design of magnetic ferrite nanoparticles with uniform tumor distribution for highly sensitive MRI/MPI performance and improved magnetic hyperthermia therapy. Nano Lett. 19 , 3618–3626 (2019).

Wang, K., Yang, P., Guo, R., Yao, X. & Yang, W. Photothermal performance of MFe 2 O 4 nanoparticles. Chin. Chem. Lett. 30 , 2013–2016 (2019).

Liu, Y. et al. The combined therapeutic effects of 131iodine-labeled multifunctional copper sulfide-loaded microspheres in treating breast cancer. Atca Pharm. Sin. B 8 , 371–380 (2018).

Hu, X. et al. Multifunctional CuS nanocrystals for inhibiting both osteosarcoma proliferation and bacterial infection by photothermal therapy. J. Nanopart. Res. 19 , 295 (2017).

Liu, R. X. K. et al. An injectable self-assembling collagen-gold hybrid hydrogel for combinatorial antitumor photothermal/photodynamic therapy. Adv. Mater. 28 , 3669–3676 (2016).

Article   PubMed   CAS   Google Scholar  

Hou, M. et al. Responsive agarose hydrogel incorporated with natural humic acid and MnO 2 nanopaticles for effective relief of tumor hypoxia and enhanced photo-induced tumor therapy. Biomater. Sci. 8 , 353–369 (2020).

Jiang, Y.-W. et al. Palladium nanosheet-knotted injectable hydrogels formed via palladium-sulfur bonding for synergistic chemo-photothermal therapy. Nanoscale 12 , 210–219 (2020).

Shan, W. et al. Improved stable Indocyanine Green (ICG)-mediated cancer optotheranostics with naturalized hepatitis B core particles. Adv. Mater. 30 , 1707567 (2018).

Pan, H., Zhang, C., Wang, T., Chen, J. & Sun, S.-K. In situ fabrication of intelligent photothermal indocyanine green-alginate hydrogel for localized tumor ablation. ACS Appl. Mater. Interfaces 11 , 2782–2789 (2019).

Cole, J. R., Mirin, N. A., Knight, M. W., Goodrich, G. P. & Halas, N. J. Photothermal efficiencies of nanoshells and nanorods for clinical therapeutic applications. J. Phys. Chem. C. 113 , 12090–12094 (2009).

Rastinehad, A. R. et al. Gold nanoshell-localized photothermal ablation of prostate tumors in a clinical pilot device study. PNAS 116 , 18590–18596 (2019).

Ni, P. Y. et al. Injectable thermosensitive PEG-PCL-PEG hydrogel/acellular bone matrix composite for bone regeneration in cranial defects. Biomaterials 35 , 236–248 (2014).

Shi, R. et al. Nano twin-fiber membrane with osteogenic and antibacterial dual functions as artificial periosteum for long bone repairing. J. Biomed. Nanotechnol. 15 , 272–287 (2019).

Li, C. et al. Glycosylated superparamagnetic nanoparticle gradients for osteochondral tissue engineering. Biomaterials 176 , 24–33 (2018).

Zhang, H. et al. Magnetic nanoparticle-loaded electrospun polymeric nanofibers for tissue engineering. Mater. Sci. Eng. C. 73 , 537–543 (2017).

Heo, D. N. et al. Inhibition of osteoclast differentiation by gold nanoparticles functionalized with cyclodextrin curcumin complex. ACS Nano 8 , 12049–12062 (2014).

Chen, L. et al. Drug-loaded calcium alginate hydrogel system for use in oral bone tissue repair. Int. J. Mol. Sci. 18 , 989 (2017).

Article   PubMed Central   CAS   Google Scholar  

Li, A., Xie, J. & Li, J. Recent advances in functional nanostructured materials for bone-related diseases. J. Mater. Chem. B 7 , 509–527 (2019).

Lin, Y., Xiao, Y. & Liu, C. The horizon of materiobiology: a perspective on material-guided cell-behavior and tissue engineering. Chem. Rev. 117 , 4376–4421 (2017).

Yang, D. et al. The immune reaction and degradation fate of scaffold in cartilage/bone tissue engineering. Mater. Sci. Eng. C. 104 , 109927 (2019).

Kossover, O. et al. Growth factor delivery for the repair of critical size tibia defect using an acellular, biodegradable polyethylene glycol-albumin, hydrogel implant. ACS Biomater. Sci. Eng. 6 , 100–111 (2020).

Ji, X. et al. Mesenchymal stem cell-loaded thermosensitive hydroxypropyl chitin hydrogel combined with a three-dimensional-printed poly(Ɛ-caprolactone)/nano-hydroxyapatite scaffold to repair bone defects via osteogenesis, angiogenesis and immunomodulation. Theranostics 10 , 725–740 (2020).

Lee, T. T. et al. Light-triggered in vivo activation of adhesive peptides regulates cell adhesion, inflammation and vascularization of biomaterials. Nat. Mater. 14 , 352–360 (2015).

Hou, S. et al. Simultaneous nano- and microscale structural control of injectable hydrogel via assembly of nanofibrous protein microparticles for tissue regeneration. Biomaterials 223 , 119458 (2019).

Huang, D. et al. Viscoelasticity in natural tissues and engineered scaffolds for tissue reconstruction. Acta Biomater. 97 , 74–92 (2019).

Zhang, K. et al. Advanced smart biomaterials and constructs for hard tissue engineering and regeneration. Bone Res. 6 , 31 (2018).

Wu, J. et al. Functionalization of silk fibroin electrospun scaffolds via BMSC affinity peptide grafting through oxidative self-polymerization of dopamine for bone regeneration. ACS Appl. Mater. Interfaces 11 , 8878–8895 (2019).

Wang, Q., Huang, Y. & Qian, Z. Nanostructured surface modification to bone implants for bone regeneration. J. Biomed. Nanotechnol. 14 , 628–648 (2018).

Hu, Q., Liu, M., Chen, G., Xu, Z. & Lv, Y. Demineralized bone scaffolds with tunable matrix stiffness for efficient bone integration. ACS Appl. Mater. Interfaces 10 , 27669–27680 (2018).

Xie, J. et al. Substrate elasticity regulates adipose-derived stromal cell differentiation towards osteogenesis and adipogenesis through β-catenin transduction. Acta Biomater. 79 , 83–95 (2018).

Sadtler, K. et al. Design, clinical translation and javascript:__doPostBack('UCCKEditor$Pane7_content$ctl18','')immunological response of biomaterials in regenerative medicine. Nat. Rev. 1 , 16040 (2016).

CAS   Google Scholar  

Gu, Z. et al. Double network hydrogel for tissue engineering. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 10 , e1520 (2018).

Article   PubMed   Google Scholar  

Brokesh, A. M. & Gaharwar, A. K. Inorganic biomaterials for regenerative medicine. ACS Appl. Mater. Interfaces 12 , 5319–5344 (2020).

Yao, Q. et al. 3D interpenetrated graphene foam/58 S bioactive glass scaffolds for electrical-stimulation-assisted differentiation of rabbit mesenchymal stem cells to enhance bone regeneration. J. Biomed. Nanotechnol. 15 , 602–611 (2019).

Farokhi, M. et al. Importance of dual delivery systems for bone tissue engineering. J. Control. Release 225 , 152–169 (2016).

Wang, W. et al. Local delivery of BMP-2 from poly(lactic-co-glycolic acid) microspheres incorporated into porous nanofibrous scaffold for bone tissue regeneration. J. Biomed. Nanotechnol. 13 , 1446–1456 (2017).

Ma, H., Feng, C., Chang, J. & Wu, C. 3D-printed bioceramic scaffolds: from bone tissue engineering to tumor therapy. Acta Biomater. 79 , 37–59 (2018).

Liu, W. et al. Application and performance of 3D printing in nanobiomaterials. J. Nanomater. 2 , 1–7 (2013).

Matai, I., Kaur, G., Seyedsalehi, A., McClinton, A. & Laurencin, C. T. Progress in 3D bioprinting technology for tissue/organ regenerative engineering. Biomaterials 226 , 119536 (2020).

Choe, G., Oh, S., Seok, J. M., Park, S. A. & Lee, J. Y. Graphene oxide/alginate composites as novel bioinks for three-dimensional mesenchymal stem cell printing and bone regeneration applications. Nanoscale 11 , 23275–23285 (2019).

Yang, C., Huan, Z., Wang, X., Wu, C. & Chang, J. 3D printed Fe scaffold with HA nanocoating for bone regeneration. ACS Biomater. Sci. Eng. 4 , 608–616 (2018).

Yang, W. F. et al. Surface-modified hydroxyapatite nanoparticle-reinforced polylactides for three-dimensional printed bone tissue engineering scaffolds. J. Biomed. Nanotechnol. 14 , 294–303 (2018).

Liu, Y. et al. 3D-printed scaffolds with bioactive elements-induced photothermal effect for bone tumor therapy. Acta Biomater. 73 , 531–546 (2018).

Wang, X. et al. A 3D-printed scaffold with MoS 2 nanosheets for tumor therapy and tissue regeneration. NPG Asia Mater. 9 , e376 (2017).

Wang, Y. et al. Selenite-releasing bone mineral nanoparticles retard bone tumor growth and improve healthy tissue functions in vivo. Adv. Health Mater. 4 , 1813–1818 (2015).

Pan, S. et al. 2D MXene-integrated 3D-printing scaffolds for augmented osteosarcoma phototherapy and accelerated tissue reconstruction. Adv. Sci. 7 , 1901511 (2020).

Zheng, Y., Yang, Y. & Deng, Y. Dual therapeutic cobalt-incorporated bioceramics accelerate bone tissue regeneration. Mater. Sci. Eng. C. 90 , 770–782 (2019).

Zhuang, H. et al. Three-dimensional-printed bioceramic scaffolds with osteogenic activity for simulataneous photo/magnetothermal therapy of bone tumors. ACS Biomater. Sci. Eng. 5 , 6725–6734 (2019).

Liu, G. et al. Modulating the cobalt dose range to manipulate multisystem cooperation in bone environment: a strategy to resolve the controversies about cobalt use for orthopedic application. Theranostics 10 , 1074–1089 (2020).

Ma, H. et al. A bifunctional biomaterial with photothermal effect for tumor therapy and bone regeneration. Adv. Funct. Mater. 26 , 1197–1208 (2016).

Dang, W. et al. A bifunctional scaffold with CuFeSe 2 nanocrystals for tumor therapy and bone reconstrcution. Biomaterials 160 , 92–106 (2018).

Ma, H. et al. 3D printing of biomaterials with mussel-inspired nanostructures for tumor therapy and tissue regeneration. Biomaterials 111 , 138–148 (2016).

Ma, H. et al. 3D printing of high-strength bioscaffolds for the synergistic treatment of bone cancer. NPG Asia Mater. 10 , 31–44 (2018).

Dang, W. et al. LaB 6 surface chemistry-reinforced scaffolds for treating bone tumors and bone defects. Appl. Mater. Today 16 , 42–55 (2019).

Fu, S., Hu, H., Chen, J., Zhu, Y. & Zhao, S. Silicone resin derived larnite/C scaffolds via 3D printing for potential tumor therapy and bone regeneration. Chem. Eng. J. 382 , 122928 (2019).

Dong, S., Chen, Y., Yu, L., Lin, K. & Wang, X. Magnetic hyperthermia-synergistic H 2 O 2 self-sufficient catalytic suppression of osteosarcoma with enhanced bone-regeneration bioactivity by 3D-printing composite scaffolds. Adv. Funct. Mater. 30 , 1907071 (2019).

