Transdermal nitroglycerin therapy may not prevent early postmenopausal bone loss

SJ Wimalawansa, JP Grimes, AC Wilson… - The Journal of …, 2009 - academic.oup.com
SJ Wimalawansa, JP Grimes, AC Wilson, DR Hoover
The Journal of Clinical Endocrinology & Metabolism, 2009academic.oup.com
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 …
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 ≥−1.50) and years since menopause (≤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 ∼16 mg/d); a sub-therapeutic dose.
No substantial bone mineral density changes were observed between postmenopausal women receiving once-daily 22.5 mg of transdermal nitroglycerin, compared to calcium plus vitamin D (compliance adjusted dose = 16 mg/day).
Oxford University Press