To the Bone: Experts Discuss Developments in Osteoporosis Care

SAN DIEGO—Ending treatment with denosumab, a RANKL-binding agent, is tricky and may result in losses of bone mineral density (BMD) gained by patients during treatment. The best strategy to optimize patient outcomes is still unclear. In a session on osteoporosis during ACR Convergence 2023, experts addressed efforts to find an optimal approach to ending treatment with denosumab, as well as the value of bone turnover markers and the need for a better way to assess vitamin D levels.

Denosumab

Dr. Langdahl

Bente Langdahl, MD, PhD, clinical professor at Aarhus University, Denmark, noted that good reasons to use denosumab exist, such as better results for BMD than with bisphosophonates and a lower of fracture risk. However, studies have shown that when denosumab is discontinued, a startling drop in BMD is typically seen in patients—but it’s not necessarily a drop to baseline levels. Also, the longer a patient is on denosumab, the worse this drop tends to be.¹

“We need to do something about it,” Dr. Langdahl said.

In one study, zolendronate was started either six or nine months after the last denosumab dose in patients who’d been treated with denosumab for a median of 4.6 years. The goal was to determine whether treatment after remodeling had begun and, therefore, later treatment may be better. Although patients had the same amount of BMD loss, with early treatment the loss happened at a slower pace. Because fast bone loss is associated with fracture risk, early treatment is still considered best, Dr. Langdahl said.²

Another study, which included 13 post-menopausal women, examined a gradual decrease in denosumab. The researchers found that BMD appeared to be satisfactory during the de-escalation. But after denosumab discontinuation, BMD loss was significant at the spine, but not at the hip. Over time, levels of C-telopeptide of type I collagen (CTX), the marker of bone resorption, increased.³

“I don’t know if this [approach] is the solution,” Dr. Langdahl said. “There would need to be longer follow-up.” But it could be an interim solution. “Maybe then you wouldn’t need to use as much bisphosphonates as we now need in most of our patients,” she added.

Dr. Langdahl emphasized—and it’s reflected in European guidelines—the need to aim for a higher target during denosumab treatment is the ultimate goal, with the expectation that BMD will be lost after treatment ends.⁴

Dr. Eastell