Xu, M. et al. Custom-made locked plating for acetabular fracture: a pilot study in 24 consecutive cases. Orthopedics 37 , 660–670 (2014).

Ma, L. et al. 3D printed personalized titanium plates improve clinical outcome in microwave ablation of bone tumors around the knee. Sci. Rep. 7 , 7626 (2017).

Li, D. et al. Self-assembled hydroxyapatite-graphene scaffold for photothermal cancer therapy and bone regeneration. J. Biomed. Nanotechnol. 14 , 2003–2017 (2018).

Saber-Samandari, S., Mohammadi-Aghdam, M. & Saber-Samandari, S. A novel magnetic bifunctional nanocomposite scaffold for photothermal therapy and tissue engineering. Inter. J. Bio. Macromol. 13 , 810–818 (2019).

Wang, G. et al. A bifunctional scaffold for tissue regeneration and photothermal therapy. J. Biomed. Nanotechnol. 14 , 698–706 (2018).

Zhou, Z.-F. et al. Calcium phosphate-phosphorylated adenosine hybrid microspheres for anti-osteosarcoma drug delivery and osteogenic differentiation. Biomaterials 121 , 1–14 (2017).

Yang, F. et al. Magnetic mesoporous calcium sillicate/chitosan porous scafflods for enhanced bone regeneration and photothermal-chemotherapy of osteosarcoma. Sci. Rep. 8 , 7345 (2018).

Lu, J. W., Yang, F., Ke, Q. F., Xie, X. T. & Guo, Y. P. Magnetic nanoparticles modified-porous scaffolds for bone regeneration and photothermal therapy against tumors. Nanomedicine 14 , 811–822 (2018).

Dong, S. et al. A novel multifunctional carbon aerogel-coated platform for osteosarcoma therapy and enhanced bone regeneration. J. Mater. Chem. B 8 , 368–379 (2020).

Zhao, P. P. et al. Ordered arrangement of hydrated GdPO 4 nanorods in magnetic chitosan matrix promotes tumor photothermal therapy and bone regeneration against breast cancer bone metastases. Chem. Eng. J. 381 , 122694 (2020).

Yu, K. et al. PMMA-Fe 3 O 4 for internal mechanical support and magnetic ablation of bone tumors. Theranostics 14 , 4192–4207 (2019).

Wang, L. et al. Multi-functional bismuth-doped bioglasses: combining bioactivity and photothermal response for bone tumor treatment and tissue repair. Light. Sci. Appl. 7 , 1 (2018).

Zhang, W. et al. A hydrogenated black TiO 2 coating with excellent effect for photothermal therapy of bone tumor and bone regeneration. Mater. Sci. Eng. C. 102 , 458–470 (2019).

Li, Q. et al. The design, mechanism and biomedical application of self-healing hydrogels. Chin. Chem. Lett. 28 , 1857–1874 (2017).

Zhang, K. et al. Adaptable hydrogels mediate cofactor-assisted activation of biomarker-responsive drug delivery via positive feedback for enhanced tissue regeneration. Adv. Sci. 5 , 1800875 (2018).

Niu, Y., Yang, T., Ke, R. & Wang, C. Preparation and characterization of pH-responsive sodium alginate/humic acid/konjac hydrogel for L-ascorbic acid controlled release. Mater. Express 9 , 563–569 (2019).

Wang, X. et al. Near-infrared light-triggered drug delivery system based on black phosphorus for in vivo bone regeneration. Biomaterials 179 , 164–174 (2018).

Wu, D., Xie, X., Kadi, A. A. & Zhang, Y. Photosensitive peptide hydrogels as smart materials for applications. Chin. Chem. Lett. 29 , 1098–1104 (2018).

Yang, Z., Liu, J. & Lu, Y. Doxorubicin and CD-CUR inclusion complex co-loaded in thermosensitive hydrogel PLGA-PEG-PLGA localized administration for osteosarcoma. Int. J. Oncol. 57 , 433–444 (2020).

Li, Q. et al. Granphene nanoparticles-based self-healing hydrogel in preventing post-operative recurrence of breast cancer. ACS Biomater. Sci. Eng. 5 , 768–779 (2019).

Liu, Q., Wang, H., Li, G., Liu, M. & Wu, H. A photocleavable low molecular weight hydrogel for light-triggered drug delivery. Chin. Chem. Lett. 30 , 485–488 (2019).

Gumustas, S. A. et al. Systematic evaluation of drug-loaded hydrogels for application in osteosarcoma treatment. Curr. Pharm. Biotechnol. 17 , 866–872 (2016).

Hu, Y., Chen, X., Li, Z., Zheng, S. & Cheng, Y. Thermosensitive in situ gel containing luteolin micelles is a promising efficient agent for colorectal cancer peritoneal metastasis treatment. J. Biomed. Nanotechnol. 16 , 54–64 (2020).

Zhao, H. et al. Dual-functional guanosine-based hydrogel integrating localized delivery and anticancer activities for cancer therapy. Biomaterials 230 , 119598 (2020).

Yang, Z. et al. The effect of PLGA-based hydrogel scaffold for improving the drug maximum-tolerated dose for in situ osteosarcoma treatment. Colloids Surf. B Biointerfaces 172 , 387–394 (2018).

Ma, H. et al. PLK1 sh RNA and doxorubicin co-loaded thermosensitive PLGA-PEG-PLGA hydrogels for osteosarcoma treatment. Biomaterials 35 , 8723–8734 (2014).

Chen, Y. et al. An injectable, near-infrared light-responsive click cross-linked azobenzene hydrogel for breast cancer chemotherapy. J. Biomed. Nanotechnol. 15 , 1923–1936 (2019).

Zheng, Y. et al. Injectable hydrogel-microsphere construct with sequential degradable for locally synergistic chemotherapy. ACS Appl. Mater. Interfaces 9 , 3487–3496 (2017).

Yu, L. & Ding, J. Injectable hydrogels as unique biomedical materials. Chem. Soc. Rev. 37 , 1473–1481 (2008).

Park, M. H., Joo, M. K., Choi, G. G. & Jeong, B. Biodegradable thermogels. Acc. Chem. Res. 45 , 424–433 (2012).

Wasupalli, G. K. & Verma, D. Injectable and thermosensitive nanofibrous hydrogel for bone tissue engineering. Mater. Sci. Eng. C. 107 , 110343 (2020).

Dimatteo, R., Darling, N. J. & Segura, T. In situ forming injectable hydrogels for drug delivery and wound repair. Adv. Drug Deliv. Rev. 127 , 167–184 (2018).

Sun, Y., Nan, D., Jin, H. & Qu, X. Recent advances of injectable hydrogels for drug delivery and tissue engineering applications. Polym. Test. 81 , 106283 (2020).

Luo, S. et al. An injectable, bifunctional hydrogel with photothermal effects for tumor therapy and bone regeneration. Macromol. Biosci. 19 , e1900047 (2019).

Wu, W. et al. Local release of gemcitabine via in situ UV-crosslinked lipid-strengthened hydrogel for inhibiting osteosarcoma. Drug Deliv. 25 , 1642–1651 (2018).

Ma, H. et al. Localized co-delivery of doxorubicin, cisplatin, and methotrexate by thermosensitive hydrogels for enhanced osteosarcoma treatment. ACS Appl. Mater. Interfaces 7 , 27040–27048 (2015).

Roodman, G. D. Mechanism of bone metastasis. N. Engl. J. Med. 350 , 1655–1664 (2004).

Yang, Y.-S. et al. Bone-targeting AAV-mediated silencing of Schnurri-3 prevents bone loss in osteoporosis. Nat. Commun. 10 , 2958 (2019).

Hirabayashi, H. et al. Bone-specific delivery and sustained release of diclofenac, a non-steroidal anti-inflammatory drug, via bisphosphonic prodrug based on the osteotropic drug delivery system (ODDS). J. Control. Release 70 , 183–191 (2001).

Chong, C. R. & Jänne, P. A. The quest to overcome resistance to EGFR-targeted therapies in cancer. Nat. Med. 19 , 1389–1400 (2013).

David, E. et al. 12b80-hydroxybisphosphonate linked doxorubcin: bone targeted strategy for treatment of osteosarcoma. Bioconjug. Chem. 30 , 1665–1676 (2019).

Thamake, S. I., Raut, S. L., Gryczynski, Z., Ranjan, A. P. & Vishwanatha, J. K. Alendronte coated poly-lactic-co-glycolic acid (PLGA) nanoparticles targeting of metastatic breast cancer. Biomaterials 33 , 7164–7173 (2012).

He, Y. et al. Bisphosphonate-functionalized coordination polymer nanoparticles for the treatment of bone metastatic breast cancer. J. Control. Release 264 , 76–88 (2017).

Ravanbakhsh, M. et al. Mesoporous bioactive glasses for the combined application of osteosarcoma treatment and bone regeneration. Mater. Sci. Eng. C. 104 , 109994 (2019).

Cole, L. E., Vargo-Gogola, T. & Roeder, R. K. Targeted delivery to bone and mineral deposits using bisphosphonate ligands. Adv. Drug Deliv. Rev. 99 , 12–27 (2016).

Low, S. A. & Kopeček, J. Targeting polymer therapeutics to bone. Adv. Drug Deliv. Rev. 64 , 1189–1204 (2012).

Hatami, E. et al. Development of zoledronic acid-based nanoassemblies for bone-targetd anticancer therapy. ACS Biomater. Sci. Eng. 5 , 2343–2354 (2019).

Yamashita, S. et al. Development of PEGylated aspartic acid-modified liposomes as a bone-targeting carrier for the delivery of paclitaxel and treatment of bone metastasis. Biomaterials 154 , 74–85 (2018).

Poznak, C. H. V. et al. American Society of Clinical Oncology executive summary of the clinical practice guideline update on the role of bone-modifying agents in metastatic breast cancer. J. Clin. Oncol. 29 , 1221–1227 (2011).

Liang, C. et al. Aptamer-functionalized lipid nanoparticles targeting osteoblasts as a novel RNA interference-based bone anabolic strategy. Nat. Med. 21 , 288–296 (2015).

Wang, Y. et al. Osteotropic peptide-mediated bone targeting for photothermal treatment of bone tumors. Biomaterials 114 , 97–105 (2017).

Feng, S. et al. Engineering of bone- and CD44-dual-targeting redox-sensitive liposomes for treatment of orthotopic osteosarcoma. ACS Appl. Mater. Interfaces 11 , 7357–7368 (2019).

Yang, L. & Webster, T. J. Nanotechnology controlled drug delivery for treating bone disease. Expert Opin. Drug Deliv. 6 , 851–864 (2009).

Raucci, M. G. et al. Exfoliated black phosphorus promotes in vitro bone regeneration and suppresses osteosarcoma progression through cancer-related inflammation inhibition. ACS Appl. Mater. Interfaces 11 , 9333–9342 (2019).

Li, K. et al. Calcium-mineralized polypeptide nanoparticle for intracellular drug delivery in osteosarcoma chemotherapy. Bioact. Mater. 5 , 721–731 (2020).

Zhang, M. et al. Fabrication of curcumin-modified TiO 2 nanoarrays via cyclodextrin based polymer functional coatings for osteosarcoma therapy. Adv. Health Mater. 8 , 1901031 (2019).

Cheng, H. et al. Development of nanomaterials for bone-targeted drug delivery. Drug Discov. Today 22 , 1336–1350 (2017).

Song, H. et al. Reversal of osteoporotic activity by endothelial cell-secreted bone targeting and biocompatible exosomes. Nano Lett. 19 , 3040–3048 (2019).

