Study Overview and Journal Context
The study, published in JBMR Plus (2026), examines the effectiveness of repeated romosozumab treatment combined with short-term ibandronate sequencing for high-risk osteoporosis patients. Conducted as a retrospective single-center cohort study, it analyzed data from 68 patients who initiated treatment between April 2020 and April 2026. Of these, 49 completed the 5-year follow-up, forming the analytical cohort. The research was supported by open-access licensing (CC BY) and is available via Europe PMC. The study focuses on skeletal outcomes, including bone mineral density (BMD) measures, bone turnover markers, and pain scores, while noting limitations such as its uncontrolled design and incomplete data. The authors emphasize that findings are descriptive and hypothesis-generating rather than definitive, given the lack of a comparator group and missing baseline data for 19 patients who discontinued treatment.
Study Methods and Patient Characteristics
The study included 68 patients with high-risk osteoporosis, 48 of whom were women, with a mean age of 84.8 years. Participants received romosozumab for 12 months, followed by oral ibandronate 100 mg monthly for 3 months, then reassessment for additional courses. All patients also took eldecalcitol 0.75 μg daily. The primary outcomes measured were lumbar spine and femoral neck young adult mean (YAM) values, bone turnover markers, numerical rating scale (NRS) pain scores, treatment persistence, fractures, and safety events. The analytical cohort of 49 patients had complete follow-up data, while 19 patients who discontinued were excluded from longitudinal analyses. The study used linear mixed-effects models to evaluate longitudinal outcomes, accounting for within-patient correlations. However, the retrospective design limited the ability to control for confounding factors such as concurrent analgesic use, rehabilitation, or natural healing processes.
Key Findings and Skeletal Outcomes
The study reported significant improvements in skeletal measures over 5 years. Lumbar spine YAM increased from 73.3% at baseline to 92.9% at year 5, with a model-estimated change of 19.6 percentage points (95% CI, 17.9–21.3; p < .001). Femoral YAM rose from 66.2% to 76.1%, a change of 9.9 percentage points (95% CI, 9.2–10.5; p < .001). Bone turnover markers also showed longitudinal changes: median bone-specific alkaline phosphatase (BAP) increased from 7.9 μg/L to 17.2 μg/L, while median TRACP-5b decreased from 411 mU/dL to 160 mU/dL. Pain scores, measured by the numerical rating scale (NRS), declined from 8.9 to 1.4 (estimated change −7.5; 95% CI, −7.9 to −7.1; p < .001). However, the authors caution that pain reduction could not be solely attributed to the treatment due to potential confounding factors. No major safety events, including cardiovascular issues, hypocalcemia, or atypical femoral fractures, were recorded. One recurrent vertebral fracture occurred, but no other fractures were reported.
Limitations and Interpretation
The study’s limitations include its retrospective, uncontrolled design and the exclusion of 19 patients who discontinued treatment, which may introduce selection bias. The authors note that baseline data for these 19 individuals were unavailable, limiting the ability to assess outcomes comprehensively. Additionally, the lack of a comparator group prevents definitive conclusions about the treatment’s efficacy relative to alternative therapies. The study also faced challenges with incomplete dual-energy X-ray absorptiometry (DXA) metadata, which affected the accuracy of BMD calculations. The authors emphasize that the observed increases in YAM may have been influenced by factors such as degenerative changes or vertebral deformities, which were not fully accounted for in the analysis. Furthermore, the association between treatment and pain reduction remains uncertain due to potential confounding variables like analgesic use and natural healing. The findings are described as descriptive and hypothesis-generating, requiring validation through prospective, controlled studies.
Implications for Osteoporosis Management
The study suggests that repeated romosozumab courses, combined with short-term ibandronate sequencing, may lead to sustained improvements in bone density and turnover markers over 5 years. However, the authors stress that these results should not be interpreted as proof of efficacy or safety without further research. The protocol used in the study aligns with Japanese reimbursement guidelines for romosozumab re-administration, which require documentation of high fracture risk and prior osteoporosis medication use. This highlights the importance of structured treatment protocols in clinical practice. The findings also underscore the need for standardized outcome measures, such as YAM, to evaluate skeletal health. While the study provides insights into long-term treatment patterns, its limitations necessitate caution in applying the results to broader patient populations. Future research should address the study’s gaps, including the role of confounding factors and the long-term safety of sequential bisphosphonate and sclerostin inhibitor therapies.