Denosumab Superior to Ibandronate at Increasing Bone Mineral Density in Osteoporosis

Researchers evaluated the effects of ibandronate and denosumab on bone mineral density following romosozumab therapy in women with postmenopausal osteoporosis.

Following treatment with romosozumab, denosumab was shown to be more effective than ibandronate at enhancing bone mineral density (BMD) in women with postmenopausal osteoporosis, according to study findings published in Bone.

Researchers sought to compare the effects of denosumab and ibandronate on BMD following romosozumab therapy. They conducted a randomized controlled trial that comprised 124 women with postmenopausal osteoporosis at severe risk for fracture. All participants were treated with 12 months of romosozumab and were randomly assigned to receive either ibandronate (n=62; mean age 74.9±8.2 years) or denosumab (n=62; mean age 74.3±9.3 years) for an additional 12 months.

The primary outcome was 6- to 12-month percent changes in BMD at the lumbar spine, femoral neck, and total hip after starting sequential therapy. Secondary outcomes included adverse events and alterations in markers for serum bone turnover, including procollagen type 1 N-terminal propeptide 1 (P1NP) and tartrate-resistant acid phosphatase isoform 5b (TRACP-5b). The Wilcoxon signed-rank test was used to evaluate percentage changes from baseline to each study time point.

The ibandronate group experienced a 2.5±0.8% increase in BMD at the lumbar spine at 12 months of sequential therapy, compared with 5.4±0.8% in the denosumab group (P <.01 between groups), with denosumab showing superior ability to increase BMD in this region. Changes in BMD at the total hip were 2.5±0.8% (ibandronate) and 4.0±0.9% (denosumab). Changes in BMD at the femoral neck were 2.7±0.8% and 3.1±0.8%, respectively, with no statistically significant differences between groups. During 12 months of sequential treatment, both P1NP and TRACP-5b decreased significantly (ibandronate group: -64.9% and -26.8%, respectively; denosumab group: -67.4% and -36.3%, respectively; P <.001 vs baseline of sequential therapy). All adverse events were minor, and none impacted continuation of the trial.

Limitations of the study included small subgroup numbers, a lack of examination into the use of active vitamin D analog in combined therapy, a lack of blinding to antiresorptive treatment, a lack of a placebo group, and a limited sample size.

The study authors concluded that “[I]bandronate and denosumab were effective antiresorptive agents for use in sequential therapy for one-step forward treatment after romosozumab to increase BMD with a low risk [for] major adverse events.” Additionally, they indicated there was a potentially “superior effect of denosumab to increase and maintain BMD, especially in patients with a treatment-naive status prior to romosozumab [therapy].”


Kobayakawa T, Miyazaki A, Takahashi J, Nakamura Y. Verification of efficacy and safety of ibandronate or denosumab for postmenopausal osteoporosis after 12-month treatment with romosozumab as sequential therapy: The prospective VICTOR study. Bone. Published online July 1, 2022. doi:10.1016/j.bone.2022.116480