CHICAGO — Postmenopausal women at high fracture risk achieved bone density benefits with just 3 months of romosozumab followed by 9 months of denosumab that were noninferior to those seen with the standard 12-month romosozumab regimen, according to new research. Some measures were even improved with the shorter treatment approach.

“To our knowledge, this is the first randomized controlled clinical trial assessing the efficacy of a shorter romosozumab course in any population,” the authors recently reported in the study, published in The Lancet Diabetes & Endocrinology.

The findings suggest that the abbreviated regimen “provides similar 12-month skeletal benefits compared to standard therapy while reducing treatment burden, cost, and potentially cardiovascular risk,” said first author Benjamin Leder, MD, professor of medicine at Harvard Medical School and the Endocrine Division at Massachusetts General Brigham in Boston, during a presentation at ENDO 2026: The Endocrine Society Annual Meeting.

Benefits and Limitations of Romosozumab

Romosozumab, a monoclonal antibody and sclerostin inhibitor, is unique among osteoporosis drugs because it both stimulates bone formation and simultaneously inhibits bone resorption.

However, while its antiresorptive effects persist, its anabolic effects are transient. Bone formation markers rise rapidly after treatment initiation but generally revert to baseline within 2-3 months, Leder explained.

Furthermore, adherence to romosozumab is often hindered by the drug’s high cost, the burden of monthly office visits for injections, and concerns about potential cardiovascular risk that prompted a black box warning from the FDA.

As a result, more than half of the US patients discontinue treatment before completing the recommended course, the authors noted.

Given these challenges, Leder and colleagues hypothesized that a shorter course might preserve efficacy while improving affordability, adherence, and safety.

Noninferior Bone Density Gains at 1 Year

For the Limited Duration Anabolic Therapy (LIDA) noninferiority trial, investigators randomized 50 postmenopausal women (mean age, 69.6 years) to either 12 months of romosozumab or 3 months of romosozumab followed by 9 months of denosumab, all at FDA-approved doses.

All participants were at a high fracture risk, defined as having either prior fragility fracture or a T-score of -2.5 or less at the total hip, femoral neck, or lumbar spine. The groups were well balanced for baseline clinical characteristics.

For the primary endpoint, the mean total hip areal bone mineral density (aBMD) increased by 5.7% at 1 year in the 3-month romosozumab group and by 6.0% in the 12-month group, meeting the prespecified noninferiority margin of 2%.

For secondary endpoints, there were no significant differences between the two treatment groups in terms of changes in aBMD at other sites, including femoral neck (5.0% vs 6.3%), lumbar spine (10.6% vs 12.5%), and distal radius (-0.3% vs -1.5 %; all between-group comparisons were not significant).

Both regimens also produced similar gains in cortical and trabecular volumetric bone mineral density (BMD), estimated bone strength, and measures of cortical and trabecular microarchitecture.

Could Less Treatment Be Better?

One finding particularly surprised the investigators. Mean increases in total volumetric BMD were significantly greater in the 3-month romosozumab group than in the 12-month group at both the tibia (2.4% vs 1.4%; P = .007) and radius (1.9% vs 0.4%; P = .008).

“Many of us have always wondered how the 12-month regimen was chosen in the first place, because if you look at phase 2 data, it really points to the anabolic importance of the drug being transient,” he said. “Obviously, one regimen had to be selected to move forward because that’s how these studies work, and 12 months was indeed effective.”

He noted that when the study was conducted, no high-resolution peripheral quantitative CT outcomes were available with romosozumab. However, the biologic rationale for the findings is plausible given denosumab’s known benefits on measures such as distal radius DEXA and ultra-distal radius BMD.

“The findings support the consideration of the LIDA regimen within the shared decision-making framework for patients at high fracture risk,” Leder said.

He added that the strategy may be particularly attractive for patients who are reluctant to start romosozumab because of cardiovascular concerns.

“It’s my sense that even a short course of romosozumab — I don’t know how short, but a much shorter course than is currently recommended — could provide additional benefits to specifically those patients.”

Expert Perspectives

During the session, moderator Heide Siggelkow, MD, associate professor of endocrinology at the Clinic of Gastroenterology, Gastrointestinal Oncology and Endocrinology at the University Medical of Göttingen in Göttingen, Germany, noted that the findings address a topic of considerable clinical interest.

“This is a very important issue because many of our patients are pretreated,” she said.

Leder responded that pretreatment did not appear to influence outcomes. However, he noted the study was not sufficiently powered to rigorously assess that question. He added that the trial is being extended for another year and that those results should be “highly interesting.”

Further commenting on the research to Medscape Medical News, Siggelkow said, “The finding — independent of industry involvement — that giving romosozumab for only 3 months not only has similar benefits vs 12 months but is even better [in some parameters] is very exciting.”

She continued, “Imagine if you just treat with romosozumab for 3 months and then are able to continue with either denosumab or IV [intravenous] bisphosphonates. It could be much easier. You give those once every 6 months or just once a year, so it could be a big benefit.”

The study’s major limitation was its small size, which precluded assessment of fracture outcomes. However, Siggelkow noted that “without industry funding, there are going to be challenges in terms of looking at outcomes in thousands of patients.”

Nevertheless, “this is very important information,” she said.

Leder reported serving as a consultant to Amgen. Siggelkow has participated in advisory boards for MSD, Lilly, Amgen, Servier, Takeda, UCB, and Kyowa Kirin; received speaker fees from MSD, Lilly, Amgen, GSK, Servier, Takeda, Alexion, Kyowa Kirin, UCB, Sandoz, and Sanofi Aventis; and reported receiving research support from Takeda.