Bone health among breast cancer survivors continues to be a heavily debated subject in medical oncology with many developments occurring during the past decade. Skeletal complications in breast cancer patient can be caused chemotherapy-induced ovarian failure, use of gonadotropin-releasing hormone (GnRH) agonists, surgical oophorectomy, and use of AI’s all of the above can cause bone loss and increased risk for fractures, however in this blog post, I will focus my discussion on bone toxicity caused by aromatase inhibitors (AI) such as anastrozole, letrozole, and exemestane. With the increasing use of AI’s in postmenopausal women, as well as, the use of AI’s in combination with GnRH agonist agents in premenopausal women, oncologists are now more than ever required to have a deep understanding of bone loss associated with AI’s (AIBL) and taking measures to help prevent such complication. For a patient-oriented discussion of bone health please click here.
Women receiving aromatase inhibitor therapy are at increased risk for fractures.
How significant is the bone loss problem in breast cancer patients?
- With early diagnosis and improved treatment, breast cancer patients are now living longer, with old age itself is a risk factor for bone loss, thus there is a higher risk for developing bone loss and fractures.
- The majority of breast cancer cases are hormone responsive, endocrine therapy is widely used, and AI’s is now the standard endocrine therapy for postmenopausal women.
- AI therapy is clearly associated with increased risk of bone loss and fractures.
- it is roughly estimated that one in five women will sustain an AI related fracture.
- The higher incidence of fractures with AI’s use was documented in several trials including ATAC, BIG 1-98, as well as ABCSG-12
How AI’s can produce bone loss?
AI’s are potent inhibitors of conversion of Androgen to Estrogen resulting in a rapid decrease in estrogen and subsequently increased bone resorption and bone loss.
How to assess for bone loss and fracture risk?
All Women starting AI’s must have a fracture risk assessment
Clinician pursue such risk assessment through the following,
A. BMD as measured by DEXA scan.
B. Other clinical risk factors such as,
- Advancing age.
- Prior history of fragility fracture.
- Chronic glucocorticoids use.
- Low body mass index (BMI)
- Parental history of hip fracture.
- Cigarette smoking
- Excessive Alcohol use.
The above is also measures is incorporated in some form in the FRAX risk assessment tool, such tool will provide the 10-year probability of hip fracture, it should be noted, however, that the FRAX tool is developed for the general population and it tends to underestimate fracture risk associated with AI’s.
In Addition, ASCO issued guidelines on when to use DEXA scan, ASCO recommendation indicate proceeding DEXA scan, in the following patient categories (regardless of cancer diagnosis)
- All women older than 65
- All women between age 60-65 with additional risk factors.
- All women starting AI’s therapy.
Are there any anticancer properties to bisphosphonate therapy?
Bisphosphonate therapy is one important AI’s bone loss (AIBL) prevention intervention. Before discussing prevention of AIBL it is important to clarify the role of bisphosphonate in the prevention of breast cancer. Multiple studies and clinical trials looked into the anti-cancer qualities of bisphosphonate showed unequivocally favorable effect of using bisphosphonate in decreasing breast cancer recurrence as well as breast cancer-specific mortality a recently published meta-analysis of all such trials by the Early Breast Cancer Clinical Trial Group (EBCTCG) indicate decreasing incidence of bone recurrence by 34% and breast cancer-specific mortality by 17%. Furthermore, a consensus statement by a panel of oncologist and bone specialist was published here, also ASCO published guidelines of bisphosphonate use, defining the role of bisphosphonate and recommendations for the age group. I strongly recommend a thorough reading of the ASCO guidelines as well as understanding the bisphosphonate-related osteonecrosis of the jaw (ONJ), a summary of the ASCO guidelines is shown below, or downloaded by clicking here.
Prevention of AIBL.
Following bone loss and fracture assessment and assessment for candidacy for bisphosphonates therapy discussed above(apart from AIBL prevention), clinicians would proceed with the following,
A. Nonpharmacologic measures:
- Adoption of a healthy lifestyle, regular exercise (please refer to my post on exercise here), smoking cessation.
- All women on AI therapy must receive Calcium and Vitamin D supplements, the recommended dose is Calcium 1200mg and Vitamin D 800IU daily.
B. Pharmacologic treatment for AIBL prevention:
There are several published guidelines for when to proceed with pharmacologic therapy in the prevention of AIBL, for example, the National Comprehensive Cancer Network (NCCN) incorporates FRAX into its guidelines. NCCN recommends treatment when the FRAX 10-year fracture risk is >20 percent for major fracture or >3 percent for hip fracture, or when the T-score is <-2.0 (<-1.5 if there has been significant loss of BMD as a result of cancer therapy), please note as mentioned above the FRAX score tend to underestimate the risk in this particular patient group.