Several research groups are investigating cancer stem cells and their potential to cause tumors along with genes and proteins causative in different phenotypes.Radiotherapy for unrelated conditions may be a rare cause.

- Familial cases where the deletion of chromosome 13q14 inactivates the retinoblastoma gene is associated with a high risk of osteosarcoma development.

- Bone dysplasias, including Paget's disease of bone, fibrous dysplasia, enchondromatosis, and hereditary multiple exostoses, increase the risk of osteosarcoma.

- Li–Fraumeni syndrome (germline TP53 mutation) is a predisposing factor for osteosarcoma development.

- Rothmund–Thomson syndrome (i.e. autosomal recessive association of congenital bone defects, hair and skin dysplasias, hypogonadism, and cataracts) is associated with increased risk of this disease.

- Large doses of Sr-90 emission from nuclear reactor, nicknamed bone seeker increases the risk of bone cancer and leukemia in animals, and is presumed to do so in people.

Despite persistent rumors suggesting otherwise, there is no clear association between water fluoridation and cancer or deaths due to cancer, both for cancer in general and also specifically for bone cancer and osteosarcoma. Series of research concluded that concentration of fluoride in water doesn't associate with osteosarcoma. The beliefs regarding association of fluoride exposure and osteosarcoma stem from a study of US National Toxicology program in 1990, which showed uncertain evidence of association of fluoride and osteosarcoma in male rats. But there is still no solid evidence of cancer-causing tendency of fluoride in mice. Fluoridation of water has been practiced around the world to improve citizens' dental health. It is also deemed as major health success. Fluoride concentration levels in water supplies are regulated, such as United States Environmental Protection Agency regulates fluoride levels to not be greater than 4 milligrams per liter. Actually, water supplies already have natural occurring fluoride, but many communities chose to add more fluoride to the point that it can reduce tooth decay. Fluoride is also known for its ability to cause new bone formation. Yet, further research shows no osteosarcoma risks from fluoridated water in humans. Most of the research involved counting number of osteosarcoma patients cases in particular areas which has difference concentrations of fluoride in drinking water. The statistic analysis of the data shows no significant difference in occurrences of osteosarcoma cases in different fluoridated regions. Another important research involved collecting bone samples from osteosarcoma patients to measure fluoride concentration and compare them to bone samples of newly diagnosed malignant bone tumors. The result is that the median fluoride concentrations in bone samples of osteosarcoma patients and tumor controls are not significantly different. Not only fluoride concentration in bones, Fluoride exposures of osteosarcoma patients are also proven to be not significantly different from healthy people.

Treatment of bone tumors is highly dependent on the type of tumor.

A bone tumor (also spelled bone tumour) is a neoplastic growth of tissue in bone. Abnormal growths found in the bone can be either benign (noncancerous) or malignant (cancerous).

Average five-year survival in the United States after being diagnosed with bone and joint cancer is 67%.

Recurrence rate of solid form of tumour is lower than classic form.

Prognosis depends on how early the cancer is discovered and treated. For the least aggressive grade, about 90% of patients survive more than five years after diagnosis. People usually have a good survival rate at the low grade volume of cancer. For the most aggressive grade, only 10% of patients will survive one year.

Tumors may recur in the future. Follow up scans are extremely important for chondrosarcoma to make sure there has been no recurrence or metastasis, which usually occurs in the lungs.

Prognosis is separated into three groups.

- Stage I osteosarcoma is rare and includes parosteal osteosarcoma or low-grade central osteosarcoma. It has an excellent prognosis (>90%) with wide resection.

- Stage II prognosis depends on the site of the tumor (proximal tibia, femur, pelvis, etc.), size of the tumor mass, and the degree of necrosis from neoadjuvant chemotherapy. Other pathological factors such as the degree of p-glycoprotein, whether the tumor is cxcr4-positive, or Her2-positive are also important, as these are associated with distant metastases to the lung. The prognosis for patients with metastatic osteosarcoma improves with longer times to metastases, (more than 12 months to 4 months), a smaller number of metastases, and their resectability. It is better to have fewer metastases than longer time to metastases. Those with a longer length of time (more than 24 months) and few nodules (two or fewer) have the best prognosis, with a two-year survival after the metastases of 50%, five-year of 40%, and 10-year of 20%. If metastases are both local and regional, the prognosis is worse.

- Initial presentation of stage III osteosarcoma with lung metastases depends on the resectability of the primary tumor and lung nodules, degree of necrosis of the primary tumor, and maybe the number of metastases. Overall survival prognosis is about 30%.

Deaths due to malignant neoplasms of the bones and joints account for an unknown number of childhood cancer deaths. Mortality rates due to osteosarcoma have been declining at about 1.3% per year. Long-term survival probabilities for osteosarcoma have improved dramatically during the late 20th century and approximated 68% in 2009.

While the exact cause of enchondroma is not known, it is believed to occur either as an overgrowth of the cartilage that lines the ends of the bones, or as a persistent growth of original, embryonic cartilage.

The cause is unknown. Patients may have a history of enchondroma or osteochondroma. A small minority of secondary chondrosarcomas occur in patients with Maffucci syndrome and Ollier disease.

