Study Finds No Effect of Organic Nitrates on Bone Mineral Density in Postmenopausal Women

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Organic nitrates did not affect bone density or turnover in postmenopausal women with osteopenia in a randomized controlled trial.

Organic nitrates do not affect bone density or turnover in postmenopausal women, according to the results of a randomized controlled trial published in the Journal of Bone and Mineral Research.

In a trial of postmenopausal women (aged ≥55 years), investigators aimed to evaluate the effect of different organic nitrate preparations on bone mineral density (BMD) and bone turnover to determine the most effective dose and preparation for promoting bone health.

A total of 240 women were randomly assigned to receive either oral isosorbide mononitrate (20-, 30-, or 60-mg dose), transdermal nitroglycerin (25- or 50-mg dose), or oral placebo.

Dual-energy x-ray absorptiometry was used to measure BMD at baseline and every 6 months at the lumbar spine, proximal femur, and total body. Treatment groups were compared with the placebo group individually and as a pooled population.

Over the 12-month treatment period, there was no significant difference in BMD changes at any site between the treatment and placebo groups, individually or combined.

Serum concentrations of bone turnover markers β-C-terminal telopeptide of type 1 collagen and procollagen type 1 N-terminal propeptide were also compared. No consistent effect of treatment was observed on either marker.

Over the course of the study, 31 patients stopped medication, including 30 in the nitrate-treated groups and 1 in the placebo group (P =.03). Of these 30 women from the treatment groups, 20 (67%) discontinued treatment due to treatment-related side effects, including 13 with headache (43%). An additional 46 women withdrew from the study during an initial run-in phase prior to random treatment assignment due to headaches as well.

A planned 12-month observation phase after treatment was forgone following the analysis of BMD and bone turnover markers at 12 months.

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The investigators noted that the study population consisted only of osteopenic postmenopausal women and that the generalizability of results to other populations may be limited.

“[D]iffering preparations and doses of nitrates had no clinically relevant effects on BMD and bone turnover and were relatively poorly tolerated,” the study authors concluded. “These results, and the null results of another similar-sized randomized trial, call into question the validity of previous clinical research reporting extremely large positive effects of nitrates on BMD or bone turnover.”

Disclosure: One study author reported affiliations with Auckland Bone Density.

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Bolland MJ, House ME, Horne AM, et al. Nitrates do not affect bone density or bone turnover in postmenopausal women: a randomized controlled trial [published online May 5, 2020]. J Bone Miner Res. doi:10.1002/jbmr.3982