March 24, 2022
7 min read
Healio could not determine Brufsky’s relevant financial disclosures at the time of publication. Ott reports no relevant financial disclosures. Shapiro reports financial connections with 2nd.MD, Cardinal Health and UpToDate.
Bone loss is a natural part of aging — especially due to menopause for women — but certain cancer treatments and prolonged cancer survival can increase the risk for bone loss and the related outcome of fractures.
The two populations at the highest risk are women with breast cancer and men with prostate cancer. This is due to the effect that reducing or blocking hormones during treatment has on bone health.
“Bone health is a significant issue for cancer survivorship, mostly in [patients with] prostate cancer and breast cancer because of the prevalence of those cancers,” Charles L. Shapiro, MD, FASCO, professor of hematology and medical oncology at the Icahn School of Medicine at Mount Sinai and a HemOnc Today Editorial Board Member, told Healio in an interview. “The fact that we do better in breast and prostate cancer leads us to prolonged survival, which increases the risk for osteoporosis.”
Shapiro continued that risk factors extend beyond cancer type and can differ by age, especially for women, whether they are premenopausal or postmenopausal, and for men who require different hormone-blocking treatments than women.
In a study published in Journal of Clinical Oncology, Saad and colleagues described bone loss resulting from anticancer treatment as an “emerging problem.” Cancer treatment-induced bone loss occurs because of states induced by cancer therapies, such as premature menopause; estrogen deficiency caused by aromatase inhibitors; and testosterone deprivation.
“The typical patient with breast cancer — either through chemotherapy-induced ovarian failure or early menopause or aromatase inhibitors — loses bone because of decreased estrogen,” Shapiro said. “Chemotherapy-induced ovarian failure is relevant to premenopausal women, whereas bone loss among postmenopausal women is relevant to the aromatase inhibitors.”
According to, Adam M. Brufsky, MD, PhD, medical director of the UPMC Magee-Women’s Cancer Program at UPMC Hillman Cancer Center, co-director of their Comprehensive Breast Cancer Center, professor of medicine at the University of Pittsburgh School of Medicine and a HemOnc Today Editorial Board Member, about 60% to 65% of all early-stage breast cancers are estrogen driven, thus requiring estrogen-blocking therapy such as aromatase inhibitors.
“In particular, aromatase inhibitors have been found to increase bone loss and fracture risk,” he told Healio. “Bone health is especially important because it’s a source of fracture and fracture risk among those undergoing therapy.”
In a study published in Clinical Breast Cancer, Mincey and colleagues focused on the risk for cancer treatment-associated bone loss and fractures among women with breast cancer who received aromatase inhibitors.
Confirming previous data, the study’s results showed a significantly higher prevalence of bone loss (8.7% vs. 7.1%; RR = 1.3; 95% CI, 1.1-1.6) and bone fracture (13.5% vs. 10.3%; RR = 1.4; 95% CI, 1.2-1.6) among patients treated with aromatase inhibitors compared with controls.
“Hormone inhibitors may be a little worse for women, because in men with prostate cancer, we’re trying to suppress testosterone but let the estrogen be. Estrogen is more important for bones, even in men, than testosterone,” Susan M. Ott, MD, professor of medicine specializing in metabolic bone disease at University of Washington School of Medicine, told Healio.
Ott said that for women with breast cancer, it is sometimes best to reduce the estrogen as low as possible, and in some cases, treatment may be to completely eliminate estrogen.
“But the bone really needs estrogen to be healthy,” she said. “The chemotherapies we use are also going to have a negative effect on any type of tissue where there is a lot of activity, so that can affect bones as well.”
The other major population at risk is men undergoing treatment for prostate cancer who receive androgen deprivation therapy.
Greenspan and colleagues of a study published in The Journal of Clinical Endocrinology & Metabolism stated that they had previously reported a significant decrease in bone mass at all skeletal sites among men with prostate cancer who received ADT. Specifically, spine bone mineral density decreased 17% after 44 months of treatment.
In the current study, they found significant reductions in bone mineral density ranging from 2.5% to 4% (P < .05) at several locations, including hip and spine, among men who received emergent ADT for less than 6 months. Men who received long-term ADT for more than 6 months showed a 2 ± 0.6% (P < .05) reduction in bone mineral density at the total radius, whereas healthy controls and men with prostate cancer who didn’t receive ADT showed no significant changes.
The authors concluded that both acute and long-term effects of androgen suppression for prostate cancer can affect bone health. Specifically, the rate of bone loss is greatest in the first year after treatment, which may mean that antiresorptive therapy would provide the best outcomes if prescribed during that early period.
