Context: Osteoporosis is common among postmenopausal women; pilot studies support the concept of nitric oxide (NO) donors reducing bone mineral density loss.

Objective: Evaluate if NO donor, nitroglycerin prevents postmenopausal bone loss.

Design: Three-year randomized, blinded, single-center, placebo-controlled clinical trial.

Setting: Single-center study at the University of Medicine and Dentistry - Robert Wood Johnson Medical School, New Brunswick, New Jersey.

Participants: 186 postmenopausal women aged 40 to 65 years, with lumbar bone mineral density (BMD) T-scores of 0 to -2.5.

Intervention: Women, stratified by lumbar T-score (< -1.50 and -1.50) and years since menopause (5 and >5 years), were randomized to receive, i) nitroglycerin ointment (22.5 mg as Nitrobid®, or ii) placebo ointment receiving daily for three years. Both groups took 630 mg daily calcium plus 400 IU vitamin D supplements.

Measurements: Bone mineral density (BMD) was measured at 6 months and annually by dual energy x-ray absorptiometry. Percent change in lumbar vertebrae BMD was the primary outcome. Hip BMD, total body bone mineral content and height were secondary outcomes.

Results: After 36 months of therapy, changes of -2.1% in the active group (n=88) and -2.5% in the placebo group (n=82) in lumbar spine BMD were seen; p = 0.59 (95% CI -1.001, 1.975). Secondary outcomes also did not differ by intervention arm. The active group reported more headaches compared to the placebo group (57% vs. 14%, p<.001). Other adverse and serious adverse events were not different.

Conclusions: BMD changes did not substantially differ between postmenopausal women who received the dose of nitroglycerin tested, in comparison to a placebo. Once-daily dosing with 22.5 mg of transdermal-administered nitroglycerin was not effective (compliance adjusted dose was 16 mg/day).