HOUSTON – One year of denosumab for treatment of men with low bone mineral density resulted in significant increases in bone density at the lumbar spine and all other measured skeletal sites in the phase III ADAMO trial.
The drug’s effects on BMD were similar regardless of patient age, baseline testosterone level, initial BMD, and estimated 10-year osteoporotic fracture risk, according to Dr. Ugis Gruntmanis of the Dallas Veterans Affairs Medical Center and the University of Texas Southwestern Medical Center.
Dr. Ugis Gruntmanis
"The increases in bone mineral density in this population were similar to those observed in earlier trials in postmenopausal women with osteoporosis and in men with prostate cancer receiving androgen deprivation therapy," he reported at the annual meeting of the Endocrine Society.
Moreover, the adverse event profile for denosumab (Prolia) in ADAMO was indistinguishable from that with placebo.
"There was no osteonecrosis of the jaw or atypical femur fractures in this study. You really wouldn’t expect to see that in a study of this size," the endocrinologist added.
ADAMO is a multicenter, double-blind, randomized, phase III clinical trial in which 242 men with low BMD were randomized to 60 mg of denosumab or to placebo given subcutaneously every 6 months for 1 year. The primary end point in ADAMO was change in BMD at the lumbar spine from baseline through 12 months. At the 12-month mark, all patients were placed on open-label denosumab for another year; the 24-month secondary outcomes are not in yet.
Participants had to have a BMD T-score of -2.0 or less and -3.5 or greater at the lumbar spine or femoral neck, or a prior major osteoporotic fracture along with a T-score of -1.0 or less and -3.5 at the lumbar spine or femoral neck. The men’s average age was 65 years, 94% were white, and one-quarter had a history of a major osteoporotic fracture. All subjects received daily calcium and vitamin D supplements.
At the 6-month mark, lumbar spine BMD had improved by 4.3% over baseline in the denosumab group compared with 0.9% in controls. At 1 year, the denosumab group averaged a 5.7% increase over baseline while the placebo group remained flat at a 0.9% gain.
Total hip BMD improved by 2.4% at 12 months in the denosumab group compared with 0.3% in controls, and by 0.6% at the distal one-third of the radius compared with a 0.3% loss with placebo; both of those differences favoring denosumab were statistically significant. So were the denosumab-induced BMD gains at the femoral neck and trochanter.
In subgroup analyses, the 15% of men with a baseline serum testosterone below 250 ng/dL had a 4.4% greater gain in lumbar spine BMD than with placebo, while those with a testosterone of 250 ng/dL or above had a similar 4.8% net gain.
Men with a baseline FRAX score placing them in the lowest tertile for 10-year major osteoporotic fracture risk, at less than 6.4%, had an absolute 5.1% greater gain in lumbar spine BMD than with placebo, while those with a 10-year risk of 6.4%-11.2% had a net 5.3% gain in lumbar spine BMD and men with a greater than 11.2% fracture risk had a net placebo-subtracted 4.0% gain; the denosumab-driven BMD gains in these three fracture risk groups were statistically similar, according to Dr. Gruntmanis.
One of the secondary end points in ADAMO was the change in the bone resorption biomarker CTX-1 between baseline and day 15 of the study. The CTX-1 level plunged by 81% in the denosumab group by day 15, with 60% suppression at 12 months.
Osteoporosis and fractures remain widely underrecognized and undertreated in men, Dr. Gruntmanis said. An estimated 2 million American men have osteoporosis. Worldwide, 39% of all osteoporotic fractures occur in men above age 50.
He reported receiving research grants from Amgen, Novartis, GlaxoSmithKline, and Procter & Gamble.