Understanding when to switch from one class of drugs to another is critical to maintaining bone health and preventing fractures in osteoporosis, according to data presented at the Congress of Clinical Rheumatology East.

“It is quite clear that the sequence in which drugs are given has important clinical consequences,” Michael R. McClung, MD, of Australian Catholic University, said in his presentation.

Describing several drugs and drug classes in the osteoporosis armamentarium, McClung first discussed the anti-remodeling agent group, which he noted inhibit bone turnover. Among this class, the first therapy is estrogen, which is approved for osteoporosis prevention only, he said. Estrogen agonists or antagonists such as raloxifene are included in this category, as are oral or intravenous bisphosphonates and the RANK ligand inhibitor denosumab.

Meanwhile, osteoanabolic agents activate bone formation. In this group are remodeling stimulators that increase formation and resorption, along with parathyroid hormone receptor activators such as teriparatide and abaloparatide (Tymlos, Radius). There are also modeling stimulators that increase formation and decrease bone resorption, including the sclerostin inhibitor romosozumab (Evenity, Amgen).

Most patients will cycle through several of these drugs and drug classes in their journey with osteoporosis, according to McClung. Each drug and class either cannot be taken indefinitely, loses efficacy after some time, or should be discontinued for other reasons.

For example, anti-resorptive agents cannot be given indefinitely.

“These drugs cannot and do not restore the architectural disruption that characterizes osteoporosis,” McClung said.

However, indefinite discontinuation is similarly not recommended.

“The skeletal benefits of all osteoporosis therapies wane upon discontinuation of treatment,” he said.

Although it would be impossible to review every potential sequence and combination of therapies in an hour-long presentation — “One can imagine a whole variety of sequences,” he said — McClung offered a few cases that demonstrate some of the choices a clinician might need to make.

In the first case, the patient was intolerant to an oral bisphosphonate. The next choice of an intravenous bisphosphonate, denosumab or osteoanabolic agent depends on determinants such as current bone mineral density and fracture risk, other medical issues, patient preference and cost, McClung said.

In the next patient, a switch from an anti-remodeling drug was required.

“The reasons to switch from an anti-remodeling drug to an osteoanabolic agent are inadequate response to an anti-remodeling agent or a marked increase in the patient’s fracture risk,” McClung said.

In treatment-naïve patients, bone mineral density and fracture protection are better with an anabolic drug compared with a bisphosphonate, he added.

In the next case, bisphosphonate therapy was discontinued after 5 years in a so-called “drug holiday,” McClung said.

“Nobody should take a bisphosphonate for more than 5 years at a time,” he said. “But that does not mean you can’t come back and do 5 years at a later time.”

Switching to either denosumab or an anabolic agent is recommended in this instance; the choice being driven by the patient’s current risk of fracture.

According to McClung, one reason these decisions can be so difficult is that “these transition studies don’t have data on the effect of this fracture risk.”

Meanwhile, for patients who discontinue estrogen therapy or denosumab, McClung recommended either zoledronate or alendronate.

“The role of anabolic agents after denosumab is less appealing,” he said.

As a closing point, McClung offered one final pearl for rheumatologists managing osteoporosis over the long term.

“The final drug of any sequence will likely be zoledronate,” he said.

“Osteoporosis requires life-long management,” he concluded. “Optimal management must be individualized but will involve sequential use of different classes of osteoporosis drugs.”