ENDO 2019: 101st Annual Meeting of the Endocrine Society:

Treating Osteoporosis Must Simultaneously Address Patient Fears, Needs

with Clifford J. Rosen, MD,  and Mone Zaidi, MD, PhD

The Endocrine Society released guidelines for the Pharmacologic Management of Osteoporosis in Postmenopausal Women,1 to draw attention to the need for earlier, wider screening and treatment of bone loss.

They were announced at ENDO 2019—the Endocrine Society annual meeting in New Orleans, and simultaneously published online in the Journal of Clinical Endocrinology and Metabolism;1,2 the document was prepared jointly by the European Society of Endocrinology.

Osteoporosis Guidelines for postmenopausal women presented at ENDO 2019.

Methodology and Drivers Behind Development of the Guidelines

Following a five-year process involving two systemic reviews of the literature and one meta-analysis, and taking into consideration values and preferences of patients and clinicians in arriving at these recommendations for osteoporosis management,2 said Nelson B. Watts, MD, director of osteoporosis and bone health services at Mercy Hospital and professor of medicine at the University of Cincinnati, in Ohio, who moderated the special scientific session at ENDO 2019.

In addition to the evidence basis, it was important to consider patient engagement in the development of these recommendations, said Dr. Watts, taking into consideration factors that are known to influence compliance and affect adherence, as well as cost.

Osteoporosis remains a significant problem because we're not treating enough people. “We're starting them on medication but 70% are not on therapy within a year after initiation,” said chair of the guidelines writing committee, Clifford Rosen, MD, who is director of the Center for Clinical & Translational Research at Main Medical Center Research Institute, and professor of Medicine at Tufts University School of Medicine in Boston, Massachusetts.

“We think that's due to worry about fractures. I think sometimes it's a lack of communication from providers about the importance of staying on therapy,” said Dr. Rosen. “It's a real dilemma for us because it's important to treat."  

“As such, these recommendations focus on initiating treatment in patients deemed at risk (BMD < -2.5 and/or a fracture) and very high risk, having had two or more vertebral fractures,” he said.

Specific Recommendations Based on Risk of Fracture

As a start, to optimization for bone health, all postmenopausal women taking osteoporosis therapies — except anabolics — should consume calcium and vitamin D preferably in their diet or by taking supplements is recommended, along with an assessment of 10-year fracture risk according to country-specific guidelines.

As in the past, bisphosphonates and denosumab are still advised as first-line therapies but the Endocrine Society now recommends anabolic treatments—teriparitide (Forteo) or abaloparatide (Tymlos)—as first-line therapy for patients with very severe osteoporosis, multiple fractures, and/or very low bone density, said guidelines committee member, Dolores Shoback, MD, professor of medicine at the University of California at San Francisco and an endocrinologist at the San Francisco Department of Veterans Affairs Medical Center in California.

“While either choice is has shown to reduce fracture risk in phase 3 studies, we have more experience with teriparatide, which good and cheaper,” she said.

There is no reason not to go to one of the anabolics, Dr. Eastell said, "when prescribing teriparatide, it is reasonable to treat for about a week and then do a biomarker check of procollagen type IN propeptide (PINP) to check for signs of anabolic activity (> 10 mcg/L). You can expect to see a linear increase in the spine, but significant changes in the hip do not occur for at least a year."

The duration of treatment is approved for 24 months but is artificially limited to 18 months in the United States due to the potential risk of osteosarcoma, said Dr. Rosen, “Therefore, I hold the extra six months in the bank to come back to if needed.”  Restarting denosumab is a developing area of research.

For these women this new recommendation, "means that we initiate intervention early, as the effects are quicker than they are with bisphosphonates," he said. And, for women who have been on bisphosphonates for 3 to 5 years, fracture risk should be assessed.

For women who remain at low-to-moderate risk of fracture, they should be prescribed a "bisphosphonate holiday."

Comparing to Existing Guidelines for Osteoporosis—What’s New?

When asked how these guidelines differ from those issued by other professional organizations such as the American Association of Clinical Endocrinologists or the National Osteoporosis Society, Dr. Rosen told EndocrineWeb, “I think the differences lie in the following:

  • For severe [very high risk] osteoporosis, we recommend starting with abaloparatide or teriparatide versus a bisphosphonate.
  • For all others, first-line is a bisphosphonate or denosumab are acceptable.
  • For those at low or moderate risk [of fracture] who are taking bisphosphonates, a drug holiday is recommended after five years.

