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.
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September 28th, 2010 at 4:55 pm
Scientists at Tokyo Medical and Dental University, Japan have discovered a protein that could help in the development of approaches to treat age-related osteoporosis.
Osteoporosis is characterized by reduced bone mass and increased risk of fracture – an imbalance created by decrease in formation of bone forming osteoblast cells from mesenchymal cells upon aging. Instead, these cells form more fat cells.
Hiroshi Takayanagi and colleagues found that the gene regulatory protein Maf promoted mesenchymal cell generation of osteoblasts and suppress their generation of fat cells.
On the other hand, mice lacking Maf showed delayed bone formation. Furthermore, Maf levels were found to decrease in mouse mesenchymal cells upon aging and to be reduced by increased oxidative stress, something that occurs upon aging.
Scientists believe that these data could lead to new approaches to treat age-related osteoporosis.
September 29th, 2010 at 10:35 pm
A drug used to prevent the crippling bone disease osteoporosis, may also protect women against breast cancer.
Researchers believe that denosumab – a medicine newly licensed for use in Britain – reduces the risk of tumours in women taking hormone replacement therapy or the contraceptive Pill.
Breast cancer is one of the most common cancers, affecting up to one in eight women during their lifetime.
Past studies have shown that synthetic sex hormones called progestins found in HRT and contraceptives can increase the risk of breast cancers.
Now an international team of researchers – including scientists at University College London – have shown exactly how these hormones affect mammary cells.
In a paper published in the journal Nature, they found that progestins activate a protein called RANKL in breast tissue which makes cells divide, multiply and fail to die – creating tumours.
The same protein is also involved in the natural breakdown of bone tissue when it needs to be replaced. When the system goes wrong and people produce too much RANKL, they suffer from osteoporosis, or bone thinning.
In a second study, also published in Nature, researchers at the Californian biotechnology company Amgen tested denosumab – a osteoporosis drug that works by blocking RANKL.
They found that the drug delayed the formation of tumours cancers in mice bred to develop the disease – leading to ‘significantly fewer’ breast cancers.