What is the best medication for osteoporosis

By Becky UphamMedically Reviewed by Sanjai Sinha, MD

Reviewed: May 14, 2019

The first sign of osteoporosis, or low bone density, is often a broken bone, frequently in the hip, forearm, wrist, or spine.

And while bone fractures may sound less serious than, say, cancer or cardiovascular diseases, fractures associated with osteoporosis can lead to pain, reduced mobility, reduced independence, depression, and even premature death.

The good news is that there are many available treatments to protect against fracture and the possible resulting complications, says Sundeep Khosla, MD, an endocrinologist at Mayo Clinic in Rochester, Minnesota.

“When I joined Mayo Clinic in 1988, basically we could offer patients estrogen and very little else other than calcium or vitamin D. Now we’ve got all of these different options that can be tailored to the needs of a given patient depending on their preferences, the severity of the disease, their age, and other risk factors,” says Dr. Khosla.

Risk of Developing Osteoporosis Rises With Age

As with many chronic diseases, simply getting older puts you at higher risk of osteoporosis. Currently, 1 in 4 American women over age 65 and 1 in 20 men in that age range have osteoporosis, according to the Centers for Disease Control and Prevention (CDC).

In adults, bones go through a continuous process of breaking down and building up again, called remodeling. Osteoblasts create bone and osteoclasts break down the tissue in bones and release the minerals into the blood.

The hormones androgen and estrogen play a role in the balance of breaking down and rebuilding bone. As people get older and these hormone levels drop, the bone is removed or damaged faster than the body is able to replace it, leaving bones weakened and vulnerable to fracture.

Unhealthy lifestyle habits, such as smoking, drinking, and lack of exercise also raise the risk of developing osteoporosis, as does the long-term use of certain types of medication, including corticosteroids.

Fractures Prevented Vastly Outnumber Serious Side Effects

Depending on the body part (whether it’s the spine or the hip or another bone in the body), taking an osteoporosis medication will reduce the chances of fracture anywhere from 50 to 70 percent — a substantial reduction in risk, says Khosla.

“The side effects are quite rare. In general, something on the order of 100 to several thousand fractures from osteoporosis would be prevented for every serious side effect that was induced from these drugs. I find putting the risks and benefits in this context conveys why it’s important to take the medication,” says Khosla.

Here’s a rundown of the benefits and risks of many commonly prescribed osteoporosis treatments:

1. Bisphosphonates Slow Bone Loss

Bisphosphonates work by reducing osteoclast activity, which slows the turnover of bone or removal of old bone and improves bone strength and bone density. “These drugs have a long track record; we know a lot about them,” says Khosla.

Some bisphosphonates, such as Fosamax (alendronate) and Actonel (risedronate), are taken as a daily or weekly tablet, while Boniva (ibandronate) is taken monthly to prevent and treat osteoporosis. Reclast (zoledronic acid) is taken intravenously once a year to treat osteoporosis and every two years to help prevent it.

“There’s a lot in favor of using a bisphosphonate,” says Khosla. According to a meta-analysis published in February 2017 in the Journal of Bone Metabolism, bisphosphonate use decreased the risk of overall osteoporotic fracture by over 60 percent.

While the common side effects of bisphosphonates — including bone, joint, or muscle pain, as well as nausea, difficulty swallowing, and heartburn for the oral drugs — may be bothersome for some, it’s the rare side effects of osteonecrosis of the jaw and atypical femoral fracture that have scared many people away from taking medication to prevent or treat osteoporosis.

Osteonecrosis of the Jaw

The risk of osteonecrosis of the jaw that comes with bisphosphonate use is very low, according to the National Center for Biotechnology Information.

Osteonecrosis of the jaw occurs when the jaw bone is exposed and begins to starve from a lack of blood. Although the risk for this adverse event is low for all bisphosphonates, it is mostly reported with Reclast and pamidronate, an older bisphosphonate that’s given intravenously. Doctors sometimes use these therapies in very potent doses to prevent fractures and bone loss associated with cancer or cancer treatments, according to American Bone Health.

There are ways to minimize the risk of jaw osteonecrosis, including getting a dental exam before starting therapy on a bisphosphonate, practicing good dental hygiene, and avoiding invasive dental procedures while taking the medication.

Atypical Femoral Fracture

Bisphosphonates can also carry a risk of atypical femoral fracture, which starts when the outer rim of the femur (thigh bone) starts to weaken. Unlike stress fractures or other bone breaks, the bone cracks from just normal activity. An aching pain in the groin or thigh can be a warning signal that this may be happening, according to American Bone Health. With no intervention, the crack continues to grow and eventually the thigh bone breaks in two.

In a meta-analysis of 14 studies published in January 2017 in the Journal of Nutrition, Health & Aging, the incidence of atypical femoral fracture was low, ranging from 3.0 to 9.8 cases per 100,000 patient-years. Most, though not all, of the fractures occurred in bisphosphonate users.