One of the keys to prevention of bone loss from cancer treatment is screening and testing. The common test for screening for osteoporosis is the dual-energy X-ray absorptiometry, also known as the DEXA scan.
Shapiro explained that, of the two output variables from the DEXA scan, the “T-score” was the most important. A normal T-score begins above –1. Osteopenia, the setting before osteoporosis, is –1 to –2.5, and osteoporosis is defined as a T-score of –2.5 or less or a nontraumatic fracture.
He continued that the score alone may not be enough to determine if a patient is at risk for bone health issues but that comorbid factors should also be considered.
“These risk factors include being on an aromatase inhibitor, chemotherapy-induced ovarian failure, rheumatoid arthritis, current smoking, chronic use of steroids and genetic history of osteoporosis,” he said. “If you put these people through cancer treatments, that compounds the problem further. Osteoporosis isn’t treated differently in cancer survivors and noncancer individuals; the important thing is awareness of the treatments given for cancer that can cause bone loss.”
Ott said that bone density testing is an “easy and painless method” to keep track of a patient’s bone health that all physicians should be aware of. It should be applied at the beginning of cancer treatment to record a patient’s baseline measurements.
She continued that patients, especially young patients, may have bone density that varies by 20% higher or lower than the average person. In this case, they may be able to either lose more bone density without it being a severe complication or they may be at greater risk for fracture than their peers.
She also noted that it’s important to take a history of fractures, even if they may have been marked as related to an accident.
Another piece of the overall prevention strategy is the use of supplements and exercise, which can be potentially useful from the beginning of treatment through survival.
“Calcium and vitamin D are necessary,” Shapiro said. “We screen for vitamin D deficiency, which is prevalent in the population of cancer survivors as well as the general population. It’s especially prevalent for survivors of [historically underrepresented groups] who often have vitamin D deficiency, in up to 75% of them.”
Besides supplements, researchers have studied the effect of exercise for improving bone health in cancer survivors.
Singh and Toohey conducted a systematic review and meta-analysis published in Journal of Science and Medicine in Sport that looked at the effect of exercise for improving bone health among cancer survivors.
The analysis included 26 trials with intervention durations that ranged between 12 weeks and 2 years. Most trials involved patients with breast cancer, were supervised and evaluated mixed-mode exercise, or combined aerobic and resistance.
Overall results showed that participation in various modes — including aerobic, resistance and mixed-mode — whether supervised or not correlated with improvements in whole body, hip, trochanter and femoral neck bone mineral density, with standardized mean differences ranging from 0.19 to 0.39 (P < .05). Their conclusion was that exercise should be recommended to prevent bone loss among cancer survivors.
Regardless of screening and prevention measures, many cancer survivors, especially those with longer survival outcomes, will face bone loss and potential fractures. In this case, each member of the patient’s care team should be aware of how best to manage bone health to avoid osteopenia and osteoporosis.
Oral bisphosphonates are key for the prevention and treatment of osteoporosis, Brufsky said, adding that their use has evolved over time.
He said that patients used to be treated with oral bisphosphonates, such as alendronate sodium, daily and then weekly, but now many of his patients are treated with ibandronate sodium monthly.
“Generally, we start with oral bisphosphonates for patients who are at least osteopenic, on antihormonal therapy, those who have risk factors related to bone density or those who have frank osteoporosis,” Brufsky said. “They would go onto these medications.”
Brufsky continued that, over time, treatment evolved to IV bisphosphonates that are given every 6 months or even once a year.
Osteoprotegerin mimics, such as denosumab (Prolia/Xgeva; Amgen), are another emerging option that can be used twice a year, with additional agents in the pipeline such as antisclerostin antibodies for benign osteoporosis, Brufsky said.
Research also has revealed that the use of bisphosphates for bone health also may improve cancer outcomes overall.
“The one thing that a lot of us physicians who have focused on this during their career have found is that if we give postmenopausal women some of the more powerful bisphosphonates, we can prevent bone metastasis,” Brufsky said. “We’re exploring a number of biomarkers for this. That’s kind of the cutting edge when it comes to bone loss. We’re trying to refine who would need pharmacological intervention for bone loss.”
With cancer survival rates generally increasing, consequences of treatment, such as bone loss, should become more top of mind, Shapiro said.
“Were increasingly getting good at achieving personal cures for patients, so it behooves us to be aware of the various problems faced by survivors, one of them being bone health,” he said. “Someone — whether it is the oncologist, local specialist or primary care physician — needs to take responsibility for a patient’s bone health.”
For more information:
Adam M. Brufsky, MD, PhD, can be reached at [email protected]
Susan M. Ott, MD, can be reached at [email protected]
Charles L. Shapiro, MD, can be reached at [email protected]