Nitrates Do Not Affect Bone Density or Bone Turnover in Postmenopausal Women: A Randomized Controlled Trial

Area of Science:

• Bone biology and pharmacology
• Clinical trial methodology
• Postmenopausal health

Background:

• Previous studies suggested organic nitrates may positively affect bone mineral density (BMD) and bone turnover.
• However, existing research presents inconsistencies, with some trials retracted due to scientific misconduct, necessitating further investigation.

Purpose of the Study:

• To determine the lowest effective dose and most suitable nitrate preparation for potential fracture prevention.
• To evaluate the efficacy and tolerability of organic nitrates in osteopenic postmenopausal women.

Main Methods:

• A 1-year, double-blind, randomized, placebo-controlled trial involving 240 osteopenic postmenopausal women.
• Investigated three nitrate preparations at two doses, assessing changes in BMD and bone turnover markers.
• Included a 2-week run-in period for tolerability and a planned 1-year observational extension.

Main Results:

• No statistically significant differences in BMD changes at any site or bone turnover markers were observed between nitrate groups and placebo.
• Pooled analysis of active treatment groups also showed no significant differences compared to placebo.
• High withdrawal rates (27% during run-in, 21% during the study) were reported, primarily due to nitrate-induced headaches, indicating poor tolerability.

Conclusions:

• Organic nitrates lack clinically relevant effects on BMD or bone turnover in postmenopausal women.
• The poor tolerability of organic nitrates, particularly headache, limits their use.
• These findings challenge the validity of prior research suggesting positive effects of nitrates on bone health.