Transdermal nitroglycerin therapy may not prevent early postmenopausal bone loss.
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. The objective of the study was to evaluate whether NO donor, nitroglycerin, prevents postmenopausal bone loss.
This was a 3-yr randomized, double blinded, single-center, placebo-controlled clinical trial.
The single-center study was conducted at the University of Medicine and Dentistry-Robert Wood Johnson Medical School (New Brunswick, NJ).
Participants included 186 postmenopausal women aged 40-65 yr, with lumbar bone mineral density (BMD) T-scores of 0 to -2.5.
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.
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.
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.
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.