It has been associated with faulty isocitrate dehydrogenase 1 and 2 enzymes, which are also associated with gliomas and leukemias.

An enchondroma may occur as an individual tumor or several tumors. The conditions that involve multiple lesions include the following:

- Ollier disease (enchondromatosis) - when multiple sites in the body develop the tumors. Ollier disease is very rare.

- Maffucci's syndrome - a combination of multiple tumors and angiomas (benign tumors made up of blood vessels).

Most cases of SPB progress to multiple myeloma within 2–4 years of diagnosis, but the overall median survival for SPB is 7–12 years. 30–50% of extramedullary plasmacytoma cases progress to multiple myeloma with a median time of 1.5–2.5 years. 15–45% of SPB and 50–65% of extramedullary plasmacytoma are disease free after 10 years.

It is common in age group of 10–30 years. It is second most common tumor of spine and commonest benign tumor of pelvis in pediatric population. Incidence is slightly more in males than females (1.3:1).

Mesenchymal chondrosarcoma is a form of malignant chondrosarcoma. Unlike most chondrosarcomas, mesenchymal chondrosarcoma grows rapidly, tends to spread, and occurs more often in children and young adults than in older adults.

Type II collagen can help distinguish it from other tumors.

Plasmacytomas are a rare form of cancer. SPB is the most common form of the disease and accounts for 3-5% of all plasma cell malignancies. The median age at diagnosis for all plasmacytomas is 55. Both SPB and extramedullary plasmacytoma are more prevalent in males; with a 2:1 male to female ratio for SPB and a 3:1 ratio for extramedullary plasmacytoma.

Age and gender have an effect on the incidence of these lesions; they are more prevalent in women than men (though still common in both genders), and they appear more frequently with age. Due to the standard of medical care and screening in developed countries, it is increasingly rare for primary hyperparathyroidism to present with accompanying bone disease. This is not the case in less developed nations, however, and the two conditions are more often seen together.

An osteoid osteoma is a benign bone tumor that arises from osteoblasts and was originally thought to be a smaller version of an osteoblastoma. Osteoid osteomas tend to be less than 1.5 cm in size. The tumor can be in any bone in the body but are most common in long bones, such as the femur and tibia. They account for 10 to 12 percent of all benign bone tumors. "Osteoid osteomas may occur at any age, and are most common in patients between the ages of 4 and 25 years old. Males are affected approximately three times more commonly than females."

Pain may be relieved by nonsteroidal anti-inflammatory drugs.

Treatment varies based on the health of the patient. If he/she is otherwise healthy and is not significantly bothered by the pain, the tumor is treated symptomatically with anti-inflammatories. If this therapy fails or the location of the tumor could lead to growth disturbances, scoliosis, or osteoarthritis, surgical or percutaneous ablation may be considered. If surgery is preferred, the individual may be referred to a podiatrist or an orthopedic surgeon to perform the procedure. Post-surgery therapy and strengthening may be needed, depending on the tumor location and health of the individual. While shown to be effective, surgical resection has many potential complications, including difficult intraoperative identification of the tumor, local recurrence from incomplete resection, and resection of weight bearing bone that can necessitate prolonged hospital stays and complicate recovery.

Recently, CT guided radiofrequency ablation has emerged as a less invasive alternative to surgical resection. In this technique, which can be performed under conscious sedation, a RF probe is introduced into the tumor nidus through a cannulated needle under CT guidance and heat is applied locally to destroy tumor cells. Since the procedure was first introduced for the treatment of osteoid osteomas in the early 1990s, it has been shown in numerous studies to be less invasive and expensive, to result in less bone destruction and to have equivalent safety and efficacy to surgical techniques, with 66 to 96% of patients reporting freedom from symptoms. While initial success rates with RFA are high, symptom recurrence after RFA treatment has been reported, with some studies demonstrating a recurrence rate similar to that of surgical treatment. As of July 17, 2014, treatment with incisionless surgery utilizing an MRI to guide high-intensity ultrasound waves to destroy a benign bone tumor in the leg has been demonstrated.

Bone metastases, or metastatic bone disease, is a class of cancer metastases that results from primary tumor invasion to bone. Bone-originating primary tumors such as osteosarcoma, chondrosarcoma, and Ewing's sarcoma are rare. Unlike hematological malignancies that originate in the blood and form non-solid tumors, bone metastases generally arise from epithelial tumors and form a solid mass inside the bone. Bone metastases cause severe pain, characterized by a dull, constant ache with periodic spikes of incident pain.

Bone lesions are caused by an imbalance of regulatory factors, characterized by an increased depletion and resorption of old bone tissue and a decrease in bone rebuilding, known as bone remodeling. This imbalance is due to a flooding of regulatory factors released by specific tumors, thus overwhelming the tissue repair system and resulting in these lesions. The over-activity of osteoclasts can also cause hypercalcemia, which can cause damage to the kidneys and requires additional medication and monitoring.

