For patients with cancer who received hormone-disrupting chemotherapy, improved long-term survival has come with a catch: decreased bone mineral density (BMD). Survivors of prostate and breast cancer and their clinicians need to monitor bone and dental health because the essential hormones used for bone remodeling have been depleted by androgen deprivation therapy and premature menopause and chemotherapy, respectively.1

Cancer treatment-induced bone loss can occur when the body is depleted of androgens and estrogens, which are essential for bone growth and maintenance.1 Evidence also points to the role of other hormones in maintaining bone health, including inhibins and activins.1

Breast Cancer and Bone Health

With more women surviving breast cancer, in large part because of the availability of tamoxifen and aromatase inhibitor therapy, lifelong monitoring for bone health has never been more important.2 In women who received chemotherapy with ovarian-suppressing agents, treatment-related lumbar spine bone loss was up to 10% after just 1 year of therapy.2

Antiresorptive medications may help prevent bone loss related to cancer treatment. A 3-year study found that 4 mg zoledronic acid every 6 months during receipt of adjuvant endocrine therapy increased bone mass in women with early-stage breast cancer who had undergone premature menopause because of cancer treatment.2

One of the main causes of bone loss in postmenopausal women who received adjuvant endocrine therapy has been aromatase inhibitors, which are linked to a 2% loss of BMD at the lumbar spine annually.2 Several international medical organizations introduced a joint statement in 2017 on monitoring and treating women who received aromatase inhibitor therapy to prevent bone loss and the resulting fractures.3 Guidelines recommend denosumab or bisphosphonates for postmenopausal women at high risk for fractures (ie, patients with a baseline T score of <-2.0 or with ≥2 clinical risk factors).3 Premenopausal women at high risk for fractures should receive zoledronic acid or clodronate to prevent bone loss and bone metastases.3

The consensus bifurcates according to the primary risk: denosumab is recommended for women whose primary concern is fracture risk, and bisphosphonate therapy for those at high risk for cancer recurrence.3 For women whose T-score is >-2.0 with no additional risk factors, the guidelines suggest exercise, supplements of vitamin D and calcium, and monitoring BMD every 1 to 2 years.3

Although first-line monitoring includes BMD testing, researchers in Italy discovered that quantitative ultrasound of the fingers may provide a radiation-free alternative to dual-energy x-ray absorptiometry scanning. Alongside trabecular bone score of the lumbar spine, quantitative ultrasound can indicate which women are at higher risk for fractures.4

Diabetes May Hasten Bone Loss in Prostate Cancer

Emerging evidence suggests that concurrent diabetes may be a catalyst for prostate cancer progression.5 A study of 148 men (113 without diabetes [median age, 68 years] and 35 with diabetes [median age, 73 years]) with castration-resistant prostate cancer found that the patients who had concurrent diabetes had a greater rate of cancer progression than those who did not have diabetes (hazard ratio, 4.58; 95% CI, 1.92-10.94; P =.0006).

“Androgen deprivation therapy is associated with bone loss and may lead to osteoporosis,” said coauthor William K. Oh, MD, chief, Division of Hematology and Medical Oncology and professor of medicine and urology at the Icahn School of Medicine at Mount Sinai in New York City. “Diabetes can also contribute to bone fragility and osteoporosis, and so the two conditions may synergistically cause bone-related issues such as pain and fracture.”

How to Improve Bone Health for Patients With Prostate Cancer

Education is key to improving bone stability in patients who have had prostate cancer.6 Shabbir M. H. Alibhai, MD, MSc, professor at the University of Toronto in Ontario, Canada, and colleagues sought to determine how to improve bone health outcomes in men who had had prostate cancer.

In a phase 2 study, 119 men (aged ≥50 years) receiving androgen deprivation therapy for prostate cancer were randomly assigned to receive a bone health pamphlet with brief instructions from a family physician, a pamphlet with support from a bone health care coordinator, or usual care.6 The primary end point was a BMD test within 6 months of intervention. Secondary end points included appropriate use of calcium, vitamin D, and bisphosphonate/denosumab prescriptions.6 Men who received support from a bone health care coordinator were more likely to get a BMD test vs those who received usual care (81% vs 36%, respectively; P <.001). The same was true for men in the intervention group who received some instruction from a family physician vs the usual care group (58% vs 36%; P =.015).6

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Both groups also benefited from greater uptake of calcium and vitamin D supplements, confirming that more education and awareness can improve bone health in men who have received androgen deprivation therapy.6

“Recent data presented at the American Society of Clinical Oncology meeting reinforce the need for good bone health care with antiresorptive therapies to prevent skeletal-related events in advanced/metastatic prostate cancer,” said Dr Alibhai. “One challenge that remains, however, is translating guidelines into usual clinical practice.”

Dr Alibhai recommended the following best practices for maintaining bone health in patients who have had prostate cancer: “First, ensure good bone health behaviors, such as stopping smoking, minimizing alcohol intake, and regular exercise, including weight-bearing exercises. Second, ensure enough calcium and vitamin D through diet and/or supplements. Third, everyone should have a baseline BMD test and subsequent treatment. Repeat testing can be based on the baseline fracture risk using a calculator such as FRAX. This should apply to men across the spectrum of disease, but particularly men receiving androgen deprivation therapy or advanced therapies for metastatic castration-resistant disease.”

Summary & Clinical Applicability

Improved survival of patients with prostate and breast cancer has come at a cost. Hormone-disrupting therapies can cause reduced bone mineral density, osteoporosis, and fractures. Clinicians need to be vigilant with preventive care for patients with these cancers to maintain their dental and bone health.

Limitations & Disclosures

None.

References

1. Handforth C, D’Oronzo S, Coleman R, Brown J. Cancer treatment and bone health. Calcif Tissue Int. 2018;102(2):251-264.

2. Bruyère O, Bergmann P, Cavalier E, et al. Skeletal health in breast cancer survivors. Maturitas. 2017;105:78-82.

3. Hadji P, Aapro MS, Body JJ, et al. Management of aromatase inhibitor-associated bone loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: joint position statement of the IOF, CABS, ECTS, IEG, ESCEO IMS, and SIOG. J Bone Oncol. 2017;7:1-12.

4. Catalano A, Gaudio A, Agostino RM, Morabito N, Bellone F, Lasco A. Trabecular bone score and quantitative ultrasound measurements in the assessment of bone health in breast cancer survivors assuming aromatase inhibitors [published online May 24, 2019]. J Endocrinol Invest. doi:10.1007/s40618-019-01063-0

5. Shevach J, Gallagher EJ, Kochukoshy T, et al. Concurrent diabetes mellitus may negatively influence clinical progression and response to androgen deprivation therapy in patients with advanced prostate cancer. Front Oncol. 2015;5:129.

6. Alibhai SMH, Breunis H, Timilshina N, et al. Improving bone health in men with prostate cancer receiving androgen deprivation therapy: results of a randomized phase 2 trial. Cancer. 2018;124(6):1132-1140.

This article originally appeared on Endocrinology Advisor