Rotman, S. G. et al. Drug delivery systems functionalized with bone mineral seeking agents for bone targeted therapeutics. J. Control. Release 269 , 88–99 (2018).

Carbone, E. J. et al. Osteotropic nanoscale drug delivery systems based on small molecule bone-targeting moieties. Nanomedicine 13 , 37–47 (2017).

Farrell, K. B., Karpeisky, A., Thamm, D. H. & Zinnen, S. Bisphosphonate conjugation for bone specific drug targeting. Bone Rep. 9 , 47–60 (2018).

Chu, W. et al. Calcium phosphate nanoparticles functionalized with alendronate-conjugated polyethlene glycol (PEG) for the treatment of bone metastasis. Int. J. Pharm. 516 , 352–363 (2017).

Wang, Y. et al. Multifunctional melanin-like nanoparticles for bone-targeted chemo-photothermal therapy of malignant bone tumors and osteolysis. Biomaterials 183 , 10–19 (2018).

Lee, K. K. et al. Bone-targeting carbon dots: effect of nitrogen-doping on binding affinity. RSC Adv. 9 , 2708–2717 (2019).

Sun, W. et al. Bone-targeted nanoplatform combining zoledronate and photothermal therapy to treat breast cancer bone metastasis. ACS Nano 13 , 7556–7567 (2019).

McClung, M. et al. Bisphosphonate therapy for osteoporosis: benefits, risks, and drug holiday. Am. J. Med. 126 , 13–20 (2013).

Zhou, Z. et al. One stone with two birds: phytic acid-capped platinum nanoparticles for targeted combination therapy of bone tumors. Biomaterials 194 , 130–138 (2019).

Lu, Y. et al. High-activity chitosan/nanohydroxyapatite/zoledronic acid scaffolds for simultaneous tumor inbibition, bone repair and infection eradication. Mater. Sci. Eng. C. 82 , 225–233 (2018).

Cojocaru, F. D. et al. Magnetic composite scaffolds for potential applications in radiochemotherapy of malignant bone tumors. Medicina 55 , 153 (2019).

Article   PubMed Central   Google Scholar  

Yang, Q. et al. Engineering 2D mesoporous silica@MXene-integrated 3D-printing scaffolds for combinatory osteosarcoma therapy and NO-augmented bone regeneration. Small 16 , e1906814 (2020).

Yu, Q. et al. Copper silicate hollow microspheres incorporated scaffolds for chemo-photothermal therapy of melanoma and tissue engineering. ACS Nano 12 , 2695–2707 (2018).

Zhou, L. et al. Injectable self-healing antibacterial bioactive polypeptide-based hybrid nanosystems for efficiently treating multidrug resistant infection, skin-tumor therapy, and enhancing wound healing. Adv. Funct. Mater. 29 , 1806883 (2019).

Li, J. et al. Lysozyme-assisted photothermal eradiction of methicillin-resistant Staphylococcus aureus infection and acceletated tissue repair with natural melanosome nanostructures. ACS Nano 13 , 11153–11167 (2019).

Yanagi, T., Kajiya, H., Kawaguchi, M., Kido, H. & Fukushima, T. Photothermal stress triggered by near infrared-irradiated carbon nanotubes promotes bone deposition in rat calvarial defects. J. Biomater. Appl. 29 , 1109–1118 (2015).

Lu, Y. et al. High-activity chitosan/nanohydroxyapatite/zoledronic acid scaffolds for simultaneous tumor inhibition, bone repair and infection eradication. Mater. Sci. Eng. C. 82 , 225–233 (2018).

Lu, Y. et al. Zero-dimensional carbon dots enhance bone regeneration, osterosarcoma ablation, and clinical bacterial eradication. Bioconjug. Chem. 29 , 2982–2993 (2018).

Ma, L. et al. A novel photothermally controlled multifunctional scaffold for clinical treatment of osteosarcoma and tissue regeneration. Mater. Today 36 , 48–62 (2020).

Wang, X. et al. Bifunctional scaffolds for the photothermal therapy of breast tumor cells and adipose tissue regeneration. J. Mater. Chem. B 6 , 7728–7736 (2018).

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Acknowledgements

This work was financially supported by the National Key Research and Development Program of China (2017YFC1103500, 2017YFC1103502), the National Natural Science Foundation (31972925, 31771096, 31930067, 31525009), the 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYGD18002), the Sichuan Science and Technology Program (2020YJ0065), the Sichuan University Spark Project (2018SCUH0029), and the State Key Laboratory of Oral Diseases Foundation (SKLOD202016).

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Jinfeng Liao, Ruxia Han, Yongzhi Wu & Zhiyong Qian

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Liao, J., Han, R., Wu, Y. et al. Review of a new bone tumor therapy strategy based on bifunctional biomaterials. Bone Res 9 , 18 (2021). https://doi.org/10.1038/s41413-021-00139-z

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Accepted : 21 December 2020

Published : 16 March 2021

DOI : https://doi.org/10.1038/s41413-021-00139-z

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• Introduction

Causes and symptoms

Diagnosis and prognosis.

• What are the major functions of bone tissue?

bone cancer

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• National Cancer Institute - Bone Cancer
• University of Maryland Medical Center - Bone cancer
• Mayo Clinic - Bone cancer
• Table Of Contents

bone cancer , disease characterized by uncontrolled growth of cells of the bone . Primary bone cancer—that is, cancer that arises directly in the bone—is relatively rare. In the United States , for example, only about 3,600 new cases of primary bone cancer are diagnosed each year. Most cancer that involves the bone is cancer that has spread (metastasized) from other tissues in the body through the blood or lymphatic systems. Different types of bone tissue give rise to different types of primary bone cancer. Osteosarcoma develops from cells that form the bone, and Ewing tumour of the bone (Ewing sarcoma) develops from immature nerve tissue within the bone. Both types most commonly affect males between 10 and 20 years of age. Chondrosarcoma , which forms in cartilage tissue, principally affects persons over age 50. More than one-half of the cases of primary bone cancer, even once-deadly types, can now be treated successfully.

Only a small portion of bone cancer cases are associated with known risk factors, which include exposure to radiation or chemotherapy, Paget disease , and rare hereditary syndromes such as hereditary retinoblastoma. The majority of cases seem to occur randomly in otherwise healthy individuals.

The most common symptom of bone cancer is pain or tenderness over the affected bone. Bone tumours often are not noticed until minor trauma causes significant pain and disability that leads to further investigation. This association has led to the mistaken conclusion that traumatic injuries can cause bone cancer. Other symptoms that can occur include bone fractures, decreased mobility of a joint, fever , fatigue , and anemia . These symptoms are not specific to bone cancer and can be the result of other, benign processes.

Preliminary investigation of a bone tumour can include a blood test for the enzyme alkaline phosphatase . As bone cancer grows, the amount of the enzyme in the blood increases dramatically, but it can also increase for other reasons. With bone cancer, unlike many other types of cancer, X-ray imaging can be very helpful in making a diagnosis . The images will show whether a tumour is creating bone tissue or destroying normal bone tissue. Images of the bone useful for making a diagnosis can also be obtained by computed tomography (CT scans), magnetic resonance imaging (MRI), and a type of radioisotope scanning commonly called a bone scan. The final diagnosis of cancer, however, requires the removal of a portion of the tumour for examination under a microscope.

The prognosis of bone cancer depends on both the type of cancer and the extent to which it has spread. Bone cancer most frequently spreads to the lungs , but it may also spread to other bones and only rarely to other tissues. Overall, the prognosis for long-term survival has improved to more than 50 percent, including cases in which the tumour has spread to other parts of the body. Of the different types of primary bone cancer, chondrosarcoma has the best prognosis and osteosarcoma the worst.

As with many cancers, the treatment of bone cancer depends on the type of cell, location, size, and spread of the primary tumour. Most cases require a combination of surgery , chemotherapy , and radiation . In some cases, surgery requires the amputation of the involved limb. In other cases, it may be possible to remove only a portion of the bone and replace it with a prosthesis or bone graft. Chemotherapy may be given before or after surgery and is tailored to the specific type of bone cancer.

Prevention of bone cancer will require a better understanding of its causes than is currently available. If a patient has a known risk factor for bone cancer, such as Paget disease, careful screening may help detect and treat the cancer in its early stages, thereby improving the chances for survival.

• Patient Care & Health Information
• Diseases & Conditions
• Bone cancer

Bone cancer diagnosis often involves imaging tests to look at the affected bone. To be certain whether a growth in the bones is cancer, a piece of tissue might be removed and tested for cancer cells.

Imaging tests

Imaging tests make pictures of the body. They can show the location and size of a bone cancer. Tests might include:

• Magnetic resonance imaging, also called MRI.
• Computerized tomography scan, also called CT scan.
• Positron emission tomography scan, also called PET scan.

A biopsy is a procedure to remove a sample of tissue for testing in a lab. For bone cancer, the sample of tissue might be collected by:

• Inserting a needle through the skin. During a needle biopsy, a healthcare professional inserts a thin needle through the skin and guides it into the cancer. The health professional uses the needle to collect small samples of tissue.
• Removing the sample during surgery. During a surgical biopsy, a surgeon makes an incision in the skin to access the cancer. The surgeon removes a piece of the cancer for testing.

Determining the type of biopsy you need and the details of how to do the biopsy requires careful planning by your medical team. Healthcare professionals need to perform the biopsy in a way that won't interfere with future surgery to remove bone cancer. For this reason, ask for a referral to a healthcare team that treats a lot of bone cancers before your biopsy.

Stages of bone cancer

If you're found to have bone cancer, often the next step is to find out the extent of the cancer. This is called the cancer's stage. Your healthcare team uses your cancer's stage to help create your treatment plan. To determine the stage of the cancer, the healthcare team considers:

• The cancer's location.
• The size of the cancer.
• How fast the cancer is growing.
• The number of bones affected, such as number of affected vertebrae in the spine.
• Whether the cancer has spread to the lymph nodes or to other parts of the body.

The stages of bone cancer range from 1 to 4. A stage 1 bone cancer generally is a small cancer that is growing slowly. As the cancer grows larger or grows more quickly, the stages get higher. A stage 4 bone cancer has spread to the lymph nodes or to other parts of the body.

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Bone cancer care at Mayo Clinic

• Needle biopsy
• Positron emission tomography scan

Bone cancer treatments include surgery, radiation and chemotherapy. Which treatments are best for your bone cancer will depend on several factors. These factors include the type, location and stage of the bone cancer. Your healthcare team also considers your overall health and your preferences.

The goal of surgery for bone cancer is to remove all of the cancer. The surgeon may remove the bone cancer and some of the healthy tissue around it. Then the surgeon repairs the bone. This might involve using a piece of bone from another part of your body. Sometimes the bone is repaired with metal or plastic material.

Sometimes surgeons need to remove an arm or leg in order to get all of the cancer, though this isn't common. It might be needed if the cancer grows very large or if the cancer is in a place that makes surgery difficult. After an arm or leg is removed, you may choose to use an artificial limb. With training and time with the new limb, you can learn to do everyday tasks.

• Chemotherapy

Chemotherapy treats cancer with strong medicines. Many chemotherapy medicines exist. Most chemotherapy medicines are given through a vein. Some come in pill form.

Chemotherapy is often used after surgery for some types of bone cancers. It can kill any cancer cells that remain and lower the risk that the cancer will come back. Sometimes chemotherapy is given before surgery to shrink a bone cancer and make it easier to remove.

Not all types of bone cancers respond to chemotherapy treatments. Chemotherapy is often used to treat osteosarcoma and Ewing sarcoma. It's not often used for chondrosarcoma.

