November 22, 2022
6 minutes read
Lewiecki reports that he is a consultant, investigator and spokesperson for Amgen and an investigator for Radius Health. Watts does not report any relevant financial disclosures.
in the last 20 years, endocrine today covered the latest advances in the treatment of osteoporosis. The publication looks back for the 20th time.
A study published in Archive of Internal Medicine in 2004 tracked trends in osteoporosis care and prescriptions from 1988 to 2003. The researchers described a fourfold increase in physician visits from 1994 to 2003 and a 15 percent increase in visits that resulted in prescriptions, 73 percent of which were bisphosphonates in 2003 were. Patients were predominantly women – 96% in 2003 – and 80% were older than 65 years.
“New osteoporosis drugs that offer improved efficacy and convenient dosing have been associated with increased frequency of patient visits and treatments,” the researchers wrote.
Since then, the field has seen more accurate assessment of fracture risk and powerful new drugs to combat it. However, experts say fewer people could benefit from these advances due to reduced reimbursement for tests, an excessive fear of rare adverse events and the need for lifelong treatment once osteoporosis is diagnosed.
“was [treating osteoporosis] now slightly different 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 the University of New Mexico Health Sciences Center, Albuquerque, opposite Healio. “When bisphosphonates first came out, the idea was that almost every postmenopausal woman could benefit from a bisphosphonate to treat and prevent osteoporosis, and now we’re more focused on identifying patients at high risk of fractures, just to be safe.” that we can do that treat these patients. Fewer low-risk patients will be treated and hopefully more high-risk patients.”
screening and risk assessment
DXA imaging to assess bone mineral density has been available since the late 1980s, but how physicians use the technology has evolved accordingly over the past 20 years Nelson B Watts, MD, FACP, MACE, CCD, Director of Osteoporosis and Bone Health Services for Mercy Health, Cincinnati.
In 2002, the US Preventive Services Task Force first recommended routine osteoporosis screening with DXA for women age 65 and older, adding younger women at high risk of osteoporosis in 2018. The organization advises against routine screening for men. In 2008, the Fracture Risk Assessment Tool (FRAX) was developed and added to the DXA software to calculate a person’s 10-year risk of hip and major fractures. Recently, DXA has also been expanded to include the Trabecular Bone Score, an assessment of bone microarchitecture.
Nelson B Watts
“The risk of fracture increases with age. Males typically erupt 5 or 10 years older than females,” Watts told Healio. “Everyone should have a bone density test at some point – women of [age] 65, men to 70. But younger, postmenopausal women and men should be tested earlier if they have a family history of osteoporosis, any of several diseases associated with bone loss or increased risk of fractures, or any of several medications associated with early bone loss or have been linked to an increased risk of fracture.”
However, in 2008, Medicare reduced DXA reimbursement, and the procedure was largely moved from physician’s offices to radiology, according to Watts.
“Radiologists generally don’t do a very good job, either with the test itself or with the reporting. Bone density testing has gone down, possibly because it’s harder for patients to get there,” Watts said. “We don’t follow patients well.”
The consequences of reduced screening are even worse for men, Lewiecki said.
“Women are underdiagnosed and undertreated, men even more so,” said Lewiecki. “It’s a lot harder to get Medicare to cover a bone density test for men. … As a result, many men with osteoporosis are not recognized until they have a fracture.”
However, according to Lewiecki, there is a bright note. Since 2002, the understanding of impending fracture risk has also evolved, meaning that someone with a fracture has a high risk of having another fracture within the next 1 to 2 years. Fracture liaison services were developed to provide urgent evaluation and treatment to patients after a fracture in hopes of avoiding a future fracture.
Powerful new drugs
In recent years, several new drugs have been approved to treat patients with severe osteoporosis.
Prior to 2002, oral bisphosphonates were the primary osteoporosis therapies. Since then, several anabolic steroids have been approved, including teriparatide (Forteo, Eli Lilly) in 2002, abaloparatide (Tymlos, Radius Health) in 2017, and romosozumab (Evenity, Amgen) in 2019. Also, the IV bisphosphonate zoledronic acid (Reclast, Novartis ) was approved in 2007 and the twice-yearly injection of denosumab (Prolia, Amgen) in 2010, expanding options for those who cannot tolerate oral medications.
