Romosozumab outperforms teriparatide and denosumab in bone strength

A recent clinical study presented by Koji Ishikawa, MD, PhD, orthopedic spine surgeon at Duke University, and Tony M. Keaveny, PhD, Founder and Chief Science Officer of O.N. Diagnostics, compared the effects of romosozumab, teriparatide, and denosumab on bone strength in patients with osteoporosis.

The analysis focused on the hip and spine, where fracture risk is particularly great. Results showed that romosozumab provided substantially greater improvements in bone strength after 1 year of treatment compared to the other 2 drugs. At the spine, for example, romosozumab increased bone density by approximately 25% but boosted bone strength by about 40%, highlighting that strength gains are not fully reflected by bone density measurements from standard DXA scans.

The findings are significant because fracture prevention depends more on improved breaking strength than on density alone. Data from real-world clinical care also suggest even greater percentage gains than those seen in earlier phase-2 and phase-3 trials.

Notably, romosozumab demonstrated the unique ability to transform highly osteoporotic vertebrae into bones at much lower risk of biomechanical failure, as shown through virtual stress testing models. According to the researchers, romosozumab stands out as the most effective treatment for strengthening both hip and spine bones, offering a compelling advantage over teriparatide and denosumab.

Below, Keaveny shares further details on their presentation ”(SUN-416) Greater increase in bone strength with romosozumab vs teriparatide or denosumab in women with postmenopausal osteoporosis in real-world clinical setting and Ishikawa provides an overview of the presentation “(SUN-564) Greater increases in bone strength estimates of virtual bone-implant constructs for spinal surgery with romosozumab vs teriparatide or denosumab in women with postmenopausal osteoporosis”. 

Contemporary OB/GYN:

Please provide an overview of your presentation about bone strength from romosozumab vs teriparatide or denosumab.

Tony M. Keaveny, PhD:

This study compared the breaking strength of the hip and spine bones for different osteoporosis drug treatments and showed that the strength benefits after 1 year of treatment were substantially greater for romosozumab compared to both teriparatide and denosumab.

Koji Ishikawa, MD, PhD:

Spinal instrumentation remains challenging in patients with bone fragility. The concept behind this project is to provide additional support for achieving favorable surgical outcomes, beyond surgical techniques. Based on simulation-based biomechanical analysis, we found that romosozumab offered multiple advantages over denosumab and teriparatide in terms of biomechanical parameters relevant to spinal surgery.

Contemporary OB/GYN:

What is the significance of these findings?

Keaveny:

Changes in bone density as measured by clinical-standard DXA testing are difficult to interpret because what matters most in terms of fracture reduction is how much the breaking strength changes. This study is significant because it demonstrates the substantial benefits for breaking strength – more than for bone density. For example, at the spine, romosozumab increased bone density by about 25% but bone strength by about 40%. So, the benefits of the treatment are underestimated when measured by bone density. And of course, those benefits were greater for romosozumab than either of the other 2 treatments.

Ishikawa:

Evaluating mechanical parameters such as screw fixation strength or bone-breaking force in clinical practice for assessing drugs effects is impractical and often difficult with traditional biomechanical methods. To address this, we developed a simulation approach using patient CT data. Our findings provide a new perspective on their effectiveness in the context of implant surgery.

Contemporary OB/GYN:

What were the main takeaways of your presentation?

Keaveny:

As we have seen in other clinical trials, romosozumab is the better treatment in terms of its bone-strengthening benefits, both at the hip and spine. Here we have data from actual clinical care.

Ishikawa:

After 1 year of treatment, romosozumab showed greater improvements than denosumab and teriparatide in surgical instrumentation-related biomechanical analyses.

Contemporary OB/GYN:

What other research about the impact of romosozumab on bone strength would you like to highlight?

Keaveny:

These results suggest even greater gains, percentage-wise at least, for these highly osteoporotic and treatment-naïve patients from clinical care than what we observed in a prior phase-2 BCT study in women with low bone mass (Keaveny JBMR 2017) and also in a phase-3 imaging substudy of osteoporotic women with prior bisphosphonate therapy (Langdahl Lancet 2017).

Ishikawa:

In a previous study, we were the first to demonstrate the potential benefits of short-term romosozumab treatment (3 months) in reducing postoperative complications after spinal surgery (Ishikawa K, JOR Spine 2024). Taken together with the present findings, our research further supports the role of romosozumab for surgical support.

Contemporary OB/GYN:

Is there anything you would like to add?

Keaveny:

These results are particularly compelling at the spine for romosozumab because the drug benefit is so large — it takes a highly osteoporotic bone and transforms it into one at much lower risk of biomechanical failure. This is seen visually with the virtual stress testing. Here, virtual forces are placed on the bone that would normally fracture and crush an osteoporotic bone. After treatment with romosozumab, that same level of force produces almost no damage in the bone. Romosozumab appears to be the only drug treatment that can transform the osteoporotic vertebra in this way.

Ishikawa:

Even the best surgeons face complications when patients have osteoporosis. Yet perioperative bone health care is often overlooked. Our studies underscore the importance of assessing and managing bone health in perioperative settings to improve surgical outcomes.