Long-term use of bone-strengthening drugs – used to treat fractures – may boost the risk of oesophageal cancer, Oxford University research suggests.
The study of 3,000 people found taking bisphosphonates for five years upped the risk from one in 1,000 to two in 1,000 for 60 to 79-year-olds.
The researchers said the risk was small, but reliable information on risks and benefits was needed.
But experts said for many, the case for taking the drugs “would be strong”.
The findings, published in the British Medical Journal, were based on an analysis of anonymised GP records.
They contrast with previous research which found no increased risk for the bone-strengthening drugs.
Those who have taken oral bisphosphonates for five years or more are twice as likely to develop the cancer than those who have not, the analysis of medical records found.
Every year almost 8,000 people in Britain are diagnosed with cancer of the oesophagus, or gullet cancer, and about 7,500 people die from it.
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 (UK Medicines and Healthcare products Regulatory Agency), 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.
In pharmacology, bisphosphonates (also called diphosphonates) are a class of drugs that prevent the loss of bone mass, used to treat osteoporosis and similar diseases. They are called bisphosphonates because they have two phosphonate (PO3) groups.
Several large clinical trials have shown that they reduce the risk of osteoporotic fracture and have an excellent safety record.
Bone has constant turnover, and is kept in balance (homeostasis) by osteoblasts creating bone and osteoclasts digesting bone. Bisphosphonates inhibit the digestion of bone by osteoclasts.
Osteoclasts also have constant turnover and normally destroy themselves by apoptosis, a form of cell suicide. Bisphosphonates encourage osteoclasts to undergo apoptosis.
Bisphosphonates were developed in the 19th century but were first investigated in the 1960s for use in disorders of bone metabolism. Their non-medical use was to soften water in irrigation systems used in orange groves. The initial rationale for their use in humans was their potential in preventing the dissolution of hydroxylapatite, the principal bone mineral, thus arresting bone loss. Only in the 1990s was their actual mechanism of action demonstrated with the initial launch of Fosamax (alendronate) by Merck.
The uses of bisphosphonates include the prevention and treatment of osteoporosis, osteitis deformans (“Paget’s disease of bone”), bone metastasis (with or without hypercalcaemia), multiple myeloma, primary hyperparathyroidism, osteogenesis imperfecta, and other conditions that feature bone fragility.