SEATTLE — Treatment with romosozumab improved lumbar spine, total hip, and femoral neck bone mineral density (BMD) in women with premenopausal idiopathic osteoporosis (IOP), according to new results from a phase 2 clinical trial. The researchers compared the gains to a historic sample treated with the recombinant human parathyroid hormone fragment teriparatide and found larger increase in lumbar spine BMD with romosozumab.

It is the first clinical trial of the drug in premenopausal IOP, which is defined as osteoporosis occurring in otherwise healthy young women who have normal gonadal function and menstruation cycles, and no known medical conditions or medical exposures that increase the risk for osteoporosis or cause bone loss.

Teriparatide has been used off label to treat premenopausal IOP, but it has a variable response rate along with other clinical issues, according to co-author Adi Cohen, MD, professor of medicine at Columbia University, New York City. “Optimizing treatment for these women was a goal,” she said in an interview.

Asked for a comment, Michael R. McClung, MD, said the results were not surprising. “Many of us have hypothesized that an active bone-forming agent like romosozumab would be helpful [for the condition].” McClung is the founding director of the Oregon Osteoporosis Center in Portland, Oregon, and moderated the session at the American Society for Bone and Mineral Research (ASBMR) 2025 Annual Meeting, where the research was presented.

One study of teriparatide 20 mcg daily for 24 months in 41 women showed increases in BMD at the lumbar spine (+13%), total hip (+5%), and femoral neck (+5%), and a decline at the distal radius (-2%). The nonresponse rate was 18%.

Romosozumab increases BMD in postmenopausal women with a nonresponse rate of just 1%, and there have been various case reports of efficacy in IOP, according to Lauren Lynch, MD, PhD, endocrinology fellow at Columbia University, New York City, who presented the study. However, there have been no previous randomized controlled trials or prospective studies in this population, added Lynch.

The group conducted a phase 2 study, enrolling 29 women aged 18-48 years with regular menses and no known secondary causes of osteoporosis, who had experienced low-trauma adult fractures and had T-score or Z-score ≤ -1.5 at lumbar spine, total hip, or femoral neck. They had to be treatment naive, or if they had received limited treatment, then had to go through a washout period.

The participants all received romosozumab 210 mg monthly for 12 months, followed by denosumab 60 mg every 6 months for 12 months.

At 12 months, romosozumab was associated with a 15% increase in BMD in the lumbar spine (P < .001), and a 5% increase in total hip and femoral neck (P < .005 for both). There was no change in the distal one-third radius. Romosozumab was also associated with gain in trabecular bone score at 12 months (+3%; P < .001).

The researchers compared the participants to a historic population treated with teriparatide drawn from the 41-patient trial, applying the same entry criteria in an effort to minimize differences between the study populations. Among 27 romosozumab patients, there was a greater improvement at 12 months in lumbar spine and distal radius BMD than in 31 women in the teriparatide study (P < .05 for both). A comparison of BMD between 12 months of romosozumab and 24 months of teriparatide showed only a between-group difference in distal radius, with no change in romosozumab and a slight decline with teriparatide (P < .001).

There were no new clinical fractures or vertebral fractures in the romosozumab-treated population.

The researchers also looked at a subgroup of 17 patients who had experienced low trauma or spontaneous fractures late in pregnancy or while lactating (PLO). These patients often have multiple vertebral fractures and very low BMD values. A previous cross-sectional study suggested substantial structural deficits and low bone remodeling rates, and 30% had known genetic causal mutations. In the current trial, PLO status did not significantly affect response to romosozumab.

During the Q&A period after the presentation, one audience member asked if the group had looked at genetic variants within the patient population. “We do plan to look at whether treatment response might differ depending on different genetic etiology,” said Cohen, the study’s primary investigator.

A key question will be how to manage patients after the first year of therapy, according to McClung. “In postmenopausal women, we have to follow treatment with an anti-remodeling drug to maintain the benefit. These [premenopausal] women have their own estrogen, which is a very effective anti-remodeling drug, and perhaps, after romosozumab and the large increase in bone density, that could simply be maintained by the person’s own estrogen. Some other follow-on studies will answer that question,” he said.

The study was funded by Amgen. McClung served as a consultant for Amgen. Cohen and another co-author reported receiving research support from Amgen. Lynch reported having no financial disclosures or conflicts of interest.

Jim Kling is a writer based in Bellingham, Washington.