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There was a report in a recent (2010) British medical Journal that noted that a case-control study found that oral bisphosphonates are associated with a 30% increase in risk for esophageal cancer, with the elevated risk largely limited to patients with 10 or more prescriptions. This contradicted a recent Journal of the American Medical Association (JAMA )study finding no such link.

The drugs did not appear to increase risk for stomach or colorectal cancer, the report noted. Bisphosphonates are a class of drugs that are used to prevent bone loss, and to treat osteoporosis and similar diseases affecting the skeleton (i.e. Paget’s Disease).

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. Several large clinical trials have shown that they reduce the risk of osteoporotic fracture and have an excellent safety record.

In the current study, British researchers used a national database to identify nearly 16,000 adults diagnosed with esophageal, stomach, or colorectal cancer over a 10-year period, and matched them with some 78,000 controls without cancer, the article said. It said that prescriptions for bisphosphonates were then assessed for the 7.5 years before diagnosis.

The researchers, noting that the contradictory JAMA study used the same database, say the disparate result may be due, in part, to the longer follow-up and greater number of subjects in the current study.

I want our readers to be aware that a 30% increase may be "trivial" especially for a rare disease (If one in a hundred people get this cancer [it is really much, much lower than that], then a 30% increase is 1.3 people in a hundred. In studies like this one, relative risk increases less than a doubling of the risk [a 100% increase] are usually thought of as being "trivial."

While it may be a statistically significant increase in risk in this study, it may not be a clinically relevant increase even if one believes it is true. Such studies are commonly used to develop hypotheses for more direct testing in the future. It should also be noted that few people use bisphosphonates for 10 or more years, that long of therapy may make them a unique group of people. They may not represent “normal” people and I stress that another study using the same data, didn’t find any effect (JAMA.)

It's also interesting to note that the risk of stomach cancer wasn’t affected. Such a finding raises further questions as to whether this class of drugs is carcinogenic or not. If the findings of an increase in esophageal cancer are really true, one would also expect that bisphosphonates would affect the nearby gastrointestinal tract structures as well.

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