Drug Holiday to Minimize Risks

The longer a person takes a bisphosphonate, the greater the risk for both jaw necrosis and atypical femoral fracture, especially after three years. In an effort to minimize the risk as much as a possible, a drug holiday is recommended. A drug holiday is a temporary stop of a medication (in this case, bisphosphonate) in an effort to prevent the potential side effects.

The American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) guidelines recommend a holiday after five years of oral and three years of intravenous bisphosphonate treatment for people with moderate fracture risk and after 10 years of oral and six years intravenous bisphosphonate treatment for people at a higher fracture risk.

A study published in December 2018 in Endocrine Practice found that 15.4 percent of patients who take a break from their bisphosphonate treatment had a bone fracture. The study authors recommended that people who have a high risk of fracture be closely followed by their doctor during drug holiday.

RELATED: Even During a ‘Drug Holiday,’ Osteoporosis Patients Should Be Monitored

2. Parathyroid Hormone Builds Bone Back Up

Parathyroid hormone drugs include Forteo (teriparatide) and Tymlos (abaloparatide), which help the body build new bone. Both drugs require patients to inject themselves on a daily basis for 18 months to two years.

“These drugs are generally reserved for people with multiple fractures or those who are continuing to lose bone or having fractures on a bisphosphonate, or a patient with very severe osteoporosis," says Khosla.

These are drugs that can build the bone back up and potentially reverse the osteoporosis, he says. People who take parathyroid hormone drugs had significantly fewer new vertebral fractures.

The long-term safety of these drugs is still unclear, which is one reason a person can only take them for two years. During the testing of both of these drugs, they were associated with an increased risk of bone cancer in animal studies.

3. Human Monoclonal Antibodies: Each Works Differently

Human monoclonal antibodies for osteoporosis include Prolia (denosumab) and the new drug Evenity (romosozumab).

Prolia is given by injection every six months, and it works by inhibiting the maturation of osteoclasts, which protects bones from degrading and slows the progression of the disease. Prolia significantly reduces vertebral, hip, and nonvertebral fracture at one, two, and three years, though it also carries a very slight risk of osteonecrosis of the jaw and atypical femoral fracture.

Evenity is a monoclonal antibody that represents a breakthrough in osteoporosis treatment: It both builds bones and decreases bone loss. Injected once a month for a year, it works by blocking sclerostin, a protein involved in bone remodeling, and it can be used in addition to other osteoporosis drugs as a bone-building medication. In clinical trials, one published in the March 2019 issue of the Journal of Bone and Mineral Research and one published in October 2017 in The New England Journal of Medicine, Evenity reduced the risk for fracture by more than 70 percent, and study participants had increases in bone density in their spines of around 15 percent — a very significant margin.

Evenity carries a warning due to an increased risk of heart problems. In one of the two studies used for FDA approval, cited above, Evenity was associated with an increased risk of cardiovascular death, heart attack, and stroke. These events occurred in 50 of 2,040 patients, or 2.5 percent taking Evenity, compared with 38 of 2,014, or 1.9 percent, taking Fosamax.

4. Estrogen Promotes Bone Production

Estrogen replacement therapy used to be the only FDA-approved treatment for the prevention of osteoporosis because of the hormone’s role in producing bone. Often women start taking estrogen for treatment of severe hot flashes around the time of menopause, says Khosla. “They feel better, and they also have the added benefit that the estrogen is helping prevent fractures and potentially other conditions, like diabetes,” he says.

However, “there is a concern about the increase for breast cancer risk and cardiovascular events, including heart disease, stroke, and blood clots,” says Khosla. After weighing the benefits and risks, some women choose to take estrogen on a short- or long-term basis for quality of life issues, he says.

Estrogen is not used to treat men who have osteoporosis, although testosterone may be used in men with low testosterone levels.

5. Calcitonin Less Effective Than Newer Options

Calcitonin is a very old drug, says Khosla. “It used to be given by injection and more recently by nasal spray, but it’s not prescribed that much anymore,” he says. “It’s not as effective as many of the other drugs that are available now, and there was some concern a number of years ago about some increase in cancer risk that’s associated with long-term use of calcitonin.”

For Most, Osteoporosis Treatment Benefits Outweigh Risks

“There’s been remarkable progress made in terms of addressing the disease, and now the real challenge is implementation: getting the message out that we have these options,” says Khosla. “When these drugs are used appropriately, they are safe as compared with many other things that we do in medicine. They will provide a lot more benefit than the risks that they pose,” he says.

There are many patients who would benefit from taking medication for osteoporosis, but they’re either not being prescribed the drugs, or they’re not taking them because of concerns about these rare side effects, says Khosla. “I think within the clinical community of physicians who care for patients with osteoporosis, we’re trying to find ways to better convey the benefit-to-risk ratio of these osteoporosis drugs so that people are appropriately treated when they need to be.”

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