Nitroglycerin applied topically increases bone formation and reduces bone resorption in women with osteopenia, and it might prove to be an effective and inexpensive agent to prevent osteoporosis, according to the results of a 2-year randomized controlled trial presented here at the American Society for Bone and Mineral Research 2010 Annual Meeting.

“Our data have demonstrated that nitroglycerin uncouples bone turnover,” said Sophie Jamal, MD, director of the Osteoporosis Clinic at Women’s College Hospital, University of Toronto, in Ontario. “We saw an increase in bone formation and a decrease in bone resorption, as well as evidence that nitroglycerin improves bone mineral density [BMD], bone geometry, and bone strength.”

The increase in bone formation, together with reduced bone resorption, has not been seen with any of the current agents used to treat osteoporosis, Dr. Jamal told Medscape Medical News. “It also appears that the bones increase in size. This has major implications for fracture reduction,” she said in an interview.

Dr. Jamal and her team decided to study the effectiveness of nitroglycerin after noticing that women who were taking nitroglycerin for angina had particularly robust bones, despite having cardiovascular disease and more risk factors for osteoporosis.

Cellular data suggest that nitric oxide, the breakdown product of nitroglycerin, improves bone cell function, and animal studies suggest that rats that were given nitroglycerin after surgically-induced menopause had maintenance of BMD similar to rats given estrogen, Dr. Jamal said.

The investigators randomized 126 women to nitroglycerin ointment, 15 mg per day, applied at bedtime instead of every 6 to 8 hours, as it is prescribed for angina, and 117 women to placebo for 24 months.

All women were postmenopausal, 50 years or older (mean age, 61 years), had lumbar spine BMD T scores between 0 and –2.0, had hip BMD T scores above –2.0, and were taking at least 1200 mg of elemental calcium and 800 IU of vitamin D3 daily.

Compared with the women in the placebo group, those in the nitroglycerin group had significant increases in BMD at the lumbar spine (6.7%), femoral neck (7.0%), and total hip (6.2%) at 24 months (P < .001 for all measures).

Nitroglycerin also significantly increased trabecular density (11.9%), cortical density (2.2%), cortical area (10.6%), cortical thickness (13.9%), periosteal circumference (7.4%), polar moment of inertia (7.3%), and polar section modulus (10.7%) (P < .05 for all measures).

Headaches were the one adverse event related to nitroglycerin, and caused 7 women in the treatment group to discontinue treatment, compared with 2 women in the placebo group.

“The group that got the nitroglycerin had huge improvements in bone geometry, density, and strength, so I’m pretty excited,” Dr. Jamal said. “The other thing about nitrates is that they’ve been around for a long time, there are lots of generic forms, they’re cheap, and they’re widely available.”

The next step is a fracture study, she added. “This is a potentially very exciting treatment that could reduce osteoporotic fractures. We’d like to show that nitroglycerin does that.”

Lorenz C. Hofbauer, MD, PhD, from the Dresden Technical University Medical Center in Germany, who moderated the session, told Medscape Medical News that Dr. Jamal’s excitement was warranted.

“She should be excited about her results,” he said. “The study was very interesting. I hadn’t heard about it, so I was very surprised. I didn’t know the concept behind it, but it looks, in terms of potency, to be very powerful; it plays in the antiresorptive bisphosphonate league in terms of that effect.”

Dr. Hofbauer said that the drug’s low cost is another benefit. “It’s very inexpensive; it’s a widely prescribed, almost forgotten, drug, and that makes it attractive. So unless you get headaches, which about 20% of the women do, and if you can tolerate it, it will be a very interesting new strategy. Absolutely.”

He called for fracture data in other studies. “It would also be interesting to have data on the mechanism, because the mechanism might tell us why it works. Perhaps it is because of its effect on blood flow or a direct effect on bone cells. We’ll see.”

The study was funded by the Canadian Institute for Health Research. Dr. Jamal and Dr. Hofbauer have disclosed no relevant financial relationships.

American Society for Bone and Mineral Research (ASBMR) 2010 Annual Meeting: Abstract 1252. Presented October 18, 2010.

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