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Breast cancer patients now experience significantly higher survival rates thanks to early diagnosis and more effective treatments. Aromatase inhibitors, a class of hormone therapy medications, stand out as one of the most effective protocols for preventing hormone receptor-positive breast cancer recurrence. While highly effective, these medications can cause bone loss as a side effect. This article explores the connection between aromatase inhibitors and bone loss, their potential to cause osteoporosis or osteopenia, and strategies to protect your bone density while using these medications.
Dr. Theresa Guise, a world-renowned expert on cancer and bone health, shares her insights throughout this article. As a professor, clinician, and chief of the Bone and Mineral Disorder section at the University of Texas MD Anderson Cancer Center, Dr. Guise has dedicated her career to understanding how cancer and its treatments affect the musculoskeletal system.
How Cancer Treatment Impacts Bone Remodeling
Cancer treatments often affect bone health more significantly than cancer itself. While we typically associate cancer’s impact on bones with metastasis (cancer spreading to bone), many cancer treatments can affect bone health even when cancer hasn’t spread to the bones.
Common cancer treatments that can affect bone mineral density include:
- Chemotherapy radiation used across many cancer types
- Anti-estrogen therapy for breast cancer
- Anti-androgen therapy for prostate cancer
- Glucocorticoids (steroid hormones like prednisone or dexamethasone)
These treatments disrupt the bone remodeling process and can lead to bone loss, fractures, muscle weakness, and potentially osteoporosis.
Breast Cancer Treatment and Osteoclasts
Cancer treatments can stimulate osteoclastic bone resorption, accelerating the bone remodeling process. In this situation, osteoclasts destroy bone faster than osteoblasts can rebuild it, resulting in net bone loss.
Breast Cancer Treatment and Osteoblasts
Some treatments, particularly glucocorticoids, directly inhibit osteoblast activity. The effects can be dramatic — radiation therapy, for example, can cause significant bone loss within a short timeframe. This makes it crucial to identify these potential effects before treatment begins and implement preventive measures, such as medications or low intensity vibration therapy.
Aromatase Inhibitors and Bone Loss During Breast Cancer Treatment
As both a researcher and patient, Dr. Guise brings unique insight into aromatase inhibitors, which have become the standard first-line treatment for estrogen receptor-positive breast cancers. These drugs have proven more effective than their predecessor, Tamoxifen, by blocking the aromatase enzyme that converts androgens to estrogens.
While effective at treating breast cancer, aromatase inhibitors reduce estrogen levels below those typically seen in menopausal women, leading to various musculoskeletal problems.
Exercise and Osteoporosis
Exercise is an essential ingredient to bone health. If you have osteoporosis, therapeutic exercise needs to be part of your osteoporosis treatment program.
But what exercises should you do and which ones should you avoid? What exercises build bone and which ones reduce your chance of a fracture? Is Yoga good for your bones? Who should you trust when it comes to exercises for osteoporosis?
A great resource on exercise and osteoporosis is my free, seven day email course called Exercise Recommendations for Osteoporosis. After you provide your email address, you will receive seven consecutive online educational videos on bone health — one lesson each day. You can look at the videos at anytime and as often as you like.
I cover important topics related to osteoporosis exercise including:
- Can exercise reverse osteoporosis?
- Stop the stoop — how to avoid kyphosis and rounded shoulders.
- Key components of an osteoporosis exercise program.
- Key principles of bone building.
- Exercises you should avoid if you have osteoporosis.
- Yoga and osteoporosis — should you practice yoga if you have osteoporosis?
- Core strength and osteoporosis — why is core strength important if you have osteoporosis?
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Do Aromatase Inhibitors Cause Osteoporosis?
Bone loss affects most women taking aromatase inhibitors. Those starting treatment with osteopenia may develop osteoporosis without preventive measures. This occurs because estrogen naturally inhibits bone-resorbing osteoclasts. When aromatase inhibitors deplete estrogen, bone loss accelerates as osteoblasts struggle to keep pace with increased resorption.
