Long-Term Denosumab Use Presents Vertebral Fracture Risk

Bisphosphonates are preferred alternative
vertebral fracture
Article

Patients with low bone mineral density (BMD) who stop denosumab after an extended treatment regimen are at risk of rebound-associated vertebral fractures (VF) that limit physical activity and may affect abdominal and pulmonary function.

Denosumab has been prescribed commonly for nearly a decade to improve bone density and reduce fracture risk, but recently there have been increased reports of BMD declining to pretreatment levels when the drug is stopped and may dip below baseline, putting the patients at risk for spontaneous VF.

Zoledronic acid, an intravenous bisphosphonate used to treat several bone diseases, is a preferred alternative that does not demonstrate the bone density reversal phenomenon seen following denosumab use. Bisphosphonates generally remain in the bone and provide prolonged benefits not offered by treatment with denosumab.

Endocrinologists specializing in metabolic bone disease often encounter patients with multiple concurrent fractures, says Rebecca Herbst, MD, a Duke endocrine fellow who has studied clinical approaches to osteoporosis. In some cases, spontaneous fractures occur when patients cough or bend to pick up an item. 

“We know that VF is a marker of high risk,” Herbst says. “Patients who experience VF are at much higher risk of hip and arm fractures.”

Specialists should focus on identifying and treating patients with low BMD, a history of fracture, or high fracture risk, Duke endocrinologists say, although the specialty is limited by a dearth of new drugs. 

Richard H. Lee, MD, MPH, a Duke endocrinologist and bone density specialist, says one of the challenges in treating osteoporotic disorders is the limited drug pipeline for the condition. “There are only a small number of new drugs in development,” Lee says, “and the currently available drugs are not being used much, even when they need to be. We are in a crisis in bone care now.”

Despite concerns about denosumab, the choice of a preferred alternative rests with the specialist, Duke endocrinologists say. No guidelines have been issued from the Endocrinology Society, but bisphosphonates improve BMD and reduce? fracture risk without the rebound-associated fracture risk, according to a recent study.

“During national conferences, we hear physicians’ personal strategies and ideas based on their experience with individual patients,” says Herbst, “but we don’t yet have a definitive recommendation.”