Should a prior fracture be a requirement for initiating osteoporosis treatment with an anabolic agent?
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Yes.
Many patients may benefit from anabolic therapies that stimulate bone formation. These may include patients who have not yet had low trauma fractures. Patients who present with very low bone density T-scores, such as below –3.5, are typically considered for an anabolic therapy, but there is flexibility in this. These patients are clearly at high risk because of their low T-scores, and with other risk factors, such as age and medical comorbidities contributing to this risk, it would be reasonable to treat them.
Other patients with medical conditions or other situations contraindicating antiresorptive therapies may be considered for anabolic therapy also. It has become apparent that many patients gain more bone density if they are given anabolic therapies first, followed by antiresorptive therapy. In those individuals who cannot take the antiresorptive therapies, such as oral bisphosphonates, IV bisphosphonates or denosumab (Prolia, Amgen), it is very reasonable to consider anabolic therapy.
Most patients who have T-scores above 2.5 would not be considered for anabolic or antiresorptive therapy, but in certain circumstances, these patients may be at high risk for fracture for other reasons, and certainly these patients might be considered.
We are talking mostly about patients who have never had therapy, although many patients that we see in practice will have had therapy of some type before we see them, which are most often bisphosphonates. In this setting, where bone density accrual did not meet expectation and T-scores after therapy are still in the osteoporotic range, argument can be made for giving these patients anabolic therapy as well to increase bone density further. When patients come without having had prior therapy, these patients will often respond more quickly and to a greater degree when given anabolic therapy if there is justification for doing this.
Decisions must be made between the patient and physician, but many factors go into these decisions, including side effects and cost that may be limiting for some patients.
Bart L. Clarke, MD, is professor in the department of endocrinology, diabetes, metabolism and nutrition at Mayo Clinic. He can be reached at clarke.bart@mayo.edu.
No.
There is suggestive evidence of bone mineral density and bone turnover marker changes that prior treatment with an antiresorptive/anticatabolic agent “blunts” the response to osteoanabolic drugs. It would be nice if there were data on fracture risk reduction for osteoanabolic after antiresorptive, but that is lacking. If one wishes to get the full benefit of an osteoanabolic agent, it should be initial therapy. Requiring a fracture for such use would deprive many high-risk patients from starting treatment with an osteoanabolic drug.
I am in favor of having a serious discussion about medication to reduce fracture risk in everyone whose risk of fracture is “high enough” that a reduction in risk would be of benefit. Exactly how to determine the risk and what level would trigger a discussion would be “guidance.” I am as reluctant to try to define “very high risk” as I would be to define a supreme being — any definition would be incomplete. However, an “official” definition of very high risk would almost certainly be used by payors to exclude any who did not check all the boxes — although some of those excluded would be at very high risk.
As for which drug to use, I’ve moved away from thinking of first-line treatment — this is not a homogeneous disorder — and prefer to think of the best initial therapy. Any of the available medications could be appropriate initial therapy under appropriate circumstances. For someone whose BMD is off the bottom of the scale on their first bone density test, starting with an osteoanabolic should be an option.
For some time now, there has been a discussion of treat to target. I am opposed to that for several reasons. First, I don’t believe there is a good target. Regarding T-scores, more than half of fractures due to osteoporosis occur in patients with T-scores above –2.5. Also, Fracture Risk Assessment Tool (FRAX) is not valid in patients on treatment. Whatever the target, there are many patients who would never reach it with our current treatments.
Instead of treat to target, I believe it is logical to consider “goal-directed” therapy. The main factor would be evidence for fracture risk reduction, but average BMD gains over time should also be considered — in addition to cost, route of administration, duration of treatment. For patients without fracture, whose BMD is 2 or more below the mean for age and sex, an osteoanabolic agent showing rapid gains in BMD should be among the choices for initial therapy.
Nelson B. Watts, MD, FACP, MACE, CCD, is director of osteoporosis and bone health services for Mercy Health. He can be reached at nelson.watts@hotmail.com.
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