No link seen between bone drugs, colon cancer

Women who use certain bone-building drugs may not have a decreased risk of colon cancer, a new study finds - despite prior evidence suggesting the drugs might offer some protection.

The drugs, called bisphosphonates, include brands like Fosamax, Boniva, Reclast and Actonel, along with generic versions.

They are used to prevent and treat the bone-thinning disease osteoporosis, which mainly strikes older women. The drugs can also be used to help treat cancer that has spread to the bone from other sites in the body.

Bisphosphonates have been tied to both good and bad side effects.

Research has found after years of use, the drug may, in rare cases, actually weaken the bones and lead to thighbone fractures or a painful breakdown of the jaw bone.

On the other hand, several studies have suggested women who use bisphosphonates may have a decreased risk of developing breast or colon cancer.

But this latest study, reported in the Journal of Clinical Oncology, found no evidence that women on the medications had lower odds of colon cancer.

Of more than 86,000 U.S. nurses followed for over a decade as part of a large health study, 801 developed colon cancer. The risk was no different among women who didn’t use bisphosphonates, versus users - regardless of how many years they had been on the medications.

FDA Drug Safety Communication: Ongoing safety review of oral osteoporosis drugs (bisphosphonates) and potential increased risk of esophageal cancer

Commonly used for the prevention and treatment of osteoporosis as well as to treat other bone diseases such as Paget’s disease. Osteoporosis is a disease that makes bones weak and more likely to break.

Include: Fosamax (alendronate), Actonel (risedronate), Boniva (ibandronate), Atelvia (risedronate delayed release), Didronel (etidronate), and Skelid (tiludronate).

May cause irritation of the esophagus. Irritation of the esophagus can lead to esophagitis (inflammation) or esophageal ulcers (sores), which may bleed. The risk of these esophageal events is low when oral bisphosphonates are prescribed appropriately and the specific directions for use are followed by patients.

“It is not clear whether bisphosphonates have any role in treatment of colorectal cancer, and our data does not support its routine use as a (prevention) agent for colorectal cancer,” lead researcher Dr. Hamed Khalili, a gastroenterologist at Massachusetts General Hospital in Boston, said in an email.

Since evidence suggests bisphosphonate users have a lower risk of certain cancers, researchers have been interested in whether the drugs might help prevent those tumors in people who are particularly at risk.

At this time, FDA believes that the benefits of oral bisphosphonate drugs in reducing the risk of serious fractures in people with osteoporosis continue to outweigh their potential risks.

FDA’s review is ongoing and the Agency has not concluded that patients taking oral bisphosphonate drugs have an increased risk of esophageal cancer. It is also important to note that esophageal cancer is rare, especially in women.

The largest studies that FDA has reviewed, thus far, are two epidemiologic studies using one patient database (the U.K. General Practice Research Database or GPRD). One study found no increase in the risk of esophageal cancer. The second study found a doubling of the risk of esophageal cancer among patients who had 10 or more prescriptions of the drugs, or who had taken the drugs over 3 years. Other external researchers investigating this issue, using different patient databases, have reported no increase in risk, or a reduced risk.

In the case of colon cancer, risk factors include inflammatory bowel disease (ulcerative colitis or Crohn’s disease) and having a strong family history of the cancer.

According to Khalili, there is evidence women on bisphosphonates have a lower risk of breast cancer - though that does not mean the drugs are the reason.

There has been less research on colon cancer. One study last year found women who used bisphosphonates had a 59 percent lower chance of developing colon cancer than non-users (see Reuters Health story of February 14, 2011).

But that study was designed differently than the current one, Khalili pointed out. In the earlier report, researchers compared colon cancer patients with a group of women who were free of the disease.

Khalili’s study, in contrast, followed a large group of initially cancer-free women over time. Thus, the researchers were able to collect information on women’s health and lifestyle habits before their cancer diagnosis, Khalili said.

That’s important because women on bisphosphonates may, for example, be more likely than other women to get screened for colon cancer.

Bisphosphonate users are also likely to be taking vitamin D and calcium to help protect their bones - and those nutrients have been linked to lower colon cancer risk themselves, Khalili added.

When Khalili’s team first looked at its data, there was in fact some weak evidence that women on bisphosphonates might have a slightly lower colon cancer risk than non-users.

But the link got even weaker when the researchers accounted for colon cancer screening and which women were taking calcium and vitamin D.

According to the American Cancer Society, one in 19 men develops colorectal cancer at some point, and slightly fewer women do. The disease is the third-leading cause of cancer deaths in the U.S.

The best way to lower your chances of developing colon cancer, the ACS says, is to get screened. Screening helps doctors detect and remove any pre-cancer growths.

In general, colon cancer screening is recommended for people age 50 to 75. That can be done with any of several tests, or a combination of them - including tests that look for hidden blood in the stool, or procedures like colonoscopy or sigmoidoscopy.

SOURCE: Journal of Clinical Oncology, online May 29, 2012


A Prospective Study of Bisphosphonate Use and Risk of Colorectal Cancer

Results Through 2008, we documented 801 cases of colorectal cancer over 814,406 person-years of follow-up. The age-adjusted HR for women who regularly used bisphosphonates was 0.92 (95% CI, 0.73 to 1.14) and was further attenuated after adjustment for other risk factors (multivariate HR, 1.04; 95% CI, 0.82 to 1.33). The risk was not influenced by duration of use (Ptrend = 0.79). Compared with nonusers, the multivariate-adjusted HRs of colorectal cancer were 1.24 (95% CI, 0.94 to 1.64) for women with 1 to 2 years of use, 1.16 (95% CI, 0.79 to 1.69) for 3 to 4 years of use, and 0.97 (95% CI, 0.60 to 1.56) for ≥ 5 years of use. There was no association between bisphosphonate use and colorectal cancer within strata of other risk factors.

Conclusion In a large prospective cohort, we did not observe an association between long-term use of bisphosphonates and risk of colorectal cancer.

  Hamed Khalili,
  Edward S. Huang,
  Shuji Ogino,
  Charles S. Fuchs and
  Andrew T. Chan

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