Wednesday March 3 2010
Osteoporosis makes the bones thin and brittle
Osteoporosis pills may cut the risk of breast cancer, the Daily Express has reported. A study suggests that women who take the drugs, called bisphosphonates, to treat brittle bones may reduce their risk of breast cancer.
The research compared almost 3,000 women who were diagnosed with breast cancer to a similar number of women without the disease. The researchers looked for characteristics in the two groups that might explain an increased cancer risk, including whether they had taken bisphosphonates. The women who had used the drugs for the longest time (two years) were found to be 40% less likely to develop breast cancer than women who had never used the pills.
These results will need to be confirmed with randomised trials that assess whether the drug really can prevent breast cancer. These trials are needed to ensure that the reduced cancer risk was not due to any other unmeasured or unknown factors that differed between the groups. Overall, there appears to be a plausible biological explanation for the effect seen, which justifies further research in this area.
Where did the story come from?
This study was conducted by Dr Polly Newcomb and colleagues from the University of Wisconsin in the US. The study was supported by the National Cancer Institute of the US National Institutes of Health and published in the peer-reviewed British Journal of Cancer.
Other newspapers also reported the findings, including the Daily Mirror, which quoted Dr Lesley Walker of Cancer Research UK. She was said to have welcomed the results, but said: "Before a drug can be recommended, thorough testing needs to be completed."
What kind of research was this?
This was a case control study in which the researchers evaluated whether the use of bisphosphonate medication for osteoporosis is associated with breast cancer. Animal studies and research using human cells in the laboratory have found some signs that the growth of cancers sampled from tumours that have spread to the bones (bone metastases) may be slowed by the drugs. These test also show that that the drugs may influence several phases of tumour growth and progression.
Among the strengths of this study are its large size and its careful, thorough adjustment to account for the influence of important confounding factors that may have affected the results. Some of the confounders adjusted for were body mass index, postmenopausal hormone use and smoking. Results from case control studies such as this one need to be confirmed in randomised trials to avoid the problem of confounding factors, a point that the authors acknowledge.
What did the research involve?
The researchers used Wisconsin’s mandatory cancer registry to identify new diagnoses of invasive breast cancer from 2003 to 2006. The identified women, who were 20 to 69 years old, were matched to similarly aged women from the general population who did not have a history of breast cancer. The women without cancer were randomly selected using state driving licence lists.
All women were asked a series of questions during structured interviews. Specific attention was given to any bisphosphonate use (the type of drug, duration and how recently it was used). The women were also asked if a doctor had made a diagnosis of osteoporosis, if they had experienced any fractures, or if their height had changed since the age of 18 (all indicators of brittle bones). Other risk factors for breast cancer were also covered in the interview.
The researchers used a complex statistical analysis technique called multivariable logistic regression in their final analysis. This analysis method was appropriate for this type of study. After excluding 55 women with incomplete data, the final analysis included 2,936 women with new diagnoses of breast cancer and a control group of 2,975 women without breast cancer to compare them against.
In their analysis, the researchers adjusted for the following risk factors, which are known to increase the risk of breast cancer or to be linked to osteoporosis:
- year of interview
- number of children (0-1, 2, 3, 4 or more)
- age at first child
- strong family history of breast cancer
- body mass index one year before the study started
- menopausal status
- age at menopause
- number of screening mammograms over the past five years
- a physician diagnosis of osteoporosis
- height change from the age of 18
What were the basic results?
The researchers report a link between use of bisphosphonates and breast cancer risk. They say that current use of bisphosphonates was associated with a 33% reduction in breast cancer risk compared with non-use (odds ratio 0.67, 95% confidence interval 0.51 to 0.89).
Increasing the duration of use was associated with a greater reduction in risk. The researchers say this risk reduction was observed in women who were not obese. Women with a BMI of over 30 showed a reverse trend, in which use of bisphosphonates was linked to a non-significant increased risk of breast cancer.
How did the researchers interpret the results?
The researchers say that use of bisphosphonates was associated with an approximately 30% reduction in breast cancer risk, and that this decrease in risk was greatest for longer durations of use and among leaner women.
They also say the link was not due to the 'primary indication for use', ie the drug’s ability to reduce bone density loss and fractures, which have been shown to be risk factors for breast cancer.
This study has several strengths and weaknesses:
- As a large case control study based on population sampling, the confidence in the results is increased.
- The researchers adjusted for several confounders in their analysis. These confounders were considered and included in the study design before the results were known. This is also a strength of the study.
- Measurements of bone mineral density were not available, so the researchers relied on patient reports of clinical symptoms and of doctors’ diagnoses of osteoporosis. Bone density is one major factor that might contribute to an increased risk of breast cancer in women taking these drugs. This means that it would have been better to have used a more accurate measurement of bone density.
- A ‘dose-response’ was seen in this study, which means that women who took the drugs for longer had a consistently reduced risk. This also suggests that the observed link is genuine.
The major problem with all case control studies is the possibility that unmeasured or unknown confounding factors may have been present, for which adjustment was not possible. For example, women who are healthier in general may have been more likely to seek treatment for osteoporosis and to have a lower breast cancer risk. Diet, physical activity and socioeconomic factors were also not adjusted for.
This was a robust study that has found a plausible link between bisphosphonate use and reduced breast cancer risk. However, as Dr Walker of Cancer Research UK has said, the link cannot be confirmed without further testing.