“A treat-to-target approach is useful in the management of osteoporosis” was the motion proposed in a debate during the recent virtual American Society of Bone and Mineral Research (ASBMR) 2020 annual meeting, and when the votes came in, Michael McClung, MD, who argued against the motion, carried the day.
Agreement with the motion dropped from 63% to 46% after McClung, of the Oregon Osteoporosis Center, Portland, put his views forward in opposition to those of Celia L. Gregson, PhD, University of Bristol, UK, who argued for the motion on behalf of the European Calcified Tissue Society (ECTS).
Disagreement with the statement rose from 37% pre-debate to 54% in the post-debate audience polls.
“The debate is part education and part entertainment,” said McClung, who represented the ASBMR. “I could just as easily have made a strong argument for the motion,” he emphasized to Medscape Medical News.
On the other hand, “had I been in the audience, as a member of ASBMR relying on data and evidence to make clinical decisions, I would have voted against the motion. As appealing as the strategy sounds, we don’t yet have the hard evidence to support its use nor is there a consensus about what an appropriate target should be,” he noted.
Similarly, the debate comoderator and incoming ASBMR President, Suzanne M. Jan de Beur, MD, from Johns Hopkins University, Baltimore, Maryland, said that a treat-to-target strategy for osteoporosis is an attractive idea, but there is no consensus on how to apply it, nor evidence that it improves clinical outcomes.
Treat to Target to Guide Osteoporosis Therapy Is Like Going “Backwards”
In treat to target, the target — such as bone mineral density (BMD) (the most common one) — is identified before treatment is started, McClung explained (and as stated in a review article he coauthored on the topic; Am J Med. 2019;132:e771-e777).
“While treat to target has appealing concepts, using risk factors to guide therapy is almost backwards,” he said. “We can’t change bone density very much.”
Treat to target is “not quite ready for prime time,” he concluded in his rebuttal.
Invited to speculate on which of McClung’s arguments swayed the audience, Gregson conceded that with a treat-to-target strategy “there is too much focus on getting one target for the whole global population with osteoporosis.”
“This is an oversimplification of a complex disease, and it misses the main message that the target should be decided with the patient not for the patient, which means one can’t just have one rule for everyone. There has to be scope to have different targets for different people so that we can deliver individualized care.”
Also, she noted, “generally people don’t vote to change familiar systems.”
Arguments For Treat to Target
Gregson began her argument, however, by stating that treat to target “is now a feasible and useful approach in osteoporosis care.”
The main reasons for adopting this treatment strategy are:
It provides a proactive approach with a clear goal.
It includes periodic treatment reassessment, allowing for prompt revisions to treatment.
Can use targets to guide treatment timing and patient monitoring.
It includes shared decision-making, the gold standard of patient care.
Could improve treatment adherence due to patient “buy-in” of the target.
Can use targets to address the risk of rare side effects.
It allows for sequential treatments, especially for patients at highest risk of fracture.
Can include more patient-centered outcomes such as reduced back pain, restored range of movement, and ability to live independently.
“Patients are not interested in their T-score. They are interested in pain,” said Gregson.
“Reduced fracture risk is a very important goal,” she emphasized. Patients “with osteoporosis and a high fracture risk have the most to gain from a treat-to-target approach.”
“Improved access to anabolic osteoporosis treatments mean achieving those goals or targets are now more achievable than ever,” she concluded.
Arguments Against Treat to Target: Do We Have a Meaningful Target?
“Do we truly have an appropriate, meaningful target for osteoporosis?” McClung began in his counter-argument, casting a seed of doubt in the minds of the audience.
Targets such as no fractures, fracture risk (FRAX score), bone turnover markers, and bone strength have limitations.
Moreover, “Do we have treatment strategies to move patients to the chosen target?” he continued. “What is the evidence that a treat-to-target strategy provides better outcomes than our current treatment paradigm?”
After pointing out a lack of evidence that treat to target leads to better outcomes in osteoporosis, he did allow that “recent data about the relationship between treatment-related BMD values and current fracture risk are appreciated and welcomed.”
“However, a treat-to-target strategy will only be successful if the targets are individualized for each patient, those targets are attainable for most patients, and we have evidence that adopting this strategy improves clinical outcomes,” he summarized.
He then quoted his late wife Betsy Love McClung, RN, MN, who had said, “We don’t treat osteoporosis, we treat patients with osteoporosis.”
McClung wrapped up by stressing: “We should not treat T-scores or any other specific target. We should individualize our therapy based upon the patient’s risk of fracture and other clinical factors.”
As members of the ECTS and ASBMR, and “proud of our reputation of our societies as being scientifically based and driven,” McClung concluded, “recognizing that a treat-to-target strategy has appeal, we should certainly encourage more research and be attentive to those results.
“But we must hold off on the adoption of the strategy until we have evidence convincing us of its clinical value.”
When to Use a Treat-to-Target Strategy
However, “There are some specific situations where I use something like a treat-to-target strategy,” McClung conceded. “That is, I make decisions and recommendations to the patients about one drug rather than another because I want to maximize the improvement in their bone density.”
For example, “We have known for 15 years that denosumab results in greater increases in bone density than do bisphosphonates,” he continued.
“So, I have used that information to make treatment decisions long before the term ‘treat to target’ entered the vocabulary of osteoporosis experts. I simply wanted to induce the largest possible gains in bone density — but I didn’t have a ‘target’ in mind.”
But for most patients, treatment decisions are made based on other factors, such as their fracture risk, he added. BMD is an important risk factor for fracture, but not as important as having had a recent fracture or being old and frail.
“Unfortunately, in most of today’s health systems, decisions about treatment are made on the basis of cost,” he continued. “More often than not, the health plan rules rather than optimal medical practice are the main guides to treatment decisions.”
According to Gregson, “in some instances, treat to target would be very helpful. I don’t think it will suit everyone, but I think we should have it in our portfolio of management approaches, and we should as an osteoporosis community be trained in its use.”
“Attractive Idea, But…”
Invited to weigh in, Jan de Beur noted that A1c, blood pressure, and LDL cholesterol targets are used to improve clinical outcomes in patients with diabetes, hypertension, and hyperlipidemia, respectively.
However, “treat to target for the treatment of low BMD is controversial because it is an attractive idea but without consensus on what the target should be and without evidence that treat to target improves clinical outcomes,” she reiterated.
“The potential benefits of treat to target are proactive, clear goals to achieve, shared decision-making with the patient, the possibility for improved adherence, justification for sequence treatments, and balancing risk of rare side effects.”
On the other hand, “barriers to operationalizing the treat-to-target concept is that there is lack of consensus on the target to be achieved (as any specific target may minimize other important risk factors),” she noted.
There is also a “lack of evidence that demonstrates improved clinical outcomes over choosing therapy based on fracture risk, and lack of ability to achieve the target with available therapies in those with very low bone density,” she concluded.
McClung has reported receiving consulting fees from Amgen and Myovant and speaker honoraria from Amgen. Gregson and Jan de Beur have reported no relevant financial relationships.
ASBMR 2020 annual meeting. Presented September 12, 2020.