Risedronate More Than Counteracts Bone-Depleting Effects of Aromatase Inhibitors

Martha Kerr

September 24, 2007

September 24, 2007 (Honolulu) — Not only is aromatase inhibitor–induced damage to bone corrected, but bone mineral density (BMD) is improved to above-baseline levels when postmenopausal women with hormone receptor–positive breast cancer on aromatase inhibitors have the bisphosphonate risedronate ( Actonel, Procter and Gamble Pharmaceuticals, Inc) added to their treatment regimen.

The 12-month results of the Study of Anastrozole with the Bisphosphonate Risedronate (SABRE) were presented here during the American Society for Bone and Mineral Research 29th Annual Meeting by lead investigator Richard Eastell, MD, professor of medicine and the Academic Unit of Bone Metabolism at the University of Sheffield, United Kingdom.

SABRE was a multicenter study consisting of 234 postmenopausal women with hormone receptor–positive early-stage breast cancer. Mean age was 64 years (range, 45 – 91 years).

Subjects were categorized into 3 groups according to fracture risk. Those in the high-risk group (38 women) had a lumbar spine or hip BMD T-score below −2.0 and a history of "fragility fracture" or were at high risk of fracture. Those with a moderate fracture risk (154 women) had T-scores below −1.0 but at least −2.0 or above and a history of fragility in a first-degree relative, early menopause or advanced age, low body weight (less than 127 lbs), or a current smoker. Those with the lowest fracture risk (42 women) had T-scores of −1.0 and above and no history of fractures or fragility.

All subjects had received the aromatase inhibitor anastrazole 1 mg/day for 2 years. They were given calcium 500 mg daily or vitamin D 200 IU daily.

Women in the high fracture risk group were prescribed risedronate 35 mg a week. Moderate-risk patients were randomly assigned to receive risedronate 35 mg/week or placebo, whereas women in the lowest-risk group did not receive bisphosphonate therapy.

At 12 months, BMD in the high-risk group had increased significantly at the lumbar spine (approximately 3.0%; P < .0001) and hip (>1.0%; P = .012). BMD in the low-risk group had decreased numerically at the lumbar spine ( P = .3511) and hip ( P = .4918), but the change was not statistically significant.

In moderate fracture risk patients, the increase in BMD was significantly greater at the lumbar spine in those on risedronate compared with those on placebo (>1.0%; P < .0001), as well as at the hip (approximately 1.0%; P = .002).

There was also a significant decrease in bone turnover markers between all risedronate-treated women and placebo-treated women. Low-risk women had an increase in serum C-terminal cross-linking telopeptide of type 1 collagen and bone alkaline phosphatase, indicating that bone degradation was taking place.

Ten women withdrew from the study, all because of adverse effects related to the aromatase inhibitor. There was 1 nontreatment related death during the year of follow-up.

"In postmenopausal women with breast cancer who are already at moderate to high risk of fragility fracture and are scheduled for treatment with anastrazole, bone health can be managed according to established guidelines," Dr. Eastell told meeting attendees. "For patients who are already at risk, risedronate at the licensed dose was sufficient to prevent a decrease in BMD and an increase in bone turnover."

In an interview with Medscape, Pauline Camacho, MD, professor of medicine at Loyola University in Chicago , Illinois, commented, "There is a trend toward switching women over to aromatase inhibitors from tamoxifen.... Physicians need to carefully calculate if this switch is necessary.

"Tamoxifen is bone-sparing. If women could be maintained on it rather than switching to an aromatase inhibitor, that would be helpful [to bonehealth]," Dr. Camacho added.

"Women on aromatase inhibit should be evaluated as if they were much older than their chronological age[, and] serum vitamin D levels should also be evaluated," she said. "Vitamin D deficiency is very common. In 37.5% of women, levels are not where they should be."

In addition, Dr. Camacho recommended routine monitoring of parathyroid hormone levels, serum calcium, 24-hour urinary calcium excretion, and calcium/creatinine clearance.

Dr. Eastell received funding from AstraZeneca. Dr. Camacho reports no relevant financial relationships.

American Society for Bone and Mineral Research 29th Annual Meeting: Abstract M300. Presented September 17, 2007.

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