Bone cancer has no single cause. In most cases, it develops when something goes wrong with the genes that control how bone cells grow and divide, but what triggers that error varies. Inherited conditions, prior radiation treatment, certain bone diseases, and rapid bone growth during adolescence all play a role, though many people diagnosed with bone cancer have no identifiable risk factor at all.
Primary bone cancer (cancer that starts in the bone itself, rather than spreading there from somewhere else) is rare. In the United States, roughly 650 to 700 new cases are diagnosed in children and young adults each year, including about 400 cases of osteosarcoma and 200 cases of Ewing sarcoma. Understanding what drives these cancers helps explain who’s most at risk and why.
Genetic Errors That Let Bone Cells Grow Unchecked
Healthy bone cells have built-in brakes that stop them from multiplying out of control. Two of the most important brakes are proteins produced by the TP53 and RB1 genes. When these genes are damaged or switched off, bone cells lose the ability to self-regulate and can become cancerous. In osteosarcoma, the most common primary bone cancer, TP53 is frequently disrupted. Researchers have found this specific mutation in roughly half of osteosarcoma tumor samples studied.
Beyond those two genes, signaling pathways that normally guide immature bone cells toward becoming mature, healthy bone tissue can also go haywire. When the molecular signals that control bone cell maturation are disrupted, immature cells keep dividing instead of settling into their final form. This runaway proliferation of immature bone-forming cells is a hallmark of osteosarcoma.
Inherited Syndromes That Raise Risk
Some people are born with a genetic predisposition to bone cancer. Two inherited conditions stand out.
Li-Fraumeni syndrome is caused by an inherited mutation in the TP53 gene. People with this syndrome face a 50% chance of developing some form of cancer by age 30 and a 90% chance by age 60. Their risk of osteosarcoma specifically is estimated at 107 times that of the general population. About 12% of people with Li-Fraumeni syndrome develop osteosarcoma, and the condition accounts for roughly 5% of all osteosarcoma cases in patients under 30.
Hereditary retinoblastoma is a rare childhood eye cancer caused by mutations in the RB1 gene. Children who survive it have excellent long-term survival from the eye cancer itself, but they carry a 69-fold increased risk of osteosarcoma later in life. If they also received radiation therapy for the retinoblastoma, that risk can jump to 400 times the normal rate.
Prior Radiation Therapy
Radiation treatment for a previous cancer is one of the clearest environmental causes of bone cancer. The risk climbs with dose: radiation below a certain threshold carries negligible risk, while high-dose treatments dramatically increase the chance of a secondary bone tumor forming in the irradiated area years later.
These radiation-induced bone cancers don’t appear quickly. The average gap between radiation treatment and a secondary bone cancer diagnosis is about 16 years in adults and closer to 9 to 10 years in young children. Among 1,200 osteosarcoma cases diagnosed at Memorial Sloan Kettering Cancer Center, 5.5% were directly linked to prior radiation. Radiation-induced bone cancers tend to be aggressive, with high rates of spreading to other parts of the body.
Paget’s Disease of Bone
Paget’s disease is a chronic condition in which the normal cycle of bone breakdown and rebuilding goes into overdrive, producing enlarged, misshapen bones. It primarily affects people over 50. In a small percentage of patients, the disordered bone growth tips into outright malignancy. Estimates put the rate of osteosarcoma developing in Paget’s disease patients at roughly 0.1% to 1%.
That sounds low, but Paget’s disease is common enough that it represents a meaningful source of osteosarcoma in older adults, an age group where primary bone cancer is otherwise unusual. The genetic link involves a gene called SQSTM1, which regulates how bone-resorbing cells respond to growth signals. Mutations in this gene make those cells overreact, accelerating bone turnover and creating conditions where cancerous changes are more likely.
Stem Cell Transplants
People who receive stem cell (hematopoietic) transplants for blood cancers or other conditions face an elevated risk of secondary cancers afterward. A large population-based study in Taiwan found that bone cancer carried the highest secondary cancer risk among transplant recipients, with a nearly 28-fold increase compared to the general population. The reasons likely involve a combination of prior chemotherapy, radiation used to prepare for the transplant, and the immune suppression that follows.
Age, Growth Spurts, and Demographics
Bone cancer is strongly linked to periods of rapid bone growth. Osteosarcoma peaks during the adolescent growth spurt, typically between ages 10 and 20, when bones are lengthening quickly. The most common sites are the ends of the long bones in the legs and arms, exactly where the fastest growth occurs. Taller children appear to be at slightly higher risk, which further supports the connection between rapid bone growth and tumor development.
Ewing sarcoma, the second most common bone cancer in young people, also appears primarily in teenagers, though it can occur in children and in adults through their 20s and 30s. It’s more common in males than females and occurs most often in non-Hispanic White people and American Indian and Alaska Native populations. Ewing sarcoma is very rare among African Americans, a disparity that researchers believe is driven by genetic differences rather than environmental ones.
Chondrosarcoma, a cancer of cartilage cells, follows a different pattern entirely. It’s most common in adults over 40 and has a notably better prognosis than other bone cancers, with an overall five-year survival rate of about 75%. When it has already spread at the time of diagnosis, though, that drops to around 28%.
Does a Bone Injury Cause Cancer?
This is one of the most common questions people have, and the answer is reassuring. There is very little scientific evidence that a knock, fracture, or other injury to a bone causes cancer. What likely happens is that the injury causes swelling or pain that leads to imaging, which then reveals a tumor that was already growing. It’s also possible that a bone weakened by an existing cancer is simply more prone to breaking, making the fracture the first noticeable symptom rather than the cause.
Why Most Cases Have No Clear Cause
Despite all of these known risk factors, the majority of people who develop bone cancer don’t have an inherited syndrome, prior radiation exposure, or Paget’s disease. Their cancers arise from random genetic errors that accumulate in bone cells over time. Cells divide billions of times over a lifetime, and each division carries a small chance of introducing a harmful mutation. When enough of these mutations pile up in the wrong genes, particularly in genes that control cell growth and repair, cancer can result. This element of biological randomness is why bone cancer can strike people with no risk factors at all.