Despite effective new therapies, osteoporosis remains undiagnosed, untreated
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During the past 20 years, Endocrine Today has covered the latest advancements surrounding osteoporosis care. For its 20th year, the publication is taking a look back.
A study published in Archives of Internal Medicine in 2004 tracked trends in osteoporosis care and prescriptions from 1988 to 2003. The researchers described a fourfold increase in office visits from 1994 to 2003 and a 15 percentage point increase in visits resulting in prescriptions, of which 73% were for bisphosphonates in 2003. Patients were overwhelmingly women — 96% in 2003 — and 80% were older than 65 years.
“New medications for osteoporosis offering improved efficacy and convenient dosing were associated with increased frequency of patient visits and treatment,” the researchers wrote.
Since then, the field has seen more accurate assessment of fracture risk and powerful new drugs to address it. However, fewer people may be benefiting from these advancements, according to experts, due to cuts in reimbursement for testing, an excessive fear of rare adverse events, and the need for lifelong treatment once osteoporosis is diagnosed.
“We’re [treating osteoporosis] a little differently now because of the concept of fracture risk stratification,” E. Michael Lewiecki, MD, FACE, FACP, CCD, director of the New Mexico Clinical Research & Osteoporosis Center and director of the Bone Health ECHO Clinic at University of New Mexico Health Sciences Center, Albuquerque, told Healio. “When the first bisphosphonates came out, the idea was that almost every postmenopausal woman might benefit from a bisphosphonate to treat and prevent osteoporosis, and now, we’re focusing more on identifying patients who are at high risk for fracture to be sure that we can treat those patients. Fewer low-risk patients are being treated, and hopefully, more high-risk patients are being treated.”
Screening and risk assessment
DXA imaging for assessing bone mineral density has been available since the late 1980s, but how physicians use the technology evolved during the past 20 years, according to Nelson B. Watts, MD, FACP, MACE, CCD, director of osteoporosis and bone health services for Mercy Health, Cincinnati.
In 2002, the U.S. Preventive Services Task Force first recommended routine osteoporosis screening with DXA for women aged 65 years and older, and in 2018, added younger women at high risk for osteoporosis. The organization does not advise routine screening for men. In 2008, the Fracture Risk Assessment Tool (FRAX) was developed and added to DXA software for calculating an individual’s 10-year risks for hip and major fractures. More recently, trabecular bone score, an assessment of bone microarchitecture, was added to DXA as well.
“The risk of fracture goes up with age. Men typically fracture 5 or 10 years older than women,” Watts told Healio. “Everybody should have a bone density test eventually — women by [age] 65, men by 70. But younger, postmenopausal women and men should be tested sooner if they have a family history of osteoporosis, any one of a number of diseases that are associated with bone loss or increased fracture risk, or any one of several drugs that have been implicated in early bone loss or increased fracture risk.”
However, in 2008, Medicare reduced DXA reimbursement, and the procedure largely moved from physician offices to radiology, according to Watts.
“Radiologists in general don't do a very good job, either with the test itself or with the reporting. The number of bone density tests went down, possibly because it's harder to get to for patients,” Watts said. “We're not following patients well.”
The consequences of reduced screening are even worse for men, Lewiecki said.
“Women are underdiagnosed and undertreated, and men, even more so,” Lewiecki said. “It is much more difficult to get Medicare to cover a bone density test on men. ... Therefore, many men with osteoporosis are not being recognized until they have a fracture.”
However, there is a bright note, according to Lewiecki. Since 2002, the understanding of imminent fracture risk has also evolved, meaning that someone with a fracture has a high risk for another fracture within the next 1 to 2 years. Fracture liaison services have been designed to evaluate and treat patients urgently after a fracture, with the hope of avoiding a future fracture.
Powerful new medications
Several new medications for treating patients with the most serious osteoporosis have been approved during the past few years.
Before 2002, oral bisphosphonates were the primary osteoporosis therapies. Since then, several anabolic agents have been approved, including teriparatide (Forteo, Eli Lilly) in 2002, abaloparatide (Tymlos, Radius Health) in 2017 and romosozumab (Evenity, Amgen) in 2019. In addition, the IV bisphosphonate zoledronic acid (Reclast, Novartis) was approved in 2007, and the twice-yearly injection denosumab (Prolia, Amgen) in 2010, expanding options for those who cannot tolerate oral medications.
