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Is osteoporosis treatable with nitrates?

Last updated: August 2011

Bones that break after a minor fall, or even a sneeze, are a hallmark of osteoporosis. It's a condition in which bone loss happens at an accelerated rate, causing weak or brittle bones. About one in two women and one in four men over age 50 will have a fracture that signals osteoporosis—typically at the hip, spine, or wrist. Older adults who experience such painful breaks are at risk of being hospitalized, having surgery, getting pneumonia, blood clots, and death.

The Food and Drug Administration has approved several drugs to treat osteoporosis, but each has drawbacks. The first choice, bisphosphonates such as alendronate (Fosamax and generic), ibandronate (Boniva), and risedronate (Actonel and generic) are linked to small but serious risks of thigh fracture and permanent bone deterioration of the jaw (osteonecrosis) after invasive dental procedures. Estrogen and raloxifene (Evista) increase the risk of blood clots, denosumab (Prolia) might cause serious infections and jaw osteonecrosis, and teriparatide (Forteo) requires daily injections. Moreover, most of the bisphosphonates are relatively expensive. And for women with osteopenia, or "pre-osteoporosis," the drugs offer limited protection. Our medical consultants have long advised against taking bisphosphonates for osteopenia and encourage lifestyle changes instead.

So researchers are hopeful that an inexpensive heart drug will prove to be a new option for osteoporosis. A 2011 study suggests that nitroglycerin—long prescribed to control chest pain (angina)—might build new bone and prevent bone loss. "All the other drugs for osteoporosis do just one or the other, so there is great interest in a drug that might do both," says Bart L. Clarke, M.D., an associate professor of medicine at the Mayo Clinic in Rochester, Minn., and a clinical researcher who studies osteoporosis. "The data are impressive, but further investigation is needed."

Nitroglycerin (Nitro-Bid and generics) and isosorbide (Dilitrate, Imdur, and generic) belong to a class of drugs called nitrates, which are approved for the treatment of angina. Available as tablets, sprays, skin patches, or ointments, nitrates provide cells in the body with nitric oxide, a chemical that relaxes blood vessels and—scientists now realize—seems to benefits the skeleton as well. "It appears to give bone cells a boost in how they form new bone and slow the breakdown of old bone," Clarke explains.

What is the evidence?

Several observational studies have compared the bone health of people who took nitrate medication for heart disease with that of people who didn't use nitrates. One study found that older women taking nitrates intermittently had higher bone-mineral density (BMD) at the hip and heel than nonusers. Another found that men and women using nitrates had lower risks of various types of fractures, including hip fractures, and a third found that daily nitrate use was associated with an increase in BMD at the hip and spine among men and women. In addition, a randomized controlled trial of 16 young women undergoing surgical removal of their ovaries—an operation that hastens the onset of osteoporosis—suggested that nitroglycerin ointment was as effective as estrogen in reducing bone loss.

In contrast, a 2009 randomized double-blind placebo-controlled trial found no benefit from nitroglycerin ointment in preventing bone loss in postmenopausal women. But the researchers noted that women in the nitroglycerin group used an inadequate dose of the drug, possibly contributing to its lack of effectiveness.

In a 2011 randomized double-blind controlled trial that has sparked interest, 243 postmenopausal women were assigned to nightly doses of nitroglycerin ointment or a placebo ointment applied to the upper arm for two years. Compared with the placebo group, women who received nitroglycerin had increased bone density in the spine, hip, and top of the thighbone (femur neck) and increased measures of BMD for bones in the forearm and lower leg. In addition, their blood tests revealed increased markers of new bone formation and decreased markers of bone loss.

Those findings suggest that daily use of nitroglycerin might reduce fractures, but larger and longer studies are needed to confirm that effect. In addition, most of the research has focused on postmenopausal white women, and the results of those studies might not apply to other populations.

What are the risks and precautions?

The information below primarily pertains to the use of nitroglycerin for heart conditions. No serious side effects were noted in trials of nitroglycerin for osteoporosis, but headaches have been commonly reported. Tell your doctor what prescription and nonprescription medication you take, especially those to treat blood pressure, heart failure, mental illness, and nausea. And men shouldn't use nitrates if they take drugs for erectile dysfunction, such as sildenafil (Viagra), tadalafil (Cialis), or vardenafil (Levitra).

Low blood pressure (hypotension)

This can cause dizziness, light-headedness, and fainting, particularly if you stand up quickly from a lying position, are very old, dehydrated, or take other medication that lowers blood pressure. Be sure to drink enough fluids and avoid alcohol, which can worsen dizziness.

Headaches

They might be throbbing, pulsating, persistent, or occasional, and range from mild to severe. Headaches were a top reason people who participated in nitrate trials for osteoporosis discontinued treatment; but they decrease over time, in some cases after a few days. Ask your doctor if you can take acetaminophen (Tylenol and generic) to prevent or reduce the severity of headaches.

Withdrawal syndrome

Chest pain, shortness of breath, palpitations, or a heart attack might occur if you have heart problems and stop taking nitrates abruptly. "Sudden withdrawal may worsen cardiac symptoms, so potentially bone loss could be made worse also," Clarke says.

Concerning conditions

Tell your doctor if you've had anemia, glaucoma, recent head trauma, low blood pressure, or heart problems, or if you're pregnant or planning to become pregnant.

Geriatric issues

Many osteoporosis patients are small, older women who might be more sensitive to the side effects of nitrates—especially the light-headedness that could lead to falls and broken bones. "A lot of older folks get light-headed and dizzy now and then just because, and a lot are on medications that lower blood pressure," Clarke says. "Researchers will need to find a nitrate dose that minimizes these side effects yet still works for bones." The form of the medicine should also be considered. When taken as a pill and absorbed through the stomach, nitrates tend to drop blood pressure. "They may be absorbed more slowly through the skin," Clarke says, "so giving them as an ointment might reduce the side effect of lowered blood pressure and subsequent lightheadedness."

What other options can you try?

To prevent further bone loss, make sure you get adequate calcium from food and vitamin D from food or supplements, and do regular exercise such as walking, jogging, weight training, tennis, or dancing. Don't smoke or drink too much alcohol, and take steps to prevent falls in your home, such as:

  • Keeping rooms free of clutter on floors and keeping extension cords secured and out of the way.
  • Installing grab bars in the bathroom and rubber mats in the bathtub or shower.
  • Keeping floors smooth, not slippery, and getting rid of loose rugs.

If you do take bisphosphonate medication for osteoporosis, consider taking a "drug holiday" after five years' use while seeing your doctor regularly to check your bone health.

Bottom line

Based on emerging evidence, nitrates might be a promising treatment for osteoporosis. But larger controlled trials involving broader populations are needed to assess their impact on fracture risk. Research is also needed to establish the optimal dose and best type of nitroglycerin product to use. Our advice: Talk with your doctor about first-line and other approved treatments for osteoporosis, as well as nondrug measures to prevent further bone loss.

This off-label drug use report is made possible through a collaboration between Consumer Reports Best Buy Drugs and the American Society of Health-System Pharmacists. This is the 27th in a series based on professional reports prepared by ASHP.

These materials were made possible by a grant from the state Attorney General Consumer and Prescriber Education Grant Program, which is funded by a multistate settlement of consumer fraud claims regarding the marketing of the prescription drug Neurontin (gabapentin).
   

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