Understanding and managing fracture risk in patients with cancer
In the global fight against cancer, a quiet revolution is taking place. Thanks to earlier detection and more effective treatments, millions of people are surviving cancer and living longer than ever before. In the UK alone, approximately 385,000 new cancer cases are diagnosed annually, with about half of individuals now surviving at least 10 years post-diagnosis. However, this remarkable success has revealed an unexpected challenge: a significantly increased risk of bone fractures among cancer survivors.
New cancer cases annually in the UK
Survive at least 10 years post-diagnosis
Common cancers with increased fracture risk
Fractures in cancer patients are not just painful incidents—they significantly impact quality of life, require substantial healthcare resources, and are associated with increased mortality. A recent UK population-based study found that survivors of 15 out of the 20 most common adult cancers had a heightened risk of fractures, with this risk persisting up to five years after diagnosis 3 . The underlying causes are complex and multifaceted, stemming from both the disease itself and the very treatments that save lives.
Cancer therapies, while essential for treating the primary disease, can inadvertently weaken the skeletal system through several mechanisms. Understanding these effects is the first step toward protecting bone health during and after cancer treatment.
For patients with hormone-responsive cancers like breast and prostate, endocrine therapies are cornerstone treatments, but they exact a toll on bones.
Chemotherapy drugs can directly damage bone cells and often induce premature menopause in younger women, creating an estrogen-deficient state that accelerates bone loss.
| Treatment Category | Examples | Effect on Bone | Associated Fracture Risk Increase |
|---|---|---|---|
| Aromatase Inhibitors | Anastrozole, Letrozole | Accelerated bone loss | 34% with extended use 7 |
| Androgen Deprivation Therapy | GnRH agonists | Reduced bone density | 54% higher than non-users |
| Chemotherapy | Doxorubicin, Methotrexate | Direct bone cell damage + premature menopause | Varies by regimen |
| Immunotherapy | Immune checkpoint inhibitors | Disrupted bone remodeling | Emerging concern 5 |
| Corticosteroids | Dexamethasone | Increased bone resorption | Significant, especially in elderly |
Used in postmenopausal breast cancer, significantly reduce estrogen levels, accelerating bone loss and increasing fracture risk.
Extended use for 5-10 years is associated with a 34% higher risk of fractures 7
For prostate cancer, suppresses testosterone, leading to increased bone resorption and fracture risk.
19.4% of patients receiving ADT experienced fractures within 12-60 months after diagnosis, compared to only 12.6% of those who did not receive ADT
Has a complex relationship with bone health—it appears protective in postmenopausal women but may promote bone loss in premenopausal women.
To understand how endocrine therapies translate into real-world fracture risks, a comprehensive nationwide cohort study in South Korea analyzed data from 63,021 newly diagnosed breast cancer patients between 2008 and 2016 9 . This research provides crucial insights into how different treatments affect various age groups.
Excluded patients with pre-existing osteoporosis, prior fractures, or conditions affecting bone health to isolate the treatment effects.
Categorized based on endocrine therapy: tamoxifen users, aromatase inhibitor (AI) users, non-users, and those who switched medications.
Used diagnostic codes, procedure codes, and imaging codes to accurately identify fractures of the hip, vertebrae, wrist, and humerus.
Patients were monitored from six months after diagnosis until their first fracture, death, or the end of the study period in 2017.
The analysis yielded nuanced findings that challenge blanket assumptions about bone risk in cancer patients:
These findings highlight that the effect of cancer treatments on bone health is not uniform across all patient groups. The researchers concluded that age and menopausal status significantly influence how endocrine therapies affect fracture risk, suggesting that bone protection strategies should be tailored to individual patient characteristics.
| Therapy Group | Age <50 | Age ≥50 | Overall Effect |
|---|---|---|---|
| Tamoxifen | No significant protection | 25% reduced risk (HR=0.75) | Protective in older women |
| Aromatase Inhibitors | 54% increased risk (HR=1.54) | No significant increase | Risk varies by age |
| Non-users | Reference group | Reference group | Baseline risk |
While much research has focused on breast and prostate cancers, recent evidence indicates that fracture risk extends across many cancer types. The negative effects on the skeletal system represent a shared challenge in oncology.
A UK population-based study using the Clinical Practice Research Datalink found that the risk of any bone fracture increased in 15 out of 20 common adult cancers, with major osteoporotic fracture risk increased in 17 out of 20 cancers 3 . The mechanisms include:
As cancer therapeutics evolve, so do their effects on bone health. The International Osteoporosis Foundation notes that immunotherapies and targeted therapies—while revolutionary for treating previously untreatable cancers—are now linked to increased fracture rates and disruptions in bone remodeling 5 . However, not all newer agents are harmful; some, like tyrosine kinase inhibitors or proteasome inhibitors, may actually be protective for bone 5 .
| Cancer Type | Any Fracture Risk | Major Osteoporotic Fracture Risk | Key Risk Factors |
|---|---|---|---|
| Breast | Increased | Increased | Aromatase inhibitors, ovarian suppression |
| Prostate | Increased | Increased | Androgen deprivation therapy |
| Lung | Increased | Increased | Bone metastases, inflammation |
| Lymphoma | Increased | Increased | Glucocorticoid use, direct bone effects |
| Multiple Myeloma | Significantly increased | Significantly increased | Direct bone destruction |
The good news is that multiple strategies exist to protect and strengthen bones during and after cancer treatment. A proactive, multidisciplinary approach can significantly reduce fracture risk.
Comprehensive fracture risk assessment should be integral to cancer care:
Both pharmacological and lifestyle interventions can make a substantial difference:
As cancer survivorship continues to grow, the medical community is increasingly recognizing the importance of addressing long-term complications like fragility fractures. Current research is exploring more refined risk-prediction models that account for cancer type, specific treatments, and individual patient factors 4 . There is also growing momentum to integrate fracture risk assessments directly into oncology care pathways, supported by clinician education and cross-disciplinary collaboration between oncologists, endocrinologists, and bone health specialists 5 .
Ultimately, protecting bone health in cancer patients is not just about preventing fractures—it's about improving survival, maintaining independence, and enhancing quality of life throughout the cancer journey and beyond. With growing awareness and proactive management, the hidden threat of cancer-related bone loss can be effectively addressed, allowing survivors to live not just longer, but better.