Shortened romosozumab course proves beneficial in postmenopausal osteoporosis

Three months of romosozumab followed by 9 months of denosumab works just as well as 12 months of romosozumab for increasing bone mass in postmenopausal women at high risk of fracture, as shown in an open-label, noninferiority trial.

From baseline to month 12, total hip bone mineral density (BMD) increased by 5.7 percent in the 3-month romosozumab group and by 6 percent in the 12-month romosozumab group (p=0.644). This small between-group difference met the prespecified noninferiority criteria, reported first author Prof Benjamin Leder from Harvard Medical School in Boston, Massachusetts, US. [Lancet Diabetes Endocrinol 2026;doi:10.1016/S2213-8587(25)00319-5]

Similarly, the 12-month BMD changes at other sites did not significantly differ between the 3-month and 12-month romosozumab groups: 5 percent vs 6.3 percent for femoral neck (p=0.29), 10.6 percent vs 12.5 percent for lumbar spine (p=0.184), and –0.3 percent vs –1.5 percent for distal radius (p=0.079).

The bone formation marker P1NP equally increased in both groups during the initial 3 months, when all participants were receiving romosozumab (p=0.0001). At month 6, participants receiving denosumab exhibited greater suppression of both P1NP (p<0.0001) and the bone resorption marker CTX (p=0.0009), and this was maintained through month 12.

In terms of safety, adverse events (AEs) occurred in 88 percent of participants in the 3-month romosozumab group and in 81 percent in the 12-month romosozumab group. The most common AEs were back pain, cough, fatigue, headache, joint pain, muscle cramps, and muscle pain.

Serious AEs occurred in three participants in the 12-month romosozumab group, and all were deemed unrelated to the study treatment. Three participants in the 3-month romosozumab group and one in the 12-month romosozumab group sustained nonvertebral fractures during the study. There were no incidents of deaths, myocardial infarction, stroke, unstable angina, osteonecrosis of the jaw, or atypical femoral fracture.

“Romosozumab is a unique osteoporosis therapy with both anabolic and antiresorptive effects and represents an important treatment option for postmenopausal osteoporosis, particularly in patients with established or severe disease,” Leder said. “However, the drug’s use is limited by high cost, payer restrictions, the need for monthly clinic-administered injections, and a possible association with increased cardiovascular risk.”

Leder emphasized that the abbreviated romosozumab strategy has the potential to improve access to the drug “by reducing insurance restrictions, increasing patient adherence, and enhancing safety perceptions.”

In an accompanying editorial, Dr Sundeep Khosla from the Mayo Clinic College of Medicine in Rochester, Minnesota, US, congratulated Leder and colleagues for developing a new therapeutic approach with considerable benefits for patients. [Lancet Diabetes Endocrinol 2026;doi:10.1016/S2213-8587(25)00323-7]

“Note that it is now widely appreciated that following treatment with a drug that stimulates bone formation, an antiresorptive drug is essential to maintain the increases in bone mass. In the absence of the antiresorptive, the skeleton somehow senses an inappropriately high bone mass and rapidly sheds the perceived excess bone back to levels present before treatment with the bone anabolic agent,” Khosla pointed out.

He echoed Leder, saying that 3-month romosozumab course is “much less expensive,” “more convenient in terms of reducing the number of monthly injections,” and mitigates some of the concerns about the potential adverse cardiovascular effects of romosozumab.

The open-label, noninferiority trial included 50 postmenopausal women (mean age 69.6 years) at high risk of fracture, defined as either previous history of fragility fracture or a BMD T score of –2.5 or less at the total hip, femoral neck, or lumbar spine.

The participants were randomly assigned to receive 3 months of romosozumab 210 mg (administered subcutaneously once a month), followed by 9 months of denosumab 60 mg (administered subcutaneously every 6 months) (n=24) or 12 months of romosozumab (n=26). The primary endpoint was the percentage change in total hip BMD.