Previous Treatment of Osteoporosis May Affect the Efficacy of Romosozumab

Introduction

It is estimated that 9 million fractures due to osteoporosis occur annually worldwide. These fractures, especially of the femoral neck, significantly contribute to the increase in healthcare costs and mortality. One of the latest options in pharmacotherapy is the treatment with osteoanabolics from the group of sclerostin inhibitors.

Sclerostin is a glycoprotein secreted by osteocytes. It inhibits the canonical Wnt/β-catenin signaling pathway, which maintains bone mass by regulating the activity of osteoblasts and osteoclasts. Inhibition of sclerostin by an anti-sclerostin antibody therefore triggers a marked increase in bone formation and inhibition of bone resorption, which in patients results in a significant increase in bone mineral density (BMD) and a reduction in the risk of new fractures.

Recent studies have shown that previous pharmacotherapy of osteoporosis may influence the effect of the anti-sclerostin antibody romosozumab. However, it remained uncertain whether not only the type but also the duration of prior treatment has a significant effect. In everyday practice, many patients have already been treated with bisphosphonates or denosumab for many years. It was therefore necessary to clarify the optimal time to switch to romosozumab.

Methodology and Course of the Study

A total of 259 patients with osteoporosis who received subcutaneous injections of romosozumab (210 mg) every 4 weeks in 2019 and 2020 were included in the retrospective observational study. The observed parameters were percentage changes in BMD after 12 months of treatment with romosozumab.

For analysis purposes, patients were divided into 7 groups according to the type and duration of prior treatment before starting romosozumab as follows:

• group without prior treatment (n = 121)
• switch from teriparatide used ≤ 1 year (n = 26)
• switch from teriparatide used > 1 year (n = 21)
• switch from denosumab used ≤ 1 year (n = 24)
• switch from denosumab used > 1 year (n = 16)
• switch from oral bisphosphonates used ≤ 1 year (n = 18)
• switch from oral bisphosphonates used > 1 year (n = 33)

Results

For the group that had been previously treated with teriparatide, there was no significant impact on the efficacy of 12-month romosozumab therapy.

In contrast, prior treatment with denosumab or oral bisphosphonates for more than 1 year affected the therapeutic efficacy of romosozumab. The authors of the study used multiple linear regression analysis to eliminate the influence of other factors, such as the T-score value before starting romosozumab, and to thoroughly investigate the specific influence of the duration of prior treatment. The impact of previous denosumab or oral bisphosphonates administration on the efficacy of 12-month romosozumab therapy was associated with statistically significant differences depending on the duration of prior treatment, with usage longer than 1 year weakening the efficacy of romosozumab. This was reflected in differences in the percentage change in spinal BMD (in both groups p < 0.05), but no significant differences were observed in the case of the hip (in both groups p > 0.05).

When compared to the group without prior pharmacotherapy for osteoporosis, no statistically significant differences were found between this group and the groups where previous medications were used for less than 1 year. However, for prior treatment longer than 1 year, differences were found in all groups (for teriparatide only in bone markers, not in overall density).

Conclusion

The retrospective study showed that the duration of prior treatment just before starting romosozumab can have a significant impact on the therapeutic efficacy of this drug. The effect of romosozumab was not significantly influenced by previous treatment with the osteo-anabolic teriparatide. However, in the case of antiresorptive agents denosumab and oral bisphosphonates, significant differences in the efficacy of romosozumab were detected depending on the duration of prior treatment. Antiresorptive treatment longer than 1 year reduced the efficacy of romosozumab.

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Source: Tominaga A., Wada K., Okazaki K. et al. Effect of the duration of previous osteoporosis treatment on the effect of romosozumab treatment. Osteoporos Int 2022; 33 (6): 1265−1273, doi: 10.1007/s00198-021-06261-2.