Nick Mulcahy

March 20, 2014

HOLLYWOOD, Florida — The National Comprehensive Cancer Network (NCCN) has issued an updated report on optimizing bone health in cancer patients.

The report keeps pace with new data on bone health and treatment that have emerged since the previous report was issued in 2009, Azeez Farooki, MD, an endocrinologist from the Memorial-Sloan Kettering Cancer Center in New York City, said here at the NCCN 19th Annual Conference.

After giving the NCCN audience a review of the basics of bone loss, assessment, and treatment in cancer settings, Dr. Farooki spoke to Medscape Medical News about what is new and noteworthy.

He highlighted 3 items in the NCCN Task Force Report: Bone Health in Cancer Care, which was published in late 2013.

Atypical Femoral Fractures

First, atypical femur fractures, which are rare events, have "come into being as a clinical entity," and are associated with the long-term use of antiresorptive drugs, said Dr. Farooki.

These antiresorptive drugs, which include bisphosphonates such as alendronate and the new product denosumab, are used to counter the bone loss caused by cancer and cancer treatments.

Androgen-deprivation therapy for the treatment of prostate cancer and aromatase inhibition for breast cancer both cause bone loss, Dr. Farooki noted.

The majority of cases of atypical femur fracture have been associated with bisphosphonates, he pointed out.

The risk factors for atypical femur fracture include bisphosphonate use longer than 5 years, younger age, Asian race, low vitamin D levels, the use of multiple antiresorptive drugs (e.g., tamoxifen plus bisphosphonate), the use of glucocorticoids or proton pump inhibitors, hypophosphatasia, and rheumatoid arthritis.

In about 75% of cases, patients who develop these rare femur fractures will have prodromal anterior thigh or groin pain, said Dr. Farooki.

He emphasized that atypical femoral fractures are rare and "fundamentally different" from common osteoporotic femur fractures. A recent review found an incidence of around 1%, he noted (J Bone Joint Surg Am. 2011;93:1235-1242).

That review was a retrospective study of 327 cancer patients with a variety of tumor types and bone metastases or myeloma. All were on intravenous bisphosphonates; the median number of doses was 43 and the median length of treatment was 66 months. There were 4 cases of atypical femoral fractures (1.2%) in the study population. All were female (3 with breast cancer; 1 with myeloma).

If a patient has been on an antiresorptive agent for a long time, especially a bisphosphonate, then consider a "drug holiday," said Dr. Farooki, echoing the new NCCN guidance.

Specifically, the task force report notes that "after 3 to 5 years of potent antiresorptive therapy (bisphosphonate or denosumab) or after cancer therapy posing a risk for bone loss is stopped, reassess fracture risk and consider a drug holiday or discontinuation."

This recommendation also reflects guidance from the federal government, said Dr. Farooki. "The FDA has weighed in on this," he said.

Calcium Issues

Second, Dr. Farooki reminded clinicians that potent antiresorptives also can cause hypocalcemia, or low serum calcium levels.

Clinicians should ensure that the vitamin D and calcium intake of their patients is sufficient. But Dr. Farooki emphasized that patients should not overdo calcium supplementation.

Many people take too much calcium.

"I think many people take too much calcium," he told Medscape Medical News.

He explained that calcium and vitamin D are critical to bone health, and that some randomized studies have shown that calcium and vitamin D supplementation decreases the risk for fracture.

The current recommendations are for 1200 mg/d of calcium (from food and supplements), said Dr. Farooki.

However, there are health risks associated with calcium supplements. "We now know that if you take too much calcium from supplements, you increase your risk for kidney stones," he said.

Furthermore, calcium supplements have been shown in some meta-analyses to raise the risk for cardiovascular disease; but this is controversial, said Dr. Farooki.

The good news is that the health risks are not related to calcium from the diet — only from supplements, he stressed.

Dietary sources of calcium include milk, cheese, broccoli, sardines, nuts and seeds, tofu, and a variety of fortified foods and drinks.

New Prostate Cancer Drug

Dr. Farooki highlighted the fact that the oral therapy radium-223 (Xofigo) was approved by the US Food and Drug Administration for use in advanced prostate cancer in men who have symptomatic bone metastases.

This product improves survival in men with advanced disease and prevents skeletal-related events (SRE). That novel combination of benefits is "impressive," said Dr. Farooki.

The approval was based on the large phase 3 ALSYMPCA trial of men with castration-resistant disease and bone metastases who previously received docetaxel or were ineligible to receive docetaxel.

In that trial, median overall survival was better with radium-223 than with placebo (14 vs 11.2 months; = .00185). In addition, time to first SRE was delayed with radium-223 (13.6 vs 8.4 months; = .00046).

Spinal cord compression and pathologic bone fractures were less frequent with radium-223 than with placebo.

Half of the study population had been on bisphosphonates, which makes the SRE results even more impressive, said Dr. Farooki.

National Comprehensive Cancer Network (NCCN) 19th Annual Conference. Presented March 14, 2014.


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