Osteoporosis Drugs

by Dorothy Foltz-Gray

Osteoporosis Drugs

TV ads for osteoporosis drugs make the medicines sound wonderfully effective. But some headlines have suggested they may cause risks such as broken thigh bones and eroding jaws. Such news is apt to make anyone with osteoporosis—a condition that results in brittle bones—feel skittish or even frightened about taking these drugs.

Still, treating the condition is essential to preventing bone fractures, says pharmacotherapy specialist Alicia B. Forinash, PharmD, Associate Professor of Pharmacy Practice at St. Louis College of Pharmacy in St. Louis, Missouri. “Fracture is associated with pain, immobility, deformity, decreased quality of life, economic burden, and death.”

What osteoporosis drugs accomplish

Bones are constantly repairing themselves. “Cells called osteoclasts break down old bone, while other cells called osteoblasts lay down new bone,” says osteopath Angela DeRosa, DO, founder of DeRosa Medical in Scottsdale, Arizona, and a former senior medical director at Procter & Gamble, where she helped launch osteoporosis treatments for women.

Unfortunately, after menopause, osteoclasts become more aggressive, and the cells laying down new bone can’t keep up. Over time, that can lead to osteoporosis.

Osteoporosis drugs fall into two classes—the first, named antiresorptive, slows bone breakdown. Antiresorptive drugs include bisphosphonates, calcitonin (brand name Rocaltrol), estrogen, and estrogen agonists/antagonists (drugs that either act like or deactivate estrogen, such as raloxifene [Evista]), and newer RANKL inhibitors, which include denosumab (Xgeva and Prolia). RANKL is a protein that activates bone removal. The second class of drugs, named anabolic, builds new bone. Teriparatide (Forteo) is the only anabolic drug currently approved by the FDA.

Although the risks of these drugs are few and rare, says Forinash, it’s important to understand what they are. In general, osteoporosis drugs do not work well, or can even be harmful, when used by people who have very low calcium or vitamin D levels, says Pauline M. Camacho, MD, director of Loyola University Osteoporosis and Metabolic Bone Disease Center in Chicago. And if a person has impaired kidneys, he or she cannot take some of the drugs, such as zoledronic acid, alendronate, and risedronate.


Bisphosphonates slow bone loss without affecting the increase of new bone. Most are taken by mouth, either daily, once or twice a week, or once a month. Some can also be administered intravenously by a health-care provider.

Bisphosphonates are not interchangeable, but in general, they may cause bone, joint, or muscle pain. Taken orally, they may also cause nausea, heartburn, esophageal irritation, or stomach ulcers. Some people initially experience flu-like symptoms, but these usually don’t persist.

“People with histories of gastric ulcers or GERD [gastroesophageal reflux disease] should avoid oral bisphosphonates,” says Camacho. Injections have fewer risks, so they would be an option.

People with severe kidney disease should also avoid bisphosphonates. And everyone should have his or her kidney function tested before taking bisphosphonates, especially zoledronic acid.

“Bisphosphonates can also increase the risk for osteonecrosis”—death of bone tissue—“of the jaw,” says Forinash. The risk is highest in people who take a high dose for other (bone) conditions besides osteoporosis or for cancer.

Bisphosphonates have also caused femur (thigh bone) fractures in about 0.1% of those who take them, says Forinash. Bisphosphonates may cause problems with bone healing as well, particularly after dental surgery. Rarely, they may cause eye inflammation.

Side effects of individual bisphosphonates vary. Below is a rundown of the effects.

Alendronate (Fosamax). Alendronate reduces bone loss, increases bone density, and may lower the risk of broken bones by 50% over two to four years, according to the National Osteoporosis Foundation. The drug is taken as a tablet or liquid daily or weekly.

A 2008 study at the University of Aberdeen found that 70 milligrams (mg) of alendronate created significantly greater bone density and larger decreases in bone turnover than 35 mg of risedronate, with no differences in heartburn and esophageal problems.

However, alendronate can also cause chest pain, mouth sores, heartburn, and damage to the esophagus.

Risedronate (Actonel, Atelvia). Risedronate slows bone loss, increases bone density, and reduces the risk of fractures by 35% to 45% over three years, according to the National Osteoporosis Foundation. It can be taken daily, weekly, or twice monthly. On the downside, according to the National Institutes of Health, risedronate may damage the esophagus and cause mouth sores if it is not taken as directed. Like the other bisphosphonates, it may cause heartburn.

Zoledronic acid (Reclast). According to a 2014 animal study at the Al-Ameen College of Pharmacy in Bangalore, India, zoledronic acid given along with alfacalcidol, a type of vitamin D, is more effective in strengthening the spine and femur than either drug given alone.

