Understanding Osteosarcoma Causes and Prevention Possibilities

When a child is seriously ill, parents understandably want to know why, and hope that knowing the cause will show ways to protect other children – or children they may have in the future. A cancer diagnosis makes finding answers about what went wrong, and if anything could have prevented it, feel especially important. However, that need to be able to do something meets the difficult fact that most childhood cancers come about unexpectedly, and with no causes that parents could have altered. 

The osteosarcoma causes are complicated genetic problems which happen at random as bone grows – not things to do with how a family lives, what a child is exposed to, or decisions parents make. It’s helpful to realise how these things work in biology, so that people can put energy into helping the child get through treatment, rather than feeling bad about things they couldn’t have changed. There aren’t many ways to prevent osteosarcoma at the moment, but research is slowly revealing things that might raise risk, and which could one day lead to ways to protect against the illness. 

Most Cases are Due to Random Genetic Changes 

Around 95% of osteosarcoma cases aren’t linked to any family problems with genes passed down that affect the whole family. These cancers develop when random mistakes build up when DNA is copied, during the quick cell division that happens as teenagers’ bones grow. Normally, systems correct most of these mistakes, but sometimes errors get through, and aren’t noticed, in genes that control cell division, DNA repair, or programmed cell death. 

In 15-30% of osteosarcoma cases, the TP53 tumour suppressor gene is damaged, which stops important systems that normally get rid of damaged cells from working. Changes to the retinoblastoma gene also remove controls on growth, allowing cells to grow out of control when combined with other genetic changes. These genetic changes happen by chance during bone formation, rather than because of exposures families could have avoided. 

A Few Patients Have Inherited Cancer Syndromes 

Li-Fraumeni syndrome is the most important inherited risk, caused by inheriting damaged TP53 genes which greatly increase the chance of getting cancer at some point in life – up to 90%. Children with these genes have a much higher chance of getting osteosarcoma, as well as breast cancer, brain tumours, adrenal gland cancers, and leukaemias. Recent research suggests that variations in the TP53 gene are more common in children with osteosarcoma than was thought, particularly in the youngest children – those aged 0-10 when diagnosed. 

Inherited retinoblastoma, caused by mutations in the RB1 gene, raises the risk of bone cancer 500 times compared to the general population, especially after radiotherapy for eye tumours as a baby. Rothmund-Thomson syndrome (linked to mutations in the RECQL4 gene), Bloom syndrome (RECQL2), and Werner syndrome (RECQL3) all make osteosarcoma more likely because of problems with DNA repair. Taken together, these syndromes account for less than 5% of cases, but studying them sheds light on the biological pathways that cause the random cancers that affect children who don’t have inherited problems. 

Radiotherapy Creates a Risk of Secondary Cancer 

Radiotherapy for childhood cancers damages DNA in both the cancer cells and the healthy bone around them, creating a risk of a second cancer appearing years after treatment has finished and been successful. Radiotherapy-caused osteosarcomas usually appear 10-15 years after the radiation, within the area of bone that was treated. Higher doses of radiation relate to a higher risk, although there is no dose which is completely safe, and below which there is no chance of a secondary cancer. 

Modern radiotherapy techniques try to reduce bone exposure as much as possible, using intensity-modulated methods and proton therapy to aim the dose exactly at the cancer. These improvements reduce the rate of secondary cancers compared to older, broad-beam techniques, but some risk remains, and cannot be avoided. Children who need radiotherapy for retinoblastoma, Ewing sarcoma or lymphoma need to be monitored for the rest of their lives, to find any secondary cancers as early as possible, when they are most able to be treated. 

The Speed of Growth in Teenagers is a Risk That Cannot Be Changed 

The fact that osteosarcoma happens most often in teenagers is because that is when bones are growing fastest, and cells are dividing most quickly. Children who are taller have a little more risk, however being tall doesn’t cause cancer: instead, the fast growth – and a lot of bone changing – that comes with it makes times when they are more open to problems. As this is a natural thing, it isn’t possible to stop it, as slowing down normal growth would be bad for their health and wouldn't stop cancer anyway. 

The way growth and cancer are connected is why osteosarcoma most often starts in the parts of bone near growth plates – the lower end of the thigh bone, the top of the shin bone, and the top of the upper arm bone; these are the bones which grow fastest. Altogether, these bones contain roughly 75% of osteosarcomas. Knowing how this happens helps parents understand that typical childhood growth is a sign of good health, and not a dangerous sign of cancer which needs doing something about. 

Why it’s Hard to Stop Osteosarcoma Happening 

Unlike lung cancer – which is clearly caused by smoking – or skin cancer – which is linked to the sun, osteosarcoma doesn’t have obvious things in the environment that families can avoid to lower the risk. No particular things people eat, chemicals they are exposed to, or activities have been shown in good research to cause bone cancer. Not being able to find things to avoid which lower the risk is upsetting for families who want to do something to protect their other children.  

Previous injuries don’t cause cancer, despite what people often think – because injuries lead to scans that find tumours which were already there. Taking part in sport, vitamin supplements, and what people eat haven’t been shown to affect the risk of osteosarcoma, as far as we know now. Families are best off putting their efforts into health maintenance that is proven to work, instead of things which haven’t been shown by science to be useful.  

Places like Fortis Hospital, Rajajinagar, Bengaluru offer genetic advice to families who are at high risk, to help them understand hereditary cancer conditions, and also offer appropriate monitoring programmes. These complete assessments tell the difference between cases which happen by chance, and those in families which need screening of the whole family and prevention plans. 

New Genetic Tests Find Families at Risk 

New research has found that changes in the SMARCAL1 gene are an important risk factor for osteosarcoma, and are in about 2.6% of children who get the disease. These changes which are passed down weaken the ways DNA is repaired, and might allow tumours to grow during the times when development makes them more open to problems. Finding these changes means family members can be screened, so that cancer can be found earlier – when treatment is more likely to work. 

Genetic testing is sensible when several family members get cancer early, unusual patterns of cancer appear, or specific medical signs suggest known hereditary conditions. More and more children who are diagnosed with osteosarcoma are having germline testing, which finds unsuspected conditions which make cancer more likely, and which affect the whole family. This has important effects for brothers and sisters, parents, and other relatives, who might benefit from more careful monitoring. 

How Osteosarcoma Compares to Other Cancers in Children 

Olfactory neuroblastoma also doesn’t have obvious environmental risk factors or ways to prevent it, although it affects the tissues in the nose and sinuses which are directly exposed to things people breathe in. Both conditions happen because of genetic events which occur during development, and not because of things families can change. The fact that these rare cancers in children have this in common suggests there are basic weaknesses in biology during growth which we can’t yet address in order to prevent them. 

This is different to cancers in adults, where there are clear ways to prevent them – stopping smoking prevents lung cancer, and HPV vaccination reduces cervical cancer – which shows the unique problems that children’s cancer doctors face. Children haven’t had the decades of environmental exposure which causes cancers in adults; instead, they develop cancer through accidents in development which happen randomly during normal growth.