Context: Osteoporosis is common among postmenopausal women; animal studies and human pilot studies support the concept of nitric oxide (NO) donors reducing bone mineral density loss.
Objective: The objective of the study was to evaluate whether NO donor, nitroglycerin, prevents postmenopausal bone loss.
Design: This was a 3-yr randomized, double blinded, single-center, placebo-controlled clinical trial.
Setting: The single-center study was conducted at the University of Medicine and Dentistry-Robert Wood Johnson Medical School (New Brunswick, NJ).
Participants: Participants included 186 postmenopausal women aged 40-65 yr, with lumbar bone mineral density (BMD) T-scores of 0 to -2.5.
Intervention: Women, stratified by lumbar T-score (<-1.50 and >or=-1.50) and years since menopause (<or=5 and >5 yr), were randomized to receive nitroglycerin ointment (22.5 mg as Nitro-Bid) or placebo ointment received daily for 3 yr. Both groups took 630 mg daily calcium plus 400 IU vitamin D supplements.
Measurements: 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% confidence interval -1.001, 1.975). Secondary outcomes also did not differ by intervention arm. The active group reported more headaches compared with the placebo group (57 vs. 14%, P < 0.001). 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 with a placebo. Once-daily dosing with 22.5 mg of transdermal-administered nitroglycerin was not effective (compliance adjusted dose was only approximately 16 mg/d); a sub-therapeutic dose.