• Radiation therapy

Radiation therapy treats cancer with powerful energy beams. The energy can come from X-rays, protons or other sources. During radiation therapy, you lie on a table while a machine moves around you. The machine directs radiation to precise points on your body.

Radiation therapy might be used after surgery to kill any bone cancer cells that might remain. It also might help control bone cancer when surgery isn't an option.

Some types of bone cancers are more likely to be helped by radiation therapy than others. Radiation therapy may be an option for treating Ewing sarcoma. It's not often used to treat chondrosarcoma or osteosarcoma.

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Coping and support

A cancer diagnosis can feel overwhelming. With time you'll find ways to cope with the distress and uncertainty of cancer. Until then, you may find it helps to:

• Learn enough about bone cancer to make decisions about your care. Ask your healthcare team about your bone cancer, including your treatment options and, if you like, your prognosis. As you learn more about bone cancer, you may feel more confident in making treatment decisions.
• Keep friends and family close. Keeping your close relationships strong can help you deal with your bone cancer. Friends and family can provide the practical support you'll need, such as helping take care of your home if you're in the hospital. And they can serve as emotional support when you feel overwhelmed by cancer.
• Find someone to talk with. Find a good listener who is willing to listen to you talk about your hopes and fears. This may be a friend or family member. The concern and understanding of a counselor, medical social worker, clergy member or cancer support group also may be helpful. Ask your healthcare team about support groups in your area.

Preparing for your appointment

If you have any symptoms that worry you, start by making an appointment with a doctor or other healthcare professional. If your health professional suspects you may have bone cancer, you may be referred to a specialist. Bone cancer is often treated by a team of specialists that may include:

• Surgeons who operate on bones and joints, called orthopedic surgeons.
• Orthopedic surgeons who specialize in operating on cancers that affect the bones, called orthopedic oncologists.
• Doctors who specialize in treating cancer with medicine, called medical oncologists.
• Doctors who use radiation to treat cancer, called radiation oncologists.
• Doctors who analyze tissue to diagnose the specific type of cancer, called pathologists.
• Rehabilitation specialists who can help you recover after surgery.

How to prepare

Because appointments can be brief, it's a good idea to be prepared. Try to:

• Be aware of any pre-appointment restrictions. At the time you make the appointment, be sure to ask if there's anything you need to do in advance, such as restrict your diet.
• Write down any symptoms you have, including any that may seem unrelated to the reason for which you scheduled the appointment.
• Write down key personal information, including any major stresses or recent life changes.
• Make a list of all medicines, vitamins or supplements that you're taking.
• Consider taking a family member or friend along. Sometimes it can be difficult to remember all the information provided during an appointment. Someone who goes with you may remember something that you missed or forgot.
• Bring your previous scans or X-rays, the related reports and any other medical records important to this situation to the appointment.

Questions to ask

Preparing a list of questions can help you make the most of your time. List your questions from most important to least important in case time runs out. For bone cancer, some basic questions to ask include:

• What type of bone cancer do I have?
• What is the stage of my bone cancer?
• How quickly is my bone cancer growing?
• Will I need any additional tests?
• What are the treatment options for my bone cancer?
• What are the chances that treatment will cure my bone cancer?
• What are the side effects and risks of each treatment option?
• Will treatment make it impossible for me to have children?
• I have other health conditions. How will cancer treatments affect my other conditions?
• Is there one treatment that you think is best for me?
• What would you recommend to a friend or family member in my situation?
• Should I see a specialist? What will that cost, and will my insurance cover it?
• If I would like a second opinion, can you recommend a specialist?
• Are there any brochures or other printed material that I can take with me? What websites do you recommend?

In addition to the questions that you've prepared, don't hesitate to ask other questions during your appointment.

What to expect from your doctor

Be prepared to answer some questions about your symptoms and your health history. Questions may include:

• When did you first begin experiencing symptoms?
• Have your symptoms been continuous or occasional?
• How severe are your symptoms?
• What, if anything, seems to improve your symptoms?
• What, if anything, appears to worsen your symptoms?
• Niederhuber JE, et al., eds. Sarcomas of bone. In: Abeloff's Clinical Oncology. 6th ed. Elsevier; 2020. https://www.clinicalkey.com. Accessed April 1, 2024.
• Primary bone cancer. National Cancer Institute. https://www.cancer.gov/types/bone/bone-fact-sheet. Accessed April 1, 2024.
• Bone cancer. National Comprehensive Cancer Network. https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1418. Accessed April 1, 2024.
• Hornicek FJ, et al. Bone tumors: Diagnosis and biopsy techniques. https://www.uptodate.com/contents/search. Accessed April 1, 2024.
• Azar FM, et al. Malignant tumors of bone. In: Campbell's Operative Orthopaedics. 14th ed. Elsevier; 2021. https://www.clinicalkey.com. Accessed April 1, 2024.
• Member institutions. National Comprehensive Cancer Network. https://www.nccn.org/home/member-institutions. Accessed April 1, 2024.
• COG institution locations. Children's Oncology Group. https://www.childrensoncologygroup.org/apps/instmap/default.aspx. Accessed April 1, 2024.
• Osteosarcoma

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Health Encyclopedia

Bone cancer: overview, what is bone cancer.

Cancer starts when cells change (mutate) and grow out of control. The changed (abnormal) cells often grow to form a lump or mass called a tumor. Cancer cells can also grow into (invade) nearby areas. They can spread to other parts of the body, too. This is called metastasis.

Primary bone cancer is cancer that starts in the cells that make up your bones. It's sometimes just called bone cancer. Primary bone cancer is very different from secondary, or metastatic, bone cancer. Metastatic bone cancer is cancer that started in another part of the body and spread to the bones. Primary bone cancers are quite rare in adults. Most of the time when an adult has cancer in the bones, it spread there from cancer that started in a different place.

The main types of primary bone cancer are:

Osteosarcoma

Chondrosarcoma

Ewing sarcoma

Who is at risk for bone cancer?

A risk factor is anything that may increase your chance of having a disease. The exact cause of someone’s cancer may not be known. But risk factors can make it more likely for a person to have cancer. Some risk factors can't be controlled. But others may be things you can change.

Anyone can get primary bone cancer. But some factors that might increase your risk for it include:

A family history of certain genetic syndromes or rare cancers, such as Li-Fraumeni syndrome or retinoblastoma

Past radiation therapy or certain chemotherapy medicines to treat another cancer during childhood

Having Paget disease of the bone

Having certain types of bone or cartilage tumors that are not cancer

Bone marrow transplant was done when you were a child (rare)

Talk with your healthcare provider about your risk factors for bone cancer and what you can do about them.

What are the symptoms of bone cancer?

Symptoms of primary bone cancer tend to develop slowly over time. They depend on the type of bone cancer, where it is, and size of the tumor. Here are some common symptoms:

Pain in the bone

Swelling or a lump or mass

A bone breaks (fractures) for no reason

Fever, weight loss, fatigue, numbness, or weakness

Many of these may be caused by other health problems. But it's important to see your healthcare provider if you have these symptoms. Only a healthcare provider can tell if you have cancer.

How is bone cancer diagnosed?

If your healthcare provider thinks you may have primary bone cancer, you will need certain exams and tests to be sure. Your healthcare provider will ask you about your health history, your symptoms, risk factors, and family history of disease. A physical exam will be done. You may also need blood tests and an X-ray or other imaging tests.

A biopsy is the only way to tell for sure if you have bone cancer. A biopsy can also show if the tumor is a primary or secondary bone cancer. (A secondary bone cancer is one that has spread to the bone from cancer that started in another part of the body.) For a biopsy, small pieces of tissue are taken out from the tumor and tested for cancer cells. The results will come back in about 1 week.

After a diagnosis of bone cancer, you’ll need more tests. These help your providers learn more about your overall health and the exact type of bone cancer. They're used to find out the stage and grade of the cancer. The stage is how much cancer there is and how far it has spread (metastasized) in your body. It's one of the most important things to know when deciding how to treat the cancer. The grade is used as part of staging. It gives an idea of how fast the cancer will grow and spread.

Once your cancer is staged, your provider will talk with you about what this means for your treatment. Ask your provider to explain the details of your cancer to you in a way you can understand.

How is bone cancer treated?

Your treatment choices depend on the type of primary bone cancer you have, test results, and the stage of the cancer. The goal of treatment may be to cure you, control the cancer, or help ease problems caused by the cancer. Talk with your healthcare team about your treatment choices, the goals of treatment, and what the risks and side effects may be. Other things to think about are if the cancer can be removed with surgery, how your body will look and work after treatment, and your overall health.

Types of treatment for cancer are either local or systemic. Local treatments remove, destroy, or control cancer cells in one area. Surgery and radiation are local treatments. Systemic treatment is used to destroy or control cancer cells that may have traveled around your body. When taken by pill or injection, chemotherapy and targeted therapy are systemic treatments.

You may have just one treatment or a combination of treatments. Tests will be done during treatment to see how well it's working.

Bone cancer may be treated with:

Radiation therapy

Chemotherapy

Targeted therapy

Supportive care

Talk with your healthcare providers about your treatment options. Make a list of questions. Think about the benefits and possible side effects of each option. Talk about your concerns with your healthcare provider before making a decision.

What are treatment side effects? 

Cancer treatment such as chemotherapy and radiation can damage normal cells. This can cause side effects such as hair loss, mouth sores, and vomiting. Talk with your healthcare provider about side effects linked to your treatment. There are often ways to manage them. There may be things you can do and medicines you can take to help prevent or control many treatment side effects.

Coping with bone cancer

Many people feel worried, depressed, and stressed when dealing with cancer. Getting treatment for cancer can be hard on your mind and body. Keep talking with your healthcare team about any problems or concerns you have. Work together to ease the effect of cancer and its symptoms that impact your daily life.

Here are some tips:

Talk with your family or friends.

Ask your healthcare team or social worker for help.

Speak with a counselor.

Talk with a spiritual advisor, such as a minister or rabbi.

Ask your healthcare team about medicines for depression or anxiety.

Keep socially active.

Join a cancer support group in person or online.

Cancer treatment is also hard on the body. To help yourself stay healthier, try to:

Eat a healthy diet, with a focus on high-protein foods.

Drink plenty of water, fruit juices, and other liquids.

Keep physically active.

Rest as much as needed.

Talk with your healthcare team about ways to manage treatment side effects.

Take your medicines as directed by your team.

When should I call my healthcare provider?

Your healthcare provider will talk with you about when to call. For instance, you may be told to call if you have:

New symptoms or symptoms that get worse

Signs of an infection, such as a fever or chills

Side effects of treatment that affect your daily function or don’t get better with treatment

Ask your healthcare provider what signs to watch for and when to call. Know how to get help after office hours and on weekends and holidays. 

Tips to help you get the most from a visit to your healthcare provider:

Know the reason for your visit and what you want to happen.

Before your visit, write down questions you want answered.

Bring someone with you to help you ask questions and remember what your provider tells you.

At the visit, write down the name of a new diagnosis and any new medicines, treatments, or tests. Also write down any new instructions your provider gives you.

Know why a new medicine or treatment is prescribed and how it will help you. Also know what the side effects are.

Ask if your condition can be treated in other ways.

Know why a test or procedure is recommended and what the results could mean.

Know what to expect if you do not take the medicine or have the test or procedure.

If you have a follow-up appointment, write down the date, time, and purpose for that visit.

Know how you can contact your provider if you have questions.

Medical Reviewers:

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• Kimberly Stump-Sutliff RN MSN AOCNS
• Todd Gersten MD

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• v.24(3); Jul-Sep 2014

Bone tumor mimickers: A pictorial essay

Jennifer ni mhuircheartaigh.