It has been found to reduce the risk of spine fracture by 70% and hip fractures by 41%.

According to the FDA, zoledronic acid, given by infusion of at least 15 minutes every year or two, raises the risk of kidney failure. Consequently, it’s not recommended for people with kidney problems, for those who already take drugs that may harm the kidneys, or for those on diuretics, which increase urination.

Initially, it may cause a flu-like reaction. Other possible risks are broken thigh bones, heartburn, and mouth sores.

Ibandronate (Boniva). According to the National Osteoporosis Foundation, ibandronate reduces spine fractures by 50% over three years. Ibandronate is taken monthly as a tablet or every three months intravenously.

The drug reduces risk of fracture only in the vertebra. The most common areas for fractures are the spine, hip, and wrist, but they can occur anywhere, says Forinash.

The drug may increase the risk of breaking thigh bones and may cause heartburn and poor healing in the jaw.


Calcitonin (Fortical and Miacalcin) is most effective for reducing the risk of spine fractures.

A synthetic hormone taken as a nasal spray or injected, calcitonin is not as effective as bisphosphonates, says Camacho. It is usually prescribed for people who cannot tolerate bisphosphonates. An oral form is currently being tested.

In 2013, a majority of experts on two FDA advisory panels voted to stop recommending calcitonin nasal spray for the treatment of osteoporosis in women who are at least five years past menopause. They cited a lack of evidence of benefit and concerns about increased cancer risk linked to the drug. The FDA is now reviewing the data and considering changing the prescribing information. In 2012, the European Medicine Agency recommended that calcitonin not be used for osteoporosis treatment, saying the risk of cancer was higher in people using the nasal spray than in those using a placebo.

Common side effects of the injected form of calcitonin include nausea and skin redness. The nasal form may cause nosebleeds or a runny nose.

RANKL inhibitors

Denosumab (Xgeva, Prolia) was the first RANKL inhibitor approved by the FDA. In a 2014 study of 852 postmenopausal women at the CHU de Quebec Research Centre and Laval University in Quebec City, Canada, researchers found that denosumab was more effective at building bone density and decreasing bone turnover than monthly oral ibandronate or risedronate.

A two-year 2014 Japanese study of almost 1,300 men and women over age 50 with fractures of the vertebrae found that those who took denosumab every six months reduced their risk of new or worsening vertebral fractures by almost 66%.

Other studies have found it reduces new spine fractures by 68%, hip fractures by 40%, and non-spine fractures by 20% over three years.

Denosumab, which inhibits osteoclast formation—cells that encourage bone breakdown—has been associated with jaw erosion, but only rarely, says Forinash. “The FDA is also monitoring risk for serious infections.” People with weakened immune systems are particularly at risk for infections.

Given by injection every six months, Denosumab also increases the risk of broken thigh bones and may cause broken bones to heal slowly. It may also decrease calcium levels. Users’ calcium levels should be tested before each dose.

Estrogen agonists/antagonists

Raloxifene (Evista) is the estrogen agonist most commonly used to treat osteoporosis. These drugs are also called selective estrogen receptor modulators, or SERMs. Taken daily as a tablet, raloxifene works by mimicking estrogen, which increases bone density. It increases bone density and reduces the risk of spine fractures.

Raloxifene is associated with increased risk of hot flashes and blood clots in the legs or lungs, and it’s not as effective as bisphosphonates. If you have heart disease, the drug may increase your chances of having a stroke.

Anabolic drugs

Teriparatide (Forteo) is the only FDA-approved drug that rebuilds bone. It also increases bone density, particularly in the spine. And studies of postmenopausal women indicate that it reduces bone fractures in the spine and non-spine.

DeRosa uses teriparatide when her patients can’t tolerate risedronate. “Teriparatide is a parathyroid derivative that works by killing osteoclasts and pumping up the osteoblasts.”

Rats that have taken the drug for two years have an increased risk of bone cancer, says Forinash, but it is a form that is rare in humans. The drug is FDA-approved, but only for self-injected daily doses over a maximum of two years.

How to reduce risks

Although the drugs carry risk, you can take steps to limit those and the risk of worsening osteoporosis. Here’s how.

Take a drug holiday. Because the difficulties linked to bisphosphonates have occurred after continued use, the FDA and other osteoporosis guidelines such as those developed by the American Association of Clinical Endocrinologists suggest that after three to five years, people with low fracture risk should stop taking them.

However, scientists don’t know what the optimal length of time for taking the drugs is, says Forinash. Sometimes, if a patient is at high risk for fractures, a doctor may switch therapies or continue the same therapy. In any case, don’t stop taking your drugs without speaking to your doctor first.