And, advising at-risk patients to get sufficient calcium and vitamin D from the diet, and only relying on supplements when dietary intake is not possible or feasible. Also, patients need to realize that increasing exercise and improving diet may slow the rate of bone loss but won’t build bone. “Only the approved medications can do that,” said Nelson Watts, in response to a discussion about applying the guidelines to real-world patient cases.2

Clinical Challenge of Getting Patients Onboard with Treatment

Patients come in for an appointment and will often say, ‘I’m not going to do it,” said Dr. Rosen. “They are uncomfortable with the suggestion that they take a drug to reduce their risk of fracture. The first step in managing women at risk for fracture is to listen to your patient. Know their knowledge base and fears. Keep in mind that getting them on board is a process; it’s not going to happen in the first 15-minute appointment. “

“Therefore, assess patients to ascertain who is at high risk of fracture in the next two years so you can convey the urgency to those with imminent risk; otherwise, observation is ok, monitoring than for acceleration of bone loss,“ he said.

Similarly, Dr. Watts said what he hears frequently is: “My Bridge partner told me about the jaw problem so I don’t want to take this medication. In response, I use the FRAX score for younger women; I discuss behavior modification for fracture risk reduction and may use an assessment tool to capture fall risk.”

Patients need reassurance. “The benefit of bisphosphonates is their long half-life, they continue to work for upwards of 10 years so many women can tolerate the drug holiday after five years and not lose all gains while on drug holiday,2 said Richard Eastell, MD, FRCP, member of the guidelines task force, and professor and director of the Mellanby Centre for Bone Research in Sheffield, England.

Certain factors may increase a woman’s risk, particularly longer duration of therapy. "That's one of the reasons we've advocated a drug holiday in many individuals who have been successfully treated for up to three years with a bisphosphonate," said Dr. Rosen.

“Some of the recent data suggest that the risk for atypical femoral fractures with bisphosphonates remains quite low," he said. Other adverse effects, such as osteonecrosis of the jaw, are less frequent.

In a patient without a history of a previous fracture, you may have to sell her on daily injections with consideration regarding reimbursement.

Other points, the guidelines panel emphasized the following key points:2

  •  In selecting initial therapy, always consider patient preference. For example, many women are excited by the prospect of a single intravenous dose of denosumab; and it is feasible for the patient to do a self-injection at home.
  • A twice weekly or a monthly dose is possible but many patients are more apt to follow a predictable schedule (ie, a regular weekly treatment), which seems to support better compliance.
  • Long-term assessment of risk and consideration of long-term IV can be reserved for 6-month injection and follow up.
  • Biomarkers are affected by time of time: PIND to assure compliance and adherence

The full osteoporosis treatment algorithm can be accessed at the Endocrine Society.

Applying the Guidelines But Starting Treatment Sooner

Mone Zaidi, MD, PhD, professor of medicine at the Icahn School of Medicine at Mount Sinai in New York City, told EndocrineWeb, that the significance of these guidelines is the need to begin treating women at perimenopause and not waiting for a full-blown diagnosis of osteoporosis, “it’s about responding to risk of fracture.”

"We need to be more aggressive about treating individuals who have had a previous fracture," Dr. Zaidi told EndocrineWeb, .and recognizing that once bone is lost, we are faced with holding off further loss so we want to help women retain as much bone as possible.”

“Osteopenia is really an epidemiological definition of bone loss in women and in men, which was derived from data generated about 20 years ago and relates to T scores, which is the number of standard deviations above or below the mean of a young reference female population with anything between a -1 and a -2.5- considered is considered osteopenia,” he said.

Dr. Zaidi offered a couple of key points regarding the management of women with osteopenia in comparison to overt osteoporosis:

“First, a woman has to progress from normal bone density through the osteopenic range in order to become osteoporotic. Women suddenly do not become osteoporotic.”

“The second point,” he said, “is that more recent evidence suggests that a woman loses bone most rapidly in the early years of menopause when she is osteopenic, primarily. Osteopenia also causes a loss of bone that predisposes the woman to fractures and if you look at the general population, there are more fractures in women who have osteopenia not because there’s a greater risk of fracture but because there are simply more women considered in the osteopenic range, yet fracture with the same kind of frequency.”

“So the idea is to treat active bone loss during perimenopause and not wait until the bone is already lost. I wrote an article some years ago on bone loss versus lost bone and the idea is that once bone is lost, it’s a sad case, so you treat bone loss either when a woman is osteopenia or indeed osteoporotic.

Monitoring of bone mineral density (BMD) for high-risk patients with low BMD should take place every 1 to 3 years, the guidelines say.  Use P1NP (or osteocalcin) by one month to monitor the efficacy of therapy; look for a doubling to demonstrate a  good response, said Dr. Eastell. “Only 5% of women don't respond as expected and they are likely noncompliant. Check again at three months to confirm response and correlations with BMD at one year."

None of the participants indicated any relevant financial conflicts.

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