1 Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States

Yu-Ching Lin

2 Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Keelung Chang Gung University, Taoyuan, Taiwan

Focal lesions in bone are very common and many of these lesions are not bone tumors. These bone tumor mimickers can include numerous normal anatomic variants and non-neoplastic processes. Many of these tumor mimickers can be left alone, while others can be due to a significant disease process. It is important for the radiologist and clinician to be aware of these bone tumor mimickers and understand the characteristic features which allow discrimination between them and true neoplasms in order to avoid unnecessary additional workup. Knowing which lesions to leave alone or which ones require workup can prevent misdiagnosis and reduce patient anxiety.

Introduction

Focal lesions in bone are very common and are frequently encountered in routine imaging studies. While many lesions are true neoplasms, a number of these abnormalities in bone are not tumors. These lesions can include normal variants, congenital abnormalities, traumatic/iatrogenic lesions, metabolic and arthritic changes, infection, and artifacts related to imaging technique. It is important for the radiologist and clinician to be aware of this possibility and to identify the characteristic features which allow discrimination between bone tumors and bone tumor mimickers. Subjecting the patient to an inappropriate workup can lead to misdiagnosis, poor management, and anxiety for both the patient and physician. In many instances, these tumor mimickers can be left alone and no treatment is necessary; however, in other cases, they can indicate a significant disease process. Although there are innumerable processes that can lead to focal lesions in bone, we present here a review of commonly encountered bone lesions [ Table 1 ] that can mimic bone tumors and discuss the key imaging and clinical features that can help distinguish these entities from neoplasms. For the purpose of this pictorial essay, we performed a systematic search of the electronic database PubMed to identify relevant studies published in the literature from 1991 to 2014 using the terms “bone tumor mimickers,” “bone tumor mimics,” and “pseudolesions of bone.” Additional targeted searches were performed for the specific disease conditions.

Common lesions mimicking bone tumors

Normal Variants

Erythropoietic or red marrow can be a common cause for concern on magnetic resonance imaging (MRI). This can be particularly problematic if the area of red marrow is mass-like in appearance. Red marrow should be hyperintense to fatty marrow on fat-suppressed T2-weighted (T2W) MRI sequences and hypointense on T1-weighted (T1W) MRI sequences.[ 1 ] The key feature is that the low signal intensity on T1W MRI sequences should be higher than that of skeletal muscle or the intervertebral discs.[ 2 ] In-phase and out-of-phase T1W MRI images can be helpful in equivocal cases as red marrow should have some intermixed fatty marrow and, consequently, should lose signal (become darker) on out-of-phase compared to in-phase MRI.[ 3 ] On the other hand, marrow-replacing tumors, such as many metastases, should replace all the fatty marrow and should not lose signal on out-of-phase T1W imaging [ Figure 1 ]. Thus, when approaching marrow abnormalities on MRI, it is important to have T1W images that include skeletal muscle for comparison and in-phase and out-of-phase T1W images to show the presence or absence of fat. Yellow marrow can reconvert to red marrow with physiologic stressors such as anemia.[ 4 ] Moreover, red marrow should not extend past the physeal scar into the epiphysis and should not distort normal trabecular pattern.[ 5 ]

Island of red marrow in the sacrum. A 49 year old man with recurrent bloating underwent a MR enterography, which demonstrated an incidental lesion in the sacrum. He was recalled for in-phase and out-of-phase T1W MRI imaging. (A) In-phase T1W MRI image demonstrates the lesion (arrow) is slightly hyperintense to skeletal muscle (B) On the out-of-phase T1W MRI image, there is loss of signal due to the presence of intermixed fatty marrow (arrow)

Humeral pseudocyst

A radiolucent area in the humeral head may be seen due to a normal decrease in the trabeculae often associated with an increase in the amount of fat.[ 6 ] This radiolucency is seen in the superolateral humeral head and may be misdiagnosed as a chondroblastoma, giant cell tumor, Langerhans cell histiocytosis, or even an osteolytic metastasis on radiographs.[ 7 ] The increased fat in this region can be readily seen on MRI and helps make the diagnosis [ Figure 2 ]. On radiographs, this pseudolesion will be seen on an external rotation view of the shoulder and there is usually a sharp line of demarcation inferiorly between the pseudolesion and adjacent marrow, which is due to the line of fusion between the epiphysis in the greater tuberosity and the shaft of the humerus. The remainder of the margin is usually ill-defined.[ 6 ]

Humeral pseudocyst. A 47 year old female with left shoulder pain. A round radiolucency in the greater tuberosity (arrow) on the external rotation shoulder radiograph (A) corresponds to normal fatty marrow (arrow) which is hyperintense on the (B) T1W and hypointense on the (C) T2W fat-saturated coronal MRI images

Ward's triangle

A focal area of increased lucency is often seen in the femoral neck at the junction of the compressive and tensile trabeculae [ Figure 3 ]. As with the humeral pseudocyst, this radiolucency can become less apparent if the patient is osteoporotic due to attenuation of the adjacent trabeculae.[ 7 , 8 ]

Ward's triangle. A 67 year old female with left hip pain. (A) Anteroposterior (AP) radiograph of the hip demonstrates a triangular radiolucency (arrows) in the femoral neck (B) The coronal CT image shows a paucity of trabecular lines in the femoral neck (arrows)

Calcaneal pseudocyst

In a similar pattern to Ward's triangle, a radiolucency in the anterior aspect of the calcaneus can be outlined by the major trabecular groups [ Figure 4 ].[ 7 ] Although this is a normal appearance, a number of pathologic lesions can occur in this location and form a radiolucent region on radiographs. These tumors include simple bone cyst, giant cell tumor, chondroblastoma, and intraosseous lipoma. Intraosseous lipomas often develop central necrosis which can cause a central dystrophic calcification and tends to have well-defined sclerotic margins.[ 7 ]

Calcaneal pseudocyst and intraosseous lipoma. (A) Lateral ankle radiograph of a 39 year old female with foot pain demonstrates a radiolucency (arrows) in the anterior calcaneus due to decrease in bony trabeculae (B) Lateral ankle radiograph of a 45 year old man with an intraosseous lipoma (arrows) shows a similar radiographic appearance to the calcaneal pseudocyst; however, there is focal central calcification (arrowhead) due to fat necrosis

Congenital and Developmental Abnormalities

Dorsal defect of the patella.

A subarticular abnormality in the superolateral aspect of the patella is known as the dorsal defect of the patella. It is seen in approximately 1% of the population and can be bilateral.[ 9 ] The dorsal patellar defect can appear as a 1-2 cm rounded area of lucency in the same location as a bipartite patella and is believed to be due to incomplete fusion of the patellar ossification centers [ Figure 5 ].[ 9 ] Another potential etiology is that it is due to traction at the insertion of vastus lateralis. Occasionally, this lesion may be symptomatic.[ 7 ]

Dorsal defect of the patella. A 38 year old female with left knee pain. (A) AP radiograph of the knee demonstrates a focal radiolucency (arrow) in the superolateral aspect of patella (B) Sagittal PDW MRI image shows a focal area of cortical irregularity with intact overlying hyaline cartilage (arrow)

Synovial herniation pit in the proximal femur

A well-defined round or oval radiolucency in the proximal superior femoral neck is known as a synovial herniation pit or Pitt's pit.[ 10 ] It is thought to represent herniation of the synovium into cortical defects created by abrasion of the hip joint capsule against the femoral neck, although it may represent a normal variant [ Figure 6 ].[ 11 ] Typically these lesions are less than 1 cm in size, but can grow up to 2-3 cm and may be lobulated.[ 12 ] Although these lesions have been considered asymptomatic, an association with femoracetabular impingement has been described.[ 11 ]

Synovial herniation pit in the proximal femur. A 60 year old female with suspected hip fracture after a fall. (A) AP radiograph shows a small round radiolucency (arrow) and sclerotic rim at the superior lateral aspect of the femoral neck. The lesion (arrow) is hypointense on the (B) coronal T1W MRI image and hyperintense on the (C) coronal T2W fat-saturated MRI image

Avulsive cortical irregularity of the posterior femur

An avulsive cortical irregularityof the posterior femur, known as a cortical desmoid, appears as an irregular focal radiolucent lesion along the posteromedial aspect of the distal femur in children [ Figure 7 ].[ 13 ] Differential diagnosis for this appearance includes osteomyelitis and surface osteosarcoma, especially if the lesion has an aggressive appearance. It has been proposed that this lesion may be caused by traction due to the medial head of gastrocnemius or adductor magnus.[ 14 ] This lesion should not be seen in skeletally mature individuals.

Avulsive cortical irregularity of the posterior femur. An 18 year old female with left knee pain. (A) Lateral radiograph of knee demonstrates an area of cortical irregularity at the medial aspect of the distal femoral metaphysis (arrow) (B) Corresponding axial T2W fat-saturated MRI image shows marrow edema (arrowhead) at the area of cortical irregularity (arrow)

Supracondylar process of the humerus

A supracondylar process in the humerus is a bony spur that arises from the anteromedial aspect of the humerus in about 1-3% of the population.[ 15 ] It is usually an incidental finding and should not be mistaken for an osteochondroma or surface osteosarcoma. Osteochondromas point away from the joint, whereas the supracondylar process points toward the elbow joint [ Figure 8 ]. Occasionally, a ligament extends from the supracondylar process to the medial epicondyle (the ligament of Struthers), forming a tunnel that can entrap the median nerve and even the brachial artery, leading to symptoms.[ 16 ]

Supracondylar process of the humerus. A 45 year old male with right elbow pain. (A) AP radiograph of elbow shows an osseous process (arrow) arising from anteromedial aspect of the distal humerus. Corresponding ultrasound image (B) demonstrates an osseous excrescence (arrow) with a hyperintense ligament of Struthers (arrowhead) attached onto it

Soleal line

The soleal line is a bony “tug lesion” that can form on the tibia at the attachment of the soleus and mimics periostitis from a tumor, infection, or stress fracture [ Figure 9 ].[ 17 ] The soleal line begins 1-2 cm below the fibular facet and may present as a line or a ridge.[ 18 ] This can arise from the tibial head of the soleus, with cortical thickening extending lateral to medial along the posterior upper one-third of the tibia. Similar bony changes can be seen at the fibular attachment of the soleus.

Soleal line. A 67 year old male with suspected right leg fracture after fall. (A) AP and (B) lateral radiographs of the proximal tibia demonstrate linear cortical thickening (arrows) along the proximal tibia and fibula, which corresponds to an enthesophyte from the attachment of the soleus. The tibial calcification extends lateral to medial along the posterior cortex

Trauma and Iatrogenic Lesions

Subperiosteal hematoma.

