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Transdermal Nitroglycerin Therapy May Not Prevent Early Postmenopausal Bone Loss

Division of Endocrinology (S.J.W.), Department of Medicine (J.P.G., A.C.W.), University of Medicine and Dentistry, New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903-0019; Department of Statistics and Biostatistics (D.R.H.), Rutgers University, Piscataway, New Jersey; and The NOVEL Study Group

Address all correspondence and requests for reprints to: Sunil J. Wimalawansa, M.D., Ph.D., 372-MEB, Division of Endocrinology, Department of Medicine, Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903-0019. E-mail: wimalasu{at}umdnj.edu.

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.