Advances in Osteoporosis Treatment-Discussion With The Experts
With 16 percent of women ages 50 and older living with osteoporosis, according to the US Centers for Disease Control and Prevention, awareness of and treatment for this bone-weakening condition is an important topic in the national women’s healthcare conversation. (This disease also affects men—4 percent among those ages 50 and older.)
Fortunately, we have effective drugs to help improve bone strength, and our understanding of how to best and most safely use these medications continues to grow. We are also learning more about prevention of osteoporosis and how to keep bones healthy through midlife and beyond.1
The National Osteoporosis Foundation (NOF) defines osteoporosis as “a disease of the bones that happens when you lose too much bone, make too little bone, or both.” As a result, says the NOF, your bones get weak and can break more easily than healthy bones—from a minor fall or even from sneezing or bumping into furniture.
Elizabeth A. Streeten, MD, an associate professor of medicine and pediatrics in the divisions of Endocrinology, Diabetes, and Nutrition and Genetics at the University of Maryland School of Medicine, describes bones affected by osteoporosis as “less dense than normal.”2
In fact, many patients learn that they have osteoporosis as the result of fracture from a seemingly innocuous fall. Samantha,* a retired public librarian and public library consultant from Baltimore City, Maryland, was in her midfifties when she had the first sign of osteoporosis—a simple fall that left her with two broken bones. “I tripped walking down the street, fell, and broke my left arm and leg,” she says. “I had no other symptoms other than the broken bones at the time.” She then consulted Dr. Streeten and underwent “a battery of tests” to confirm the diagnosis.
Dr. Streeten says that, according to the World Health Organization definition of osteoporosis, a fracture of the hip or spine can make the diagnosis of osteoporosis without additional testing. “If a patient has either one of those [hip or spine fracture], that makes the diagnosis without needing anything else,” she explains.
Testing can also diagnose osteoporosis, namely dual-energy X-ray absorptiometry (DXA), which is an enhanced type of X-ray that can measure bone density and compare it with normal values. Dr. Streeten explains that DXA works by comparing the bone density of postmenopausal women (and men over 50) with that of healthy adults in their twenties. The difference in bone density between older patients and younger individuals is measured numerically and referred to as a T-score. As Dr. Streeten explains, “We diagnose osteoporosis if the bone density is 2.5 standard deviations below young [individuals].” In other words, if you are a postmenopausal woman (or a man over 50) and if your T-score is –2.5 or lower, you’d be diagnosed with osteoporosis.
If you have lower bone density according to your T-score, but it’s not low enough to qualify as osteoporosis, you have a condition known as low bone mass (or osteopenia). The T-score for osteopenia is between –1 and –2.5. Low bone mass puts you at greater risk of osteoporosis, making awareness and prevention of bone loss paramount.
Premenopausal women have separate criteria for an osteoporosis diagnosis. For this age group, the DXA scoring system is called a Z-score. The Z-score is based on the standard deviation (or difference) between patients and same-age individuals (controls) with healthy bone density. To be diagnosed with osteoporosis, a premenopausal woman must have a Z-score two points lower than the control (–2) and what’s known as a fragility fracture—which, says Dr. Streeten, is “a fracture resulting from a fall from standing or equivalent,” as opposed to a high-trauma fall, such as from a roof.
Treatment: From Diet to Drugs
Before discussing available medical treatments for osteoporosis, Dr. Streeten emphasizes the importance of calcium and vitamin D in bone health. “Everyone—whether they’re trying to prevent osteoporosis or be treated—should get enough calcium and enough vitamin D to keep bones healthy,” she says. This means 1,000 to 1,200 milligrams (mg) of calcium per day, preferably by diet (as it is absorbed better than through supplements) and enough vitamin D to keep the blood level of D normal—at least 30 nanograms per milliliter (ng/mL). In addition to calcium and vitamin D, Dr. Streeten encourages exercise for building bone.
Beyond these bone-health lifestyle measures, drug therapy can play a role. Dr. Streeten names the following drugs as “first-line treatment”: bisphosphonates, such as Fosamax® (alendronate) and Reclast® (zoledronic acid); the anabolic drug Forteo® (teriparatide)®; and the biologic Prolia® (denosumab). Bisphosphonates slow the rate of bone breakdown and improve bone strength, Forteo increases the rate of bone formation, and Prolia targets a chemical signal to slow the process of bone breakdown.
In addition to these first-line therapies, there are osteoporosis treatments that Dr. Streeten says the Endocrine Society (the international professional organization for the fields of endocrinology and metabolism) does not consider first-line; these are Evista® (raloxifene), Boniva® (ibandronate), and Calcitonin® (thyrocalcitonin). “While the others [first-line therapies] reduce hip and spine fracture risk,” she says, “these three don’t reduce hip fracture risk,” rendering them less effective.
