Effect of nitroglycerin ointment on bone density and strength in postmenopausal women: a randomized trial

JAMA. 2011 Feb 23;305(8):800-7. doi: 10.1001/jama.2011.176.


Context: Nitroglycerin stimulates bone formation and inhibits bone resorption, is inexpensive, and is widely available. Its effects on bone density, bone structure, and bone strength are unknown.

Objectives: To determine if nitroglycerin increases lumbar spine bone mineral density (BMD) and to evaluate changes in hip BMD, bone geometry, and density at the radius and tibia, and markers of bone turnover.

Design, setting, and participants: A single-center, double-blind, placebo-controlled randomized trial conducted in Toronto, Ontario, Canada, for 24 months starting in November 2005 and completed in March 2010, of 243 postmenopausal women with lumbar spine T scores of between 0 and -2.0 who completed a 1-week run-in period taking nitroglycerin ointment. Intervention Nitroglycerin ointment (15 mg/d) or placebo applied at bedtime for 24 months.

Main outcome measures: Areal 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: At 2 years, women randomized to the nitroglycerin group had significant increases in areal BMD at the lumbar spine (from 1.05 to 1.14 g/cm(2) vs placebo from 1.06 to 1.08 g/cm(2); percentage change, 6.7%; 95% confidence interval [CI], 5.2%-8.2%; P < .001); total hip (from 0.92 to 0.97 g/cm(2) vs placebo from 0.93 to 0.92 g/cm(2); 6.2%; 95% CI, 5.6%-7.0%; P < .001); and femoral neck (from 0.88 to 0.93 g/cm(2) vs placebo from 0.87 to 0.86 g/cm(2); 7.0%; 95% CI, 5.5%-8.5%; P < .001). At 2 years, nitroglycerin also increased volumetric trabecular BMD (11.9% and 8.5%), cortical thickness (13.9% and 24.6%), periosteal circumference (7.4% and 2.9%), polar section modulus (10.7% and 9.8%), and polar moment of inertia (7.3% and 14.5%) at the radius and tibia, respectively (all P < .001); and increased bone-specific alkaline phosphatase by 34.8% and decreased urine N -telopeptide by 54.0% (P < .001). Incidence of serious adverse events did not differ between nitroglycerin (5 [4.2%]) and placebo (5 [4.3%]) groups. Among those women who continued treatment for 24 months, headaches were reported by 40 (35%) in nitroglycerin and 6 (5.4%) in placebo groups during the first month, decreasing substantially after 12 months.

Conclusion: Among postmenopausal women, nitroglycerin ointment modestly increased BMD and decreased bone resorption.

Trial registration: isrctn.org Identifier: ISRCTN94484747.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Administration, Topical
  • Aged
  • Bone Density / drug effects*
  • Bone Density Conservation Agents / administration & dosage*
  • Bone Density Conservation Agents / adverse effects
  • Bone Resorption / drug therapy*
  • Double-Blind Method
  • Female
  • Fractures, Bone / prevention & control
  • Humans
  • Lumbar Vertebrae
  • Middle Aged
  • Nitroglycerin / administration & dosage*
  • Nitroglycerin / adverse effects
  • Postmenopause


  • Bone Density Conservation Agents
  • Nitroglycerin

Associated data

  • ISRCTN/ISRCTN94484747