| Background. In vitro, animal, and human studies indicate that the use of organic nitrates is associated with increased bone mineral density (BMD).; Objectives. To determine if healthy postmenopausal women randomized to the organic nitrate isosorbide mononitrate (ISMO), compared with women randomized to placebo, have a greater mean percent decrease in N-telopeptide (NTx; a marker of bone resorption), a greater mean percent increase in bone specific alkaline phosphatase (BSAP: a marker of bone formation), or both.; Design. A randomized, double-blind placebo controlled trial. The study had a 3 month run in period during which all women received 500 mg/day of calcium and 400IU/day of vitamin D. At the end of this period, participants were randomly assigned to one of three treatment groups; placebo, 5 mg/day of ISMO, or 20 mg/day of ISMO. The treatment period lasted 3 months and women in all treatment groups were prescribed 500 mg/day of calcium and 400IU/day of vitamin D during the treatment period.; Participants. 144 healthy postmenopausal women with osteopenia or normal BMD by BMD testing. Main outcome measures. Mean percent change in urine NTx and mean percent change in serum BSAP.; Results. Women randomized to ISMO (5 mg and 20 mg) had a 37% mean percent decrease in NTx (95% Confidence Interval: 22.9 to 52.9) and an 18.7% mean increase in BSAP (95% CI: 8.6 to 29.1) compared with women randomized to placebo. Results were not changed after adjustment for age and weight. Further, there appeared to be a dose response, such that women randomized to 20 mg of ISMO had a 9.8% greater mean decrease in NTx (95% CI: 4.8 to 16.8) and a 13.7% greater mean increase (95% CI: 2.5 to 24.9) in BSAP, compared with women randomized to 5 mg of ISMO.; Conclusions. Our study suggests that use of ISMO in healthy postmenopausal women is associated with a decrease in bone resorption and an increase in bone formation. Ultimately, this may increase BMD and decrease osteoporotic fractures. |