Beyond bone loss from aromatase inhibitors, many postmenopausal women with breast cancer experience muscle weakness and generalized aches in their muscles, bones, and joints. These side effects are associated with aromatase inhibitors and sometimes lead to treatment discontinuation.
Aromatase Inhibitors and Bone Loss: How to Counter Bone Loss
Several strategies can help counter bone loss during aromatase inhibitor therapy:
- Medications like Prolia (denosumab) or bisphosphonates like zoledronate
- Low intensity vibration therapy, particularly helpful for patients experiencing muscle weakness
- Mechanical loading exercises, when tolerated
Research in Dr. Guise’s laboratory shows that low intensity vibration can prevent bone loss, improve muscle strength, and reduce fat in mouse models. A clinical trial at Indiana University is currently evaluating these effects in women taking aromatase inhibitors.
Aromatase Inhibitors and Osteoporosis: Dr. Guise's Personal Journey
Dr. Guise shares her personal experience as a breast cancer patient taking aromatase inhibitors. By combining a low intensity vibration platform (used twice daily) with zoledronate treatment, she achieved a 3% increase in bone density — a marked improvement over the bone loss typically seen with aromatase inhibitors alone.
Aromatase Inhibitor Therapy and Bone Loss: Updated Guidelines for 2025
A group of clinicians and researchers (including Dr. Guise) recently published a joint position statement for a number of leading osteoporosis organizations in the August 2025 edition of the Journal of Bone Oncology. (1) The statement provides updated guidelines for the management of aromatase inhibitor associated bone loss in women with hormone sensitive breast cancer.
The key message for you is that women taking aromatase inhibitors for breast cancer face a 2 to 4 times higher risk of bone loss and fractures compared to normal menopause, making early bone-protective treatment essential rather than optional. The good news is that effective treatments like denosumab (Prolia) and bisphosphonates not only prevent fractures but may also improve breast cancer survival outcomes.
We review this joint statement in this section.
Elevated Risk of Vertebral and Hip Fractures
Women with hormone-responsive breast cancer who receive adjuvant endocrine treatment with aromatase inhibitors are known to be at higher fracture risk due to a marked increase in bone resorption.
Studies have shown that aromatase inhibitor associated bone loss in postmenopausal women with hormone-sensitive breast cancer, where estrogen is already naturally depleted, can lead to a 2 to 4 fold increase in bone loss compared to the usual postmenopausal decrease in BMD, leaving them at high risk of fragility fractures.
The relative risk (RR) for hip fractures and non-vertebral fractures was 1.18 versus controls, while the RR for vertebral fractures was much higher, at 1.84. This means women on aromatase inhibitor therapy face nearly double the risk of spine fractures compared to those not on this treatment.
Extended Aromatase Inhibitor Treatment Increases Bone Loss Risk
A systematic review and meta-analysis of seven trials of 16,349 breast cancer patients treated with either extended-duration aromatase inhibitors, placebo or no treatment found that longer treatmen
Aromatase Inhibitors and Bone Loss Risk Factors
The updated guidelines identify several key risk factors that increase your fracture risk beyond Aromatase inhibitors therapy itself. These include:
- Age over 65 years
- T-score below -1.5 on bone density testing
- Current or history of smoking
- Body mass index (BMI) less than 24
- Family history of hip fracture
- Personal history of fragility fracture after age 50
- Previous vertebral fracture
- Use of oral corticosteroids for more than 6 months
Advanced Assessment Techniques
Modern fracture risk assessment goes beyond traditional bone density (DXA) scans. The FRAX® tool was developed for use in the general population and was not specifically designed for use in patients with breast cancer undergoing aromatase inhibitor treatment.
However, newer techniques are showing promise. Trabecular bone score (TBS) utilizes grey-level texture measurements on lumbar spine DXA images to capture information relating to trabecular microarchitecture and has been shown to be an independent indicator of increased fracture risk.
