Pam Harrison

September 08, 2016

Please note that an earlier version of this story failed to note that the investigational osteoporosis agent odanacatib has now been discontinued by Merck.

ATLANTA — A "call to action" will be issued here during the American Society of Bone and Mineral Research (ASBMR) 2016 Meeting as experts grapple with the reality that federal funding for dual-energy X-ray absorptiometry (DEXA) no longer makes screening for osteoporosis all that viable.

"One of the major focuses of our meeting is the crisis we have in osteoporosis," ASBMR president Douglas Kiel, MD, MPH, professor of medicine, Harvard Medical School, Boston, Massachusetts, told Medscape Medical News.

As Dr Kiel explained, this crisis — at least in part — is the result of declining reimbursement for DEXA, the gold-standard screening test to identify patients with osteoporosis.

This has now reached a level where it is "incompatible" for clinics to run the DEXA machines and pay the technicians to keep the units functioning, he added. As a result, "people are closing down their units and are going out of business because reimbursement is so low," Dr Kiel said. "So now we have declining rates of detection as well as declining levels of treatment for patients with the disorder."

Patients Refusing Treatment, Doctors Declining to Prescribe It

A drop in federal funding for DEXA does not, however, tell the whole story. As reported last year, oral bisphosphonate use declined by more than 50% between 2008 and 2012 (J Bone Miner Res. 2015;30:2179–2187).

The plateauing and subsequent decline in oral bisphosphonate use since 2006 coincided with largely media-driven hysteria surrounding safety concerns with these bone-building agents, even though neither the Food and Drug Administration nor the ASBMR had concerns enough themselves to put restrictions on their use.

Many patients refuse to accept treatment for osteoporosis, at least with a bisphosphonate, including those who have already experienced a hip fracture, and many of those who are already taking a bisphosphonate want to stop treatment.

The public's main concern regarding the bisphosphonates appears to center on an extremely rare risk of developing an atypical fracture on treatment. For example, osteonecrosis of the jaw, one of the rare atypical fractures associated with bisphosphonate use, is estimated to occur in fewer than one in 100,000 patients taking the agents.

Indeed, some of that concern appears to have filtered down to prescribing physicians, as fewer than 20% of patients discharged from the hospital after a hip fracture are receiving treatment, according to Dr Kiel.

"This would be like sending someone home after a heart attack with absolutely no treatment and telling them, 'Good luck. I hope you don't have another one and die from it,' " he added.

"The reality is patients are more likely to die of a regular hip fracture that could be prevented by treatment than to sustain a rare side effect in the form of an unusual fracture," he stressed.

"You have to weigh the risks and the benefits of treatment."

According to the National Osteoporosis Foundation, some 54 million Americans over the age of 50 are already affected by osteopenia or osteoporosis, and osteoporosis is responsible for approximately two million fractures every year in the United States.

Important Clinical-Trial Results Will Keep Docs Up-to-Date

Dr Kiel said that, in parallel to a number of sessions devoted to identifying patients at risk for fracture and closing the obvious treatment gap, the annual meeting will do what it does best each year, namely present the latest in the field of bone and mineral research and ensure attendees are kept up-to-date.

For example, three new medications for the treatment of osteoporosis will likely come onto the market by the end of this year, and all of the pivotal trials detailing their safety and efficacy will be presented at this year's meeting.

These include results from the Fracture Study in Postmenopausal Women With Osteoporosis (FRAME), which are expected to show that romosozumab (Amgen), a drug with the dual effect of promoting bone formation and inhibiting bone resorption, reduces the incidence of new vertebral fractures as well.

Similarly, trial results investigating the parathyroid-hormone–related protein analog abaloparatide (Radius Health) will likely provide ongoing evidence that the agent again reduces fractures in high-risk postmenopausal women with osteoporosis.

And although the investigational once-weekly oral cathepsin-K inhibitor odanacatib has now been discontinued by Merck due to an increased risk for stroke in a late-stage study in postmenopausal women, the company had planned to report 5-year data from the previously reported Long-Term Odanacatib Fracture Trial (LOFT) at the ASBMR meeting. It is not known at this stage whether this presentation will still go ahead.

New Developments in Rare Bone Diseases

"There have also been new developments in rare diseases that affect the skeleton for which industry is developing novel treatments," Dr Kiel observed.

One of these rare diseases is hypophosphatasia, which affects children and is associated with severe disability. Now, there is a replacement enzyme in the form of asfotase alfa that has been shown to improve skeletal mineralization and help children regain their strength and mobility.

Another rare bone disease is X-linked hypophosphatemia (XLH), where the body loses all of its phosphate due to excess levels of FGF23. The company Ultragenyx makes a drug called KRN23, which binds and therefore inhibits the excessive biological activity of FGF23, as Dr Kiel pointed out.

"By blocking excess FGF23 in patients with XLH, KRN23 is intended to restore normal phosphate reabsorption from the kidney and increase the production of vitamin D, which enhances intestinal absorption of phosphate and calcium," he explained.

Both of these rare diseases, among others, will be featured during special sessions during the meeting.

Diet, Exercise, and the Gut Microbiome Contribute to Bone Health

"There is also a connection between the gut and the skeleton," Dr Kiel continued. As has increasingly been reported elsewhere, there is a connection between the gut microbiome and a whole host of diseases, and bone disease is no exception, offering the potential for novel treatment strategies.

Much will also be said about the protective effect of exercise on bone, the importance of good nutrition in building bone strength, and how modern lifestyle either contributes to or detracts from strong, healthy bones.

"ASBMR is the premier scientific meeting in our field where all the best science is shared," Dr Kiel reaffirms.

"It's like going to the big American Society of Clinical Oncology meeting for oncologists — all of the big studies are presented at our meeting — so it's very exciting, and that's why everyone tries to go to this meeting, because of the caliber of the science."

Dr Kiel has served on a scientific advisory board for Merck Sharp & Dohme and has received royalties from Wolters Kluwer.

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