Dr. Streeten says that for many patients, bisphosphonates are the preferred first-line treatment—specifically, intravenous Reclast or oral Fosamax, as they are the most effective in this class and the most thoroughly researched. “They’re very effective,” she explains, “have a good risk/benefit ratio, and are generally easy to take.”
After trying several drugs, Samantha is currently enjoying the benefits of Reclast, which she started taking in 2015. “I have had no side effects,” she says, adding that her most recent DXA (which she gets annually) showed that her bone density was in the normal range for her age group and has improved over previous studies.
An exception to first-line bisphosphonates is made for patients who have multiple compression fractures of the spine. For many such cases, Dr. Streeten recommends starting with the anabolic Forteo and then proceeding to bisphosphonates: “Forteo is best for the spine in terms of improving bone strength and reducing fractures in the spine.”
The biologic Prolia is also effective for many patients but has a notable limitation compared with bisphosphonates and Forteo. Whereas bisphosphonates and Forteo can protect you from fracture for at least two years if you stop using them after a treatment period, the protective effects of Prolia cease when you stop taking it. “Fracture rate goes right back to where it was before you were ever treated,” Dr. Streeten explains, “so it’s a drug that has to be used continuously.” As a result, she says, Prolia is likely a better option for older patients, who will stay on the drug for the rest of their lives, versus younger patients, who may want to take time off between treatment cycles.
Dr. Streeten also adds a cautionary note about bisphosphonates: patients need to understand that while three out of four bisphosphonates (Fosamax, Reclast, and Actonel® [risedronate]) reduce both spine and hip fracture, the fourth— Boniva—reduces risk of spine fracture but has not been proven to reduce hip fracture risk.
This limitation of Boniva, as well as the reversible effects of Prolia when treatment is stopped, underscore the importance of seeing an expert in osteoporosis (such as an endocrinologist), as opposed to a family practitioner, who may not know the various nuances of these medications and how to best use them.
Another of Dr. Streeten’s patients, Beth,* an office manager from Baltimore City, Maryland, in her early sixties, learned firsthand the importance of seeing an expert. When she was first diagnosed, she received Actonel, which, she says, “did nothing for me.” Beth then consulted with Dr. Streeten, who started her on Forteo and then switched her to Prolia after two years, with great results.
“Prolia is working wonders and miracles for me now!” Beth says. “I have improved each time I use it, and now I am in the osteopenia range and very happy about this.” In addition, Beth has had no side effects from Prolia.
Side Effects of Treatment: Likely More Benefit Than Risk
Treatment of osteoporosis is a long-term, or lifelong, prospect. As a result, many patients are rightly concerned about possible side effects. According to Dr. Streeten, however, the reduction in fracture risk for patients at high risk “tremendously” outweighs the risk of side effects.
Each type of osteoporosis drug carries its own risk. With bisphosphonates, for example, a portion of patients (5 percent) may experience bone pain. Though uncomfortable, this pain is not associated with any bone damage. Individuals taking Reclast sometimes experience flulike symptoms for a day or two after early infusions. These symptoms tend to lessen with subsequent infusions.
Another rare risk of bisphosphonate treatment that Dr. Streeten mentions is what’s known as atypical femur fracture, which occurs when the femur breaks without trauma. Incidence of atypical femur fracture is going down, however, as we’ve learned more about risk factors for this type of fracture and alter treatment to reduce the risk. For example, the risk of this complication increases with the number of years of treatment, so continuous treatment over 10 years is generally not given. In addition, vitamin D deficiency increases the risk of atypical femur fracture and can be prevented by monitoring vitamin D blood level and adjusting vitamin D supplement dose to keep the level normal.
In addition, Dr. Streeten says that the US Food and Drug Administration (FDA) indications for using bisphosphonates have changed in such a way that fewer patients at risk of atypical femur fracture are receiving the drugs. “Prior to 2003,” she explains, “we were treating basically every postmenopausal woman with low bone mass,” as Fosamax was initially FDA approved for prevention of osteoporosis. “In other words,” she adds, “you didn’t have to have osteoporosis or fracture risk to be treated.” Today only those at high risk of fracture receive bisphosphonates. In addition, patients can get their vitamin D blood levels tested regularly during treatment to make sure they’re staying within the normal range.
Living with Osteoporosis
For Beth, Samantha, and all patients diagnosed with osteoporosis, treatment and management of the condition is ongoing. In addition to treatment with Prolia, Beth exercises three times a week. As a result, she is able to work full-time and is confident in the steps she’s taking to stay strong and reduce her risk of fracture. “I am very optimistic about my bone health and future,” she says.
