Every year thousands are diagnosed with cancer of the oesophagus, or gullet cancer, and more than 90% of people die from it.
Survival rates are low compared to other cancers, with only three in 10 surviving more than a year after diagnosis.
Among the general population of people aged 60 to 79, the incidence of oesophageal cancer is about one in 1,000.
But researchers found that among those who had taken oral bisphosphonates for five years or more the rate doubled to two in 1,000.
Among men it increased from 1.5 to three per 1,000 and among women from 0.5 to to one per 1,000.
Last night the Medicines and Healthcare products Regulatory Agency (MHRA), the Government's medicine's regulator, said there was "no need" for patients to stop taking the medication on the basis of the study alone.
The MHRA collaborated with academics at Oxford University's Cancer Epidemiology Unit to look at data from the UK General Practice Research Database, which has anonymised patient records for around six million people.
Among those aged 40 and over, 2,954 had oesophageal cancer, 2,018 had gastric cancer and 10,641 had bowel cancer, all diagnosed between 1995 and 2005.
The results also showed that the chance of oesophageal cancer was 30 per cent higher in people with one or more previous prescriptions for oral bisphosphonates, compared to people who had never taken the drugs.
The risk was almost double for those who had 10 or more prescriptions compared with those who had had between one and nine, according to the study, published today in the British Medical Journal (BMJ).
There were no links between the drugs and stomach or bowel cancer.
Some three million people suffer from osteoporosis, according to the National Osteoporosis Society. The Duchess of Cornwall, whose mother and grandmother both died of the disease, is president of the charity.
More than a million people were prescribed a bisphosphonate in 2009/10, according to the MHRA, which work by preventing bone loss and rebuilding lost bone. More than 6.5 million prescriptions were issued.
They are a group of drug that include alendronate, etidronate and risedronate, also marketed under the brand names Fosamax, Didronel and Actonel.
Doctors often prescribe them as a preventative measure for those who might be at a higher risk of osteoporosis, such as post-menopausal women.
However, some doctors are becoming concerned that they are being over-prescribed with scant thought of their side effects, which are known to include difficulty swallowing, chest pain and heartburn.
Dr Des Spence, a Glasgow GP who has also written on the subject in the BMJ, said doctors should focus less on the drugs and more on how to avoid falls, as well as on improving diet and increasing targeted exercise.
Dr Jane Green, lead author of the study, said their results were "part of a wider picture" because bisphosphonates were "increasingly prescribed to prevent fractures".
She said: "what is lacking is reliable information on the benefits and risks of their use in the long-term."
But she added: "Oesophageal cancer is uncommon. The increased risks we found were in people who used oral bisphosphonates for about five years, and even if our results are confirmed, few people taking bisphosphonates are likely to develop oesophageal cancer as a result of taking these drugs."
Their study contradicts one published only a few weeks ago, using the same dataset, that showed no link between the drugs and the disease.
However, the latest research followed patients for almost twice as long and had greater statistical power.
A spokesman for the MHRA said: "On the basis of the findings of this study there is no need for patients to stop taking their bisphosphonate medicine.
"However, in order to reduce the risk of oesophageal irritation, which is a recognised risk associated with bisphosphonate use it is important to carefully follow the instructions in the Patient Information Leaflet.
"Patients should also report any signs of oesophageal irritation such as difficulties or pain on swallowing, chest pain, or heartburn to their doctor."
He added: "The safety of all bisphosphonates will continue to be closely monitored."
Dr Laura Bell, science information officer at Cancer Research UK, said: "This is an important study that will help doctors understand more about the risks and benefits of oral bisphosphonates but it's important to stress that even if people take oral bisphosphonates for a long time the risk of developing oesophageal cancer is still small.
"Anyone who is taking these drugs and is worried about their risk of cancer should talk to their doctor."