Speak up. If you have bothersome side effects from any osteoporosis drug, let your doctor know right away. Side effects from oral bisphosphonates may include irritation of the esophagus—the tube that connects your throat to your stomach—or heartburn. You may also experience headache, constipation, diarrhea, gas, and muscle and joint pain from intravenous bisphosphonates.

Also, let your doctor know if you have any pain in your thigh or groin area. That may indicate bone weakness that could lead to fracture.

If you are planning to have oral bone surgery, tell your dentist know that you are taking bisphosphonates.

Understand what you’re taking. According to the American Association of Clinical Endocrinologists (AACE), the therapies recommended first because of their effectiveness in reducing fractures of the vertebra, hip, and non-spinal bones are alendronate, risedronate, zoledronic acid, and denosumab. “The other therapies reduce the risk [only] of vertebral fractures,” says Forinash.

Take calcium and vitamin D. Women over 51 should consume 1,200 mg of calcium per day. Men between ages 50–70 should consume 1,000 mg daily. People of both sexes age 50 and over should take 800-1,000 IU of vitamin D per day.

Exercise. Do weight-bearing exercise like walking and strength training, says Forinash. Both strengthen bone.

The AACE recommends 30 to 40 minutes of exercise on most days of the week. Talk with your doctor before starting any exercise program.

Review your options. Before you start taking drugs for osteoporosis, weigh the risks and benefits of your medication options with your doctor, says Forinash. Also, ask your doctor or pharmacist to check the medicines you’re already taking for any that may increase your risk of fracture, such as corticosteroids or some antacid drugs.

Overhaul bone-weakening habits. If you smoke, quit, and don’t drink alcohol excessively. Both habits undermine bone strength.

Take medicines as directed. For instance, if you are taking bisphosphonates by mouth, most should be taken with a glass of water at least 30 minutes before eating. If you are taking delayed-release risedronate (Atelvia), take it with water right after breakfast. Do not take any other medicines or lie down for at least 30 minutes, which will help minimize heartburn. If you are taking ibandronate, wait 60 minutes before eating and don’t lie down for an hour.

Also, take bisphosphonates and calcium at least half an hour apart. Calcium supplements can interfere with your body’s absorption of bisphosphonates.

Bottom line

“Osteoporosis drugs have [yielded] very good safety data,” says Camacho. “The side effects in the news such as atypical fractures and jaw [erosion] are very rare.” The risk of a rare side effect is less than 0.01%, she adds. But in some women, the risk of fracture can be as high as 50%.

Other experts are perhaps more moderate in their praise but still are largely positive. Each of the therapies has some risk, says Forinash. “But the benefits often outweigh the risks.” Talk with your doctor and pharmacist about the best therapy for you.

Lifestyle Tips for Stronger Bones

Maintaining a healthy, active lifestyle can protect your bone health and reduce your risk of a fracture.


• If you do not have osteoporosis, you can maintain your bone strength, build muscle, and improve your balance by performing weight-bearing, resistance, and balance exercises.

• If you do have osteoporosis, you should focus on exercises that improve balance, muscle strength, and hip and torso stability. You should not do sit-ups, perform twisting movements like swinging a golf club, or attempt to bend forward to touch your toes. Work with an exercise specialist to develop a safe exercise program that will build your muscles while protecting your bones.


• Consume foods that are high in calcium. These include dairy products, kale, collard greens, mustard greens, turnip greens, bok choy, broccoli, sesame seeds, canned salmon or sardines with bones, figs, and tofu made with calcium sulfate (check the label).

• Maintain adequate protein intake. Although many Americans consume more than enough protein, some, particularly older individuals, do not. Inadequate protein intake can lead to weak muscles.

• Increase the amount of fruits and vegetables you eat.

• Limit your salt intake. Consuming more than 2,300 milligrams of sodium per day appears to increase urinary calcium loss.

• Avoid heavy alcohol consumption.

• Avoid “crash” diets that cause you to lose weight rapidly.

• Speak to your doctor about taking calcium and/or vitamin D supplements. Getting calcium from food is preferable, but your health-care provider may recommend taking supplements, as well.

Get outside

Your body manufactures its own vitamin D when you spend time in natural sunlight. Even spending 10 to 20 minutes outside several days a week makes a difference.

Quit Smoking

Smoking tobacco raises your risk of osteoporosis.

Last Reviewed October 30, 2014.

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Dorothy Foltz-Gray is a freelance health writer specializing in arthritis. Her memoir, With and Without Her, won the 2013 American Society for Journalists and Authors Award for Memoir.

Statements and opinions expressed on this Web site are those of the authors and not necessarily those of the publishers or advertisers. The information provided on this Web site should not be construed as medical instruction. Consult appropriate health-care professionals before taking action based on this information.

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