Category Archives: Bisphosphonates

The Tradeoffs


The practice of medicine comes with tradeoffs. Most of risks associated with treatment are small, usually inconsequential and obvious during or immediately after the treatment is given. Cancer results from damage to genes involved in growth and regulation of cells. Growth regulatory systems have multiple damage control and backup pathways. The regulatory systems fail only after multiple hits. Years of exposure is required to carcinogens is needed to cause enough DNA damage for a cancer to emerge. Unlike other drug toxicity, the carcinogenic potential of a therapy may take years to manifest. The same can be said about heart disease which along with cancer is responsible for the largest disease burden in an ageing population.

I had earlier written about the protective effect of bisphosphonates in breast cancer. Within few years of introduction of oral bisphosphonates for the therapy of osteoporosis, it became clear that these agents carried a risk of oesophagitis and oesophageal perforation. About a decade later a concern about the association of oesophageal cancer emerged. A recently published study (BMJ 341:4444c; 2010) has concluded that the use of oral bisphosphonates increases the risk of oesophageal cancer. The study found that one (or more) prescription for oral bisphosphonates increased the risk of oesophageal cancer by 30%. Ten or more prescriptions nearly doubled the risk. Using the same database another study, with a shorter follow up, (JAMA304:657-63;2010) had failed to show an increased risk. Selective oestrogen receptor modifiers (tamoxifen and raloxifene) are used to treat osteoporosis and are effective in and under evaluation for chemoprevention of breast cancer. Tamoxifen increases the risk of endometrial cancer. Both increase the risk of thrombosis.

This is not the first time a therapy has been implicated in a serious adverse effect after years of use and this will not be the last. Intervention in chronic disease improves the health of ageing population. A chronic disease also provides a large market for the pharmaceutical industry. It is for the medical community to recognize that there are tradeoffs in medical practice. As we treat an aging population the need becomes more acute.

Osteoporosis Therapy Reduces the Risk of Breast Cancer


The drug therapy of postmenopausal osteoporosis includes hormone replacement therapy, selective oestrogen receptor modifiers (SERMS) and bisphosphonates. Unlike hormone replacement therapy and SERMS bisphosphonates do not carry the risk of breast cancer. In fact, in vitro studies have shown that bisphosphonates may have an anti-cancer effect and this effect may not be limited to bone metastasis. There are two classes of bisphosphonates nitrogen containing (alendronate, risedronate, zoledronate and ibandronate) and those without nitrogen (clodronate, etidronate). Nitrogen containing bisphosphonates have anti-cancer properties. Are women receiving bisphosphonates for osteoporosis protected from cancer?

Two recently published studies suggest that bisphosphonates taken for osteoporosis reduce the risk of cancer. The Women’s Health Initiative Observational Study, that included 154,768 women receiving bisphosphonates for osteoporosis suggest that bisphosphonates reduce the risk of breast cancer by 32%. The Breast Cancer in Northern Israel Study showed a 28% risk reduction in breast cancer in receiving bisphosphonates for osteoporosis. An earlier study has shown a 33% reduction in breast cancer with the use of bisphosphonates.

Breast cancer is one of the most common cancers in women. Breast cancer accounts for about one million cancers per year. Bisphosphonates could prevent 300,000 of these. Should bisphosphonates be used for chemoprophylaxis of breast cancer?

Bisphosphonates are associated with rare serious adverse effects including gastric and oesophageal ulcers, jaw necrosis and possible atrial fibrillation and increased risk of oesophageal carcinoma. Use of bisphosphonates for chemoprophylaxis of breast cancer would expose normal individuals to this risk. Unless the benefits of bisphosphonates in breast cancer prevention are documented in a controlled trial, bisphosphonates can not be recommended for use in prophylaxis of breast cancer. However the reduction in the risk of breast cancer may be a reason of choosing bisphosphonates over other drug therapy for osteoporosis.