Samantha also keeps up a regular fitness routine of walking, stretching, and light strength training. In addition, her diet is heavy on plant-based foods and includes two servings of dairy per day, as well as calcium and vitamin D supplements. She still considers her bone health “somewhat precarious” and says, “I am doing everything I can to maintain or improve it.”
Together both Beth’s and Samantha’s stories speak to the potential effectiveness of treatment for osteoporosis, the benefits of seeing a specialist, and the importance of healthy lifestyle practices in maintaining strong bones. On the whole the message is promising for those affected by low bone density and osteoporosis.
\This name is an alias, as the patient asked that her real name not be used.*
Promise in the Pipeline: Osteoporosis Drugs Used to Treat Other Conditions
The promise of some of our current osteoporosis drugs even extends beyond treatment of osteoporosis, as researchers are finding uses in patients with both rheumatoid arthritis (RA) and breast cancer. In people with RA, for example, studies suggest that bisphosphonates may reduce the risk of heart attack and that Prolia might prevent joint erosion among patients taking the drug methotrexate. Breast cancer studies show that bisphosphonates may reduce the risk of developing the disease and may improve survival and reduce bone recurrence in postmenopausal women with early-stage disease.3,4,5,6
With Osteoporosis, Prevention Means Strong Bones and Avoiding Falls
As options for drug treatment for osteoporosis continue to evolve, the fundamentals of bone-loss prevention have remained fairly consistent in recent decades—namely the combination of the right amount of calcium and vitamin D and bone-building exercise. An additional aspect of the prevention conversation is the importance of preventing falls among people affected by low bone density, as these events are a major cause of fracture.
According to Heather Hofflich, DO, FACE, an associate clinical professor in the Department of Medicine at the University of California San Diego Health System, women over 50 (as well as men over 70) should aim for 1,200 mg per day of calcium. “Try to meet this amount with food sources first and then with a supplement,” Dr. Hofflich recommends. In other words, if you’re not getting 1,200 mg per day through diet (such as dairy products, leafy greens, and certain seafood), add a supplement to make up the difference.
The general recommendation for vitamin D is between 800 and 1,000 international units (IU) per day. Our bodies produce vitamin D with sunlight, but too much sun exposure is a risk for skin cancer and other skin damage, so it’s good not to rely on the sun for your vitamin D and instead take a supplement. You can have your vitamin D levels checked to determine if you need a supplement and how much to take.
Along with calcium and vitamin D, exercise is a major component of bone health. This is especially true of weight-bearing activities, such as walking, running, jogging, and using an elliptical machine. “These exercises help stimulate new bone and should be done for at least 30 minutes, five to seven days per week,” Dr. Hofflich says.
If you have low bone density, preventing falls is essential because osteoporosis increases your risk.
“Have your eyes checked routinely and have medications checked to make sure you’re not taking anything that causes problems like dizziness,” Dr. Hofflich advises. She also recommends using a walker or cane and seeing a physical therapist to help improve balance and stamina. At home, handrails on stairs and in bathrooms can help you stay on your feet, as can keeping floors clean (but not slippery) and free of clutter and using rubber mats in the bathtub and shower. Good lighting, Dr. Hofflich says, can also help reduce the risk of tripping and falling at home.
Finally, Dr. Hofflich recommends not smoking and, if you drink alcohol, do so only moderately. Both are linked with osteoporosis.
- Osteoporosis. Centers for Disease Control and Prevention website. Available at: http://www. cdc.gov/nchs/fastats/osteoporosis.htm. Accessed April 18, 2016.
- Learn about Osteoporosis. National Osteoporosis Foundation website. Available at http:// nof.org/learn. Accessed April 18, 2016.
- Wolfe F, Bolster MB, O’Connor CM, Michaud K, Lyles KW, Colón-Emeric CS. Bisphosphonate use is associated with reduced risk of myocardial infarction in patients with rheumatoid arthritis. Journal of Bone and Mineral Research. 2013;28(5):984-91. doi: 10.1002/jbmr.1792.
- Takeuchi T, Tanaka Y, Ishiguro N, et al. Effect of denosumab on Japanese patients with rheumatoid arthritis: A dose-response study of AMG 162 (Denosumab) in patients with Rheumatoid arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE)—a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial. Annals of the Rheumatic Diseases. 2015 2015;0:1-8. doi:10.1136/annrheumdis-2015-208052.
- Newcomb PA, Trentham-Dietz A, Hamptom JM. Bisphosphonates for osteoporosis treatment are associated with reduced breast cancer risk. British Journal of Cancer. 2010;102:799-802. doi:10.1038/sj.bjc.6605555.
- Coleman R, Gnant M, Paterson A, et al. Effects of bisphosphonate treatment on recurrence and cause-specific mortality in women with early breast cancer: A meta-analysis of individual patient data from randomised trials. Presented at: 2013 San Antonio