After decades of promotion on ways to guard against osteoporosis, recent studies indicate that late-life bone resiliency has been eroding, and newly released clinical guidelines suggest diagnostic and treatment strategies to counteract that slide among women.
To detect osteoporosis sooner, all women should get a bone density test starting at age 65, and even earlier in life if a fracture assessment identifies an above-average vulnerability, according to the latest guidelines for postmenopausal women from the American Association of Clinical Endocrinologists and the American College of Endocrinology (AACE/ACE). The guidelines, published in September 2016, also provide a two-track treatment algorithm based on a patient's fracture risk, with recommendations on which drugs doctors should start and when a bisphosphonate holiday might be considered.
Also last fall, nearly three dozen national and international groups, including the American Society for Bone and Mineral Research (ASBMR) and the National Osteoporosis Foundation, highlighted statistics in a “call to action” to spur quicker treatment of porous bones, which develop in 16% of U.S. women ages 50 and older, according to CDC data. Osteoporosis specialists cite reduced access to bone density testing, along with inflated patient fears about rare drug-related side effects, as setting the stage for worsening rates of bone breaks in the decades to come.
The rate of hip fractures in the U.S. has been steadily declining since 2002, but that decline appears to have begun to level off by 2013 and 2014, according to data presented at the annual ASBMR meeting in September 2016. “Many women who meet the indications for bone density testing are not getting it,” said Michael Lewiecki, MD, FACP, one of the researchers involved and a coauthor of the recent AACE/ACE guidelines.
“Actually the number of women getting bone density testing is going down, the number of women getting diagnosed with osteoporosis is going down, and the data we presented at ASBMR showed that hip fracture rates in Medicare-population women are higher than were projected [to be],” he said. “This is considered to be a crisis in the care of osteoporosis.”
Diagnosing porous bones
The frequency of hospitalizations and related costs for older women with osteoporosis are greater than for other common conditions, according to an analysis of data from 2000 to 2011 published in the January 2015 Mayo Clinic Proceedings. During that 12-year stretch, researchers identified 4.9 million hospitalizations in women ages 55 and older for osteoporotic fractures compared with 2.9 million for myocardial infarction, 3 million for stroke, and 0.7 million for breast cancer. Moreover, the annual hospital-related price tag to treat those fractures, $5.1 billion, was the highest, followed by myocardial infarction ($4.3 billion), stroke ($3 billion), and breast cancer ($0.5 billion).
To avoid those disabling consequences, primary care doctors can intervene far earlier in life, starting in young adulthood, said Andrea Singer, MD, FACP, one of the study's authors and division director of women's primary care at MedStar Georgetown University Hospital in Washington, D.C. They can emphasize bolstering strong bones through good nutrition and weight-bearing exercise, as well as avoiding risk factors such as smoking and excessive alcohol consumption, she said.
When taking a medical history, doctors should be sure to ask if any immediate family members, and particularly any parents, have had a fracture, said Dr. Singer, who is also clinical director at the National Osteoporosis Foundation. Once patients reach age 50, and possibly sooner, ask them about their own personal fracture history, and don't let them downplay any breaks, she said. “Patients will always say, ‘Oh, but it was a bad fall.’ I'm not sure any fall is good.”
If the fall occurred at standing height or lower—considered to be a low-trauma tumble—that's a warning sign for osteoporosis, Dr. Singer said. The patient might have stepped clumsily off a curb and fractured her hip, or tripped while walking and, by catching herself with an outstretched arm, broken her wrist. “The reason that [patient history] is so important is that a prior osteoporosis fracture is probably the most significant risk factor for future fracture,” Dr. Singer said.
One analysis, published in JAMA in 2009, found that even one low-trauma fracture substantially boosted the risk of both another break and increased mortality. The study, which tracked slightly more than 4,000 Australian men and women ages 60 and older for nearly two decades, found that those who had a low-trauma fracture faced an elevated mortality risk within the next 5 years; for hip fractures specifically, this increased risk persisted for a decade.
The new AACE/ACE guidelines, which emphasize the importance of routine clinical assessment for osteoporosis in women ages 50 and older, suggest that doctors consider using the World Health Organization's FRAX (Fracture Risk Assessment Tool). One advantage of calculating a patient's FRAX score is that it might help a doctor to diagnose someone, for example, a patient who smokes or someone with a history of falls, who might not make the cut based on bone density results alone, said Arti Bhan, MBBS, division head of endocrinology at Henry Ford Health System in Detroit.
“Of all the risk factors for a fracture, bone density contributes to less than 50% of the information,” Dr. Bhan said. “Some of the risk is related to bone architecture, which currently there is no test for.”
But bone density testing, typically with dual-energy X-ray absorptiometry (DXA), still figures prominently in diagnostic criteria for considering drug treatment, according to the AACE/ACE guidelines. For example, the new guidelines agree with the recent guidance of the National Bone Health Alliance to diagnose osteoporosis in a postmenopausal woman with a high FRAX score as long as she also has osteopenia, with a T-score of between −1.0 and −2.5.
It is more difficult for patients to obtain DXA tests these days, though, since CMS officials decreased reimbursement in physician offices to the point that the cost of the service is not covered, said Dr. Lewiecki, who also directs the New Mexico Clinical Research & Osteoporosis Center in Albuquerque. His abstract on hip fractures, presented at the ASBMR meeting, found that rates of DXA testing began to decline in 2009, which was two years after those office-based rates were cut.
