Women taking certain breast cancer medications called aromatase inhibitors often experience bone loss, which can lead to fractures. Researchers analyzed 17 studies involving nearly 7,000 postmenopausal women to compare six different bone-protecting treatments. They found that denosumab worked best for protecting the lower spine bones, while ibandronate was most effective for hip bones. For longer-term treatment, a combination of two drugs showed promise for hip protection. The study suggests doctors should choose treatments based on which bones need the most protection and how long the patient will need treatment.

The Quick Take

  • What they studied: Which medicines work best at preventing bone loss in women with breast cancer who are taking aromatase inhibitor drugs (a type of hormone therapy)
  • Who participated: 6,932 postmenopausal women with early-stage breast cancer who were receiving aromatase inhibitor therapy. The analysis combined results from 17 different research studies.
  • Key finding: Denosumab was the best single medicine for protecting spine bones, while ibandronate worked best for hip bones. A combination of two drugs (eldecalcitol plus risedronate) showed the most promise for hip protection over two years, though this was based on limited evidence.
  • What it means for you: If you’re a postmenopausal woman taking aromatase inhibitors for breast cancer, your doctor may now have better information about which bone-protecting medicine to prescribe based on where your bones need the most protection. However, individual factors matter, so discuss options with your healthcare team.

The Research Details

This was a network meta-analysis, which is a special type of research that combines results from multiple studies to compare different treatments. The researchers searched five major medical databases for all randomized controlled trials (the gold standard of research) that tested bone-protecting medicines in postmenopausal women with breast cancer taking aromatase inhibitors. They found 17 studies that met their criteria and combined the data using advanced statistical methods called Bayesian analysis.

The researchers looked at how well six different bone-protecting treatments worked: denosumab, alendronate, zoledronic acid, ibandronate, risedronate, and a combination of eldecalcitol plus risedronate. They measured bone density (how thick and strong the bones are) at two important locations—the lower spine and the hip—at both 12 months and 24 months of treatment.

They ranked each treatment based on how well it performed compared to the others, using a scoring system called SUCRA (Surface Under the Cumulative Ranking Curve). A higher SUCRA score means the treatment ranked better overall.

This research approach is important because it allows doctors to compare treatments that may never have been directly tested against each other in a single study. By combining evidence from multiple studies, researchers can give a more complete picture of which treatments work best. This is especially valuable for cancer patients who need the most effective options.

This study has several strengths: it included a large number of patients (nearly 7,000), used only randomized controlled trials (the most reliable type of research), and searched multiple medical databases to find all relevant studies. However, readers should know that the individual studies included varied in size and quality. One important limitation is that the combination treatment (eldecalcitol plus risedronate) was only tested in one small study, so those results are less certain. The researchers were transparent about this limitation.

What the Results Show

At 12 months, denosumab was the clear winner for protecting spine bones, with a score of 0.88 out of 1.0 (higher is better). It improved spine bone density by about 5.63 units more than the comparison treatment. For hip bones at 12 months, ibandronate performed best with a score of 0.94, improving hip bone density by about 4.23 units more.

At 24 months (two years), denosumab maintained its advantage for spine protection with a score of 0.83. However, for hip protection over two years, a combination of eldecalcitol plus risedronate showed the highest score of 0.83, with improvements of about 6.38 units. Importantly, all active treatments significantly outperformed simply taking calcium and vitamin D supplements alone.

The improvements in bone density translate to reduced risk of fractures, though the study measured bone density rather than actual fracture rates. The differences between treatments were statistically significant, meaning they’re unlikely to be due to chance.

The study found that all six active bone-protecting treatments worked better than calcium and vitamin D alone, which is important because it confirms that patients need more than basic supplementation. The research also showed that different treatments worked better at different body locations—no single treatment was best everywhere. This suggests that doctors should consider which bones are most at risk when choosing a treatment.

This analysis builds on previous research by directly comparing multiple treatments in one analysis. Earlier studies typically compared one new treatment to a standard treatment or placebo. By combining 17 studies, this research provides a more comprehensive picture. The findings generally align with previous knowledge that denosumab and bisphosphonates (a class of drugs including alendronate, zoledronic acid, ibandronate, and risedronate) are effective, but this is the first large-scale comparison of how they rank against each other for specific body locations.

The main limitation is that the combination treatment (eldecalcitol plus risedronate) was only tested in one study with a relatively small number of patients, so those results are less reliable and need confirmation from larger studies. Additionally, the analysis measured bone density changes rather than actual fracture rates, so we can’t be completely certain how much these improvements reduce real-world fracture risk. The studies included varied in their methods and quality, which can affect the overall results. Finally, most participants were from specific geographic regions, so results may not apply equally to all populations.

The Bottom Line

For postmenopausal women with early breast cancer taking aromatase inhibitors: (1) Denosumab appears to be the best choice for protecting spine bones (high confidence based on multiple studies). (2) Ibandronate appears optimal for hip bone protection at 12 months (high confidence). (3) For longer-term hip protection, eldecalcitol plus risedronate may be beneficial, but this needs more research (low confidence due to limited evidence). (4) All active treatments are better than calcium and vitamin D alone (high confidence). Discuss these options with your oncologist to determine which is best for your individual situation.

This research is most relevant for postmenopausal women with early-stage breast cancer who are taking or considering aromatase inhibitor therapy. It’s also important for oncologists and other doctors who prescribe these treatments. Women should NOT use this information to change their medications without consulting their healthcare team. This research does not apply to premenopausal women or men with breast cancer.

Bone density improvements typically become measurable within 6-12 months of starting treatment. The most significant benefits appear at 12-24 months. However, the real benefit—reduced fracture risk—may take longer to become apparent and depends on individual factors like age, baseline bone health, and overall health status.

Want to Apply This Research?

  • Track bone health appointments and medication adherence: Log dates of bone density scans (DEXA scans), record which bone-protective medication you’re taking and when you take it, and note any bone-related symptoms like pain or discomfort. Set reminders for medication doses and upcoming bone health check-ups.
  • If prescribed a bone-protective medication, use the app to: (1) Set daily reminders to take your medication at the same time each day, (2) Track any side effects you experience, (3) Log weight-bearing exercises (walking, dancing, light resistance training) which support bone health, (4) Record calcium and vitamin D intake through food or supplements, (5) Schedule and track follow-up appointments with your oncologist.
  • Create a long-term bone health dashboard that tracks: medication compliance over months, scheduled bone density scan dates and results, exercise frequency (aim for 150 minutes weekly of moderate activity), dietary calcium and vitamin D intake, and any fractures or bone-related injuries. Review this data quarterly with your healthcare provider to assess whether your current treatment is working effectively.

This research summary is for educational purposes only and should not replace professional medical advice. The findings compare bone-protective treatments but do not measure actual fracture rates. Individual responses to medications vary based on age, overall health, genetics, and other factors. If you have breast cancer and are taking or considering aromatase inhibitors, discuss bone health options with your oncologist or healthcare provider before making any treatment changes. Do not start, stop, or change any medications without medical supervision. This analysis is current as of the publication date but medical recommendations may evolve as new research emerges.