In multiple myeloma, an increased number of myeloma cells block osteoblasts from creating new bone, while these cancerous cells also release factors that cause an upregulation on osteoclasts, causing an increasing in bone tissue resorption and an overall breakdown of bone integrity. This breakdown often begins in the bone marrow near tumor sites and spreads outward to the surface of the implicated bone.

The most common cancers that metastasize to osteolytic lesions are prostate, thyroid, lung and breast, though any cancer can cause bone lesions. Lesions are most often found in larger bones, such as the skull, pelvis, radius, and femur.

Osteochondromas are benign lesions and do not affect life expectancy. Complete excision of osteochondroma is curative and the reoccurrences take place when the removal of tumor is incomplete. Multiple reoccurrences in a well-excised lesion indicate that it may be malignant. The risk of malignant transformation takes place in 1–5% of individuals. If any symptoms of cancerous tumor takes place, then the patient should be evaluated by a bone specialist. No treatment is necessary for Solitary osteochondromas that are asymptomatic. Treatments for solitary osteochondroma are careful observation over time and taking regular x-rays to monitor any changes in the tumor. If the lesion is causing pain with activity, nerve or vessel impingement, or if the bone growth has fully matured and the presence of a large cartilage cap is prominent, then it is advised that the tumor be surgically removed.

Osteochondromas have a low rate of malignancy (<1%) and resection of the tumor is suggested if symptoms such as pain, limitation of movement, or impingement on nerves or vessels occur. Resection of the tumor also takes place when the tumor increases in size and progresses towards malignancy. During surgical resection, the entire lesion along with the cartilaginous cap should be removed to minimize any chances of reoccurrences. Surgical treatment becomes the sole treatment of choice if common complications such as fractures, symptoms of peripheral nerves such as paresthesia, paraplegia, peroneal neuropathy, and upper limb neuropathy take place. A prophylactic resection is suggested if the lesion lies next to a vessel.

Depending on the size and location of the tumor, the time it takes to return to normal daily activities varies between individuals. Limitation on some activities is advised if pain or discomfort persists after surgical excision.

An osteolytic lesion (from the Greek words for "bone" (ὀστέον), and "to unbind" (λύειν)) is a softened section of a patient's bone formed as a symptom of specific diseases, including breast cancer and multiple myeloma. This softened area appears as a hole on X-ray scans due to decreased bone density. Osteolytic lesions can cause pain, increased risk of bone fracture, and spinal chord compression. These lesions can be treated using biophosphonates or radiation, though new solutions are being tested in clinical trials.

One person in every 100,000 is affected. Ollier disease is not normally diagnosed until toddler years because it is not very visible.

Limited normal functions and movements are caused by osteochondromas growing slowly and inwardly. The majority of osteochondromas are symptomless and are found incidentally. Each individual with osteochondroma may experience symptoms differently and most of the time individuals will experience no symptoms at all. Some of the most common symptoms are a hard immobile painless palpable mass, adjacent muscle soreness, and pressure or irritation with heavy exercising.

Major symptoms arise when complications such as fractures, bone deformity or mechanical joint problems occur. If the occurrence of an osteochondroma is near a nerve or a blood vessel, the affected limb can experience numbness, weakness, loss of pulse or color change. Periodic changes in the blood flow can also take place. Approximately 20% of patients experiencing nerve compression commonly acknowledge vascular compression, arterial thrombosis, aneurysm, and pseudoaneurysm. Formation of pseudoaneurysm and venous thrombosis lead to claudication, pain, acute ischemia, and symptoms of phlebitis. If the tumor is found under a tendon, it can cause pain during movement causing restriction of joint motion. Pain can also occur due to bursal inflammation, swelling or fracture at the base of the tumor stalk. Some of the clinical signs and symptoms of malignant osteochondroma are pain, swelling, and mass enlargement.

Acidosis is the increased acidity in a given location, whether it is blood, urine, or tissues. Osteoclasts generate extracellular protons, lowering the pH of the extracellular matrix (ECM) around the osteoclast to approximately 4.5. Nociceptors in the bone trigger a pain response in the brain in response to this acidosis. It is thought that this is the primary source of the dull, chronic pain experienced by patients with bone metastasis.

The uncoupled regulation of the osteoclasts and osteoblasts leads to malformation of the bone. Malformed bones are unable to withstand the normal mechanical stresses placed on them in day-to-day activity, leading to fractures, spinal compression, and spinal instability. Malformed bones may also mechanically trigger pain receptors both within the bone and in the surrounding tissue.

The disease has been reported to affect 3 per 1000 infants younger than 6 months in the United States. No predilection by race or sex has been established. Almost all cases occur by the age of 5 months. The familial form is inherited in an autosomal dominant fashion with variable penetrance. The familial form tends to have an earlier onset and is present at birth in 24% of cases, with an average age at onset of 6.8 weeks. The average age at onset for the sporadic form is 9–11 weeks.

Cortical hyperostosis is a potential side effect of long-term use of prostaglandins in neonates.

Myxoid chondrosarcoma is a type of Chondrosarcoma.

It has been associated with a t(9;22) (q22;q12) EWS/CHN gene fusion.