A study of 100 patients with early-stage ER-positive breast cancer treated with aromatase inhibitors assessed elevated fracture risk using BMD alone, BMD plus FRAX® and a combination of BMD, FRAX® and TBS. The use of multiple assessment techniques incrementally improved the identification of patients at increased fracture risk with the combination of all three procedures maximizing the number detected.
Treatment Options: What Works Best
The good news is that effective treatments are available. The updated guidelines provide clear evidence-based recommendations:
- Denosumab (Prolia) emerges as a first-line therapy. Denosumab is recommended as a first-line therapy for aromatase inhibitor associated bone loss prevention by the European Society for Medical Oncology (ESMO) and in the 2021 updated guidance on management of cancer treatment-induced bone loss (CTIBL).
- Intravenous bisphosphonates have been upgraded to Level I evidence. Adjuvant zoledronate was found to significantly reduce the incidence of fractures in this patient cohort, with a 5-year fracture rate of 3.8 % compared to 5.9 % in the control arm.
- Oral bisphosphonates have also shown efficacy, though with some limitations regarding absorption and compliance.
Treatment Guidelines and Monitoring
The updated algorithm is straightforward: All women receiving aromatase inhibitor treatment should be informed of this significantly increased risk and its consequences and have their individual fracture risk evaluated to determine an appropriate management strategy.
For women with T-scores below -2.0 or those with T-scores between -1.5 and -2.0 plus additional risk factors, bone-protective therapy should be initiated alongside aromatase inhibitor treatment. BMD should then be monitored every two years.
Discussion
If you’re receiving aromatase inhibitor therapy, don’t wait to address bone health. The evidence overwhelmingly supports early intervention. Work with your healthcare team to assess your individual risk, consider the most appropriate bone-protective therapy, and establish a monitoring plan. Remember, protecting your bones isn’t just about preventing fractures—it may also improve your overall cancer outcomes.
Aromatase Inhibitors and Bone Loss: Conclusion and Summary
Aromatase inhibitors are an effective treatment for breast cancer. However, they have side effects that patients and clinicians need to address.
There is a relationship between aromatase inhibitors and bone loss, osteoporosis and bone density. Aromatase inhibitors disrupt the bone remodeling process and can lead to a reduction in bone density and cause osteoporosis. In summary:
- Aromatase inhibitors effectively treat estrogen receptor-positive breast cancer but can cause significant bone loss
- Cancer treatments often affect bone health more than cancer itself through various mechanisms
- Without preventive measures, aromatase inhibitors may lead to osteoporosis, especially in patients who already have osteopenia
- Multiple treatment options exist to counter bone loss, including medications and low intensity vibration therapy
- A combined approach using both medication and mechanical stimulation, specifically low intensity vibration, appears most effective at maintaining bone density during treatment
Margaret Martin
Further Readings
Reference
- Peyman Hadji, Matty Aapro, Nasser Al-Dagri, Majed Alokail, Emmanuel Biver, Jean-Jacques Body, Maria Luisa Brandi, Janet Brown, Cyrille Confavreux, Bernard Cortet, Matthew Drake, Peter Ebeling, Erik Fink Eriksen, Ghada El-Hajj Fuleihan, Theresa A. Guise, Nick C. Harvey, Andreas Kurth, Bente Langdahl, Willem Lems, Radmila Matijevic, Eugene McCloskey, Rossella Nappi, Santiago Palacios, Georg Pfeiler, Jean-Yves Reginster, René Rizzoli, Daniele Santini, Sansin Tuzun, Catherine Van Poznak, Tobias De Villiers, M. Carola Zillikens, Robert Coleman, Management of aromatase inhibitor-associated bone loss (AIBL) in women with hormone-sensitive breast cancer: An updated joint position statement of the IOF, CABS, ECTS, IEG, ESCEO, IMS, and SIOG, Journal of Bone Oncology, Volume 53, 2025, 100694, ISSN 2212-1374, https://doi.org/10.1016/j.jbo.2025.100694.
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