Last summer, CMS officials also proposed changes in reimbursement for some hospital-based imaging services, including ultrasound and DXA. In a Sept. 6, 2016, letter, the AACE opposed the move, saying that the new rates would reduce DXA reimbursement by more than 30%, making it financially infeasible for hospitals to offer. In the end, the final rates reflected a slight increase in reimbursement from $100.69 to $112.69 per test.
To ensure that more women get screened, primary care doctors can ask a nurse or a medical assistant to help by identifying eligible patients and then following through to make sure they got the DXA, Dr. Lewiecki said. Sometimes hospitals have fracture liaison services that can help outpatient doctors, he said, by watching for patients with fractures and then following up after discharge to make sure they get the treatment they need.
One benefit of the new AACE/ACE guidelines is that they offer doctors more drug guidance by providing two sets of recommendations based on a patient's fracture risk, Dr. Singer said. For patients at moderate risk, with no prior breaks, the treatment algorithm recommends one of four medication options to start: alendronate, denosumab, risedronate, or zoledronic acid.
But the set of suggested first-line options differs for patients who are at the highest fracture risk or have already experienced a break, including denosumab, teriparatide, or zoledronic acid. “People who are at the highest risk should get medications for which we have the best data in terms of fracture reduction,” Dr. Singer said.
At this point, the only approved drug that helps to build bone rather than guard against further bone loss is teriparatide, Dr. Bhan said. The medication is expensive and requires a daily injection, so she typically recommends it for patients who are at the highest fracture risk or who have dealt with one or more fractures already.
Otherwise, the patient's other medical conditions should be taken into account when considering options, Dr. Bhan said. For example, denosumab isn't cleared by the kidneys and thus might be a possibility for those with some degree of kidney dysfunction. For oral bisphosphonates, heartburn is a potential side effect, so doctors might want to consider denosumab or an intravenous bisphosphonate for those women who already cope with heartburn or stomach ulcers, she said.
But Dr. Bhan and others worry particularly that extensive media coverage of rare but still notable side effects from bisphosphonates, including atypical femoral fractures and osteonecrosis of the jaw, continues to unduly discourage patients from starting or sticking with drug treatment. One analysis, which looked at nearly 100,000 patients ages 50 and older hospitalized for hip fracture, 70% of whom were women, found that 40.2% had started a medication within a year after discharge in 2002 but just 20.5% had done so in 2011. In those patients, bisphosphonates were most frequently prescribed (70.9%), followed by hormone replacement therapy (10.7%), calcitonin (9.6%), raloxifene (6%), teriparatide (2.6%), and denosumab (0.3%), according to the findings in the September 2014 Journal of Bone and Mineral Research.
The new guidelines tackle that fear of side effects—along with medication benefits—directly in a series of charts. One illustrates that an 80-year-old woman with a T-score of −3.3 faces a 25% risk of a fracture within the next decade. If treated, that risk is reduced to 12.5%. The risk of osteonecrosis of the jaw while on treatment, in contrast, is calculated to be 0.01%.
“It's about the same,” Dr. Lewiecki noted wryly, “as the risk of being killed by a lightning strike if you live in New Mexico.”
Weighing risks and benefits
The AACE/ACE guidelines also align with a recent ASBMR report on long-term bisphosphonate treatment, published in the January 2016 Journal of Bone and Mineral Research, regarding which patients might be eligible for a drug holiday, Dr. Lewiecki said. It's an option only available in certain circumstances and only for patients taking bisphosphonates, he stressed, saying the beneficial effects of other drugs, such as denosumab and teriparatide, wane more quickly after withdrawal.
“Another myth is that bisphosphonates should be stopped after 3 to 5 years of treatment regardless of the level of fracture risk,” Dr. Lewiecki said. Instead, the AACE/ACE guidelines specify that a holiday should be considered after at least 3 years on an intravenous bisphosphonate or 5 years on the oral form. The option to take a bisphosphonates break after that stretch should only be considered in lower-risk patients, the guidelines said.
The optimal duration of a bisphosphonate holiday “has not been established,” the authors wrote. Instead, they recommend that doctors annually check fracture risk and consider resuming the drug in patients who have a fracture or show significant bone mineral density loss.
Primary care doctors can treat “the vast majority of patients,” Dr. Bhan said. But they should consider referring a woman to an endocrinologist or a bone specialist in several circumstances, such as when someone has a fracture despite normal bone density or experiences more than one break while taking medication. “One fracture while on treatment does not constitute treatment failure,” she said, “but more than one fracture is something to worry about.”
When discussing the pros and cons of taking drugs, doctors should never minimize the side effects and should be sure to listen to patients' concerns as they weigh medication options, Dr. Singer said. “I would rather have patients on something than have them on nothing,” she said.
But family doctors who have likely known patients for years are best positioned to describe the stakes they run without drug treatment, she said.
“We know them and we know their families,” Dr. Singer said. “So being able to say to them, ‘If we do nothing and you have another fracture, you may not be able to pick up your new grandchild. Or be able to drive to go visit them. Or play golf.’ Or whatever resonates with them, and that's important to them.”