Another drug, odanacatib (Merck), was assessed in a $1.1 billion study of more than 15,000 women over more than 5 years, but did not make it into the osteoporosis pipeline due to associated risks for myocardial infarction and stroke.
All of the approved drugs are currently allowed for use by postmenopausal women, but abaloparatide and romosozumab have not been approved for use in men. The bisphosphonates and denosumab reduce the risk for spine fracture by approximately 70%, the risk for hip fracture by 40% to 50% and the risk for nonvertebral fractures by 20%, according to Watts.
“Medications for osteoporosis do not eliminate the possibility of having a fracture, but they do reduce the chances at the two more important sites — spine fracture, where it’s the most common, and hip fracture, which is probably the most serious,” Watts said.
Researchers have also gained a stronger understanding of how to use these drugs most effectively, particularly sequentially and in combinations; for example, starting with an anabolic agent and then following with an antiresorptive agent is preferable to the opposite order of treatment for high risk patients, according to Lewiecki.
“We've learned that beginning with a potent antiresorptive agent and then switching to an anabolic agent might delay or attenuate the anabolic effects,” Lewiecki said.
Challenges: Public perception, lifelong therapy
Reports of rare adverse events associated with osteoporosis treatment alarmed the public during the past 2 decades and led many to discontinue prevention and therapy.
Before 2002, the only adverse events of concern associated with osteoporosis therapy were upset stomachs or heartburn caused by oral bisphosphonate treatment. However, reports of osteonecrosis of the jaw emerged in 2003 and reports of atypical femur fracture in 2008. A study reporting increased MI and stroke associated with calcium supplementation was not replicated.
The adverse events gained media attention and frightened many patients despite being “extraordinarily rare,” Lewiecki said.
The issue of jaw necrosis arose in patients with metastatic bone cancer who were receiving IV bisphosphonate at doses 10 times higher than what is used in osteoporosis treatment, Watts said.
“Denosumab that we use to treat osteoporosis is used in higher doses in patients with solid tumors (breast cancer, colon cancer, prostate cancer), metastatic cancer to bone, and we see the same jaw problem in 1% or 2% of those patients with advanced cancer,” Watts said.
The atypical femur fractures “appear to be related to bisphosphonate use, not to the other drugs that we use,” Watts said. “They're much less common than hip fractures and probably much less serious than hip fractures. We're beginning to understand why they occur, but the occurrence rate is more like one in 10,000 patients.”
Additionally, for patients not concerned over rare events, adherence to therapy can be a challenge.
“Even when osteoporosis is diagnosed, most people who can benefit from treatment are not being treated, and even those who are treated, often don’t take the medication long enough to benefit from therapy,” Lewiecki said.
Osteoporosis is a lifelong disease that cannot be cured, although some treatment regimens allow patients to pause medications for months or years with “drug holidays.”
“Sooner or later, the benefits will wane, and it's time to resume the therapy, [but] all too often patients have had their medication stopped, and no further attention has been paid. Sooner or later fracture risk will rise,” Lewiecki said. “It's become a particular problem that we've recognized with denosumab, which is not a candidate for a drug holiday. Discontinuation of denosumab without follow-up treatment, in some cases, is then associated with multiple vertebral fractures.”
The good news is that since 2002 all bisphosphonate drugs for osteoporosis have become available as generics, with their prices decreased drastically. Newer agents remain expensive.
“Right now, since there are basically no drugs in the clinical pipeline, the emphasis is on better use of the drugs that we do have,” Lewiecki said. “Hopefully, as time passes, the prices will get lower and lower to make more of these drugs more accessible for patients, because the cost of drugs, especially the anabolic agents, has been very high and that’s made it difficult for some of the patients who need these drugs to have it affordable enough that they can actually take it.”
Reference:
- Stafford RS, et al. Arch Intern Med. 2004;doi:10.1001/archinte.164.14.1525.
For more information:
E. Michael Lewiecki, MD, FACE, FACP, CCD, can be reached at mlewiecki@gmail.com.
Nelson B. Watts, MD, FACP, MACE, CCD, can be reached at nwatts@mercy.com.
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