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Jamal and colleagues recently published their results from a randomized, controlled trial on the effects of nitroglycerin ointment on bone density and strength [1]. This study follows several previous ones [2,3] which showed that the use of nitrates had a positive impact on bone mineral density (BMD) in men and women. 

 

The present cohort included 243 postmenopausal women (who were at least 1 year postmenopausal), mean age 62 years, with BMD [i]T[/i]-scores between 0 and -2.0 at the lumbar spine. The daily dose was 15 mg (2% nitroglycerin ointment) applied at bedtime to their upper outer arm. The intake of calcium was 1200–1500 mg/day and that of vitamin D was 800 IU/day from food and provided supplements. The duration of treatment was 24 months, and the study ran from November 2005 until March 2010. The primary endpoint was BMD [i]T[/i]-score measured at 12 and 24 months, at the lumbar spine, femoral neck and total hip. At 24 months, 118 of 126 women in the nitroglycerin group and 111 of 117 women in the placebo group completed all the assessments. 

 

At 24 months, spine and femoral neck BMD significantly increased by 6–7% in the nitroglycerin-treated group compared with placebo: lumbar spine BMD increased from 1.05 g/cm[+]2[/+] to 1.14 g/cm[+]2[/+], vs. 1.06 g/cm[+]2[/+] to 1.08 g/cm[+]2[/+], respectively. The corresponding figures for total hip were 0.92 to 0.97 g/cm[+]2[/+] vs. 0.93 to 0.92 g/cm[+]2[/+], and for femoral neck 0.88 to 0.93 g/cm[+]2[/+] vs. 0.87 to 0.86 g/cm[+]2[/+]; [i]p[/i] = 0.001). Cortical bone parameters assessed using peripheral quantitative computerized tomography also demonstrated an increase in volumetric trabecular BMD, cortical thickness and periosteal circumference at the radius and tibia compared with placebo. Urine N-telopeptide, the marker for bone resorption, decreased by 54%, while bone-specific alkaline phosphatase, the marker for bone formation, increased by 35% in women treated with nitroglycerin. There were two fractures in both the treated and the placebo groups, and one death by stroke in the treated group. The adverse events in the active group were dominated by headaches and were frequent at the beginning of the treatment, but rarer as a new event in the second year. The conclusions of the study were that daily administration of nitroglycerin ointment increased bone formation and decreased bone resorption, improved BMD, bone structure and indices of bone strengths ‘at least as much as existing treatments’ and also ‘may reduce the risk of vertebral fractures and non-vertebral fractures’.

Author(s)

  • Iuliana Ceausu
    Senior Lecturer, Obstetrics and Gynecology, ‘Carol Davila University of Medicine and Pharmacy, and Senior Specialist in Obstetrics and Gynecology, Department of Obstetrics and Gynecology, ‘Dr. I. Cantacuzino Hospital, Bucharest, Romania

Citations

  1. Jamal SA, Hamilton CJ, Eastell R, Cummings SR. Effect of nitroglycerin ointment on bone density and strength in postmenopausal women: a randomized trial. JAMA 2011;305:800-7.
    http://www.ncbi.nlm.nih.gov/pubmed/21343579
  2. Jamal SA, Browner WS, Bauer DC, Cummings SR. Intermittent use of nitrates increases bone mineral density: the study of osteoporotic fractures. J Bone Miner Res 1998;13:1755-9.
    http://www.ncbi.nlm.nih.gov/pubmed/9797485
  3. Jamal SA, Goltzman D, Hanley DA, et al. Nitrate use and changes in bone mineral density: the Canadian Multicentre Osteoporosis Study. Osteoporos Int 2009;20:737-44.
    http://www.ncbi.nlm.nih.gov/pubmed/18800179
  4. Laws CE, Du Pont W. Nitroglycerin head. JAMA 1910;54:73, reprinted in JAMA March 3, 2010;303:891
  5. Wimalawansa SJ, Grimes JP, Wilson AC, Hoover DR. Transdermal nitroglycerin therapy may not prevent early postmenopausal bone loss. J Clin Endocrinol Metab 2009;94:3356-64.
    http://www.ncbi.nlm.nih.gov/pubmed/19549739
  6. Rejnmark L, Vestergaard P, Mosekilde L. Decreased fracture risk in users of organic nitrates: a nationwide case-control study. J Bone Miner Res 2006;21:1811-17.
    http://www.ncbi.nlm.nih.gov/pubmed/17054422
  7. Khosla S. Is nitroglycerin a novel and inexpensive treatment for osteoporosis? JAMA 2011;305:826-7.
    http://www.ncbi.nlm.nih.gov/pubmed/21343584
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