Intermittent Use of Nitrates Increases Bone Mineral Density: The Study of Osteoporotic Fractures*

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Nitric oxide slows bone remodeling and bone loss in animals. Because nitroglycerin and other nitrates increase nitric oxide levels, we hypothesized that nitrate use may be associated with greater bone mineral density (BMD) and decreased risk of fracture in humans. Further, intermittent nitrate use may be associated with greater benefits than daily nitrate use, which results in tachyphylaxis. We tested this hypothesis using data from the Study of Osteoporotic Fractures. We prospectively studied 6201 elderly women of whom 317 took nitrates on a daily basis and 74 used them intermittently. We measured BMD at the hip and the heel and adjusted all comparisons for multiple potential confounders. We found that women taking daily nitrates had slightly greater hip BMD (difference, 1.3%; 95% confidence interval [CI], 0.14-4.1%) but the same heel BMD (difference, 0%; 95% CI −2.6-2.6%) as nonusers. By contrast, women using nitrates intermittently had substantially greater hip (difference, 2.6%; 95% CI, 0.4-6.8%) and heel BMD (difference, 5.3%; 95% CI, 2.6-11%) than nonusers. This study suggests that the intermittent administration of nitrates may enhance BMD.

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