Mike: Hello, I'm Mike Clarke, podcast editor for the Cochrane Library. Cochrane has produced several systematic reviews that assess the potential benefits and harms of medicine that might help to prevent bone loss in people with breast cancer. In this podcast, Claire Iannizzi talks with lead author Anne Adams, both from the University Hospital Cologne in Germany, about a review of different bone-modifying agents for reducing bone loss in women with non-metastatic breast cancer, which was published for the first time in July 2024.

Claire: Hello Anne. First of all, what is bone loss and why do women with breast cancer develop it?

Anne: Hello Claire. People develop bone loss when more old bone is broken down than new bone is formed, causing an imbalance. Women with breast cancer are especially prone to this because cancer treatments like chemotherapy and endocrine therapy can weaken the bones.

Claire: So, are there treatments for women with breast cancer suffering from bone loss?

Anne: Bone-modifying agents such as bisphosphonates or denosumab can help by slowing down the breakdown of bones, and thereby reduce the risk of fractures, and we look at the effects of these agents in the review.

Claire: Could you tell us a little more about why it’s important to do this review and why you conducted a network meta-analysis?

Anne: We wanted to find out which are the most effective treatments for reducing bone loss in people with breast cancer and whether they cause any unwanted effects. By using a network meta-analysis, we were able to bring together the results of many studies, in the hope of comparing all treatment options against each other and ranking them in order of their effectiveness and unwanted effects.

Claire: What studies did you want to include and were there enough of them?

Anne: We searched for studies comparing different bone-modifying agents for preventing or treating bone loss resulting from cancer treatment in pre or postmenopausal women with non-metastatic breast cancer. In total, we found 47 relevant studies including approximately 35,000 women of different ages and receiving a mix of anti-cancer treatments. Of these, 34 studies reported data that we could use in the review, allowing us to compare eight different treatment options in total.

Claire: And what did you find?

Anne: Treatment with most bone-modifying agents (except alendronate and pamidronate) seems to improve bone mineral density and lower the risk of fractures but they don’t seem to have an impact on quality of life. While these medicines might not affect survival when combining evidence from pre and postmenopausal women, as we did, an independent systematic review has found a small survival benefit in postmenopausal women. In regard to unwanted effects, these medicines do seem to cause some, such as osteonecrosis of the jaw.

Claire: Overall, how certain are you about these findings?

Anne: Overall, we are moderately confident in the evidence, but we sometimes found different results for the same treatments. This means that a particular treatment might be good for some patients but bad for others. This limits our confidence in the results for individual treatments and we could not reach firm conclusions or provide a ranking of all treatment options for women with breast cancer.

Claire: Finally, what’s your take-home message?

Anne: Our key message is that when considering bone-modifying agents for reducing bone loss in women with breast cancer, one has to balance between effectiveness and unwanted effects. Our network meta-analysis suggests that treatment with bone-modifying agents probably increases bone mineral density and decreases the number of fractures but may also increase the number of unwanted effects. To help improve the certainty of the evidence, and because we were not able to produce a ranking of all included treatment options, we need more studies that compare these treatments directly against each other, especially to compare denosumab with any bisphosphonate.

Claire: Thanks Anne. If people would like to read the review, how can they get hold of it?

Anne: Thanks Claire. Our review is available online. If listeners go to Cochrane Library dot com and type “bone-modifying agents” in the search box, they’ll see the review near the top of the list.