Denosumab after a decade of Tx: Subsequent strategies and BMD trajectories

Continuing denosumab beyond 10 years results in further increases in lumbar spine bone mineral density (BMD) and preserves femoral neck BMD, while switching to zoledronic acid leads to partial loss of previous gains and switching to romosozumab produces additional BMD gain at the lumbar spine, a cohort study in Hong Kong has shown.

Approved by the US FDA in 2010, denosumab may have been used by many patients with osteoporosis for ≥10 years. In the FREEDOM trial and its extension, denosumab demonstrated BMD gains for up to 10 years when given on schedule, but data supporting its efficacy beyond 10 years are limited. [Denosumab US Prescribing Information; N Engl J Med 2009;361:756-765; Lancet Diabetes Endocrinol 2017;5:513-523]

Hence, researchers from the University of Hong Kong and the Asia Pacific Consortium on Osteoporosis conducted a retrospective single-centre cohort study in 54 patients with osteoporosis who received ≥20 doses of denosumab Q6M (mean age, 72.9 years; female, 98.1 percent; history of fragility fracture, 70.4 percent) at the Osteoporosis Centre of Queen Mary Hospital between June 2012 and December 2024. [Endocr Pract 2026;doi:10.1016/j.eprac.2026.01.751]

“This cohort represented a population at high fracture risk, given the high prevalence of fragility fractures upon the initiation of denosumab. Indeed, most of the patients had been exposed to other anti-osteoporosis treatments,” noted the researchers.

The 20^th-dose BMD T-score was the major determinant of subsequent treatment. After 20 doses of denosumab, two patients (3.7 percent) with the lowest T-scores transitioned to romosozumab, four (7.4 percent) with the highest T-scores transitioned to zoledronic acid, and 48 (88.9 percent) continued denosumab.

Compared with year 10, continuing denosumab beyond 10 years led to further BMD gains at both the lumbar spine (+3.56 percent) and femoral neck (+0.61 percent).

“However, there was an unexpected small drop in total hip BMD [-5.52 percent] after the 10-year mark,” noted the researchers. “The reason for this was not entirely clear, but this plateauing in total hip BMD gain has previously been predicted in a computational model of BMD trajectory with 20 years of denosumab treatment.”

Switching to zoledronic acid after 10 years of denosumab therapy led to partial loss of the year-10 BMD gains at the lumbar spine (-6.75 percent), femoral neck (-4.24 percent), and total hip (-4.36 percent).

“Fixed zoledronic acid schedules after long-term denosumab may be insufficient to control rebound bone turnover and bone loss,” commented the researchers. “C-terminal telopeptide [CTX]–guided retreatment may be more appropriate.”

Transitioning to romosozumab after 10 years of denosumab led to further BMD gain at the lumbar spine only (+ 4.15 percent), but not the femoral neck (-4.36 percent) and total hip (-7.81 percent).

“The main reason for these two patients to transition to romosozumab was their persistently very low BMD T-score after 10 years of denosumab [-3.2 over femoral neck],” added the researchers. “Hence, this raised the question of whether concurrent osteoanabolic agent [either teriparatide or romosozumab] with continued denosumab would be the most appropriate action in case of persistently very low BMD T-score after 10 years of denosumab treatment.”

One of the study’s limitations was the small number of patients who switched to zoledronic acid (n=4) or romosozumab (n=2).