Romosozumab one-ups denosumab in boosting bone mineral density for chronic steroid users

In the treatment of chronic glucocorticoid users with high fracture risk, romosozumab yields higher gains in spine bone mineral density (BMD) compared with denosumab, as shown in a pilot trial presented at EULAR 2023.

At month 12, the primary endpoint of BMD at the lumbar spine increased by 7.3 percent among patients on romosozumab and by 2.3 percent among those on denosumab. These improvements were meaningful in both treatment groups relative to baseline (p<0.001), but the magnitude of increase was significantly greater with romosozumab than with denosumab (p<0.001). [EULAR 2023, abstract OP0246]

These data suggest that romosozumab may provide a new treatment option for glucocorticoid-induced osteoporosis in high-risk patients, according to lead study investigator Dr Chi Chiu Mok of Tuen Mun Hospital in Hong Kong.

Study details

For the study, Mok and colleagues recruited 70 adult patients who were receiving daily prednisolone dose of ≥5 mg/day for at least 12 months. These patients had moderate-to-high risk of osteoporotic fracture (defined as a history of fragility fracture, DEXA T score ≤–2.5 [age ≥40 years] or Z scores ≤–3.0 [age <40 years] or high risk of 10-year major fracture estimated by FRAX).

The patients were randomly assigned to receive either romosozumab 210 mg subcutaneously every month (n=35) or denosumab 60 mg subcutaneously every 6 months (n=35) for 12 months, after which both groups received denosumab 60 mg every 6 months for 12 more months. All patients were given daily calcium and vitamin D, and existing bisphosphonates were discontinued.

Of the patients recruited, 63 (90 percent; mean age 62.6 years, 96 percent women) completed the study. The most common underlying medical disease was systemic lupus erythematosus (51 percent), followed by rheumatoid arthritis (29 percent), inflammatory myopathies (9 percent), and others.

Overall, the patients were taking a mean prednisolone dose of 6.6 mg/day at baseline. Thirty-four (48.6 percent) patients had osteoporosis at spine/hip/femoral neck, while 35 (50.0 percent) had a history of fragility fracture. Oral bisphosphonates use at baseline was documented in 33 (47.0 percent) patients.

While the baseline demographics and osteoporosis risk factors were not significantly different between the two treatment groups, patients in the romosozumab group had lower hip/femoral neck BMD and serum vitamin D3 levels than those in the denosumab group.

Other endpoints

At month 12, hip BMD significantly improved from baseline in both groups, with an increase of 1.6 percent in both the romosozumab (p=0.01) and denosumab (p=0.003) groups. However, the between-group difference was not significant.

On the other hand, the increase in femoral neck BMD was not significant in both groups, Mok noted.

With regard to bone turnover markers, there was a significant drop in the markers of bone formation (P1NP; –35.1 percent, p<0.001) and bone resorption (CTX; –34.7 percent, p=0.002) in the denosumab group, according to Mok. In the romosozumab group, there was a numerical increase in bone formation marker (P1NP; 1.7 percent, p=0.89) and a nonsignificant drop in bone resorption marker (CTX; –18.1 percent, p=0.18).

“Only one new vertebral fracture developed in the romosozumab group at 12 months,” he said.

As for safety, both drugs were tolerated well, with self-limiting injection site pain being the most frequent adverse event (AE) in the romosozumab group. This, according to Mok, could be attributed to more frequent injections.

Postinjection musculoskeletal pain occurred in two romosozumab-treated patients and in three denosumab-treated patients. Mild hypocalcaemia and hypercalcaemia were seen in two patients on denosumab. None of the patients overall had serious AEs.

“The 24-month data of this study are pending,” Mok said.