Romosozumab vs. Teriparatide in Sequential Treatment of Osteoporosis in Women with a History of Fracture

Antiresorptive and Osteoanabolic Treatment

Bisphosphonates have been the first-line treatment for osteoporosis over the past few decades. These antiresorptive drugs primarily prevent further deterioration of bone architecture. In patients with an inadequate response to therapy (persistent low bone mineral density /BMD/ or fractures occurring during treatment), a transition to osteoanabolic therapy is usually indicated.

Osteoanabolics can induce a significant increase in BMD in a relatively short timeframe. Recently, a new molecule has been registered in this drug category — romosozumab. It is a monoclonal antibody that inhibits the functions of sclerostin, thereby stimulating bone formation and simultaneously inhibiting bone resorption by affecting the expression of osteoclast mediators. The dual effect of romosozumab leads to faster and more significant BMD increases compared to bisphosphonates or parathyroid hormone analogs like teriparatide.

However, data from previous clinical studies indicated that patients previously treated with bisphosphonates might achieve lower clinical benefits from subsequent osteoanabolic therapy compared to untreated patients. The STRUCTURE clinical study examined whether this statement holds true for romosozumab.

Methodology and Study Progress

The multicenter, randomized, open-label phase III study presented results from 46 centers in America and Europe. Inclusion criteria included a diagnosis of postmenopausal osteoporosis and previous oral bisphosphonate treatment in the past 3 years, with alendronate taken for 1 year before study entry. The BMD T-score had to be ≤ –2.5 in the total hip, femoral neck, or lumbar spine, and patients had to have a history of fracture.

Patients (n = 436) aged 55–90 years were randomized in a 1:1 ratio to receive romosozumab subcutaneously (210 mg once monthly; n = 218) or teriparatide subcutaneously (20 µg once daily; n = 218). The primary endpoint was the percentage change in total hip BMD measured by dual-energy X-ray absorptiometry (DXA) over the 12-month treatment period.

Results

Efficacy

Over 12 months, the average change in total hip BMD in the romosozumab group was 2.6% (95% confidence interval [CI] 2.2–3.0), compared to –0.6% (95% CI –1.0 to –0.2) in the teriparatide group. The difference between the two groups was 3.2% (95% CI 2.7–3.8; p < 0.0001).

Safety

The incidence of adverse events was similar in both treatment groups. The most commonly reported were nasopharyngitis (13% in the romosozumab group vs. 10% in the teriparatide group), hypercalcemia (< 1% vs. 10%), and arthralgia (10% vs. 6%). Serious adverse events were reported in 8% of patients on romosozumab and 11% on teriparatide, but none were deemed related to the treatment. Adverse events led to discontinuation of therapy in 3% of patients on romosozumab and 6% on teriparatide.

Conclusion

Transitioning from bisphosphonate therapy to osteoanabolics is common practice for high-risk patients. The STRUCTURE study showed that switching to romosozumab in these patients increased hip BMD, unlike the group using teriparatide. It was thus demonstrated that prior bisphosphonate therapy indeed weakens the osteoanabolic effect of teriparatide, but likely has no significant impact on the effect of romosozumab.

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Sources:
1. Langdahl B. L., Libanati C., Crittenden D. B. et al. Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomized, open-label, phase 3 trial. Lancet 2017; 390 (10102): 1585–1594, doi: 10.1016/S0140-6736(17)31613-6. 
2. Lim S. Y., Bolster M. B. Clinical utility of romosozumab in the management of osteoporosis: focus on patient selection and perspectives. Int J Womens Health 2022; 14: 1733–1747, doi: 10.2147/IJWH.S315184.
3. SPC Evenity. Accessible at: www.ema.europa.eu/en/documents/product-information/evenity-epar-product-information_cs.pdf