No change in postmenopausal BMD with nitroglycerin vs. placebo

Results of the Nitroglycerin as an Option: Value in Early Bone Loss (NOVEL) study do not support the effectiveness of nitroglycerin for the prevention of postmenopausal bone loss.

Three-year data indicate that bone mineral density changes did not differ between postmenopausal women randomly assigned to nitroglycerin compared with placebo.

The NOVEL study was a randomized, double-blind, placebo-controlled trial conducted at the University of Medicine and Dentistry-Robert Wood Johnson Medical School in New Brunswick, N.J.

Researchers enrolled 186 postmenopausal women aged 40 to 65 years with lumbar BMD T-scores of 0 to –2.5. Women were randomized to 22.5 mg nitroglycerin ointment (Nitro-Bid 2%) or placebo daily for three years. Both groups also took daily calcium and vitamin D supplements.

After 36 months of therapy, the researchers observed no significant difference for any absolute BMD measure or percent BMD change from baseline.

Percent change in lumbar vertebrae BMD — the primary endpoint — changed by –2.1% in the nitroglycerin group and –2.5% in the placebo group (P=.59).

Further, the researchers reported no difference in secondary outcomes with nitroglycerin vs. placebo. The BMD percent change in femoral neck was –5.2% in the active arm vs. –4.8% in the placebo arm. The percent change in trochanter was also similar, –5.2% in the active arm vs. –4.8% in the placebo arm.

“There were no qualitative or statistical differences between the active and placebo arms in posttreatment BMD levels and percent changes from baseline for all skeletal sites studied,” the researchers wrote. “After 36 months of treatment, both groups demonstrated decreases in bone density; the annual lumbar spine BMD decrease was 0.70% in the active arm and 0.83% in the placebo arm.”

Stratification by menopausal status revealed that women five years or less into menopause experienced greater decreases in BMD than women more years into menopause, especially in the total hip/femoral neck.

Prior use and adherence to calcium and vitamin D had no effect on BMD, according to the researchers.

Of note, the nitroglycerin group reported more headaches than the placebo group (57% vs. 14%).

Further studies that evaluate higher doses of nitric oxide donors are “warranted before discarding this as a novel therapy for osteoporosis,” the researchers concluded.

Wimalawansa SJ. J Clin Endocrinol Metab. 2009;94:3329-3336.