Early administration of romosozumab prevents rebound of bone resorption related to denosumab withdrawal in fractured post-menopausal women: a real-world prospective study.

Abstract

Purpose: The real-world effectiveness of switching from denosumab to romosozumab remains controversial. Sequential therapy with romosozumab was shown to be associated with inadequate suppression of bone resorption and there was anecdotal evidence of major osteoporotic fractures (MOFs) after transitioning from denosumab to romosozumab. This study evaluated the effects on bone resorption of early romosozumab administration 3 months after denosumab withdrawal in fractured women with post-menopausal osteoporosis.

Methods: This prospective, single-center cohort study included 39 post-menopausal women with osteoporosis experiencing either MOFs or decrease in bone mineral density during long-term treatment with anti-resorptive drugs. Eighteen received romosozumab either 6 months (Group A) or 3 months (Group B) after their last denosumab dose, while 21 women switched from bisphosphonates to romosozumab and were enrolled as controls (Group C). Serum C-terminal telopeptide of type I collagen (CTX) levels were measured at baseline, 3 and 6 months.

Results: All women of group A and 4 out of 8 women of group B showed a clinically significant increase of CTX values (i.e., change above the least significant change) (p = 0.023), which occurred earlier in group A as compared to group B. Moreover, 9/10 women of group A and 2/8 women of group B achieved values above the mean of reference range for pre-menopausal women (p = 0.013). In group C, serum CTX values did not change significantly during the follow-up. Two women in Group A experienced MOFs during the follow-up.

Conclusions: Early romosozumab administration after denosumab withdrawal may control bone turnover rebound and possibly prevent incidence of fractures in post-menopausal osteoporosis.