A Commentary on “Comparative Analysis of Romosozumab Versus Vertebroplasty With Denosumab: Efficacy, Safety, and Secondary Bone Mineral Density Outcomes”
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Osteoporotic vertebral compression fractures (OVCFs) are a major health concern among the elderly, leading to chronic pain, reduced mobility, and increased fracture risk. Traditionally, vertebroplasty has been the standard treatment, offering rapid pain relief and structural stabilization. However, its long-term efficacy has been questioned, with randomized controlled trials (RCTs) suggesting that it may not always be superior to placebo [1]. Concurrently, pharmacological advancements, particularly bone-forming agents like romosozumab, have introduced less invasive treatment options [2]. Recent studies have also compared romosozumab with other pharmacological treatments such as teriparatide, highlighting its efficacy in managing osteoporotic fractures [3].
This study [4] is significant as it directly compares romosozumab, which has both bone-forming and anti-resorptive properties, with vertebroplasty. Over 2 years, it assesses pain relief, bone mineral density (BMD) changes, radiological outcomes, and fracture risk. Given concerns about vertebroplasty’s overuse [5] and the lack of comparative data between pharmacological and surgical treatments, this research provides a timely perspective on treatment selection.
Key Findings
A notable outcome of this study is romosozumab’s long-term pain relief. While vertebroplasty provided better short-term pain reduction, its effect diminished over time. In contrast, romosozumab recipients had significantly lower Numerical Rating Scale (NRS) scores at 1 year (p= 0.015), indicating sustained pain relief. However, the impact of denosumab on pain relief in the vertebroplasty group remains an important consideration. These results challenge traditional pain management approaches in OVCF and suggest that pharmacological therapy may offer more durable relief.
Romosozumab also showed superior BMD improvement. Lumbar BMD increased by 28.8% in the romosozumab group versus 15.3% in the vertebroplasty group. Total hip BMD change also showed a trend toward greater improvement with romosozumab compared to vertebroplasty (p= 0.190). Additionally, the incidence of major osteoporotic fractures was significantly lower in the romosozumab group (7.1%) than in the vertebroplasty group (25.0%), underscoring its role in fracture prevention. A systematic review and meta-analysis further support the superior bone-forming effects of romosozumab compared to teriparatide in postmenopausal osteoporosis [6]. However, since the vertebroplasty group received denosumab, it is crucial to examine whether this contributed to the observed BMD improvements and fracture risk reduction.
Furthermore, a noninferiority analysis between patients aged 80 and older versus younger patients found no significant differences in BMD changes or NRS score improvements at 1 month and 1 year, a critical finding in an aging population.
Safety Considerations
Safety remains a key concern. The ARCH trial linked romosozumab to an increased risk of cardiovascular events [7]. However, this study found no significant difference in cardiovascular events between the romosozumab and vertebroplasty groups. The exclusion of patients with recent cardiovascular disease may explain this discrepancy, but long-term safety evaluations remain necessary. Further studies are needed to determine whether romosozumab inherently increases cardiovascular risk or if the association is limited to high-risk patients.
Considerations on Limitations
This study has several limitations. It is a small-scale, single-center study with 86 patients (42 in the romosozumab group, 44 in the vertebroplasty group), limiting its generalizability. Moreover, it focused on acute OVCF, leaving uncertainty about romosozumab’s efficacy in patients with severe vertebral collapse or high pseudarthrosis risk (e.g., high or extensive low signal intensity on T2-weighted imaging, intravertebral clefts, or extensive endplate destruction) [5,8].
Another limitation is the low treatment completion rate in the romosozumab group, where only 35.3% completed all 12 doses, while 64.7% discontinued treatment prematurely. The reasons—pain relief, high drug cost (often not covered by insurance), and other factors—could not be identified due to the study’s retrospective nature. Future research should analyze discontinuation factors and explore ways to improve adherence in clinical practice.
Additionally, this study did not assess known pseudarthrosis risk factors such as smoking and alcohol consumption, making it difficult to evaluate their contribution. Future research should consider these confounding factors.
Imaging limitations also exist, as the study relied solely on plain x-rays without dynamic evaluation, potentially underestimating intravertebral clefts and pseudarthrosis prevalence. Advanced imaging techniques should be incorporated in future studies to improve structural evaluations.
Furthermore, BMD follow-up beyond 24 months was limited, restricting assessments to 12 months. Extended follow-up studies are necessary to better evaluate romosozumab’s long-term effects on BMD and fracture prevention.
Lastly, while this study addresses medical costs and insurance coverage, further evaluation is needed. In South Korea, vertebroplasty plus one year of denosumab treatment costs approximately the same as 12 doses of romosozumab ($1,500–$2,500). However, medical expenses and insurance policies vary by region, requiring broader cost-effectiveness analyses.
Future Research Directions
Several key research areas emerge from these findings. First, large-scale, multicenter RCTs are needed to determine romosozumab’s efficacy compared to vertebroplasty across diverse patient populations. Comparative studies with other osteoporosis treatments, such as teriparatide and bisphosphonates, would also help identify optimal pharmacological strategies. A recent meta-analysis comparing anabolic agents with bisphosphonates suggests that anabolic treatments may be more effective in fracture prevention [9].
Combination therapy should be further explored. A treatment approach integrating vertebroplasty for immediate pain relief with romosozumab for long-term bone strengthening may offer a well-balanced strategy, although a cost-effectiveness analysis is necessary.
Finally, given romosozumab’s high cost, cost-effectiveness analyses and policy discussions regarding insurance coverage are essential to ensure broader accessibility.
Conclusion
This study highlights romosozumab’s advantages over vertebroplasty in terms of long-term pain relief, BMD improvement, and fracture risk reduction. These findings strongly support pharmacological therapy as a viable alternative to traditional surgical approaches for OVCF treatment. However, challenges remain, including low treatment adherence, small sample size, imaging limitations, and cardiovascular risk uncertainties. Further well-designed studies are needed to address these concerns. Additionally, although not examined in this study, from the perspective of immediate pain relief, the pharmacological treatment group with romosozumab is likely inferior to the surgical treatment group with vertebroplasty.
Despite these challenges, this study underscores the potential of noninvasive treatment options and could significantly impact future treatment decisions, especially for elderly and high-risk patients. If validated in larger trials, romosozumab may drive a paradigm shift in osteoporosis treatment, making this research particularly noteworthy.
Notes
Conflict of Interest
The author has nothing to disclose.