The periosteum is a highly vascular thick fibrous membrane that is closely adherent to the bone.[ 19 ] Injury to the periosteum can result in a subperiosteal hematoma, which lifts the periosteum off the bone and can resemble a focal mass such as a parosteal osteosarcoma or osteochondroma [ Figure 10 ]. Most often, they resolve without treatment; however, they may ossify and persist.[ 19 ] On imaging, these lesions have a non-aggressive appearance and are centered in the subperiosteum. If they ossify, they can contain fatty marrow.[ 20 ]

Subperiosteal hematoma. A 53 year old male with history of remote thigh trauma. (A) AP radiograph and (B) coronal CT image of left hip show a lesion (arrows) arising from the medial femoral cortex with central ossification (C) Axial T1W MRI image demonstrates a chronic subperiosteal hematoma that contains central fatty marrow (arrowhead) and cortical bone (arrow)

Stress fracture

Stress fractures may be related to fatigue, when excessive repetitive force is applied to a normal bone, or insufficiency, when normal stress is applied to abnormal bone such as in osteoporosis or Paget's disease. Common sites for stress fractures include the metatarsals, tarsals, and tibia.[ 21 ] Initially, stress fractures may not be visible on radiographs and are better detected on technetium-99 m pyrophosphate bone scintigraphy (bone scan) or MRI [ Figure 11 ]. With time, periosteal reaction and cortical resorption may be seen. A fracture line may be visible on radiographs, but could be better seen on computed tomography (CT). The fracture line is usually perpendicular to the cortex, and vertically oriented fractures can be difficult to detect. Radiographic features of stress fracture in the tibia can resemble a soleal line or osteoid osteoma, but can be differentiated from one another on CT [ Figure 12 ]. Moreover, if the periosteal reaction appears aggressive, it can mimic infection or an aggressive tumor.[ 22 ] The presence of a fracture line, lack of a soft tissue mass, and evidence of healing on follow-up studies should help distinguish stress fractures from other entities.

Stress fracture. A 68 year old female with right hip and thigh pain. (A) AP radiograph of the hip shows cortical thickening (arrow) in the lateral aspect of tibial shaft (B) Coronal and (C) axial CT images demonstrate a linear fracture line (arrows) within the cortical thickening

Axial CT images of the tibia show how CT can be helpful in distinguishing the soleal line (A) from a stress fracture (B) indicated by arrows

Myositis ossificans

Myositis ossificans is heterotopic ossification that occurs in muscle usually following trauma, although the patient may be unable to recall the precipitating trauma.[ 23 ] This commonly occurs in the upper and lower extremities, usually in the lateral muscles. Patients may be asymptomatic or present with pain, swelling, or an elevated erythrocyte sedimentation rate (ESR). Ossification develops 3-8 weeks after onset, beginning peripherally and progressing centrally. Initially, myositis ossificans forms faint irregular densities; but with time, a rim of mature lamellar bone and central osteoid matrix can develop [ Figure 13 ]. The MRI appearance is variable depending on the stage of development, and earlier on, can mimic a sarcoma as there may be enhancement following contrast administration.[ 24 ] Differentiation from an osteochondroma or osteosarcoma may also be difficult if the area of ossification is adherent to the adjacent bone. CT can be helpful in demonstrating a plane of soft tissue between the mass and the bony cortex. Myositis ossificans may be difficult to distinguish from an osteosarcoma even on biopsy specimens.[ 25 ]

Myositis ossificans. A 53 year old female with a palpable mass along the right distal tibia. (A) Lateral radiograph shows an oval nodule (arrow) with dense periphery at the anterior aspect of tibial shaft (B) Sagittal and (C) axial CT images demonstrate a peripheral rim of calcification and central ossification in the lesion (arrows) and a small cleft (black arrowheads) between the mass and the tibial cortex

Biceps tenodesis

In biceps tenodesis, the intra-articular portion of the long head of the biceps tendon is cut and the proximal portion of the tendon is reattached to the proximal humeral diaphysis.[ 26 ] The site of attachment can mimic a radiolucent lesion with a sclerotic border [ Figure 14 ]. This classic location along the proximal humerus should raise suspicion for this tumor mimicker, which can be confirmed by reviewing patients’ surgical notes.

Biceps tenodesis. A 58 year old female with history of rotator cuff and labral tear. AP radiograph of right shoulder shows a focal lucent lesion (arrow) in the proximal humeral shaft from a biceps tenodesis. Suture anchor on the humeral head is also noted from rotator cuff surgery

Bone marrow biopsy and bone graft donor sites

Bone marrow aspiration and biopsy for hematological diagnosis is most often obtained from the iliac bone via a posterior approach.[ 27 ] If the biopsy has been recently performed, there may be marrow edema or cystic changes in the region, which can be mistaken for a focal lesion [ Figure 15 ]. Similarly, bone graft donor sites can demonstrate edema in the early post-procedure period. In both cases, review of the patient's clinical history is essential to confirm that a procedure has been performed.

Bone marrow biopsy site. A 23 year old female with lymphoma and recent left iliac bone biopsy. Axial T2W fat-saturated MRI image shows a hyperintense lesion with irregular borders (arrow) in the left iliac bone, consistent with changes from a bone marrow biopsy

Particle disease

Particle disease can present as areas of radiolucency surrounding the hardware components, usually following arthroplasty.[ 28 ] However, unlike mechanical loosening, the lucent areas seen with particle disease typically do not follow the outline of the prosthesis [ Figure 16 ].[ 29 ] The arthroplasty components can incite a macrophage-mediated granulomatous response, which then stimulates osteoclast activity.[ 28 ] Particle disease can mimic osteolytic tumors or infection; however, particle disease can be distinguished by the presence of hardware and the fact that abnormal lucencies are seen on both sides of a joint.

Particle disease. An 82 year old male who had undergone total hip replacement for hip pain. (A) AP radiograph of the right hip shows multiple lucent lesions (arrows) on both sides of the right hip joint, abutting both the femoral and acetabular components (B) Axial CT image demonstrates multiple cavities (arrows) around the prosthesis, which do not confine to the outline of the prosthesis

Radiation changes

Initially, radiotherapy causes vascular congestion, edema, and decreased cellularity in the bone marrow.[ 30 ] This will cause decreased signal on T1W sequences and increased signal on T2W sequences [ Figure 17 ]. With time, the bone marrow will be replaced with fat and occasionally with fibrosis, with high signal on T1W and intermediate signal on T2W sequences.[ 30 ] There can be a clear line of demarcation along the borders of the radiation field. Irradiated bone can be at increased risk for insufficiency factures, osteonecrosis, and radiation-induced sarcomas.[ 31 ]

Radiation changes. A 59 year old female with history of endometrial cancer Salpingohysterectomy and radiation therapy. Axial short tau inversion recovery (STIR) MRI image shows a regional distribution of bony edema in the iliac bone and sacrum with demarcated borders (dotted lines), indicating the radiation field

Metabolic Disease and Arthritic Changes

Brown tumor of hyperparathyroidism.

Longstanding untreated hyperparathyroidism can result in osteolytic lesions known as brown tumors (osteoclastomas) [ Figure 18 ]. They can be seen in either primary or secondary hyperparathyroidism and are seen in 5% of patients with hyperparathyroidism.[ 32 ] However, the incidence has decreased with improved early diagnosis of the disease. The typical appearance of a brown tumor is a well-defined osteolytic lesion, which may have septations, be expansile, and can sometimes have aggressive features. Common sites include the long bones, ribs, pelvis, and facial bones.[ 33 ] The lesions improve with treatment, often becoming sclerotic. If lesions fail to improve in appearance with treatment, an alternative diagnosis should be considered.

Brown tumor of hyperparathyroidism. A 42-year-old female with history of parathyroid adenoma. Focused AP radiograph of the humerus shows multiple well-defined lytic lesions (arrows) in the right humeral shaft

Melorheostosis

Melorheostosis is a benign bone dysplasia characterized by sclerotic bone lesions, often described as “dripping candle wax.”[ 34 ] Melorheostosis is not a hereditary disorder and is often asymptomatic; however, when symptoms do occur, they include pain, limb deformities and contractures related to muscle and tendon shortening, skin disorders, and poor circulation.[ 35 ] There is an association with soft tissue hemangiomas and neurofibromas.[ 36 ] The lesions can be mistaken for a surface osteosarcoma or osteochondroma. On imaging, there is characteristic flowing cortical hyperostosis [ Figure 19 ] and can involve multiple contiguous bones in a sclerotomal distribution.[ 37 ] Low signal intensity is seen on all MRI sequences, but there may be surrounding soft tissue edema. The lesions may also be active on technetium-99 m pyrophosphate bone scintigraphy.[ 38 ]

Melorheostosis. A 43 year old male with knee pain. (A) Lateral lower leg radiograph and (B) sagittal CT image of the tibia demonstrate dense cortical thickening (arrows) along the posterior fibula that simulates dripping candle wax

Osteonecrosis

Ischemic necrosis of the bone and marrow can be due to a variety of causes including trauma, steroids, hemoglobinopathies, alcoholism, radiotherapy, and chemotherapy.[ 39 ] When osteonecrosis involves the epiphysis (avascular necrosis), it can lead to subchondral bony collapse and osteoarthritis. Initially, osteonecrosis may be occult on radiography; but over time, it can manifest as a central radiolucency with a sclerotic margin. It may mimic enchondromas, but lacks central calcifications. MRI is sensitive for detection of bone infarcts. Initially, these areas appear as non-specific regions of marrow edema; but with time, the characteristic features of an outer band of low signal associated with an inner band of high signal on non-fat-saturated T2W images (double line sign) can develop.[ 22 ]

Calcific tendinitis (resorptive phase)

Calcific tendinitis is a common cause of joint pain and stiffness, and is caused by the deposition of calcium hydroxyapatite crystals in the tendons.[ 40 ] The tendons of the rotator cuff and around the hip [ Figure 20 ] are most commonly involved; however, it can involve any tendon.[ 41 ] During the resorptive phase, calcific tendinitis can mimic an aggressive process such as infection or neoplasm.[ 42 ] Calcific tendinitis can be associated with erosions of the adjoining bone, mimicking a destructive bone lesion. This aggressive pattern is common along the posterior proximal femoral diaphysis. The process is typically self-limiting, but needle barbotage and steroid injection can provide symptomatic relief.[ 42 ]

Calcific tendinitis (resorptive phase). A 47 year old male with left thigh pain. (A) Axial and (B) coronal CT images show calcifications at the insertion site of the gluteus maximus tendon to the posterior femur (arrow). Mild cortical erosion is also noted at the gluteal insertion site (arrowhead)

Subchondral cyst (geode)

In osteoarthritis, defects in the overlying cartilage can allow synovium and joint fluid to enter the subchondral bone causing subchondral cysts (geodes). They are typically small, about the articular surface, and have a sclerotic margin [ Figure 21 ]. However, they can be large, but may extend down the shaft of a tubular bone mimicking a neoplasm.[ 22 ] CT can be helpful in demonstrating the sclerotic margin. On MRI, the lesion behaves like a cyst and is typically isointense to muscle on T1W images and hyperintense on T2W images. High T1 signal may occur in lesions that contain proteinaceous material, and internal enhancement may be seen if the lesions contain fibrous material. There should be evidence of osteoarthritis in the joint to support this diagnosis and changes are most often seen on both sides of the joint.[ 22 ]

Subchondral cyst. A 61 year old male with left knee pain. (A) AP radiograph of knee shows large subarticular lucencies with sclerotic rims (arrows) in the medial and lateral femoral condyles. There is narrowing of the joint space and osteophytosis (arrowheads) consistent with degenerative osteoarthritis (B) Coronal T2W fat-saturated MRI image demonstrates cystic lesions (arrows) abutting the narrowed joint space (arrowheads)

Osteomyelitis/Brodie's abscess

In acute osteomyelitis, the radiographic findings include areas of aggressive periostitis, cortical destruction, endosteal scalloping, and intracortical tunneling. There may be soft tissue swelling or gas formation. However, the radiographic findings may not be present for 1-2 weeks. MRI and technetium-99 m pyrophosphate bone scintigraphy (bone scintigraphy) are more sensitive in the detection of early osteomyelitis.[ 43 ] Subacute or chronic osteomyelitis can cause an intraosseous abscess (Brodie's abscess), commonly in the metaphysis of tubular bones [ Figure 22 ]. On radiographs, these lesions appear as single or multilobulated radiolucent lesions with surrounding sclerosis that fades toward the periphery. These lesions can mimic an osteoid osteoma or osteosarcoma.[ 44 ] Lesions without significant sclerosis can mimic Langerhans cell histiocytosis, chondroblastoma, giant cell tumor, and Ewing's sarcoma. CT can be helpful to delineate a sinus tract extending away from the central abscess, excluding other lesions.[ 45 ] Systemic signs of infection can be helpful; however, several of the lesions listed in the differential can also present with fever, pain, and other clinical signs of infection. Bone biopsy is often necessary for diagnosis and to identify an organism to guide appropriate antibiotic therapy.[ 43 ]

