Effect of Nitroglycerin Ointment on Bone Density and Strength in Postmenopausal Women: A Randomized Trial

Study Questions:

What is the effect of nitroglycerin on bone mineral density (BMD) in postmenopausal women?

Methods:

This was a single-center, double-blind, placebo-controlled randomized trial conducted between November 2005 and March 2010. Postmenopausal women with lumbar spine T-scores between 0 and -2.0 who completed a 1-week run-in period taking nitroglycerin ointment were followed for 24 months. Women were randomized to nitroglycerin ointment (15 mg/d) or placebo applied at bedtime. The primary outcome measures were BMD at the lumbar spine, femoral neck, and total hip. Secondary outcomes included indices of bone geometry and strength at the distal radius and tibia, and biomarkers of bone formation (bone-specific alkaline phosphatase) and bone resorption (urine N-telopeptide).

Results:

A total of 243 postmenopausal women were included in the study. At 2 years, women randomized to nitroglycerin had significant increases in BMD at the lumbar spine (from 1.05 to 1.14 g/cm2) versus placebo (percent change 6.7%; 95% confidence interval, 5.2%-8.2% p < 0.001). Significant changes were also observed for total hip and femoral neck. At 2 years, women receiving nitroglycerin also had increased volumetric trabecular BMD, increased cortical thickness, periosteal circumference, polar section modulus, and polar moment of inertia at the radius and tibia. Increases in bone-specific alkaline phosphatase and decreased urine N-telopeptide were observed. Incidence of serious adverse events was similar between the two groups. Among women who continued the treatment with nitroglycerin for 24 months, headaches were reported in 35% of women compared to 5.4% of the control group during the first month, with a significant decrease after 12 months.

Conclusions:

The investigators concluded that nitroglycerin ointment modestly increased bone mineral density and decreased bone resorption among postmenopausal women.

Perspective:

This interesting study suggests a benefit to nitroglycerin ointment for postmenopausal women, although it is likely that the high incidence of headache will limit its use related to improving bone density.

Keywords: Biomarkers, Bone Resorption, Bone and Bones, Osteogenesis, Bone Density, Nitroglycerin


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