Another drug, odanacatib (Merck), was studied in a $1.1 billion study involving more than 15,000 women over more than 5 years, but failed to make it into the osteoporosis community due to associated risks of myocardial infarction and stroke. Pipeline.
All approved drugs are currently approved for use in postmenopausal women, but abaloparatide and romosozumab are not approved for use in men. According to Watts, the bisphosphonates and denosumab reduce the risk of spinal fractures by about 70%, the risk of hip fractures by 40% to 50%, and the risk of nonvertebral fractures by 20%.
“Medications for osteoporosis don’t eliminate the possibility of a fracture, but they do reduce the likelihood at the two more important sites — spinal fracture, where it’s most common, and hip fracture, which is probably the most serious,” Watts said.
Researchers have also gained a better understanding of how to use these drugs most effectively, particularly sequentially and in combinations; For example, according to Lewiecki, starting with an anabolic steroid and then an antiresorptive is preferable to the reverse order of treatment in high-risk patients.
“We learned that starting with a strong antiresorptive agent and then switching to an anabolic agent can delay or attenuate the anabolic effects,” said Lewiecki.
Challenges: Public perception, lifelong therapy
Reports of rare adverse events associated with the treatment of osteoporosis have alarmed the public over the past two decades, prompting many to abandon prevention and therapy.
Prior to 2002, the only worrisome adverse events associated with osteoporosis therapy were indigestion or heartburn caused by oral bisphosphonate treatment. However, reports of osteonecrosis of the jaw appeared in 2003 and reports of atypical femoral fractures in 2008. A study reporting increased heart attack and stroke associated with calcium supplementation was not replicated.
The adverse events attracted media attention and frightened many patients, although they were “extraordinarily rare,” Lewiecki said.
The problem of necrosis of the jaw emerged in patients with metastatic bone cancer who received intravenous bisphosphonate at doses 10 times higher than those used for osteoporosis treatment, Watts said.
“Denosumab, which we use to treat osteoporosis, is used in higher doses in patients with solid tumors (breast cancer, colon cancer, prostate cancer) and bone metastases, and we see the same jaw problem in 1% or 2% of these advanced cancer patients,” said Watts.
The atypical femoral fractures “appear to be related to bisphosphonate use, not the other drugs we use,” Watts said. “They are much less common than hip fractures and probably much less severe than hip fractures. We are beginning to understand why they occur, but the frequency is closer to 1 in 10,000 patients.”
In addition, adherence to therapy can be challenging for patients who are not concerned about infrequent events.
“Even when osteoporosis is diagnosed, most people who might benefit from treatment are not treated, and even those who are treated often do not take the medication long enough to benefit from therapy,” Lewiecki said.
Osteoporosis is a lifelong disease with no cure, although some treatment regimens allow patients to go off medication for months or years with “drug vacations.”
“Sooner or later the benefit wears off and it’s time to start therapy again, [but] All too often, patients’ medications were discontinued without further attention being paid to them. Sooner or later the fracture risk will increase,” said Lewiecki. “It has become a particular concern that we have recognized with denosumab not being a candidate for a drug holiday. Discontinuation of denosumab without follow-up treatment is then associated with multiple vertebral fractures in some cases.”
The good news is that since 2002 all bisphosphonate drugs for osteoporosis have been available generically, although their prices have come down drastically. Newer means remain expensive.
“Right now, with basically no drugs in the clinical pipeline, the focus is on making better use of the drugs that we have,” Lewiecki said. “Hopefully over time the prices will come down to make more of these drugs more accessible to patients because the cost of drugs, especially the anabolic agents, has been very high and this has made it difficult for some patients who need these drugs to to have them affordable enough that they can actually take them.”
- Stafford RS, et al. Arch Intern Med. 2004;doi:10.1001/archinte.164.14.1525.
For more informations:
E. Michael Lewiecki, MD, FACE, FACP, ccd, can be reached at [email protected]
Nelson B. Watts, M.D. FACP, MACE, CCD, can be reached at [email protected]