Osteomyelitis with Brodie's abscess. A 29 year old female with left lower leg pain. (A) AP radiograph of ankle demonstrates a faint radiolucency (arrow) in the distal tibial diaphysis (B) Coronal CT image shows that the lesion (arrow) is well demarcated with a non-sclerotic rim (C) Sagittal T2W fat-saturated MRI image shows the hyperintense intraosseous abscess (arrow) with surrounding marrow edema (arrowheads)

Tuberculosis infection of bone deserves special mention and has been called “the great mimicker.”[ 46 ] Most prevalent in underdeveloped countries, tuberculous osteomyelitis differs from pyogenic osteomyelitis as fever and pain can be absent and the symptoms are more insidious in onset.[ 47 ] Nearly any bone can be affected [ Figure 23 ] and it is primarily caused by hematogenous spread from other sites, most commonly lung.[ 47 ] Bony destruction, loss of normal T1 marrow signal, marrow enhancement, and adjacent abscess or septic arthritis can occur. Spinal involvement by tuberculosis is not uncommon and can differ from bacterial spinal infection in that the disc spaces are preserved until late in the disease due to the lack of proteolytic destructive enzymes by Mycobacterium tuberculosis.[ 47 , 48 ] Finally, due to the hematogenous nature of spread, multifocal lesions can occur in the spine and appendicular skeleton, mimicking malignancy.[ 47 , 48 ]

Tuberculous osteomyelitis. A 32 year old male with buttock pain. (A) Coronal T1W and (B) coronal T2W fat-saturated MRI images show marrow signal abnormality in the sacrum (arrows) (C) Coronal T2W fat-saturated MRI image shows hyperintense abscess (arrowheads) abutting the inferior border of sacral lesion (arrows). (Images courtesy of Dr. Aditya Daftary, MD)

Technical Artifacts

Humeral head - internal rotation view.

On internal rotation radiographs of the shoulder, a pseudolesion with a sclerotic border and radiolucent center can appear in the humeral head [ Figure 24 ]. A sharp sclerotic border is seen at the humeral neck as the diameter of the bone changes abruptly. The pseudolesion should not be seen on the external rotation or other views and should not be mistaken for an osteolytic lesion.

Humeral head pseudolesion. A 30 year old male with right shoulder pain. (A) Internal rotation view of right shoulder shows a lucent pseudolesion with a pseudosclerotic border (arrows) (B) This pseudolesion disappears on the external rotation view

Radial tuberosity - lateral view

The radial tuberosity is a normal anatomic structure in the proximal radius; however, on lateral projections, it is imaged en face and can appear as an ovoid radiolucent lesion [ Figure 25 ]. On other projections, the tuberosity becomes clear and the artifactual radiolucency disappears. The bony protuberance of an osteochondroma can mimic a radiolucent lesion when seen en face as well. To avoid this pitfall, it is important to review additional projections.

Radial tuberosity pseudolesion. A 33 year old female with medial elbow pain. (A) Lateral radiograph of elbow shows a lucent pseudolesion (arrows) in the radial tuberosity that disappears on the AP radiograph (B)

Wrap-around/aliasing in MRI

The field of view (FOV) in MRI refers to the anatomic region being imaged. Deciding on an appropriate FOV depends on the size of the structure being imaged and taking into account the trade-offs between spatial resolution and the signal-to-noise ratio. If a FOV is chosen which is smaller than the anatomy being imaged, wrap-around or aliasing artifacts can occur.[ 49 ] This can lead to image data that are outside the FOV being “wrapped around” and artifactually included within the image [ Figure 26 ]. This can be corrected by using a large enough FOV in the phase-encoding direction to include the entire body part or by using phase oversampling techniques during imaging.

Wrap-around/aliasing in MRI. A 47 year old male with lower buttock pain. Axial STIR MRI image shows a wrap-around/aliasing artifact from right hand (arrowhead) and mimicking a focal lesion of right femoral head (arrow)

Pulsation artifact on MRI

Pulsation of vascular structures can cause “ghosting” on MRI.[ 49 ] This can mimic bone lesions as artifactual image data from the vessels are superimposed onto bone [ Figure 27 ]. Repeating the imaging sequence after swapping the phase- and frequency-encoding directions can help to determine whether or not the lesion is real. To reduce pulsation artifact, one can place a saturation band over the vessels or not align the vessel and target lesion in the same phase-encoding direction.[ 50 ]

Pulsation artifact. A 31 year old male with right knee pain. Axial T1W MRI image shows a low signal rounded focus (arrow) in fibula, which is caused by pulsation artifact from popliteal artery (arrowhead) and mimics a tumor

External objects

External objects lying on a patient's skin can mimic bone lesions [ Figure 28 ]. This commonly occurs in the acute trauma setting when urgent imaging is required and the technique may be suboptimal.

External object. A 60 year old female with left hip pain. (A) Frog view of left hip shows a tiny radiolucency (arrow) in proximal femoral shaft, which disappears on (B) AP radiograph of left hip. The radiolucency is caused by a small hole in the side locator tag

Numerous normal anatomic variants and non-neoplastic lesions can have an imaging appearance, which raises concern for a bone tumor. Awareness of these lesions and an understanding of their discriminating features are essential to avoid unnecessary additional imaging and procedures. Knowing which lesions to leave alone or which ones require workup can prevent misdiagnosis and reduce patient anxiety.

Source of Support: Nil

Conflict of Interest: None declared.

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Synthetic Blood Stem Cells Herald New Era in Bone Marrow Transplants

Researchers have achieved a significant advancement by developing lab-generated blood stem cells that mirror those found in the human embryo, offering hope for personalized treatments for children with leukemia and bone marrow failure.

This breakthrough allows for the creation of transplantable blood cells from any cell of the patient, potentially transforming the lives of those with severe blood disorders. The successful application in immune-deficient mice opens the door to clinical trials and future therapies.

Breakthrough in Blood Stem Cell Research

Scientists in Melbourne have made a world-first breakthrough in creating blood stem cells that closely resemble those in the human body. The discovery could soon lead to personalized treatments for children with leukemia and bone marrow failure disorders.

The research, published today (September 2) in Nature Biotechnology , has overcome a major hurdle in producing human blood stem cells, which can create red cells, white blood cells, and platelets, that closely match those in the human embryo. Murdoch Children’s Research Institute (MCRI) led the study.

Enhancing Blood Stem Cell Development

MCRI Associate Professor Elizabeth Ng said the team had made a significant discovery in human blood stem cell development, paving the way for these lab-grown cells to be used in blood stem cell and bone marrow transplants.

“The ability to take any cell from a patient, reprogram it into a stem cell, and then turn these into specifically matched blood cells for transplantation will have a massive impact on these vulnerable patients’ lives,” she said.

Advancements in Lab-Generated Blood Stem Cells

“Prior to this study, developing human blood stem cells in the lab that were capable of being transplanted into an animal model of bone marrow failure to make healthy blood cells had not been achievable. We have developed a workflow that has created transplantable blood stem cells that closely mirror those in the human embryo.

“Importantly, these human cells can be created at the scale and purity required for clinical use.”

In the study, immune deficient mice were injected with the lab-engineered human blood stem cells. It found the blood stem cells became functional bone marrow at similar levels to that seen in umbilical cord blood cell transplants, a proven benchmark of success.

The research also found the lab-grown stem cells could be frozen prior to being successfully transplanted into the mice. This mimicked the preservation process of donor blood stem cells before being transplanted into patients.

Potential Treatments and Future Research

MCRI Professor Ed Stanley said the findings could lead to new treatment options for a range of blood disorders.

“Red blood cells are vital for oxygen transport and white blood cells are our immune defense, while platelets cause clotting to stop us bleeding,” he said. Understanding how these cells develop and function is like decoding a complex puzzle.

“By perfecting stem cell methods that mimic the development of the normal blood stem cells found in our bodies we can understand and develop personalized treatments for a range of blood diseases, including leukemias and bone marrow failure.”

MCRI Professor Andrew Elefanty said while a blood stem cell transplant was often a key part of lifesaving treatment for childhood blood disorders, not all children found an ideally matched donor.

“Mismatched donor immune cells from the transplant can attack the recipient’s own tissues, leading to severe illness or death,” he said.

“Developing personalized, patient-specific blood stem cells will prevent these complications, address donor shortages and, alongside genome editing, help correct underlying causes of blood diseases.”

Professor Elefanty said the next stage, likely in about five years with government funding, would be conducting a phase one clinical trial to test the safety of using these lab-grown blood cells in humans.

A Personal Journey Through Blood Disorder

Riya was diagnosed at the age of 11 with aplastic anemia, a rare and serious blood disorder where the body stops producing enough new blood cells.

Riya’s family, including parents Sonali and Gaurav Mahajan, were in India at the time when she started to feel fatigued, rapidly lost weight, and developed bruises on her thighs.

“We took Riya for a simple blood test, her very first one. But as soon as the results came in, we were told to rush her to the emergency department due to her being so low on platelets and red blood cells,” Sonali said.

Overcoming Challenges in Blood Disorder Treatment

“Riya was originally diagnosed with leukemia because the symptoms are very similar to aplastic anemia. When we got the eventual diagnosis, it was a complete shock and a condition we had never heard of before.

“The doctors told us she had bone marrow failure and she started needing regular platelet and blood transfusions to get her blood cell count up.”

Sonali said the family had already planned to return to Australia for Riya’s high school education, but the diagnosis fast-tracked the return.

“Once they were able to stabilize her, we were given a two-day window to fly her to Australia to be hospitalized,” she said.

The Impact of Stem Cell Research on Real Lives

“As soon as we got off the plane we went straight to The Royal Children’s Hospital. Within days Riya started therapy, but she never really responded to the medications.

“Eventually a bone marrow transplant was recommended due to the amount of transfusions she was needing to have and the concerns around possible long-term complications.”

Sonali said over six months they struggled to find a perfectly matched donor and were losing hope. Despite being a half match, Sonali, following specialist advice, became her daughter’s donor.

Following the bone marrow transplant in June last year, Riya remained in the hospital for three months where she had minor complications.

Without a perfect donor match, Riya’s platelet count took more time to return to normal, she required longer immunosuppressive therapy and was more susceptible to infections. Riya only recently started to be re-vaccinated.

“She had a weakened immune system for a long time after the transplant but thankfully once she was discharged from the hospital she hasn’t needed another transplant,” Sonali said.

Riya, 14, said after a painful few years she was now feeling well, took hydrotherapy classes and was glad to be back at school with her friends.

Sonali said the new MCRI-led research on blood stem cells was a remarkable achievement.

“This research will come as a blessing to so many families,” she said. The fact that one day there could be targeted treatments for children with leukemia and bone marrow failure disorders is life-changing.”

Reference: “Long-term engrafting multilineage hematopoietic cells differentiated from human induced pluripotent stem cells” by Elizabeth S. Ng, Gulcan Sarila, Jacky Y. Li, Hasindu S. Edirisinghe, Ritika Saxena, Shicheng Sun, Freya F. Bruveris, Tanya Labonne, Nerida Sleebs, Alexander Maytum, Raymond Y. Yow, Chantelle Inguanti, Ali Motazedian, Vincenzo Calvanese, Sandra Capellera-Garcia, Feiyang Ma, Hieu T. Nim, Mirana Ramialison, Constanze Bonifer, Hanna K. A. Mikkola, Edouard G. Stanley and Andrew G. Elefanty, 2 September 2024, Nature Biotechnology . DOI: 10.1038/s41587-024-02360-7

Prof Elefanty, Prof Stanley and Associate Professor Ng are also Principal Investigators at the Melbourne node of the Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), a global consortium, that aims to pave the way for future stem cell-based treatments.

Researchers from the University of Melbourne, Peter MacCallum Cancer Centre, University of California Los Angeles, University College London, and the University of Birmingham also contributed to the findings.

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Bone Cancer

• What Is Bone Cancer?
• Key Statistics About Bone Cancer
• What’s New in Bone Cancer Research?
• Risk Factors for Bone Cancer
• What Causes Bone Cancer?
• Can Bone Cancer Be Prevented?
• Can Bone Cancer Be Found Early?
• Signs and Symptoms of Bone Cancer

Tests for Bone Cancer

• Bone Cancer Stages
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• Questions to Ask About Bone Cancer
• Surgery for Bone Cancer
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• Chemotherapy for Bone Cancer
• Targeted Therapy and Other Drugs for Bone Cancer
• Treating Specific Types of Bone Cancer
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• If You Have Bone Cancer

Primary bone cancers are usually found when  signs or symptoms  a person is having prompt them to visit a doctor.

Medical history and physical exam

Imaging tests.

The information here focuses on primary bone cancers (cancers that start in bones) that most often are seen in adults. Information on  Osteosarcoma,   Ewing Tumors  (Ewing sarcomas), and  Bone Metastasis  is covered separately.

Symptoms and the results of physical exams and imaging tests might suggest that a person has bone cancer. But in most cases, doctors need to confirm this by taking and testing a tissue or cell sample (a procedure known as a biopsy ).

It’s important for doctors to distinguish primary bone cancers from cancers that have spread to the bones from other parts of the body ( bone metastasis ), as well as from bone tumors that are benign (not cancer) and from other types of bone problems. These conditions might need different types of treatment.

Accurate diagnosis of a bone tumor often depends on combining information about which bone and what part of the bone is affected, how it looks on imaging tests, and what the tumor cells look like under a microscope.

If a bone cancer is found, other tests might then be needed to learn more about it.

If a person has signs or symptoms that suggest they might have a bone tumor, the doctor will want to take a complete medical history to find out more about the symptoms.

A physical exam can sometimes provide information about a possible tumor. For example, the doctor may be able to see or feel an abnormal mass.

The doctor may also look for problems in other parts of the body. When adults have cancer in the bones, it’s most often the result of cancer that started somewhere else and then spread to the bones (bone metastasis).

After the exam, if the doctor suspects it could be bone cancer (or another type of bone tumor), more tests will be done. These might include imaging tests, biopsies, and/or lab tests.

Imaging tests use x-rays, magnetic fields, or radioactive substances to create pictures of the inside of the body. Imaging tests might be done for a number of reasons, including:

• To help find out if a suspicious area might be cancer
• To help determine if a cancer might have started in another part of the body
• To learn how far cancer has spread
• To help determine if treatment is working
• To look for signs that the cancer might have come back

People who have or might have bone cancer will have one or more of these tests. For more information on these tests, see Imaging (Radiology) Tests for Cancer .

An x-ray of the bone is often the first test done if some type of bone tumor is suspected. Tumors might look “ragged” instead of solid on an x-ray, or they might look like a hole in the bone. Sometimes doctors can see a tumor that might extend into nearby tissues (such as muscle or fat).

Doctors might strongly suspect an abnormal area is a bone cancer by the way it appears on an x-ray, but usually a biopsy (described below) is needed to tell for sure.

Adults with bone tumors might have a chest x-ray done to see if the cancer has spread to the lungs. But this test isn't needed if a chest CT scan (discussed below) has been done.

Magnetic resonance imaging (MRI)

MRI scans create detailed images of the inside of the body using radio waves and strong magnets instead of x-rays, so no radiation is involved. A contrast material called gadolinium is often injected into a vein before the scan to better see details.

An MRI is often done to get a more detailed look at an abnormal area of bone seen on an x-ray. MRIs can usually show if it’s likely to be a tumor, an infection, or some type of bone damage from another cause.

MRIs can help determine the exact extent of a tumor, as they can show the marrow inside bones and the soft tissues around the tumor, including nearby blood vessels and nerves. MRIs can also show any small bone tumors several inches away from the main tumor (called skip metastases ). Knowing the extent of tumor is very important when planning surgery.

Computed tomography (CT) scan

A CT scan combines many x-ray pictures to make detailed cross-sectional images of parts of the body. 

CT scans aren’t usually as helpful as MRIs in showing the detail in and around bone tumors. But they are often done to look for possible cancer spread in other parts of the body, such as the lungs, liver, or other organs.

CT scans can also be used to guide a biopsy needle into a tumor (a CT-guided needle biopsy ). For this test, you stay on the CT scanning table while the doctor moves a biopsy needle toward the tumor. CT scans are repeated until the tip of the needle is within the mass. (See Needle biopsy below.)

A bone scan can show if a cancer has spread to other bones, and is often part of the workup for people with bone cancer. This test is useful because it can show the entire skeleton at once. A positron emission tomography (PET) scan, described below, can often provide similar information, so a bone scan might not be needed if a PET scan is done.

For this test, a small amount of low-level radioactive material is injected into the blood and travels to the bones. A special camera that can detect the radioactivity then creates a picture of the skeleton.

Areas of active bone changes attract the radioactivity and appear as “hot spots” on the skeleton. Hot spots may suggest areas of cancer, but other bone diseases can also cause the same pattern. To make an accurate diagnosis, other tests such as plain x-rays, MRI scans, or even a bone biopsy might be needed.

Positron emission tomography (PET or PET scan)

For a PET scan , a form of radioactive sugar (known as FDG) is injected into the blood. Because cancer cells in the body are growing quickly, they absorb large amounts of the sugar. A special camera then creates a picture of areas of radioactivity in the body. The picture is not detailed like a CT or MRI scan, but it provides useful information about the whole body.

PET scans can help show the spread of bone cancer to the lungs, other bones, or other parts of the body. They can also be used to see how well the cancer is responding to treatment.

Many machines can do a PET and CT scan at the same time ( PET/CT scan ). This lets the doctor compare areas of higher radioactivity on the PET scan with the more detailed appearance of that area on the CT scan.

The results of imaging tests might strongly suggest that a person has bone cancer, but a biopsy (removing some of the abnormal area and checking it under a microscope and with other lab testing) is usually the only way to be certain.

If the tumor is most likely a primary bone cancer, it’s very important that the biopsy is done by doctors experienced in treating bone tumors. Whenever possible, the biopsy and surgical treatment should be planned together, and the same doctor should do both. Proper planning of the biopsy can help prevent later complications and might reduce the amount of surgery needed later on.

Sometimes the wrong kind of biopsy can make it hard for the surgeon to later remove all of the cancer, which might then require more extensive surgery. It might also increase the risk of the cancer spreading.

The type of biopsy done is based on whether the tumor looks benign (not cancer) or malignant (cancer) and exactly what type of tumor it most likely is (based on imaging tests, the patient’s age, and where the tumor is). Some kinds of bone tumors can be diagnosed from needle biopsy samples, but larger samples (from a surgical biopsy) are often needed to diagnose other types. Plans to remove the entire tumor during the biopsy will also impact the type of biopsy done.

Needle biopsy

For these biopsies, the doctor uses a hollow needle to remove a small cylinder of tissue from the tumor. The biopsy is usually done with local anesthesia, where numbing medicine is injected into the skin and other tissues over the biopsy site. In some cases, the patient might need sedation or general anesthesia (where the patient is asleep).

Often, the doctor can aim the needle by feeling the suspicious area if it's near the surface of the body. If the tumor can’t be felt because it's too deep, the doctor can guide the needle into the tumor using an imaging test such as an ultrasound or CT scan. These types of image-guided biopsies are usually done by a doctor who is an interventional radiologist .

There are 2 types of needle biopsies:

• A core needle biopsy uses a large needle to remove a cylinder of tissue. This is the most common type of needle biopsy used for bone tumors.
• A fine needle aspiration (FNA) biopsy uses a very thin needle on the end of a syringe to suck out a small amount of fluid and some cells from the tumor. This type of biopsy is less likely to be helpful for bone tumors, as the smaller needle might not be able to get through the bone. And even if it can be done, it might not remove enough of a sample for testing. But FNA can sometimes be useful for checking abnormal areas in other parts of the body for cancer cells.

Surgical (open) biopsy

For this type of biopsy, a doctor (typically an orthopedic surgeon ) cuts through the skin to reach the tumor. If only a piece of it is removed, it is called an incisional biopsy . If the entire tumor is removed (not just a small piece), it's called an excisional biopsy .

These biopsies are often done in an operating room with the patient under general anesthesia (in a deep sleep). They can also be done using a nerve block, which numbs a large area of the body.

Again, it’s important that the biopsy is done by an expert in bone tumors, or it could result in problems later on. For example, if the tumor is on the arm or leg and the biopsy isn’t done properly, it might lower the chances of saving the limb. If possible, the incision for the biopsy should be lengthwise along the arm or leg because this is the way the incision will be made during the operation to remove the cancer. The entire scar of the original biopsy will also most likely need to be removed, so making the biopsy incision this way means less tissue will need to be removed later on.

Testing the biopsy samples

All samples removed by biopsy are sent to a pathologist (a doctor specializing in lab tests) to be looked at with a microscope. If cancer cells are seen, other types of lab tests might also be done to learn more about the exact type of cancer. 

The pathologist will also assign the cancer a grade , which is a measure of how quickly it is likely to grow and spread, based on how the tumor cells look. Cancers that look somewhat like normal bone tissue are described as low grade (and tend to grow more slowly), while those that look very abnormal are called high grade. For more on grading, see Bone Cancer Stages .

Blood tests

Blood tests are not needed to diagnose bone cancer, but they may be helpful once a diagnosis is made. For example, high levels of chemicals in the blood such as alkaline phosphatase and lactate dehydrogenase (LDH) can suggest that the cancer may be more advanced.

Other tests such as blood cell counts and blood chemistry tests are done before surgery and other treatments to get a sense of a person’s overall health. These tests can also be used to monitor the person’s health while they are getting treatments such as chemotherapy.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as editors and translators with extensive experience in medical writing.

Anderson ME, Dubois SG, Gebhart MC. Chapter 89: Sarcomas of bone. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds.  Abeloff’s Clinical Oncology . 6th ed. Philadelphia, Pa:Elsevier; 2020.

Hornicek FJ, McCarville B, Agaram N. Bone tumors: Diagnosis and biopsy techniques. UpToDate. 2020. Accessed at https://www.uptodate.com/contents/bone-tumors-diagnosis-and-biopsy-techniques on August 28, 2020.

National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: Bone Cancer. Version 1.2020. Accessed at www.nccn.org/professionals/physician_gls/pdf/bone.pdf on July 28, 2020.

Last Revised: June 17, 2021

American Cancer Society medical information is copyrighted material. For reprint requests, please see our Content Usage Policy .

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More in Bone Cancer

• About Bone Cancer
• Causes, Risk Factors, and Prevention
• Early Detection, Diagnosis, and Staging
• After Treatment

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